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Amines (organic ammonia) :NH3 :NH2R or RNH2 1o amine :NHR2 or R2NH 2o amine :NR3 3o amine NR4+ or R3N (R may be Ar) 4o ammonium salt Amines are classified by the class of the nitrogen, primary amines have one carbon bonded to N, secondary amines have two carbons attached directly to the N, etc. Nomenclature. Common 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 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 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: change amine ammonium + anion change aniline anilinium + anion CH3CH2CH2NH3+Cl- n-propylammonium chloride (C6H5NH3)2SO4 anilinium sulfate N Amines, physical properties: Nitrogen is sp3 hybridized, amines are polar and can hydrogen bond. mp/bp are relatively high for covalent substances amines are basic and will turn litmus blue insoluble in water (except for four-carbons or less) soluble in 5% HCl “fishy” smell RNH2 + HCl RNH3+ + Clwater water insoluble soluble RNH3+ + OH- RNH2 + H2O water water soluble insoluble 1. test for amines 2. can be used to separate amines from neutral or acidic organic compounds 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 N H Cl 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 Amines, syntheses: 1. Reduction of nitro compounds Ar-NO2 + H2,Ni Ar-NH2 2. Ammonolysis of 1o or methyl halides R-X + NH3 R-NH2 3. Reductive amination R2C=O + NH3, H2, Ni R2CHNH2 4. Reduction of nitriles R-CN + 2 H2, Ni RCH2NH2 5. Hofmann degradation of amides RCONH2 + KOBr RNH2 1. Reduction of nitro compounds: NH2 NO2 metal + acid; then OHor H2 + Ni, Pt, or Pd R NO2 $$$ Chiefly for primary aromatic amines. R NH2 CH3 HNO3,H2SO4 CH3 + orthoNO2 H2,Ni CH3 NH2 p-toluidine 2. 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 Et N Et N,N-diethylaniline (xs) CH3I H2 C NH2 benzylamine H2 CH3 C N CH3 CH3 I benzyltrimethylammonium iodide Ammonolysis of alkyl halides is an SN2 reaction. The alkyl halide must be primary or methyl. If the alkyl halide is secondary or tertiary, then an E2 reaction will take place and the product will be an alkene! Br NH2 + NH3 2o RX 3. Reductive amination: O + NH3 O + RNH2 O + R2NH Avoids E2 H2, Ni or NaBH3CN H2, Ni CH NH2 1o amine CH NHR 2o amine CH NR2 3o amine or NaBH3CN H2, Ni or NaBH3CN 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 4. Reduction of nitriles R-CN + 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 5. 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 Amines, syntheses: 1. Reduction of nitro compounds 1o Ar Ar-NO2 + H2,Ni Ar-NH2 2. Ammonolysis of 1o or methyl halides R-X = 1o,CH3 R-X + NH3 R-NH2 3. Reductive amination avoids E2 R2C=O + NH3, H2, Ni R2CHNH2 4. Reduction of nitriles + 1 carbon R-CN + 2 H2, Ni RCH2NH2 5. Hofmann degradation of amides RCONH2 + KOBr RNH2 - 1 carbon Outline possible laboratory syntheses for each of the following amines, starting with toluene. Use a different method for each compound. NH2 H3C aniline NH2 p-toluidine CH2CH2NH2 1-amino-2-phenylethane CH2NH2 benzylamine H3C NH2 CHCH3 1-amino-1-(p-tolyl)ethane First decide which method you are going to use for which compound… NH2 H3C 1. nitration 5. Hofmann degradation CH2CH2NH2 4. Reduction of nitrile CH2NH2 2. ammonolysis NH2 H3C NH2 CHCH3 3. Reductive amination CH3 H2, Ni HNO3 H2SO4 H3C Br2,hv KMnO4,heat O CCH3 H3C PCl3 H2,Ni H3C 2 H2 CH2CH2NH2 Pt OBr- NH3 COCl NH2 CHCH3 NH3 CH2CN CH2Br NH2 CH2NH2 NaCN Br2,hv COOH NH3 CH2Br (CH3CO)2O AlCl3 H3C NO2 CONH2 NH2