2.6- Methano-3-benzazocines

Dimethyl-3-(3-methyl-but-2-enyl)-1,2,3,4,5,6-hexahydro-2,6-methano-benzo[c/]azocin-8-ol, (2a,6a,11R )-1,2,3,4,5,6-hexahydro-6,11 -dimethyl-3-(3-mmethyl-2-butenyl)-2,6-methano-3-benzazocin-8-ol, C19H27NO, Mr 285.42, mp 145-148 °C hydrochloride [2276-52-0], C19H27NO. ... 

Phenazocine (Prinadol ), 1,2,3,4,5,6-hexahydro-8-hydroxy-6,11-dimethyl- 3-phenethyl-2,6-methano-3-benzazocine hydrobromide, was synthesized at the National Institutes of Health in a search for new analgesics with low addictive liability. Addiction to phenazocine develops more slowly and is less intense when dosages equivalent to morphine are administered chronically for 30 d. The incidence of side effects (respiratory depression, hypotension, and nausea and vomiting) are less with phenazocine than with morphine. 

Chemical Name (-)-3-(3-Butynyl)-l,2,3,4,5,6-hexahydro-ll,ll-dimethyl-2,6-methano-3-benzazocine-6,8-diol... 

Chemical Name 2,6-Methano-3-benzazocin-8-ol, 1,2,3,4,5,6-hexahydro-6,ll-dimethyl-3-(3-methyl-2-butenyl)-, hydrochloride, (2R,6R,llR)-rel-... 

To the 2-(4-methoxybenzyl)-l,3,4-trimethyl-l,2,5,6-tetrahydropyridine the solution of hydrobromic acid was added and heated under reflux.The product obtained was recrystallized and yield N-methyl-l,2,3,4,5,6-hexahydro-6,ll-dimethyl-8-hydroxy-2,6-methano-3-benzazocine (2 -hydroxy-2,5,9-trimethylbenzo-6-morphen), which then was demethylated by bromcyan (BrCN). As a result the racemic cis-l,2,3,4,5,6-hexahydro-6,ll-dimethyl-8-hydroxy-2,6-methano-3-benzazocine was obtained (that is a. 2 -hydroxy-5,9-dimethyl-6,7-benzomorphen). 

Thel, 2,3,4,5,6-hexahydro-3-(3-methyl-2-butenyl)-6,ll-dimethyl-8-hydroxy-2,6-methano-3-benzazocinewas soluble in a mixture of 0.35 ml of 2 N hydrochloric acid and 0.15 ml of water to the extent of 10%, the pH of the 1% solution being 2.80 and when the pH of the 1% solution was gradually raised by addition of 10 N sodium hydroxide solution, a precipitate formed at pH 5.4. The 1,2,3,4,5,6-hexahydro-3-(3-methyl-2-butenyl)-6,ll-dimethyl-8-hydroxy-2,6-methano-3-benzazocine hydrochloride melted at 245°-247°C, dec. 

CN l,2,3,4,5,6-hexahydro-6,l l-dimcthyl-3-(2-phenylethyl)-2,6-methano-3-benzazocin-8-ol hydrobromide... 

SYNS 2-DIMETHYL LLYI 5,9-DIMETHY1 2 -HYDRO-XYBENZOMORPHAN 2-(3,3-DIMETHYLALLYL)-2, 2 -HYDROXY-5,9-DlMETHYL-6,7-BENZOMORPHAN FORTALGESIC FORTALIN FORTRAL 1,2,3,4,5,6-HEXAHYDRO-6,ll-DIMETHYI 3-(3-METHYL-2-BUTENYL)-2,6-METHANO-3-BENZAZOCINE 2 -HYDROXY-5,9-DIMETHYL-2-(3,3-DIMETHYLALLYL)-6,7-BENZOMORPHAN dl-2 -HYDROXV-5,9-DIMETHYI 2-(3,3-DIMETH i LALLYL)-6,7-BENZOMORPHAN II-C-2... 

HEXAHYDRO-6,l 1 -DIMETHYL-2,6-METHANO-3-BENZAZOCIN-8-OL NIH 7958 NSC-107430 PENTAGIN PENTAZOCINE SOSIGON TALWAN... 

HEXAHYDRO-6,ll-DIMETHYL-3-(3-METHYL-2-BUTENYL)-2,6-METHANO-3-BENZAZOCINE see DOQ400... 

The 93-propyl levo Isomer (3c) was considerably more potent subcutaneously than morphine, while the 9oi-propyl levo Isomer (3d) was equipotent with morphine as an analgesic. None of the optical isomers suppressed withdrawal signs in monkeys the 9f5-propyl levo isomer exacerbated the withdrawal syndrome, indicating that it possesses some narcotic antagonist activity.The most active compound (4) of six homobenzomorphans was as potent subcutaneously as morphine (measured by pressure stimuli on mouse tail).115,116 Simplified procedures for the synthesis of the 6,7-benzomor-phan series have been described.117,118 Several 11-hydroxy and 11-alkoxy-2,6-methano-3-benzazocines display as potent analgesic and narcotic antagonist activity as cyclazocine.H ... 

Synthesis by Other Cyclizations. The epimeric amines (49) have been made by means of a novel S 2 reaction of the corresponding 2-bromo-6-amino-cyclohexanone derivative. Double Michael addition of (+)-a-methylbenzyl-amine to cyclo-octa-2,7-dienone derivatives forms the basis of a synthesis of the enantiomeric forms of adaline (50). Intramolecular Friedel-Crafts alkylation has been used in the synthesis of derivatives of the 2,6-methanobenz-azepine, 2,6-methano-3-benzazocine, 2,6-methano-3-benzazonine, and... 

It may be prepared by the eondensation of 1,2,3,4,5,6-hexahydro-6,11 -dimethyl-2,6-methano-3-benzazocin-8-ol with l-bromo-3-methyl-2-butene by refluxing them together in dimethylformamide as a medium and in the presenee of sodium bicarbonate. The crude pentazoeine is extraeted with an appropriate solvent and purified by recrystallization from aqueous methanol. 

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