1、Chapter 17 Amines (胺),17.1 Amine Nomenclature 17.2 Structures of amines 17.3 Basicity of amines 17.4 Preparation of amines 17.4.1 Preparation of aminesby alkylation of ammonia 17.4.2 The Gabriel synthesis of primaryamines 17.4.3 Preparation of amines by reduction 17.5 Reactions of amines 17.5.1 Alky
2、lation of amines 17.5.2 Acylation of amines 17.5.3 The Hofmann Elimination,17.5.4 Reactions of amines with nitrous acid (A) Reactions of primary aliphatic amines with nitrous acid (B) Reactions of primary arylamineswith nitrous acid (C) Reactions of secondary amineswith nitrous acid (D) Reactions of
3、 tertiary amineswith nitrous acid 17.5.5 Synthetic transformations of aryldiazonium salt (A) Replacement of the diazonium group by OH,(B) Replacement of the diazonium groupby X, CN (c) Replacement of the diazonium groupby H 17.5.6 Azo coupling 17.6 Spectroscopic analysis of amines,17.1 Amine Nomencl
4、ature,Organic derivatives of ammonia,Alkylamines,Arylamines,Methylamine (甲胺),Isobutylamine (异丁胺) 2-Methylpropylamine (2-甲基丙胺),Benzylamine (苄胺),Primary amines (伯胺):,P380,Aniline (苯胺),Ethylmethylamine (甲乙胺) N-Methylethylamine (N-甲基乙胺),Diethylamine (二乙胺),Secondary amines: (仲胺),Trimethylamine N,N-Dimeth
5、ylmethylamine (三甲胺) (N,N-二甲基甲胺),N,N-Dimethyl- aniline (N,N-二甲基苯胺),Tertiary amines: (叔胺),Cyclohexylamine (环己胺),1,2-Ethyldiamine (1,2-乙二胺),Diamines:,Ammonium ions (铵离子) Aminium salts (铵盐),Anilinium chloride (盐酸苯胺),Quaternary ammonium salts(季铵盐),2-Aminoethanol (2-氨基乙醇),N-Ethyl-N-methylcyclohexylamine (
6、N-甲基-N-乙基环己胺),Heterocyclic amine: (杂环胺),17.2 Structures of amines,sp3-hybrid,Tertiary amines with 3 different groups:,Interconversion of amine enantiomers,N: 1s22s22px12py12pz1,P383, 12.2,Pyramid(棱锥型),17.3 Basicity of amines,Quarternary ammonium salt:,Weak bases,P384, 12.3,Table 1 Basic strength of
7、some amines,P385, Table 12.1,1. All amines are weak bases:,H2O RNH2 OH -,2.,Alkylamines are slightly stronger bases than ammonia; Arylamines are much weaker bases than ammonia and alkylamines.,+I,p -conjugation,Delocalization of nitrogen lone-pair electrons,Decreasing the electron density at nitroge
8、n.,P384, 12.3,pKa = -logKa,pKa + pKb = 14,Weaker base:Smaller pKa for ammonium ion Stronger base: Larger pKa for ammonium ion,3. R2NH RNH2 R3N NH3,Poorer solvation,Separation of amines from neutral organic compounds,17.4 Preparation of amines,17.4.1 Preparation of amines by alkylation of ammonia,P38
9、4, 12.3,Anilinium ion,17.4.2 The Gabriel synthesis of primary amines,Reagent:,Potassium salt of Phthalimide (邻苯二甲酰胺钾盐),Imide (酰亚胺),Ch.P436,Primary alkyl halide, SN2,ArX,17.4.3 Preparation of amines by reduction,LiAlH4,Reduction of nitriles to amines,Gabriel Synthesis. Gabriel, Ber. 20, 2224(1887). M
10、. S. Gibson, R. W. Bradshaw, Angew. Chem. Int. Ed. 7, 919 (1968); B. Dietrich et al., J. Am. Chem. Soc. 103, 1282 (1981); O. Mitsunobu, Comp. Org. Syn. 6, 79-85 (1991).Modified conditions: S. E. Sen, S. L. Roach, Synthesis 1994, 756; M. N. Khan, J. Org. Chem. 61, 8063 (1996). Stereoselectivity: A. K
11、ubo et al., Tetrahedron Letters 37, 4957 (1996).,Reduction of nitro compounds to arylamines,H2, cat,Reduction of amides to amines:,P389,Reductive amination:,Imine (亚胺),Ch.P435,17.5 Reactions of amines,Unshared electron pair of nitrogen:,Basicity:,Nucleophilicity:,17.5.1 Alkylation of amines,17.5.2 A
12、cylation of amines,Acylating agents: acyl chlorides, carboxylicacid anhydrides,Synthesis of Paracetamol (扑热息痛):,17.5.3 The Hofmann Elimination,Decreasing the activity of aryl ring or Protecting amino groups :,Methylation of an amine by excess CH3I:,Ch.P448 (六),Quaternary ammonium hydroxides (氢氧化季铵碱)
13、can be prepared from Quaternary ammonium halides:,Quaternary ammonium hydroxides,heat,- Elimination,to form alkenesand an amine,Methylenecyclohexane (亚甲基环己烷) (69%),The base attacks the most acidic hydrogen or least hinder hydrogen.,E2 Reaction,Anti relationship,Regioselectivity of Hofmann eliminatio
14、n:,To give a less substituted alkene.,Hofmann rule is opposed to the Zaitsev rule.,August Wilhelm von 18181892,August Wilhelm von , 18181892, German organic chemist. He was Professor at the Univ. of Berlin from 1865 and was a founder (1868) of the German Chemical Society. He studied the constitu- ti
15、on of aniline and was the first to prepare rosaniline and its derivatives, thereby laying the basis for the aniline dye industry. He also discovered a reaction for deriving amines from amides and developed the Hofmann method of finding the vapor densities, and from these the molecular weights, of li
16、quids. He also helped to popularize the concept of valence (the word comes from his term quantivalence,17.5.4 Reactions of amines with nitrous acid (Nitrosation 亚硝化反应),(A) Reactions of primary aliphatic amineswith nitrous acid,Nitrosating agent:,Primary aliphatic amines,Nitrous acid,to yield unstabl
17、e aliphatic diazonium salt (重氮盐),Diazotization (重氮化反应),Aliphatic diazonium salts decompose to form carbocations and nitrogen:,Alkene, alcohol, alkyl halide,(B) Reactions of primary arylamineswith nitrous acid,Primary arylamines form diazonium salt on nitrosation:,Aryl diazoniumsalts are stable below
18、 5,P390,(C) Reactions of secondary amineswith nitrous acid,Secondary amines: both aryl amines and alkyl amines react with nitrous acid to yield N-nitrosoamines(亚硝胺),N-nitrosoamines are usually separated from the reaction mixture as oily yellow liquids,(D) Reactions of tertiary amineswith nitrous aci
19、d,Tertiary aryl amines react with nitrous acidto form C-nitroso aromatic compounds:,Electrophilic aromatic substitution,17.5.5 Synthetic transformations of aryldiazonium salt,The diazonium group (重氮基)may be replaced by other atomes or groups: X, OH, CN and H.,( ),P391,:Electron-withdrawing group,Ary
20、l diazonium salts can be preparedfrom arene:,(A) Replacement of the diazonium group by OH,Aryl diazonium ion is converted to phenols(酚),Sulfuric acid is usually used instead of hydrochloric acid,Question: Design a synsthesis of,Hydrolysis,(B) Replacement of the diazonium group by X, CN,The preparati
21、on of aryl iodides,The preparation of aryl fluorides:,Treating the diazonium salt with fluoboric acid (HBF4),(69%),(81%),The Sandmeyer reaction:,Aryl diazonium salts react with cuprous chloride, cuprous bromide, cuprous cyanide,(70% overall),(65% overall),Born inWettingen near Zurich, and lived in t
22、he Zurich area for nearly all of his life. He trainedas a precision instrument-maker, but becameinterested in chemistry. Self-educated in chemistry, he carried out chemical experiments in his kitchen. In 1881, he becamea lecture assistant to Victor Meyer (1848-1897). He followed Meyer to Gttingen in
23、 1886, but soon returned toZurich and worked for Arthur Hantzsch (1857-1935). Sandmeyer joined Geigy as a research scientist in 1888, and eventually became a director of the firm. He discoveredthe decomposition of aryl diazonium Chlorides to chloroarenes in the presence of copper (I) chloride in 188
24、4. He also worked on the triphenylmethane dyes and the synthesis of isatin. Many years before, he had suggested to Victor Meyer an impurity in commerical benzene was responsible for the isatin reactionwith sulphuric acid, thereby paving the way for Meyers discovery of thiophen.,Traugott Sandmeyer(18
25、54-1922).,(C) Replacement of the diazonium group by H,Aryl diazonium salts react with hypophosphorous acid (H3PO2) (次磷酸) or ethanol to yield the product:,Deamination (脱氨基作用),(85%),P392,The value of diazonium salts in synthesis: Substituents that are otherwise accessibleonly with difficulty, such as
26、F, I, CN, OH, may be introduced onto a benzene ring. Compounds that have substitution patternsnot directly available by electrophilic aromatic substitution can be prepared,17.5.6 Azo coupling (偶氮偶合反应),Aryl diazonium salts are weak electrophiles, they react with highly reactive aromaticcompounds, to
27、yield azo compounds,Azo dyes (偶氮染料),Orange II:,P393,Alkaline solution,17. 6 Spectroscopic analysis of amines,IR:,Streching vibration,Primary amine,3000-3500 cm-1 two peaks,Secondary amines,3280 cm-1 one peak,Tertiary amines,No peak,Streching vibration,1020-1220 cm-1,Aliphatic amines,Aromatic amines,
28、1250-1360 cm-1,Ch.P437(四),Infrared spectrum of isobutylamine,CN Stretching vibration,NH Stretchingvibration,N-甲基苯胺的红外光谱,N-H伸缩,C-N伸缩,苯环 伸缩,1H NMR,N - H,:0. 6 5 ppm,:2.2 2.8 ppm,Problems to Chapter 17,P402 12.21 (a), (d),(e) 12.22 (a), (c),(f) 12.24 酶斯卡灵,一种高效的致幻剂。从仙人掌中得来。 12.27(b), (d), 12.29(b), (c)
29、12.30 (a) 12.31(b), (c) 12.37 12.39,12.41 12.42 12.48 12.51 12.52,Additional Problems to Chapter 17,1,What are the major products you would expect from Hofmann elimination of the following amines? Show the reactions.,N-Methylcyclopentylamine (c),2. Predict the product(s) of the following reactions.Give the major product.,(3) How would you prepare the following compounds from toluene? A diaonio(重氮盐)replacement reaction is neededin some instances.,(4) Ch.P464(十六), (十七),