Patent GB-583190-A (GB)
Title: Manufacture of oxazolone compounds
Inventor: DAVIES JOHN S H
IPC: C07D263/42
Filed: 1944-06-05
Abstract: Oxazol-5-ones of general formula <FORM:0583190/IV/1> wherein R and R1 each represent a hydrocarbon radical, or acyl derivatives thereof, are obtained by reaction of an appropriately disubstituted formamidine, e.g. a dialkyl or diaryl formamidine, with an acylglycine, R.CONH.CH2COOH and an organic acid anhydride, e.g. acetic anhydride.  The formamidine and the acylglycine may first be reacted and the product then dehydrated by treatment with the anhydride, or the three reactants may be heated together, or the acylglycine may first be dehydrated to give the corresponding 2-substituted oxazol-5-one and this then treated with the formamidine.  Specified disubstituted formamidines are the N : N1-diphenyl-, N : N1-dibenzyl- and N : N1-diethylformamidines and specified acylglycines are benzoylglycine, cinnamylglycine, hexen-(2)-oylglycine and phenacetylglycine.  The acyl (probably o-acyl) derivatives are obtained by heating for prolonged periods and at higher temperatures.  Deacylation is achieved by heating with an amine, preferably an amine R1-NH2, where R1 has the foregoing significance.  In examples: (1) a mixture of hippuric acid, N : N1-diphenyl formamidine and acetic anhydride is heated for 2 hours under reflux prior to distilling in vacuo and treating the residue with alcohol to isolate the acetyl derivative of 2-phenyl-4-anilinomethylene-oxazol-5-one; (2) N : N1-diphenyl formamidine is heated with hippuric acid to 125 DEG  C. for 4 hours and the product heated for 3 hours under reflux with acetic anhydride, prior to isolating the product as in (1); (3) a mixture of hippuric acid, N : N1-diphenyl formamidine and acetic anhydride is heated at 100 DEG  C. for 30 minutes and the product 2-phenyl-4-anilinomethylene-oxazol-5-one isolated as in (1); (4) a mixture of 2-phenyloxazole-5-one, N : N1-diphenyl formamidine and acetic anhydride is heated for 20 minutes at 100 DEG  C. prior to concentration in vacuo and trituration with alcohol to yield the product of (3); (5) a mixture of cinnamyl glycine, N : N1-diphenyl formamidine and acetic anhydride is heated for 20 minutes under reflux to yield 2-styryl-4-anilinomethylene-oxazol-5-one, the corresponding acetyl derivative being isolated from the filtrate on concentration in vacuo; (6) a mixture of hexen-(2)-oylglycine, N : N1-diphenyl formamidine and acetic anhydride is heated as in (3), and the residue is triturated with ethyl acetate to yield crude 2-penten-(21)-oyl-4-anilinomethylene-oxazol-5-one; (7) a mixture of 2 - benzyl - oxazol - 5 - one, N : N1 - diphenyl formamidine and acetic anhydride is heated as in (4) to yield 2-benzyl-4-anilinomethylene-oxazol-5-one; (8) a mixture of hippuric acid, N : N1-dibenzyl formamidine and acetic anhydride is heated as in (3), and the mixture is concentrated in vacuo to yield the acetyl derivative of 2-phenyl-4-benzylaminomethylene-oxazole-5-one; (9) the product of (8) is heated with aniline for 1 hour at 110 DEG  C. to yield 2-phenyl-4-anilinomethylene-oxazol-5-one; (10) the product of (8) is heated as in (9) with benzylamine to yield 2-phenyl-4-benzylaminomethylene-oxazol-5-one; (11) a mixture of phenacetylglycine, N : N1-dibenzylformamidine and acetic anhydride is heated as in (3) to yield the acetyl derivative of 2-benzyl-4-benzylaminomethylene-oxazol-5-one, and the product is heated with benzylamine as in (10) to yield the free amine; (12) a mixture of hippuric acid, N : N1-diethyl formamidine and acetic anhydride is heated as in (3) to yield the acetyl derivative of 2-phenyl-4-ethylaminomethylene-oxazol-5-one, and deacetylation is effected by heating with ethylamine.  Hexen-(2)-oyl glycine is prepared by reaction of the sodium salt of glycine with hexen-(2)-oyl chloride in presence of aqueous sodium hydroxide, followed by concentrated hydrochloric acid.  2-Benzyl-oxazol-5-one is prepared by standing a mixture of phenacetyl glycine, dry dioxan and phosphorus tribromide for 1 hour and adding ethereal diazomethane (made by decomposing nitrosomethylurea with concentrated aqueous caustic potash and separating the ether layer), to isolate the product.  N : N1-Dibenzylformamidine is prepared by reaction of formimido-ethyl-ether hydrochloride with benzylamine in absolute alcohol at 0 DEG  C., followed by treatment with aqueous sodium carbonate.  N : N1-Diethylformamidine is prepared by reaction of formimido-ethyl-ether hydrochloride with ethylamine in alcohol and treating the hydrochloride product with ethereal diazomethane.