NTA Level 5 • Semester 1 • PST05106

Ketones of Pharmaceutical Importance

Pharmaceutical Organic Chemistry • Source Session/Topic 17

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Session 17: Ketones 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:

• Define ketones

• List ketones and their isomers

• Explain nomenclature of ketones

• Draw chemical structure of ketones

• List chemical properties of ketones

• Explain chemical reactions of ketones

Resources Needed:

• Flip charts, marker pens, and masking tape.

• Black/white board and chalk/whiteboard markers.

SESSION OVERVIEW

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 |

• A ketone is a carbonyl compound which has two alkyl (or aryl) groups

bonded to the carbonyl carbon atom.

[pic]

• Aldehydes and Ketones are similar in structure, and they have similar

properties

• There are some differences, particularly in their reactions with

oxidizing agents and with nucleophiles

• In most cases Aldehydes are more reactive than Ketones

STEP 3: Ketones and their Isomers (10 minutes).

Ketones exhibit the following type of isomerism:

• Chain (nuclear) Isomerism.

o Aldehydes with 4 or more carbon atoms and ketones with five or more

carbon atoms show chain isomerism. For example:

[pic]

• Position lsomerism.

o Aromatic aldehydes and higher ketones give position isomers. For

example:

[pic]

• Functional Isomerism.

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).

• The longest chain carrying the –CHO group is considered as the parent

structure.

o Ketones are named by replacing the ‘-e’ of the corresponding

alkane by the ending ‘-one’

o The alkane name becomes alkanone

[pic]

• The position of the attached group is indicated with number. The

carbonyl carbon= 1

o When R is aromatic just the word ketone is added to the

aromatic name

• In open-chain ketones, we number the longest chain that includes the

carbonyl carbon from the end closest to the carbonyl group, and we

indicate the position of the carbonyl group by a number

• In cyclic ketones, the carbonyl carbon atom is assigned the number 1

[pic]

4-hydroxy-4-methyl-2-pentanone

4-hydroxy-4-methylpentan-2-one

• The common names of ketones are derived from the two alkyl groups

that are attached to the carbonyl carbon & followed by the word

‘ketone’

[pic]

• Some ketones have historical common names.

o Dimethyl ketone is always called acetone, and alkyl phenyl

ketones are usually named as the acyl group followed by the

suffix -phenone.

[pic]

STEP 5: Chemical Structure of Ketones (15 minutes).

• In a ketone, two carbon groups are attached to the carbonyl carbon atom.

• The following general formulas, in which R represents an alkyl group and

Ar stands for an aryl group, represent ketones.

[pic]

• In condensed formulas, we use CHO to identify an aldehyde rather than

COH, which might be confused with an alcohol.

• This follows the general rule that in condensed structural formulas H

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 |

• Ketones undergoes addition reactions in presence of catalyst like finely

divided platinum, palladium and nickel.

• Ketones having at least one methyl group linked to the carbonyl carbon

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.

• Ketones can be reduced to a variety of compounds under different

conditions with different reducing agents.

• Ketones are oxidised only under vigorous conditions using powerful

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

and a proton across the C = O double bond.

• The reactivity of the carbonyl group arises from the electronegativity of

the oxygen atom and the resulting polarization of the carbon-oxygen

double bond.

• The electrophilic carbonyl carbon atom is sp2 hybridized and flat,

leaving it relatively unhindered and open to attack from either face of

the double bond.

• As a nucleophile attacks the carbonyl group, the carbon atom changes

hybridization from sp2 to sp3.

• The electrons of the pi bond are forced out to the oxygen atom to form an

alkoxide anion, which protonates to give the product of nucleophilic

addition.

[pic]

• The Witting Reaction

o The Witting reaction converts the carbonyl group of a ketone or an

aldehyde into a new C = C double bond where no bond existed before.

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

▪ Example 1.

[pic]

Example 2.

[pic]

• Hydration of Ketones and Aldehydes

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]

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

• Acid-catalyzed addition of Water and Alcohols

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]

o The base-catalyzed addition to a carbonyl group results from

nucleophilic attack of a strong nucleophile followed by

protonation.

• Base-catalyzed addition of water

[pic]

STEP 8: Key Points (05 minutes)

• A ketone is a carbonyl compound which has two alkyl (or aryl) groups

bonded to the carbonyl carbon atom.

• Ketones shoes chain, position and functional isomerism.

• 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.

• Ketones undergoes oxidation-reduction and nucleophilic addition

reactions.

STEP 9: Evaluation (05 minutes)

• What are ketones?

• List three isomers of ketones

• How are ketones named?

• Draw general chemical structure of ketones.

• What is the Witting Reaction?

References

Ternay, A.L (1976). Contemporary Organic Chemistry. Philadelphia, United

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

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