Patent GB-1221598-A (GB)
Title: Improvements in or relating to dihydro- and tetrahydronaphthalenes and the manufacture thereof
IPC: A01N33/10
Filed: 1968-12-17
Abstract: 1,221,598. 4 - Phenyl - 3 - Cycloalkyl - 1,2 - dihydro- and 1,2,3,4-tetrahydro-naphthalenes. UPJOHN CO. 17 Dec., 1968 [2 Jan., 1968], No. 60016/68. Heading C2C. [Also in Division A5] Novel 4 - phenyl - 3 - cycloalkyl - 1,2 - dihydro- and 1,2,3,4-tetrahydronaphthalenes of the general formulµ wherein R is a C 1-4  alkoxy or C 3-6  cycloalkoxy group; R 1  is a hydrogen atom or a C 1-4  alkyl group; R 2  is a hydrogen or halogen atom, a C 1-4  alkyl, C 1-4  alkoxy or hydroxy group or a C 1-4  alkoxy group substituted by a dihydroxyalkyl group, having from 2 to 5 carbon atoms, a group of the formula NR 3 R 4  in which R 3  and R 4  are each alkyl groups or, together with the nitrogen atom to which they are attached, form the residue of a saturated heterocyclic amino group having from 5 to 7 ring members, or a group of the formula -C m H 2m R 5 , in which m is an integer from 1 to 6 and R 5  is a carboxy or carb-C 1-4  alkoxy group; and n is 4 or 5, and pharmacologically acceptable acid addition, alkali and alkaline earth metal (when R 2  is a hydroxy group) and quaternary ammonium (when R 2  contains an amino substituent) salts thereof are prepared (a) when R 2  is a C 1-4  alkoxy group or a substituted alkoxy group in a compound of the first general formula above, by dealkylation of a butanone derivative of the general formula wherein R<SP>1</SP> 1  is a C 1-4  alkyl group, cyclization of the resulting hydroxy ketone of the general formula and alkylation of the resulting 4-hydroxyphenyl- 3 - cycloalkyl - 1,2 - dihydronaphthalene of the general formula with a compound of the general formula R 2 X, in which X is a halogen atom; (b) when R 2  is a C 1-4  alkoxy group or a substituted alkoxy group in a cis-isomer of the second general formula above, by dealkylation of a butanone derivative of the third general formula above, cyclization of the resulting hydroxy ketone of the fourth general formula above, catalytic reduction of the resulting 4-hydroxyphenyl-3- cycloalkyl - 1,2 - dihydronaphthalene of the fifth general formula above and alkylation of the resulting cis - 4 - hydroxyphenyl - 3 - cycloalkyl- 1,2,3,4-tetrahydronaphthalene of the general formula with a compound of the sixth general formula above; (c) when R 2  is a C 1-4  alkoxy or a substituted alkoxy group in a trans-isomer of the second general formula above, by dealkylation of a butanone derivative of the third general formula above, reduction of the resulting hydroxy ketone of the fourth general formula above with lithium aluminium hydride, cyclization of the carbinol of the general formula so obtained and alkylation of the resulting trans - 4 - hydroxyphenyl - 3 - cycloalkyl - 1,2,3,4- tetrahydronaphthalene of the general formula (d) when R 2  is a C 1-4  alkoxy group substituted by a group of the formula -C m H 2m R 5  in a cisisomer of the second general formula above, by reaction of a haloester of the general formula Hal-C 1-4  alkylene-C m H 2m R<SP>1</SP> 5 , in which Hal is a halogen atom and R<SP>1</SP> 5  is a carb-C 1-4  alkoxy group, with an alkali metal salt of a cis-4- hydroxyphenyl - 3 - cycloalkyl - 1,2,3,4 - tetrahydronaphthalene of the seventh general formula above, followed optionally by hydrolysis of the resulting ester in which R 5  is a carb-C 1-4  alkoxy group to the corresponding free acid in which R 5  is a carboxy group; (e) when R 2  is an alkoxy group substituted by a dihydroxyalkyl group in a cis-isomer of the second general formula above, by reaction of a cis-4-hydroxyphenyl - 3 - cycloalkyl - 1,2,3,4 - tetrahydronaphthalene of the seventh general formula above with a dihydroxyalkyl halide; (f) when R 2  is other than a C 1-4  alkoxy group or a substituted C 1-4  alkoxy group in a compound of the first general formula above, by cyclization of a butanone derivative of the general formula wherein Ra is a hydrogen or halogen atom or a hydroxy or C 1-4  alkyl group; (g) when R 2  is other than a C 1-4  alkoxy group or a substituted C 1-4  alkoxy group in a cis-isomer of the second general formula above, by a cyclization as in (f) above, followed by catalytic reduction of the resulting compound of the first general formula above, (h) when R 2  is other than a C 1-4  alkoxy group or a substituted C 1-4  alkoxy group in a trans-isomer of the second general formula above, by reduction of a butanone derivative of the eleventh general formula below with lithium aluminium hydride and cyclization of the resulting carbinol of the general formula and (i) when R 2  is a C 1-4  alkoxy group or a substituted C 1-4  alkoxy group in a compound of the second general formula above, by catalytic reduction of the corresponding compound of the first general formula above; followed optionally by salification. Butanone derivatives of the general formula wherein R 6  is a hydrogen or halogen atom or a C 1-4  alkyl or C 1-4  alkoxy group, by formylation of a phenyl cycloalkylmethyl ketone of the general formula subjection of the resulting keto-aldehyde of the general formula to a modified Wittig reaction and catalytic reduction of the resulting unsaturated ketones of the general formulµ 2 - Cyclopentyl - p - methoxyacetophenone is prepared by reaction of anisole with cyclopentylacetyl chloride in the presence of aluminium chloride. Methoxybenzyltriphenylphosphonium chlorides are prepared by reaction of methoxybenzyl chlorides with triphenylphosphine.