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-1H-pyrazole-5-carboxylates as stable intermediates in the pyrazole ring formation

✍ Scribed by Andrej Hanzlowsky; Blanka Jelenčič; Simon Rečnik; Jurij Svete; Amalija Golobič; Branko Stanovnik

• Publisher: Journal of Heterocyclic Chemistry
• Year: 2003
• Tongue: English
• Weight: 147 KB
• Volume: 40
• Category: Article
• ISSN: 0022-152X
• DOI: 10.1002/jhet.5570400313

✦ Synopsis

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.