Patent GB-767027-A (GB)
Title: Thiosalicylhydrazide, dithiosalicylhydrazide and their derivatives
IPC: C07D215/12
Filed: 1954-03-08
Abstract: The invention comprises thiosalicylhydrazide, dithiosalicylhydrazide and derivatives of each represented by the formula: Z-S-R-CO-NH-W in which R is an ortho-phenylene radical or an ortho-phenylene radical substituted by not more than 4 chlorine or bromine atoms; W is an amino, benzalimino or benzylamino radical or a benzalinimo or benzylamino radical substituted by not more than 5 chlorine or bromine, hydroxyl, lower alkyl, lower alkoxy, lower alkylsulphonyl, lower carboxyalkoxy, lower dialkylaminoalkyl, or lower chloralkoxy radicals ("lower" signifying a radical of 5 or less carbon atoms) or a radical of the formula -N = CH-Q in which Q is a quinolyl radical, and Z is hydrogen or a radical identical with the group-S-R-CO-NH-W as defined above.  The terms thiosalicylhydrazide and dithiosalicylhydrazide refer, respectively, to compounds of the formulae: <FORM:0767027/IV(b)/1> and <FORM:0767027/IV(b)/2> Thiosalicylhydrazide and its substitution derivatives are obtained by reaction of an alkyl ester of thiosalicylic acid or a substituted thiosalicylic acid with hydrazine hydrate.  The products can be oxidized in air or with iodine or other mild oxidizing agents such as iodine to give the dithiosalicylhydrazides which can also be obtained by the reaction of hydrazine with dithiosalicylic acid esters.  These compounds can be reacted with benzaldehydes to give the benzal derivatives, which on reduction are converted to the benzyl derivatives.  The products have bactericidal and fungicidal activity (see Group VI). In examples: (1) thiosalicylhydrazide is prepared by reacting methyl thiosalicylate with hydrazine hydrate in isopropyl alcohol; (2) dithiosalicylhydrazide is prepared by oxidizing thiosalicylhydrazide with iodine; (3) salicylalthiosalicylhydrazide is prepared by reacting thiosalicylhydrazide with salicylhydrazide; (4) 4-ethylsulphonylbenzalthiosalicylhydrazide is prepared similarly; (6) bis-(4-quinolylmethylene) dithiosalicylhydrazide is prepared by the reaction of dithiosalicylhydrazide dihydrochloride with 4-formylquinoline.  In a generally similar manner there are obtained (5) 2,4-dichlorobenzalthiosalicylhydrazide; (7) bis-(2-quinolylmethylene)-dithiosalicylhydrazide; (8) and (9) bis-(2,4- or 3,4-dichlorobenzal) dithiosalicylhydrazides; (10) 5,51-dibromodithiosalicylhydrazide; (11) bis-(2,4-dichlorobenzal) - 5,51 - dichlorodithiosalicylhydrazide; (12) bis-(2-methoxybenzal)-5,51-dichlorodithiosalicylhydrazide; (13) 3,31,5,51-tetrachlorodithiosalicylhydrazide; (15) bis-(4-b  - chlorethoxybenzal) - dithiosalicylhydrazide; (16) bis - (2 - n - propoxybenzal) - dithiosalicylhydrazide.  In Example (14) bis-[N-(2,4-dichlorobenzyl)] dithiosalicylhydrazide is prepared by the electrolytic reduction of 2,4-dichlorobenzalthiosalicylhydrazide. Thiosalicylic acid is obtained by the reduction of dithiosalicylic acid with zinc and acetic acid or with sodium hydrosulphite in alkaline solution.  Substituted thiosalicylic acids are obtained by diazotization of a substituted anthranilic acid and condensation of the diazonium compound with potassium ethyl xanthate followed by hydrolysis, the preparation of 4- and 5-chloro-, 3,5 - dichloro -, 5 - bromo - and 3,5 - dibromothio-salicylic acids by this method being described.  5,51 - Dichloro - dithiosalicylic acid is prepared by the oxidation of 5-chlorothiosalicylic acid with iodine.  The acids are converted to esters by reaction with alkanols, e.g. methanol. Alkoxybenzaldehydes are obtained by the reaction of a hydroxy-benzaldehyde with an excess of alkyl halide (or, in the preparation of 2-formyl phenoxyacetic acid, with chloracetic acid). In this manner there are prepared benzaldehydes having 2 - methoxy, ethoxy, n-propoxy, n-butoxy, isobutoxy, sec.-butoxy, n-amyloxy, isoamyloxy, carboxymethoxy, 2-chlorethoxy substituents, or 4-(2-chloroethoxy) or 2-diethylaminoethoxy substituents.ALSO:A bactericidal and fungicidal composition comprises as active ingredients thiosalicylhydrazide, dithiosalicylhydrazide and derivatives of each represented by the formula Z - S - R - CO - NH - W in which R is an ortho-phenylene radical or an orthophenylene radical substituted by not more than 4 chlorine or bromine atoms; W is an amino, benzalamino or benzylamino radical or such a radical substituted by not more than 5 chlorine, bromine, hydroxyl, lower - alkyl, lower alkoxy, lower chloralkoxy, lower alkylsulphony, lower carbalkoxyalkoxy or lower dialkylaminoalkyl radicals, or W is a quinolylmethyleneamino radical, and Z is hydrogen or a radical identical with the radical represented by -S-R-CO-NH-W and salts of such derivatives.  The preparation of such compounds is also described (see Group IV(b)).  In examples (17) polyethylene glycol wax, polyethylene glycol liquid, sorbitan monopalmitate and water are stirred together at 70 DEG C. and to this base are added bis-(4-quinolylmethylene) dithio-salicylhydrazide dihydrochloride, ethyl p - aminobenzoate and b  - phenylethyl alcohol.  Alternative ingredients are geraniol, 2 - dimethylaminoethyl p - butylaminobenzoate and sodium lauryl sulphate; (18) a thixotropic suspension is prepared by passing mixed suspensions of bis -(2, 4 - dichlorobenzal) dithio-salicylhydrazide in water and of complex colloidal magnesium aluminium silicate, polyethylene glycol wax and water through a colloid mill; (19) a vaginal suppository is prepared from spermaceti, cocoa butter and bis - (3, 4 - dichlorobenzal) dithiosalicylhydrazide.  As a dusting powder may be employed a mixture of talcum powder, colloidal kaolin and one or more of the active compounds.