A New Convenient Liquid- and Solid-Phase Synthesis of Quinoxalines from (E)-3-Diazenylbut-2-enes

Abstract

3-{[(tert-Butoxy)carbonyl]diazenyl}but-2-enoates react in tetrahydrofuran at room temperature with aromatic 1,2-diamines to give 3-methylquinoxaline-2-carboxylates. These products were also obtained in solidphase synthesis, by using polymer-bound 3-diazenylbut-2-enes.Introduction. ± In recent years, quinoxalines have received much attention owing to their biological activities [1]. The often diffused methods reported for their synthesis, in general, involve the condensation of aromatic 1,2-diamines with a-diketones [2]. Based on our previous experience on the chemistry of 3-diazenylbut-2-enes [3 ± 5], we considered a retrosynthetic route to readily obtain quinoxalines from these starting materials in one pot and under very mild conditions. In fact, we previously reported the easy nucleophilic attack of amino groups at the terminal C-atom of the heterodiene system to give the corresponding a-aminohydrazones by 1,4-addition [5]. In the case of further internal attack of a second amino group at the CNÀ hydrazone C-atom, followed by loss of the hydrazino residue, quinoxalines could be obtained.Our initial hypothesis was successfully verified, thus, we now report a new and convenient access to quinoxalines, not easily accessible by the classical methods, by reaction of 3-diazenylbut-2-enes with aromatic 1,2-diamines both via liquid-and solidphase procedure.

TsNBr2 Mediated Synthesis of 2‐Acylbenzothiazoles and Quinoxalines from Aryl Methyl Ketones under Metal Free Condition

“…Owing to these important applications, a number of synthetic strategies have been developed for the synthesis of quinoxalines. One of the most common methods for this type of heterocycles involves the condensation of 1,2‐diamines with two carbon synthons, such as α‐dicarbonyl compounds, α‐hydroxy ketones, α‐halo‐β‐keto ester, α‐halo ketones, oxalic acid, diazenyl butenes, epoxides, alkynes, aldehyde, vicinal diols, or diazoketones . However, many of these two carbon synthons are neither environmentally friendly nor easily available commercially.…”

Recent Advances in the Solid-Phase Combinatorial Synthetic Strategies for the Quinoxaline, Quinazoline and Benzimidazole Based Privileged Structures

“…Another similar methodology has been reported by aromatic nucleophilic substitution of the polymer linked o-nitro Wu and Ede [20] described a solid-phase synthesis of quinoxaline by employing polymer-bound ophenylenediamine (6) and its reaction with α-bromoketones to produce quinoxaline (9) as shown in Scheme 1. The use of polymer-bound 3-diazenylbut-2-enes as building blocks for the facile solid-phase preparation of quinoxaline derivatives has been reported by Santeusanio and co-workers and same group reported an improved synthesis for quinoxaline derivatives from N=N-polymer-bound 1,2-diaza-1,3-butadienes [21,22].…”

Improved Synthesis of SubstitutedQuinoxalines from New N=N-Polymer-bound 1,2-Diaza-1,3-butadienes

“…8,9 In respect to our previous work in this field, 8 this new method simplifies the work-up procedure by avoiding the cleavage step and permits the introduction of different functional groups at position 2 of the quinoxaline system. Furthermore, in contrast with the article of Wu and Ede,9 which reported the synthesis of a mixture of quinoxaline isomers, we obtained pure final products.…”

“…In order to test the reactivity of these new polymer-bound compounds and considering that quinoxaline derivatives are attractive due to their wide range of biological activi-ties, 7 we decided to submit 1,2-diaza-1,3-butadienes in solid-phase 5a-e to treatment with aromatic 1,2-diamines 6a-c. 8 Reaction occurs in tetrahydrofuran (THF) under reflux and gives directly free 3-methyl quinoxaline-2-carboxylates 9a-h that were easily purified by chromatographic methods (Scheme 2, Table 2). The reaction takes place by the nucleophilic attack of an NH 2 group of compounds 6 at position four of the azo-ene systems with formation of 1,4 adducts 7.…”