Premium
Design, synthesis and crystallographic study of novel indole‐based cyano derivatives as key building blocks for heteropolycyclic compounds of major complexity
Author(s) -
García Andrés C.,
Abonía Rodrigo,
Jaramillo-Gómez Luz M.,
Cobo Justo,
Glidewell Christopher
Publication year - 2017
Publication title -
acta crystallographica section c
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.304
H-Index - 17
ISSN - 2053-2296
DOI - 10.1107/s2053229617015789
Subject(s) - chemistry , acrylonitrile , stereochemistry , chalcone , nuclear magnetic resonance spectroscopy , supramolecular chemistry , indole test , molecule , organic chemistry , copolymer , polymer
A four‐stage reaction sequence has been designed and developed for the synthesis of highly functionalized enolate esters as key building blocks for the synthesis of novel heteropolycyclic compounds of potential pharmaceutical value. The sequence starts with simple commercially available indoles and proceeds via 3‐(indol‐3‐yl)‐3‐oxopropanenitriles, which react with 2‐bromobenzaldehyde to form the corresponding chalcones; these are readily reduced to dihydrochalcones, which are in turn acylated to form the enolate esters. The compounds in this sequence have been characterized by IR and 1 H and 13 C NMR spectroscopy, by mass spectrometry and by elemental analysis. The molecular and supramolecular structures are reported for representative examples, namely ( E )‐3‐(2‐bromophenyl)‐2‐(1‐methyl‐1 H ‐indole‐3‐carbonyl)acrylonitrile, C 19 H 13 BrN 2 O, (I b ), (2 RS )‐2‐(2‐bromobenzyl)‐3‐(1‐methyl‐1 H ‐indol‐3‐yl)‐3‐oxopropanenitrile, C 19 H 15 BrN 2 O, (II b ), and (2 RS )‐3‐(1‐benzyl‐1 H ‐indol‐3‐yl)‐2‐(2‐bromobenzyl)‐3‐oxopropanenitrile, C 25 H 19 BrN 2 O, (II c ), the latter two of which crystallize with Z ′ = 2, and ( E )‐1‐(1‐acetyl‐1 H ‐indol‐3‐yl)‐3‐(2‐bromophenyl)‐2‐cyanoprop‐1‐en‐1‐yl acetate, C 22 H 17 BrN 2 O, (III), and ( E )‐1‐(1‐benzyl‐1 H ‐indol‐3‐yl)‐3‐(2‐bromophenyl)‐2‐cyanoprop‐1‐en‐1‐yl benzoate, C 32 H 23 BrN 2 O, (IV). The structure of the related chalcone ( E )‐2‐benzoyl‐3‐(2‐bromophenyl)prop‐2‐enenitrile, (V), has been redetermined at 100 K, where it is monoclinic, as opposed to the triclinic form reported at ambient temperature.