Patent GB-611991-A (GB)
Title: Improvements in or relating to the production of heterocyclic substituted phenacylpyridines
IPC: C07D215/04
Filed: 1946-06-05
Abstract: Heterocyclic substituted phenacylpyridines of the general formula <FORM:0611991/IV(b)/1> where R is a pyridine, benzopyridine or alkylpyridine radical, R1 is an aryl radical and Z is the residue of a heterocyclic ring, are prepared by mixing together in an inert anhydrous organic solvent o -halophenacyl pyridine and a secondary heterocyclic amine, preferably at a temperature of 20 DEG  to 25 DEG C. Suitable o -halophenacyl pyridines are: the o -chloro- and o -bromo-phenacyl pyridines, the corresponding benzopyridines and similar derivatives of the alkyl pyridines, such as those from 6-methyl pyridine, 4 : 6-dimethyl pyridine and 3-ethyl-6-methyl pyridine.  The radical R1 may carry substituent radicals such as chlorine, bromine, methyl, methoxy, nitro and carbethoxy. Suitable heterocyclic secondary amines are piperidine, piperazine, morpholine, thiomorpholine, tetrahydroisoquinoline, thiazoline and pyrollidine. Preferred solvents include benzene, diethyl ether, dibutyl ether, toluene, anisol, chlorobenzene, hexane, chloroform and isopropyl acetate.  In examples: (1) 2-(o -bromophenacyl) pyridine is refluxed with piperidine in benzene to give 1-phenyl-2-(2-pyridyl)-2-(N-piperidyl) ethanone-1; (2) the process of (1) is carried out at room temperature; (3) 2-(o -bromophenacyl) pyridine is treated with morpholine in benzene yielding 1-phenyl-2-(2-pyridyl)-2-(N-morpholyl) ethanone; (4) 4-(o -bromophenacyl) pyridine hydrobromide is treated as in (2) giving 1-phenyl-2-(4-pyridyl)-2-(N-piperidyl) ethanone which is isolated as the dihydrochloride; (5) by replacing the piperidine by morpholine in the procedure of (4) 1-phenyl-2 - (N - morpholyl) - 2 - (4 - pyridyl) ethanone dihydrochloride is obtained; (6) 2-phenacylquinoline is treated with bromine and calcium carbonate in ether and piperidine is added to the reaction product giving as the final product 1 - phenyl - 2 - (N - piperidyl) - 2 - (2 - quinolyl) ethanone, which is isolated as the monohydrochloride; (7) o -bromo-4-phenacylquinoline is treated as in (4) to give 1-phenyl-2-(N-piperidyl)-2-(4-quinolyl) ethanone dihydrochloride; (8) 4 - (o  - bromo - o i carbethoxyphenacyl) pyridine hydrobromide is treated as in (4) to give 2-(N-piperidyl)-2-(4-pyridyl)-1-(2-carbethoxyphenyl) ethanone dihydrochloride and (9) o -chloro-2-phenacylpyridine is treated as in (2) to give 2-(N-piperidyl)-2-(2-pyridyl) phenylethanone.  2-(o -Bromophenacyl) pyridine is prepared by brominating 2-phenacylpyridine in acetic acid.  4-(o -Bromophenacyl) pyridine hydrobromide is prepared by brominating 4-phenacylpyridine in acetic acid.  o -Bromo-4-phenacylquinoline and the corresponding 2-phenacyl quinoline are prepared by brominating the 2- or 4-phenacyl quinolines in acetic acid.  4-Phenacylquinoline is prepared by boiling phenyl-4-quinolylacetylene with 65 per cent sulphuric acid and neutralizing.  Phenyl-4-quinolylacetylene is prepared by treating dibromo-4-styrylquinoline hydrochloride with alcoholic potassium hydroxide.  Dibromo-4-styrylquinoline is prepared by treating 4-styrylquinoline hydrochloride with bromine in chloroform.