Reactions of 2,3-Dioxopyrrolo[2,1-a]isoquinolines with Active N-Nucleophiles

Abstract

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).

Reactions of enamino keto esters of 1,2,3,4-tetrahydroisoquinoline series with nucleophiles

“…The investigations showed that on boiling dioxopyrroline 1a with the hydrazides of cyanoacetic and p-aminobenzoic acids reaction proceeds according to the previously known scheme with the formation of the corresponding hydrazones 6 and 7, i.e. without opening of the pyrroledione ring [5].…”

“…On interacting ester 2a with other hydrazides, such as cyanoacetylhydrazide and benzoic acid hydrazide in boiling glacial acetic acid or 2-propanol, no new products were isolated, which may be explained by the weak nucleophilic properties of the reactants used. It is known that 2,3-dioxopyrrolo[2,1-a]isoquinolines frequently play the role of acylating reagents, interacting with N-nucleophiles with opening of the pyrrole ring [4][5][6][7]. It therefore seemed of interest to study the acylation reaction of hydrazides with these reagents with the aim of obtaining substances analogous to compounds 5a,b in structure.…”

“…The mass spectrum of compound 3 contains a peak* for the molecular ion of 300 [M] + (27), and also a peak for the 3,3-dimethyl-1-methylidenecarbonyl-1,2,3,4-tetrahydroisoquinoline fragment at 200 (35), characteristic for compounds having this fragment in their structure [4][5][6][7]. In the mass spectrum of tricyclic ketone 4a a peak was observed for the molecular ion at 284 [M] + (12), and also a peak corresponding to cleavage of the semicarbazide fragment 211 [M] + (17).…”

Reaction of 2,3-dioxopyrrolo-[2,1-a]isoquinolines with anthrone

“…The 1 H NMR spectra were taken on a Bruker-300 spectrometer at 300 MHz with HMDS as the internal standard (δ 0.05 ppm). The assignment of the singlet of the vinyl proton in the enamino ketone fragment is based on extensive data, for example, the results of our previous work [2]. The position of the singlet of the vinyl proton of the anthrone side chain corresponded to the calculated value [3].…”