Metal-Free Iodine-Catalyzed Synthesis of Fully Substituted Pyrazoles and Its Sulphenylation

Abstract

A direct and metal-free access toward fully substituted pyrazoles and its sulphenylation has been established through an iodine-mediated three-component [3 + 2] annulation of β-ketonitrile (or pentane-2,4-dione), arylhydrazines, and aryl sulfonyl hydrazides. The reaction allows the formation of one C-S and two C-N bonds by the multiple bond cleavage including sulfur-oxygen, sulfur-nitrogen, and carbon-oxygen bonds. The method features low-cost and readily accessible substrates, bond-forming efficiency, and broad substrate scopes as well as simple one-pot operation, which makes this strategy highly attractive.

Sulfonyl Hydrazides in Organic Synthesis: A Review of Recent Studies

“…Furthermore, sulfonyl hydrazides could act as precursors of electrophilic RSX (X=Br, I). Thiodiazonium, thiosulfonates or disulfides were conducted as key intermediates.…”

“…Both Tu and Chen have developed the sulfurization by in situ generated pyrazoles (or imidazo[1,2‐a]pyridines) and RSI. They were three‐component reactions of ketones, amines, and sulfonyl hydrazides.…”

Molecular iodine-catalyzed one-pot multicomponent synthesis of 5-amino-4-(arylselanyl)-1H-pyrazoles

“…On the basis of previous reports [21,25] a mechanism can be proposed for this reaction as depicted in Scheme 4. Initially, we believe that arylhydrazine 2 reacts with benzoylacetonitrile 1 by a 1,2-addition reaction in the presence of iodine as Lewis acid to generate the hydrazone intermediate A .…”

“…Thus, an effective strategy for the design and the preparation of new pharmacologically promising drugs that combine at least two bioactive moieties in one molecule avoiding residual metal in transition-metal catalysis in environmental benign conditions is desired. Recently, Sun and co-workers described their interesting results on the I 2 -catalyzed efficient synthesis of 5-amino-4-sulfanylpyrazoles using diverse β-ketonitriles, arylhydrazines and aryl sulfonyl hydrazides as sulfur source [21]. The chemistry of iodine-catalyzed transformations has emerged as a greener, efficient and economical alternative to transition metals in organic synthesis [22–24].…”

Five-Membered Ring Systems

“…β-Ketonitriles 7 underwent an iodine-mediated three-component [3 + 2] annulation reaction with arylhydrazines and arylsulfonyl hydrazides to give fully sulfenylated pyrazoles 8 (15JOC8217), while β-ketonitrile 7 (Ar = 4-OMePh) on reaction with hydrazine hydrate afforded 5-aminopyrazole 9 (15JOC7212). The syntheses of substituted pyrazoles 2 from α,β-unsaturated ketones 1 with various hydrazines are presented in tabular format below.…”