Patent GB-615136-A (GB)
Title: A process for the manufacture of amino-substituted tertiary carbinols
IPC: C07D295/084
Filed: 1946-07-27
Abstract: Tertiary carbinols <FORM:0615136/IV(b)/1> are prepared by treating ketones <FORM:0615136/IV(b)/2> in an inert solvent with organo-magnesium halides R5 - Mg - X.  In the above formul  R1 is hydrogen, alkyl or aralkyl, R2 is alkyl or R1 and R2 together with the N atom to which they are attached may form a heterocyclic ring, R3 is hydrogen, R4 is aryl, or R3 and R4 together with the carbon atoms to which they are attached may form a cyclohexane or tetrahydronaphthalene ring system, R5 is alkyl, cycloalkyl, aralkyl, aryl or alkaryl and X is halogen, preferably bromine or iodine.  The ketones are preferably used as their mineral acid salts and substantially anhydrous ether is the preferred solvent.  The carbinols may be acylated and R1 when aralkyl converted to hydrogen by catalytic hydrogenation.  In examples, phenyl magnesium bromide treated with (1) 2-(dimethylamino-methyl)-cyclohexanone and (9) the hydrochloride thereof yields 2 - (dimethylamino - methyl) - 1 - phenylcyclohexanol-1 the acetyl and propionyl derivatives thereof being obtained on treatment with the corresponding anhydride; (2) 2-(piperidinomethyl) - cyclohexanone yields 2 - (piperidinomethyl)-1-phenylcyclohexanol-1; (4) 2-(methylbenzylaminomethyl) - cyclohexanone yields 2 - (methylbenzylaminomethyl) - 1 - phenylcyclo - hexanol-1 which on hydrogenation with palladium charcoal yields 2-(methylaminomethyl)-1-phenylcyclohexanol-1; (5) b -dimethylaminopropiophenone yields g -hydroxy-g :g -diphenylpropyl-dimethylamine the acetyl and propionyl derivatives thereof being obtained in the usual manner, the hydrochloride and allyl bromide quaternary salt of the propionyl derivative also being described; (7) 2-methyl-6-(dimethylaminomethyl)-cyclohexanone yields 1-phenyl-2-methyl-6-(dimethylaminomethyl)-cyclohexanol-1; (8) b -(dimethylaminomethyl)-a -tetralone; and (10) the hydrochloride thereof yields 1-phenyl - 2 - (dimethylaminomethyl) - 1 : 2 : 3 : 4 - tetrahydronaphthol-1, the acetyl and propionyl derivatives of which are also obtained together with the hydrochloride of the acetate; (14) 2-(piperidinomethyl)-tetralone-1 hydrochloride yields 1-phenyl-2-(piperidinomethyl)-1 : 2 : 3 : 4-tetrahydronaphthol - 1 hydrochloride and (15) b  - (methylbenzylamino) - ethyl phenyl ketone hydrochloride yields 1 : 1-diphenyl-3-(methylbenzylamino)-propanol-1, the hydrochloride of which is also prepared, the free base yields 1 : 1-diphenyl - 3 - (methylamino) - propanol - 1, the hydrochloride of which is also described, on hydrogenation with a palladium charcoal catalyst; o-tolyl magnesium bromide treated with (3) 2 - (dimethylaminomethyl) - cyclo - hexanone yields 2-(dimethylaminomethyl)-1-(o - tolyl) - cyclohexanol - 1 and (6) b  - dimethylamino - propiophenone yields g  - hydroxy - g  - phenyl-g -(o-tolyl) - propyldimethylamine, the propionyl derivative of which is also prepared; (11) ethyl magnesium iodide and (13) cyclohexyl magnesium bromide and 2-(dimethylaminomethyl)-tetralone-1 hydrochloride yield 1-ethyl-and 1 - cyclohexyl - 2 - (dimethylaminomethyl) - 1 : 2 : 3 p  : 4-tetrahydronaphthol-1 hydrochloride respectively and (12) benzyl magnesium bromide and o  - dimethylaminopropiophenone hydrochloride yield 1 : 2-diphenyl-4-dimethylaminobutanol-2. The hydrochlorides of the ketones used in examples (1), (4), (7) and (15) are obtained by the condensation of the appropriate ketone and amine hydrochloride with paraform thus in (7) 2-methyl-6-(dimethylaminomethyl)-cyclohexanone hydrochloride is obtained from 2-methyl-cyclohexanone, dimethylamine hydrochloride and paraform.