1. Nucleophilic Substitution in Acyl Chlorides3

2. General Mechanism for Nucleophilic Acyl Substitution
involves formation and dissociation of a tetrahedral intermediate O ••
• • C R X C R OH X Y O ••
• • C R Y HY
-HX
1 4

3. Preparation of Acyl Chlorides
from carboxylic acids and thionyl chloride
(CH3)2CHCOH O
(CH3)2CHCCl O
SOCl2 +
SO2 +
HCl
heat
(90%)
1 7

4. Reactions of Acyl Chlorides
RCCl O
RCOCR' O
RCOR' O
RCNR'2 O
RCO– O 4

5. Reactions of Acyl Chlorides
Acyl chlorides react with carboxylic acids to give acid anhydrides:
RCCl O
R'COH O
RCOCR' O + +
HCl 4

6. Reactions of Acyl Chlorides
Acyl chlorides react with carboxylic acids to give acid anhydrides:
RCCl O
R'COH O
RCOCR' O + +
HCl C R O Cl
OCR' H
via: 4

7. Example CH3(CH2)5CCl O CH3(CH2)5COH O + pyridine CH3(CH2)5COC(CH2)5CH3
(78-83%) 4

8. Reactions of Acyl Chlorides
Acyl chlorides react with alcohols to give esters:
RCCl O
RCOR' O +
R'OH +
HCl 4

9. Reactions of Acyl Chlorides
Acyl chlorides react with alcohols to give esters:
RCCl O
RCOR' O +
R'OH +
HCl C R O Cl
OR' H
via: 4

10. Example
C6H5CCl O
C6H5COC(CH3)3 O
pyridine +
(CH3)3COH
(80%) 4

11. Reactions of Acyl Chlorides
Acyl chlorides react with ammonia and amines to give amides:
RCCl O
RCNR'2 O +
R'2NH
+ HO– +
H2O +
Cl– 4

12. Reactions of Acyl Chlorides
Acyl chlorides react with ammonia and amines to give amides:
RCCl O
RCNR'2 O +
R'2NH
+ HO– +
H2O C R O Cl
NR'2 H +
Cl–
via: 4

13. Example
C6H5CCl O
C6H5CN O HN
NaOH +
H2O
(87-91%) 4

14. Reactions of Acyl Chlorides
Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base):
RCCl O
RCOH O +
H2O +
HCl
RCCl O
RCO– O +
2HO– +
Cl– +
H2O 4

15. Reactions of Acyl Chlorides
Acyl chlorides react with water to give carboxylic acids (carboxylate ion in base):
RCCl O
RCOH O +
H2O +
HCl C R O Cl OH H
via: 4

16. Example
C6H5CH2CCl O
C6H5CH2COH O +
H2O +
HCl 4

17. Relative rates of hydrolysis (25°C) 1,000 1
Reactivity
Acyl chlorides undergo nucleophilic substitution much faster than alkyl chlorides.
C6H5CCl O
C6H5CH2Cl
Relative rates of hydrolysis (25°C)
1,000 1 4

18. Preparation of Carboxylic Acid Anhydrides
Anhydrides can be prepared from acyl chlorides 3

19. Some anhydrides are industrial chemicals
CH3COCCH3 O
Acetic anhydride
Phthalic anhydride
Maleic anhydride 4

20. From dicarboxylic acids
Cyclic anhydrides with 5- and 6-membered rings can be prepared by dehydration of dicarboxylic acids C H
COH O O H
tetrachloroethane
130°C
+ H2O
(89%) 4

21. Reactions of Carboxylic Acid Anhydrides3

22. Reactions of Anhydrides
RCOCR' O
RCOR' O
RCNR'2 O
RCO– O 4

23. Reactions of Acid Anhydrides
Carboxylic acid anhydrides react with alcohols to give esters:
RCOCR O
RCOR' O
RCOH O +
R'OH +
normally, symmetrical anhydrides are used (both R groups the same)
reaction can be carried out in presence of pyridine (a base) or it can be catalyzed by acids 4

24. Reactions of Acid Anhydrides
Carboxylic acid anhydrides react with alcohols to give esters:
RCOCR O
RCOR' O
RCOH O +
R'OH + C R O
OCR
OR' H
via: 4

25. Example +
CH3COCCH3 O
CH3CHCH2CH3 OH
H2SO4
CH3COCHCH2CH3 O
CH3
(60%) 4

26. Reactions of Acid Anhydrides
Acid anhydrides react with ammonia and amines to give amides:
RCOCR O
RCNR'2 O
RCO– O +
2R'2NH +
R'2NH2 + 4

27. Reactions of Acid Anhydrides
Acid anhydrides react with ammonia and amines to give amides:
RCOCR O
RCNR'2 O
RCO– O +
2R'2NH + C R O
OCR
NR'2 H
R'2NH2 +
via: 4

28. Example
CH3COCCH3 O
H2N
CH(CH3)2 + O
CH3CNH
CH(CH3)2
(98%) 4

29. Reactions of Acid Anhydrides
Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base):
RCOCR O O +
H2O
2RCOH
RCOCR O O +
2HO–
2RCO– +
H2O 4

30. Reactions of Acid Anhydrides
Acid anhydrides react with water to give carboxylic acids (carboxylate ion in base):
RCOCR O O +
H2O
2RCOH C R O
OCR OH H 4

31. Example
COH O O +
H2O 4