Multicomponent Reactions of Arylglyoxal, 4‐Hydroxycoumarin, and Cyclic 1,3‐C,N‐Binucleophiles: Binucleophile‐Directed Synthesis of Fused Five‐ and Six‐Membered N‐Heterocycles

Abstract

The multicomponent reaction (MCR) of arylglyoxal, 4‐hydroxycoumarin, and various cyclic 1,3‐C,N‐binucleophiles in acetic acid under microwave conditions provides fused five‐ or six‐ membered N‐heterocycles depending on the ring size of the binucleophiles. 1,3‐C,N‐binucleophiles, such as amino‐pyrazole/oxazole, that have a five‐membered ring provide fused six‐membered dihydropyridines or pyridine derivatives, whereas aminouracil, cytosine, and 4/3‐aminocoumarines that have a six‐membered ring provide the corresponding five‐membered fused pyrroles. By using DFT calculations, the mechanism of the ring‐size‐dependent multicomponent cyclization reaction is explained. Cyclic 1,3‐C,N‐binucleophiles, such as aminopyrazole, aminooxazole, aminocoumarin, aminouracil, and cytosine, were explored in this MCR, and the corresponding fused pyrroles/dihydropyridines or pyridines were obtained in very good yields. The structures of the fused molecules were unambiguously confirmed by spectroscopic techniques and single‐crystal X‐ray analysis.

4‐Hydroxycoumarin: A Versatile Substrate for Transition‐metal‐free Multicomponent Synthesis of Bioactive Heterocycles

“…In 2017, Mishra et al developed a novel one-pot multicomponent strategy under microwave irradiation for the synthesis of pyrrole-coumarin hybrids (Scheme 3A). [42] With the help of acetic acid as the reaction medium, the treatment of 4hydroxycoumarin 1, arylglyoxal 8, and various 1,3-C,N-binucleophiles such as 3-amino coumarin 9, 4-amino coumarin 11, cytosine 13, and amino uracil 15 delivered diverse pyrrolylcoumarin derivatives 10, 12, 14, and 16 within very short reaction time. In all the cases, the products were synthesized in moderate to high yield.…”

Modular Synthesis and Antiproliferative Activity of New Dihydro-1H-pyrazolo[1,3-b]pyridine Embelin Derivatives

“…Of special interest are those based on multicomponent reactions (MCRs), such as those involving the condensation of 1,3-dicarbonyl compounds with aldehydes and aminopyrazole derivatives [ 10 ]. Thus, for instance, some coumarin-fused pyridines/dihydropyridines were obtained from aminopyrazoles, 4-hydroxycoumarin and arylglyoxals [ 11 , 12 ]. Another example is the preparation of spiro[indoline-3,4′-pyrazolo[3,4- b ]pyridines] from isatins, pyrazol-5-amines and β-ketonitriles [ 13 ].…”

3‐Aminothieno[2,3‐b]pyridine‐2‐carboxylate: Effective precursor for microwave‐assisted three components synthesis of new pyrido[3′,2′:4,5]thieno[3,2‐d]pyrimidin‐4(3H)‐one hybrids

“…On the other hand, the rapid synthesis of biologically relevant heterocycles has remained one of the fascinating tasks for organic and medicinal chemists [42,43]. In recent years, multicomponent reactions have emerged as efficient methods for the synthesis of various polyfunctionalized heterocyclic hybrids, which involves the transformation of more than two reactants into the desired products in a one‐pot one‐step fashion [44,45].…”