General Methods of Preparation of Amines

Both aliphatic and aromatic amines are built by five general strategies. (1) FROM NITRO COMPOUNDS: reduction with H2/Ni (or Sn/HCl, or Pd/H2) converts a nitroalkane or nitroarene into the corresponding PRIMARY amine, e.g. nitroethane gives ethanamine, nitrobenzene gives aniline. (2) FROM NITRILES: reduction of an alkyl or aryl cyanide with H2/Ni (or LiAlH4, or Na/C2H5OH) gives a primary amine -- the Na/ethanol variant is specifically called the Mendius reaction, e.g. ethanenitrile gives ethanamine; separately, reduction of an ISOCYANIDE with Na(Hg)/C2H5OH gives a SECONDARY amine instead, e.g. methyl isocyanide gives N-methylmethanamine. (3) FROM AMIDES: LiAlH4 reduction of an amide gives the corresponding amine (one carbon retained); alternatively, HOFMANN'S DEGRADATION REACTION treats an amide with Br2 in aqueous or ethanolic KOH to give a primary amine with ONE CARBON FEWER than the parent amide (plus K2CO3, KBr, H2O) -- this carbon-shortening step is the key diagnostic of the Hofmann bromamide reaction. (4) FROM ALKYL HALIDES: the GABRIEL PHTHALIMIDE SYNTHESIS reacts phthalimide with ethanolic KOH to form potassium phthalimide, which is heated with an alkyl halide (SN2) to give N-alkylphthalimide, and finally hydrolysed with aqueous KOH to release the pure primary amine -- this method CANNOT make aniline, since aryl halides do not undergo SN2 with the phthalimide anion; alternatively, HOFMANN'S AMMONOLYSIS heats an alkyl (or benzyl) halide with alcoholic ammonia in a sealed tube, giving a mixture of primary, secondary, tertiary amines and quaternary ammonium salt (excess ammonia favours the primary amine; excess alkyl halide favours the quaternary salt; alkyl halide reactivity order RI > RBr > RCl); a THIRD alkyl-halide route converts the halide to an azide with NaN3 and then reduces it with LiAlH4 to the primary amine; and chlorobenzene heated with alcoholic ammonia o …