Patent GB-609919-A (GB)
Title: A process for the manufacture of 4.2-(substituted thiazolinyl)-2-substituted-oxazolones
IPC: C07D417/04
Filed: 1946-03-25
Abstract: 4-21-(Substituted thiazolinyl)-2-substituted-oxazolones of the general formula <FORM:0609919/IV(b)/1> or a tautomeric form thereof (wherein R1 represents hydrogen or a methyl group, R2 a methyl group, and R4 an alkyl, aryl or aralkyl group which may contain substituents) are manufactured by heating a compound of the general formula <FORM:0609919/IV(b)/2> (wherein R3 represents an alkyl or aralkyl group) with phosphorous pentachloride, oxychloride or trichloride or mixtures thereof in the presence of a solvent. Examples describe the heating with phosphorus pentachloride and chloroform, under reflux, of 4-carbomethoxy-5 : 5-dimethyl-2-(phenylacetamido-, p - nitrobenzamido- and n-caproamido-carbobenzoxy and -carbethoxy)-methylthiazoline (i.e. compounds of the second general formula above, in which R1=R2=CH3, R3= - CH2.C6H5 or - C2H5 and R4 = - CH2.C6H5, - C6H4 - NO2(p or n-C5H11) to produce 4-21-(51 : 51-dimethyl-41-carbomethoxythiazolinyl)-2-benzyl-, 2-p-nitrophenyl- and 2-n-amyloxazolone.  2-(Acylamido-carboalkoxy or -carboaralkoxy)-methylthiazolines, of the second general formula above, are obtainable by the action of the appropriate acid chloride in ether in the presence of sodium bicarbonate on the corresponding free amino compounds (or their salts), which compounds may in turn be made by nitrosation and reduction from the corresponding 4-carbomethoxy-5-methyl- or 5 : 5-dimethyl - 2 - carboalkoxy - or - carboaralkoxymethylthiazolines.  When R3 is alkyl, the nitrosation may be effected by adding sodium nitrite solution to a cooled alcoholic solution of the starting material in the presence of acid (e.g. acetic or preferably hydrochloric acid), and the reduction by catalytic methods or preferably by warming with an ammoniacal solution of sodium hydrosulphite.  When R3 is aralkyl, the nitrosation may be effected by addition of sodium nitrite to a solution of the starting material in acetic acid, and the reduction by means of aluminium amalgam and alcohol.  In examples: (1) 4-carbomethoxy-5 : 5-dimethyl-2-carbobenzoxymethylthiazoline is treated with sodium nitrite and acetic acid in dioxane, and the resulting nitroso compound is refluxed with aluminium amalgam and alcohol in ether to form 4-carbomethoxy-5 : 5 - dimethyl - 2 - (amino - carbobenzoxy)-methylthiazoline (isolated in the form of its oxalate); (2) 2 - carbethoxymethyl - 4 - carbomethoxy-5 : 5-dimethylthiazoline is treated with sodium nitrite solution and dilute hydrochloric acid in alcohol, and the resulting nitroso compound is warmed with aqueous ammonia and sodium hydrosulphite solution to give 2-(amino-carbethoxy)-methyl-4-carbomethoxy-5 : 5-dimethylthiazoline (isolated as the hydrochloride or oxalate); (3) to (8) the products of (1) and (2) (oxalate) are treated in ether in the presence of sodium bicarbonate with n-caproyl, phenylacetyl or p-nitrobenzoyl chloride.  Specification 590,040 is referred to.  4 - Carbomethoxy - 5 - methyl - or 5 : 5 - dimethyl-2-carbobenzoxymethylthiazolines are obtainable by treating benzyl cyanoacetate with absolute alcohol and dry hydrogen chloride and condensing the resulting imino-ether hydrochloride with the appropriate b -mono- or di-substituted cysteine methyl ester, e.g. penicillamine methyl ester (R1=R2=CH3).  Benzyl cyanoacetate is prepared by heating ethyl cyanoacetate with benzyl alcohol.