Chapter 12. Carboxylic Acid Derivatives （ 羧酸衍生物）

1. Chapter 12.Carboxylic Acid Derivatives（羧酸衍生物） Text 1: chapter 21 Test 2: 第13章

2. esters 酯 acid anhydride 酸酐 Acid or base acid halides 酰卤 Carboxylic acids water amides 酰胺 nitriles 腈

3. 12.1 Nomenclature -yl (-oic acid)-ate ×酸×酯 Esters ethyl acetate ethyl ethanoate 乙酸乙酯 vinyl acetate ethenyl ethanoate 乙酸乙烯酯 tert-butyl propanoate 丙酸叔丁酯 isopentyl acetate (used in synthetic banana flavor) 乙酸异戊酯 isopentyl pentanoate (used in synthetic apple flavor) 戊酸异戊酯

4. methyl benzoate 苯甲酸甲酯 methyl p-chlorobenzoate 对-氯苯甲酸甲酯 diethyl malonate 丙二酸二乙酯

5. Cyclic Esters Are Known as Lactones 6-methyl-tetrahydropyran-2-one 5-hydroxyhexanoic acid lactone

6. acid anhydrides 酸酐 --oic acid ——— --oic anhydride acetic anhydride 乙酐 醋酐 succinic anhydride 环丁酐 丁二酸酐 琥珀酸酐 phthalic anhydride 邻苯二甲酸酐 maleic anhydride 环丁烯酐 顺丁烯二酸酐 马来酐

7. acyl chlorides (acid chlorides酰氯) --ic acid ——--yl chloride Acyl group 酰基 acetyl chloride 乙酰氯 benzoyl chloride 苯甲酰氯 propanoyl chloride 丙酰氯

8. --ic acid——--amide amides propanamide 丙酰胺 acetamide 酰胺 benzamide 苯甲酰胺 N-phenylacetamide N-苯基乙酰胺 N,N-dimethylformamide N,N-二甲基甲酰胺 DMF • primary amide 伯酰胺 • secondary amide 仲酰胺 • tertiary amide 叔酰胺

9. Cyclic Amides Are Known as Lactams(内酰胺) d-valerolactam d-戊内酰胺 g-butyrolactam g-丁内酰胺 b-propiolactam b-丙内酰胺

10. Nitriles alkanenitrile ethanenitrile (acetonitrile) 乙腈 butanenitrile 丁腈 propenenitrile 丙烯腈 benzenecarbonitrile (benzonitrile) 苯甲腈 cyclohexanecarbonitrile 环己基甲腈

11. Main groups in order of decreasing priority

12. 12.2 Structure and physical properties bp, mp: (Figure 21-2, p 948) • amide > acid > nitrile > alcohol > ester≈acid chloride ≈alkane • amide: primary > secondary > tertiary

13. Solubility: (Table 21-2) All are soluble in common organic solvents. Some are common organic solvents. • ethyl acetate (EtOAc，乙酸乙酯，bp 77 ℃, 10% ) • acetonitrile (CH3CN， 乙腈，bp 82 ℃，misible with water) • DMF (N,N-dimethylformamide, N,N-二甲基甲酰胺，bp 153 ℃, misible with water,)

14. 12.3 Spectroscopy IR

15. 1735 1770 1800 （cm-1）. 1670 1700 1745 （cm-1）. Ring strain in a lactone or lactam increases the carbonyl streching frequency.

16. 1743

17. 1827 1766

18. 3348 3173 1681

19. 1H NMR Amide: N - H δ: 5 ~8 ppm α - H δ: 2 ~ 3 ppm 13C NMR C=O δ: ~120 ppm δ: ~ 170 ppm

20. 2.05 1.25 4.15 60 14 20 171 1H NMR: 13C NMR:

21. More reactive Less reactive 12.4 Interconversion of acid derivatives by nucleophilic acyl substitution (亲核酰基取代) Reactivity and interconversion of acid derivatives:

22. transesterification 酯交换反应 ammonolysis 酯氨解反应 acid chlorides and anhydrides are used as acylation reagents.(酰化试剂)

23. Mechanism: nucleophilic acyl substitution （亲核酰基取代） addition elimination deprotonation acid-catalyzed mechanism: protonation of carbonyl oxygen, addition, elimination base-catalyzed mechanism： addition, elimination

24. Acid-catalyzed transesterification 酸催化的酯交换反应

25. Base-catalyzed transesterification 碱催化的酯交换反应

26. 12.5 Hydrolysis of acid derivatives Mechanism: nucleophilic acyl substitution Neutral hydrolysis Acid-catalyzed hydrolysis Base-catalyzed hydrolysis

27. 1. Hydrolysis of acid halides and anhydrides • Acid chlorides and anhydrides hydrolyze under neutral condition.

28. 2. Hydrolysis of esters • Acid–catalyzed hydrolysis of esters • is the reverse of the Fisher esterification, • is a equilibrium. • Base–catalyzed hydrolysis of esters • is also called saponification (皂化反应), • avoids the equilibrium of the Fisher esterification.

29. 3. Hydrolysis of amides • Acid–catalyzed hydrolysis of amides: 6 mol/L HCl

30. Base–catalyzed hydrolysis of amides: 40% aqueous NaOH

31. 4. Hydrolysis of nitriles • Acid–catalyzed hydrolysis of nitriles amides Amides can be hydrolyzed to carboxylic acid under stronger conditions.

32. Base–catalyzed hydrolysis of nitriles amides Amides can be hydrolyzed to carboxylic acid under stronger conditions.

33. LiAlH4 LiAlH4 esters acid chlorides carboxylic acid aldehydes 1° alcohols LiAl(OC(CH3)3)H acid chlorides aldehydes 12.6 Reduction of acid derivatives 1. Reduction to alcohols 2. Reduction to aldehydes

34. LiAlH4 amides nitriles amines 3. Reduction to amines

35. 12.7 Reaction of acid derivatives with organometallic reagents esters: acid chlorides: tertiary alcohols 三级醇 nitriles: amides: NO reaction.

36. 1. Synthesis of acyl chlorides 12.8 The chemistry of acyl chlorides

37. 2. Reactions of acyl chlorides Acid chloride is important acylation reagent (酰化试剂)

39. 1. Synthesis of carboxylic acid anhydrides 12.9 The chemistry of acid anhydrides

40. 2. The reactions of acid anhydride

41. Useful anhydrides: acetic anhydrides(醋酐) acetic formic anhydrides （甲乙酐） cyclic anhydrides （环状酸酐）

42. 12.10 The chemistry of esters • 1. Synthesis of esters

43. 2. The reactions of esters

44. 12.11 The chemistry of amides 1. Synthesis of amides

45. 2. The reactions of amides only primary amides Hoffmann rearrangement (霍夫曼重排，霍夫曼降解) only primary amides

46. Polyamides （聚酰胺） Nylon 6 Nylon 6,6

47. 12.12 The chemistry of Nitriles 1. Synthesis of nitriles

48. 2. The reactions of nitriles

49. 12.13 Thioesters (硫酯) 21-15, p 988 thiol 硫醇 thioesters 硫酯 Reactivity as acylating reagents: acid chlorides > acid anhydrides > thioesters > esters Thioesters are common acylating reagents in living systems. 常用来代替在水中不稳定的酰氯和酸酐作酰化试剂。

50. 12.14 Derivatives of carbonic acid（碳酸的衍生物） carbonyl dichloride phosgene 碳酰氯，光气 carbonate esters 碳酸酯 urea 尿素，脲 carbonic acid 碳酸 carbamic acid 氨基甲酸 unstable carbamate，urethane 氨基甲酸酯