NPTEL-PMRF Tutorials
Introductory Organic Chemistry II
Instructor: Prof. Neeraja Dashaputre and Prof. Harinath Chakrapani
IISER Pune
PMRF TA: Khushboo Chaudhary (IIT Bombay)
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Carboxylic Acid and its Derivatives
The product of nucleophilic addition to a carbonyl group is not always a stable
compound
● Leaving groups
Leaving groups are anions such as Cl−, RO−, and RCO2− that can be expelled from
molecules taking their negative charge with them.
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Carboxylic Acid and its Derivatives
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Carboxylic Acid and its Derivatives
Acid chlorides and acid anhydrides react with alcohols to make esters
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Carboxylic Acid and its Derivatives
● Tetrahedral intermediates
Substitutions at trigonal carbonyl groups go through a tetrahedral intermediate and then
on to a trigonal product.
Why are the tetrahedral intermediates unstable?
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Carboxylic Acid and its Derivatives
How do we know that the tetrahedral intermediate exists?
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Carboxylic Acid and its Derivatives
pKa is a useful guide to leaving group ability
● Leaving group ability
The lower the pKa of HX, the better the leaving group of X− in carbonyl substitution
reactions.
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Carboxylic Acid and its Derivatives
Amines react with acyl chlorides to give amides
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Carboxylic Acid and its Derivatives
Using base strength to predict the outcome of substitution reactions of carboxylic
acid derivatives
which group will leave from the
common tetrahedral
intermediate? The answer is
MeO− and not NH2−. From the
stability of the anions, Alkoxides
are reasonably strong bases (pKa
of ROH about 15) so they are not
good leaving groups. But NH2− is
a very unstable anion (pKa of
NH3 about 25) and is a very bad
leaving group.
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Carboxylic Acid and its Derivatives
Factors other than leaving group ability can be important
● Conditions for reaction
If this reaction is to go:
1 X− must be a better leaving group than Y− (otherwise the reverse reaction would take
place).
2 Y− must be a strong enough nucleophile to attack RCOX.
3 RCOX must be a good enough electrophile to react with Y−
.
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Carboxylic Acid and its Derivatives
Strength of nucleophile and leaving group ability are related and pKa is a guide to
both
● Guide to nucleophilicity
In general , the higher the pK a of AH the better A− is as a nucleophile.
good nucleophiles are bad leaving groups. A stable anion is a good leaving group but a
poor nucleophile. Anions of weak acids (HA has high pKa) are bad leaving groups but
good nucleophiles towards the carbonyl group.
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Carboxylic Acid and its Derivatives
Not all carboxylic acid derivatives are equally reactive
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Carboxylic Acid and its Derivatives
Delocalization and the electrophilicity of carbonyl compounds
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Carboxylic Acid and its Derivatives
Carboxylic acids do not undergo substitution reactions under basic conditions
Acid catalysts increase the reactivity of a carbonyl group
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Carboxylic Acid and its Derivatives
Acid catalysts can make bad leaving groups into good ones
● Acid catalysts catalyse substitution reactions of carboxylic acids.
• They make the carbonyl group more electrophilic by protonation at carbonyl oxygen.
• They make the leaving group better by protonation there too.
Ester formation is reversible: how to control an equilibrium
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Carboxylic Acid and its Derivatives
Acid-catalysed ester hydrolysis and transesterification
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Carboxylic Acid and its Derivatives
Amides can be hydrolysed under acidic or basic conditions too
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Carboxylic Acid and its Derivatives
Hydrolysing nitriles: how to make the almond extract, mandelic acid
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Carboxylic Acid and its Derivatives
Acid chlorides can be made from carboxylic acids using SOCl2 or PCl5
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Carboxylic Acid and its Derivatives
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Carboxylic Acid and its Derivatives
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Carboxylic Acid and its Derivatives
Making carboxylic acids from organometallics and carbon dioxide
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Carboxylic Acid and its Derivatives
Oxidation of alcohols
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Carboxylic Acid and its Derivatives
Oxidation of alcohols
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Carboxylic Acid and its Derivatives
Diazomethane makes methyl esters from carboxylic acids
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Carboxylic Acid and its Derivatives
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Alcohols
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Ethers
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Ethers
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Epoxides
Oxidation of alkenes to form epoxides
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Carboxylic Acid and its Derivatives
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Reduction
How to reduce aldehydes and ketones to alcohols
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Reduction
How to reduce esters to alcohols
How to reduce amides to amines
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Reduction
How to reduce carboxylic acids to alcohols
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Reduction
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Reduction
How to reduce esters or amides to aldehydes
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Reduction
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Carboxylic Acid and its Derivatives
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Elimination Reaction
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Elimination Reaction
E1cB eliminations in context
With E1cB, the
regioselectivity is
straightforward: the
location of the double
bond is defined by the
position of (a) the acidic
proton and (b) the
The less sterically hindered (usually E) product is preferred leaving group.
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Elimination Reaction
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Week 4 Assignment
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Question 1
1. The correct order of IR stretching frequency of the C=O in the following molecules is
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Question 2
2. Which of the following has highest pKa ?
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Question 3
3. Predict the correct order of pKa of these coumpounds ?
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Question 4
4. An ether is more volatile than an alcohol having the same molecular formula. This is due to
a. Dipolar character of ethers
b. Alcohols having resonance structures
c. Intermolecular hydrogen bonding in ethers
d. Intermolecular hydrogen bonding in alcohols
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Question 5
5. In Fischer esterification, it is necessary to employ which catalyst among the following?
a. Nitric Acid
b. Hydrichloric Acid
c. Sulphuric Acid
d. All of the above
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Question 6
6. Predict A, B in the following rection sequence
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H E
C M
I I T B
Question 7
7. Predict A, B in the following reaction sequence
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Question 8
8. Predict the product of the following reaction
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Question 9
9. Predict the major product formed in the following reaction
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Question 10
10. Complete the following reaction
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