Modern Friedel-Crafts chemistry. Part 32. Facile synthesis of some new fused heteropolycycles via direct intramoleclar Friedel-Crafts cyclialkylations of suitable heteroarylalkanols

Ali Ali Khalaf,Ibrahim M Awad,Hassan A K Abd El-Aal,Ahmed M El-Khawaga

doi:10.3998/ark.5550190.0011.a28

Abstract

This study provides expedient methods for the synthesis of some novel fused heteropolycycles. Thus, a variety of fused di-, tri- and tetracyclic nitrogen and nitrogen-sulfur heteropolycycles 8, 9, 11-15 were smoothly synthesized by Friedel-Crafts intramolecular alkylations of heteroarylalkanols 1-7 in the presence of both Bronsted (PPA and PTSA) and Lewis (AlCl3/CH3NO2) acid catalysts. The precursor alkanols were readily prepared by reaction of the corresponding carboxylic acid esters with methylmagnesium iodide. The structures of the compounds are established using both spectral and analytical data. A plausible carbocation mechanism is proposed to account for the results.

Highlights

A variety of methods have been developed for the synthesis of biologically and pharmacologically active heteropolycycles that bear quinoline or tetrahydroquinoline fragments.[1,2]
Synthesis and cyclialkylation of 4-(9H-carbazol-9-yl)-2-methylbutan-2-ol (1). This hitherto unknown 4-(9H-carbazol-9-yl)-2-methylbutan-2-ol 1 was synthesized in two consecutive steps starting from 3-(9H-carbazol-9-yl)propanoic acid[6] by conversion to ethyl ester followed by reaction with methylmagnesium iodide
The results of this study proved that Friedel-Crafts cyclialkylation can be considered as one of the most useful pathways to the synthesis of di, triand higher condensed polycycles enclosing one or more heteroatoms

Summary

Introduction

A variety of methods have been developed for the synthesis of biologically and pharmacologically active heteropolycycles that bear quinoline or tetrahydroquinoline fragments.[1,2] Among these methods, intramolecular Friedel-Crafts reactions (called cyclialkylations)[3] prompted by both Brönsted and Lewis acid catalysts proved to introduce powerful pathways for the facile construction of homo- and heteropolycycles.[4,5]. We introduce the construction of seven nitrogen and nitrogen-sulfur polycycles. 8, 9, 11-15 containing fused quinoline, tetrahydroquinoline, acridine, phenothiazine and indole moieties via Friedel-Crafts cyclialkylations of seven new heteroarylalkanols 1-7 (Scheme 1). For preceding paper of the series see ref 19.

Results and Discussion

Conclusions

Cyclialkylation procedures