1. Nucleophilic Acyl Substitution
Organic Chemistry
4th Edition
Paula Yurkanis Bruice
Chapter 17
Carbonyl Compounds I
Nucleophilic Acyl Substitution
Irene Lee
Case Western Reserve University
Cleveland, OH
©2004, Prentice Hall

2. Carbonyl Compounds with Groups that Can Be Replaced by a Nucleophile

3. Nomenclature of Carboxylic Acids

6. Acyl Halides Acid Anhydrides 3-methylpentanoyl bromide
ethanoyl chloride
acetyl chloride
3-methylpentanoyl bromide
b-methylvalerylbromide
cyclopentanecarbonyl
chloride
Acid Anhydrides

7. Esters

8. Salts of Carboxylic Acids

9. Cyclic Esters Are Known as Lactones

10. Amides

11. Amides with Substituent(s) Bonded to the Nitrogen
N-cyclohexylpropanamide
N-ethyl-N-methylpentanamide
Cyclic Amides Are Known as Lactams a b g d
2-azacyclobutanone
b-propiolactam
2-azacyclohexanone
d-valerolactam
2-azacyclopentanone
g-butyrolactam

12. Nitriles ethanenitrile acetonitrile methylcyanide benzenecarbonitrile
benzonitrile
phenyl cyanide
5-methylhexanenitrile
d-methylcapronitrile
isohexyl cyanide
propenenitrile
acrylonitrile

13. Two major resonance contributors in esters,
carboxylic acids, and amides

14. Carboxylic acids have relatively high boiling points
because
Amides have the
highest boiling
points

15. The reactivity of carbonyl compounds resides in the
polarity of the carbonyl group in a nucleophilic acyl
substitution reaction
Z– will be expelled if it is a much weaker base than Y–
(k–1 >> k2)
Y– will be expelled if it is a much weaker base
(k2 >> k–1)

16. Reaction Coordinate Diagrams for
Nucleophilic Acyl Substitution Reactions
(a) the Nu– is a weaker base
(b) the Nu– is a stronger base
(c) the Nu– and the leaving group have similar basicities

17. A Molecular Orbital Description of How Carbonyl Compounds React

19. All carboxylic acid derivatives react by the same general
mechanism
The tetrahedral intermediate eliminates the weakest base

20. If the nucleophile is neutral …

21. Reactions of Acyl Halides

24. Formation of Amides from Acyl Halides
Tertiary amines cannot form amides

25. Reactions of Acid Anhydrides
Acid anhydrides do not react with sodium chloride or with
sodium bromide

27. Reactions of Esters
a hydrolysis reaction
a transesterification

28. an aminolysis reaction

29. There are no negatively
charged species in the
reaction

30. Excess water will force the equilibrium to the right
Alcohols that have low boiling points can be removed by
distillation as they are formed

31. Acid catalyzes the reaction by …

32. Esters with tertiary alkyl groups undergo hydrolysis much
more rapidly than do others

33. Hydroxide ion increases the rate of formation of the
tetrahedral intermediate
This reaction is not reversible

34. Elucidating the reaction mechanism of nucleophilic acyl
substitution

35. Fats and Oils Are Triesters of Glycerol

36. Nucleophilic Acyl Substitution of Carboxylic Acids

37. Carboxylic acids do not undergo nucleophilic acyl
substitution reactions with amines

38. Hydrolysis of Amides

39. Dehydration of an Amide
Dehydration reagents commonly used are SOCl2, P2O5,
or POCl3

40. An amide cannot be hydrolyzed without a catalyst
An acid catalyst can make a group a better leaving group

41. Hydrolysis of an Imide
The Gabriel Synthesis

42. Nitriles are harder to hydrolyze than amides

43. Designing the Synthesis of Cyclic Compounds
Formation of lactones

44. Preparation of a compound with a ketone group attached
to a benzene ring

45. Preparation of a cyclic ester

46. Activation of Carboxylic Acids

47. The goal is to convert the OH group into a better leaving
group such that the acyl chloride can be prepared

48. The acyl halide can be used to prepare other carboxylic
acid derivatives

49. Activated Carboxylic Acid Derivatives
in Living Organisms

53. Dicarboxylic acids readily lose water when heated if they
can form a cyclic anhydride with a five- or a six-membered ring