Patent GB-1138242-A (GB)
Title: Nitrogen-containing heterocyclic compounds and processes for their production
IPC: C07D487/06
Filed: 1966-04-04
Abstract: 1,138,242. 1,2,8,9-Tetraazaphenalene derivatives. J. R. GEIGY A.G. 4 April, 1966 [5 April, 1965], No. 14763/66. Heading C2C. Novel compounds of the tautomeric formulµ and acid addition salts thereof, wherein X is O or S, and R 1  is H, C 1-6  alkyl or aryl, may be prepared either by heating a compound of formula wherein R 2  is H or C 1-6  alkyl, one of the radicals A and B is -CHO or a group of equivalent oxidative state, and the other is -COOH or a group of equivalent oxidative state, whereby the two vicinal COOH groups can be linked to form an anhydride or a CHO group can be linked with a vicinal COOH group to form a lactone, with at least two equimolecular amounts of hydrazine hydrate until ring-closure is complete, and if desired converting the OH group of the product to SH by treatment with at least an equimolar amount of P 2 S 5  followed by optional conversion of the OH or SH group to an acid addition salt; or alternatively by heating a compound of the formula wherein R 1  is as defined and R 4  is Cl, Br, OH or C 1-6  alkoxy with at least an equimolar amount of hydrazine hydrate and optionally treating the product with P 2 S 5  and/or an acid as above. 3-Dibromomethylphthalic anhydride is prepared by bromination of 3-methylphthalic anhydride with N-bromosuccinimide. This product is hydrolysed to give 3-hydroxy-7-carboxyphthalide and its tautomer 3-aldehydo-phthalic acid. It is also hydrolysed to give 7-carboxyphthalide, which is subsequently treated with POCl 5  or SOCl 2  to give 7-chlorocarbonyl-phthalide, which is in turn brominated with N-bromosuccinimide to give 7-chlorocarbonyl-3-bromophthalide. 2 - Carbomethoxy - 6 - dibromomethyl - benzoic acid is prepared by bromination of 2-carbomethoxy - 6 - methyl - benzoic acid, which has been itself prepared by esterification of 3-methylphthalic acid. 8 - Carboxy " 1 - (2H) - phthalazinone is prepared by refluxing with hydrazine hydrate either 3 - dibromomethylphthalic anhydride, or 7 - chlorocarbonyl - 3 - bromo - phthalide. Esters of this acid are made either by treatment thereof with a diazoalkane, or by treatment with SOCl 2 , followed by reaction of the intermediate product with an alkanol (EtOH and MeOH exemplified). The ethyl esters of this acid are N-alkylated with Et 2 SO 4  or Me 2 SO 4 . 8 - Carbethoxy - 1(2H) - phthalazinone is prepared by alcoholysing 7-chlorocarbonylphthalide with EtOH to give 7-carbethoxy-phthalide which is then brominated to give 3-bromo-7- carbethoxy phthalide, which is finally reacted with hydrazine hydrate. 2 - Phenyl - 8 - carboxy - 1(2H) - phthalazinone is prepared by reacting phenylhydrazine with 3-hydroxy-7-carboxy-phthalide. Pharmaceutical compositions having hypotensive and sedative action comprise at least one compound of the first formula given above or a physiologically acceptable salt thereof, together with at least one pharmaceutically acceptable inert carrier. They may take the forms of tablets, capsules, suspensions, solutions, syrups, powders &c., and may be administered orally or parenterally.