Chapter 14. Amines ( 胺）

1. Chapter 14. Amines (胺） Text 1 Chapter 19, p 836-899 Text 2 Chapter 14

2. Nitro-compounds 硝基化合物 1. Structure of nitro group 硝基的结构 N：sp2 硝基化合物是强极性分子；硝基是强吸电子基

3. 2. Physical properties of nitro-compounds 硝基化合物的物理性质 偶极矩: 3.5 ~ 4.0 D， bp: 比相同分子量的酮沸点高（挥发慢）。 CH3NO2 bp 101℃ CH3COCH3 bp 56 ℃ Solubility: 意外地，在水中溶解度低，在水中硝基甲烷的饱和溶液，以重量计少于10%，而丙酮完全溶于水。 香味；毒；多硝基芳香化合物多为黄色固体。 3. Preparation of nitro-compounds 硝基化合物的制备。 卤代烃与亚硝酸盐反应。 芳烃的硝化。

5. 4. Reactions of nitro-compounds 硝基化合物的反应 （1）Reduction of nitro-compounds 还原 Fe、Zn、Sn和盐酸或催化氢化为胺。 若选用适当的还原剂，在不同的条件下可以使硝基苯生成各种不同的还原产物，又在一定的条件下相互转变。

6. （2）acidity of α-H (α-H的酸性） 假酸式 酸式

7. （3）Condensation with carbonyl compounds 与羰基化合物缩合 ----Henry反应 Similar to aldol condensation

8. 3．Aromatic nitro-compounds 芳香族硝基化合物 • Increasing the reactivity of halobenzene for aromatic nucleophilic substitution 使卤苯易发生亲核芳香取代，如水解、氨解、烷基化 • Increasing the acidity of phenol (使酚的酸性增强)

9. Amine (胺) 叶绿素 a

10. Some biologically important amines

11. Alkaloid 生物碱

12. 14.1 structure of amines ammonia 氨 ammonium salts 铵盐 amine 胺 primary amine secondary amine tertiary amine quaternary ammonium salts季铵盐 Which is chiral compound ?

13. enantiomers that can not be resolved 对映体不能拆分开

14. enantiomers that can be resolved 对映体可以能拆分开

15. 14.2 Nomenclature Common name: alkylamine IUPAC name: alkane------- alkanamine methylamine methanamine 甲胺 ethylamine ethanamine 乙胺 propylamine propanamine 丙胺 ethylmethylamine N-methylethanamine 甲乙胺 cyclohexylmethylamine N-methylcyclohexanamine N-甲基环己基胺

16. triethylamine N,N-diethylethanamine 三乙胺 ethylmethylpropylamine N-ethyl-N-methyl-1-propanamine N-甲基-N-乙基-1-丙胺 aniline benzeneamine 苯胺 N,N-dimethylaniline N,N-dimethylbenzenamine N,N-二甲基苯胺 N-methylaniline N-methylbenzenamine N-甲基苯胺

17. Heterocyclic amines 杂环胺 Indole 吲哚(yĭnduŏ) Pyrrole 吡咯 Pyrazole 吡唑 Imidazole 咪唑 Pyridine 吡啶 Pyridazine 哒嗪 Pyrimidine 嘧啶 Quinoline 喹啉 Isoquinoline 异喹啉 Piperidine 哌啶 Pyrrolidine 四氢吡咯

18. ethylenediamine ethane-1,2-diamine 乙二胺 2-aminoethanol 2-氨基乙醇 3-aminopropanoic acid 3-氨基丙酸

19. 14.3 Physical properties and spectroscopy of amines polar substances boiling points: alcohol > amine > alkanes soluble in water, alcohols

20. IR N-H streching vibration C-N Streching vibration

21. IR CH3CH2CH2NH2 3369 3291

22. 1.24 N-H 0.92 2.65 1.45 1H NMR CH3CH2CH2NH2 N-H: 1~4 ppm α-H: 2~3 ppm β-H: 1.1~1.8 ppm

23. 27.1 11.4 44.4 13C NMR α-C: 30~50 ppm β-C: 15~40 ppm CH3CH2CH2NH2

24. 30 59 MS CH3CH2CH2NH2 M+：odd mass number when one nitrogen is present.含一个N原子时质量数为奇数。 α-cleavage (α-裂解) Iminium ion 亚胺离子 Similar to alcohol and ether

25. 14.4 Basicity of amines (胺的碱性） Basicity: H2O < RNH2 < OH- < RO- < C- Effects on amine basicity Substituent effects 取代基效应 Resonance effects 共振效应（共轭效应）: weaken Hybridization effects 杂化效应 N: sp3 > sp2

26. increasing basicity increasing basicity

27. decreasing basicity decreasing basicity In gas phase 气相中 in aqueous solution 水溶液中

28. pKb ~15 2.73 pKb ~8.75 2.88 < < Resonance effects Hybridization effects

29. 14.5 Salts of amines (胺盐）

30. Ag2O, H2O 季铵盐 季铵碱 Q+X- Q+OH-are strong bases---as strong as sodium or potassium hydroxide.

31. Quaternary ammonium salts as Phase-Transfer catalysts (PTC, 相转移催化) Without catalyst, long time is needed to finish this reaction. Addition of Q+X- can speed up the reaction.

32. 14.6 Reactions of amines 1. Reactions with ketones and aldehydes (review) 1°amine 伯胺 imine 亚胺 Shiff base 西佛碱 2°amine 仲胺 enamine 烯胺

33. 2. Acylation 酰化(review)

34. 3. Reactions of amines with sulfonyl chlorides(胺与磺酰氯的反应) 19-14 sulfonamide 磺酰胺 Ar: Ph, p-CH3Ph R3N：no reaction

35. The Hinsberg test (兴斯堡试验） No reaction soluble insoluble

36. The Sulfa Drugs:Sulfanilamide 磺胺

37. Synthesis of sulfa Druges

38. 4. Reactions with alkyl halides: direct alkylation(直接烷基化) 19-12 1°amine 2°amine 3°amine Reactivity: 2°> 1°amine Products: mixture of 1,2,3,4°amines

39. Useful direct alkylation • Exaustive alkylation(彻底烷基化) • Reaction with a large excess of ammonia (与过量的氨反应)

40. 5. Amines as leaving groups -NH2， -NHR， -NRR’ are poor leaving groups. -NR3+ are good leaving groups.(similar to –OH2+) ----The Hofmann elimination (霍夫曼消除) 19-15 Hofmann alkene

41. Hofmann alkene Saytzeff alkene A Hofmann elimination is an E2 reaction. TS: anti-coplanar 反式共平面过渡态

42. anti-coplanar but unstable anti-coplanar but unstable stable but not anti-coplanar stable anti-coplanar The Hofmann rule----yield mainly the least substituted alkene. 霍夫曼规则-----主要消除产物是取代基较少的烯烃。

43. Problem: predict products for the following reactions. major major 与β-碳上氢的酸性有关。酸性强的先失去。 当β-碳上有苯基、乙烯基、羰基等拉电子基团时不按Hofmann规则。

44. Summary for the The Hofmann elimination • A Hofmann elimination is an E2 reaction. TS: anti-coplanar 反式共平面过渡态； • Yield mainly the least substituted alkene ----The Hofmann rule. 主要消除产物是取代基较少的烯烃 -----霍夫曼规则 • The β-H with stronger acidity is eliminated first. 酸性强β-氢优先失去。（当β-碳上有苯基、乙烯基、羰基等拉电子基团时不按Hofmann规则。） • The Hofmann elimination is frequently used to determine the structures of complex amines. 常用于测定胺化合物结构。有时可用于合成。

45. 6. Oxidation of amines ----The Cope elimination (科普消除) 19-16 1°amine hydroxylamine 羟胺 nitroso nitro hydroxylamine 羟胺 2°amine 3°amine amine oxide 氧化胺 [O]: H2O2, etc

46. 5 membered ring β-H The Cope elimination (科普消除) • TS: 5 membered ring; 五元环过渡态 • stereochemistry: syn-elimination 顺式消除 • milder condition than Hofmann elimination中性条件 • product: Hofmann products 霍夫曼烯

47. Problem: predict products for the following reactions.

48. minor major

49. Primary amines: 7. Reactions of amines with nitrous acid（亚硝酸） 脂肪重氮盐，不稳定，释放N2 芳香重氮盐，低温稳定

50. Mechanism of diazotization 重氮化机理