Patent GB-682261-A (GB)
Title: Improvements in or relating to araliphatic amines and their salts
IPC: C07D295/03
Filed: 1950-01-27
Abstract: The invention comprises compounds of the general formula <FORM:0682261/IV (b)/1> (wherein R1 represents an alkyl or alkenyl radical of 4-6 carbon atoms, Y an a  : b -alkylene radical, and -N=B a dialkylamino group or a saturated heterocyclic amino group such as a piperidino, morpholino, thiomorpholino, pyrrolidino or piperazino group) and their non-toxic salts (including quaternary ammonium salts), and the preparation thereof and of compounds in which R1 represents a cycloalkyl radical by reacting, in the presence of sodium amide, a compound of the general formula <FORM:0682261/IV (b)/2> with an aminalkyl halide X-Y-N=B (where X=halogen) or salt thereof, or a compound of the general formula <FORM:0682261/IV (b)/3> with an alkyl halide RX (wherein R is an alkyl radical of 4-6 carbon atoms), and then in either case replacing the cyano group by hydrogen by treatment with sodium amide.  The nitriles of the second general formula above are obtainable by the treatment of phenylacetonitrile with an alkyl, alkenyl or cycloalkyl halide (a list of which is given), and reference is also made to an alternative procedure for the production of compounds in which R1 is an alkenyl group with a double bond in the vinyl position, in which phenyl-acetonitrile is first condensed with an aldehyde or ketone and the resulting alkylidene derivative is reacted with the compound X-Y-N=B, the double bond shifting into the vinyl position.  The products are useful as antispasmodic agents, preferably in the form of their water-soluble salts, e.g. salts with inorganic or strong organic acids having non-toxic anions (e.g. hydrochloric, hydrobromic, hydriodic, sulphuric, citric, tartaric, lactic, sulphamic or ethanesulphonic acid) or quaternary ammonium salts obtained by the action of alkyl or aralkyl esters of inorganic or strong organic acids (e.g. halides, sulphates or sulphonates, of which a list is given). Interconversion of one quaternary salt of another (e.g. a methiodide to a methochloride) may be effected by liberating the quaternary ammonium hydroxide by the action of silver oxide and neutralizing it with the desired acid.  Reference is also made to the salts (including quaternary ammonium salts) of the intermediate nitriles.  Examples illustrate the various features of the invention, and the alternative procedure described above, as applied to the preparation of: (1) N-(5-methyl - 3 - phenylhexyl) - piperidine and its hydrochloride and methiodide; (2) N-(3-phenyl - 3 - cyclohexylpropyl) - piperidine and its hydrochloride; (3) 3-phenyl-3-cyclohexylpropyldimethylamine and its hydrochloride; (4) N - (3 - phenyl - 3 - cyclohexylpropyl)-pyrrolidine and its hydrochloride; (5) 3-phenyl-3-cyclohexylpropyldiethylamine and its hydrochloride; (6) N : N - diethyl - 5 - methyl - 3-phenylhexylamine and its hydrochloride and methiodide; (7) N : N : 5-trimethyl-3-phenylhexylamine and its hydrochloride and methiodide; (8) N : N-dimethyl-3-phenyl-3-cyclopentylpropylamine and its hydrochloride and methiodide; (9) N : N-diethyl-3-phenylnonylamine and its hydrochloride; (10) N-(3-phenylnonyl)-piperidine and its hydrochloride; (11) N - (5 - methyl - 3 - phenyl - 5 - hexenyl)-piperidine and its hydrochloride; (12) N-(5-methyl - 3 - phenyl - 4 - hexenyl) - piperidine and its hydrochloride and methiodide.