Patent GB-1173215-A (GB)
Title: Derivatives of Thebaine and Oripavine
Inventor: BENTLEY KENNETH WALTER
IPC: C07D489/12
Filed: 1967-06-20
Abstract: 1,173,215. Derivative of thebaine and oripavine. RECKITT & SONS Ltd. 12 June, 1968 [20 June. 1967], No. 28488/67. Heading C2C. Novel compounds have the Formula (I) in which Y represents -CH = CH- or -CH 2 CH 2 -; R represents H or CH 3 ; R<SP>1</SP> represents C 1-8  alkyl which may be substituted on carbon atoms 1-4 by a phenyl, tolyl or a C 5-7  cycloalkyl group; R<SP>2</SP> is H; or R<SP>1</SP> and R<SP>2</SP> together represent -(CH 2 ) 4 -; R<SP>3</SP> represents H, alkyl, alkenyl or alkynyl each of which may contain up to 8 carbon atoms, or C 4-7  alicyclicsubstituted methyl group. They may be prepared (a) (where R = H) by heating compounds of formula (II) or (III) wherein R<SP>4</SP> represents H, a phenyl, tolyl or C 5-7  cycloalkyl group, or C 1-7  alkyl group substituted on carbon atoms 1-3 by a phenyl, tolyl or C 5-7  cycloalkyl group, in diethylene glycol with hydrazine hydrate, and then heating the mixture with an alkali metal hydroxide at a temperature of about 200‹ C; or (b) (where R<SP>2</SP> = H) by hydrogenating a compound of formula (I) where R<SP>2</SP> = H and R<SP>1</SP> is -C(R<SP>5</SP>) = CHR<SP>6</SP>, where R<SP>5</SP> is H, CH 3  or phenyl; R<SP>6</SP> is H, phenyl, tolyl or a C 1-6  alkyl substituted on carbons 1-3 by a C 5-7  alicyclic group, a phenyl or tolyl group, in the presence of hydrogenation catalysts, such as Pd/C or PtO 2 ; or (c) (where R<SP>2</SP> = H and R<SP>1</SP> = CH 3  or C 2 H 5 ) by hydrogenating a compound of formula (V) where R' represents H or CH 3 , in the presence of hydrogenation catalysts such as Pd/C or PtO 2 ; or (d) (where R<SP>2</SP> is H and R<SP>1</SP> is CH 3  or C 2 H 5 ) by treating a compound of Formula I in which R<SP>1</SP> represents -CH(R<SP>7</SP>)-OTosyl, R<SP>7</SP> being H or CH 3 , by hydrogenolysis with LiAlH 4 . Compounds of Formula I in which R is H are obtained from those in which R is CH 3  by heating with an alkali metal hydroxide in diethylene glycol at a temperature above 180‹ C. Compounds of Formula I in which R is CH 3  can be obtained from those in which R is H by methylation with (CH 3 ) 2 SO 4  or CH 3 I. Compounds in which R<SP>3</SP> is H can be made from those in which R<SP>3</SP> is CH 3  by treatment with CNBr forming the N-cyano compound and treatment of this with an alkali at temperatures up to 180‹ C. By effecting this treatment at 200-210‹ C. compounds in which both R and R<SP>3</SP> are H atoms are obtained. Compounds in which R<SP>3</SP> is other than H can be obtained from those in which R<SP>3</SP> is H by treatment with an appropriate halide R<SP>3</SP>X or by acylation with an appropriate acid halide or anhydride followed by reduction with LiAlH 4 . Compounds in which Y is -CH = CH- can be converted to those in which Y is -CH 2 CH 2 - by hydrogenation in the presence of Pd/C or PtO 2 . Salts may be formed with pharmaceutically acceptable acids. Pharmaceutical compositions, having central nervous system effects such as analgesic, sedative and antitussive actions, and depressant effects on peripheral autonomic nerve function, comprise a compound of Formula I as defined above, or a pharmaceutically acceptable salt thereof, and a pharmaceutical carrier, preferably in the form of tablets.