第十七章 胺、重氮和偶氮化合物

1、2022-6-261第10章 胺及含氮化合物 Chapter 10 Amines & Other Nitrogen Compounds2022-6-262Natural Nitrogen Compounds 2022-6-26310.1 Nomenclature and Structure of Amines Common Names：CH3CH2NH2(CH3CH2)2NHNH2CH3NCH2CH3CH2CH2CH3乙胺 二乙胺 苯胺 甲（基）乙（基）丙胺ethanamine diethylamine aniline Nethylmethylpropanamine2022-6-264

2、选择含氮的最长碳链为母体，称为“某胺”，氮上的其它烃基则作为取代基，在其前面加上N-，以明确取代基的位置。 系统命名法：CH3ONCH3CH3CH3CH2NHCH2CH2CHCH2CH3CH3N, N-二甲基-4-甲氧基苯胺 3-甲基-N-乙基戊胺结构比较复杂的胺和含有多官能团的化合物，也可以把烃或其它官能团作为母体，氨基作为取代基来命名。 HO2CNCH3CH3NH2CH2CH2CHCH2CH2OHCH34-(N, N-二甲氨基)苯甲酸 3-甲基-5-氨基-1-戊醇 2022-6-2652022-6-266胺类化合物形成铵盐或季铵盐后，命名如下例：CH3NH2HCl(C6H5NH2)2H2S

3、O4(CH3CH2)4NBr甲胺盐酸盐 苯胺硫酸盐 溴化四乙铵Methylammonium Aniline sulfate Tetraethylammoniumchloride bromideNCH3HCH2CH3 ClC6H5CH2N(CH2CH3)3BrN-甲基-N-乙基环戊烷基铵盐酸盐 溴化三乙基苄基铵N-Ethyl-N-methylcyclopentylammonium Benzyltriethylammonium chloride bromide 2022-6-267100.8pmNHHH107.3o147.4pmNH3CHH112.9o147pmNH3CCH3CH3108o 氨的结

4、构 甲胺的结构 三甲胺的结构105.9o2022-6-268NHH142.5oNH3CH2CHH3CNCH2CH3HCH32022-6-2692022-6-2610NNCH3CH3NNCH3CH3(+)-Trger base (-)-Trger base 特勒格尔 2022-6-2611CH3NC6H5C2H5CH2CH CH2CH3NC6H5CHCC2H5CH2H2+II-（S) (R)2022-6-261210.2 Boiling Point and Water Solubility CompoundCH3CH3CH3OHCH3NH2CH3CH2CH3CH3CH2OHCH3CH2NH2Mo

5、l.Wt.303231444645BoilingPoint C-88.665-6.0-4278.516.6CCH3(CH2)2CH3CH3(CH2)2OHCH3(CH2)2NH2CH3CH2NHCH3(CH3)3CH(CH3)2CHOH(CH3)2CHNH2(CH3)3NMw.5860595958605959Bp-0.5974837-12823432022-6-261311.3 Basicity of Amines ： RNH2H2ORNH3+OH-碱共轭酸RNH2HClRNH3+Cl-RNH3+Cl-NaOHRNH2H2ONaCl2022-6-2614气相中测定的碱性强弱次序为： (C2H5

6、)3N (C2H5)2NH C2H5NH2 NH3， 水溶液中测定的碱性强弱次序为： (C2H5)2NH (C2H5)3N C2H5NH2 NH3， 烷基给电子和氢键的共同作用结果2022-6-2615q 烷基的给电子作用q 氢键的作用 C2H5NHHHOOOHHHHHH+C2H5NHHC2H5OOHHHH+C2H5N HOHHC2H5C2H5+氢键的生成使铵离子更加稳定，从而使碱性增强。 2022-6-2616胺pKa（25oC, H2O）胺pKa（25oC, H2O）NH3CH3NH2(CH3)2NH(CH3)3NCH3CH2NH2(CH3CH2)2NH(CH3CH2)3N 9.24 10

7、.62 10.73 9.79 10.64 10.94 10.75C6H5CH2NH2C6H5NH2(C6H5)2NHC6H5NHCH3o-NO2-C6H4NH2m-NO2-C6H4NH2p-NO2-C6H4NH2 9.34 4.60 1.20 4.40 -0.26 2.47 1.00NHH142.5o2022-6-2617NH2OCH3NH2OCH3NH2碱性（pKa)：OMeNH3OMeNH3OMeNH3OMeNH3负电荷有利于稳定铵正离子Strong bases have weak conjugate acids, and weak bases have strong conjugate

8、acids. 2022-6-2618NH2NO2NH2NO2NH2碱性（pKa)：4.58 2.47 1.002022-6-2619pKa = 13.6 Here, resonance stabilization of the base is small, due to charge separation, while the conjugate acid is stabilized strongly by charge delocalization. Consequently, aqueous solutions of guanidine are nearly as basic as are

9、 solutions of sodium hydroxide. 2022-6-2620Base NamePyridineTriethyl AmineHnigs BaseDBUBartons BasePotassium t-ButoxideSodium HMDSLDAFormula (C2H5)3N (CH3)3CO() K(+)(CH3)3Si2N() Na(+) (CH3)2CH2N() Li(+)pKa5.310.711.41214192635.7Important Reagent Bases pKa 8.8pKa 12pKa 6.79pKa 12.32022-6-2621问题问题11-8

10、 DBN和DBU比一般胺的碱性强得多，是有机合成中广泛使用的有机碱，试指出DBN和DBU分子中哪一个氮原子最容易被质子化，并解释它们比简单胺碱性增强的原因。NNNNDBNDBU2022-6-262211.4 Acidity of AminesB-R NHHBR NH2pKa 36 氨基离子 (CH3CHCH2)2NHCH3n-BuLi(CH3CHCH2)2NLiCH3n-BuH pKa 50二异丙基氨基锂（LDA）2022-6-2623Compound C6H5SO2NH2 pKa33271915109.62022-6-262411.5 Preparation of Amines uPrepa

11、ration of 1-Amines ExampleNitrogenReactantCarbonReactant1st ReactionTypeInitial Product2nd ReactionConditions2nd ReactionTypeFinal Product1.N3()RCH2-X or R2CH-XSN2RCH2-N3 orR2CH-N3LiAlH4 or4 H2 & Pd HydrogenolysisRCH2-NH2 orR2CH-NH22.C6H5SO2NH()RCH2-X or R2CH-XSN2RCH2-NHSO2C6H5 orR2CH-NHSO2C6H5N

12、a in NH3 (liq) HydrogenolysisRCH2-NH2 orR2CH-NH23.CN()RCH2-X or R2CH-XSN2RCH2-CN orR2CH-CNLiAlH4 ReductionRCH2-CH2NH2 orR2CH-CH2NH24.NH3RCH=O or R2C=OAddition /EliminationRCH=NH orR2C=NHH2 & Nior NaBH3CN ReductionRCH2-NH2 orR2CH-NH25.NH3RCOXAddition /EliminationRCO-NH2LiAlH4ReductionRCH2-NH26.NH

13、2CONH2(urea)R3C(+)SN1R3C-NHCONH2NaOH soln.HydrolysisR3C-NH22022-6-26252022-6-26262022-6-2627Gabriel合成合成法法 NHOOKOHN-K+OORXNOORNaOHH2OH2NNH2CO2-Na+CO2-Na+NHNHOO+RNH2RNH22022-6-2628HC6H5OHCH3TsClPyHC6H5OTsCH3N-K+OOSN2构型翻转NOOC6H5CH3HNH2NH2H2NC6H5HCH3(R) (R) (S) (S)R OHTsClR OTsN-K+OONOORNH2NH2R NH2SN220

14、22-6-2629硝基的还原Reduction of Nitro Groups NO21. Fe, HCl, H2O2. OH-NH297%NO2CHOZn, HClSnCl2, HClNH2CH3NH2CHO常用的还原剂：锡、铁、锌、氯化亚锡等 2022-6-2630NO2CH(CH3)2H2, Raney-NiMeOHNH2CH(CH3)292%2022-6-2631肟的还原 CH3(CH2)6CCH3ONH2OHCH3(CH2)6CCH3NOHNa, EtOHCH3(CH2)6CHCH3NH262%69%CH3CH2CH2CCH3NOHCH3CH2CH2CHCH3NH285%H2, Ra

15、ney-NiEtOH2022-6-26322022-6-2633Hofmann Rearrangement and Curtius Reaction NH-OHH2OCROCRNHOX XNCRO酰基氮烯异氰酸酯HO CORNH2CO2H-X-N-OHH2OCROHXCRNO-XbaabOH-O COHNO=C=N RRNH RRCONH2NaOH, Br2RNCOH2ORNH2缺电子，缺电子，空轨道空轨道N2022-6-2634CC6H5CH2HCH3CONH2Br2, NaOH, H2OCC6H5CH2HCH3NH2在Hofmann 重排反应中，如果发生迁移的烃基碳原子为手性碳，迁移时其构

16、型保持。 2022-6-2635NaN3-N2CONNNRCOClRR C NORNCOH2O-CO2RNH2Curtius Reaction酰基氮烯2022-6-26362022-6-26372022-6-2638 (i) Alkylation of the sulfonamide derivative of a 1-amine. Gives 2-amines. (ii) Reduction of alkyl imines and dialkyl iminium salts. Gives 2 & 3-amines. (iii) Reduction of amide derivativ

17、es of 1 & 2-amines. Gives 2 & 3-amines u合成合成2级和级和3级级 胺胺2022-6-26392022-6-2640CHOOCH3OCH3+ CH3NH2H2, Raney-NiCH2NHCH3OCH3OCH386%93%+NHCH2C6H5NaBH3CNMeOHNCH2C6H5CH3100%HCHOReductive Amination2022-6-2641完成下列转变2022-6-2642The Leuckart Reaction A useful variant of the reductive amination method us

18、es formic acid or formate salts as reductants. CCH3OHCO2NH4185oCCHCH3NH266%2022-6-2643Mannich ReactionO+ CH2O+(CH3)2NH1.HCl, EtOH2. OH-OCH2N(CH3)285%Mannich碱OHCH3+CH2O + HN(CH3)21. HCl, EtOH2. OH-OHCH3CH2N(CH3)2+OHCH3CH2N(CH3)2(CH3)2NCH22022-6-2644CH2=O(CH3)2NH2ClCH2=N(CH3)2ClH2OOH+OHOHCH2=N(CH3)2Cl

19、OH Cl-CH2N(CH3)2OH Cl-CH2N(CH3)2OCl-CH2N(CH3)2Mannich碱盐酸盐H2022-6-264511.6 胺的反应（Reactions of Amines）11.6.1 烷基化反应（Alkylation of Amines）CH3(CH2)6CH2BrCH3(CH2)6CH2NH2 + CH3(CH2)6CH22NH过量NH345% 43%(CH3)2CHNH2+ClCH2ClCl(CH3)2CHNHCH2ClCl71%(C2H5)2NH + O(C2H5)2NCH2CH2OH90%2022-6-264611.6.2 胺的酰化（Acylation of

20、 Amines）CH3CH2CH2NH2 + C6H5COCl CH3CH2CH2NHCOC6H5NH2(AcO)2ONHAcNHAcO2NHNO3H2SO4OH-NH2O2NAza-Michael Addition： NHOO+ONO2022-6-2647Reaction with Benzenesulfonyl chloride (磺酰化，磺酰化，Hinsberg test) 可用于鉴别：与对甲基苯磺酰氯作用可用于鉴别：与对甲基苯磺酰氯作用产物可溶于强碱的为伯胺；产物可溶于强碱的为伯胺；有固体析出的为仲胺；有固体析出的为仲胺；不反应，出现分层现象的为叔胺。不反应，出现分层现象的为叔胺。 可

21、用于分离伯、仲、叔胺。在混合物中加入对甲苯磺酰氯，进行作用，然后可用于分离伯、仲、叔胺。在混合物中加入对甲苯磺酰氯，进行作用，然后: 蒸出叔胺；蒸出叔胺；过滤得到仲胺的磺酰胺，滤液为伯胺的磺酰胺钠盐。过滤得到仲胺的磺酰胺，滤液为伯胺的磺酰胺钠盐。产物经过水解得到原来的胺。产物经过水解得到原来的胺。2022-6-264810.6.3胺的氧化和Cope消除N(CH3)2H2O2N(CH3)2ON, N-二甲基苯胺-N-氧化物Cope Elimination occurs when 3-amine oxides are heated at temperatures of 150 to 200 C +

22、HN(CH3)2O+(CH3)NOH160oC98%2022-6-2649N(CH3)2DHHHODHHH+(1:1)CH3CH2CHCH3N(CH3)2OCH3CHCHCH3CH3CH2CHCH2反型 21%顺型 12%67消除机理：消除机理：E2 syn-Eliminations有两个消除位点时：1）Hofmann产物为主；2）如有顺反，反式为主2022-6-26502022-6-265111.6.4 与亚硝酸的反应（与亚硝酸的反应（Reaction of Amines with Nitrous Acid） Nitrous acid: HNO2 or HONO1-Amines + HONO

23、 (cold acidic solution) Nitrogen Gas Evolution from a Clear Solution2-Amines + HONO (cold acidic solution) An Insoluble Oil (N-Nitrosoamine)3-Amines + HONO (cold acidic solution) A Clear Solution (Ammonium Salt Formation)(1) Aliphatic Amines2022-6-2652Under the acidic conditions of this reaction, al

24、l amines undergo reversible salt formation:This happens with 3-amines, and the salts are usually soluble in water. The reactions of nitrous acid with 1- and 2- aliphatic amines may be explained by considering their behavior with the nitrosonium cation (NO+), an electrophilic species present in acidi

25、c nitrous acid solutions. 亚硝酰正离子亚硝酰正离子nitrosonium cation2022-6-2653Primary Amines 生成的烷基重氮盐在低温下也会放出氮气生成碳正离子，并按碳正离子的机理继续反应。 2022-6-2654(CH3)2NH (CH3)2N NONaNO2, HClH2ON-亚硝基胺亚硝基胺Secondary Amines 2022-6-2655(2) Aryl Amines 1-Aryl Amines NH2NaNO2, HClH2O, 0-5oCN N Cl氯化重氮苯芳香族伯胺与亚硝酸反应生成的芳香重氮盐比烷基重氮盐稳定得多，可在水

26、溶液中，010oC下保存一段时间，并用于多种芳香族化合物的合成中。 2022-6-26562-Aryl Amines 3-Aryl Amines 2022-6-265711.6.5 芳胺的亲电取代（Electrophilic Substitution of Aryl Amines）NH2CO2HBr2, AcOHNH2CO2HBrBr82%NH2NHAc(AcO)2OAcONaNHAcBrHH2ONH2BrBr2, H2ONH2CH(CH3)2(AcO)2ONHAcCH(CH3)2HNO3NHAcCH(CH3)2NO2KOHEtOHNH2CH(CH3)2NO298% 94% 100%2022-

27、6-2658NH2H2SO4NH3HSO4180190oC-H2ONHSO3HNH2SO3HN-磺基苯胺对氨基苯磺酸2022-6-265911.7 季铵盐的消除反应季铵盐的消除反应 （Elimination Reactions of 4-Ammonium Salts）PhCH2BrEt3NPhCH2NEt3Br溴化三乙基苄基铵R4NXKOHR4NOHKX季铵碱R4NX + AgOH R4NOH + AgXCH3CH2N(CH3)3OHCH2=CH2(CH3)3NH2O2022-6-2660Hofmann Elimination 含有-氢的季铵碱，在受热时则分解为烯烃、叔胺和水。 2022-6-

28、2661N(CH3)3 OHCHCH3CH2CH3CH3CH2CH CH2 + CH3CH CHCH3(95%) (5%)Hofmann Rule The tendency of Hofmann eliminations to give the less-substituted double bond isomer. This contrasts strikingly with the Zaitsev Rule. 2022-6-2662CN(CH3)3CH2HOHE2CH2CH2 + N(CH3)3 + H2O2022-6-2663注意消除的方向2022-6-26641.8 重氮化合物（Dia

29、zo Compounds） H2C N NH2C N NFormula：R2CN2 2022-6-266511.8.1重氮化合物的制备（Preparation of Diazo Compounds ）N=N=CHCO2EtNH2CH2CO2EtNaNO2, HCl085%H3CSO2NCH3NOH3CSO2OEtC2H5OHKOH, H2OCH2N2H2OEt2O,064%69%2022-6-266611.8.2 重氮化合物的反应（Reactions of Diazo Compounds） CO2HCH2N2, Et2OCO2CH3100%ArOH + CH2N2 ArOCH3 + N2CH3

30、CCH CCH3OOH+ CH2N2CH3CCH CCH3OOCH3+ N2重氮甲烷2022-6-2667H2C N NH2C + N Nhv或或 Cu亚甲基卡宾+ CH2N2HH双环4.1.0庚烷40%hvcarbene 2022-6-2668重氮化合物的制备1. Primary Amines 生成的烷基重氮盐在低温下也会放出氮气生成碳正离子，并按碳正离子的机理继续反应。 2022-6-2669(CH3)2NH (CH3)2N NONaNO2, HClH2ON-亚硝基胺亚硝基胺Secondary Amines 2022-6-2670(2) Aryl Amines 1-Aryl Amines

31、NH2NaNO2, HClH2O, 0-5oCN N Cl氯化重氮苯芳香族伯胺与亚硝酸反应生成的芳香重氮盐比烷基重氮盐稳定得多，可在水溶液中，010oC下保存一段时间，并用于多种芳香族化合物的合成中。 2022-6-26712-Aryl Amines 3-Aryl Amines 2022-6-267211.9 芳基盐的反应（Reactions of Aryl Diazonium Salts） 1. Substitution with Loss of Nitrogen 2022-6-2673CH3NH2NaNO2, H2O H2SO4CH3N NHSO4CuBrCH3Br70%CuCNKCNCH3CN67%ArN2X+ KIArI + N2 + KINH2NO2NaNO2, H2O HClN NClNO2NO2NO2NaBF4N NBF4NO269%NaNO2 CuC6H5N2Cl + Na2SO3 C6H5SO3 NaCu+ N2 + NaClNH2NaNO2, H2OHClNNClNaBF