Amines I Introduction II Synthesis III Reaction I Amines :NH3 RNH2 1o amine (R or Ar) R2NH 2o amine R3N 3o amine NR4+ 4o ammonium salt Amines Antidepressant Neurotransmitter Neurotransmitter Treatment of chronic urticaria and Allergy Amines Mushroo m Neurotransmitter Hallucinogenic Amines Ecstasy drug Dopamine Nomenclature Aliphatic amines are named as “alkylamines” CH3NH2 methylamine 1o CH3CH2NHCH3 ethylmethylamine 2o (CH3)2NH dimethylamine 2o CH3CH2CHCH3 NH2 sec-butylamine 1o (CH3)3N trimethylamine 3o CH3 CH3CCH3 NH2 tert-butylamine 1o Nomenclature NH2 CH2NH2 cyclohexylamine 1o benzylamine Complex amines are named by prefixing "amino"-" ( or N-methylamino, N,N-dimethyl amino-, etc.) to the parent chain: CH3CH2CHCH2CH2CH3 NH2 3-aminohexane CH3NHCH2CH2OH 2-(N-methylamino)ethanol Nomenclature Aromatic amines NH2 NH2 NH2 NH2 CH3 CH3 o-toluidine aniline H3C N CH3 m-toluidine p-toluidine CH3 H N N,N-dimethylaniline diphenylamine Salts of amines amine  ammonium + anion aniline  anilinium + anion CH3CH2CH2NH3+Cln-propylammonium chloride (C6H5NH3)2SO4 anilinium sulfate Conversion to sulfonamides R-NH2 + ArSO2Cl  ArSO2NHR + HCl 1o N-subst.sulfonamide R2NH + ArSO2Cl  ArSO2NR2 + HCl 2o R3N N,N-disubst.sufonamide + ArSO2Cl  NR O S O KOH NH2 + SO2Cl N water sol O CH2CH3 S N CH2CH3 O KOH (CH3CH2)2NH + SO2Cl ppt N CH3 CH3 KOH + SO2Cl NR OH N N H2N N H2 H C N O H COOH C N CH CH2CH2COOH N folic acid H2N COOH p-aminobenzoic acd H2N SO2NH2 sulfanilamide 5.Electrophilic Aromatic Substitution -NH2, -NHR, -NR2 are powerful activating groups and ortho/para directors a) nitration b) sulfonation c) halogenation d) Friedel-Crafts alkylation e) Friedel-Crafts acylation f) coupling with diazonium salts g) nitrosation a) nitration NH2 HNO3 H2SO4 TAR! (CH3CO)2O NHCOCH3 NH2 NHCOCH3 HNO3 H2O,OH- H2SO4 ∆ NO2 + ortho- NO2 b) sulfonation NH3 NH2 + H2SO4 SO3 cold H2SO4 NH3 HSO4 c) halogenation NH2 NH2 Br Br polyhalogenation! + Br2, aq Br no catalyst needed use polar solvent Br Br2,Fe Br HNO3 Br H2/Ni H2SO4 NO2 + ortho- NH2 Swimming pool test kit for chlorine NH2 CH3 o-toluidine Cl2 (aq.) NH2 Cl CH3 Cl bright yellow! e)Friedel-Crafts alkylation NR with –NH2, -NHR, -NR2 NH2 CH3 + CH3CH2Br, AlCl3 NR Do not confuse the above with the alkylation reaction: NH2 NHCH2CH3 CH3 CH3 + CH3CH2Br f) Friedel-Crafts acylation NR with –NH2, -NHR, -NR2 NH2 CH3 + O H3C C Cl AlCl3 NR Do not confuse the above with the formation of amides: O NH2 NHCCH3 CH3 CH3 O + H3C C Cl g) nitrosation H3C N H3C CH3 N CH3 NaNO2, HCl O N The ring is sufficiently activated towards EAS to react with the weak electrophile NO+ h) coupling with diazonium salts  azo dyes N2 Cl NH2 NH2 CH3 CH3 + benzenediazonium chloride an azo dye N N 6.Hofmann elimination step 1, methylation  4o salt step 2, reaction with Ag2O  4o hydroxide + AgX step 3, heat to eliminate  alkene(s) + R3N (xs) CH3I CH3 CH3CH2CH2CH2 N CH3 CH3 CH3CH2CH2CH2 NH2 CH3 CH3CH2CH2CH2 N CH3 CH3 I- CH3 CH3CH2CH2CH2 N CH3 OH CH3 Ag2O ∆ I- CH3 CH3CH2CH2CH2 N CH3 OH- + AgI CH3 CH3CH2CH=CH2 + (CH3)3N CH3CH2CHCH3 + (xs) CH3I NH2 CH3CH2CHCH3 H3C N CH3 CH3 CH3CH2CHCH3 H3C N CH3 CH3 I- OH Ag2O ∆ CH3CH2CHCH3 H3C N CH3 CH3 CH3CH2CHCH3 H3C N CH3 CH3 I- OH + AgI CH3CH2CH=CH2 + CH3CH=CHCH3 chief product + (CH3)3N Hofmann orientation Reactions with nitrous acid primary amines R-NH2 N N + HONO NH2 + HONO diazonium salt N2 + mixture of alchols & alkenes secondary amines H N R O N N R + HONO N-nitrosamine tertiary amines N R + HONO R O N N R R p-nitrosocompound [...]... CH3 CH3CH2CH2CH2Br NH3 CH3CH2CH2CH2NH2 n-butylamine CH3CH2CH2NH2 n-propylamine NH2 CH3Cl CH3CH2CH2NHCH3 methyl-n-propylamine 2 CH3CH2Br aniline N Et Et N,N-diethylaniline (xs) CH3I H2 C NH2 benzylamine H2 CH3 C N CH3 CH3 I benzyltrimethylammonium iodide 3 Reductive amination C O + RNH2 C O + R2NH H2, Ni or NaBH3CN H2, Ni or NaBH3CN CH NHR 2o amine CH NR2 3o amine ... NaBH3CN CH NH2 1o amine CH NHR 2o amine CH NR2 3o amine H2, Ni or NaBH3CN H2, Ni or NaBH3CN Avoids E2 Reductive amination via the imine O C NH3 H2,Ni H C NH2 H2, Ni OH C NH2 - H2O C NH imine H3C O C NH3, H2/Ni CH3 NH2 CH3CHCH3 isopropylamine acetone O CCH2CH3 + CH3CH2NH2 propiophenone O cyclohexanone NaBH3CN CH2CH3 NH CHCH2CH3 1-(N-ethylamino)-1-phenylpropane NH3, H2/Ni NH2 cyclohexylamine Reduction... primary aromatic amines R NH2 CH3 HNO3,H2SO4 CH3 + orthoNO2 H2,Ni CH3 NH2 p-toluidine Ammonolysis of 1o or methyl halides NH3 R-X RNH2 R-X R2NH 2o 1o R-X R3N 3o R-X R-X must be 1o or CH3 R4N+X4o salt CH3CH2CH2CH2Br NH3 CH3CH2CH2CH2NH2 n-butylamine CH3CH2CH2NH2 n-propylamine NH2 CH3Cl CH3CH2CH2NHCH3 methyl-n-propylamine 2 CH3CH2Br aniline N Et Et N,N-diethylaniline (xs) CH3I H2 C NH2 benzylamine H2 CH3... + 2 H2, catalyst  R-CH2NH2 1o amine R-X + NaCN  R-CN  RCH2NH2 primary amine with one additional carbon (R must be 1o or methyl) CH2Br benzyl bromide NaCN CH2C N 2 H2, Ni CH2CH2NH2 1-amino-2-phenylethane Hofmann degradation of amides O R C NH2 KOBr R-NH2 Removes one carbon! CH3 O CH3C C CH3 NH2 OBr 2,2-dimethylpropanamide CH3 CH3C NH2 CH3 tert-butylamine Synthesis of amines 1 Reduction of nitro compounds... OBrCONH2 NH2 III Reactions of amine 1 Basicity 2 Alkylation 3 Reductive amination 4 Conversion into amides 5 EAS 6 Hofmann elimination from quarternary ammonium salts 7 Reactions with nitrous acid 1 Basicity: react with acids NH2 + HCl NH3+Clanilinium chloride (CH3CH2)2NH + CH3COOH (CH3CH2)2NH2+, -OOCCH3 diethylammonium acetate Basicity Aliphatic amines Ammonia Aromatic amines NH3 + H2O  NH4+ + OHR-NH2...O C O O C OCH3 N CH3 cocaine 3o amine m 98o C water insoluble volatile "free base" "crack" smoked shorter "high" lower dose, cheaper 5 g = 5 years HCl NaHCO3 O C O O C OCH3 H Cl N CH3 cocaine.HCl HCl salt of 3o amine m 195o C water soluble non-volatile "powder", "blow" "snow" snorted longer "high" higher dose, expensive 500 g = 5 years II Synthesis of amines 1 Reduction of nitro compounds Ar-NO2... of electrons helps to stabilize the ammonium ion by decreasing the positive charge, lowering the ΔH, shifting the ionization farther to the right and increasing the basicity Aromatic amines are less basic than aliphatic amines? R-NH2 + H2O  R-NH3+ + OHNH3 NH2 + H2O NH2 NH2 + OH NH2 NH2 NH3 NH2 NH3 Effect of substituent groups on basicity NH2 NH3 + H2O G + OH G Electron donating groups make the compounds... nitriles + 1 carbon R-C≡N + 2 H2, Ni  RCH2NH2 5 Hofmann degradation of amides RCONH2 + KOBr  RNH2 - 1 carbon Syntheses for each of the following amines, starting with toluene? NH2 H3C aniline NH2 p-toluidine CH2CH2NH2 1-amino-2-phenylethane CH2NH2 benzylamine H3C NH2 CHCH3 1-amino-1-(p-tolyl)ethane Solution NH2 H3C 1 nitration 5 Hofmann degradation CH2CH2NH2 4 Reduction of nitrile CH2NH2 2 ammonolysis