ORGANIC CHEMISTRY II

CHM 301
( CHAPTER 4)
CARBOXYLIC ACIDS
DERIVATIVES
1

SUBTOPICS
General formula
Nucleophilic acyl substitution
- mechanism
Reactivity of carboxylic acid derivatives
toward nucleophilic acyl substitution reaction

GENERAL FORMULA
Carboxylic acid derivatives:
- groups of compounds which the acyl group (RCO-)
attached to electronegative atom or substituent.
The OH group in carboxylic acid is replaced by
nucleophiles (Cl-, RCOO2-, RO- or NH2-).

O
R

OH

Carboxylic acid

Carboxylic acid derivatives

Four common derivatives:

- acyl chlorides/acid chlorides, acid anhydrides, esters and
amides.

CARBOXYLIC ACID DERIVATIVES

Group replacing
the OH group
of RCOOH
-Cl

Classes of
compound
Acyl
chloride/acid
chlorides

-OR

Ester

General
formula

O
R C Cl

Amide

O C R'

Acid anhydride

ethanoyl chloride

H3C C OC2H5
ethyl ethanoate

O
R C NH2

H3C C CI

O
R C OR'

-NH2

Example

R C O C R'

H3C C NH2
ethanamide

H3C C O C CH3
ethanoic anhydride

NUCLEOPHILIC ACYL SUBSTITUTION

REACTION
O

O
R C Y

Nu-H

R C Nu

H-Y

Carboxylic acids (and their derivatives) more

commonly react by nucleophilic acyl substitution.
- one nucleophile replaces another on the acyl
(C=O) carbon atom.
The nucleophile forms a new bond with
nucleophilic site and the leaving group (Y = Cl-, Br-,
RO- or RNH-) detaches from the molecule.

MECHANISM OF NUCLEOPHILIC ACYL SUBSTITUTION

Occurs through an addition-elimination process in which a nucleophile
forms a bond with the electrophilic carbonyl carbon atom forming a
tetrahedral intermediate.
The tetrahedral intermediate undergoes an elimination to yield the
products.
STEP 1: Nucleophile attacks on carbonyl carbon results in the bond
cleaved.
O

R C Y

R C Y

Nuc-H

Nuc-H

Step 2: The regeneration of the double bond and the leaving group Y
detaches from the molecule.
O
R

O
Y

Nuc-H

Nuc H

 Step 3: H+ ion is removed from the molecule by the leaving group Y.

O
R

O
Nuc

Nuc = OH, OR, OCOR, NH2, NHR

Y = Cl, Br, OCOR, OR, NHR

Nuc

HY

ACID CATALYZED VARIATION MECHANISM

STEP 1: Protonation of carbonyl oxygen to increase the reactivity
which carbonyl carbon becomes more positive for the
nucleophilic attack.
O
R C

OH
Y

HA

R C

STEP 2: The -bond breaks as nucleophile attached to the

molecule.
OH
R C

OH
Y

Nuc H

R C

Nuc H

 STEP 3: As H+ ion bonded to nucleophile detaches, double

bonds regenerates and the leaving group is pushed out from
the molecule.
OH
R C

OH
Y

R C

Nuc

Nuc

STEP 4: The leaving group, Y- removes the H+ ion, reestablishes

carbonyl carbon in the product.

O
R C

H
Nuc

O
Y

R C

Nuc

HY

RELATIVE REACTIVITIES OF CARBOXYLIC ACID

DERIVATIVES TOWARD NUCLEOPHILIC ACYL
SUBSTITUTION REACTION
Example: Hydrolisis of carboxylic acid derivatives.
- Carboxylic acid derivatives, RCOY undergoes hydrolysis with
water.
- During hydrolysis, the C-Y bond is broken.
- The rate of hydrolysis depends on the bond strength of C-Y.
The bond length decreases in the order:
C-Cl (in acyl chlorides) > C-O (in anhydride) > C-O (in ester) > C-N (in amide)
(longest bond)

(shortest bond)

Bond strength is inversely proportional to bond length. The longest

bond is the weakest bond. Bond strength increases in the order:
C-Cl (in acyl chlorides) > C-O (in anhydride) > C-O (in ester) > C-N (in amide)
(weakest bond)

(strongest bond)

 Reactivity carboxylic acid derivatives decreases in the

order:
RCOCl
(most reactive)

>

(RCO)2O > RCOOR >

RCONH2
(least reactive)

Carboxylic acids and esters are very similar in reactivity.

The less reactive acid derivatives can be prepared from
the more reactive ones.
- Example, anhydrides, esters and amides can be prepared
from acid chlorides.
- Esters, anhydrides and acid chlorides cannot be prepared
from amides.

 The order of reactivity can be explained by

considering the basicity of the leaving group.
- strong bases are not good leaving groups.
- the reactivity of derivatives decreases as the
leaving group become more basic.
- example: Cl- is a weakest base and a good
leaving group. Acyl chlorides is the most reactive
compared to other carboxylic acid derivatives.

 The reactivity of the carboxylic acid derivatives

are influences by the substituents:
i) if the substituent is electron donating, the
carbonyl carbon becomes less reactive.

ii) if the substituents is electron withdrawing, the

carbonyl carbon become more reactive.

The End.TQ
Love Organic Chemistry in shaa Allah