Patent GB-912552-A (GB)
Title: Process for the production of 3-oxo-1.2.6-thiadiazine-1.1-dioxides
Filed: 1959-09-30
Abstract: The invention comprises compounds of the general formula <FORM:0912552/IV (b)/1> (wherein R1 represents a hydrogen atom or a low molecular (i.e. up to 6 C) alkyl or alkenyl, a cycloalkyl, cycloalkenyl, aryl or benzyl radical, which can be bound direct or through CO, CO2, SO2 or S and can contain O, S, SO2, CO and/or NH as chain or ring members instead of methylene groups, or N instead of methine groups, and which can have halogen atoms or nitro, cyano, hydroxy, carbamoyl or sulphamoyl groups as substituents, R2 represents a hydrogen atom or a low molecular alkyl, a phenyl, benzyl or cycloalkyl radical, R3 represents a hydrogen atom or a low molecular alkyl, a phenyl or benzyl radical and R4 a hydrogen or halogen atom or a radical as defined for R3, or R3 and R4 with the adjacent carbon atoms form a benzene ring, Y represents a hydrogen atom or a radical as defined for R3 and Z a hydrogen atom, or Y and Z together form an additional C-C linkage, and wherein any aromatic rings represented by or contained in R2, R3, R4 or Y and any fused-on benzene ring may contain low molecular alkyl or alkoxy radicals or halogen atoms as substituents) and the preparation thereof by heating to cyclize, with elimination of hydrogen halide, an N-acylsulphamide of the general formula <FORM:0912552/IV (b)/2> (wherein X1 represents a chlorine, bromine or iodine atom), or by splitting off water in the presence of condensing agents from a b -sulphamidocarboxylic acid of the general formula <FORM:0912552/IV (b)/3> or by cyclizing by gentle warming, with elimination of HX2, a b -sulphamidocarboxylic acid ester of the general formula <FORM:0912552/IV (b)/4> (wherein X2 represents an alkoxy or aryloxy radical), or by reacting a compound of the general formula I above, in which at least one of R1 and R2 represents a hydrogen atom, with a reactive compound R1X3 or R2X3 (in which R1 and R2 are other than hydrogen and X3 represents an inorganic acid radical), followed in all cases, if desired and if at least one of R1 and R2 represents a hydrogen atom, by conversion of the product into a salt with an inorganic or organic base, or, in particular cases, by treating a compound of the general formula <FORM:0912552/IV (b)/5> (wherein R11 and R12 have the meanings given for R1 and R2 other than hydrogen atoms or radicals substituted by hydroxy or amino groups), or the enol form thereof, with a halogenating agent, and, if desired, treating the resulting product of the general formula <FORM:0912552/IV (b)/6> (wherein R14 represents a halogen atom) with a reducing agent (to replace the halogen atom by hydrogen, with or without saturation of the double bond), followed, if desired, by conversion of a saturated reduction product into a salt with an inorganic or organic base.  The products are useful as therapeutic agents, intermediates for the preparation of other therapeutic substances, and, in the case of the alkali metal salts, as solubility promoters for other therapeutic substances. Aqueous solutions of salts of the compounds of general formula I (R1 and/or R2 = H) may be administered parenterally as antiphlogistic, analgesic or antipyretic agents.  N-Acylsulphamides of the general formula II above are prepared by acylating, with b -halocarboxylic acids or reactive functional derivatives thereof, substituted sulphamides of the general formula R1-NH-SO2-NH-R2, themselves obtainable by reacting N-substituted N-acylsulphamic acid chlorides with ammonia or a primary amine (R1-NH2) and splitting off the N-acyl group by the action of excess amine or of alkalies.  b -Sulphamidocarboxylic acids and esters of the general formulae IVa and IV above are prepared by reacting unsubstituted or suitably substituted sulphamic acid chlorides with b -aminocarboxylic acids or esters.  Thiadiazine derivatives of the general formula VII above are prepared by reacting correspondingly substituted malonic acid dihalides with substituted sulphamides.  Specifications 763,390 and 859,316 are referred to.