《哥伦比亚大学有机化学-第20章-羧酸衍生物亲核酰基取代-酰胺的制备20.13》由会员分享，可在线阅读，更多相关《哥伦比亚大学有机化学-第20章-羧酸衍生物亲核酰基取代-酰胺的制备20.13（50页珍藏版）》请在金锄头文库上搜索。
1、20.13 Preparation of Amides,acyl chlorides (Table 20.2) anhydrides (Table 20.3) esters (Table 20.6),Preparation of Amides,Amides are prepared from amines by acylation with:,Preparation of Amides,Amines do not react with carboxylic acids to give amides. The reaction that occurs is proton-transfer (ac
2、id-base).,+,RNH2,+,RNH3,+,If no heat-sensitive groups are present, the resulting ammonium carboxylate salts can be converted to amides by heating.,Preparation of Amides,Amines do not react with carboxylic acids to give amides. The reaction that occurs is proton-transfer (acid-base).,+,RNH2,+,RNH3,+,
3、heat,+,H2O,Example,+,H2N,225C,+,H2O,(80-84%),20.14 Lactams,Lactams,Lactams are cyclic amides. Some are industrial chemicals, others occur naturally.,e-Caprolactam*: used to prepare a type of nylon,a,b,g,d,e,*Caproic acid is the common name for hexanoic acid.,Lactams,Lactams are cyclic amides. Some a
4、re industrial chemicals, others occur naturally.,Penicillin G: a b-lactam antibiotic,20.15 Imides,Imides,Imides have 2 acyl groups attached to the nitrogen.,Imides,The most common examples are cyclic imides.,NH,O,O,Phthalimide,Succinimide,Preparation of Imides,Cyclic imides are prepared by heating t
5、he ammonium salts of dicarboxylic acids.,NH3,heat,20.16 Hydrolysis of Amides,Hydrolysis of Amides,Hydrolysis of amides is irreversible. In acid solution the amine product is protonated to give an ammonium salt.,+,RNH3,+,+,H2O,H,+,+,Hydrolysis of Amides,In basic solution the carboxylic acid product i
6、s deprotonated to give a carboxylate ion.,+,RNH2,HO,+,Example: Acid Hydrolysis,(88-90%),H2O,H2SO4 heat,+,Example: Basic Hydrolysis,(95%),KOH,H2O heat,+,Acid-catalyzed amide hydrolysis proceeds via the customary two stages: 1) formation of tetrahedral intermediate 2) dissociation of tetrahedral inter
7、mediate,Mechanism of Acid-Catalyzed Amide Hydrolysis,First stage: formation of tetrahedral intermediate,H+,water adds to the carbonyl group of the amide this stage is analogous to the acid-catalyzed addition of water to a ketone,Second stage: cleavage of tetrahedral intermediate,+,H+,Mechanism of fo
8、rmation of tetrahedral intermediate,Step 1,Step 1,Step 1,carbonyl oxygen is protonated because cation produced is stabilized by electron delocalization (resonance),Step 2,Step 2,Step 3,Step 3,Cleavage of tetrahedral intermediate,Step 4,Step 4,Step 5,Step 5,+,Step 6,+,NH4,+,Step 6,Step 6,Involves two
9、 stages: 1) formation of tetrahedral intermediate 2) dissociation of tetrahedral intermediate,Mechanism of Amide Hydrolysis in Base,First stage: formation of tetrahedral intermediate,water adds to the carbonyl group of the amide this stage is analogous to the base-catalyzed addition of water to a ketone,HO,Second stage: cleavage of tetrahedral intermediate,+,NH3,HO,Mechanism of formation of tetrahedral intermediate,Step 1,Step 1,Step 2,Step 2,RC,O,NH2, ,O, ,H, ,H,Dissociation of tetrahedral intermediate,Step 3,Step 3,Step 4,RC,O,H3N, ,OH,+,H,Step 4,RC,O,H3N, ,OH,+,H,Step 5,HO,
