Synthesis of Carbolines via Microwave‐Assisted Cadogan Reactions of Aryl‐Nitropyridines

Abstract

Dedicated to the memory of Prof. Dr. Helmut Bönnemann Suzuki-Miyaura-couplings to aryl-nitropyridines followed by Cadogan reactions is a straight-forward method for the synthesis of d-and b-carbolines. Microwave irradiation of the nitrobiaryls in triethyl phosphite solutions conveniently gives moderate to very good yields of the carbolines. Reduction to the amines without cyclization occurs on certain substrates, and alkylation of the products is observed as a follow-up reaction. Instead of a-carbolines, naphthonitriles are generated by phosphite reduction and ring transformation.

Design, Synthesis and Cytotoxicity of Thiazole-Based Stilbene Analogs as Novel DNA Topoisomerase IB Inhibitors

“…Interestingly, the obtained compounds 6 – 32 were found to have no bromine atom at the 5-position of the thiazole ring. A reasonable explanation is that the bromine at the 5-position was reduced in the Arbuzov reaction procedure due to the known reducibility of triethyl phosphite [ 29 ]. Taking intermediate 4b (X = Cl) as an example to confirm this result, the corresponding phosphonate 5b bearing no bromine atom at the 5-position of thiazole was isolated and identified.…”

A Minireview on the Scope of Cadogan Cyclization Reactions Leading to Diverse Azaheterocycles

“…The possible route for the formation of naphthonitriles 6 could be explained based on the investigation done by Wentrup, [19] suggesting this formation could be due to the exchange of endo‐ and exocyclic nitrogen atoms in α‐pyridylnitrenes ( 3 a ). Further, based on his study, it can be proposed that the formation of such compound happen via nitrene intermediate ( 3 b ) leading to the opening of pyridine ring to produce a cyanobutadiene fragment with a nitrene substituent ( 3 d ), followed by addition of triethyl phosphate to form phosphineimine ( 3 e ) [20] . Thereafter, an intramolecular cyclization of butadienylbenzene takes place to produce cyanonaphthalene skeleton ( 3 f ), which finally undergoes the elimination of the iminophosphorane leading to the formation of naphthonitriles ( 6 ) as shown in Scheme 2.…”

C‐N and N‐N bond formation via Reductive Cyclization: Progress in Cadogan /Cadogan‐Sundberg Reactionǂ

“…An attempt was also made for the synthesis of α‐carbolines 181–18 4 from α‐nitro‐biarylpyridines (Scheme ), but the substrate was found to be inappropriate. However, naphthonitriles were obtained as main products along with small amount of dimethoxy‐α‐carbolines due to greater electron density and supposed to form via nitrene pathway …”

“…However, naphthonitriles were obtained as main products along with small amount of dimethoxy-a-carbolines due to greater electron density and supposed to form via nitrene pathway. [63]…”