附件2 粒大浮 教 案 2003~~2004学年第Ⅱ学期 院(系、所、部)化学与环境学院有机化学研究所 教研室有机化学 课程名称有机化学(双语教学) 授课对象化学教育 授课教师杨定乔 职称职务教授 教材名称 Organic Chemistry 2004年03月01日
附件 2 教 案 2003~~ 2004 学年 第 II 学期 院（系、所、部）化学与环境学院有机化学研究所 教 研 室 有机化学 课 程 名 称 有机化学（双语教学） 授 课 对 象 化学教育 授 课 教 师 杨定乔 职 称 职 务 教授 教 材 名 称 Organic Chemistry 2004 年 03 月 01 日
有机化学(双语教学)课程教案 授课题目(教学章节或主题):第十四章.含氮有机|授课类型|理论课 化合物( Amine) 授课时间第7周第6974节 教学目标或要求:了解硝基化合物的分类,命名。了解胺的分类,命名,重氮和偶尔 氮化合物及分子重排。重点掌握胺的化学性质及重氮和偶氮化合物。 教学内容(包括基本内容、重点、难点) 含氮化合物 本章的重点是各种含氮化合物的重要反应及其在有机合成中的应用、芳环上的亲核取 代反应历程、Cope消去和 Hofmann消去反应的机理和立体化学、活泼中间体碳烯和类 碳烯的生成及其应用、烯胺的生成及其在有机合成中的应用等。 Nomenclature of Aliphatic Amines Simple amines are named as derivatives of the parent alkane, using the suffix-amine, or by using-amino to name a numbered substituent, using the following rules by replacing the-e ending with -amine, or by nam ing the nitrogen as an amino substrat a rent name elect the longest continuous carbon chain, containing the amino group, and derive the 2. Number the carbon chain, beginning at the end nearest to the amino group or, to give the lowest number at the first point of difference 3. Num ber the substituents and write the name, listing substituents alpha betically. Thus for the following example, you would number from the end closest to the nitrogen, generating the names, 3-methylpentanamine(or 1-amino-3-methy lpentane) and 5-methy 1-2-he 2-amino-5-methy1-2-hexane), respectively NH2 5 In this example, however, you number to give the lowest number at the first point of difference generating the name, 5-amino-2, 3-dimethy lhexane(not
有机化学(双语教学) 课程教案 授课题目（教学章节或主题）：第十四章．含氮有机 化合物 (Amine) 授课类型 理论课 授课时间 第 7 周第 69-74 节 教学目标或要求：了解硝基化合物的分类，命名。了解胺的分类，命名，重氮和偶尔 氮化合物及分子重排。重点掌握胺的化学性质及重氮和偶氮化合物。 教学内容（包括基本内容、重点、难点）： 含氮化合物 本章的重点是各种含氮化合物的重要反应及其在有机合成中的应用、芳环上的亲核取 代反应历程、Cope 消去和 Hofmann 消去反应的机理和立体化学、活泼中间体碳烯和类 碳烯的生成及其应用、烯胺的生成及其在有机合成中的应用等。 Nomenclature of Aliphatic Amines Simple amines are named as derivatives of the parent alkane, using the suffix -amine, or by using -amino to name a numbered substituent, using the following rules: 1. Select the longest continuous carbon chain, containing the amino group, and derive the parent name by replacing the -e ending with -amine, or by naming the nitrogen as an amino substituent. 2. Number the carbon chain, beginning at the end nearest to the amino group, or, to give the lowest number at the first point of difference. 3. Number the substituents and write the name, listing substituents alphabetically. Thus for the following example, you would number from the end closest to the nitrogen, generating the names, 3-methylpentanamine (or 1-amino-3-methylpentane) and 5-methyl-2-hexanamine (or 2-amino-5-methyl-2-hexane), respectively. In this example, however, you number to give the lowest number at the first point of difference, generating the name, 5-amino-2,3-dimethylhexane (not
2-amino-4, 5-dimethy lhexane) NH2 Some examples ar-13-diammocycloherane Nh 1-amino-4-pheny pentane ar4-phenytpentanamin H2N CH3 4amino-1 1-dimethyicycloherane Multiple substituents on the nitrogen are named using simple multipliers CH H2C一 HsC-N-CH3 amine Tetramethylammonium 2NH NN-dimethylpropylamme Benzylamine (phenyimethyanamime) quarternary based on the number of substituents on the nitrogen. o Amines are further categorized as primary, secondary, tertiary ar
2-amino-4,5-dimethylhexane). Some examples: Multiple substituents on the nitrogen are named using simple multipliers: Amines are further categorized as "primary, secondary, tertiary and quarternary" based on the number of substituents on the nitrogen:
CHa N-h HoC- H3C—CH3 Secondary Amme Tertiary Amine Quatermary Ammonium H Secondary Amme Primary Amine Reactions of Aliphatic Amines Simple amines and ammonia are strong nucleophiles and will undergo an S,2 reaction with alkyl halides ( or alkyl groups with good leaving groups")to give further substitution on the nitrogen, as described previously. They will also react with activated carbony l compounds to undergo acyl transfer reactions; thus amides are readily formed by the reaction of amines with acid halides, acid anhydrides or carboxylate esters CH2 CH2NH2 The reaction of an amine with a sulfony l halide forms the sulfonamide. A common reagent utilized in this reaction is p-toluenesulfonyl chloride, producing the corresponding p-toluenesulfonamide
Reactions of Aliphatic Amines Simple amines and ammonia are strong nucleophiles and will undergo an SN2 reaction with alkyl halides (or alkyl groups with "good leaving groups") to give further substitution on the nitrogen, as described previously. They will also react with activated carbonyl compounds to undergo acyl transfer reactions; thus amides are readily formed by the reaction of amines with acid halides, acid anhydrides or carboxylate esters. The reaction of an amine with a sulfonyl halide forms the sulfonamide. A common reagent utilized in this reaction is p-toluenesulfonyl chloride, producing the corresponding p-toluenesulfonamide
+ cha- H.CHN-SO sulfonamide The base solubility of sulfonamides forms the basis of the Hinsberg test, for distinguishing primary, secondary and tertiary amines; primary p-toluenesulfonamides undergo ionization in strong base to give the base-soluble anion, secondary p-toluenesul fonamides lack the acidic hydrogen and do not form a soluble anion; tertiary amines would yield highly unstable cationic quarternary sulfonamides, and generally do not react at all. Thus the formation of a base-soluble sulfonamide indicates the presence of a primary CH2CH2N CISO2 CH2CH2N-SO2 primary sulfonamide, base soluble H,CHN-S .a secondary sulfonamide, not base soluble Reaction of primary amines with an excess of iodome thane converts the primary amine into the quarternary ammonium salt. The cationic nitrogen which is now formed is a good leaving group and will undergo E2 elimination on reaction with Ag.0 to give the alkene, in a reaction known as the Hofmann Elimination
The base solubility of sulfonamides forms the basis of the Hinsberg test, for distinguishing primary, secondary and tertiary amines; primary p-toluenesulfonamides undergo ionization in strong base to give the base-soluble anion, secondary p-toluenesulfonamides lack the acidic hydrogen and do not form a soluble anion; tertiary amines would yield highly unstable cationic quarternary sulfonamides, and generally do not react at all. Thus, the formation of a base-soluble sulfonamide indicates the presence of a primary amine. Reaction of primary amines with an excess of iodomethane converts the primary amine into the quarternary ammonium salt. The cationic nitrogen which is now formed is a good leaving group, and will undergo E2 elimination on reaction with Ag2O to give the alkene, in a reaction known as the Hofmann Elimination
CH2CH2NH2 H-CH HO CH3Br(excess) CH3 H3C Ag2O, H2o H,CHN-CH Bf CH=CH CH3 H3C The Hofmann elimination is unusual for an e2 elimination because the least substituted alkene is typically formed. 2,H2 mot formed Amides and acid azides can also be converted to amines using the Hofmann and Curtius rearrangements, respectively. Both the amide and acyl azide can be prepared from an intermediate acid halide, and the reaction results in the shortening of the alkyl chain by one carbon (the carbonyl is lost as co NaoH, Br2lH2o The Hofmann rearrangement. H2 o. heat + NEN he Curtins rearrangement Reactions of Aryl Amines Ary l amines, like aliphatic amines and ammonia, are strong nucleophiles and
The Hofmann Elimination is unusual for an E2 elimination because the least substituted alkene is typically formed. Amides and acid azides can also be converted to amines using the Hofmann and Curtius rearrangements, respectively. Both the amide and acyl azide can be prepared from an intermediate acid halide, and the reaction results in the shortening of the alkyl chain by one carbon (the carbonyl is lost as CO2). Reactions of Aryl Amines Aryl amines, like aliphatic amines and ammonia, are strong nucleophiles and
will undergo an S, 2 reaction with alkyl halides (or alkyl groups with good leaving groups") to give further substitution on the nitrogen, as described previously. They will also react with activated carbony l compounds to undergo acyl transfer reactions; thus amides are readily formed by the reaction of of an aryl amine into an amide is a convenient method for limiting rill e on amines with acid halides, acid anhydrides or carboxy late esters. The conversion bromination to the para- position on the ring, the intermediate amide being simply hydrolyzed in a second step. CH CH H This intermediate step is necessary, since the free amine highly activates the ring to substitution, yielding tri-substitution Perhaps the most useful reactions of ary l amines involve the intermediat conversion into the corresponding diazonium salt by reaction with nitrous acid. HNO diazonium salt These diazonium salts undergo a series of replacement reactions, collectively known as the Sandelmyer Reaction to give aryl nitriles or aryl halides. A copper salt is generally required to catalyze the reaction, with the exception of iodination, which occurs spontaneously
will undergo an SN2 reaction with alkyl halides (or alkyl groups with "good leaving groups") to give further substitution on the nitrogen, as described previously. They will also react with activated carbonyl compounds to undergo acyl transfer reactions; thus amides are readily formed by the reaction of amines with acid halides, acid anhydrides or carboxylate esters. The conversion of an aryl amine into an amide is a convenient method for limiting ring bromination to the para- position on the ring, the intermediate amide being simply hydrolyzed in a second step. This intermediate step is necessary, since the free amine highly activates the ring to substitution, yielding tri-substitution. Perhaps the most useful reactions of aryl amines involve the intermediate conversion into the corresponding diazonium salt by reaction with nitrous acid. These diazonium salts undergo a series of replacement reactions, collectively known as the Sandelmyer Reaction to give aryl nitriles or aryl halides. A copper salt is generally required to catalyze the reaction, with the exception of iodination, which occurs spontaneously
KCN CuCN HCl Cucl N2 HBr. CuBr Aryl diazonium salts also undergo reduction to yield the arene on reaction with phosphouous acid (not phosphoric), and hydrolysis in the presence of aqueous acid to give the corresponding phenol. The cationic nitrogen of diazonium salts also adds to the para- position of highly activated aryl rings (generally aryl amines and phenols) to give coupling products, as shown below. H3PO2, H2O H,O H Reactions that Yield aliphatic amines Simple amines and ammonia are strong nucleophiles and will undergo an S,2 reaction with alkyl halides (or alkyl groups with "good leaving groups")to give further substitution on the nitrogen. Ammonia reacts with alkyl halides to give a mixture, consisting largely of the corresponding primary and secondary amines, with a trace of tertiary and quarternary amines. Since a mixture is obtained, this is generally a poor method for the preparation of amines
Aryl diazonium salts also undergo reduction to yield the arene on reaction with phosphouous acid (not phosphoric), and hydrolysis in the presence of aqueous acid to give the corresponding phenol. The cationic nitrogen of diazonium salts also adds to the para- position of highly activated aryl rings (generally aryl amines and phenols) to give coupling products, as shown below. Reactions that Yield Aliphatic Amines Simple amines and ammonia are strong nucleophiles and will undergo an SN2 reaction with alkyl halides (or alkyl groups with "good leaving groups") to give further substitution on the nitrogen. Ammonia reacts with alkyl halides to give a mixture, consisting largely of the corresponding primary and secondary amines, with a trace of tertiary and quarternary amines. Since a mixture is obtained, this is generally a poor method for the preparation of amines
CH3(CH2)6CH2NH2 一[CHCH2)eCH2l2lH CH3(CH2)6CH2Br nH3 CH3(CH2)6CH2I3N -(CH3(CH2)6CH214N Br Smaller Trace Better methods for the preparation of primary amines involve the reduction of a intermediate alkyl azide, or the Gabriel Synthesis, involving an intermediate phtalimide. In the first method, the alky l halide reacts with azide anion in a simple s,2 reaction to give the intermediate alkyl azide. This is generally not isolated, but is reduced immediately with Lialh, to give the corresponding primary amine. 2Br—>CH3(CH2)CH21 CHa(CH2) 6CH2NH In the Gabriel Synthesis, pthalimide anion is reacted with the alky l halide to give the intermediate N-substituted pthalimide. On acid hydrolysis, this gives pthalic acid and the corresponding primary amine KOH R-X COo HTH2O H2N. Primary amines can also be prepared by the reduction of two other functional groups; nitriles and amides. The reduction of a nitrile by lialh gives the primary amine, as shown below. Reduction of a an amide can yield a primary
Better methods for the preparation of primary amines involve the reduction of a intermediate alkyl azide, or the Gabriel Synthesis, involving an intermediate phtalimide. In the first method, the alkyl halide reacts with azide anion in a simple SN2 reaction to give the intermediate alkyl azide. This is generally not isolated, but is reduced immediately with LiAlH4 to give the corresponding primary amine. In the Gabriel Synthesis, pthalimide anion is reacted with the alkyl halide to give the intermediate N-substituted pthalimide. On acid hydrolysis, this gives pthalic acid and the corresponding primary amine. Primary amines can also be prepared by the reduction of two other functional groups; nitriles and amides. The reduction of a nitrile by LiAlH4 gives the primary amine, as shown below. Reduction of a an amide can yield a primary
secondary or tertiary amine depending on the amide H2CH2CN CH2,NH2 HO CH,CHaNH iAH Amines can also be prepared by the process of reductive amination of aldehydes and ketones. An aldehyde or ketone will react with ammonia to give an intermediate imine. Reduction of this imine with Raney Ni/H, gives the corresponding amine CH2CH2NH2 H2/Raney Ni NH3 H2/Raney Ni Primary and secondary amines can also be utilized in reductie amination reactions, typically using cyanoborohydride(NaBh, CN) to trap the intermediate ammonium lon
secondary or tertiary amine, depending on the amide. Amines can also be prepared by the process of reductive amination of aldehydes and ketones. An aldehyde or ketone will react with ammonia to give an intermediate imine. Reduction of this imine with Raney Ni/H2 gives the corresponding amine. Primary and secondary amines can also be utilized in reductie amination reactions, typically using cyanoborohydride (NaBH3CN) to trap the intermediate immonium ion