Patent GB-966972-A (GB)
Title: Substituted oxadiazolones and oxadiazolthiones
Filed: 1960-02-12
Abstract: The invention comprises compounds of the general formulae <FORM:0966972/C1/1> <FORM:0966972/C1/2> wherein R and R1 may be the same or different and represent hydrogen atoms or acyl groups, Y represents an oxygen or sulphur atom, and the symbols X which may be the same or different represent hydrogen or halogen atoms or amino, acylamido, hydroxy, alkoxy, acyloxy, alkyl, aralkyl, isocyano or nitro groups but do not all represent hydrogen when R and R1 represent hydrogen and Y represents oxygen, and salts with bases of the compounds of the above formulae wherein R represents hydrogen, the physiologically acceptable acid addition salts of compounds of the above formula having basic substituents, and salts with bases of compounds of the above formulae wherein R1 represents hydrogen, and the preparation thereof by reacting a hydrazide of the general formula <FORM:0966972/C1/3> wherein R1 has the above significance, and the symbols Z represent hydrogen or halogen atoms or amino, acylamido, hydroxy, alkoxy, acyloxy, alkyl, aralkyl or nitro groups with an agent to condense with the hydrazide to form an oxadiazolone or oxadiazolthione, for example, a carbonyl in thiocarbonyl dihalide such as phosgene or thiophosgene, a haloformic ester or a dialkyl carbamyl halide and, if necessary, heating the product with acid to convert any complex products or isocyanates into the required diazolones followed, where required, by acylating the product to produce compounds in which R and or/R1 is an acyloxy group.  The compounds of the first general formula above wherein one or more of the groups X is a free amino group may also be prepared by reducing the corresponding compound wherein one or more of the groups X represents a nitro group or by hydrolysing the corresponding compound wherein one or more of the groups X is an amido group. In the case of hydrazide reactants of the third general formula above in which one or more of the symbols Z represents an unsubstituted amino group, it is possible to use an excess of the carbonyl or thiocarbonyl dihalide to form compound of the first two general formulae above in which one or more of the symbols X represents an isocyano group, and it is possible to convert a resulting isocyano group to an amino group by hydrolysis, for example with aqueous mineral acid. The above processes may be modified in that the hydrazide reactants of the general formula <FORM:0966972/C1/4> wherein R1 and Z have the above significance, are prepared by reacting esters of the general formula <FORM:0966972/C1/5> wherein R2 represents a carboxylic ester group, with hydrazine or its hydrate.  Therapeutic compositions which may be in a form suitable for oral, rectal or parenteral administration and have antiphlogistic, antipyretic and analgetic activity contain as the active ingredient a compound of one of the first two general formulae above wherein R, R1, X and Y have the significance indicated and wherein all the symbols X represent hydrogen when R and R1 represent hydrogen and Y represents oxygen.  The Provisional Specification refers to compounds of the second of the first two general formulae above wherein X additionally represents a substituted amino, substituted or unsubstituted acyl, aryl or alkaryl group, and R and R1 represent alkyl, aryl, aralkyl or alkaryl groups, and wherein the phenyl group is replaced by a heterocyclic residue such as a morpholine, pyridine, piperidine, pyrrole, pyrrolidine, pyrimidine or quinoline residue-particularly a phenyl substituted quinoline residue, and therapeutic compositions containing the said compounds.  Methyl -pnitrosalicylate, methyl g -resorcylate, methyl 2, 5-dihydroxybenzotae and methyl p-amino-salicylate are prepared by esterifying the required carboxylic acids with methanol.  Methyl p-acetamido-salicylate is prepared by treating methyl p-amino-salicylate with acetyl chloride.