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

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

2. Physical properties of nitro-compounds 硝基化合物的物理性质 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。

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。

（2）acidity of α-H (α-H的酸性） 假酸式 酸式

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

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)

Amine (胺) 叶绿素 a

Some biologically important amines

Alkaloid 生物碱

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 ?

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

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

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

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-methylaniline N-methylbenzenamine N-甲基苯胺 N,N-dimethylaniline N,N-dimethylbenzenamine N,N-二甲基苯胺

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

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

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

IR Primary amine 3200-3500 cm-1 two peaks Secondary amines 3280 cm-1, one peak Tertiary amines No peak N-H streching vibration Aliphatic amines 1020-1220 cm-1 Aromatic amines 1250-1360 cm-1 C-N Streching vibration

IR CH3CH2CH2NH2 3369 3291

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

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

Similar to alcohol and ether 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

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

increasing basicity increasing basicity

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

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

14.5 Salts of amines (胺盐）

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

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.

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

2. Acylation 酰化(review)

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

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

The Sulfa Drugs: Sulfanilamide 磺胺

Synthesis of sulfa Druges

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

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

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

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

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。

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。

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。

----The Cope elimination (科普消除) 19-16 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

The Cope elimination (科普消除) 5 membered ring 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

Problem: predict products for the following reactions.

major minor

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

Mechanism of diazotization 重氮化机理

Secondary amines: Tertiary amines: N-亚硝基化合物 黄色油状或固体 脂肪胺不反应。 芳胺得芳环亚硝化产物。

Distinguish of 1, 2, and 3° amine 伯、仲、叔胺的鉴别 RNH2 RNH2 RNH2 R2NH R2NH R2NH R3N R3N R3N gas 气体产生N2 Yellow oil or solid 黄色油状物或固体 No reaction 不反应

8. Reactions of arylamines 芳胺的反应 aniline (1) Aromatic substitution (芳香取代) Amino group: electron donating, activiting group, o-, p- directing group， easily to be oxidized to give a complicated mixture

Strongly acidic reagents are unsuitable for substitution of aniline 强酸性试剂不适于苯胺的取代。 Oxidizing acids (such as nitric acid and sulfuric acid) may oxidize the amino group. 氧化性酸(如硝酸或硫酸)会氧化氨基。

(2) reactions of arenediazonium salts (芳香族重氮盐的反应） Substitution (取代反应) Coupling reactions of arenediazonium salts (重氮盐的偶联反应）

The Sandmeyer reaction 桑德迈耶反应 Substitution (取代反应) Hydrolysis 水解 phenol The Sandmeyer reaction 桑德迈耶反应 The Schiemann reaction席曼反应 Deamination脱氨基

Coupling reactions of arenediazonium salts (重氮盐的偶联反应） a diazo coupling reaction(重氮偶合反应）. azo compounds 偶氮化合物 weak electrophiles

Azo dyes 偶氮染料 methyl orange 甲基橙

Synthesis of methyl orange 甲基橙的合成

1. Amines through alkylation of ammonia or amines 14.7 Preparation of amines 1. Amines through alkylation of ammonia or amines

2. Preparation of amines through reduction of nitro compounds 硝基化合物还原 H2 / Pt, Pd, or Ni Fe, HCl Reduction methods：

3. Preparation of amines through reduction of azides 叠氮化物的还原 [H]： LiAlH4, H2/cat Primary amine

4. Preparation of amines through reduction of amides, nitriles Primary amine

5. Preparation of amines through reductive amination 还原氨化 [H]： LiAlH4, NaBH4, H2/cat, Na(CH3COO)3BH

Primary amine

Mechanism for reductive amination

Na(CH3COO)3BH, NaBH3CN can reduce imines and imine salts, but does not reduce the carbonyl group. (可选择性还原亚胺及亚胺盐，不还原羰基。)

1) Hofmann rearrangement or Hofmann degradation （霍夫曼重排或霍夫曼降级） 6. Preparation of amines through the Hofmann and curtius rearrangements 1) Hofmann rearrangement or Hofmann degradation （霍夫曼重排或霍夫曼降级） Primary amine Primary amide R = alkyl, Ar

the Curtius rearrangement (库尔提斯重排）

7. Gabriel synthesis (盖布里尔合成) Primary amine

Assignment 19-2, 6, 37, 38, 40, 41, 42, 44, 51 中文：5，6，8