Structures Related to Morphine. XIV.¹ 2'-Hydroxy-5-methyl-2-phenethyl-6,7-benzomorphan, the 9-Demethyl Analog of NIH 7519 (Phenazocine) from 3,4-Dihydro-7-methoxy-2(1H)naphthalenone

Benzomorphans: synthesis, stereochemistry reactions, and spectroscopic characterizations

“…Both of the diastereomers 282a and 282b have been prepared by Grignard addition to the appropriate 11-oxobenzomorphans obtained via the tetralone route. 19,22 Addition of methylmagnesium Iodide to the quaternary salt 279 gives, after pyrolytic extrusion of MeBr, the carbinol 282b with hydroxyl anti to the benzofusion, whereas Grignard addition to the demethylated compound 280 yields the carbinol The structures shown indicate one enantiomorph, but a racemic mixture is implied in our discussion as three-dimensional structures more effectively show stereochemical relationships. Similar modes of addition occur during catalytic reduction128•130 resulting in 281a and 281b.…”

“…Although this latter synthesis suffers from low yield, it represents the first preparation of the benzomorphan ring skeleton. Following Barltrop's initial work, May reported the synthesis of 3,6-dimethylbenzomorphan (21), initiating his extensive investigations into the synthesis and pharmacology of these compounds.19 His first approach to 21 was analogous to Barltrop's synthesis of 17. Owing to low yields (e.g., 15 -* 18 (20-30%); 20 -21 (30%)), this method was abandoned in favor of a longer synthesis beginning with hydratropanitrile (22) which afforded 21 in 5% overall yield. Alkylation of 22 with ßdimethylaminoethyl chloride followed by lithium aluminum hydride reduction afforded amino aldehyde 23 which was converted in four steps to the tetralone 25 in 61 % overall yield.…”

“…20 Although not applicable for the direct preparation of compounds like 28, the tetralone synthesis has been a useful route to 6-substituted benzomorphans. [22][23][24][25] As a hybrid of both the benzomorphan and meperidine ring systems, 3-methyl-6-carboethoxybenzomorphan (31a) was prepared in eight steps from phenylacetonitrile in a manner analogous to that used for 21.26 Although 31a and 31b show 30 meperidine…”

Substituted 5-Allyl-9-oxobenzomorphans. Versatile Intermediates for Investigations in the Field of Analgesics and Narcotic Antagonists. Part 1

“…278-280"; n.m.r. (free base, CCI,) 6 7 This work was supported in part by the National Research Council of Canada with a grant through its Industrial Research Assistance Programme.…”

9-Hydroxy-1,2,3,4,5,6-hexahydro-1,5-methano-3-benzazocine derivatives as analgesics

“…On the other hand, ketone 2 was treated with Ph3P=CH2 to give the 11-methylene compound 4. Hydrogenation of 4 isomer 5, while the hydrogenation in Ac0H-HC104 gave a mixture of the 11/3-methyl isomers 6 and 5 (ratio, 7:1). 6 The stereochemistry of 5 Pharmacology.…”