Pharmaceutical Organic Chemistry – Complete Full Notes
UNITED REPUBLIC OF TANZANIA
[pic]
Ministry of Health, Community Development, Gender, Elderly and Children
Facilitator Guide
Copyright © Ministry of Health, Community Development, Gender, Elderly and
Children – 2018
Table of Contents
Table of Contents iii
Background iv
Acknowledgment v
Introduction vii
Abbreviations/Acronym xi
Session 1: Introduction to Pharmaceutical Organic Chemistry. 1
Session 2: Classification of Organic Compounds. 8
Session 3: Classification of Drugs According to Their Chemical Nature.
14
Session 4: Nomenclature of Organic Compounds. 17
Session 5: General Properties of Organic Compounds. 23
Session 6: Chemical Reaction in Organic Compounds. 32
Session 7: Isomerism. 38
Session 8: Alkanes of Pharmaceutical Importance. 48
Session 9: Alkenes of Pharmaceutical Importance. 57
Session 10: Alkynes of Pharmaceutical Importance. 73
Session 11: Alcohols of Pharmaceutical Importance. 84
Session 12: Carboxylic Acids of Pharmaceutical Importance. 101
Session 13: Esters of Pharmaceutical Importance. 114
Session 14: Acyl Chlorides of Pharmaceutical Importance. 122
Session 15: Ethers of Pharmaceutical importance. 128
Session 16: Aldehydes of Pharmaceutical Importance. 138
Session 17: Ketones of Pharmaceutical Importance. 148
Session 18: Aromatic Organic Compounds of Pharmaceutical Importance .
161
Session 19: Phenols of Pharmaceutical Importance. 175
Session 20: Aryl Halides of Pharmaceutical Importance. 188
Session 21: Amines of Pharmaceutical Importance. 200
Session 22: Amides of Pharmaceutical Importance. 216
Session 23: Introduction to Heterocyclic Compounds. 224
Session 24: Chemical Reactions of Heterocyclic Compounds. 234
Session 25: Introduction to Structure – Activity Relationship of Drugs.
243
Session 26: Structure – Activity Relationship of Penicillins. 247
Session 27: Structure – Activity Relationship of Cephalosporins. 257
Session 28: Structure – Activity Relationship of Quinolones. 264
Session 29: Structure – Activity Relationship of Sulphonamides. 271
Session 30: Structure – Activity Relationship of Aspirin. 279
Session 31: Structure – Activity Relationship of Paracetamol. 285
Session 32: Biotransformation of Medicinal Products. 290
Background
There is currently an ever-increasing demand for pharmaceutical personnel
in Tanzania. This is due to expanding investment in public and private
pharmaceutical sector. Shortage of trained pharmaceutical human resource
contributes to poor quality of pharmaceutical services and low access to
medicines in the country (GIZ, 2012).
Through Public-Private-Partnership (PPP) the Pharmacy Council (PC) together
with Development Partners (DPs) in Germany and Pharmaceutical Training
Institutions (PTIs) worked together to address the shortage of human
resource for pharmacy by designing a project named “Supporting Training
Institutions for Improved Pharmaceutical Services in Tanzania” in order to
improve quality and capacity of PTIs in training, particularly of lower
cadre pharmaceutical personnel.
The Pharmacy Council formed a Steering committee that conducted a
stakeholder’s workshop from18th – 22ndAugust 2014 in Morogoro to initiate
the implementation of the project.
Key activities in the implementation of this project included carrying out
situational analysis, curriculum review and harmonization, development of
training manual/facilitators guide, development of assessment plan,
training of trainers and supportive supervision.
After the curricula were reviewed and harmonized, the process of developing
standardised training materials started through Writer’s Workshop approach.
The approach included a number of workshops for developing, reviewing,
editing and formatting the sessions of the modules.
The goals of writer’s workshops were to build capacity of tutors in the
development of training materials and to develop high-quality, standardized
teaching materials.
The training package for pharmacy cadres includes a facilitator guide,
assessment plan and practicum. There are 11 modules for NTA level 5 making
11 facilitator guides including one practicum guide.
Acknowledgment
The development of standardized training materials of a competence-based
curriculum for pharmaceutical sciences has been accomplished through
involvement of different stakeholders.
Special thanks go to the Pharmacy Council for spearheading the
harmonization of training materials in the pharmacy after noticing that
training institutions in Tanzania were using different curricula and train
their students differently.
I would also like to extend my gratitude to Christian Social Service
Commission (CSSC) for their tireless efforts to mobilize funds from
development partners. Special thanks to Multi Actors Partnership (MAP)
for the financial and technical support.
Particular thanks are due to those who led this important process to its
completion, Centre for Education Development in Health Arusha (CEDHA), Ms.
Diana Gamuya, Mr. Dickson Mtalitinya and Members from the secretariat of
National Council for Technical Education (NACTE) for facilitating the
process.
Finally, I very much appreciate the contributions of the tutors and content
experts representing PTIs, hospitals, and other health training
institutions. Their participation in meetings and workshops, and their
input in the development of this training manual/facilitators guide have
been invaluable.
These participants are listed with our gratitude below:
Ms. Elizabeth Shekalaghe Registrar, Pharmacy Council of Tanzania
Dr. Catherine Jincen Principal, CEDHA
Dr. Saitore Laizer Deputy Principal, CEDHA
Dr. Sungwa N. Kabissi Project Manager – MAP, CSSC
Ms. Diana Gamuya CEDHA
Ms. Emily Mwakibolwa Pharmacy Council
Ms. Tumaini H. Lyombe MUHAS
Ms. Dilisi J. Makawia KSP
Director of Human Resources Development
Ministry of Health, Community Development, Gender, Elderly and Children
Introduction
Module Overview
This module content is a guide for tutors of Pharmaceutical schools for
training of students. The session contents are based on sub-enabling
outcomes and their related tasks of the curriculum for Basic Technician
Course in Pharmaceutical Sciences. The module sub-enabling outcomes and
their related tasks are as indicated in the Ordinary Technician Certificate
in Pharmaceutical Sciences (NTA Level 5) Curriculum.
Target Audience
This module is intended for use primarily by tutors of pharmaceutical
schools. The module’s sessions give guidance on the time, activities and
provide information on how to teach the session. The sessions include
different activities which focus on increasing students’ knowledge, skills
and attitudes.
Organization of the Module
The module consists of thirty-two (32) sessions; each session is divided
into several parts as indicated below:
indicated in minutes
teaching the session.
learn by the end of the session.
including handouts and worksheets.
step, the activity or method used in each step and the step title.
step has a heading and an estimated time to teach that step as shown in
the overview box. Also, this section includes instructions for the tutor
and activities with their instructions to be done during teaching of the
contents.
of a session. This step summarizes the main points and ideas from the
session, based on the learning tasks of the session.
based on the learning tasks to check the understanding of students.
teaching or later for students’ further learning. Handouts are used to
provide extra information related to the session topic that cannot fit
into the session time. Handouts can be used by the students to study
material on their own and to refer to them after the session. Sometimes,
a handout will have questions or an exercise for the participants
including the answers to the questions.
o Tutors are expected to use the module as a guide to train students in
the classroom and skills laboratory.
o The contents of the modules are the basis for teaching and learning
Pharmaceutical Organic Chemistry.
o Use the session contents as a guide.
o The tutors are therefore advised to read each session and the relevant
hand-outs and worksheets as preparation before facilitating the
session.
o Tutors need to prepare all the resources, as indicated in the resource
section or any other item, for an effective teaching and learning
process.
o Plan a schedule (timetable) of the training activities.
o Facilitators are expected to be innovative to make the teaching and
learning process effective.
o Read the sessions before facilitation; make sure you understand the
contents in order to clarify points during facilitation.
o Time allocated is estimated, but you are advised to follow the time as
much as possible and adjust as needed.
o Use session activities and exercises suggested in the sessions as a
guide.
o Always involve students in their own learning. When students are
involved, they learn more effectively.
o Facilitators are encouraged to use real life examples to make learning
more realistic.
o Make use of appropriate reference materials and teaching resources
available locally.
3 Preparation with Hand-outs and Worksheets
o Go through the session and identify hand-outs and worksheets needed for
the session.
o Reproduce pages of these hand-outs and worksheets for student use while
teaching the session. This will enable students to refer to hand-outs and
worksheets during the session in the class. You can reproduce enough
copies for students or for sharing.
o Give clear instructions to students on the student activity in order for
the students to follow the instructions of the activity.
o Refer students to the specific page in the student manual as instructed
in the facilitator guide.
4 Using Students Manual When Teaching
o The student manual is a document which has the same content as the
facilitator guide, which excludes facilitator instructions and answers
for exercises.
o The student manual is for assisting students to learn effectively and
acts as a reference document during and after teaching the session.
o Some of the activities included in facilitator guide are in the student
manual without facilitator instructions.
Abbreviations/Acronym
CEDHA Centre for Educational Development in Health Arusha
COX Cyclooxygenase
CUHAS Catholic University of Health and Allied Sciences
ELCT Evangelical Lutheran Church in Tanzania
Giz Deutsche GesellschftFürInternationaleZusammenarbeit
HKMU Hurbert Kairuki Memorial University
JSI John Snow Inc
KSP Kilimanjaro School of Pharmacy
LZHRC Lake Zone Health Resource Centre
MoHCDGEC Ministry of Health, Community Development, Gender, Elderly and
Children
MUHAS Muhimbili University of Health and Allied Sciences
NACTE National Council for Technical Education
NTA National Technical Award
PTI Pharmaceutical Training Institution
RuCU Ruaha Catholic University
SAR Structure-Activity Relationship
SIBS Spring Institute of Business and Science
SLF Saint Luke Foundation
USP United States Pharmacopeia
Session 1: Introduction to Pharmaceutical Organic Chemistry.
Total Session Time: 120 minutes
Prerequisites: PST 04210 Inorganic Chemistry
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW.
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |15 minutes |Buzzing. |Definition of Pharmaceutical Organic|
| | |Presentation. |Chemistry. |
|3 | |Brainstorming.| |
| |35 minutes |Presentation. |Characteristics of Organic |
| | | |Compounds. |
|4 |45 minutes |Group |Importance of Organic Chemistry in |
| | |discussion. |Pharmacy. |
| | |Presentation. | |
|5 |10minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENT.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Pharmaceutical Organic Chemistry (15 minutes)
|Activity: Buzzing (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is a pharmaceutical Organic Chemistry? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below. |
of carbon and its compounds.
o However, carbon monoxide, carbon dioxide, carbonates, hydrogen
carbonates, carbides and cyanides are excluded.
containing carbon which are involved with design, chemical synthesis and
development of bioactive molecules (drugs).
o Medicinal Chemistry – which is devoted to discovery and
development of new agents for treating diseases.
o Biochemistry – study of the cell & analysis of its structure to
identify factors necessary for life of every cell.
o Carbon is the principle element in organic compounds; most also
contain hydrogen and others contain the halogens, nitrogen, oxygen,
phosphorus, sulphur etc.
o Occurs widely in carbohydrates, proteins, fats, vitamins, nucleic
acids, hormones and synthetic materials such as drugs, ink and
dyes.
o Major sources are petroleum, coal and natural gases.
o Other sources include wood, oils and agricultural waste products
o Biggest source of organic compounds – plants & animals
o Ability to catenate
branched chains and rings of different sizes
o Ability to form four strong single covalent bonds (tetravalency)
a 4A element in the periodic table, it can share 4 valence
electrons – tetravalent, Tend to form four strong covalent bonds
o Ability to Form Multiple Bonds
with itself.
(ii) triple bonds eg C≡C.
compounds of the same elements but single bond.
o Carbon atom can vary in oxidation state from -4 to +4
CH4 Carbon oxidation number -4
CCl4 Carbon oxidation number +4
STEP 3: Characteristics of Organic Compounds (35 minutes).
|Activity: Brainstorming (10minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What are the characteristics of organic compounds? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
The following are the characteristics of organic compounds
o Carbon atom from strong covalent bonds with one another, most
organic compounds are stable because of the strong carbon -carbon
bonds, since they have a covalent nature they do not ionizes in
solution and are non-conductors of electricity.
o Carbon-hydrogen bonds are non-polar like carbon-carbon bonds; this
is because of the almost equal electro negativities of the two
elements.
o Most of the organic compounds are non-polar unless the compounds
consist of very electronegative elements like chlorine or groups
like the hydroxyl group, they cannot therefore form bonds with
water molecules (insoluble in water).
o If an organic compound contain polar groups hydrogen bond can form
between polar group in the molecule of organic compound and the
water molecule.
o For the example ethanol molecule contains a hydroxyl group which is
polar, so it is soluble in water.
o Organic compounds generally have low melting and boiling points
than inorganic compounds; this is because these compounds possess
relatively weak intermolecular bonds which can easily broke by heat
energy.
o Many organic compounds are; thermally unstable, decomposing into
simpler molecules when heated to temperature above 5000C.
o However, this property is sometimes of commercial importance as in
the cracking of petroleum.
o This property is very useful in the fractional distillation of
crude oils.
o Most organic compounds are flammable (catch fire easily) and burn
exothermically in a plentiful supply of air to yield carbon (IV)
oxide and water.
o Thus, most fuels such as woods, coal, oil, petrol and natural gas
are organic, and their combustion provides our main source of heat
energy.
o Reactions involving organic compounds tend to be much slower than
the ionic reactions commonly encountered in inorganic Chemistry.
o They usually require heating, thoroughly mixing and catalyst to
speed up the reaction.
STEP 4: Importance of Pharmaceutical Organic Chemistry (45 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question |
|What is the importance of Pharmaceutical Organic Chemistry? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below. |
The following are the importance of pharmaceutical organic chemistry
o Many medicines (most of which are organic compounds) come from
natural source in which the right extraction will benefit human
health.
o Moreover, medicines from organic compounds tend to be safer
compared to medicines from laboratory experiments.
o Example cambogia from mangosteen that helps to treat cancer and
prevents cell damage.
o Knowledge of Pharmaceutical Organic Chemistry can also help in
discovering the cause of disease since many diseases originate from
natural source.
o For example, in order to understand G.I.T problems scientist can
learn from the organic chemicals inside the organ such as acids and
amino acids as well as strange intrusion of the chemicals.
o This can be done in various ways, for example the study of
chemicals within brain will help to identify any disturbance inside
the brain and hence help to diagnose the disease occurring within
the brain.
o It is important that the right medicine or treatment will help
human to have better health through the attachment of proper
patterns of diet, example the amount of carbohydrate, protein,
mineral, and the level of acid in the body as well as the reaction
between two chemicals in the body helps to determine the food
intake for daily consumption and regulation of the diet based on
the balance of chemical in the body.
o In industries and laboratories organic solvents are widely used to
clear impurities. For example, in the drug extraction from plants,
the fatty matter from the pulp is removed using petroleum ether.
o Thus, organic chemistry through its knowledge of polarity,
solubility, partition factors uses solvents to separate components
for better use.
o Most of the sterilizing agents and disinfectants like phenol,
formaldehyde etc. are carbon compound.
o Due to their properties like solubility, pH, they can kill microbes
and even human body cells.
o Most substances we use like drugs, pesticides, etc. are analysed
qualitatively and quantitatively using different types of
titrations, chromatograph techniques, and spectrophotometry.
o Here the reagents used like acids or bases or reductive oxidative
species is organic in nature, further, the end point indicators in
titration are developed by organic chemistry.
STEP 5: Key Points (10 minutes)
study of carbon and its compounds
having low boiling points and melting points compared to inorganic
compounds.
other agents used in medical field, diagnosis and study of diseases.
STEP 6: Evaluation (10 minutes)
References.
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama R. N. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 2: Classification of Organic Compounds.
Total Session Time: 60 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |40 minutes |Presentation |Classification of Organic compounds |
| | |Group | |
| | |Discussion | |
|3 |05 minutes |Presentation |Key Points |
| 4 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Classification of Organic Compounds (40 minutes)
| |
|Activity: Small Group Discussion (20 minutes). |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question. |
|How do we classify Organic Compounds? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
o Acyclic or open chain compounds,
o Alicyclic or closed chain or ring compounds,
o Aromatic compounds and
o Heterocyclic aromatic compounds
Acyclic or open chain compounds:
o These compounds are also known as aliphatic compounds, they have
branched or straight chains. Following are the examples in this
category.
[pic]
o These are cyclic compounds which contain carbon atoms connected to
each other in a ring (homocyclic).
o When atoms other than carbon are also present then it is called as
heterocyclic. Examples of this type are as follows:
[pic]
o They are a special type of compounds which contain benzene and other
ring related compounds.
o Similar to alicyclic, they can also have heteroatoms in the ring.
o Such compounds are called as heterocyclic aromatic compounds.
o Some of the examples are as follows:
[pic]
[pic]
Eg Tropolone
[pic]
hydrocarbons.
o Hydrocarbons are compounds containing carbon and hydrogen
o Saturated hydrocarbons are those in which adjacent carbon atoms are
joined by a single covalent bond and all other bonds are satisfied
by hydrogen.
o Unsaturated hydrocarbons have at least two carbon atoms that are
joined by more than one covalent bond and all remaining bonds are
satisfied by hydrogen.
[pic] [pic]
Fig.1. Diagrammatic Classification of Organic Compounds
[pic]
STEP 3: Key Points (05 minutes).
Alicyclic or closed chain or ring compounds, Aromatic compounds and
Heterocyclic aromatic compounds.
hydrocarbons.
STEP 4: Evaluation (10 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama R. N. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 3: Classification of Drugs According to Their Chemical Nature.
Total Session Time: 60 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 | |Presentation |Classification of Drugs According to|
| |45 minutes |Small group |Their Chemical Nature |
| | |discussion | |
|3 |05 minutes |Presentation |Key Points |
| 4 | |Presentation |Evaluation |
| |05 minutes | | |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Clasification of Drugs According to Their Chemical Nature (45
minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups |
| |
|ASK students to discuss on the following question |
|How do you classify drugs according to their chemical nature? |
| |
|ALLOW students to discuss for 15 minutes |
| |
|ALLOW few groups to present and the rest to add points not mentioned |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Chemically, drugs are classified as follows:
This includes:
o Metals and their salts (ferrous sulphate, zinc sulphate and magnesium
sulphate)
o Non-metals such as sulphur
They include the following:
o Alkaloids; examples are atropine, strychnine and morphine
o Glycosides; examples are digitoxin and digoxin
o Proteins; examples are oxytocin and insulin
o Esters, amides, alcohols, glycerides, carboxylic acids, phenols
STEP 4: Key Points (5 minutes).
STEP 5: Evaluation (5 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama R. N. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 4: Nomenclature of Organic Compounds.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Buzzing |Definition of Nomenclature of |
| | |Presentation |Organic Compounds |
|3 |85 minutes |Group |Nomenclature of organic compounds |
| | |discussion | |
| | |Presentation | |
|4 |10 minutes |Presentation |Key Points |
| 5 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Nomenclature of Organic Compounds (10 Minutes).
|Activity: Buzzing (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is nomenclature of organic compounds? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
naming organic chemical compounds as recommended by the International
Union of Pure and Applied Chemistry (IUPAC).
STEP 3: Nomenclature of organic compounds (85 minutes).
|Activity: Small Group Discussion (20 minutes). |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question |
|What are the rules for naming organic compounds? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below. |
The following are the rules that are followed in naming organic
compounds
1. Identification of the parent chain. This chain must obey the following
rules, in order of precedence:
functional group. By suffix, it is meant that the parent functional
group should have a suffix, unlike halogen substituents. If more
than one functional group is present, the one with highest
precedence should be used.
2. Identification of the parent functional group, if any, with the
highest order of precedence.
3. Identification of the side-chains. Side chains are the carbon chains
that are not in the parent chain but are branched off from it.
4. Identification of the remaining functional groups, if any, and naming
oxyalkane for O-R, etc.).
Different side-chains and functional groups will be grouped together
in alphabetical order. (The prefixes di-, tri-, etc. are not taken
into consideration for grouping alphabetically. For example, ethyl
comes before dihydroxy or dimethyl, as the "e" in "ethyl" precedes the
"h" in "dihydroxy" and the "m" in "dimethyl" alphabetically. The "di"
is not considered in either case). When both side chains and secondary
functional groups are present, they should be written mixed together
in one group rather than in two separate groups.
5. Identification of double/triple bonds.
6. Numbering of the chain. This is done by first numbering the chain in
both directions (left to right and right to left), and then choosing
the numbering which follows these rules, in order of precedence
functional group. Locants are the numbers on the carbons to which
the substituent is directly attached.
multiple bond is the number of the adjacent carbon with a lower
number).
7. Numbering of the various substituents and bonds with their locants. If
there is more than one of the same type of substituent/double bond, a
prefix is added showing how many there are ( di – 2 tri – 3 tetra – 4
then as for the number of carbons below with 'a' added)
order and written before the name of the side-chain. If there are two
side-chains with the same alpha carbon, the number will be written
twice. Example: 2,2,3-trimethyl- . If there are both double bonds and
triple bonds, "en" (double bond) is written before "yne" (triple
bond).
which can exist only at the end of a chain, like formyl and carboxyl
groups), there is no need to number it.
1. Arrangement in this form: Group of side chains and secondary
functional groups with numbers made in step 3 + prefix of parent
hydrocarbon chain (eth, meth) + double/triple bonds with numbers (or
"ane") + primary functional group suffix with numbers.
Wherever it says "with numbers", it is understood that between the
word and the numbers, the prefix(di-, tri-) is used.
2. Adding of punctuation:
trimethylheptane becomes 2,5,5-trimethylheptane)
becomes trimethylheptane)
Note: IUPAC uses one-word names throughout. This is why all
parts are connected.
Example
Here is a sample molecule with the parent carbons numbered:
[pic]
For simplicity, here is an image of the same molecule, where the hydrogens
in the parent chain are removed and the carbons are shown by their numbers:
[pic]
Now, following the above steps:
1. The parent hydrocarbon chain has 23 carbons. It is called tricosa-.
2. The functional groups with the highest precedence are the two ketone
groups.
write 3,9-dione.
When numbering from left to right, the ketone groups are
numbered 3 and 9. When numbering from right to left, the ketone
groups are numbered 15 and 21. 3 is less than 15, therefore the
ketones are numbered 3 and 9. The smaller number is always used,
not the sum of the constituent’s numbers.
3. The side chains are: an ethyl- at carbon 4, an ethyl- at carbon 8, and
a butyl- at carbon 12.
Note:The -O-CH3 at carbon atom 15 is not a side chain, but it is a
methoxy functional group.
diethyl.
(But this is not necessarily the final grouping, as functional
groups may be added in between to ensure all groups are listed
alphabetically.)
1. The secondary functional groups are: a hydroxy- at carbon 5, a chloro-
at carbon 11, a methoxy- at carbon 15, and a bromo- at carbon 18.
Grouped with the side chains, this gives 18-bromo-12-butyl-11-chloro-
4,8-diethyl-5-hydroxy-15-methoxy
2. There are two double bonds: one between carbons 6 and 7, and one
between carbons 13 and 14. They would be called "6,13-diene", but the
presence of alkynes switches it to 6,13-dien. There is one triple bond
between carbon atoms 19 and 20. It will be called 19-yne.
3. The arrangement (with punctuation) is: 18-bromo-12-butyl-11-chloro-4,8-
diethyl-5-hydroxy-15-methoxytricosa-6,13-dien-19-yne-3,9-dione
4. Finally, due to Cis-trans isomerism, we have to specify the relative
orientation of functional groups around each double bond. For this
example, we have (6E,13E)
The final name is (6E,13E)-18-bromo-12-butyl-11-chloro-4,8-diethyl-5-
hydroxy-15-methoxytricosa-6,13-dien-19-yne-3,9-dione.
STEP 3: Key Points (5minutes)
which is a systematic method of naming organic chemical compounds as
recommended by the International Union of Pure and Applied Chemistry
(IUPAC).
STEP 4: Evaluation (5 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama R. N. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 5: General Properties of Organic Compounds.
Total Session Time: 120 minutes + 10 minutes home assignment.
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |25 minutes |Buzzing |Physical Properties of Organic |
| | |Presentation |Compounds |
|3 |60 minutes |Small group |General properties of Organic |
| | |discussion |Compounds |
| | |Presentation | |
|4 |10 minutes |Presentation |Key Points |
|5 | |Presentation |Evaluation |
| |10 minutes | | |
|6 |10 minutes |Presentation |Take Home Assignment |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Physical Properties of Organic Compounds (25 minutes).
|Activity: Buzzing (10minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the physical properties of organic compounds? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below. |
The following are the physical properties of organic compounds;
Melting Point.
changes from solid to liquid state.
o Size of a molecule:
compound.
arrangement of atoms or possess different configurations will have
difference of melting point.
configurations.
o Force of attraction between the molecules:
attraction between the molecules.
to a higher melting point.
Boiling Point:
boiling point when atmospheric pressure is low.
o Polarity: Greater the polarity the higher the boiling point, that is,
polarity determines the force of attraction between the molecules.
Molecules are attracted by opposite charges in a polar compound.
o Carbon-carbon chain: Boiling point decreases with the increase in the
length of a carbon-carbon chain.
o Strength of Intermolecular forces: Various effects such as Vander
Waals dispersion hydrogen – bonding. Ionic bonding will affect the
strength of intermolecular forces.
Solubility
alcohol or white spirits.
Flammability and vapour pressure
catch alight and burn.
molecules in the gas state. The weaker the intermolecular forces within a
substance the higher the vapour pressure will be.
therefore more flammable.
STEP 3: General properties of organic compounds (60 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question; |
|What are the general properties of organic compounds? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points have not been |
|mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
explain, on a molecular level, many observable physical properties of
organic compounds.
o Intermolecular forces
o Type of function group
o Chain length
o Shape of the molecule
include;
o Van der waals forces –dipole-dipole forces
forces)
o Hydrogen bonding.
Flammability
catch alight and burn. The flash point of a substance is the lowest
temperature that is likely to form a gaseous mixture you could set
alight.
to be ignited easily) while those with higher flash points are considered
nonflammable.
burn, but it will not ignite easily.
Vapor pressure
molecules in the gas state. These molecules have enough energy to
overcome the intermolecular forces holding the majority of the substance
in the liquid or solid phase
container) and that pressure is the vapour pressure of that compound
vapour pressure will be
therefore more flammable
Solubility
Solubility is a chemical property referring to the ability for a given
substance, the solute, to dissolve in a solvent.
solvent at equilibrium. The resulting solution is called a saturated
solution.
Solubility of polar compounds in water
solvent, the most important issue to consider is how strong the
noncovalent interactions between the compound and the solvent molecules
are.
and/or more charged, hydrogen bonding, and other polar groups will tend
to increase the solubility.
true.
immediately in water, because water, as a very polar molecule, is able to
form many ion-dipole interactions with both the sodium cation and the
chloride anion, the energy from which is more than enough to make up for
energy required to break up the ion-ion interactions in the salt
crystal.
have individual sodium cations and chloride anions surrounded by water
molecules – the salt is now in solution.
are very hydrophilic (water-loving).
Solubility of non-polar compounds
water.
and carbon-hydrogen bonds.
o It is able to bond to itself very well through nonpolar van der Waals
interactions, but it is not able to form significant attractive
interactions with very polar solvent molecules like water.
o Thus, the energetic cost of breaking up the biphenyl-to-biphenyl
interactions in the solid is high, and very little is gained in terms
of new biphenyl-water interactions.
o Therefore, water is a terrible solvent for nonpolar hydrocarbon
molecules: they are very hydrophobic (water-fearing).
Solubility of alcohol in water
and ending with octanol (8 carbons).
water, at any water/alcohol ratio that you try.
hydroxyl group in these molecules, and the combined energy of formation
of these water-alcohol hydrogen bonds is more than enough to make up for
the energy that is lost when the alcohol-alcohol (and water-water)
hydrogen bonds are broken up.
are increasingly non-soluble in water.
regions in addition to their hydrophilic hydroxyl group.
the molecule begins to overcome that of the hydrophilic part, and water
solubility is lost.
Boiling point and melting point
provides an additional illustration of the effects of noncovalent
interactions.
between identical molecules in a pure sample are disrupted.
required, in the form of heat, to break them apart
Butane versus Octane
hydrocarbons.
der Waals interaction, and thus higher boiling points.
liquid, because the butane molecules are held together by Van der Waals
forces.
break apart and enter the gas phase.
due to the increased van der Waals interactions made possible by the
larger surface area of the individual molecules.
interactions is reflected in higher boiling points.
hexanone (dipole-dipole interactions), and 3-hexanol (hydrogen bonding).
dipole interactions, in addition to the weaker van der Waals
interactions. 3-hexanol, because of its hydroxyl group, is able to form
intermolecular hydrogen bonds, which are stronger yet.
bonds, water remains in the liquid phase at temperatures up to 100 OC
despite its small size.
STEP 4: Key Points (10 minutes).
boiling points, Solubility, flammability and vapor pressure
solvent, the most important issue to consider is how strong are the
noncovalent interactions between the compound and the solvent molecules
between identical molecules in a pure sample are disrupted.
STEP 5: Evaluation (10 minutes).
STEP 6: Take Home Assignment (10 minutes)
|Activity: Take home Assignment (10 minutes) |
| |
|DIVIDE students in groups or individual. |
| |
|ASK the students to work on the following assignment |
| |
|Write short notes on the solubility of glucose, benzoic acid and |
|acetic acid in water. |
| |
|ALLOCATE time for students to do the assignment and submit. |
| |
|REFER students to recommended references |
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama R. N. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams.
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services.
Session 6: Chemical Reaction in Organic Compounds.
Total Session Time: 60 minutes
Prerequisites
Students Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |15 minutes |Presentation |Definition of the term chemical |
| | |Buzzing |reaction |
|3 | |Group |Types of chemical reactions |
| |30 minutes |discussion |involving organic compounds |
| | |Presentation | |
|4 |05 minutes |Presentation |Key Points |
|5 | | Presentation |Evaluation |
| |05 minutes | | |
CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Chemical Reaction (15 minutes)
|Activity: Buzzing (10minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What is chemical reaction? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
Definition
new substance through chemical change, OR
reactants, are converted to one or more different substances, the
products, substances are either chemical elements or compounds.
create different substances as products.
STEP 3: Types of Chemical Reactions Involving Organic Compounds (30
minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
|ASK students to discuss on the following question. |
| |
|What are the types of chemical reactions involving organic compounds? |
| |
|ALLOW students to discuss for 15 minutes |
|ALLOW few groups to present for 5 minutes and the rest to add points |
|not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
There are five main types of organic reactions that can take place. They
are as follows:
Let us study each of these reactions in detail, to understand more about
them.
[pic]
o In a substitution reaction, one atom or a group of atoms take place of
another atom or a group of atoms which leads to the formation of an
altogether new substance.
o We can take an example of C – Cl bond, in which the carbon atom
usually has a partial positive charge due to the presence of highly
electronegative chlorine atoms.
o In a nucleophilic substitution reaction, it is important that the
nucleophile must have a pair of electrons and it also should have a
high affinity for the electropositive species in comparison to the
substituent which was originally present in the element.
o In order for the substitution reaction to occur, there are certain
conditions that have to be present such as maintaining low
temperatures same as room temperature.
o These are reactions which involve the elimination and removal of the
adjacent atoms.
o After these multiple bonds are simultaneously formed and there is a
release of small molecules as product.
o One of the examples of a typical elimination reaction is the
conversion of ethyl chloride to ethylene.
o In the above reaction, the eliminated molecule is HCl, which can form
out of the combination of H+ from the carbon atom which is on the left
side and Cl– from the carbon atom which is on the right side.
o An addition reaction is simply just the opposite of an elimination
reaction.
o In an addition reaction, the components or molecules of A and B are
added to the carbon-carbon multiple bonds and this is called an
addition reaction.
o In the reaction given below when HCl is added to ethylene, it will
give us ethylene chloride.
o Most of the organic reactions involve radicals and their movement.
o Addition of a halogen to a typically saturated hydrocarbon involves
free radical mechanism.
o There are usually three stages involved in a radical reaction which
are;
o Initially when the weak bond is broken initiation of the reaction
takes place with the formation of free radicals.
o After that when the halogen is added to the hydrocarbon a radical is
produced and finally, it gives alkyl halide.
o Electrons in an organic redox reaction often are transferred in the
form of a hydride ion – a proton and two electrons.
o Because they occur in conjunction with the transfer of a proton, these
are commonly referred to
as hydrogenation and dehydrogenation reactions: a hydride plus a
proton adds up to a hydrogen (H2) molecule.
o When a carbon atom in an organic compound loses a bond to hydrogen and
gains a new bond to a heteroatom (or to another carbon), this means
the compound has been dehydrogenated, or oxidized.
o A very common biochemical example is the oxidation of an alcohol to a
ketone or aldehyde:
[pic]
o Conversely, when a carbon atom in an organic compound gains a bond to
hydrogen and loses a bond to a heteroatom (or to another carbon atom),
it means the compound has been hydrogenated, or reduced.
o The hydrogenation of a ketone to an alcohol, for example, is overall
the reverse of the alcohol dehydrogenation shown above.
o Illustrated below is another common possibility, the hydrogenation
(reduction) of an alkene to an alkane
[pic]
STEP 4: Key Points (5 minutes)
reactants, are converted to one or more different substances, the
products, substances are either chemical elements or compounds.
reactions, addition reactions, radical reactions and Oxidation-Reduction
Reactions.
STEP 5: Evaluation (10 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama R. N. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 7: Isomerism.
Total Session Time: 60 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |15 minutes |Buzzing |Definition of Isomer and Isomerism |
| | |Presentation | |
|3 |40 minutes |Group |Types of Isomers |
| | |discussion | |
| | |Presentation | |
|4 |40 minutes |Presentation |Importance of Isomerism in Pharmacy |
| | |Brainstorming | |
|5 |10 minutes |Presentation |Key Points |
|6 | | Presentation |Evaluation |
| |10 minutes | | |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Isomer and Isomerism (15 minutes).
|Activity: Buzzing (10 minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What is an isomer? |
|What is isomerism? |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
structural formula
formula but different structural formula
STEP 3: Types of Isomerism (40 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the types of isomerism |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
The following are the descriptions of types of isomerism;
o Arises due to restricted rotation across the C-C double bonds.
o Occurs only when two atoms/groups attached to each carbon of the
double bond are different from one another.
o This type of isomerism is also known as cis-trans isomerism.
o The cis-isomer has like groups on the same side of the double bond,
whereas the trans-isomer has like group on opposite sides of the
double bond.
Example,
[pic]
o Cis Butene (the methyl groups are on the same side)
[pic]
o Trans Butene (the methyl groups are on the opposite side)
o Another way to name the cis-trans isomers is to use the Z and E
nomenclature
[pic] E
Zusammen, means together
which means on opposite sides.
o These are Isomers which have the atoms of their molecules linked in a
different order
o The structural isomerism is further subdivided in the following
categories;
Chain Isomerism
different arrangement of carbon chain within the molecule.
boiling point due to different strengths of intermolecular bonding.
[pic]
Positional Isomerism
and same carbon skeleton but differ in the position of attached atoms or
groups or in position of multiple bonds.
usually very similar.
properties.
[pic]
propyl alcohol; I) and propan-2-ol (isopropyl alcohol; II)
attached to an end carbon in the first isomer and to the center carbon in
the second.
increases; for example, the next largest alcohol, named butanol (C4H10O),
has four different structural isomers.
[pic]
Functional Group Isomers
formula but different functional groups.
chemically dissimilar.
[pic]
o Isomers that differ in connectivity are called constitutional
(sometimes structural) isomers.
o They have the same parts, but those parts are attached to each other
differently.
o The bracelets of red and green beads mentioned above are analogous to
constitutional isomers.
o The simplest hydrocarbons—methane (CH4), ethane (CH3CH3), and propane
(CH3CH2CH3)—have no constitutional isomers, as there is no other way
to connect the carbons and hydrogens of these molecules consistent
with the tetravalency of carbon and the univalency of hydrogen.
[pic]
o However, there are two different butanes, C4H10, and these two
molecules, called butane and isobutane, are constitutional isomers.
o They are different molecules with different chemical and physical
properties.
o Butane has its four carbon atoms bonded in a continuous chain.
Isobutane has a branched structure.
o [pic]
o The number of possible constitutional isomers increases greatly with
the number of available atoms.
o There are only two butanes, but there are three pentanes (C5H12), 18
octanes (C8H18), and no fewer than 366,319 constitutional isomers of
the hydrocarbon containing 20 carbon atoms and 42 hydrogens.
o Stereoisomers are isomers that have the same composition (that is, the
same parts) but that differ in the orientation of those parts in space.
o There are two kinds of stereoisomers:
an object and its non-superimposible mirror image, like one’s
hands.
type of a stereoisomer.
compound have different configurations at one or more (but
not all) of the equivalent (related) stereocenters and are
not mirror images of each other.
one stereocenter they are epimers. Each stereocenter gives
rise to two different configurations and thus increases the
number of stereoisomers by a factor of two.
are pairs of stereoisomers that differ in all stereocenters
and are therefore mirror images of one another.
o Enantiomers of a compound with more than one stereocenter are also
diastereomers of the other stereoisomers of that compound that are not
their mirror image.
o Diastereomers have different physical properties (unlike enantiomers) and
different chemical reactivity.
[pic]
Fig. Isomerism
[pic]
STEP 4: The importance of Isomerism in Pharmacy (40 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is the importance of isomerism in pharmacy? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
and more effective drug alternatives of the newer as well as existing
drugs.
racemic mixture to one of its isomers.
and safer drug has been made available.
reactions like Quinine has antimalarial activity while quinidine has
an antiarrythmic property.
Levomethorphan is a potent opiod analgesic while dextromethorphan
is a cough suppressant
o R-Thalidomide is sedative while S-Thalidomide has been shown
teratogenic effects;
o R-Naproxen is used for arthralgic pain while S-Naproxen is
teratogenic
found to cause blindness
dopa which has never been used because it causes deficiency of
white blood cells and thus susceptibility to infections.
STEP 5: Key Points (10 minutes).
structural formula.
Constitutional isomerism and Stereoisomerism.
pharmacokinetic and pharmacodyanmic properties which has helped in
introducing safer and more effective drug alternatives of the newer as
well as existing drugs.
STEP 6: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama Rao Nadendla (2005). Principles of Pharmaceutical Organic Chemistry.
New Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R. (2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 8: Alkanes of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Alkanes |
| | |Presentation | |
|3 |15 minutes |Buzzing |Alkanes and their Isomers |
| | |Presentation | |
|4 |15 minutes |Presentation |Nomenclature of Alkanes |
|5 |15 minutes |Presentation |Chemical Structure of Alkanes |
|6 |10 minutes |Brainstorming |Chemical Properties of Alkanes |
| | |Presentation | |
|7 |30 minutes |Group |Chemical Reactions and Uses of |
| | |discussion |Alkanes |
| | |Presentation | |
|8 |10 minutes |Presentation |Key Points |
|9 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Alkanes (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is Alkane? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below; |
carbons and hydrogen atoms and contain carbon-carbon single bonds.
Homologous series (homo is Greek for “the same as”) is a family of
compounds in which each member differs from the next by one methylene
group (CH2).
integer.
o Methane CH4
o Ethane C2H6
o Propane C3H8
o Butane C4H10
o Pentane C5H12
o Hexane C6H14
o Heptane C7H16
o Octane C8H18
o Nonane C9H20
o Decane C10H22
o Undecane C11H24 etc
if it has two carbon atoms, it must have six hydrogen.
NOTE; Only one possible structure for an alkane with molecular formula CH4
(methane) and molecular formula C2H6 (ethane)
branched structure.
four bonds and each hydrogen forms only one bond.
STEP 3: Alkanes and their Isomers (15 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What is an isomer? |
|What is isomerism? |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content below |
but different structural formula (have different arrangements of atoms in
space).
rise to a linear chain.
formed.
Example.1; C6H14 has 5 isomers as follows:
o Hexane
o 2-Methylpentane
o 3-Methylpentane
o 2,2-Dimethylbutane
o 2,3-Dimethylbutane
Example.2; C7H16 has 9 isomers as follows:
o Heptane
o 2-Methylhexane
o 3-Methylhexane
o 2,2-Dimethylpentane
o 2,3-Dimethylpentane
o 2,4-Dimethylpentane
o 3,3-Dimethylpentane
o 3-Ethylpentane
o 2,2,3-Trimethylbutane
Example 3; C5H12 has 3 isomers which are:
o Pentane
o 2-Methylbutane
o 2,2-Dimethylpropane
Example 4; C4H10 has 2 isomers which are;
o Butane
o 2-Methylpropane
STEP 4: Nomenclature of Alkanes (15 Minutes).
o This chain is called the parent hydrocarbon.
Carbon to which the alkyl group is attached.
in the use of the lowest numbers; thus, II is called 2–‐ methylpentane
rather than 4–‐ methylpentane.
indicate this by the prefix di-, tri-, tetra- etc., to show how many of
these alkyl groups are there and indicate by various numbers the position
of each group, as in 2,2,4‐trimethyl-pentane.
[pic]
parent chain, name them in alphabetical order, as in 3,3‐diethyl-5-
isopropyl-4-methyloctane
[pic]
STEP 5: Chemical Structure of Alkanes (15 minutes).
molecular formula CnH2n+2, where n is the number of carbon atoms in
the chain.
and n-alkanes (n stands for normal)
[pic]
STEP 6: Chemical Properties of Alkanes (10 minutes).
|Activity: Brainstorming (5minutes) |
| |
|ASK students to pair up and brainstorm on the following question for 5 |
|minutes. |
| |
|What are the chemical properties of Alkanes? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
o Complete combustion (Under sufficient amount of oxygen (Air)) any
hydrocarbon produces carbon dioxide and water.
o Also, can react with very strong oxidizing agents like Potassium
permanganate, potassium dichromate, Manganese oxide, to produce carbon
dioxide and water.
o Halogenation is the replacement of one or more hydrogen atoms in an
organic compound by a halogen (Fluorine, Chlorine Bromine or Iodine).
o Under ultra violet light or temperature that makes up the free radical
chain for halogenation reaction to proceed and that is the first step.
o Cracking is the breakdown of large alkanes under high temperature and
pressure into smaller, more useful alkenes.
o Cracking of alkanes produce a mixture of alkenes and alkanes, cracking
is an example of thermal decomposition reaction.
o Conditions are Temperature of about 500°C and moderately low
pressures.
STEP 7: Chemical Reactions and Uses of Alkanes (30 minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the reactions involving Alkanes? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
o Complete combustion (Under sufficient amount of oxygen (Air)) any
hydrocarbon produces carbon dioxide and water.
o Example; [pic]
o Halogenation is the replacement of one or more hydrogen atoms in an
organic compound by a halogen (Fluorine, Chlorine Bromine or
Iodine).
o Example;
[pic]
o Cracking is the breakdown of a large alkanes under high temperature
and pressure into smaller, more useful alkenes.
o Product of cracking of alkanes are alkenes and alkanes.
o Cracking is an example of thermal decomposition reaction at
temperature of about 500°C and moderately low pressures.
o Example;
[pic]
Uses of alkanes
o Alkane is a compound of halothane which is a general anesthetic agent.
diesel, furnace oil and wax which are used as fuels.
useful organic compounds.
o For example, methane on chlorinate on gives chloromethane,
dichloromethane, trichloromethane (chloroform) and tetrachloromethane.
STEP 8: Key Points (10 minutes).
carbons and hydrogen atoms and contain carbon-carbon single bonds.
structure.
have no isomers because there is only one way in arranging the molecule
in 3D structures but the rest of the alkane’s series might have an
isomer, which is called structure isomers.
names also called general or primary names or the un-systematic name and
The IUPAC name, or the systematic name.
cracking.
which is a general anaesthetic.
STEP 9: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama Rao Nadendla (2005). Principles of Pharmaceutical Organic Chemistry.
New Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R. (2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 9: Alkenes of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Alkenes |
| | |Presentation | |
|3 |15 minutes |Buzzing |Alkenes and their Isomers |
| | |Presentation | |
|4 |15 minutes |Presentation |Nomenclature of Alkenes |
|5 |15 minutes |Presentation |Chemical Structure of Alkenes |
|6 |10 minutes |Presentation |Chemical Properties of Alkenes |
| | |Brainstorming | |
|7 |40 minutes |Group |Chemical Reactions and Uses of |
| | |discussion |Alkenes |
| | |Presentation | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Alkenes (5 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Alkenes? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
as compared to corresponding alkanes (sp2 hybrid), also known as OLEFINS
or ALKYLENES, general formula: (CnH2n).
feature of the alkenes.
STEP 3: Alkenes and their Isomers (15 minutes).
|Activity: Buzzing (10minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What is the isomer of Alkenes? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
Geometric isomerism
bond are different from one another
whereas the trans-isomer has like group on opposite sides of the double
bond
Example,
[pic]
Cis Butene (the methyl groups are on the same side)
[pic]
Trans Butene (the methyl groups are on the opposite side)
Structural isomerism
order
o Chain Isomerism
[pic] [pic][pic]
melting or boiling point due to different strengths of
intermolecular bonding.
o Positional Isomers
[pic] [pic]
properties are usually very similar.
different properties
Example of isomerism is given by propanol
(n-propyl alcohol; I) and propan-2-ol (isopropyl alcohol; II)
two: it is attached to an end carbon in the first isomer, and to
the center carbon in the second.
of atoms increases;
For example; the next largest alcohol, named butanol
(C4H10O), has four different structural isomers.
[pic] [pic]
STEP 4: Nomenclature of Alkenes (15 minutes).
be added to name and locate the double bond.
o Rule 1: Select as the parent structure the longest continuous chain
that contains the C-C double bond:
one double bond is present, the ending is diene, triene, tetraene,
etc.
o Rule 2: Indicate by a number the position of the double bond in the
chain. Number it so that the C-atoms in the double bond have the
lowest possible numbers.
o Rule 3: The position of the double bond(s) is indicated by the
number(s) of the lower numbered carbon atom of each double bond. These
numbers are placed in front of the name of the compound.
Example,
[pic]
o Rule 4: In cyclic hydrocarbons, start numbering around the ring with
the carbons of the double bond indicates by numbers the positions of
alkyl groups attached to the parent chain.
Example,
[pic]
3-Methylcyclopenten
Table 1. Nomenclature of simple alkenes
|COMPOUND |COMMON NAME |IUPAC NAME |
STEP 5: Chemical Structure of Alkenes (15 minutes).
Definition
iron or radical with multiple atoms) especially which atoms are
chemically bonded to what other atoms with what kind of chemical bonds,
together with any information on the geometric shape of the molecule
needed to uniquely identify the type of molecule.
OR
bonds that holds the atoms together. Example diatomic oxygen or nitrogen
molecules or DNA molecules.
Table 2: Chemical stuctures of alkenes CnH2n
| IUPAC Name | Molecular Formula |Condensed Structural |
| | |Formula |
STEP 6: Chemical Properties of Alkenes (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are chemical properties of Alkenes? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
carbon atoms, almost all of the chemical reactions of alkene occur at the
double bond.
Isomerization
temperatures (200-300°C) isomerizes in the presence of catalyst, such as
Al2(SO4)3.
o The shifting of the double bond which tends to move towards the center
pentene-1 pentene-2
methylpropene (iso-butene).
[pic]
and halogen acids to produce di halo alkanes, alcohol, alkane and halo
alkanes, also with oxygen to form epoxides.
+HCl
STEP 7: Chemical Reactions and Uses of Alkenes (40 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical properties of Alkanes? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
double bond.
most common reactions of double bonds transform the pi bond into a sigma
bond.
H sigma bond into two C – H sigma bonds
o These are because atoms are added & the double bond becomes a
single bond
[pic]
o Electrophilic addition
o Dimerazation
o Polymerisation
o Combustion
o Addition is the most common reaction of alkenes
o Most addition reactions involve a second step in which a nucleophile
attacks the carbocation (as in the second step of the SN1 reaction),
forming a stable addition product.
o In the product, both the electrophile and the nucleophile are bonded
to the carbon atoms that were connected by the double bond.
o Example 1;
[pic]
Step 1: Attack of the pi bond on the electrophile forms a carbocation.
[pic]
Step 2: Attack by a nucleophile gives the addition product.
[pic]
o Example 2: Ionic addition of HBr to 2-butene
o When gaseous HBr adds to 2-butene the proton in HBr is electrophilic;
it reacts with the alkene to form a carbocation.
o Bromide ion reacts rapidly with the carbocation to give a stable
product in which the elements of HBr have added to the ends of the
double bond.
o Step 1: Protonation of the double bond forms a carbocation.
[pic]
Step 2: Bromide ion attacks the carbocation.
[pic]
The electrophilic addition reactions to alkenes include the following
reactions
presence of a small amount of Ni / pt catalyst.
compound (heterogeneous)
[pic]
2. Addition of Halogens to Alkenes.
adjacent carbon atoms.
[pic]
EXAMPLE: Addition of Br2 to propene.
Step 1: Electrophilic attack forms a bromonium ion.
[pic]
Step 2: Bromide ion opens the bromonium ion
[pic]
mechanism.
easily.
(CH2CI2), chlorofonn (CHCI3 ), and carbon tetrachloride (CCI4) are the
most frequent choices.
3. Addition of Hydrogen Halides to Alkenes
[pic]
an alkene results in a product with the acid proton bonded to the carbon
atom that already holds the greater number of hydrogen atoms’.
orientation and give the Markovnikov product.
to the double bonds of alkenes.
additions, based on the addition of the electrophile in such a way as to
produce the most stable carbocation
‘In an electrophilic addition to an alkene, the electrophile adds in such
a way as to generate the most stable intermediate’.
Step 1: Protonation of the pi bond forms a carbocation.
[pic]
Step 2: Attack by the halide ion gives the addition product .
[pic]
Example.
[pic]
rearrangement
[pic]
[pic]
stabilized by the alkyl groups which release electrons
[pic]
Order of stability of carbocations: 3o>2o>1o
4. Hydration of Alkenes: Addition of Water
catalyst to form an alcohol.
hydrogen atom adding to one carbon and a hydroxyl group adding to the
other.
[pic]
the equilibrium toward the alcohol.
EXAMPLE: Acid-catalyzed hydration of propene.
Step 1: Protonation of the double bond forms a secondary carbocation.
[pic]
Step 2: Nucleophilic attack by water gives a protonated alcohol
[pic]
Step 3: Deprotonation gives the alcohol
[pic]
o Under proper conditions isobutene is converted by sulfuric acid/
phosphoric acid into a mixture of two (2) alkenes – C8H16
o Hydrogenation of these alkenes produce the same alkane 2,2,4-
trimethylpentane.
[pic]
o The alkenes produced contain exactly twice the number of carbon and
hydrogen atoms as the original isobutylene, they are known as
dimers of isobutylene
[pic]
[pic]
[pic]
o A polymer is a large molecule composed of many smaller repeating
units (the monomers) bonded together.
o Alkenes serve as monomers for some of the most common polymers,
such as polyethylene, polypropylene, polystyrene, poly (vinyl
chloride), and many others.
o Alkenes generally undergo addition polymerization, the rapid
addition of one molecule at a time to a growing polymer chain.
o There is generally a reactive intermediate (cation, anion, or
radical) at the growing end of the chain; for that reason, addition
polymers are also called chain-growth polymers
o Polymerization is an important industrial process to produce
plastic, nylon & Bakelite
o In nature there are some natural polymers as well such as; starch,
cellulose, proteins & rubber
o Alkenes, like alkanes, are highly combustible.
o Alkenes burn with a luminous flame to give carbon dioxide and
water; the flame becomes luminous because of the higher carbon
content of alkenes than alkanes.
o Their combustion reactions are exothermic.
[pic]
o Due to the luminosity of the flame, the lower alkenes may be used
as illuminants.
Uses of Alkenes
plastic material.
o These polymers are used in making plastic bags, pipes electrical
insulation.
dioxane.
o Ethylene glycol is also used as an antifreeze in automobile
radiators.
fruit development.
o Therefore, ethene is used for artificial ripening of fruits,
flower maturation.
compounds such as alkyl halides, ethylene oxide, ethanol and other
alkanols.
STEP 8: Key Points (05 minutes).
one or more carbon- carbon double bonds.
Polymerization and Combustion reactions.
and 1,3-butadiene which are used as starting materials in the syntheses
of alcohols, plastics, detergents, and fuels
STEP 9: Evaluation (05 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 10: Alkynes of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Alkynes |
| | |Presentation | |
|3 |15 minutes |Buzzing |Alkynes and their Isomers |
| | |Presentation | |
|4 |15 minutes |Presentation |Nomenclature of Alkynes |
|5 |15 minutes |Presentation |Chemical Structure of Alkynes |
|6 |10 minutes |Brainstorming |Physical Properties of Alkynes |
| | |Presentation | |
|7 |40 minutes |Group |Chemical Reactions involving Alkynes|
| | |discussion | |
| | |Presentation | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Alkynes (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Alkynes? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
as compared to corresponding alkanes, also known as Acetylenes, general
formula: (CnH2n-2).
feature of the alkynes.
STEP 3: Alkynes and their Isomers (15 minutes).
|Activity: Buzzing (10minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the isomers of Alkynes? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
Structural isomerism
order
o Chain Isomerism.
melting or boiling point due to different strengths of
intermolecular bonding.
o Positional Isomer
properties are usually very similar.
different properties
STEP 4: Nomenclature of Alkynes (15 minutes).
must be added to name and locate the triple bond.
o Rule 1: Select as the parent structure the longest continuous chain
that contains the C-C triple bond:
triple bond is present, the ending is diyne, triyne, tetrayne, etc.
o Rule 2: Indicate by a number the position of the triple bond in the
chain. Number it so that the C-atoms in the triple bond have the
lowest possible numbers.
o Rule 3: The position of the triple bond(s) is indicated by the
number(s) of the lower numbered carbon atom of each triple bond. These
numbers are placed in front of the name of the compound.
Examples
o [pic] [pic]
o [pic][pic]
o [pic][pic]
o Rule 4: In cyclic hydrocarbons, start numbering around the ring with
the carbons of the double bond indicates by numbers the positions of
alkyl groups attached to the parent chain.
STEP 5: Chemical Structure of Alkynes (15 minutes).
[pic]
a
cylindrical shape.
[pic]
overlaps, so shorter
[pic]
[pic]
[pic]
Table 2: Chemical stuctures of alkynes CnH2n-2
| IUPAC Name | Molecular Formula |Condensed Structural |
| | |Formula |
|Ethyne |C2H2 |CHCH |
|Propyne |C3H4 |CHCCH3 |
|1-butyne |C4H6 |CHCCH2CH3 |
|1-pentyne |C5H8 |CHC(CH2)2CH3 |
|1-hexyne |C6H10 |CHC(CH2)3CH3 |
|1-heptyne |C7H12 |CHC(CH2)4CH3 |
|1-octyne |C8H14 |CHC(CH2)5CH3 |
STEP 6: Physical Properties of Alkynes (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are physical properties of Alkynes? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
STEP 7: Chemical Reactions involving Alkynes (40 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical properties of Alkanes? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
| |
o Addition of Hdrogen; Alkynes can be reduced to form alkenes and/or
alkanes depending on upon the reaction condition.
Examples;
o Reduction with Metal – Amonia: Alkynes on treatment with sodium or
lithium in liquid ammonia produce trans- alkenes as almost exclusive
product.
[pic]
o Catalytic reduction: Catalytic reduction of alkynes to alkanes
[pic]
o Addition of halogens:Addition of halogens to alkyenes takes place in
two stages, first forming a trans-1, 2-dihaloalkene and then
1,1,2,2,-tetrahaloalkane
[pic]
o Addition of halogen acids: On treatment with halogens acids, alkynes
first form vinly halides followed by alkylidene halides. The second
molecule of halogens acid adds according to Markowkwnikoff’s rule
[pic]
o Hydration (addition of water): React with water in presence of
sulphuric acid and mercuric sulphate to form a vinyl alcohol which
readily tautomerizes to the corresponding carbonyl derivative.
[pic]
o Ozonization: Ozon adds to carbon-carbon triple bond forming ozonide.
The ozonides are hydrolyzed by water and the products – the 1,2-
diketones undergo oxidative cleavage to acids by hydrogen peroxide
formed in the reaction.
[pic]
o Hydroboration: Addition of borane to carbon –carbon triple bond
produces vinlyboranes which is oxidized by hydrogen peroxide to
given enol. Tautomerazation then gives either ketone or aldehyde
depending on the structure of alkyne reactant.
[pic]
[pic]
STEP 8: Key Points (05 minutes)
–carbon triple bond and having general formula (CnH2n-2).
noretynodrel, antiretroviral Efavirenz and antifungal terbinafine.
STEP 9: Evaluation (05 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 11: Alcohols of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Alcohols |
| | |Presentation | |
|3 |15 minutes |Presentation |Alcohols and their Isomers |
|4 |15 minutes |Presentation |Nomenclature of Alcohols |
|5 |15 minutes |Presentation |Chemical Structure of Alcohols |
|6 |15 minutes |Presentation |Chemical Properties of Alcohols |
| | |Buzzing | |
|7 |35 minutes |Group |Chemical Reactions involving |
| | |discussion |Alcohols |
| | |Presentation | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Alcohols (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Alcohols? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
group bonded to an sp3 hybridized carbon atom.
–e from alkanes is replace by –ol.
tertiary, depending on the carbon atom bonded to the – OH group.
compound is a primary alcohol.
carbon atoms, it is a secondary alcohol, and the carbon atom to which it
is attached is a secondary carbon atom.
other carbon atoms, it is a tertiary alcohol, and the carbon atom to
which it is attached is a tertiary carbon atom.
Primary alcohols
[pic]
[pic]
[pic]
STEP 3: Alcohols and their Isomers (15 Minutes).
o Chain isomerism.
o Position isomerism.
o Functional isomerism.
Chain isomerism
to the different structure of C-skeleton in the longest chain.
[pic]
Position isomerism
a different position of a hydroxyl group (OH).
Example
[pic]
Functional isomer
The functional isomer of an alcohol is ether.
Example
[pic]
STEP 4: Nomenclature of Alcohols (15 minutes).
are similar to those for other classes of compounds.
give the location of the hydroxyl group
Rules
1. Select the longest continuous carbon atom chain containing the carbinol
(hydroxyl) group(s).
2. Number the chain, giving the hydroxyl (alcohol) substituent(s) the
lowest number possible.
3. Name the longest chain as an alkane, but drop the terminal -e and add
-ol. Ethane would become ethanol.
4. For monohydric alcohols the letter ‘-e’ at the end of the root name is
replaced by the ending ‘-ol’ with a number, when necessary, to show the
position of the –OH group on the carbon skeleton.
[pic]
5. If more than one hydroxyl group is present (for polyols i.e.
dihydric,trihydric etc.) the name becomes -diol, -triol, etc. and the
terminal -e in the parent name is not dropped from the alkane name.
But the letters ‘diol’ ‘triol’ etc & numbers 1,2,3 etc are added to the
ending to show how many –OH groups & their position
needs to specify where the hydroxyl groups are attached.
(vicinal) carbon atoms.
diol rather than 1,2-ethanediol.
6. Indicate by numbers the positions of other groups attached to the
parent chain
[pic]
[pic]
group it locates (-ol), giving the name 1-bromo-3,3-dimethylbutan-2-
ol.
7. Cyclic alcohols are named using the prefix cyclo-; the hydroxyl
group is assumed to be on carbon number 1, C1.
[pic]
[pic]
STEP 5: Chemical Structure of Alcohols (15 minutes).
positioned on the chain of carbon atoms. There are some chemical
differences between the various types.
Primary alcohols
is only attached to one alkyl group. Some examples of primary alcohols
are shown below:
[pic]
group holding the -OH group.
alcohol even though there are no alkyl groups attached to the the -OH
carbon atom.
In a secondary (2°) alcohol, the carbon atom with the -OH group attached is
joined directly to two alkyl groups, which may be the same or different.
Examples include the following:
[pic]
attached directly to three alkyl groups, which may be any combination of
the same or different groups.
[pic]
STEP 6: Chemical Properties of Alcohols (15 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What are the chemical properties of Alcohols? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content below |
The following are some chemical properties of alcohols
o Alcohols burns in oxygen to produce carbon dioxide and water. An
alcohol burns cleanly and easily and does not produce soot.
o It becomes increasingly more difficult to burn alcohols as the
molecules get bigger.
o The general molecular equation for the reaction is:
CnH2n+1OH + (1.5n)O2 → (n+1)H2O + nCO2
o Dehydration of alcohols is done by heating with concentrated sulfuric
acid, which acts as the dehydrating agent, at 180°C.
o This reaction uses alcohols to produce corresponding alkenes and water
as byproduct.
[pic]
o Primary alcohols (R-CH2-OH) can be oxidized either to aldehydes (R-
CHO) or to carboxylic acids (R-CO2H), while the oxidation of secondary
stage.
o Tertiary alcohols (R1R2R3C-OH) are resistant to oxidation.
o e.g. oxidation of ethanol:
C2H5OH + [O] → CH3COOH + H2O
o Oxidation can be done by using oxidising agents such as acidified
potassium dichromate (VI), acidified potassium manganate (VII) etc
o Alcohols can be reacted with carboxylic acid to form esters.
[pic]
STEP 7: Chemical Reactions involving Alcohols (35 minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions. |
|What are the chemical reactions involving Alcohols? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 10 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
o Oxidation products depend on whether the alcohol is 1o, 2o or 3o.
o In oxidation one or more hydrogen atoms are lost from the carbon
having OH group
o Primary and secondary alcohols are easily oxidized by a variety of
reagents, including chromium reagents, permanganate, nitric acid, and
even household bleach (NaOCl, sodium hypochlorite).
o Oxidation of a primary alcohol initially forms an aldehyde.
o Unlike a ketone, however, an aldehyde is easily oxidized further to
give a carboxylic acid.
[pic]
o Chromic acid generally oxidizes a primary alcohol all the way to the
carboxylic acid.
[pic]
o A better reagent for the limited oxidation of primary alcohols to
aldehydes is pyridinium chlorochromate (PCC), a complex of chromium
trioxide with pyridine and HCI.
[pic]
o Secondary alcohols are easily oxidized to give excellent yields of
ketones.
o The chromic acid reagent is often best for laboratory oxidations of
secondary alcohols.
[pic]
[pic]
Example:
[pic]
o Oxidation of tertiary alcohols is not an important reaction in organic
chemistry.
o Tertiary alcohols have no hydrogen atoms on the carbinol carbon atom,
so oxidation must take place by breaking carbon-carbon bonds.
o These oxidations require severe conditions and result in mixtures of
products.
[pic]
Summary of alcohol oxidations
[pic]
o Two other strong oxidants are potassium permanganate and nitric
acid.
o Both of these reagents are less expensive than the chromium
reagents, and both of them give byproducts that are less
environmentally hazardous than spent chromium reagents.
o Both permanganate and nitric acid oxidize secondary alcohols to
ketones and primary alcohols to carboxylic acids.
o Dehydration requires an acidic catalyst to protonate the hydroxyl
group of the alcohol and convert it to a good leaving group.
o Loss of water, followed by loss of a proton, gives the alkene
o Dehydration results from E1 elimination of the protonated alcohol
o Example:
[pic]
o Alcohol dehydrations generally take place through the E1 mechanism.
o Protonation of the hydroxyl group converts it to a good leaving
group.
o Water leaves, forming a carbocation.
o Loss of a proton gives the alkene.
[pic]
[pic]
o Because the rate limiting step is formation of a carbocation, the
ease of dehydration follows from the ease of formation of
carbocations: 3° > 2° > 1
o As in other carbocation reactions, rearrangements are common.
o Alcohols can combine with many kinds of acids to form esters.
o When no type of acid is specified, the word ester is assumed to
mean a carboxylic ester, the ester of an alcohol and a carboxylic
acid.
o The reaction, called Fischer esterification, is characterized by
the combining of an alcohol and an acid (with acid catalysis) to
yield an ester plus water.
[pic]
o Under appropriate conditions, inorganic acids also react with
alcohols to form esters.
reagents and conditions can be used.
[pic]
Acidity of alcohols: formation of alkoxides
acidic as water, and most other alcohols are somewhat less acidic.
atom of an alcohol.
by reducing the proton to hydrogen gas.
[pic]
an alkoxide ion on an alkyl halide.
Summary of common reactions of alcohols
[pic]
STEP 8: Key Points (10 minutes)
group bonded to an sp3 hybridized carbon atom.
tertiary, depending on the carbon atom bonded to the – OH group.
or to carboxylic acids (R-CO2H), while the oxidation of secondary
STEP 9: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 12: Carboxylic Acids of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks.
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Carboxylic Acids |
| | |Presentation | |
|3 |15 minutes |Presentation |Nomenclature of Carboxylic Acids |
|4 |15 minutes |Presentation |Chemical Structure of Carboxylic |
| | | |Acids |
|5 |15 minutes |Buzzing |Chemical Properties of Carboxylic |
| | |Presentation |Acids |
|6 |40 minutes |Group |Chemical Reactions involving |
| | |discussion |Carboxylic Acids |
| | |Presentation | |
|7 |10 minutes |Presentation |Key Points |
|8 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Carboxylic Acids (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is carboxylic acid? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
atom is called a carboxyl group.
called carboxylic acids.
[pic]
Condensed structures
[pic]
carboxyl group as a functional group, attached to hydrogen HCOOH or an
alkyl group as RCOOH or an aryl group as ArCOOH
STEP 3: Nomenclature of Carboxylic Acids (15 minutes).
IUPAC Names
that corresponds to the longest continuous chain of carbon atoms.
positions of substituents along the chain.
In naming, the carboxyl group takes priority over any of the functional
groups discussed previously
[pic]
[pic]
[pic]
[pic]
[pic]
[pic]
[pic]
[pic]
Some more examples of traditional names most widely used are:
STEP 4: Chemical Structure of Carboxylic Acids (15 minutes)
resonance interaction of the lone pairs of the hydroxyl oxygen with the π
system of the carbonyl.
| Carboxylic Acid | | |
| |Structure | |
|Ethanoic acid |CH3CO2H | |
|Propanoic acid |CH3CH2CO2H | |
|Fluoroethanoic acid |CH2FCO2H | |
|Chloroethanoic acid |CH2ClCO2H | |
|Dichloroethanoic acid |CHCl2CO2H | |
|Trichloroethanoic acid |CCl3CO2H | |
|Nitroethanoic acid |O2NCH2CO2H | |
STEP 5: Chemical Properties of Carboxylic Acids (15 minutes).
|Activity: Buzzing (10minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What are the chemical properties of carboxylic acid? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
The following are chemical properties of carboxylic acids;
Acidity of Carboxylic Acids
Carboxylic acids are weak acids and their carboxylic anions are strong
conjugate bases are slightly alkaline due to the hydrolysis of carboxylate
anion compared to other species, the order of acidity and basicity or
corresponding conjugate bases are as follows:
Acidity RCOOH > HOH > ROH > HC[pic] CH > NH3 > RH
Basicity RCOO– < HO– < RO– < HCC– < NH2-< R–
Reaction of Carboxylic Acids with Metals
soluble in both NaOH and NaHCO3 solutions.
For example;
carboxylate anions and hydronium ion.
[pic]
Effect of substituents on the acidity of Carboxylic Acids
would increase the acidity of carboxylic acids.
acidity of carboxylic acids.
stabilize the anion which results in increase in acidity of the
carboxylic acids.
the anion which results in decrease in acidity of carboxylic acid.
[pic]
Conversion of Carboxylic Acids into functional derivatives
as derivatives of carboxylic acids or simply acid derivatives)
by replacement of its –OH group by a Cl, OR or NH2 .
o Replacement of -OH by -Cl forms acid chlorides.
o Replacement of -OH by -OR forms ester.
o Replacement of -OH by -NH2 forms amide.
derivatives or one can say that the functional derivatives are all
readily reconverted into the acid by simple hydrolysis.
Conversion of Carboxylic Acids into Amide
ammonium salt which on further heating at high temperature give
amides.
[pic]
Conversion of Carboxylic Acids into Acid Anhydrides
Lower monocarboxylic acid on heating with dehydrating agent (say P2O5)
forms anhydrides
[pic]
Note: Anhydride of formic acid is not known, it gives CO and H2O on
heating with conc. H2SO4.
HCOOH +Conc. H2SO → H2O + CO
Reduction of Carboxylic Acids to Alcohols
Lithium aluminium hydride can reduce an acid to an alcohol; the
initial product is an alkoxide from which the alcohol is liberated by
hydrolysis.
4 R–COOH + 3LiAlH4 → 4H2 + 2LiAlO2 + (RCH2O)4 AlLi + H2
Hydrolysis of (RCH2O)4 → alcohols
STEP 6: Chemical Reactions involving Carboxylic Acids (40 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving carboxylic acids? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
An overview of the chemical reactions involving carboxylic acids
[pic]
Acid chloride (ROCl)
chloride (SOCl2).
[pic]
Ester (RCOOR’)
and vegetable fats and oils.
commonly used in fragrances.
[pic]
The acid-catalyzed esterification of carboxylic acids with alcohols to give
esters is termed Fischer esterification.
Thioester (RCOSR’)
reacts with a thiol (RSH) in the presence of an acid.
[pic]
being acetyl CoA.
Acid anhydride
to the same oxygen atom.
chloride in the presence of a base.
[pic]
follows;
[pic]
chloride anion (Cl-) is the leaving group.
o In the first step, the base abstracts a proton (H+) from the
carboxylic acid to form the corresponding carboxylate anion (1).
o The carboxylate anion's negatively charged oxygen attacks the
considerably electrophilic acyl chloride's carbonyl carbon.
o As a result, a tetrahedral intermediate (2) is formed.
o In the final step, chloride – a good leaving group – is eliminated
from the tetrahedral intermediate to yield the acid anhydride.
Amide
because amines are very basic and tend to convert carboxylic acids to
their highly unreactive carboxylate ions.
o Therefore, DCC (Dicyclohexylcarbodiimide) is used to drive this
reaction.
[pic]
[pic]
group, which can then be displaced by an amine during nucleophilic
substitution to form the corresponding amide.
Relative reactivity of the carboxylic acid derivatives towards a
nucleophilic substitution reaction
[pic]
attached to a substituent (X).
o These derivatives also undergo a nucleophilic substitution reaction
with a nucleophile (Nu) as shown above.
o The reactivity of these derivatives towards nucleophilic substitution
is governed by the nature of the substituent X present in the acid
derivative.
o If the substituent (X) is electron donating, it reduces the
electrophilic nature of the carbonyl group by neutralizing the partial
positive charge developed on the carbonyl carbon, and thus makes the
derivative less reactive to nucleophilic substitution.
o If the substituent (X) is electron withdrawing, then it increases the
electrophilic nature of carbonyl group by pulling the electron density
of the carbonyl bond towards itself, making the carbonyl carbon more
reactive to nucleophilic substitution.
|Derivative |
|Substituent (X) |
|Electronic effect of X |
|Relative reactivity |
| |
|Acid chloride |
|-Cl |
|electron withdrawing |
|1 (most reactive) |
| |
|Acid anhydride |
|electron withdrawing |
|2 (almost as reactive as 1) |
| |
|Thioester |
|-SR |
|weakly electron donating |
|3 |
| |
|Ester |
|-OR |
|alkoxy (-OR) group is weakly electron donating |
|4 |
| |
|Amide |
|-NH2 |
|very strongly donating |
|5 |
| |
|Carboxylate ion |
|-O |
|Carboxylate ions are not reactive because their negative charge |
|repels the approach of other nucleophiles |
|6 (least reactive) |
| |
carboxylic acid derivatives towards nucleophilic substitution is as
follows:
Acid halide > acid anhydride > thioester > ester > amide
STEP 7: Key Points (10 minutes)
to the rest of the molecule.
organic compounds containing hydroxyl groups but are generally weaker
than the familiar mineral acids (e.g., hydrochloric acid,
HCl, sulfuric acid, H2SO4, etc.).
of carboxylic acids into esters, amides, carboxylate salts, acid
chlorides, and alcohols.
the hydrogen of the hydroxyl (–OH) group is replaced with a
metal cation.
STEP 8: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 13: Esters of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Esters |
| | |Presentation | |
|3 |15 minutes |Presentation |Nomenclature of Esters |
|4 |15 minutes |Presentation |Chemical Structure of Esters |
|5 |20 minutes |Buzzing |Chemical Properties of Esters |
| | |Presentation | |
|6 |40 minutes |Group |Chemical Reactions involving Esters |
| | |discussion | |
| | |Presentation | |
|7 |05 minutes |Presentation |Key Points |
|8 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Esters (10 minutes)
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is Ester? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
carboxylic acid in which there is a carbon group connected to the single-
bonded oxygen:
[pic] [pic]
Some common esters are as follows;
[pic]
STEP 3: Nomenclature of Esters (15 minutes).
first.
[pic]
changed to -ate
[pic]
[pic]
STEP 4: Chemical Structure of Esters (15 minutes).
and O-C-O bond angles due to sp2 hybridization.
rotation about the C-O-C bonds has a lower energy barrier.
macroscopic scale.
volatile, leading to a lower boiling point, than the corresponding
amides.
adjacent to the carbonyl, on esters is around 25, making them essentially
non-acidic except in the presence of very strong bases.
[pic]
shown, where R and R’ are both carbon-initiated chains of varying length,
also known as alkyl groups.
carbon.
has been replaced by an alkoxy (O-R) group.
with an alcohol.
STEP 5: Chemical Properties of Esters (20 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What are the chemical properties of Esters? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
In acid hydrolysis
[pic]
Base hydrolysis
Base hydrolysis is the reaction of an ester with a strong base. Produces
the salt of the carboxylic acid and an alcohol.
[pic]
STEP 6: Chemical Reactions involving Esters (40 minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving Esters? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 10 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Esterification Reaction
an alcohol or phenol (plus an acid catalyst).
o The oxygen of the alcohol adds to the carboxyl group, splitting out
a molecule of water in the process (an esterification reaction).
[pic]
equilibrium with a large amount of unreacted starting material still
present.
as starting materials.
o These reactions are nonreversible
[pic]
Examples
[pic]
Ester Hydrolysis
reaction) to form a carboxylic acid and an alcohol.
[pic]
carboxylic acids and alcohols.
Base hydrolysis (Saponification)
Esters may be broken apart under basic conditions by sodium hydroxide (lye)
or potassium hydroxide to form carboxylate salts and alcohols.
[pic]
This reaction is important in the production of soaps
STEP 8: Key Points (05 minutes)
at least one –OH (hydroxyl) group is replaced by an –O–alkyl (alkoxy)
group.
reaction) to form a carboxylic acid and an alcohol.
STEP 9: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R. (2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 14: Acyl Chlorides of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of acyl chlorides |
| | |Presentation | |
|3 |15 minutes |Presentation |Nomenclature of acyl chlorides |
|4 |15 minutes |Presentation |Physical Properties of Acyl |
| | | |Chlorides |
|5 |20 minutes |Buzzing |Preparation of Acyl Chlorides |
| | |Presentation | |
|6 |40 minutes |Group |Chemical Reactions involving acyl |
| | |discussion |chlorides |
| | |Presentation | |
|7 |05 minutes |Presentation |Key Points |
|8 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Acyl Chlorides (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
|What are acyl chlorides? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
[pic]
acid is replaced by something else.
acid derivative.
[pic]
STEP 3: Nomenclature of Acyl Chlorides (15 minutes).
with the corresponding.
|carboxylic acid |acyl chloride |acyl chloride |
|name |name |formula |
|ethanoic acid |ethanoyl |CH3COCl |
| |chloride | |
|propanoic acid |propanoyl |CH3CH2COCl |
| |chloride | |
|butanoic acid |butanoyl |CH3CH2CH2COCl |
| |chloride | |
replacing -oic acid by -ly.
in the -COCl group counts as the number 1 carbon.
[pic]
from methanoic acid.
carbon monoxide and HCl.
STEP 4: Physical properties of acyl chlorides (15 minutes).
o An acyl chloride like ethanoyl chloride is a colourless fuming liquid.
o The strong smell of ethanoyl chloride is a mixture of the smell of
vinegar (ethanoic acid) and the acrid smell of hydrogen chloride gas.
o The smell and the fumes are because ethanoyl chloride reacts with
water vapour in the air.
o Acyl chlorides can't be said to dissolve in water because they react
(often violently) with it.
o The strong reaction means that it is impossible to get a simple
aqueous solution of an acyl chloride.
o Taking ethanoyl chloride as typical:
o Ethanoyl chloride boils at 51°C.
o It is a polar molecule, and so has dipole-dipole attractions between
its molecules as well as van der Waals dispersion forces.
o However, it doesn't form hydrogen bonds.
o Its boiling point is therefore higher than, say, an alkane of similar
size (which has no permanent dipoles), but not as high as a similarly
sized alcohol (which forms hydrogen bonds in addition to everything
else.)
STEP 5: Preparation of Acyl Chlorides (20 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
|How are acyl chlorides prepared? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
thionyl (SOCl2).
[pic]
[pic]
STEP 6: Chemical Reactions involving acyl chlorides (40 minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving Esters? |
|[pic]REFER Students to Book |
|ALLOW students to discuss for 10 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
o Acyl chlorides are extremely reactive, and in their reactions the
chlorine atom is replaced by other groups.
o In each case, in the first instance, hydrogen chloride gas is produced
as steamy acidic fumes.
o However, in some cases the hydrogen chloride goes on to react with one
of the substances in the reaction mixture.
o Taking ethanoyl chloride as typical, the initial reaction is of this
kind:
[pic][pic]
o The reactions involve compounds like water, alcohols and phenols, or
ammonia and amines.
o All of these particular cases contain a very electronegative element
with an active lone pair of electrons – either oxygen or nitrogen.
STEP 8: Key Points (05 minutes).
which at least one –OH (hydroxyl) group is replaced by a halogen
chlorine.
thionyl.
chlorine atom is replaced by other groups
STEP 9: Evaluation (10 minutes).
References.
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama R. N. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams.
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services.
Session 15: Ethers of Pharmaceutical importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Ethers |
| | |Presentation | |
|3 |10 minutes |Presentation |Ethers and their Isomers |
|4 |15 minutes |Presentation |Nomenclature of Ethers |
|5 |15 minutes |Presentation |Chemical Structure of Ethers |
|6 |15 minutes |Buzzing |Chemical Properties of Ethers |
| | |Presentation | |
|7 |35 minutes |Group |Chemical Reactions involving Ethers |
| | |discussion | |
| | |Presentation | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Ethers (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Ethers? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
groups or aryl (benzene ring) groups.
replacing an H with an R group.
[pic]
ethers.
compounds.
Examples of ethers
[pic]
ether’’, or simply "ether."
STEP 3: Ethers and their Isomers (10 minutes).
Aliphatic Ethers can give two different types of isomers.
o Ethers with the same formula and having different carbon chain
skeletons are called chain isomers.
o Examples:
[pic]
o Ethers are isomeric with alcohols.
o Example:
[pic] is isomeric with ethyl alcohol C2H5OH
o Isomers with the same molecular formula but different alkyl groups
(around the functional group) are called metamers. An ether with
formula C4H10O has 3 metamers.
[pic]
STEP 4: Nomenclature of Ethers (15 minutes).
sometimes called the alkoxy alkane system.
alkyl ether system has also been widely used
rest of the ether as an alkoxy group.
ethers.
Example,
[pic]
[pic]
|Table 1: Common Alkyl and Alkoxy Groups |
|Alkyl Group |Name | |Alkoxy Group |Name |
|CH3– |Methyl | |CH3O– |Methoxy |
|CH3CH2– |Ethyl | |CH3CH2O– |Ethoxy |
|(CH3)2CH– |Isopropyl | |(CH3)2CHO– |Isopropoxy |
|(CH3)3C– |tert-Butyl | |(CH3)3CO– |tert-Butoxy |
|C6H5– |Phenyl | |C6H5O– |Phenoxy |
Common Names (Alkyl Alkyl Ether Names)
oxygen and adding the word ether.
alphabetical order, but many people still use the old system, which named
the groups in order of increasing complexity.
butyl, the current common name should be "t-butyl methyl ether,’’
symmetrical, as in "ethyl ether."
STEP 5: Chemical Structure of Ethers (15 minutes).
characterized by bond angles of 104.5 degrees, with the C-O distances
being about 140 pm.
chains.
[pic]
STEP 6: Chemical Properties of Ethers (15 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What are the chemical properties of Ethers? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
donors to form oxonium salts.
STEP 7: Chemical Reactions involving Ethers (35 minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving Ethers? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 10 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Reactions of Ether Due to an Alkyl Group
explosive mixtures with air giving CO2 and water.
C2H5O C2H5 + 6O2 → 4CO2 + 5H2O
chlorine or bromine. The resultant product is halogenated ether in
absence of sunlight. However, in presence of sunlight, it substitutes all
the hydrogen atoms of ethers.
CH3CH2OCH2CH3 [pic] CH3CHCIOCHCICH3 (α α’-dichloro diethyl ether)
CH3CH2OCH2CH3 [pic] C2CI2OC2CI5 (Perchloro diethyl ether)
Reaction of Ether Due to Ethereal Oxygen
electrons on the oxygen atom.
regeneration of ether by hydrolysis of these salts.
Ethers also form coordination complexes with Lewis acids like BF3, AICI3,
RMgX etc.
Grignard reagents.
Formation of Peroxides
ozonized oxygen in presence of sunlight or ultraviolet light.
might lead to explosive reactions.
anaesthetic agent.
with ferrous ammonium sulphate and potassium thiocyanate.
anaesthesia.
On mixing with KI solution, it liberates I2 which turns starch paper
blue.
[pic]
them with highly concentrated sulphuric acid, H2SO4.
amount of Cu2O to the ether.
Reactions of Ether Involving Cleavage of Carbon-Oxygen Bond
pressure, hydrolyse to corresponding alcohols.
hydrogen sulphate.
R-OR + conc. H2SO4 → 2R HSO4
R-OR’ + conc. H2SO4 → RHSO4 + R’HSO4
mainly upon the temperature in which we carry out the reaction.
simpler alkyl group.
• CH3OC2H5 + HI → CH3I + C2H5OH
We would observe similar reactions with HCI, HBr & the reactivity order is
HI > HBr > HCI.
R-O-R + PCI5 [pic] 2RCI + POCI3
[pic]
Action of Carbon Monoxide:
C2H5OC2H5, + CO [pic] C2H5COOC2H5
ROR + CO → RCOOR
STEP 8: Key Points (05 minutes).
oxygen atom connected to two alkyl or aryl groups.
alkyl or aryl groups.
of the oxygen atom in alphabetical order, then write “ether” or by
using the formal, IUPAC method.
reactive than alkanes.
acids, which results in the formation of an alkyl halide and an alcohol.
STEP 9: Evaluation (05 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 16: Aldehydes of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Aldehydes |
| | |Presentation | |
|3 |10 minutes |Presentation |Aldehydes and their Isomers |
|4 |15 minutes |Presentation |Nomenclature of Aldehydes |
|5 |15 minutes |Presentation |Chemical Structure of Aldehydes |
|6 |15 minutes |Buzzing |Chemical Properties of Aldehydes |
| | |Presentation | |
|7 |35 minutes |Group |Chemical Reactions involving |
| | |discussion |Aldehydes |
| | |Presentation | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Aldehydes (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Aldehydes? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
Aldehydes are compounds of the general formula RCHO (R may be aliphatic or
aromatic group)
Examples of aldehydes
In aldehydes, the carbonyl group has a hydrogen atom attached to it
together with either
containing a benzene ring.
[pic]
ALDEHYDE
STEP 3: Aldehydes and their Isomers (10 minutes).
Aldehydes exhibit the following type of isomerism:
o Aldehydes with 4 or more carbon atoms show chain isomerism. For
example:
[pic]
o Aromatic aldehydes and higher ketones give position isomers. For
example:
[pic]
o The general formula of aldehydes, ketones, unsaturated alcohols
oxiranes and oxolanes is CnH2nO
o C3H6O has isomers as:
[pic]
STEP 4: Nomenclature of Aldehydes (15 minutes).
structure. Aldehydes are named by replacing the ‘-e’ of the
corresponding alkane by the ending ‘-al’ [pic]
III.The common name of simple aldehydes end with ‘aldehyde’
Examples:
carbaldehyde is used.[pic]
[pic]
STEP 5: Chemical Structure of Aldehydes (15 minutes).
In an aldehyde, at least one of the attached groups must be a hydrogen
atom. The following compounds are aldehydes:
[pic]
COH, which might be confused with an alcohol.
comes after the atom it is attached to (usually C, N, or O).
[pic]
Some structures of simple aldehydes
[pic]
STEP 6: Chemical Properties of Aldehydes (15 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the chemical properties of Aldehydes? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
conditions with different reducing agents.
o Addition of hydrogen in the presence of catalysts like finely divided
platinum, palladium, nickel and ruthenium.
o Treatment with chemical reagents such as sodium borohydride (NaBH4) or
Lithium aluminium hydride (LiAlH4).
oxidising agents like nitric acid, potassium permanganate, potassium
dichromate etc.
o Fehlings' solution is an alkaline solution of copper sulphate
containing sodium potassium tartrate (Rochelle Salt) as a complexing
agent.
o Aldehydes on warming with solution, give a red precipitate of cuprous
oxide as a result of the redox reaction.
o Aromatic aldehydes give very poor results in this test.
STEP 7: Chemical Reactions involving Aldehydes (35 Minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving Aldehydes? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 10 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
derivatives.
the oxygen atom and the resulting polarization of the carbon-oxygen
double bond.
leaving it relatively unhindered and open to attack from either face of
the double bond.
hybridization from sp2 to sp3
alkoxide anion, which protonates to give the product of nucleophilic
addition.
[pic]
[pic]
Nucleophilic addition of Grignard Reagents
attacks the electrophilic carbonyl carbon atom to give an alkoxide
intermediate.
o [pic]
Hydride Reduction of Aldehydes
addition, with hydride ion (H : -) serving as the nucleophile.
[pic]
STEP 8: Key Points (05 minutes).
the structure −CHO, consisting of a carbonyl center (a carbon double-
bonded to oxygen) with the carbon atom also bonded to hydrogen and to
an R group, which is any generic alkyl or side chain.
commonly represented as −CHO.
presence of a hydrogen atom on carbonyl group which can be easily
converted to OH group.
functional group consisting of one —OH group and one —OR group bonded
to the same carbon) or acetals (a functional group consisting of two
—OR groups bonded to the same carbon), depending upon conditions
STEP 9: Evaluation (05 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 17: Ketones of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Ketones |
| | |Presentation | |
|3 |15 minutes |Presentation |Ketones and their Isomers |
|4 |15 minutes |Presentation |Nomenclature of Ketones |
|5 |15 minutes |Presentation |Chemical Structure of Ketones |
|6 |15 minutes |Buzzing |Chemical Properties of Ketones |
| | |Presentation | |
|7 |35 minutes |Group |Chemical Reactions involving Ketones|
| | |discussion | |
| | |Presentation | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Ketones (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is Ketone? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
bonded to the carbonyl carbon atom.
[pic]
properties
oxidizing agents and with nucleophiles
STEP 3: Ketones and their Isomers (10 minutes).
Ketones exhibit the following type of isomerism:
o Aldehydes with 4 or more carbon atoms and ketones with five or more
carbon atoms show chain isomerism. For example:
[pic]
o Aromatic aldehydes and higher ketones give position isomers. For
example:
[pic]
o The general formula of aldehydes, ketones, unsaturated alcohols
oxiranes and oxolanes is CnH2nO
o C3H6O has isomers as:
[pic]
STEP 4: Nomenclature of Ketones (15 minutes).
structure.
o Ketones are named by replacing the ‘-e’ of the corresponding
alkane by the ending ‘-one’
o The alkane name becomes alkanone
[pic]
o When R is aromatic just the word ketone is added to the
aromatic name
carbonyl carbon from the end closest to the carbonyl group, and we
indicate the position of the carbonyl group by a number
[pic]
[pic]
4-hydroxy-4-methyl-2-pentanone
4-hydroxy-4-methylpentan-2-one
that are attached to the carbonyl carbon & followed by the word
‘ketone’
[pic]
o Dimethyl ketone is always called acetone, and alkyl phenyl
ketones are usually named as the acyl group followed by the
suffix -phenone.
[pic]
[pic]
STEP 5: Chemical Structure of Ketones (15 minutes).
Ar stands for an aryl group, represent ketones.
[pic]
COH, which might be confused with an alcohol.
comes after the atom it is attached to (usually C, N, or O).
[pic]
Some simple structures of ketones
[pic]
STEP 6: Chemical Properties of Ketones (15 minutes).
|Activity: Buzzing (5minutes). |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the chemical properties of Ketones? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
divided platinum, palladium and nickel.
atom (i.e., methyl ketones) are oxidised by sodium hypohalite to sodium
salts of carboxylic acids with one carbon atom less than that of the
ketones.
conditions with different reducing agents.
oxidising agents such as conc. HNO3, KMnO4/H2SO4, K2Cr2O7/H2SO4 etc.
o Oxidation of ketones involves cleavage of bond between carbonyl
carbon and a-carbon on either side of keto group giving a mixture
of carboxylic acids.
STEP 7: Chemical Reactions involving Ketones (35 Minutes)
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions. |
|What are the chemical reactions involving Ketones? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 10 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Most common reaction is nucleophilic addition, addition of a nucleophile
the oxygen atom and the resulting polarization of the carbon-oxygen
double bond.
leaving it relatively unhindered and open to attack from either face of
the double bond.
hybridization from sp2 to sp3.
alkoxide anion, which protonates to give the product of nucleophilic
addition.
[pic]
o The Witting reaction converts the carbonyl group of a ketone or an
o A phosphorus-stabilized carbanion is added to a ketone or aldehyde.
o The product is not an alcohol, however, because the intermediate
undergoes elimination to an alkene.
[pic]
o The phosphorus-stabilized carbanion is an ylide (pronounced "ill -id")-
a molecule that bears no overall charge but has a negatively charged
carbon atom bonded to a positively charged heteroatom.
o Because of its carbanion character, the ylide carbon atom is strongly
nucleophilic.
o It attacks a carbonyl group to give a charge-separated intermediate
called a betaine
[pic]
Example 2.
[pic]
o In an aqueous solution, a ketone or an aldehyde is in equilibrium with
its hydrate, a geminal diol.
o With most ketones, the equilibrium favors the unhydrated keto form
of the carbonyl
[pic]
[pic]
o Hydration occurs through the nucleophilic addition mechanism, with
water (in acid) or hydroxide ion (in base) serving as the
nucleophile.
o The electrophilic carbonyl group of a ketone is stabilized by its
two electron-donating alkyl groups
o Weak nucleophiles, such as water and alcohols, can add to activated
carbonyl groups under acidic conditions.
o A carbonyl group is a weak base, and it can become protonated in
an acidic solution.
o A carbonyl group that is protonated (or bonded to some other
electrophile) is strongly electrophilic, inviting attack by a weak
nucleophile.
[pic]
o The following reaction is the acid-catalyzed nucleophilic addition
of water across the carbonyl group of acetones.
[pic]
[pic]
o The base-catalyzed addition to a carbonyl group results from
nucleophilic attack of a strong nucleophile followed by
protonation.
[pic]
STEP 8: Key Points (05 minutes)
bonded to the carbonyl carbon atom.
and a-carbon on either side of keto group giving a mixture of carboxylic
acids.
reactions.
STEP 9: Evaluation (05 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R, (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 18: Aromatic Organic Compounds of Pharmaceutical Importance .
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Aromatic Organic |
| | |Presentation |Compounds |
|3 |15 minutes | |Aromatic organic compounds and their|
| | |Buzzing |Isomers |
| | |Presentation | |
|4 |15 minutes |Presentation |Nomenclature of Aromatic Organic |
| | | |Compounds |
|5 |15 minutes |Presentation |Chemical Structure of Aromatic |
| | | |Organic Compounds |
|6 |10 minutes |Presentation |Chemical Properties of Aromatic |
| | |Brainstorming |Organic Compounds |
|7 |40 minutes |Group |Chemical Reactions and Uses of |
| | |discussion |Aromatic Organic Compounds |
| | |Presentation | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Aromatic Organic Compounds (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Aromatic Organic Compounds? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
Aromatic hydrocarbons are those compounds that have molecular structures
based on that of benzene C6H6 & resemble benzene in chemical behaviour.
[pic]
The Kekule Benzene structure
[pic]
STEP 3: Aromatic Organic Compounds and their Isomers (15 minutes).
|Activity: Buzzing (10minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes |
| |
|What are the isomers of Aromatic organic compounds? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content in the table 1 below |
depending upon the position of one substituent with respect to the other.
substituents is 1,2−. Similarly, meta (m−) and para (p−) are used to
indicate the relative positions 1,3− and 1,4− respectively.
ortho, meta and para isomers of dimethylbenzene (xylene)
[pic]
STEP 4: Nomenclature of Aromatic Organic Compounds (15 minutes)
group to the word benzene.
name of the attached substituent group.
[pic]
[pic]
[pic]
STEP 5: Chemical Structure of Aromatic Organic Compounds (15 minutes)
participant in a bond, resulting in delocalized electron density on both
sides of the ring.
boat or table structures typical of cycloalkanes.
Structure of benzene: resonance theory
difference between the structures is in the position of electrons.”
[pic]
[pic]
must be indicated. The three possible isomers of di-substituted benzene
are differentiated by use of the names;
o ortho-(o) at carbon 1 & 2,
o meta-(m) at carbon 1 & 3
o para-(p) at carbon 1 &4
[pic]
[pic]
[pic]
groups are named successively, and the name is ended with –benzene:
[pic]
[pic]
[pic]
STEP 6: Chemical Properties of Aromatic Organic Compounds (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are chemical properties of Aromatic Organic Compounds? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
Petroleum and coal.
o Poly-aromatic hydrocarbons are defined as aromatic compounds with
more than one benzene.
o When they include in atmospheric pollution then it is known as
carcinogenic in nature.
aromatic substitution.
alkenes and alkynes.
o They tend to give addition reactions due to this unsaturation.
reactions aromatic hydrocarbons are stable.
o The carbon ring acts as a nucleophile in these reactions and to
form a substituted product an electrophile attack on benzene.
because of this the product also holds its stability and aromatic in
nature.
o On the opposite side in the addition reactions, aromatic compound
may lose their aromaticity, so they do not prefer to give such
reactions.
STEP 7: Chemical Reactions and Uses of Aromatic Organic Compounds (40
minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions. |
|What are the chemical reactions involving Aromatic Organic Compounds? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Reactions with Substituent Effects
[pic]
substitutes it for one hydrogen.
General Mechanism
[pic]
There are five types of EAS reactions
o Halogenation
o Nitration
o Sulfonation
o Friedel-Crafts Alkylation
o Friedel-Crafts Acylation
o Nitration
[pic]
o Sulfonation
electrophile being HSO3+
[pic]
o Halogenation
(generally Cl or Br)
[pic]
o Friedel-Crafts Alkylation
electrophile—a carbocation; the overall reaction remains the same.
rearrangements are always possible.
R-X and AlX3 where X is either Br or Cl
[pic]
o Friedel-Crafts Acylation
[pic]
that otherwise cannot be prepared directly by alkylation through
Clemmensen Reduction.
to a CH2.
[pic]
hydrochloric acid.
via direct FC alkylation), acetalization using propanoyl chloride
can be done, and then reduce the phenyl ketone product which gives
our final product.
[pic]
The Benzene Elimination Addition Mechanism
electron withdrawing groups on the benzene ring.
with strong bases.
[pic]
hydroxide with chlorobenzene.
sodium amide.
[pic]
below reaction:
[pic]
substituted compounds.
a Benzyne.
Addition reactions of benzene
Although substitution is by far the most common reaction type of benzene
and its derivatives, addition reactions can occur if forcing conditions are
employed.
o For example, if benzene is treated with an excess of chlorine under
conditions of heat and pressure, then 6 chlorine atoms will add,
generating 1,2,3,4,5,6-hexachlorocyclohexane.
[pic]
o This is believed to proceed through free radical intermediates, but
the mechanism is not relevant here.
o The addition of hydrogen to benzene occurs at elevated temperatures
and pressures, and requires a catalyst
[pic]
o Intermediate unsaturated compounds like cyclohexene or dienes
cannot be prepared because of the high pressures involved
Reactions of the Side Chains in Benzene Derivatives
o An aromatic ring imparts extra stability to the carbon atoms directly
bonded to it.
o Therefore, when an alkyl benzene is oxidized with permanganate, the
product is the carboxylate salt of di-benzoic acid.
[pic]
o Alkyl benzenes undergo free radical halogenation very easily at the
benzylic position, since the required intermediate radical is a
benzylic radical, and is therefore resonance stabilized
o For example, ethylbenzene reacts with bromine (or NBS) under UV
irradiation to give (1-bromoethyl)benzene and (1,1-
dibromoethyl)benzene.
[pic]
Uses of aromatic hydrocarbons
o For example, for model glues, toluene is used as solvent while
naphthalene is used as mothballs.
intermediate product which has a different synthetic process.
o Trinitrotoluene (TNT) or 2, 4, 6 trinitrotoluene is an important
aromatic compound which is mainly used as explosive along with
the preparation of explosive.
one of the most important components of a photographic developer.
STEP 8: Key Points (05 minutes).
compounds characterized by one or more planar rings of atoms joined
by covalent bonds of two different kinds.
which numerous other aromatic compounds are related.
the hydrogens of benzene are replaced by some other atom or group, as
in toluene (C6H5CH3) and benzoic acid (C6H5CO2H).
aromatic hydrocarbons are named as derivatives of benzene.
addition reactions than those found in typical alkenes.
STEP 9: Evaluation (05 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama Rao Nadendla (2005). Principles of Pharmaceutical Organic Chemistry.
New Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 19: Phenols of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Presentation |Definition of Phenols |
| | |Brainstorming | |
|3 |15 minutes |Presentation |Phenols and their Isomers |
|4 |15 minutes |Presentation |Nomenclature of Phenols |
|5 |15 minutes |Presentation |Chemical Structure of Phenols |
|6 |15 minutes |Presentation |Chemical Properties of Phenols |
| | |Buzzing | |
|7 |35 minutes |Presentation |Chemical Reactions involving Phenols|
| | |Group | |
| | |discussion | |
|8 |05 minutes |Presentation |Key Points |
|9 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Phenols (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Phenols? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
attached to a carbon atom in a benzene ring.
they are not capable of undergoing the same oxidation reactions that
alcohols participate it.
generated by the loss of the hydroxyl proton is resonance-stabilized:
[pic]
[pic]
is found in several lozenges and throat sprays.
and Bakelite.
STEP 3: Phenols and their Isomers (10 minutes).
ortho-Cresol
[pic]
isomers are shown below.
2,6 xylenol
[pic]
deodorizers, and in the manufacture of other compounds (for example, the
BHA and BHT shown below).
isomeric dimethylbenzenes.
other isomers are shown below.
[pic]
manufacture of many other compounds.
STEP 4: Nomenclature of Phenols (15 minutes).
the Greek numerical prefixes such as di, tri, tetra to denote the number
of similar hydroxyl groups attached to the benzene ring.
benzene ring, it is named as benzene1, 2-diol
other function groups with respect to the position where the hydroxyl
group is attached. For example, if a methyl group is attached at fourth
carbon atom with respect to hydroxy group; compound is named as, 4-Methyl
phenol.
[pic]
the hydroxyl group, words like ortho (when the functional group is
attached to the adjacent carbon atom), para (when the functional group is
attached to the third carbon atom from the hydroxyl group), meta (when
the functional group is attached to the second carbon atom from the
hydroxyl group) are also used for the nomenclature of phenols.
[pic]
priority; the –OH group is then used as a modifying prefix:
STEP 5: Chemical Structure of Phenols (15 minutes).
[pic]
ring and one of the lone pairs on the oxygen atom.
the -OH group.
electron system
[pic]
Giving a structure rather like this
[pic]
electron density around the ring. That makes the ring much more reactive
than it is in benzene itself. That is explored in another page in this
phenol section.
is in alcohols. That will also be explored elsewhere in this section.
STEP 6: Chemical Properties of Phenols (15 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the chemical properties of Phenols? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content below |
Acidity:
acidic than carboxylic acids (pKa»5).
to electron delocalisation onto the ring as shown below:
[pic]
alcohols and/or carboxylic acids.
o Mixing an ether solution, of phenol and alcohol or phenol and
carboxylic acid, with dilute base (sodium hydroxide and sodium
bicarbonate, respectively), results in the stronger acid being
converted to its alkali salt, this is then extracted to the aqueous
phase and can be separated from the organic phase.
under basic conditions as the phenolate ion is a better nucleophile.
Substituent Effects on Acidity
can dramatically influence the acidity of the phenol due to resonance and
/ or inductive effects.
substituents decrease the acidity. The resonance stabilisation of o-
nitrophenol is shown below:
[pic]
|Compound | | |Compound | |
| |pKa | | |pKa |
|Phenol | | | | |
| |10.0| | | |
|o-Methoxyphenol | | |p-Methoxyphenol | |
| |10.0| | |10.2|
|o-Methylphenol | | |p-Methylphenol | |
| |10.3| | |10.3|
|o-Chlorophenol | | |p-Chlorophenol | |
| |8.6 | | |9.4 |
|o-Nitrophenol | | |p-Nitrophenol | |
| |7.2 | | |7.2 |
|m-Nitrophenol | | | | |
| |8.4 | | | |
Reactivity
|[pic] |The image to the left shows the |
|[pic] |electrostatic potential for phenol. |
| |The redder an area is, the higher the |
| |electron density and the bluer an area is,|
| |the lower the electron density. |
| |The hydroxyl O atom is a region of high |
| |electron density (red) due to the lone |
| |pairs. |
| |The hydroxyl O atom can function as a |
| |nucleophile or Lewis base. |
| |There is low electron density (blue) on H |
| |atom of the hydroxyl group, i.e. H+ |
| |character, therefore phenols are acidic |
| |(pKa ~ 10) |
| |Due to conjugation with the ring, phenols |
| |are more acidic than alcohols (pKa ~ 16). |
| |Removal of the proton generates a |
| |phenolate ion. |
| |Note the increased electron density on the|
| |oxygen compared to the phenol |
STEP 7: Chemical Reactions involving Phenols (35 minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving Phenols? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 10 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Electrophilic Aromatic Substitution Reactions of Phenols
substitution.
/ para- directing substituent.
position is blocked, then ortho substitution occurs.
those used for benzene itself can be used (see table below for a
comparison).
problems occur with anilines).
[pic]
Summary
|Reaction |Phenol |Benzene |
|Nitration |dil. HNO3 in H2O or |HNO3 / H2SO4 |
| |CH3CO2H | |
|Sulfonation |conc. H2SO4 |H2SO4 or SO3 / H2SO4 |
|Halogenation |X2 |X2 / Fe or FeX3 |
|Alkylation |ROH / H+ or RCl / AlCl3 |RCl / AlCl3 |
|Acylation |RCOCl / AlCl3 |RCOCl / AlCl3 |
|Nitrosation |aq. NaNO2 / H+ | |
o Phenols are examples of bidentate nucleophiles, meaning that they can
react at two positions:
Friedel-Crafts reaction or,
esterification
o Reagents:
|C-acylation: acylating agent (acyl chloride or anhydride) and |
|AlCl3 |
|O-acylation: acylating agent (acyl chloride or anhydride) |
o The product of C-acylation is more stable and predominates under
conditions of thermodynamic control (i.e. when AlCl3 is present).
o The product of O-acylation forms faster and predominates under
conditions of kinetic control.
o O-acylation can be promoted by either:
increasing its' electrophilicity or
its' nucleophilicity.
o It is also known that aryl esters readily rearrange to aryl ketones
in the presence of AlCl3, a reaction known as the Fries
rearrangement:
[pic]
[pic]
o Heating the nucleophilic phenolate salt with carbon dioxide under high
pressure / temperature results in regioselective ortho-substitution.
o This process is also known as the Kolbe-Schmitt synthesis.
o O-hydroxybenzoic acid is more commonly known as salicyclic acid.
[pic]
|MECHANISM FOR CARBOXYLATION OF PHENOLS |
| |[pic] |
|The nucleophilic phenolate (reacting | |
|like an enolate) reacts with the | |
|electrophilic carbon of carbon dioxide | |
|in the ortho position (compare this | |
|with an Aldol reaction) | |
| | |
|The non-aromatic | |
|cyclohexadienonecarboxylate | |
|intermediate tautomerises to the more | |
|stable aromatic enol which is further | |
|stabilised by an intramolecular | |
|hydrogen bond. An acidic work-up will | |
|generate the carboxylic acid. | |
o In general, phenols are more easily oxidized than simple alcohols.
o Oxidation can be achieved by reaction with silver oxide (Ag2O) or
chromic acid (Na2Cr2O7), or other oxidizing agents.
o Particularly important are the oxidation of 1,2- and 1,4-benzenediol
(pyrocatechol and hydroquinone, respectively) and their derivatives
(see examples below):
[pic] [pic]
o These types of systems are important in biological redox-systems such
as coenzyme Q and vitamin K.
o Here's a closer look at the two one electron transfers that are
believed to take place when hydroquinone is oxidized to benzoquinone.
|[pic] |Loss of a proton and|
| |an electron |
| |generates a phenoxy |
| |radical |
|[pic] |Loss of a second |
| |proton and a second |
| |electron completes |
| |the oxidation. |
STEP 8: Key Points (05 minutes)
consisting of an OH group directly connected to a benzene ring.
acidic than carboxylic acids (pKa»5).
substitution.
STEP 9: Evaluation (05 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 20: Aryl Halides of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Aryl Halides |
| | |Presentation | |
|3 |15 minutes |Presentation |Nomenclature of Aryl Halides |
|4 |15 minutes |Presentation |Chemical Structure of Aryl Halides |
|5 |20 minutes |Buzzing |Chemical Properties of Aryl Halides |
| | |Presentation | |
|6 |45 minutes |Group |Chemical Reactions involving Aryl |
| | |discussion |Halides |
| | |Presentation | |
|7 |05 minutes |Presentation |Key Points |
|8 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Aryl Halides (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Phenols? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
Aryl halides are the compounds that contain halogen atom directly attached
to the benzene ring. They have general formula ArX.
[pic]
Any halogen compound that contains a benzene ring is not classified as aryl
halide. e.g. Benzyl chloride is not an aryl halide but is a substituted
alkyl halide.
STEP 3: Nomenclature of Aryl Halides (15 minutes).
Numbering of the ring begins at the halogen-substituted carbon and
proceeds in the direction of the next substituted carbon that possesses
the lower number.
), meta (m-) or para (p-) depending on the placement of the substituent
from the halogen or the halogen from a higher priority functional group:
1,2-, 1,3- or 1,4- respectively.
| | | |
|1-chloro-2-ethylbenze|1-chloro-3-ethylbenze|1-chloro-4-ethylbenze|
|ne |ne |ne |
|or |or |or |
|o-ethylchlorobenzene |m-ethylchlorobenzene |p-ethylchlorobenzene |
STEP 4: Chemical Structure of Aryl Halides (15 minutes).
directly to a benzene ring.
o From a structural standpoint, one of the more important things to
realize is the trend in bond lengths of the four aryl halides.
is smaller than chlorine, which is smaller than bromine, etc.) it's
probably not surprising that in terms of bond length, the observation is
as follows:
|[pic] |
|Bond lengths (given in picometers) of the four |
|aryl halides |
of measurement used because we are talking about chemical bonds on a
microscopic scale.
the bond lengths get longer and longer.
elongate to make room for the larger atom that's bonded to the benzene
ring.
STEP 5: Chemical Properties of Aryl Halides (20 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the chemical properties of Aryl Halides? |
| |
|ALLOW pairs to respond on the question |
| |
|WRITE their response on the flip chart/board |
| |
|CLARIFY and SUMMARIZE by using the content below |
Reactivity of Aryl halides
while in case of haloarene, the carbon atom attached to halogen is sp2-
hybridised.
[pic]
more electronegative and can hold the electron pair of C—X bond more
tightly than sp3 -hybridized carbon in haloalkane with less s-
character.
in haloarene.
therefore, haloarenes are less reactive than haloalkanes towards
nucleophilic substitution reaction.
Nucleophilic substitution reactions, this can be attributed to their
electron release via resonance
[pic]
double bond character to the carbon-chlorine bond.
aryl halides are more stable towards Nucleophilic substitution reactions.
and in aryl halides it is sp2, hybridized, as sp2 hybridized carbon is
more electronegative it does not permit the chlorine atom to get
displaced with the bonded pair of electrons.
Nucleophilic Substitution Reactions of Aryl Halides
Electron withdrawing group is present on the benzene ring.
nucleophilic substitution in aryl halides whereas Electron donating
groups deactivate the ring.
Elimination – Addition Mechanism
substitution takes place in presence of very strong bases, but the
mechanism is entirely different from what we have seen in bimolecular
nucleophilic substitution reactions.
STEP 6: Chemical Reactions involving Aryl Halides (45 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions. |
|What are the chemical reactions involving Aryl Halides? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Preparations of Aryl Halides
|Halogenation of |[pic] |
|arenes | |
|Via Aryl Diazonium |[pic] |
|salts | |
Electrophilic Aromatic Substitution of Aryl Halides
substitution but they are less reactive than benzene.
directing, deactivators meta-directing).
making the intermediate cations less stable than those produced when
benzene undergoes substitution:
[pic]
cationic intermediates derived by ortho or para attack but not by meta
attack. For example, the stabilisation during ortho attack is shown
below:
[pic]
substitution reactions that benzene can (review) including nitration,
sulfonation, further halogenation and Friedel-Crafts alkylation or
acylation reactions.
o Halogenation of Aryl halides
[pic]
o Nitration of Aryl halides
[pic]
o Sulphonation of Aryl halides
[pic]
o Friedel-Crafts reaction for Aryl halides
an aromatic ring with an alkyl halide using a strong Lewis
acid catalyst.
group attaches at the former site of the chloride ion.
[pic]
Addition-Elimination Mechanism
in nitro-substituted aryl halides is shown by example below:
[pic]
carbon forming an anionic intermediate.
the presence of a strong electron withdrawing group (esp. NO2) ortho or
para to the site of substitution, which stabilize the cyclohexadienyl
anion through resonance.
[pic]
simple nucleophilic substitution)
electrons which increases the rate of formation of the cyclohexadienyl
anion.
[pic]
Elimination-Addition Mechanism:
withdrawing groups:
[pic]
[pic]
o the same carbon that bore the leaving group (see addition mechanism
above) or on an adjacent carbon (see addition mechanism below)
[pic]
[pic]
Aryl Grignards
with magnesium metal
[pic]
other than via Friedel-Crafts alkylation or acylation reactions.
Reaction of Haloarenes With Metals
o The Wurtz–Fittig reaction is the chemical reaction of aryl halides
with alkyl halides and sodium metal in the presence of dry ether to
give substituted aromatic compounds
[pic]
o Fittig reaction is a chemical reaction of two Aryl halide and
sodium metal in presence of dry ether to give biphenyl as the
product.
[pic]
STEP 7: Key Points (05 minutes).
attached to the benzene ring.
Electron withdrawing group is present on the benzene ring
presence of a strong electron withdrawing group (esp. NO2) ortho or
para to the site of substitution, which stabilize the cyclohexadienyl
anion through resonance
STEP 8: Evaluation (05 minutes).
of Aryl Halides
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 21: Amines of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Amines |
| | |Presentation | |
|3 |15 minutes |Presentation |Nomenclature of Amines |
|4 |15 minutes |Presentation |Chemical Structure of Amines |
|5 |20 minutes |Buzzing |Chemical Properties of Amines |
| | |Presentation | |
|6 |45 minutes |Group |Chemical Reactions involving Amines |
| | |discussion | |
| | |Presentation | |
|7 |05 minutes |Presentation |Key Points |
|8 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Amines (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Amines? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
aryl groups bonded to the nitrogen atom.
nucleophilic.
neurotransmission, and defense against predators.
Examples of some biologically active amines
[pic]
[pic]
[pic]
[pic]
[pic]
STEP 3: Nomenclature of Amines (15 minutes).
name.
the position of the amino group along the chain.
N- is used for each substituent on nitrogen.
Examples
[pic]
Common Names
bonded to nitrogen, followed by the suffix –amine
identical substituents
Examples
[pic]
[pic]
called the amino group.
other symbol indicating its position on the ring or carbon chain.
Examples
[pic]
[pic]
as derivatives of aniline.
[pic]
[pic]
Heterocyclic amines
Examples
[pic]
STEP 4: Chemical Structure of Amines (15 minutes).
being the central nitrogen atom.
replaced by alkyl groups to form amines.
|[pic] |
| |Secondary amine | |
| | | |
[pic]
Primary amine
[pic]
Tertiary amine
things like methylamine (CH3-NH2) and ethylamine (CH3-CH2-NH2).
is CH3-NH-CH3 and trimethylamine is CH3-N(CH3)-CH3.
-CH2-CH2-CH3 is called 2-aminopentane.
STEP 5: Chemical Properties of Amines (15 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the chemical properties of Amines? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content below |
the presence of alumina catalyst.
STEP 6: Chemical Reactions involving Amines (45 minutes)
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving Amines? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Due to the unshared electron pair, amines can act as both bases and
nucleophiles.
When reacted with acids, amines donate electrons to form ammonium
salts.
[pic]
o Acid halides react with amines to form substituted amides.
[pic]
o Aldehydes and ketones react with primary amines to give a reaction
product (a carbinolamine) that dehydrates to yield aldimines and
ketimines (Schiff bases).
[pic]
o If you react secondary amines with aldehydes or ketones, enamines
form.
[pic]
o Amines react with sulfonyl chlorides to produce sulfonamides. A
typical example is the reaction of benzene sulfonyl chloride with
aniline.
[pic]
o The Hinsberg reaction is a lab test for the detection of primary,
secondary and tertiary amines.
o In this test, the amine is shaken well with Hinsberg reagent in the
presence of aqueous alkali (either KOH or NaOH).
o A reagent containing an aqueous sodium hydroxide solution
and benzenesulfonyl chloride is added to a substrate.
o A primary amine will form a soluble sulfonamide salt.
the primary amine.
o A secondary amine in the same reaction will directly form an insoluble
sulfonamide.
o A tertiary amine will not react with the sulfonamide but is insoluble.
soluble Ammonium salt.
o In this way the reaction can distinguish between the three types of
amines.
[pic]
o Although you can oxidize all amines, only tertiary amines give easily
isolated products.
o The oxidation of a tertiary amine leads to the formation of an amine
oxide.
[pic]
o Arylamines tend to be easily oxidized, with oxidation occurring on the
amine group as well as in the ring.
o Nitrous acid is unstable and must be prepared in the reaction solution
by mixing sodium nitrite with acid.
o Primary amines react with nitrous acid to yield a diazonium salt,
which is highly unstable and degradates into a carbocation that is
capable of reaction with any nucleophile in solution.
o Therefore, reacting primary amines with nitrous acid leads to a
mixture of alcohol, alkenes, and alkyl halides
[pic]
o Primary aromatic amines form stable diazonium salts at zero degrees.
[pic]
o Secondary aliphatic and aromatic amines form nitrosoamine with nitrous
acid.
[pic]
o Tertiary amines react with nitrous acid to form N‐nitrosoammonium
compounds.
[pic]
Reactions of aromatic diazonium salts
other compounds.
(zero degrees and below), warming these salts initiates decomposition
into highly reactive cations.
variety of compounds. Figure below illustrates the diversity of the
reactions.
[pic]
STEP 7: Key Points (05 minutes)
aryl groups bonded to the nitrogen atom
being the central nitrogen atom
nucleophiles
secondary and tertiary amines
STEP 8: Evaluation (05 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R. (2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 22: Amides of Pharmaceutical Importance.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Amides |
| | |Presentation | |
|3 |15 minutes |Presentation |Nomenclature of Amides |
|4 |15 minutes |Presentation |Chemical Structure of Amides |
|5 |20 minutes |Buzzing |Chemical Properties of Amides |
| | |Presentation | |
|6 |45 minutes |Group |Chemical Reactions involving Amides |
| | |discussion | |
| | |Presentation | |
|7 |05 minutes |Presentation |Key Points |
|8 |05 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Amides (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Amides? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the content below |
the hydroxyl group has been replaced by an amine or ammonia.
carbonyl, thus forming a partial double bond between N and the carbonyl
carbon.
STEP 3: Nomenclature of Amides (15 minutes).
-oic acid or -ic acid endings and adding -amide.
is assumed that the functional group will be on the end of the parent
chain.
[pic] [pic] [pic]
methanamide or formamide (left), ethanamide or acetamide (center) ,
benzamide (right).
[pic]
alkyl group is on the nitrogen atom.
[pic]
Tertiary amides are named in the same way as secondary amides, but with two
N's
[pic]
STEP 4: Chemical Structure of Amides (15 minutes).
carbon atom.
atoms, the compound is a simple amide.
alkyl or aryl groups, the compound is a substituted amide.
[pic]
molecules, where it is called a peptide linkage.
Union of Pure and Applied Chemistry (IUPAC) name of the carboxylic acid
is replaced with the suffix –amide
[pic]
STEP 5: Chemical Properties of Amides (20 minutes).
|Activity: Buzzing (5minutes) |
| |
|ASK students to pair up and buzz on the following question for 5 |
|minutes. |
| |
|What are the chemical properties of Amides? |
| |
|ALLOW pairs to respond on the question. |
| |
|WRITE their response on the flip chart/board. |
| |
|CLARIFY and SUMMARIZE by using the content below |
o Amides are very weak bases.
o This is due to the fact that the lone pair of electrons on nitrogen
atom is involved in resonance with carbonyl group.
o This is due to the contribution of resonating structure II as shown
below;
[pic]
o Thus, electron pair of nitrogen is not easily available for
protonation.
o Consequently, the basic character is considerably decreased.
o However, under suitable conditions amides can also exhibit a feeble
acidic character.
o In accordance with resonating structure I already shown, it is evident
that nitrogen atom of amide molecule has a lone pair of electrons.
o Therefore, it can act as a base.
o For example, acetamide (as base) reacts with hydrochloric acid (an
acid) to form a salt.
o CH3 CONH2 + HCl à CH3 CONH2 HCl
o In accordance with resonating structure II shown earlier, it is clear
that the development of positive character on nitrogen atom
facilitates the release of proton.
o Thus, amide can act as acid.
o For example, acetamide (as acid) reacts with mercuric oxide (a base)
to form mercury salt and water.
o 2CH3 COHN2 + HgO → (CH3 CONH)2 Hg + H2O
o On boiling with dilute acid or alkali, amides rapidly undergo
hydrolysis.
o For example:
[pic]
STEP 6: Chemical Reactions involving Amides (45 minutes).
|Activity: Small Group Discussion (20 minutes). |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions. |
|What are the chemical reactions involving Amides? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
o Amides are dehydrated by heating a solid mixture of the amide and
phosphorus(V) oxide, P4O10.
o Water is removed from the amide group to leave a nitrile group, -CN.
o The liquid nitrile is collected by simple distillation.
o For example, with ethanamide, the product is ethanenitrile.
[pic]
o The Hofmann degradation is a reaction between an amide and a mixture
of bromine and sodium hydroxide solution.
o The net effect of the reaction is a loss of the -CO- part of the amide
group.
o The product is primary amine with one less carbon atom than the
original amide.
o [pic]
o If ethanamide is used, the product will be methylamine.
o CH3CONH2+Br2+4NaOH→CH3NH2+Na2CO3+2NaBr+2H2O
o The Hofmann degradation is used as a way of cutting a single carbon
atom out of a chain.
o Amides can be reduced to primary amines by reaction with lithium
tetrahydridoaluminate, LiAlH4, in dry ether (ethoxyethane) at room
temperature.
o The initial reaction is followed by treatment with dilute acid, such
as dilute sulphuric or hydrochloric acid.
o CH3CONH2+4[H]→CH3CH2NH2+H2O
o Amides react with nitrous acid to give carboxylic acids. and nitrogen
gas.
o Nitrous acid required is prepared in situ by reaction of NaNO2 and
HCI.
[pic]
STEP 7: Key Points (05 minutes).
the hydroxyl group has been replaced by an amine or ammonia
hydrolysis and dehydration reactions
presence of alkali to form a primary amine carrying one carbon atom less
than the parent amide.
STEP 8: Evaluation (05 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R. (2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 23: Introduction to Heterocyclic Compounds.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Heterocyclic Compounds|
| | |Presentation | |
|3 |25 minutes |Presentation |Classification of Heterocyclic |
| | | |Compounds |
|4 |30 minutes |Presentation |Nomenclature of Heterocyclic |
| | | |Compounds |
|5 |30 minutes |Presentation |Chemical Structure of Heterocyclic |
| | | |Compounds |
|6 |10 minutes |Presentation |Key Points |
|7 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Heterocyclic Compounds (10minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Heterocyclic compounds? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the content below |
organic chemical compounds characterized by the fact that some or all of
the atoms in their molecules are joined in rings containing at least one
atom of an element other than carbon (C).
indicates that at least one ring structure is present in such a compound,
while the prefix hetero- (from Greek heteros, meaning “other” or
“different”) refers to the noncarbon atoms, or heteroatoms, in the ring.
to life. For example, nucleic acids, pigments, vitamins, and antibiotics.
STEP 3: Classification of Heterocyclic Compounds (25 minutes).
heterocyclic rings of a given size has many common features.
o Three-membered rings
o four-membered rings
o Five-membered rings
o six-membered rings
o Seven-membered rings
o The three-membered ring heterocycles containing single atoms of
nitrogen, oxygen, and sulfur—aziridine, oxirane (or ethylene oxide),
and thiirane, respectively—and their derivatives can all be prepared
by nucleophilic reactions, of the type shown.
o Thus, aziridine is formed by heating β-aminoethyl hydrogen sulfate
with a base (in this case Y is −OSO3H).
[pic]
o Azetidine, oxetane, and thietane—four-membered rings containing,
respectively, one nitrogen, oxygen, or sulfur atom—are prepared by
nucleophilic displacement reactions similar to those used to prepare
the corresponding three-membered rings.
[pic]
o The parent aromatic compounds of this family—pyrrole, furan, and
thiophene—have the structures shown.
[pic]
o The saturated derivatives are called pyrrolidine, tetrahydrofuran, and
thiophane, respectively.
o The bicyclic compounds made of a pyrrole, furan, or thiophene ring
fused to a benzene ring are called indole (or isoindole), benzofuran,
and benzothiophene, respectively.
o The nomenclature used for the various monocyclic nitrogen-containing
six-membered ring compounds is given below.
o Positions on the ring are shown for pyridine, Arabic numerals being
preferred to Greek letters, although both systems are used.
o The pyridones are aromatic compounds because of contributions to the
resonance hybrid from charged resonance forms such as that shown for 4-
pyridone.
[pic]
STEP 4: Nomenclature of Heterocyclic Compounds (30 minutes).
received trivial names which are still preferred.
with the common (trivial) name in bold and a systematic name based on the
Hantzsch-Widman system given beneath it in blue.
[pic]
elemental prefix for the heteroatom followed by the appropriate
carbocyclic name.
priority order increasing from right to left.
1-oxa-4-azacyclohexane.
|Element|oxygen|sulfu|seleniu|nitroge|phosphorou|silic|boron|
| | |r |m |n |s |on | |
|Valence|II |II |II |III |III |IV |III |
|Prefix |Oxa |Thia |Selena |Aza |Phospha |Sila |Bora |
| | | | | | | | |
heterocyclic compounds that is not dependent on prior carbocyclic names.
final "a"), followed by a suffix designating ring size and saturation.
root (blue) and an ending intended to designate the degree of
unsaturation in the ring.
applies only to completely saturated ring systems, and the unsaturated
suffix applies to rings incorporating the maximum number of non-cumulated
double bonds.
prefix, such as "dihydro"or "tetrahydro".
|Ring Size |3 |4 |5 |6 |7 |8 |9 |10 |
|Suffix | | | | | | | | |
| |iren|ete |ole |ine |epine|ocine|onine|ecine|
|Unsaturated|e |etan|olan|inane|epane|ocane|onane|ecane|
| Saturated|iran|e |e | | | | | |
| |e | | | | | | | |
several exceptions and modifications have been incorporated to
accommodate conflicts with prior usage.
o The terminal "e" in the suffix is optional though recommended.
o Saturated 3, 4 & 5-membered nitrogen heterocycles should use
respectively the traditional "iridine", "etidine" & "olidine"
suffix.
o Unsaturated nitrogen 3-membered heterocycles may use the
traditional "irine" suffix.
o Consistent use of "etine" and "oline" as a suffix for 4 & 5-
membered unsaturated heterocycles is prevented by their former use
for similar sized nitrogen heterocycles.
o Established use of oxine, azine and silane for other compounds or
functions prohibits their use for pyran, pyridine and
silacyclohexane respectively.
previous diagram and that shown below.
its location may be designated by a "#H " prefix to avoid ambiguity, as
in pyran and pyrrole above and several examples below.
atom is #1 and continues in the direction that gives the next priority
atom the lowest number.
[pic]
compounds incorporating one or more heterocyclic rings are well known.
nomenclature.
which designates the edge of the heterocyclic ring involved in the
fusion, as shown by the pyridine ring in the green shaded box.
[pic]
polysaccharides, and the four DNA bases that establish the genetic code.
STEP 5: Chemical Structure of Heterocyclic Compounds (30 minutes).
geometrically strained and thus readily opened; they are also readily
formed.
o Such heterocycles are well-known reactive intermediates.
their sizes also allow the development of aromatic character.
relatively less well investigated.
[pic]
[pic]
[pic]
[pic]
STEP 6: Key Points (10 minutes)
has atoms of at least two different elements as members of its
ring(s).
heterocyclic rings of a given size have many common features.
heterocyclic compounds that is not dependent on prior carbocyclic
names.
their small size, and thus readily opened.
STEP 7: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 24: Chemical Reactions of Heterocyclic Compounds.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |35 minutes |Brainstorming |Chemical Properties of Heterocyclic |
| | |Presentation |Compounds |
|3 |60 minutes |Group |Chemical Reactions involving |
| | |discussion |Heterocyclic Compounds |
| | |Presentation | |
|4 |10 minutes |Presentation |Key Points |
|5 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Chemical Properties of Heterocyclic Compounds (35 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are the chemical properties of heterocyclic compounds? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the table below |
|Chemical Name |Chemical properties |
|2-AMINOPYRIDINE |The substance decomposes on burning |
| |producing toxic gases and vapours |
| |including nitrous oxides |
| |Reacts with strong oxidants causing |
| |fire and explosion hazard |
| |The substance is a strong base that |
| |is soluble in water |
|3,6-DICHLOROPICOLINIC ACID |The substance decomposes on burning |
| |producing toxic and corrosive gases |
| |Reacts with bases forming salts |
| |Solutions of them are corrosive to |
| |aluminum, iron, and tin |
|2-MERCAPTOBENZOTHIAZOLE |On combustion, forms toxic gases |
| |(carbon monoxide and sulphur |
| |compounds) |
| |The substance decomposes on heating |
| |and on burning producing toxic and |
| |irritating fumes (sulphur and |
| |nitrogen oxides) |
| |Reacts with acids with the formation |
| |of highly toxic fumes of sulphur |
| |compounds |
| |Reacts with acids or acid fumes |
| |producing toxic fumes (sulphur |
| |compounds) |
|2-MERCAPTOBENZOTHIAZOLE |On combustion, forms toxic gases: |
|DISULPHIDE |carbon, sulphur and nitrogen oxides |
| |Reacts with strong oxidants and acids|
| |The substance decomposes on heating |
|2-METHYLPYRIDINE |producing toxic fumes (nitrogen |
| |oxides) |
| |Reacts with oxidants and strong acids|
| | |
| |Attacks copper and its alloys |
|3-METHYLPYRIDINE |The substance decomposes on heating |
| |producing toxic fumes (nitrogen |
| |oxides) |
| |Reacts with oxidants and strong acids|
|4-METHYLPYRIDINE |The substance decomposes on heating |
| |producing toxic fumes (nitrogen |
| |oxides) |
| |Reacts with oxidants and strong acids|
|1-METHYL-2-PYRROLIDONE |The substance decomposes on heating |
| |above 315 °C producing toxic fumes |
| |Reacts with strong acids |
| |Attacks aluminium |
|MORPHOLINE |The substance decomposes on heating |
| |producing toxic fumes (nitrogen |
| |oxides) |
| |The substance is a weak base |
| |Reacts with strong oxidants causing |
| |fire hazard |
| |Attacks copper and its compounds |
|PHENOTHIAZINE |The substance decomposes on heating |
| |and on burning producing toxic and |
| |irritating fumes including nitrogen |
| |oxides and sulphur oxides |
|PHENYLENEPYRENE |Upon heating, toxic fumes are formed |
|PIPERIDINE |The substance decomposes on heating |
| |and on burning producing toxic gases |
| |such as nitrogen oxides |
| |The substance is a medium strong base|
| | |
| |Reacts violently with oxidants |
|PYRIDINE |On combustion, forms toxic fumes |
| |(amines) |
| |The substance decomposes on heating |
| |or on burning producing toxic fumes |
| |(nitrogen oxides and hydrogen |
| |cyanide) |
| |Reacts violently with strong oxidants|
| |and strong acids |
|2-PYRROLIDINONE |The substance decomposes on heating |
| |producing toxic fumes |
| |Reacts with strong acids cf |
| |• methylpyrrolidone Attacks aluminium|
|QUINOLINE |The substance decomposes on heating |
| |and on burning producing toxic fumes |
| |of nitrogen oxides |
| |Reacts with strong oxidants and |
| |maleine anhydride |
|TETRAHYDROTHIOPHENE |On combustion, forms toxic fumes |
| |• Reacts violently with strong |
| |oxidants and nitric acid • Attacks |
| |rubber |
|THIOPHENE |The substance decomposes on heating |
| |and on burning producing toxic and |
| |irritating fumes (sulphur oxides) |
| |• Reacts violently with oxidizing |
| |materials, including fuming nitric |
| |acid |
STEP 3: Chemical Reactions involving Heterocyclic Compounds (60 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small groups |
| |
|ASK students to discuss in groups on the following questions |
|What are the chemical reactions involving heterocyclic compounds? |
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 15 minutes |
| |
|ALLOW each group to present for 5 minutes |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Three-Membered Rings
heterocycles. Epoxides are easily prepared by reaction of alkenes with
peracids, usually with good stereospecificity.
more reactive that unstrained ethers.
the ring constitute the most general reaction class.
is interesting due to subsequent conversion of the addition intermediate
into the corresponding thiirane.
o The initial ring opening is stereoelectronically directed in a
trans-diaxial fashion, the intermediate relaxing to the
diequatorial conformer before cyclizing to a 1,3-oxathiolane
intermediate.
o Other examples show similar addition reactions to thiiranes and
aziridines.
influence of substituents on the regioselectivity of addition.
attack on the protonated aziridine (the less substituted carbon is the
site of addition).
o The phenyl substituent in example 3 serves to stabilize the
developing carbocation to such a degree that SN1 selectivity is
realized.
o The reduction of thiiranes to alkenes by reaction with phosphite
esters (example 6) is highly stereospecific and is believed to take
place by an initial bonding of phosphorous to sulfur.
[pic]
Four-Membered Rings
strain.
shown by examples 1, 2 & 3a.
chlorination to form a chlorosulfonium intermediate followed by a ring-
opening chloride ion substitution.
reaction 3b.
acyl exchange, as in 4a, or by alkyl-O rupture by nucleophiles, as in 4b.
ortho-ester.
the enhanced acylating reactivity of this fused ring system.
stabilization by p-π resonance.
leaving the nitrogen with a pyramidal configuration and the carbonyl
function more reactive toward nucleophiles.
[pic]
Five-Membered Rings
The chemical reactivity of the saturated members of this class of
heterocycles: tetrahydrofuran, thiolane and pyrrolidine, resemble that of
acyclic ethers, sulfides, and 2º-amines, and will not be described here.
ketones, and may be hydrolyzed by the action of aqueous acid.
It is the "aromatic" unsaturated compounds, furan, thiophene and pyrrole
that require our attention.
electrons that may combine with the four π-electrons of the double bonds
to produce an annulene having an aromatic sextet of electrons.
following diagram.
its electron pair is delocalized around the ring.
dipole moment compared with the analogous saturated heterocycles, which
all have strong dipoles with the heteroatom at the negative end.
or in the case of pyrrole a large dipole in the opposite direction.
stability, and this is usually demonstrated by relative heats of
hydrogenation or heats of combustion measurements.
stabilized, but to a lesser degree than benzene.
Additional evidence for the aromatic character of pyrrole is found in its
a 2º-amine.
basicity 11.2 and acidity 32.
[pic]
Electrophilic Substitution of Pyridine
sextet, as in pyrrole, pyridinium species produced by N-substitution
retain the aromaticity of pyridine.
stable crystalline solids in the absence of water or other reactive
nucleophiles.
esters and amides. Because of the stability of the pyridinium cation, it
has been used as a moderating component in complexes with a number of
reactive inorganic compounds.
the bottom of the diagram.
addition to alkenes and conversion of alcohols to alkyl fluorides,
pyridinium chlorochromate (PCC) and its related dichromate analog are
versatile oxidation agents and the tribromide salt is a convenient source
of bromine.
conveniently and safely handled as pyridine complexes.
Amine oxide derivatives of 3º-amines and pyridine are readily prepared by
oxidation with peracids or peroxides, as shown by the upper right
equation.
zinc (or other reactive metals) in dilute acid.
[pic]
Other Reactions of Pyridine
nucleophilic substitution reactions more easily than equivalent benzene
derivatives.
chloro substituent by ethoxide anion.
nitrogen's ability to support a negative charge.
halopyridine, but substitution at the 3-position is prohibited by the the
failure to create an intermediate of this kind.
that the leaving anion is hydride (or an equivalent). Hydrogen is often
evolved in the course of these reactions.
Addition of strong nucleophiles to N-oxide derivatives of pyridine
proceed more rapidly than to pyridine itself, as demonstrated by
reactions 4 and 5.
elimination of the –OM substituent on nitrogen.
[pic]
STEP 4: Key Points (10 minutes)
on the class of the compound.
the heterocyclic compound.
STEP 5: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama Rao Nadendla (2005). Principles of Pharmaceutical Organic Chemistry.
New Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 25: Introduction to Structure – Activity Relationship of Drugs.
Total Session Time: 60 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of structure – activity |
| | |Presentation |relationship |
|2 |30 minutes |Group |Importance of structure – activity |
| | |discussion |relationship in pharmacy |
| | |Presentation | |
|4 |05 minutes |Presentation |Key Points |
| 5 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Structure – Activity Relationship (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is structure- activity relationship? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the table below |
Structure Activity Relationship (SAR):
structure to a property, effect, or biological activity associated
with that chemical.
relationships between the chemistry of a particular compound or group
of compounds and their interaction with the body hence activity.
STEP 3: Importance of Structure – Activity Relationship in Pharmacy (30
minutes).
|Activity: Small Group Discussion (15 minutes) |
| |
|DIVIDE students into small groups. |
| |
|ASK students to discuss in groups on the following questions. |
|What is the importance of structure- activity relationship in Pharmacy?|
| |
|[pic]REFER Students to Book |
| |
|ALLOW students to discuss for 10 minutes. |
| |
|ALLOW each group to present for 5 minutes. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
evoking a target biological effect in the organism.
compound (typically a drug) by changing its chemical structure
chemical groups into the biomedical compound and test the modifications
for their biological effects.
STEP 4: Key Points (05 minutes).
the chemical or 3D structure of a molecule and its biological activity.
evoking a target biological effect in the organism.
compound (typically a drug) by changing its chemical structure.
chemical groups into the biomedical compound and test the modifications
for their biological effects.
STEP 5: Evaluation (10 minutes)
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R. (2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 26: Structure – Activity Relationship of Penicillins.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Penicillins |
| | |Presentation | |
|3 |40 minutes |Presentation |Chemical Structure of Penicilins |
|4 |45 minutes |Group |Structure – Activity Relationship of|
| | |discussion |Penicillins |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Penicillins (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are penicillins? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the table below |
inhibiting ell wall synthesis.
penicillins and semisynthetic penicillins.
are mainly active against gram (+) ve bacteria.
STEP 3: Chemical Structure of Penicillins (40 minutes).
Fig. 24.1 General Chemical structure of penicillin
[pic]
G.L Patrick, an introduction to medical chemistry.
consisting of a four membered β-lactam ring fused to a five-membered
thiazolidine ring.
amino acids cysteine and valine. According to biogenesis, antibiotics
can be derived from various natural substances like β-lactam
antibiotics from cysteine and valine amino acids.
[pic]
Penicillin appears to be derived from
cysteine and valine
[pic]
Side chain varies according to carboxylic acids presents in
fermentation medium.
[pic]
that contains three chiral centers.
active forms.
activity, has the stereochemistry of 3S:5R:6R. (According to BP & USP
2S:5R:6R).
[pic]
Penicillin analogues
[pic]
STEP 4: Structure – Activity relationship of Penicillins (45 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question. |
|What is the importance of structure activity relationship of |
|Penicillins? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
A large number of penicillin analogues have been synthesized and studied.
The results of these studies have demonstrated following features are
important for penicillins activity.
side-chain is important.
Very little variation is possible in penicillin nucleus.
Structure activity relationships of penicillin
[pic]
The acid sensitivity of penicillin.
There are three reasons for the acid sensitivity of penicillin.
o The bicyclic system in penicillin consists of a four-membered ring and
a five membered ring.
o As a result, penicillins suffers large angle and torsional strains.
o Acid-catalyzed ring opening relieves these strains by breaking open
the more highlystrained four-memberedβ-lactam ring.
[pic]
[pic]
Ring opening
o The carbonyl group in the β-lactam ring is highly susceptible to
nucleophiles and it does not behave like a normal tertiary amide which
is usually quite resistant to nucleophilic attack.
o A normal tertiary amide is far less susceptible to nucleophiles since
the resonance structures reduce the electrophilic character of the
carbonyl group.
o The β-lactam nitrogen is unable to show such effect.
o To show the similar effect like tertiary amide, penicillin had to
obtain astrained flat structure, which is highly unstable.
o As a result, the lone pair is localized on the nitrogen atom and the
carbonyl group is far more electrophilic than a tertiary amide.
[pic]
o Figure above demonstrates how the neighboring acyl group canactively
participate in a mechanism to open up the lactam ring.
o Thus,penicillin Ghas a self-destruct mechanism built into its
structure.
[pic]
Influence of the acyl side chain on acid sentivity
[pic]
STEP 5: Key Points (10 minutes).
molds of genus Penicillium and also semi-synthetically, having a
bactericidal action on many susceptible Gram positive and Gram-
negative bacteria.
negative cocciand bacilli, some also being effective against certain sp
irochetes.
member of the penicillins which has the molecular formula R-
C9H11N2O4S, where R is the variable side chain that differentiates the
penicillins from one another.
such as ampicillin, improving their spectrum of activity and
bioavailability (amoxicillin), development of beta-lactamase resistant
drugs, (oxacillin, cloxacillin), and broad spectrum penicillins
(Carbenicillin, ureidopenicillins)
STEP 6: Evaluation (10 minutes)
penicillins?
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 27: Structure – Activity Relationship of Cephalosporins.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Cephalosporins |
| | |Presentation | |
|3 |40 minutes |Presentation |Chemical Structure of Cephalosporins|
|4 |45 minutes | Group |Structure – Activity Relationship of|
| | |discussion |Cephalosporins |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Cephalosporins (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Cephalosporins? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the table below |
wall synthesis.
discovered after penicillin, which showed broad spectrum of action
against Staphylococcus aureus, Vibrio cholerae, and B. anthracis, but
moderate antibacterial activity was isolated from the fermentation broth
of a strain of A. chrysogenum
to penicillins, and have the same mode of action, disrupting the
synthesis of the peptidoglycan layer of bacterial cell walls of bacteria,
causing their death.
STEP 3: Chemical Structure of Cephalosporins (40 minutes).
wall synthesis.
Cephalosporium acremonium.
one of the cephalosporins is active against MRSA and enterococci.
Basic structure of cephalosporin is 7-aminocephalosporanic acid
[pic]
Structural classification of cephalosparins
[pic]
[pic]
STEP 4: Structure – Activity relationship of Cephalosporins (45 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question |
|What is the importance of SAR of Cephalosporins? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
Many analogues of Cephalosporin C have been made and the structure-activity
relationship (SAR) conclusions are as follows
These are very close to penicillin and there are only a limited number of
place where modifications can be made. Those places are:
[pic]
Positions which can be varied
Beta-Lactam Ring:
penicillins
2-Carboxyl Group:
X-Substituent:
3- Substituent (R3)
7-Substituent (R7)
Cephalosporin analogues
[pic]
attached at the 3 and/or 7 positions of the 7-ACA.
properties, whereas those at C-7 (R1) alter the antibacterial
spectrum.
resistance and its activity against Gram –ve and/or Gram +ve bacteria
(its spectrum).
activity, the extent of metabolism, and the duration of action.
structure and thus increase stability of the structure.
mimics the carboxylic acid group of alanine when binding the enzyme
active site.
[pic]
STEP 5: Key Points (10 minutes)
from the fungus Acremonium, which was previously known as
"Cephalosporium".
of the cephalosporins is active against MRSA and enterococci. Basic
structure of cephalosporin is 7-aminocephalosporanic acid.
modify its activity includes beta lactam ring, 2-Carboxyl Group, X-
Substituent,3- Substituent (R3) and 7- substituent (R7).
STEP 6: Evaluation (10 minutes)
cephalosporins?
References.
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Service
Session 28: Structure – Activity Relationship of Quinolones.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Quinolones. |
| | |Presentation | |
|3 |40 minutes |Presentation |Chemical Structure of |
| | | |Quinolones. |
|4 |45 minutes | Group |Structure – Activity |
| | |discussion |Relationship of Quinolones. |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Quinolones (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Quinolones? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the table below |
particular activity against gram-negative organisms,
especially Pseudomonas aeruginosa.
specifically targeting DNA gyrase.
o Fluoroquinolones can be classified as;
STEP 3: Chemical Structure of Quinolones (40 minutes).
The following are chemical structure of quinolones; [pic]
STEP 4: Structure – Activity relationship of Quinolones (45 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question |
|What is the importance of SAR of fluoroquinolones? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
[pic]
Structure of quinolone
for positions on the molecule.
however, the most commonly used structure is shown.
Position 1.
hydrophobic interaction with the major grove of DNA.
here, followed by addition of a 2,4-difluorophenyl.
position ((R)-ofloxacin) can presumably lower the number of molecules
capable of binding to the enzyme-DNA pocket, and therefore reduce
potency.
attached to the asymmetric C-3 position on the oxazine ring, thus
connecting positions 1 and 8 with a fused ring.
substituent, the S- isomer exhibits twice the order of magnitude of
activity as the R- isomer, which seems to be determined by the number of
molecules that can be assembled, or stacked, in the enzyme-DNA complex
binding pocket.
of the cyclopropyl substituent, suggesting the difficulty of improving
upon this latter modification.
Position 2.
results in a lower level of microbiological activity.
hydrogen at the R-2 position.
Positions 3 and 4.
binding to cleaved or perturbed DNA, and no useful substitutions have yet
been reported.
essential for antimicrobial activity.
Oxoquinolizines.
the carbon between ring carbons C-4 and C-5.
, 6- becomes 7-, 7- becomes 8-, and 8- becomes position 9.
activity against gram-positive cocci, including methicillin-resistant S.
aureus (MRSA) that are resistant to ciprofloxacin.
Position 5.
have the capacity to alter overall stearic configuration (planar
structure) of the molecule, which is how changes here are thought to
affect activity.
markedly increase in vitro activity against gram-positive bacteria, as
well as enhance potency against Toxoplasma gondii.
positive but not against gram-negative bacteria.
Position 6.
The addition of a fluorine molecule here markedly improved antimicrobial
activity compared to the original quinolone agents and gave rise to the now
widely used and clinically successful fluoroquinolone compounds.
Position 7.
gyrase, or topoisomerase IV. The optimal substituents at this position
have been found to be groups that contain, at a minimum, a 5- or 6-
membered nitrogen heterocycle.
a piperazine generally enhances potency against gram-negative bacteria.
(pyrrolidines and piperazines, respectively) also enhances activity
against gram-positive bacteria.
Position 8.
configuration, similar to position 5.
drug access to the enzyme or DNA binding sites.
vitro activity against gram-positive cocci, even in those bacteria
resistant to older fluoroquinolones.
bacteriostatic and lethal activities against GyrA mutants of both E. coli
and Mycobacterium species. Furthermore, in S. aureus a substitution here
created the most lethal agent for both wild type cells as well as those
strains with a preexisting topoisomerase IV mutation.
core quinolone molecule substantially reduce the likelihood of emergence
of resistant microbial strains that have no preexisting QRDR mutations.
addition at the C-7 position, and has also been shown to markedly reduce
the development of fluoroquinolone resistance in S. aureus.
STEP 5: Key Points (10 minutes).
particular activity against gram-negative organisms,
especially Pseudomonas aeruginosa.
specifically targeting DNA gyrase.
fluoroquinolones that may result in modification of their therapeutic
effect.
STEP 6: Evaluation (10 minutes).
Quinolones?
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama Rao Nadendla (2005). Principles of Pharmaceutical Organic Chemistry.
New Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R. (2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 29: Structure – Activity Relationship of Sulphonamides.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Sulphonamides. |
| | |Presentation | |
|3 |40 minutes |Presentation |Chemical Structure of Sulphonamides.|
|4 |45 minutes | Group |Structure – Activity Relationship of|
| | |discussion |Sulphonamides. |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS.
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Sulphonamides (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What are Sulphonamides? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the table below |
Sulphonamides are antibacterial agents which acts against cell metabolism
(antimetabolites).
Sulfonamides:
attractive features and accounts for much of their persistence in the
market.
STEP 3: Chemical Structure of Sulphonamides (40 minutes).
double bonds to two oxygen atoms, a carbon-based side group, and a
nitrogen atom bonded to the sulphur itself.
nitrogen atom.
sulfone sulphur with two oxygen atoms).
[pic]
General structure of amides and
sulphonamides.
side chain and could be virtually anything.
ring, or some other group.
classified primary, if there is one hydrogen it's secondary, and if no
hydrogens are present on the nitrogen, it's a tertiary sulphonamide
[pic]
Structures of primary, secondary, and tertiary
sulphonamides.
Important Sulfonamide Derivatives
and is commonly used in the treatment of urinary tract infections and
bronchitis.
structure but contains an extra ring system called an oxazole.
[pic]
STEP 4: Structure – Activity Relationship of Sulphonamides (45 minutes).
|Activity: Small Group Discussion (20 minutes). |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question. |
|What is the importance of SAR of sulphonamides? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
The synthesis of a large number of sulphonamide analogues led to the
following conclusions
[pic]
Sulfonamides analogues
regenerate the active compound.
activity.
[pic]
Metabolism of acyl group to regenerate active
compound
required.
replaced by other acidic groups (sulfonic, phosphoric etc.)
(acidic proton is essential for antibacterial activity).
Sulphonamide analogues
aromatic structures, which affects the extent to which the drug binds to
plasma protein.
short acting or long acting.
released into the blood circulation and will be longer lasting.
properties.
Sulfonamide analogues with reduced toxicity
toxicity of some sulfonamides.
the resulting amides have reduced solubility which can lead to toxic
effects.
and can prove fatal if it blocks the kidney tubules
[pic]
Insoluble
replacing the thiazole ring in sulfathiazole with a pyrimidine ring to
give sulfadiazine.
[pic]
sulphonamide NH proton.
blood pH.
ring increases the acidity of the NH proton by stabilizing the resulting
anion.
blood pH.
Treatment of intestinal infections
[pic]
is ionized in the slightly alkaline conditions of the intestine.
the intestine.
sulfathiazole where it is needed.
[pic]
prodrugs, which are poorly absorbed through the gut wall since they
are too hydrophobic
STEP 5: Key Points (10 minutes).
bonds to two oxygen atoms, a carbon-based side group, and a nitrogen atom
bonded to the sulphur itself.
sulfonamides.
STEP 6: Evaluation (10 minutes).
sulphonamides?
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama Rao Nadendla (2005). Principles of Pharmaceutical Organic Chemistry.
New Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Service
Session 30: Structure – Activity Relationship of Aspirin.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Aspirin |
| | |Presentation | |
|3 |40 minutes |Presentation |Chemical Structure of Aspirin |
|4 |45 minutes |Group |Structure – Activity Relationship of|
| | |discussion |Aspirin |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify.
ASK students if they have any questions before continuing.
STEP 2: Definition of Aspirin (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is Aspirin? |
| |
|ALLOW few students to respond |
| |
|WRITE their responses on the flip chart/ board |
| |
|CLARIFY and SUMMARISE by using the table below |
treating fever, pain, and inflammation in the body.
NSAIDs are non-narcotic relievers of mild to moderate pain of many
causes, including
o Headaches,
o Injury,
o Menstrual cramps,
o Arthritis, and other musculoskeletal conditions
o ibuprofen (Motrin),
o indomethacin (Indocin),
o nabumetone (Relafen) and several others.
are released when there is inflammation and that cause pain and fever.
resulting in lower concentrations of prostaglandins.
and the ability of blood to clot.
STEP 3: Chemical Structure of Aspirin (40 minutes).
simple chemical structure.
form the chemical bonding patterns shown below.
[pic]
aspirin, which is prepared by the esterification of the phenolic
hydroxyl group of salicylic acid.
[pic]
recommended drug which are;
o analgesia, leading to pain relief
o anti-inflammatory effect, providing some relief from the swelling
associated with arthritis and minor injuries.
o antipyretic effect, which means it reduces fever.
Synthesis
prepared from phenol by Kolbe synthesis (also known as the Kolbe-
Schmitt reaction) whereby sodium phenoxide is heated with CO2 under
pressure and the reaction mixture is subsequently acidified to yield
salicylic acid.
[pic]
STEP 4: Structure – Activity relationship of Aspirin (45 minutes).
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question |
|What is the importance of SAR of aspirin? |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
“better” aspirin—that is, one possessing fewer GI side effects, but a
greater potency and a longer duration of action yet is inexpensive and an
antipyretic, analgetic, and anti-inflammatory agent that is overall
superior to aspirin—none has yet to be discovered.
The following structure–activity relationships have been established:
[pic]
the positively charged arginine residue at the active site of the
cyclooxygenases (i.e., Arg-120 in COX-1 or Arg-106 in COX-2 isozymes).
heteroaromatic) ring for binding to either the Δ5-double-bond or Δ8-
double-bond binding regions.
associated with the carboxylic acid function.
salicylamide) maintains the analgesic actions of salicylic acid
derivatives but eliminates the anti-inflammatory properties.
affect potency and toxicity.
abolishes this activity.
and toxicity.
STEP 5: Key Points (10 minutes).
treating fever, pain, and inflammation in the body.
interaction with the positively charged arginine residue at the active
site of the cyclooxygenases.
reducing its GI toxicity.
STEP 6: Evaluation (10 minutes).
aspirin?
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Rama Rao Nadendla (2005). Principles of Pharmaceutical Organic Chemistry.
New Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). Calfornia, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 31: Structure – Activity Relationship of Paracetamol.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Paracetamol |
| | |Presentation | |
|3 |40 minutes |Presentation |Chemical Structure of Paracetamol |
|4 |45 minutes |Group |Structure – Activity Relationship of|
| | |discussion |Paracetamol |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes).
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Paracetamol (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is paracetamol? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the table below |
derivative of acetanilide.
common analgesic, but may cause liver, blood cell, and kidney damage.
antipyretic activities.
effects has yet to be fully determined, acetaminophen may inhibit the
nitric oxide (NO) pathway mediated by a variety of neurotransmitter
receptors including N-methyl-D-aspartate (NMDA) and substance P,
resulting in elevation of the pain threshold.
synthesis and release in the central nervous system (CNS) and
prostaglandin-mediated effects on the heat-regulating center in the
anterior hypothalamus.
medication for mild-to-moderate pain and fever.
when taken as an overdose and can cause acute liver injury and death from
acute liver failure.
aminotransferase elevations.
Summary
aches, arthritis, backache, toothaches, colds, and fevers. It relieves
pain in mild arthritis but has no effect on the underlying
inflammation and swelling of the joint.
STEP 3: Chemical Structure of Paracetamol (40 minutes).
its chemical formula us C8H9NO2 and its extended formula is
HOC6H4NHCOCH3.
substituents in position -para (1,4).
a hydroxy group (-OH).
representations used for organic molecules.
[pic]
STEP 4: Structure – Activity relationship of Paracetamol (45 minutes)
|Activity: Small Group Discussion (20 minutes) |
| |
|DIVIDE students into small manageable groups |
| |
|ASK students to discuss on the following question. |
|What is the importance of SAR of paracetamol? |
| |
| |
|ALLOW students to discuss for 15 minutes. |
| |
|ALLOW few groups to present for 5 minutes and the rest to add points |
|not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
hydroxyl group and the nitrogen atom of an amide group in the para
(1,4) pattern.
hydroxyl oxygen, the benzene pi cloud, the nitrogen lone pair, the p
orbital on the carbonyl carbon, and the lone pair on the carbonyl
oxygen is all conjugated.
highly reactive toward electrophilic aromatic substitution.
each other, all positions on the ring are more or less equally
activated.
the nitrogen, while making the hydroxyl acidic through delocalisation
of charge developed on the phenoxide anion.
properties
aminophenols are less toxic than the corresponding aniline derivatives,
although p-aminophenol itself is too toxic for therapeutic purposes.
produces derivatives with greater side effects than with ethyl groups.
Substituent
substituent is metabolically labile (e.g., acetyl).
active or inactive.
acetaminophen. Additionally, both undergo hydrolysis to yield Aniline
derivatives that produce directly, or through their conversion to
hydroxylamine derivatives, significant methemoglobinemia and hemolytic
anemia, which resulted in their removal from the U.S. market.
STEP 5: Key Points (10 minutes)
derivative of acetanilide
STEP 6: Evaluation (10 minutes)
paracetamol?
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
Session 32: Biotransformation of Medicinal Products.
Total Session Time: 120 minutes
Prerequisites
None
Learning Tasks
By the end of this session students are expected to be able to:
Resources Needed:
SESSION OVERVIEW
|Step |Time |Activity/ |Content |
| | |Method | |
|1 |05 minutes |Presentation |Introduction, Learning Tasks |
|2 |10 minutes |Brainstorming |Definition of Biotransformation |
| | |Presentation | |
|3 |60 minutes |Presentation |Metabolism of Organic Compounds |
|4 |25 minutes |Group |Importance of Biotransformation |
| | |discussion | |
| | |Presentation | |
|5 |10 minutes |Presentation |Key Points |
| 6 |10 minutes |Presentation |Evaluation |
SESSION CONTENTS
STEP 1: Presentation of Session Title and Learning Tasks (5 minutes)
READ or ASK students to read the learning tasks and clarify
ASK students if they have any questions before continuing.
STEP 2: Definition of Biotransformation (10 minutes).
|Activity: Brainstorming (5 minutes) |
| |
|Ask students to brainstorm on the following question: |
| |
|What is Biotransformation? |
| |
|ALLOW few students to respond. |
| |
|WRITE their responses on the flip chart/ board. |
| |
|CLARIFY and SUMMARISE by using the table below |
converts non-polar or lipid soluble compounds to polar or lipid
insoluble compounds.
OR
nutrients, amino acids, toxins, and drugs in the body.
not reabsorbed in renal tubules and are excreted.
more water-soluble, to increase the rate of its excretion through the
urine.
STEP 3: Metabolism of Organic Compounds (60 minutes).
involves mainly 2 processes: one of them is drug metabolism.
enzymes
o Microsomal mixed function oxidases (MFOs) system involved.
o Cytochrome P450 enzymes play important role.
o Lungs
o Kidney
o Intestine
o Placenta
o Skin
o Brain
o Testes
o Muscle
o Spleen
o More polar
o Ionizable
o Water soluble to enhance renal excretion
o More active (for pro drugs)
Drug Metabolism in the Liver
PHASE I REACTIONS
water-soluble & less active to be excreted.
enzyme system known as Cytochrome P450.
o Oxidation
o Reduction
o Hydrolytic cleavage
o Dealkylation
o Ring cyclization
o N-carboxylation
o Dimerization
o Transamidation
o Isomerization
o Decarboxylation
[pic]
hydroxylation. i.e. it proceeds via formation of epoxides to yield 1,2-
dihydrodiols
[pic]
o Carbon atoms attached directly to the aromatic ring are hydroxylated.
[pic]
o Carbon atoms adjacent to Olefinic double bonds (are allylic carbon
atoms) also undergo hydroxylation in a manner similar to Benzylic
Carbons.
[pic]
o Several Benzodiazepines contain a carbon atom (C-3) alpha to both
Hydroxylation.
[pic]
o Terminal hydroxylation of methyl group yields primary alcohols which
undergoes further oxidation to aldehydes and then to carboxylic acid.
[pic]
o Cyclohexane (alicyclic) and piperidine (non-aromatic heterocyclic)
rings are commonly found in a number of molecules.
o Such rings are generally hydroxylated at C-3 or C-4 positions.
[pic]
o Biotransformation of C-N, C-0 & C-S system proceed in one of the two
ways:
dealkylation, oxidative deamination & desulfuration.
o N-DEALKYLATION:
generate an intermediate carbinolamine which rearranges by cleavage of
C-N bond to yield the N dealkylated product and the corresponding
carbonyl of the alkyl group.
[pic]
undergoes dealkylation by removal of smaller alkyl group first.
Example:
o Amides e.g. Diazepam
o N-HYDROXYLATION:
is usually displayed by non-basic nitrogen atoms such as amide
Nitrogen.
[pic]
o S-DEALKYLATION:
dealkylation .IT proceed via α-carbon hydroxylation.
product.
[pic]
o Such a desulfuration reaction is commonly observed in thioamides such
as thiopental
[pic]
o Apart from S-dealkylation, thioethers can also undergo S-oxidation
reaction to yield sulfoxides which may be further oxidized to sulfones
several phenothiazines.
o O-Dealkylation:
carbon hydroxylation to form an unstable hemiacetal or hemiketal
intermediate.
a carbonyl moiety.
[pic]
o In case of ethanol, Oxidation to acetaldehyde is reversible and
further oxidation of the latter to acetic acid is very rapid since
Acetaldehyde is highly toxic and should not accumulate in body.
[pic]
o Oxidative Aromatization /Dehydrogenation
o E.g. Metabolic aromatization of drugs is
[pic]
o This reaction is common with halogen containing drugs such as
chloroform.
o Dehalogenation of this drug yields phosgene which may results in
electrophiles capable of covalent binding to tissue.
[pic]
o Bioreductions are also capable of generating polar functional group
such as hydroxy and amino which can undergo further biotransformation
or conjugation.
o Reduction of carbonyls:
[pic]
[pic]
[pic]
o These two reductions are considered together because the groups are
interconvertible by simple addition or loss of a water molecule.
[pic]
o Reduction of nitro groups proceeds via formation of nitro so and
hydroxyl amine intermediates to yield amines.
[pic]
o Reduction of azo compounds yield primary amines via formation of
hydrazo intermediate which undergo cleavage at N-N bond.
[pic]
o It is reduced to active Sulfanilamide.
o REDUCTIVE DEHALOGENATION:
carbon with the H-atom
[pic]
o REDUCTION OF SULFUR CONTAINING FUNCTIONAL GROUPS:
[pic]
o The reaction doesn’t involve change in the state of oxidation of
substrate.
o The reaction results in a large chemical chain in the substrate
brought about by loss of relatively large fragments of the molecule.
o HYDROLYSIS OF ESTERS AND ETHERS:
o Esters on hydrolyisis yield alcohol & carboxylic acid. The reaction is
catalyzed by esterases.
[pic]
o The reactions catalyzed by amides, involves C-N cleavage to yield
carboxylic acid and amine.
[pic]
PHASE II REACTIONS
glucuronic acid, sulfate, or glycine to form water-soluble compounds
They involve the following metabolic processes;
o Glucuronidation by UDP-Glucuronosyltransferase:
(on -OH, -COOH, -NH2, -SH groups)
o Sulfation by Sulfotransferase:
(on -NH2, -SO2NH2, -OH groups)
o Acetylation by acetyltransferase:
(on -NH2, -SO2NH2, -OH groups)
o Methylation
o Amino acid conjugation (on -COOH groups)
o Glutathione conjugation by Glutathione-S-transferase:
(to epoxides or organic halides)
o Fatty acid conjugation (on -OH groups)
o Glycine Conjugation
o Cyanide Conjugation
o Condensation reactions
o Very important Synthetic reactions carried out by Uridine Di Phosphate
Glucuronosyl Transferase.
o Hydroxyl & Carboxylic acid groups are easily combined with Glucuronic
acid
Glucuronide formation occurs in 2 steps: –
1. Synthesis of an activated coenzyme uridine-5’- diphospho – ( – D-
Glucuronic acid (UDPGA) from UDP- glucose (UDPG).
[pic]
2. Transfer of the glucuronyl moiety from UDPGA to the substrate RXH in
presence of enzyme UDP- glucuronyl transferase to form the conjugate.
[pic]
FACTORS AFFECTING OF BIOTRANSFORMATION OF DRUGS:
o Induction of drug metabolizing enzyme.
o Inhibition of drug metabolizing enzyme
o Environmental chemicals.
o Species differences.
o Strain differences.
o Sex differences.
o Pharmacogenetics – genetic differences in metabolic pathways
affecting individual responses to drugs effects.
o Pregnancy.
o Hormonal imbalance.
o Disease state.
STEP 4: Importance of Biotransformation (25 minutes).
|Activity: Small Group Discussion (10 minutes). |
| |
|DIVIDE students into small manageable groups. |
| |
|ASK students to discuss on the following question. |
| |
|What is the importance of biotransformation? |
| |
|ALLOW students to discuss for 8 minutes. |
| |
|ALLOW few groups to present and the rest to add points not mentioned. |
| |
|CLARIFY and SUMMARIZE by using the contents below |
nutrients (food, oxygen, etc.) into substances required for normal
body functions.
not the absorbed drug.
o For Example, phenoxybenzamine, a drug given to relieve hypertension
caused by pheochromocytoma, a kind of tumor, is biotransformed into a
metabolite, which is the active agent.
toxic xenobiotics and body wastes are converted into less harmful
substances and substances that can be excreted from the body.
STEP 5: Key Points (10 minutes).
converts non-polar or lipid soluble compounds to polar or lipid insoluble
compounds.
readily excreted renally.
STEP 6: Evaluation (10 minutes).
References
States: W.B. Saunders Co.
Morrison R.T and Boyd R N (1997). Organic Chemistry (6th Ed.). New Delhi,
India: Prentice Hall of India
Graham Solomon et al (2014). Organic Chemistry (11th Ed.). New Jeysey,
United States: John Willey and Sons.
Nadendla R. R. (2005). Principles of Pharmaceutical Organic Chemistry. New
Delhi, India: MacMillan Publishers
Bruice Y (2013). Organic Chemistry (7th ed.). New York, United States:
Prentice Hall Pearson.
Delgado J. N. Et al (1998). Wilson and Gisvold's Textbook of Organic
Medicinal and Pharmaceutical Chemistry (10th Ed.). California, United
States: Lippincott Williams
Bhassin S.K, Gupta R.(2013). Pharmaceutical organic chemistry (E-book
Kindle edition). New Delhi, India: Elsevier Publishing Services
———————–
| |
PST 05106 Pharmaceutical Organic Chemistry
NTA Level 5 Semester 1
December 2018
Z
N
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