1、 Chapter 22 Amines Amines are organic derivatives of ammonia in the same way that alcohols and ethers are organic derivatives of water.The important organic reactions of amines(nucleophiles)are with the common electrophiles:lalkyl halides via nucleophilic substitution,laldehydes or ketones via nucle
2、ophilic addition lcarboxylic acid derivatives,especially acid chlorides or anhydrides via nucleophilic acyl substitution.22.1 NomenclatureFunctional group suffix=-amine Functional group prefix=aminoThe suffix -amine is added to the name of the alkyl substituent.Alternatively,the suffix amine can be
3、used in place of the final e in the name of the parent compound.ChenliChenliChenliChenlilPrimary amines are named in the IUPAC system in several ways depending on their structure.For simple amines,the suffix -amine is added to the name of the alkyl substituent.lAlternatively,the suffix amine can be
4、used in place of the final e in the name of the parent compound.In secondary and tertiary amines,the alkyl groups may be the same or different.Compounds with four groups attached to nitrogen are also known,but the nitrogen atom must carry a positive charge.Such compounds are called quaternary ammoni
5、um salts.C H3CC H3C H3N H2N H2tert-Butyl am i neC ycl ohexyl am i neN H2N H2N H2C H3C H31,4-Butanedi am i ne4,4-D i m ethyl cycl ohexanam i ne An-NH2 group,when not the principal group,is named by the prefix amino-.C O2HN H2C O2HH2NON H22-A m i nobutanoi c aci dN H22,6-D i am i nobenzoi c aci d4-A m
6、 i no-2-butanoneN H2N H22-A m i nobutane4-A m i no-2-m ethyl hexaneN(C H3)2N(C H2C H3)2D i m ethyl am i noethane2-(di ethyl am i no)-4-m ethyl pentanelSymmetrical secondary and tertiary amines are named by adding the prefix di-or tri-to the alkyl group.NHD i phenyl am i neTri ethyl am i ne(C H3C H2)
7、3NlUnsymmetrically substituted secondary and tertiary amines are named as N-substituted primary amines.The largest alkyl group is chosen as the parent name,and the other alkyl group are considered N-substituents on the parent(N since theyre attached to nitrogen).N(C H3)2NC H2C H3C H3N,N-D i m ethyl
8、propyl am i neN-Ethyl-N-m ethyl cycl ohexyl am i ne22.2 Structure and Bondingl The amine functional group consists of an N atom bonded either to C or H atoms via s s bonds.l Both the C-N and the N-H bonds are polar due to the electronegativity of the N atom.l The trigonal(三角形的)pyramidal(金字塔形的,锥体的)ar
9、rangement of bonds around nitrogen is shallower in aryl amines vs alkyl amines.ChenliChenliStructure and Bonding in AminelThe bonding in amines is similar to the bonding in ammonia.lThe nitrogen atom is sp3 hybridized,with the three substituents occupying three corners of a tetrahedron and the nitro
10、gen nonbonding lone pair of electrons occupying the forth corner.NCH3CH3CH3sp3 hybridizedChenliChenliChenliChenliCH3NH2 The more red an area is,the higher the electron density and the more blue an area is,the lower the electron density1.Amines can react as either bases or nucleophiles at the nitroge
11、n.2.There is low electron density(blue)on H atom of the-NH group.3.Removal of the proton generates the amide ion(care:not to be confused with the carboxylic acid derivative RCONH2)4.The-NH group is a very poor leaving group and needs to be converted to a better leaving group before substitution can
12、occur.陈立The amine N atom is a region of high electron density(red)due to the lone pair.ChenliChenliChenliChenli陈立CH3NH3+The more red an area is,the higher the electron density and the more blue an area is,the lower the electron density1.The ammonium N atom is a region of low electron density(blue)du
13、e to the positive charge.2.Ammonium ions are not nucleophilic.3.There is low electron density(blue)on H atom of the-NH3 group.Removal of the proton regenerates the amine.4.The-NH3 group is a potential leaving grouplThis is a result of resonance delocalisation of the lone pair into the aromatic p p s
14、ystem(such delocalisation is also responsible for the decreased basicity of aryl vs alkyl amines).ChenliChenliChenliChenlialkyl ammonium pKa 10,aryl ammonium pKa 522.3 Physical properties of Amines The polar nature of the N-H bond(due to the electronegativity difference of the two atoms)results in t
15、he formation of hydrogen bonds with other amine molecules,see below,or other H-bonding systems(e.g.water).The implications of this are:vhigh melting and boiling points compared to analogous alkanes vhigh solubility in aqueous media intermolecular H-bonding in amineslAmines are highly polar and there
16、fore have higher boiling points than alkanes of equivalent molecular weight have.lLike alcohols,amines with b H b H b b H +NR3 消除产物消除产物取代多烯烃取代多烯烃取代少烯烃取代少烯烃消除产物类型消除产物类型热力学控制产物为主热力学控制产物为主动力学控制产物为主动力学控制产物为主C CH H3 3C CH H2 2C CH HH HC CH HC CH H2 2N N(C CH H3 3)3 3H HB BC CH H3 3C CH H2 2C CH HH HC CH
17、HC CH H2 2X XH HB BaabbbbHofmann EliminationHNRRRBrHNRRRHOLessThermallyUnstableMoreThermallyUnstableHofmann EliminationHNRRRHO:leavinggroupE2EliminationRNRRalkenetertiaryaminePreparation of Quaternary Ammonium Hydroxides?HNRRRBrHNRRRHOAcccesible directly fromprimary aminesNot acccesible directly fro
18、mprimary aminesIon Exhangeare prepared from trialkylammonium halides through ion exchange with silver(I)oxide.Preparation of Quaternary Ammonium Hydroxides(1 mols)(3 mols)NH3CIHHheatmethanolNCH3CH3CH3IAg2OMeOH,H2ONCH3CH3CH3HOAg(I)IodideHighly InsolubleHofmann EliminationNCH3CH3CH3HOGood Leaving Grou
19、p160 CNCH3H3CCH3H2OHofmann Elimination-MechanismHNCH3H3CCH3HONCH3H3CCH3HOHHH160 CHofmann Elimination-RegioselectivityH3CNH3CCH3CH3CH3heatH3CCH3HHHCH3HCH3CH3HHHHHO94.6%2.2%3.2%85-150 CHofmann productSaitsev productsHofmann Elimination-RegioselectivityConformational Analysis ofsec-Butyltrimethylammoni
20、um HydroxideHHHNCH3CH3HCH3H3CCH3HHCH3NHCH3CH3H3CCH3HCH3HNHCH3CH3H3CCH3ELowest energyconformerHighest energyconformerH3CNH3CCH3CH3CH3HHHOHofmann Elimination-RegioselectivityMajor ProductHHCH2CH3HHHHNCH3CH3HCH3H3CCH3HOHofmann Elimination-RegioselectivityHH3CCH3HMinor ProductHHCH3NHCH3CH3H3CCH3HOHofman
21、n Elimination-RegioselectivityCH3HCH3HMinor ProductHCH3HNHCH3CH3H3CCH3HORecent ExamplesBerkes,D.;Netchitailo,P.;*Morel,J.;Decroix,B.Synth.Commun.,1998,28,949-956.Berkes,D.;Netchitailo,P.;*Morel,J.;Decroix,B.Synth.Commun.,1998,28,949.Reference:Morphy JR,Rankovic Z,York M TETRAHEDRON LETTERS22.6.7 Oxi
22、dation of Amine:The Cope EliminationOxidant:H2O2,RCOOOHR3NH2O2 or R C O3HR3NOterti ary am i ne oxi deR3NOC6H5ONCH3CH2CH3OC6H5NH3CH3CH2CCope Elimination(Cope Reaction)An elimination reaction,occurs when 3 amine oxides,prepared by oxidizing 3 amines with peroxides,are heated at temperatures of 150 to
23、200.This reaction is known as the Cope Elimination.C H2N(C H3)2C H2N(C H3)2O160C H2+(C H3)2N O HH2O2CCHN(C H3)3CC+H O N(C H3)3OUnlike the Hofmann elimination,this reaction takes place by a concerted cyclic reorganization,as shown in the following diagram.For such a mechanism,the b b-hydrogen and ami
24、ne oxide moieties (一部分)necessarily have a syn-relationshipE2 顺式消除：顺式消除：有两种有两种 b-b-氢存在时，以氢存在时，以Hofmann产物为主产物为主baN aN O2,H C l0 5 RNNdi azoni um sal tN2R O H +R X+CC.重氮盐R N H2C lR22.6.8 Reaction with Nitrous AcidPrimary aminePrimary alkyl or aryl amines yield diazonium salts(hence the diazotisation re
25、action)Alkyl diazonium salts are very unstable and yield carbocation-derived products by loss of the very good leaving group,N2.Secondary amineSecondary alkyl or aryl amines yield N-nitrosoamines亚硝胺亚硝胺:黄色油状液体或固体,可用于鉴别仲胺Tertiary amineTertiary alkyl amines do not react in a useful fashionR3NN aN O2,H
26、C l0 5 R3N HN O2O HArylaminesN aN O2,H C l0 5 A r NNarenedi azoni um sal t芳香重氮盐N aN O2,H C l0 5 NON(C H3)2O NN(C H3)2N aN O2,H C lA rN H2C lA r2N HA r2NMechanism The actual nitrosation reagent is the nitrosyl(亚硝酰基的)cation,NO+which is formed in situ:Nitrosyl cationH ONO+H+H2ONOH2ONONOR N H2NOR N HNON
27、O HR NNO H2R NN+H2O N2R N H2H+R NRlTypical reagents:sodium nitrite and aq.HCl or H2SO4(this mixture yields nitrous acid,HNO2)lThe most useful reactions are probably those of primary aryl amines,Ar-NH2,which give aryl diazonium salts,Ar-N2+which can then be used to prepare substituted benzenes.1-Amin
28、es+HONO(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)Nitrous acid(HNO2 or HONO)reacts with aliphatic amines in a fashion that provides a useful test for distinguishing primary,secondary and tertiary amines.ChenliChenli陈立
