One‐Pot Synthesis of 4‐(Alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐ dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones via a Multicomponent Reaction

Abstract

An effective route to novel 4‐(alkylamino)‐1‐(arylsulfonyl)‐3‐benzoyl‐1,5‐dihydro‐5‐hydroxy‐5‐phenyl‐2H‐pyrrol‐2‐ones 10 is described (Scheme 2). This involves the reaction of an enamine, derived from the addition of a primary amine 5 to 1,4‐diphenylbut‐2‐yne‐1,4‐dione, with an arenesulfonyl isocyanate 7. Some of these pyrrolones 10 exhibit a dynamic NMR behavior in solution because of restricted rotation around the CN bond resulting from conjugation of the side‐chain N‐atom with the adjacent α,β‐unsaturated ketone group, and two rotamers are in equilibrium with each other in solution (10 ⇌ 11; Scheme 3). The structures of the highly functionalized compounds 10 were corroborated spectroscopically (IR, 1H‐ and 13C‐NMR, and EI‐MS), by elemental analyses, and, in the case of 10a, by X‐ray crystallography. A plausible mechanism for the reaction is proposed (Scheme 4).

Synthesis of novel functionalized dihydroimidazo[2,1-a]isoquinolines and dihydroimidazo[2,1-a] quinolines: single crystal X-ray studies of (Z)-methyl 2-(1-(benzo[d]thiazol-2-yl)-2-oxo-1,2-dihydroimidazo[2,1-a]isoquinolin-3(10bH)-ylidene)acetate

“…22,23 In recent years some interesting research based on using isoquinoline derivatives and activated acetylenes in the presence of compounds containing acidic hydrogen, with analogous transformations have been reported. [29][30][31][32][33][34] In this communication as part of our continuing effort into the design of new routes for the preparation of biologically active heterocyclic compounds [24][25][26][27][28] using the synthesis and reactions of activated acetylenes and isoquinoline in the presence of 2-aminobenzothiazole. Herein we describe a simple, one-pot, three-component synthesis of dihydroimidazo [2,1-a]isoquinolines and dihydroimidazo[2,1-a] quinolines.…”

One-Pot Synthesis of Arylsulfonamides and Azetidine-2,4-diones via Multicomponent Reaction of an Amine, an Acetylenic Compound, and an Arylsulfonyl Isocyanate

“…[14][15][16][17][18][19] In the context of our ongoing studies on heterocyclic synthesis mediated by enamine intermediates, the possibility of trapping the 1:1 intermediate 5, formed between an acetylenecarboxylate 2 and a primary or secondary amine 1, with an arysulfonyl isocyanate 3 appeared attractive from the viewpoint of devising a novel multicomponent reaction (MCR). Although the trapping of the 1:1 intermediate formed between dibenzoylacetylene or dialkyl acetylenedicarboxylate and amines with arylsulfonyl isocyanate has been studied in detail by our research group, [20][21][22] trapping of the initially formed 1:1 intermediate between primary amines and alkyl propiolates has not been reported.…”

“…Compounds 4 apparently result from the initial addition of an amine to the acetylenic system and subsequent attack of the resulting reactive enamine 5 on the arylsulfonyl isocyanate [20][21][22][23][24] to yield a betaine 6, which under hydrogen shift produce 4 (Scheme 1).…”

“…Although we have not established the mechanism of the reaction of the enamine derived from the addition of Et 2 NH to 2a and 3 in an experimental manner, a possible explanation is proposed in Scheme 2. Compound 7 appar-ently results from the initial addition of Et 2 NH to the acetylenic system and subsequent attack of the resulting reactive enamine 8 to the arylsufonyl isocyanate [20][21][22][23][24] to yield betaine 9, which apparently cyclizes, under the reaction condition employed with loss of methanol to produce the malonimide 7.…”

“…We have unraveled some interesting reactivity profiles of the intermediates 12, 13, 14, and 15. [20][21][22] In summary, the reaction between Et 2 NH, methyl propiolate (2a) and an arylsulfonyl isocyanate 3 provides a simple one-pot synthesis of 3-[(diethylamino)methylene]-1-(arylsulfonyl)-2,4-azetidinedione derivatives 7 of potential synthetic and pharmaceutical interest. With other amines, the reaction leads to the formation of the corresponding arylsulfonamides.…”