Studies on the Syntheses of Heterocyclic Compounds. Part DCXXXVI. An Alternative Synthesis of Pentazocine

Abstract

TETSUJI KAMETANI, TOSHIO HONDA, SHYH-PYNG HUANG, and KEIICHIRO FUKUMOTO. Can. J. Chern. 53, 3820-3823 (1975).The important starting material in a synthesis of pentazocine (1) was easily prepared by treating gaseous formaldehyde with 2-lithio-2-butene. Both E-and Z-2-bromo-2-butenes (2, 3) gave the same Z-type of alcohol (4) which was converted into pentazocine.TETSUJI KAMETANI, TOSHIO HONDA, SHYH-PYNG HUANG et KEIICHIRO FUKUMOTO. Can. J. Chern. 53,3820-3823 (1975).On a pr6par6, par rkaction de la formaldehyde i l'dtat gazeux avec le lithio-2 butkne-2, le compos6 important pour la synthke de la pentazocine (1). Les deux bromo-2 butiines-3 E et Z (2,3) conduisent au m2me alcooI de type Z (4) qui peut &re transform6 en pentzzocine. praduit par le journal]Previously, we reported two simple syntheses of pentazocine (1) (1, 2), an analgesic agent having no addiction liability (3-7), by PictetSpengler type reaction and Bischler-Napieralski type reaction. In both cases, the starting material is a mixture of two isomers, l-cyano-2-methyl-lbutene (14) and 1-cyano-2-methyl-2-butene (13), obtained by condensation of ethyl methyl ketone with cyanoacetic acid, and the stereochemistry of both compounds (13 and 14) is unknown. In order to clarify these points we have investigated the selective synthesis of 1-cyano-2-methyl-2-butene (6) whose stereochemistry was also determined easily, and here we wish to report a novel synthesis of 2-type 1-cyano-2-methyl-2-butene and the conversion of 6 into pentazocine (1).The lithium derivatives (8) of E-and 2-2-bromo-2-butenes were prepared at -10 to -20°C by reaction with lithium metal, and these were treated with formaldehyde gas separately to give the same 2-type alcohol (4) in 63% yield. The structure was easily determined by n.m.r. spectral analysis which showed a methylene proton at 6 3.96 as a singlet, indicating a 2-type olefin, while the corresponding signal in the E-isomer (1 1) should appear at higher field (6 3.75-3.80). It has been reported by Lenox and Katzenellenbogen (I 1) that both the E-and 2-isomer were separable by gas chroma- For personal use only.

Benzomorphans: synthesis, stereochemistry reactions, and spectroscopic characterizations

“…An improved stereospecific synthesis of (Z)-1-cyano-2-methyl-2-butene, a key intermediate in earlier preparations of pentazocine,54•71 has been reported. 148 The Stevens rearrangement has been used to prepare highly substituted 2-benzyl derivatives of 1,3,4-trimethyl-1,2,5,6-tetrahydropyridine. These compounds were also obtained by condensation of 2-lithio-3,4-dimethylpyridine with the appropriate benzaldehyde followed by conversion of the alcohol to the chloride, methylation, and reductive dechlorination.…”