CERTAIN ETHERS,ESTERS OR NON-TOXIC ACID ADDITION SALT DERIVATIVES OF 2,2-DI-AND 2,2,3-TRI-LOWER ALKYL CHROMAN-AND CHROMEN-OLS

1314428 Pyridine substituted chromenols BEECHAM GROUP Ltd 26 April 1971 [11 May 1970] 11307/71 Headings C2C and C2P Novel substituted chromenols of the Formula (I) and non-toxic acid addition salts, wherein R 1 is C 1-6 alkyl, R 2 is C 1-20 alkyl or C 3-8 cycloalkyl- C 1-20 -alkyl, and X is an optionally substituted etherified or esterified hydroxyl group (exeluding amino acid esters) may be obtained by conventional esterification or etherification of a chromenol of Formula I in which X is OH. Examples of X are acyloxy, e.g. acetoxy, hemisuccinate ester, ethyl carbonate ester, diethylaminoethyl ether, alkyl ether, e.g. methyl ether, monophosphate ester or carbamate ester groups. Thus compounds in which X is an ester group, such as acyloxy, may be formed by reacting the chromenol with a mono or polybasic organic or inorganic acid or its acid halide or anhydride. Compounds in which X is an etherified hydroxy group may be obtained from a compound in which X is OH or ONa by reaction with an alkylhalide or, e.g. diethylaminoethyl halide. Where X is a phosphate ester, a compound where X is OH is reacted with Cl.P(O)(OCH 2 C 6 H 5 ) 2 to form an intermediate [X=-O-P(O)(OCH 2 C 6 H) 2 ] which is catalytically hydrogenated to yield a compound in which X is -OP(O)(OH) 2 which can be obtained in Na salt form. Pharmaceutical compositions, useful as antidepressants, anti-anxiety agents, hypotensives and analgesics, comprise compounds of Formula (I) above together with pharmaceutical diluents in forms suitable for administration orally or by injection.