Patent GB-613111-A (GB)
Title: New ª‡-disubstituted derivatives of the aralkyl and hydroaralkyl isocyanate and the aralkyl and hydroaralkylamine group and process for the preparation thereof
IPC: C07C263/12
Filed: 1945-04-30
Abstract: a -Disubstituted aralkyl and hydroaralkyl isocyanates and amines, of the general formula <FORM:0613111/IV(b)/1> (wherein X represents an aromatic or hydroaromatic radical, substituted or not, R and R1 represent alkyl groups, =R2 represents =H2 or =CO and n is 1 or 2), are manufactured by treating a ketone of the general formula <FORM:0613111/IV(b)/2> with sodamide in solution in benzene or a homologue thereof, converting the resulting amide by the action of potassium hypobromite into the isocyanate, and, if desired, treating this with concentrated hydrochloric acid in the hot state to obtain the amine in the form of its hydrochloride, from which the base may be liberated by treatment in aqueous solution with an alkali, and extraction with an organic solvent, e.g. ether.  The isocyanates may be used as auxiliary bodies in the textile industry, in perfumery or as antiseptic and deodorizing substances, whilst the amines may serve as intermediates for the synthesis of pharmaceutical materials.  In an example, a -p-methoxybenzylisopropyl phenyl ketone is refluxed with sodamide in toluene, and the resulting p-methoxy-a  : a -dimethylhydrocinnamic amide is stirred with potassium hypobromite solution to produce the corresponding isocyanate, which is heated with concentrated hydrochloric acid to form b -p-methoxyphenyl-a  : a -dimethylethylamine hydrochloride. There may similarly be prepared the hydrochlorides of a -methyl-a -ethyl-b -phenyl-, a  : a -diethyl-b -phenyl-, a  : a -dimethyl - b  - cyclohexyl-, a  : a  - dimethyl - b  - p-tert.-butylphenyl- and a  : a -dimethyl-b -p-tert.-butyl-o : o1-dimethylphenyl-ethylamine (and the corresponding isocyanates).  A sample has been furnished under Sect. 2 (5) of a  : a  - dimethyl - g  - phenyl - n - propylamine hydrochloride, prepared by the process of the invention, via a  : a -dimethyl-g -phenyl-n-butyric acid amide and the corresponding isocyanate, from (a  : a -dimethyl-g -phenyl-n-propyl) phenyl ketone, which in turn is made by treating isopropyl phenyl ketone with sodamide in dry benzene and stirring the resulting solution of the sodio derivative with phenylethyl bromide.  The Specification as open to inspection under Sect. 91 comprises also the manufacture of compounds of the first general formula above in which X may represent a heterocyclic or aliphatic radical, R and R1 may represent aryl or aralkyl groups, =R2 may represent =RR1 and n may be zero; and the following alternative methods of manufacture: (a) (when R and R1 are identical) treating an ester of the formula <FORM:0613111/IV(b)/3> with an organo-magnesium compound RMgHal to produce a carbinol of the formula <FORM:0613111/IV(b)/4> converting this to the corresponding chloride by the action of dry hydrogen chloride in the cold, replacing the chlorine atom by a cyano group by the action of potassium cyanide, hydrolysing the resulting nitrile to the amide and treating this as above (exemplified by the preparation of a  : a -diethyl-b -phenylethylamine hydrochloride from ethyl phenylacetate and magnesium ethyl bromide); (b) (when not prevented by steric hindrance) converting a ketone of the second general formula above into its oxime, subjecting this to the Beckmann transposition to form the benzoylamide <FORM:0613111/IV(b)/5> and hydrolysing this with hydrochloric acid to the amine hydrochloride (exemplified by the preparation of g -phenyl-a  : a -dimethyl-n-propylamine hydrochloride from the oxime of (a  : a  - dimethyl - g  - phenyl - n - propyl) phenyl ketone).  This subject-matter does not appear in the Specification as accepted.