Patent GB-654975-A (GB)
Title: Improvements relating to the synthesis of diphenyl ketones
Inventor: OFNER PETER
IPC: C07D295/104
Filed: 1948-02-09
Abstract: Compounds of the general formula <FORM:0654975/IV (b)/1> wherein R is an ethyl radical and R1 and R2 are different from each other and are either H or CH3 are made by heating piperidine with propylene oxide, treating the resulting 1-piperidino-propane-2-ol with a chlorinating agent to replace the hydroxy group by chlorine, treating the chlorinated compound so obtained with diphenyl acetonitrile in the presence of an alkaline condensing agent, separating each individual nitrile from the mixture of 1,1-diphenyl - 2 - methyl - 3 - piperidino - butyro-and 1,1 - diphenyl - 3 - piperidino - valero-nitriles so formed, treating one or both of these nitriles separately with an organo-metallic reagent of the Grignard type and hydrolysing the piperidino diphenyl imino derivative of an alkane thus formed. Salts of the base may be obtained either by treatment with an acid or by hydrolysing in the presence of an acid.  Alkaline condensing agents specified are sodamide, potassium, potassamide and alcoholates.  Chlorinating agents specified are phosphorus tri- or penta-chloride and thionyl chloride.  In examples (1) piperidine and propylene oxide are refluxed in methyl alcohol and 1-piperidino-propane-2-ol so obtained purified by distillation, treated with thionyl chloride to form the hydrochloride of 1-piperidino-2-chloropropane from which the free base is obtained by benzene extraction from caustic soda solution, when it is treated with diphenyl acetonitrile in benzene solution at 80 DEG  C. in the presence of sodamide to give a mixture of 1,1-diphenyl-2-2 - methyl - 3 - piperidino - butyro - and 1,1-diphenyl - 3 - piperidino - valero - nitriles which are precipitated as their hydrochlorides and purified by recrystallization from alcohol-ether mixture containing from 20 to 30 per cent by volume of alcohol the hydrochloride of the butyronitrile precipitating the mother liquors on evaporation to dryness, dissolution in water and treatment with excess caustic soda solution gave a basic oil which on crystallization from pet. ether yields the valeronitrile, the free butyronitrile being obtainable in a similar fashion and is dissolved in xylene, excess ethyl magnesium bromide added, ether of the Grignard reagent distilled off and the mixture heated for four hours when the product 11-piperidino - 21 - methyl - 31,31 - diphenyl - 41-imino hexane is isolated by the usual technique appropriate to such reactions and converted to its dihydrochloride by treatment with a saturated alcoholic solution of hydrogen chloride, the dihydrochloride is hydrolysed with 20 per cent hydrobromic acid, optionally after liberation of the free base, and 1-piperidino-2-methyl - 3,3 - diphenyl - hexane - 4 one hydrobromide isolated being recrystallized from water and alcohol-ether mixture, the free base may be obtained by treatment with excess caustic soda solution and extraction with ether and the hydrochloride prepared, in (2) a similar Grignard reaction to the one described above is carried out using the valero-nitrile in place of the butyro-nitrile when by similar methods 2-piperidino-4,4-diphenyl-heptan-5 one hydrochloride may be obtained and the corresponding free base.  In the Provisional Specification R is an alkyl group containing 1-5 C atoms.