D. V. Sokolov

Analogs of desmethylprodine synthesized from 1-(4-phenoxybutine-2-yl)-4-phenyl-oxypiperidine

The resultant l-(4-phenoxybutine-2yl)-4-oxypiperidine (II) is esterfied by propionic anhydride in the presence of propionic acid to l-(4-phenoxybutine-2-yl)-4-phenyl-4-propionyloxypiperidine which is converted to the hydrochloride salt (III). Upon partial hydrogenation of the latter in ethanol on a palladium catalyst placed on calcium carbonate (containing i% of the active metal) the salt III is converted to l-(4-phenoxybutene-2-yl)-4-phenyl-4-propionyloxypiperidine HCI (IV) at a 86.8% yield of the theoretical. Complete hydrogenation of the aminoester hydrochloride (III) in ethanol at room temperature on a palladium catalyst applied on barium sulfate (containing 6% of the active metal) results in the formation of l-(4-phenoxybutyl(-4-phenyl-4-propionyloxypiperidine hydrochloride (V) at a yield of 84.2% [3]. The latter is also obtained by hydrogenation of the double bond of compound IV on a palladium catalyst applied on calcium carbonate (containing 5% of the active metal), in ethanol at a yield of 88.1%

New method for the preparation of 4-phenyl-4-piperidinol

The reaction of CICOOEt with I in a boiling benzene solution leads to the formation of l-carbethoxy-4-piperidone (II) in 76% yield. Condensation of the latter with phenylmagnesium bromide gives l-carbethoxy-4-phenyl-4-piperidinol (III) in 68% yield. The desired end product IV is synthesized in 71.4% yield by treating III with an alcoholic solution of KOH. The overall yield of IV, based on I, is 36.5%.

Synthesis of piperidines and decahydroquinolines, and their analgetic and psychotropic properties

In a previous communication [2] on the stereochemistry of ethynylation, we examined the steric course of the addition of acetylene to the carbonyl group in 1,2,3-trimethylpiperidin4-one. In the case of the trans isomer, Favorskii ethynylation gives both of the theoretically possible stereoisomers of the acetylenic piperidol, the isomer with an axial ethynyl group preponderating. Continuing synthetic and sterochemical studies of piperidine derivatives with the objects both of finding novelphysiologically active compounds and examining the effects of the substituent at nitrogen on the stereochemical course of the acetylenic synthesis of substituted piperidin-4-ones , we have examined the stereochemistry of the ethynyl ation of the pure trans isomer of l-(3-phenylpropyn-2-yl)-2,3-dimethylpiperidin-4-one (1)[8].

Synthesis of derivatives of piperidine and decahydroquinoline, their analgesic and psychotropic properties. X. Mono- and bicyclic analogs of prodine

In an earlier paper [I], we reported on a detailed study of the analgesic activity of three isomers of the propionic ester of 1,2-dimethyl-4-phenyl-4-hydroxydecahydroquinoline with a trans-fused ring, and an unusual dependence of the activity on the spatial orientation of the methyl group at C 2 was shown to exist. In order to study the influence of the position of the methyl group on the pharmacological activity of the compound, and in particular the effect of transferring the methyl group from C 2 to C a of the piperidine ring, we have synthesized and studied the neurotropic activity of the hydrochloride of 1,3-dimethyl-4-phenyl-4hydroxydecahydroquinoline hydrochloride (IV). The pharmacological properties of the hydrochloride of 1,3-dimethyl-2,4-diphenyl-4-propionylhydroxypiperidine (Vl) [2], which had a phenyl group at C 2, was studied for comparison. The propionates IV and VI are similar to ~prodine [3] both in the nature of the substituent group at C a and C 4, and also in their spatial orientation.

Synthesis and pharmacological activity of cefedrin

On heating ephedrine (I) with acrylonitrile in anhydrous alkaline medium, to exclude participation of the hydroxyl group in the reaction [6], l-phenyl-2-[methyl-(B-cyanoethyl)amino]propan-l-ol was formed in good yield (97%) and had mp 59 ~ [7]. The reaction was carried out equally smoothly (without resinification of the products) both at 115-120 ~ for 1/2 h, and at 80-90 ~ for 2 h although the main part of the acrylonitrile reacted in the first 25-30 min which was easily followed by the cessation of boiling of the reagent.

Synthesis of derivatives of piperidine and decahydroquinoline, their analgesic and psychotropic properties VII. 1,2,5-Trimethyl-4-(N-propionylphenylamino)piperidine

4. V.P. Borisov, In: Distribution, Biological Action, and Acceleration of Elimination of Radioactive Isotopes [in Russian], Moscow (1964), pp. 71-77. 5. F. Umland, A. Jansen, D. Tirig, et al., Complex Compounds in Analytical Chemistry. Theory and Practice [Russian translation], Moscow (1975), pp. 183-184. 6. B.N. Laskorin, A. G. Maurina, and R. A. Sviridova, in: Ion Exchange Sorbents in Industry [in Russian], Moscow (1963), pp. 124-131. 7. N.M. Sobinyakova, G. M. Anuchina, V. V. Stepanova, et al., ibid., pp. 132-143. 8. V.M. Balakin and V. V. Glukhikh, Izv. Vyssh. Uchebn. Zaved., Set . Khim. Khirn.-Teklmol., 18, No. 9, 1466-1469 (1975). 9. V.M. Balakin, V. V. Glukhikh, Yu. L Litvinets, et al., Zh. Obshch. Khim., 4__8, No. 12, 2782-2786 (1978). 10. V.M. Balakin, Yu. I. Litvinets, arid V. V. Glukhikh, USSR Patent No. 470521, Otkrytiya, No. 18, 53-54 (1975). 11. V.M. Balakin, V. V. Glukhikh, and S. M. Balakin, USSR Patent No. 407922, Otkrytiya, No. 47, 86 (1973).

Synthesis of piperidines and decahydroquinolines, and their analgesic and psychotropic properties. V. N-γ-phenylpropargyl-substituted mono- and bicyclic 4-piperidones and their neurotropic activity

I. A.N. Grinev, S. A. Zotova, N. S. Bogdanova, et al., Khim. Farm. Zh., No. 12, 16 (1973). 2. A.N. Grinev~ B. I. Shvedov, E. K. Panisheva, et al., Khim. Farm. Zh., No. i, 26 (1970). 3. M.A. Salimov, E. G. Rukhadze, S. F. Zapuskalova, et al., Vestn. Mosk. Gos. Univ., No. 6, 720 (1970). 4. N.S. Bogdanova, in: Methods of Experimental Chemotherapy [in Russian], Moscow (1970), pp. 246-248. 5. S.N. Milovanova, in: Methods of Experimental Chemotherapy [in Russian], Moscow (1971), pp. 100-106.

Stereochemistry of nitrogen-containing heterocycles

The reduction of the α- and Β-isomers of 2-methyl-4-oxooctahydro-1-pyrindine in the presence of Raney nickel and sodium in ethanol has been studied, and four isomers of 2-methyloctahydro-1-pyrindin-4-ol have been obtained. On the basis of an analysis of IR spectra, basicity constants, and the conditions for the reduction of the ketones, the most probable spatial structures have been assigned to all four piperidols.