Patent GB-795174-A (GB)
Title: Heterocyclic sulphonamides
IPC: C07D285/125
Filed: 1955-09-22
Abstract: The invention comprises C-polyheterocyclic sulphonamides, i.e those containing 2 or more hetero atoms in the heterocycle, containing a sulphur atom in the alpha position to the sulphonamide group and/or having the heterocycle at least partly reduced; compounds of the formula R-SO2NR1R11 wherein -NR1R11 is a primary, secondary or tertiary amido group and R is a partially or wholly reduced thiazole, oxazole, imidazole, pyrimidine, pyrazine, pyridazine, oxazine, thiazine or thiadiazole radical; 6-ethoxybenzothiazole-2-sulphonamide; 4-phenyl-5-thiono-4 : 5-dihydro-1 : 3 : 4 - thiadiazole - 2 - sulphonamide; 6 - carboxamidobenzothiazole - 2 - sulphonamides and 6 - carboxamido - 4 - hydroxy - pyrimidine-2-sulphonamides containing from 1 to 8 carbon atoms in the carboxamido radical; and the preparation of C-heterocyclic sulphonamides in general by the oxidative condensation of a C-heterocyclic thiol and ammonia or a primary or secondary amine followed by oxidation of the resulting sulphenamide.  In a modification of this process the sulphenamide is prepared by reacting a C-heterocyclic thiol with an N-chloramine.  Preferably, the oxidative condensation is brought about with the aid of a hypohalite or a halogen in aqueous alkaline solution, with addition of a water-miscible solvent, e.g. ethanol or dioxan, if necessary, the temperature preferably being kept below 30 DEG  C. and advantageously at 0 DEG  to 10 DEG  C.  Acid oxidation or a two-stage process via the disulphide may also be used.  The oxidation of the sulphenamides to the sulphonamides is advantageously achieved with aqueous potassium permanganate in a suitable solvent, although other oxidizing agents such as alkaline hydrogen peroxide and sodium peroxide, hydrogen peroxide in acetic acid, chromic acid, nitric acid or permanganic acid can also be used, at temperatures normally between 0 DEG  and 50 DEG  C.  In examples: (1) 6-ethoxybenzothiazole-2-thiol in sodium hydroxide solution reacts with sodium hypochlorite solution and ammonium hydroxide at a low temperature to give 6-ethoxybenzothiazole-2-sulphenamide which on permanganate oxidation gives the corresponding sulphonamide; (2) 6-acetamidobenzothiazole-2-sulphenamide, the corresponding 4- and 6-propionamido-, 4- and 6-valeramido-, 4- and 6-caprylamido-, 4- and 6-benzamido- and 4-carboxy-6-benzamido-compounds, and the sulphonamides corresponding to all these sulphenamides are similarly prepared; (3) 4-phenyl-5-thiono-4 : 5-dihydro-1 : 3 : 4-thiadiazole-2-sulphenamide is prepared either as in (1) or by treating the corresponding disulphide with alcoholic ammonia and is then oxidized as in (1) to the corresponding sulphonamide; 4 : 4 : 6-trimethyl-1 : 2 : 3 : 4-tetrahydropyrimidine-2-, 4 : 5-dihydrothiazole-2-, 4-methyl - 4 : 5 - dihydrothiazole - 2 -, 5 : 5- di-methyl - 4 : 5 - dihydrothiazole - 2 -, 5 - ethyl - 5 - methyl - 4 : 5 - dihydrothiazole - 2 -, imidazoline-2- and 2 : 4-diketo-1 : 2 : 3 : 4-tetrahydropyrimidine-6-sulphonamides are similarly prepared; (4) 6-acetamido-4-acetoxypyrimidine 2-thiol (prepared from 6-amino-4-hydroxypyrimidine-2-thiol and acetic anhydride in pyridine) is reacted as in (1) to give 6-acetamido-4-hydroxypyrimidine-2-sulphenamide and this is oxidized as in (1) to the corresponding sulphonamide; the 6-propionamido-, 6-valeramido-, 6-caprylamido- and 6-benzamido-compounds are similarly obtained; (5) 5-acetamido-1 : 3 : 4-thiadiazole-2-sulphenamide and the corresponding sulphonamide, and the corresponding 5-propionamido-, 5-valeramido-, 5-caprylamido- and 5-benzamido-compounds are prepared as in (1).  Reference is also made to the preparation of sulphonamides from thiols containing other heterocyclic radicals with one, two or more hetero atoms, not reduced or wholly or partly reduced, substituted or unsubstituted, which may be fused with one or more homo or heterocyclic rings.  Specific reference is made to isoxazole, pteridine, purine, pyrrole, isoxazoline, pyrrolidine, tetrazole, triazole, pyridine, thiophene, furan, pyran, thiapyran, benzimidazole, naphthothiazole, benzoxazole, quinoline, and pyrido[2 : 1-c-]-s-triazole, in addition to the rings referred to above, to dithiols such as 1 : 2 : 4-thiadiazole-3 : 5- and -2 : 5-dithiols, to alkyl, aryl, aralkyl, alkoxy, carboxamido, halogen, thiono, oxo and hydroxy substituents in the heterocyclic rings and these and nitro groups in the fused-on aromatic rings, to N-alkyl-, N : N-dialkyl-, N-2-aminoethyl-, N-cycloalkyl-, N-alkyl-N-cycloalkyl-, N-2-pyridyl-, N-2-thiazolyl-, N-2-pyrimidyl-, N-phenyl-, N-methyl-N-phenyl-, N-2-thienyl-, N-thenyl-, N-2-furyl-, N-tolyl-, N-benzyl- and N-phenylethyl-sulphonamides and to sulphonamides in which the amide nitrogen forms part of a heterocycle such as piperidine, pyrrolidine, piperazine and morpholine and alkyl substituted derivatives thereof.  Specification 377,730, [Group IV], is referred to.ALSO:Heterocyclic sulphenamides wherein the sulphenamide group is attached to a carbon atom of the heterocycle are used as vulcanization accelerators in the compounding and vulcanization of rubber.  Specific reference is made to the use of 6-ethoxybenzothiazole-2-sulphenamide, 6-acetamidobenzothiazole-2-sulphenamide, 4-phenyl-5-thiono-4 : 5-dihydro-1 : 3 : 4-thiadiazole-2-sulphenamide and 5-acetamido-1 : 3 : 4-thiadiazole-2-sulphenamide as vulcanization accelerators.