Patent GB-589625-A (GB)
Title: Manufacture of new pyridine and piperidine compounds
IPC: C07D213/81
Filed: 1945-01-18
Abstract: Pyridine-, or piperidine - substituted aryl acetonitriles are prepared by condensing a mono-aryl-acetonitrile containing at least one hydrogen atom in the acetonitrile residue with a pyridine or piperidine compound halogenated in the nucleus in the presence of a metal or metal compound capable of eliminating halogen hydride.  The condensation is preferably conducted in an inert solvent such as ether, benzene or toluene.  As agents suitable for eliminating hydrogen halide there are mentioned sodium, potassium or lithium either as such or as the amide, hydride, alcoholate or hydrocarbon compound, such as sodamide, sodium hydride, potassium tertiary butylate, potassium tertiary amylate, lithium butyl, sodium phenyl and lithium phenyl.  The condensation products so obtained may be further treated to replace by an alkyl residue a hydrogen atom attached to the carbon atom to which the nitrile group is connected, for example by reaction with an alkylamine halide, such as methylamino-, ethylamino-, or diethylamino-ethyl chloride, in the presence of an agent capable of eliminating hydrogen halide.  The products may also be converted into the corresponding acids, amides, esters, ketones or amines.  Mild hydrolysis yields the amide, more active hydrolysis yields the acid.  The amides may also be obtained from the acids or their halides by means of ammonia or an amine.  The esters are obtained from the nitriles, acids or amides by means of the appropriate esterifying agent.  The ketones are obtained from the nitrile by the action of an organo metal compound, and the amines are obtained by reduction of the nitriles with hydrogen in the presence of a catalyst such as platinum or nickel.  The conditions of reduction may be selected so that when starting with an a -pyridyl nitrile, the product obtained is an a -piperidyl amine.  In examples: (1) phenyl acetonitrile is condensed with 2-chloropyridine in toluene solurion in the presence of sodamide to give a -phenyl-a -pyridyl-(2)-acetonitrile.  Instead of phenyl acetonitrile there may be used compounds in which the phenyl nucleus is substitued by 3 : 4-dimethoxy-, 3-methoxy-, and 3 : 4-methylene-dioxy-groups.  Other acetonitrates specified are the naphthyl-, and a -phenyl-a -methyl-acetonitrals.  Other pyridine components are the 4-chloro-, and N-methyl-3-chloro-pyridines. Hydrolysis of a -phenyl-a -pyridyl-(2)-acetonitrile with cold concentrated sulphuric acid gives the corresponding amide. Treatment of the amide or the nitrile with hydrogen chloride in methyl alcohol gives the methyl ester, which when hydrogenated in the presence of a platinum catalyst gives the corresponding piperidyl compound.  A list of a -pyridyl and a -piperidyl amides and esters which may be similarly obtained is given; (2) a  - phenyl - a  - ethyl - a  - pyridyl - (4) - acetonitrile obtained as in example (1) is reacted with anisole and n-propyl-magnesium bromide to form a -phenyl-a -pyridyl-(4)-di-n-propyl ketone. Other analogous ketones similarly obtained are mentioned; (3) a  - phenyl - a  - pyridyl - (2) - acetonitrile obtained as in example (1) is reduced with hydrogen in the presence of a nickel catalyst to form b -phenyl-b -pyridyl-(2)-ethylamine.  Other analogous amines similarly obtained are mentioned.  The conversion of the amines into their N - methyl derivatives by treatment with formaldehyde and formic acid is also mentioned.