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It is shown that 2,3-dioxopyrrolo [2,1-a]isoquinolines react readily with aliphatic diamines and hydroxyamine with opening of the dioxopyrrole ring and formation of the corresponding bisenaminoketoamides and hydroxamic acids. Reaction with the thiosemicarbazide and hydrazides of aromatic acids proceeds without opening of the pyrrole ring at the ketone carbonyl. Derivatives of hexahydropyridazine are formed when compounds with carboxyethyl groups at position 1 react with hydrazine.It has been shown previously that 2,3-dioxopyrrolo[2,1-a]isoquinolines react with N-nucleophiles with opening of the pyrrole ring to give enaminohydrazides [1] and enaminoketoamides [2][3][4].The objective of the present work was to investigate the dependence of the direction of the reaction on the structures of the N-nucleophiles. The most reactive compounds, such as aliphatic diamines, hydroxylamine, hydrazides of aromatic and heteroaromatic acids, and hydrazine, were chosen as the N-nucleophiles.It was shown that the bisamides 2a,b were formed on simply mixing compound 1a with ethylenediamine or pentamethylenediamine in 2-propanol at 20°C. The hydroxamic acids 3a,b were formed on heating solutions of 1a,b in the same solvent for a short time with an excess of hydroxylamine. Analogously interaction of a derivative of benzo[f]isoquinoline with hydroxylamine gave compound 4. When thiosemicarbazide or the hydrazides of benzoic, nicotinic, or isonicotinic acids were used as the nucleophile opening of the pyrrole ring did not occur and the imines 5a-d were formed.The dioxopyrroline 6 with a carbethoxy group at position 1 formed derivatives of perhydropyridazine 7 on opening of the pyrrole ring. The course of the reaction is readily controlled by the decoloration of the solution of the original substance, which is deep red with the exception of compounds 5a-d which are orange, and for them reaction is monitored by TLC.The fact that opening of the dioxopyrrole ring did not occur with thiosemicarbazide or the hydrazides (compounds 5a-d) is explained by the lower reactivity of these nucleophiles in comparison with aliphatic amines, hydroxylamine, and hydrazine. It was shown previously that opening of the dioxopyrrole ring in compounds 1a,b by N-nucleophiles was facilitated by acid catalysis (heating in glacial acetic acid) [4]. Investigation showed that on boiling (2 h) compound 1a in acetic acid with the nucleophiles used to obtain compounds 5a-d, ring opening did not occur and the same products were obtained as from simply boiling in alcohol (Table 1).

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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,

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