FUNCTIONAL DERIVATIVES

OF CARBOXYLIC ACIDS
ACID DERIVATIVES
 These are compounds in which the –OH of a
carboxyl group has been replaced by:
–Cl (acyl chloride)

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
 –OOCR (anhydride)
 –OR’ (ester)
 –NH2 (amide)

 They all contain the acyl group,

 Whatever structure of the rest of the molecule,

properties of the acyl group remain essentially
the same.
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ACID DERIVATIVES
Acid Derivative Structure, e.g.
Acyl chloride

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(a.k.a. acid chloride)

Anhydride

Ester

Amide
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NUCLEOPHILIC ACYL
SUBSTITUTION
 Much of the chemistry of acid derivatives
involves their conversion
one into another (transacylation),

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
 into the parent acid.

 A more reactive derivative may be used to

prepare a less reactive one by reaction with the
appropriate nucleophile.
 The reverse is not possible.

 All acid derivatives undergo hydrolysis to form

their parent carboxylic acids.
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NUCLEOPHILIC ACYL
SUBSTITUTION
 As in aldehydes and ketones, C=O group provides
a site for nucleophilic attack.
 Unlike aldehydes and ketones, acid derivatives

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undergo substitution instead of addition,
 in which –Cl, –OOCR, –OR’ or –NH2 is replaced by
some other group,
 C=O group is retained in the product.

 To differentiate from alkyl substitution reactions

(e.g. involving alkyl halides), acid derivatives are
said to undergo nucleophilic acyl
substitution. 5
NUCLEOPHILIC ACYL
SUBSTITUTION
 Nucleophilic substitution takes place more
readily at an acyl carbon than at saturated
carbon.

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more reactive than R–Cl

Acyl chloride Alkyl chloride

more reactive than R–NH2

Amide Amine

more reactive than R–OR’ 6

Ester Ether
RELATIVE REACTIVITY

Acyl chloride > Anhydride > Ester > Amide

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 Reactivity depends on base strength of leaving
group.
 The weaker the base, the better the leaving
group, the more reactive the acid derivative.

leaving group
W 7
 RELATIVE REACTIVITY

Relative
Leaving
Acid Base, ease with

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group, Basicity
derivative W:– which W:
W
is lost
Acyl
–Cl Cl– Very weak 1
chloride
Moderately
Anhydride –OOCR RCOO– 2
weak
Ester –OR’ R’O– Strong 3
Very
Amide –NH2 NH2– 4 8
strong
 REACTIONS
Conversion into
Acid Parent Acyl An-
Ester Amide
derivative acid chloride hydride

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Acyl ✔ ✔
✔ – ✖
chloride
Anhydride ✔ ✖ – ✔ ✔
Ester ✔ ✖ ✖ ✔ ✔
Amide ✔ ✖ ✖ ✖ –

✖ – anhydrides are synthesised from ketenes

✔ – transesterification / alcoholysis 9
REACTIONS
 General equation:

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+ HZ + HW
W Z

 Conversion to parent acid: Hydrolysis

 Conversion to ester: Alcoholysis

 Conversion to amide: Ammonolysis

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