Patent GB-979994-A (GB)
Title: Isoindolinone derivatives
Inventor: LEE GLYN EVAN
IPC: C07D209/46
Filed: 1961-07-28
Abstract: The invention comprises compounds of formula <FORM:0979994/C1/1> (where R1 is a hydrogen atom, an alkyl group having 1 to 6 carbon atoms, a saturated cyclic or bicyclic hydrocarbon group containing 5 to 8 endocyclic carbon atoms optionally substituted by one or more alkyl groups having 1 to 6 carbon atoms, or an alkyl group having 1 to 6 carbon atoms and substituted by such a cyclic or bicyclic hydrocarbon group, and R2 is a hydrogen atom or an alkyl group having 1 to 6 carbon atoms) and alkali metal salts thereof, and their preparation (1) by reducing substituted phthalimides of formula <FORM:0979994/C1/2> by known methods for reduction of a keto-group, e.g. treatment with tin and hydrochloric acid, or by electrolysis (see Division C7), (2) by reacting an isoindolinone-6-sulphonyl halide with ammonia or an amine of formula R2NH2, (3) by reducing 2-cyclohexenyl-isoindolinone by known methods for reduction of an ethylenic double bond, e.g. catalytic hydrogenation, or (4) by treating compounds of the invention where R2 is hydrogen with an alkylating agent.  Compounds of formula <FORM:0979994/C1/3> are prepared by diazotization in hydrochloric acid of the corresponding amino-phthalimides of formula <FORM:0979994/C1/4> treating the diazonium product with sulphur dioxide in glacial acetic acid to give the corresponding sulphonyl chloride, and reaction of this product with ammonia or an amine of formula R2NH2.  Compounds of formula <FORM:0979994/C1/5> are prepared by nitrating compounds of formula <FORM:0979994/C1/6> reducing the nitro-group formed to an amino-group, diazotizing this group and reacting the product with sulphur dioxide in glacial acetic acid.  Compounds of formula <FORM:0979994/C1/7> are prepared by reaction of a compound of formula <FORM:0979994/C1/8> with 1-amino-cyclohex-3-ene.  Compounds of formula <FORM:0979994/C1/9> are obtained as by-products in the electrolytic preparation of the compounds of the invention.  The compounds of the invention have diuretic, natriuretic, saluretic and hypotensive activity, and may be used in pharmaceutical compositions in combination with a pharmaceutical carrier in forms suitable for oral or parenteral administration, e.g. as tablets, pills, dispersible powders, granules, emulsions or suspensions.ALSO:Isoindolinone derivatives (see Division C2) of formulae: <FORM:0979994/C6-C7/1> (where R1 is a hydrogen atom or an alkyl group with 1-6 carbon atoms optionally substituted by a saturated cyclic or bicyclic hydrocarbon group having 5-8 endocyclic carbon atoms, said hydrocarbon group being optionally substituted by an alkyl group having 1-6 carbon atoms, and R2 is a hydrogen atom or an alkyl group having 1-6 carbon atoms) are prepared by electrolysis of the corresponding substituted phthalimides.  In specific examples electrolysis is effected in a methanol-sulphuric acid solution using (a) a lead cathode and carbon anode at a current density of 0.03 Amp<\>geres per sq. cm. and a cathode potential of -0.7 Volts relative to a calomel electrode, the cathode being arranged around the periphery of the vessel, and (b) a mercury cathode and carbon anode at a current density of 0.1 Amp<\>geres per sq. cm. and a cathode potential of -1.25 Volts relative to a saturated calomel electrode, the anode being in both cases in the form of a rod enclosed by a sausage-skin bag.