| 摘要 |
<p>1,203,147. 4H - Benzo[5,6]cyclohepta[1,2-d]- oxazole and -thiazole derivatives. SANDOZ Ltd. 16 May, 1968 [17 May, 1967], No. 23331/68. Heading C2C. Novel 4H - benzo[5,6]cyclohepta[1,2-d]-oxazole and -thiazole derivatives of the general formula wherein Y is a hydrogen, chlorine, or bromine atom; R is a C 1-4 alkyl group; X is an oxygen or sulphur atom; Q is a hydrogen atom or a C 1-4 alkyl, cyano, 2-hydroxyethyl or 2-acetoxyethyl radical; x y is -CH 2 CH 2 - or -CH = CH-; and w z is >-CH-CH< or > C = C < ; with the provisos (i) that when X is an oxygen atom, #x y is -CH 2 CH 2 - and #w z is >C=C< and (ii) that #x y and #w z do not both contain a double bond and do not both contain a single bond between the two carbon atoms; and pharmaceutically acceptable acid addition salts thereof except wherein Q is a cyano radical are prepared (a) when Q is a C 1-4 alkyl radical, by dehydration of a 4H-benzo[5,6]cyclohepta[1,2- d]-oxazol- or thiazol-4-ol derivative of the general formula wherein Q<SP>1</SP> is a C 1-4 alkyl radical; (b) when Q is a cyano radical, by subjection of the corresponding compound wherein Q is a C 1-4 alkyl radical to a von Braun cyanogen bromide reaction; (c) when Q is a hydrogen atom, by heating of the corresponding compound wherein Q is a cyano radical with aqueous mineral acid; (d) when Q is a 2-hydroxyethyl radical, by hydroxyethylation of the corresponding compound wherein Q is a hydrogen atom; or (e) when Q is a 2-acetoxyethyl radical, by acetylation of the corresponding compound wherein Q is a 2-hydroxyethyl radical; followed optionally, except in (b), by conversion of the product to a pharmaceutically acceptable acid addition salt thereof. Pharmaceutical compositions having antihistaminic, anti-Parkinsonian, tranquillizing and anti-depressant activity comprise, as active ingredient, a 4H-benzo[5,6]cyclohepta[1,2-d]- oxazole or -thiazole derivative of the first general formula above, other than wherein Q is a cyano radical, or a pharmaceutically acceptable acid addition salt thereof, in association with a pharmaceutically acceptable diluent or carrier, and may be administered orally. 4H - Benzo[5,6]cyclohepta[1,2-d]oxazol- and thiazol-4-ol derivatives of the second general formula above are prepared by reaction of a 4H - benzo[5,6]cyclohepta[1,2-d]oxazol- or thiazol-4-one of the general formula with a Grignard reagent of the general formula wherein M is a magnesium atom and Hal is a chlorine, bromine or iodine atom, and hydrolysis of the resulting Grignard adduct. 4H - Benzo[5,6]cyclohepta[1,2-d]ozaxol- or thiazol-4-ones of the third general formula above are prepared (a) when X is an oxygen atom, by nitrosation of a 6,7,8,9-tetrahydro- 5H-benzocyclohepten-5-one of the general formula followed by treatment of the resulting 6-isonitroso - 6,7,8,9 tetrahydro - 5H - benzocyclohepten- 5-one of the general formula with an alkanoylating agent in which the alkanoylating group is a RCO-group, in the presence of a hydrohalic acid of the general formula HHal; or (b) when X is a sulphur atom, by treatment of the corresponding benzo[5,6]cyclohepta[1,2-d]- oxazol - 4 - one of the third general formula above wherein X is an oxygen atom with a thiating agent. 3 - Chloro - 6,7,8,9 - tetrahydro - 5H - benzocyclohepten-5-one is prepared by treatment of 6,7,8,9 - tetrahydro - 5H - benzocyclohepten - 5- one with chlorine in the presence of aluminium chloride.</p> |
