Patent GB-789057-A (GB)
Title: 2, 4-diaminothiazoles containing a halogenated aryl radical in the 5-position and derivatives
IPC: C07D277/42
Filed: 1956-05-18
Abstract: The invention comprises thiazoles of the general formula <FORM:0789057/IV (b)/1> (wherein n is 1 or 2 and R is hydrogen or a hydrocarbon carboxylic acid acyl radical of 1 to 8 carbon atoms and "Halogen" is fluorine, chlorine, bromine or iodine) and non-toxic salts thereof, and the preparation of the diamines by treating a compound of the formula Halophenyl-CH(X)-CN(X being an alkyl- or arylsulphonoxy group) with a substantially equivalent proportion of thiourea.  The diacylamino compounds are prepared by treatment of the diamines or their salts with acyl halides or anhydrides with or without the presence of an additional base, e.g. pyridine, for a short period of time.  Similar treatment in the presence of a base for a relatively long period of time results in the formation of 2:4-diacylamino-3-acyl-5-(halophenyl) - thiazolidines.  Treatment of the thiazoles with hydrochloric acid converts them to thiazolones and thiazolidine-2:4-diones.  In the examples: 2:4-diamino-5-(p-fluorophenyl)-thiazole benzenesulphonate (free base and hydrochloride also described) is prepared from p-fluoro-benzaldehyde, benzenesulphonyl chloride, sodium cyanide and thiourea, the corresponding p-iodo compound and 2:4-diamino-5-(m-chloro- and m:p-dichloro-phenyl)-thiazoles (hydrochlorides also described) are prepared similarly, 2:4-diamino-5-(o-chlorophenyl)-thiazole benzenesulphonate (hydrochloride also described) is prepared by mixing o-chlorobenzaldehyde, benzenesulphonyl chloride and sodium cyanide to give 2-chloro-a -cyanobenzyl benzenesulphonate and reacting this with thiourea, 2:4 - diamino - 5 - (p - chloro - and o:p-dichloro - phenyl) - thiazole benzenesulphonates (hydrochlorides and free base of the former also described) are similarly prepared via 4-chloro-and o,p - dichloro - a  - cyanobenzyl benzenesulphonates respectively, 2:4 - diacetylamino is prepared by acylation with acetic anhydride of the corresponding diamine for 2 1/2 hours at room temperature, 2:4-dibutylamino - 5 - (p - chlorophenyl) - thiazole and 2:4 - diacetylamino - 5 - (o,p - dichlorophenyl)-thiazole are similarly prepared, reaction times being 5 hours and 1 hour respectively, 2:4-dibenzoylamino- and 2:4-di-(b -cyclopentylpropionylamino) - 5 - (p - fluorophenyl) - thiazoles are prepared by acylation of 2:4-diamino-5 - (p - fluorophenyl) - thiazole benzenesulphonate with benzoyl chloride and b -cyclopentylpropionyl chloride respectively for 2 and 3 hours respectively in presence of pyridine, and 2:4-diacetylamino - 3 - acetyl - 5 - (o-chloro-, p-chloro-and o:p-dichloro-phenyl)-thiazolidines are prepared by acylation of 2:4-diamino-5-(o-chloro-, p-chloro- and o:p-dichloro-phenyl)-thiazole benzenesulphonates with acetic anhydride for 1 day, 1 day and 12 hours respectively in presence of pyridine.  Reference is also made to formyl, propionyl, pentanoyl, hexanoyl, toluyl, phenacetyl and cyclohexane-acetyl radicals as acylating groups and to the following further acids and acidic like compounds as salt forming agents: sulphuric, phosphoric, hydrohalic, sulphamic, citric, lactic, maleic, malic, succinic, tartaric, cinnamic, acetic, benzoic, gluconic and ascorbic acids, 8-halotheophyllines and 8-chlorotheobromine.  In further examples 2:4-diamino-5-(o-chlorophenyl)-thiazole is (1) refluxed with dilute hydrochloric acid, added to ice, filtered and the filtrate neutralized to give 2 - amino - 5 - (o - chlorophenyl) - 4(5) - thiazolone; and (2) refluxed with dilute hydrochloric acid, added to ice and the precipitate again refluxed with hydrochloric acid with subsequent ice cooling to yield 5 - (o - chlorophenyl)-thiazolidine-2:4-dione.