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Abstract:
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Multi-component reactions are effective in building complex molecules in a single step in a
minimum amount of time and with facile isolation procedures; they have high economy1–7
and thus have become a powerful synthetic strategy in recent years.8–10 The multicomponent
protocols are even more attractive when carried out in aqueous medium. Water
offers several benefits, including control over exothermicity, and the isolation of products
can be carried out by single phase separation technique. Pyranopyrazoles are a biologically
important class of heterocyclic compounds and in particular dihydropyrano[2,3-c]pyrazoles
play an essential role in promoting biological activity and represent an interesting template
in medicinal chemistry. Heterocyclic compounds bearing the 4-H pyran unit have received
much attention in recent years as they constitute important precursors for promising
drugs.11–13 Pyrano[2,3-c]pyrazoles exhibit analgesic,14 anti-cancer,15 anti-microbial and
anti-inflammatory16 activity. Furthermore dihydropyrano[2,3-c]pyrazoles show molluscidal
activity17,18 and are used in a screening kit for Chk 1 kinase inhibitor activity.19,20 They
also find applications as pharmaceutical ingredients and bio-degradable agrochemicals.21–29
Junek and Aigner30 first reported the synthesis of pyrano[2,3-c]pyrazole derivatives from
3-methyl-1-phenylpyrazolin-5-one and tetracyanoethylene in the presence of triethylamine.
Subsequently, a number of synthetic approaches such as the use of triethylamine,31
piperazine,32 piperidine,33 N-methylmorpholine in ethanol,34 microwave irradiation,35,36
solvent-free conditions,37–39 cyclodextrins (CDs),40 different bases in water,41 γ -alumina,42
and l-proline43 have been reported for the synthesis of 6-amino-4-alkyl/aryl-3-methyl-
2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles. Recently, tetraethylammonium bromide
(TEABr) has emerged as mild, water-tolerant, eco-friendly and inexpensive catalyst. To
the best of our knowledge, quaternary ammonium salts, more specifically TEABr, have notbeen used as catalysts for the synthesis of pyrano[2,3-c]pyrazoles, and we decided to investigate
the application of TEABr as a catalyst for the synthesis of a series of pyrazole-fused
pyran derivatives via multi-component reactions |