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

Abstract

Keywords: benzo[f]isoquinoline, benzo[f]coumarin, 3-bromoacetylcoumarin, enamines of the 3,3-dimethyl-1,2,3,4-tetrahydroisoquinoline series, 2-(3-coumarinyl)-5,5-dimethyl-5,6-dihydropyrrolo[2,1-a]-isoquinolines, Chichibabin reaction.The classical method for the construction of the pyrrolo[2,1-a]isoquinoline system is the Chichibabin reaction, which involves the reaction of 1-methylisoquinoline with α-halo ketones [1, 2]. 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. Structures of such a type are practically unknown in the literature. The aim of the present work was to investigate the possibilities of annelation of the pyrrole ring depending on the structure of the initial reagents.The investigations showed that the reaction of the isoquinoline 1 with 3-bromoacetylcoumarin takes place readily with boiling in 2-propanol in the presence of Na 2 CO 3 , with the formation of compound 2. If compounds 3a,b are used as initial enamines the reaction products are compounds 4a,b. The corresponding bromoacetyl derivative of benzo[f]coumarin gives compound 5a in reaction with the enamine 1 and the amide 5b in reaction with the enamino amide 3b. In reaction with 3-bromoacetylcoumarin the benzo[f]isoquinoline derivative 6 forms the tetracyclic system 7. The obtained coumarin derivatives 2, 4, 5, and 7 (Table 1) are yellow crystalline substances.In the 1 H NMR spectra of the synthesized compounds (Table 2), in contrast to the spectra of the initial enamines, there are singlets for the pyrrole ring (6.28-7.12 ppm), the shift of which depends on the substituent at position 1 of the pyrrolo[2,1-a]isoquinoline system. All the spectra contain singlets for the HC= group of the coumarin ring (7.80-8.56 ppm) [4].

Synthesis of Pyrrolo[2,1-a]isoquinolines by Multicomponent 1,3-Dipolar Cycloaddition

“…In this regard efforts were directed to synthesize aromatic or hydrogenated pyrrolo[2,1- a ]-isoquinoline frameworks in the search for molecules relevant for medicinal purposes. The synthesis and properties of the pyrrolo[2,1- a ]isoquinolines were reviewed in 1997 by Mikhailovskii and Shklyaev [15], but the synthesis and characterization of these compounds is still of current interest, the proof being the important number of very recently reported papers [16,17,18,19].…”