Synthesis of substituted 3‐phenyl‐6h‐pyrazolo[4,3‐d]isoxazoles from corresponding 4‐benzoyl‐5‐hydroxypyrazoles

Abstract

Treatment of 1,(3)‐(di)substituted 4‐benzoyl‐5‐hydroxypyrazoles with phosphorus oxychloride affords the corresponding 4‐benzoyl‐5‐chloropyrazoles. Reaction of the latter with hydroxylamine leads to oximes, which can be cyclized to novel 3‐phenyl‐6H‐pyrazolo[4,3‐d]isoxazoles by treatment with sodium hydride in dimethyl formamide. Detailed nmr spectroscopic studies (1H, 13C) with all obtained compounds are presented.

Synthesis of New Pyrazolones and Fused Pyrazole Derivatives as Antimicrobial Agents

“…It is noteworthy to mention here that the synthesis of 4-methyl-6H-pyrazolo [4,3-d]isoxazole (4) was claimed before by the reaction of 5-chloro-3-methyl-1H-pyrazole-4-carbaldehyde with hydroxylamine (41)(42)(43) . However, these reports are mystic since neither experimental procedure nor spectroscopic data of the reaction product was provided (44) . Interaction of 2 with hydrazine hydrate in ethanol containing acetic acid afforded pyrazolo [3,4-c]pyrazole 5 in 78% yield.…”

5-Chloropyrazole-4-carboxaldehydes as synthon in heterocyclic synthesis

“…El-atif et al [59] and Pawar [46] studied the reactivity of 4 with hydroxyl amine in pyridine, and they separate the oxazole derivative 124, whereas Holzer et al [58] reported that compound 4 reacted with hydroxylamine hydrochloride in ethanol to give the corresponding oxime 94, which does not undergo cyclization in either refluxing pyridine or sodium hydride to the corresponding pyrazolo [4,3-d]oxazole 124 (Scheme 27) [60].…”

“…Compound 4 reacted with hydroxide amine hydrochloride in ethanol in the presence of sodium acetate to give the oxime 94 [57,58], which converted into the cyano derivative 95 after treating with acetic anhydride (Scheme 21) [57,58].…”

An unusual thionyl chloride-promoted C−C bond formation to obtain 4,4'-bipyrazolones

“…Such conversions of a hydroxy (oxo) into a chloro function is very common with many N-heterocyclic systems, such as, for instance the transformations of 2-pyridones into 2-chloropyridines or 3-pyridazinones into 3-chloropyridazines [ 19 – 20 ]. In the course of the preparation of substituted 6 H -pyrazolo[4,3- d ][1,2]oxazoles we thus obtained the required 4-benzoyl-5-chloropyrazoles by treatment of the relevant 4-benzoyl-5-hydroxypyrazoles with POCl 3 [ 21 ].…”