1、Amines, reactions Amines are similar to ammonia in their reactions. Like ammonia, amines are basic. Like ammonia, amines are nucleophilic and react with alkyl halides, acid chlorides, and carbonyl compounds. The aromatic amines are highly reactive in electrophilic aromatic substitution.,Amine, react
2、ions: As bases Alkylation Reductive amination Conversion into amides EAS Hofmann elimination from quarternary ammonium salts Reactions with nitrous acid,As basesa) with acidsb) relative base strengthc) Kbd) effect of groups on base strength,with acids,relative base strengthRNH2 NH3 ArNH2 Kb ionizati
3、on of the base in water:Base + H2O H:Base+ + OH-Kb = H:Base+ OH- / :Base Kbaliphatic amines 10-3 10-4ammonia 1.8 x 10-5anilines 10-9 or less,Why are aliphatic amines more basic than ammonia?NH3 + H2O NH4+ + OH-R-NH2 + H2O R-NH3+ + OH-The alkyl group, -R, is an electron donating group. The donation o
4、f electrons helps to stabilize the ammonium ion by decreasing the positive charge, lowering the H, shifting the ionization farther to the right and increasing the basicity.,Why are aromatic amines less basic than aliphatic amines?R-NH2 + H2O R-NH3+ + OH-,resonance stabilization of the free base, inc
5、reases the H, shifts the ionization to the left, decreasing base strength.,Effect of substituent groups on base strength:,Electron donating groups will stabilize the anilinium ion, decreasing the H, shifting the ionization farther to the right and making the compound a stronger base. Electron withdr
6、awing groups destabilize the anilinium ion, increasing the H, shifting the ionization towards the reactants, making the compound a weaker base.,Common substituent groups:-NH2, -NHR, -NR2-OH-OR-NHCOCH3 electron donating-C6H5 groups-R-H-X-CHO, -COR-SO3H electron withdrawing-COOH, -COOR groups-CN-NR3+-
7、NO2,Number the following in decreasing order of base strength (let #1 = most basic, etc.,4 1 5 3 2,2. Alkylation (ammonolysis of alkyl halides),3. Reductive amination,Conversion into amidesR-NH2 + RCOCl RCONHR + HCl 1o N-subst. amideR2NH + RCOCl RCONR2 + HCl 2o N,N-disubst. amideR3N + RCOCl NR3o,Con
8、version into sulfonamidesR-NH2 + ArSO2Cl ArSO2NHR + HCl 1o N-subst.sulfonamideR2NH + ArSO2Cl ArSO2NR2 + HCl 2o N,N-disubst.sufonamideR3N + ArSO2Cl NR,Schotten-Baumann technique: reactions of aromatic acid chlorides are sped up by the addition of base.R-NH2 + ArSO2Cl + KOH ArSO2NHR 1o acidicArSO2NRwa
9、ter soluble saltR2NH + ArSO2Cl + KOH ArSO2NR2 + HCl 2o N,N-disubst.sufonamidewater insoluble,Hinsberg Test: unknown amine + benzenesulfonyl chloride, KOH (aq)Reacts to produce a clear solution and then gives a ppt upon acidification primary amine.Reacts to produce a ppt secondary amine.Doesnt react
10、tertiary amine.,sulfanilamide “magic bullet” antibiotic,EAS -NH2, -NHR, -NR2 are powerful activating groups and ortho/para directorsa) nitrationb) sulfonationc) halogenationd) Friedel-Crafts alkylatione) Friedel-Crafts acylationf) coupling with diazonium saltsg) nitrosation,a) nitration,b) sulfonati
11、on,c) halogenation,Swimming pool test kit for chlorine:,Friedel-Crafts alkylationNR with NH2, -NHR, -NR2,Friedel-Crafts acylationNR with NH2, -NHR, -NR2,g) nitrosation,h) coupling with diazonium salts azo dyes,Hofmann elimination from quarternary hydroxidesstep 1, exhaustive methylation 4o saltstep
12、2, reaction with Ag2O 4o hydroxide + AgXstep 3, heat to eliminate alkene(s) + R3N,7. Reactions with nitrous acid,note: 90% of all tested nitrosamines are carcinogenic in man. Many nitrosamine cancers are organ specific. For example, dimethylnitrosamine causes liver cancer while the nitrosamines in t
13、obacco smoke cause lung cancer. Sodium nitrite (“cure”) is used as a preservative in meats such as bacon, bologna, hot dogs, etc. to kill the organism responsible for botulism poisoning. In the stomach, the nitrous acid produced from sodium nitrite can react with secondary and tertiary amines to for
14、m nitrosamines. To reduce the formation of nitrosamines, ascorbic acid (Vitamin C) is now added to foods cured with sodium nitrite. Nitrosamines are also found in beer!,Amines, reactions Amines are similar to ammonia in their reactions. Like ammonia, amines are basic. Like ammonia, amines are nucleo
15、philic and react with alkyl halides, acid chlorides, and carbonyl compounds. The aromatic amines are highly reactive in electrophilic aromatic substitution.,Amine, reactions: As bases Alkylation Reductive amination Conversion into amides EAS Hofmann elimination from quarternary ammonium salts Reactions with nitrous acid,
