Water Mediated Construction of Trisubstituted Pyrazoles/Isoxazoles Library Using Ketene Dithioacetals

Abstract

A small molecule library of alkyl, sulfone, and carboxamide functionalized pyrazoles and isoxazoles has been developed via a rapid sequential condensation of various alpha-acylketene dithioacetals (1a-o) with hydrazine hydrate or hydroxylamine hydrochloride, followed by oxidation of sulfide to sulfone using water as the reaction medium. An efficient and safe oxidation of sulfides (4/5a-o) to the corresponding sulfones (6/7a-o) using sodium per borate system in aqueous medium is reported. The concise and two step synthesis of trisubstituted pyrazoles and isoxazoles was investigated under variety of reaction condition. The newly developed methodology has the advantage of excellent yield and chemical purity with short reaction time using water as a solvent.

A Concise [3 + 3] Heteroaromatization Synthetic Strategy Afford Dicarboxamide Functionalized Novel Pyrazolo[1,5‐a]Pyrimidines

“…Synthesis of second intermediate oxoketene dithioacetals was achieved by our previously reported method with modification (Scheme 2). Reaction of substituted aniline ( 14a–h ) with various β‐ketoesters ( 13a–c ) in the presence of catalytic amount of KOH in refluxing toluene generated acetoacetanilide derivatives ( 15a–x ) in excellent yield.…”

“…Reaction of substituted aniline ( 14a–h ) with various β‐ketoesters ( 13a–c ) in the presence of catalytic amount of KOH in refluxing toluene generated acetoacetanilide derivatives ( 15a–x ) in excellent yield. Further treatment of 15a–x with carbon disulfide in the presence of K 2 CO 3 followed by the S‐methylation using methyl iodide furnished oxoketene dithioacetals ( 16a–x) in high yields.…”

“…Recently, we have reported the synthesis of trisubstituted pyrazoles/isooxazoles and functionalized pyrimidines using oxoketene dithioacetals . To explore further the utility of oxoketene dithioacetals in the synthesis of novel heterocyclic compounds, herein, we describe versatile and efficient synthetic methods for dicarboxamide functionalized pyrazolo[1,5‐ a ]pyrimidines ( 17a–x ) (Fig.…”

Water Mediated Synthesis ofN′-Arylmethylene-4,5,6,7-tetrahydro-2H-indazole-3-carbohydrazide Library

“…Our Continuous efforts for the synthesis of various novel heterocycles for biological interest using various catalyst and green approaches [22][23][24][25][26] and the remarkable pharmaceutical importance of fused hydrazide and pyrazole derivatives, prompted us to design and synthesize a scaffold 4,5,6,7tetrahydro-2H-indazole-3-carbohydrazide using water as a green solvent.…”

Novel 1<i>H</i>-Pyrazole-3-carboxamide Derivatives: Synthesis, Anticancer Evaluation and Identification of Their DNA-Binding Interaction

“…[10][11][12] In addition to the creation of C-N and C-C bonds by cross-coupling reactions of aryl electrophiles with substituted pyrazoles, more promising alternative methods have been used in further synthesis and chemical purification with short reaction time and excellent yield, including ultrasound depositing, using condensation reagents and microwave synthesis and so on. [13][14][15][16][17] All these greatly promote the progress of research in pyrazole compounds and recently such scaffold is not only employed in developing various kinase inhibitors, 10) but also in molecules that directly interact with DNA stands, such as metal complexes, alkylating agents, dimeric analogues, polyamide derivatives and some pyrazolefused derivatives. [18][19][20][21][22][23][24][25] The unexpected interaction between DNA and pyrazole-derived kinase inhibitors can cause offtarget effects, including potential improvement of cell toxicity and anticancer activity.…”