Elsevier

Tetrahedron Letters

Volume 46, Issue 37, 12 September 2005, Pages 6345-6348
Tetrahedron Letters

Molecular iodine: a powerful catalyst for the easy and efficient synthesis of quinoxalines

https://doi.org/10.1016/j.tetlet.2005.07.026Get rights and content

Abstract

Various biologically important quinoxaline derivatives were efficiently synthesized in excellent yields using inexpensive, nontoxic, and readily available bench top chemical, iodine in catalytic amount (10 mol %). Besides this, a systematic study was carried out to evaluate parameters such as solvent and catalyst loading. Several aromatic as well as aliphatic 1,2-diketones and aromatic 1,2-diamines, such as substituted phenylene diamines, tetra amines were further subjected to condensation using catalytic amounts of iodine to afford the products in excellent yield.

Introduction

Among the various classes of nitrogen containing heterocyclic compounds, quinoxaline derivatives are important components of several pharmacologically active compounds.1 Although rarely described in nature, synthetic quinoxaline ring is a part of a number of antibiotics such as echinomycin, leromycin, and actinomycin, which are known to inhibit the growth of Gram-positive bacteria and are also active against various transplantable tumors.2 Besides this, it has been reported for their application in dyes,3 efficient electroluminescent materials,4 organic semiconductors,5 building blocks for the synthesis of anion receptor,6 cavitands,7 dehydroannulenes,8 and DNA cleaving agents.9 A number of synthetic strategies have been developed for the synthesis of substituted quinoxalines and the most common method is the condensation of an aryl 1,2-diamine with 1,2-dicarbonyl compounds in refluxing ethanol or acetic acid.10 However, many improved methods have been reported for the synthesis of quinoxalines using catalytic amounts of various metal precursors, acids, and zeolites.11 In addition to the above catalytic methods, reports were also known with microwave12 and solid phase synthesis.13 Nevertheless, most of these methods suffer from unsatisfactory product yields, critical product isolation procedures, expensive and detrimental metal precursors, and harsh reaction conditions, which limit their use under the aspect of environmentally benign processes.

The use of molecular iodine in organic synthesis has been known for a long time. In recent years, molecular iodine has received considerable attention as an inexpensive, nontoxic, readily available catalyst for various organic transformations14 under mild and convenient conditions to afford the corresponding products in excellent yields with high selectivity. However, there is no example of quinoxaline synthesis using molecular iodine as a catalyst. As part of our on going interest, in the use of cheap and ecofriendly materials as catalysts for various organic transformations, we had the opportunity to look into the synthesis of quinoxalines using molecular iodine.

Section snippets

Results and discussion

In the beginning, a systematic study was carried out for the catalytic evaluation of iodine toward the synthesis of quinoxalines. Initially, a blank reaction was conducted using benzil and o-phenylenediamine in boiling ethanol, which resulted in the formation of a condensation product after 45 min (60% Y). With the same substrates, the reaction in ethanol, using catalytic amount of iodine at room temperature afforded the products in quantitative yield during 15 min. Thus, in the absence of

Conclusion

In summary, we describe a simple, efficient, and ecofriendly method for the synthesis of quinoxalines from various 1,2-diketones and 1,2-diamines using cheap and readily available molecular iodine as a catalyst. The ambient conditions, high reaction rates, excellent product yields, and easy workup procedure not only make this methodology an alternative platform to the conventional acid/base catalyzed thermal processes, but also makes it significant under the umbrella of environmentally greener

Acknowledgments

Financial support of this work was provided by the National Science Council of the Republic of China and National Taiwan Normal University (ORD93-C) is gratefully acknowledged.

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