Enamines of the 1,2,3,4-tetrahydroiso-quinoline series in the Chichibabin synthesis of pyrrolo[2,1-a]isoquinolines and in reaction with oxalyl chloride

Abstract

Pyrrolo[2,1-a]isoquinolines are used widely in organic synthesis, medicine, and other areas [1]. The classical method of design the pyrrolo[2,1-a]isoquinoline system is the interaction of 1-alkylisoquinolines with α-halo ketones (the Chichibabin reaction) [1,2]. It is known [3] that on cyclization with the formation of condensed systems a determining role is played by the radicals in position 3 of the isoquinoline ring. The aim of the present work is an investigation of the potentialities of this reaction in the presence of two methyl groups in position 3 and also of a different structure for the enamine fragment.The reaction of enamines of the 1,2,3,4-tetrahydroisoquinoline series with oxalyl chloride has also been widely investigated [1,4,5]. In the given examples, both bases, in the molecules of which the structure of the enamine is already fixed, and compounds in the imino form, enter into this reaction. The latter is characteristic for derivatives of 1-alkylisoquinoline [6,7], the alkyl residue in the structure of which, unlike carbonyl or just withdrawing groups, does not aid stabilization of the enamine form. Consequently our aim is the study of the conditions of carrying out and the structures of the products of the named reaction in the presence of an alkyl residue at position 1 of the isoquinoline ring.The investigations showed that the reaction of enamines 1a-c with p-bromophenacyl bromide proceeds readily on boiling in alcohol in the presence of Na 2 CO 3 and compounds 2a-c are formed. On using drotaverine (no-spa) base as the initial enamine the reaction product is compound 2d. Enamino amides and enamino esters of the benzo[f]isoquinoline series, analogous in structure to compounds 1a-c, form the corresponding tetracyclic derivatives 3a-c in this reaction. __________________________________________________________________________________________ Perm State Pharmaceutical Academy,

Synthesis of 2-(3-coumarinyl)pyrrolo[2,1-a]isoquinoline derivatives by the chichibabin reaction

“…The successful use not only of heteroaromatic compounds such as pyridines and their benzo analogs but also of cyclic enamine derivatives in this reaction is well known [2,3]. Here 3-bromoacetylcoumarins are also worthy of attention as α-halo ketones in so far as the formation of a system consisting of two independent heterocyclic fragmentspyrrolo[2,1-a]isoquinoline and coumarin -has been proposed in this case.…”

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

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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].

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“…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].…”