Regioselective synthesis of ethyl pyrazolecarboxylates from ethyl 3‐[(dimethylamino)methylidene]pyruvate and diethyl 3‐[(dimethylamino)methylidene]‐2‐oxosuccinate. Isolation of ethyl 4,5‐dihydro‐1‐heteroaryl‐5‐hydroxy‐1<b>H</b>‐pyrazole‐5‐carboxylates as stable intermediates in the pyrazole ring formation

Abstract

Abstract Reactions of ethyl 3‐[( E )‐(dimethylamino)methylidene]pyruvate ( 3 ) and 3‐[(dimethylamino)methyl‐idene]‐2‐oxosuccinate ( 4 ) with hydrazine monohydrochloride ( 5a ) and (hetero)arylhydrazines ( 5b‐i ) afforded, regioselectively, 1‐substituted ethyl 1 H ‐pyrazole‐5‐carboxylates 9a‐f and diethyl 1 H ‐pyrazole‐3,4‐dicarboxylates, 11a‐i , respectively. Upon treatment of 3 with pyridazinylhydrazines 5d‐f , the stable intermediates, 1‐substituted ethyl 4,5‐dihydro‐5‐hydroxy‐1 H ‐pyrazole‐5‐carboxylates 8d‐f , were isolated. Treatment of compounds 8d‐f in acetic acid under reflux furnished the pyrazoles 9d‐f . On the other hand, reaction of 3 with N,N ′‐dimethylhydrazine ( 51 ) gave ethyl 1‐methyl‐1 H ‐pyrazole‐3‐carboxylate ( 14 ). The structures of compounds 3, 4, 14 were determined by nmr (noesy and hmbc techniques), while the structures of compounds 8f, 9f , and 11e, f were determined by X‐ray diffraction.