Reaction of 2,3-dioxopyrrolo[2,1-a]iso-quinolines with binucleophiles

Abstract

Keywords: o-aminobenzyl alcohol, 2-amino-4-methylphenol, o-aminothiophenol, N-benzylamide, benzyl ester, anthranilic acid hydrazide, caprolactam hydrazidine, o-hydroxybenzylamine, diacyl hydrazide, 5,5-dialkyl-2,3-dioxopyrrolo[2,1-a]isoquinolines, benzoxazole, benzothiazole, and 1,2,4-triazole derivatives.We have already studied the reactions of 2,3-dioxopyrrolo[2,1-a]isoquinolines with several binucleophiles such as aliphatic diamines [1], o-phenylenediamine [2][3][4], and o-aminophenol [5]. These examples show that the reactions of these compounds with binucleophiles may proceed through various pathways, namely, ordinary acylation of the amino group [1], annelation of the heterocycle [2, 4], and heterocyclization with benzoxazole formation [5]. In the present work, we studied the dependence of the structure of the products on the structure of both the binucleophile and the dicarbonyl reagent.Brief heating of 2,3-dioxopyrrolo[2,1-a]isoquinolines 1a,c with 2-amino-4-methylphenol in 2-propanol at reflux gives heterocyclic enamino ketones 2a,b, which contain the benzoxazole residue. The use of o-aminothiophenol as the binucleophile in the reaction with dioxopyrrolines 1a-d leads to benzothiazole derivatives 2c-f. We have recently shown that dioxopyrroline ring opening occurs in the reaction of pyrroloisoquinoline 1a with caprolactam hydrazidine to give the bicyclic 1,2,4-triazolo[4,5-a]azepine system [6].When amide 1d or ester 1e is used as the starting reagent, the reaction proceeds analogously to give the corresponding amide 3a and ester 3b. In the latter case, caprolactam hydrazidine does not attack the ester group. The retention of the ester group provides the potential for further chemical transformations. When a spirocyclopentyl substituent is present in the starting dicarbonyl compound 1c, annelation of the triazole ring is not observed. This failure may be attributed to the large bulk of the spirocyclopentyl substituent in comparison with two methyl groups. On the other hand, the bulky structure of benzo[f]isoquinoline is not a hindrance to annelation of the triazole ring in the formation of morpholide 4.