Issidorides

Perhaps one of the most exciting developments in the chemistry of quinoxalines and phenazines in recent years originates from the American University of Beirut in Lebanon, where Haddadin and Issidorides first made the observation that benzofuroxans undergo reaction with a variety of alkenic substrates to produce quinoxaline di-AT-oxides in a one-pot reaction which has subsequently become known as the Beirut reaction . Many new reactions tend to fall by the wayside by virtue of the fact that they are experimentally complex or require starting materials which are inaccessible however, in this instance the experimental conditions are straightforward and the starting benzofuroxans are conveniently prepared by hypochlorite oxidation of the corresponding o-nitroanilines or by pyrolysis of o-nitrophenyl azides. 

In 1965, Haddadin and Issidorides, at the American University of Beirut, observed that combining 1 with morpholinocyclohexene 5 in methanol afforded quinoxaline-1,4-dioxide 6 in 48% yield." Shortly thereafter, the same authors reported that 1 also reacts with 1,3-dicarbonyl compound 7 in the presence of triethylamine to give the quinoxaline-1,4-dioxide 8 in 38% yield. This reaction has been referred to in the chemical literature as the Beirut reaction to acknowledge the city in which it was discovered. 

The generation of other heteroq cles from Bfx and Fx has been the subject of exhaustive investigation. The most important transformation of Bfx to other heterocycles has been described by Haddadin and Issidorides, and is known as the Beirut reaction . This reaction involves a condensation between adequate substituted Bfx and alkene-type substructure synthons, particularly enamine and enolate nucleophiles. The Beirut reaction has been employed to prepare quinoxaline 1,4-dioxides [41], phenazine 5,10-dioxides (see Chap. Quinoxahne 1,4-dioxide and Phenazine 5,10-dioxide. Chemistry and Biology ), 1-hydroxybenzimidazole 3-oxides or benzimidazole 1,3-dioxides, when nitroalkanes have been used as enolate-producer reagent [42], and benzo[e] [ 1,2,4]triazine 1,4-dioxides when Bfx reacts with sodium cyan-amide [43-46] (Fig. 4). 

Jacobs, B. L., and Trulson, M. E. (1981) An animal behavior model for decreased central serotonergic function. In Serotonin Current Aspects of Neurochemistry and Function, edited by B. Haber, S. Gabay, M. R. Issidorides, and S. G. A. Alivisatos, pp. 657-680. Plenum, New York. 

Haddadin, M. J. Issidorides, C. H. Heterocycles 1976, 4, 767. The authors named the reaction after the city where it was discovered, Beirut, the capital of Lebanon. 

A simple, efficient, one-step synthesis of quinoxaline 1,4-dioxides from the reaction of benzofurazan oxide 179 with activated alkenes such as enamines was named the Beirut reaction in honor of the city of its discovery. Developments up to 1993 were surveyed by Haddadin and Issidorides <1993H(35)1503>, who first demonstrated this reaction. The benzofurazan oxide 179 (Scheme 52) also condenses with 1,3-diketones <1995M1217, 1996JHC1057, 1999CHE459, 2003EJM791, 2005H(65)1589>, /3-keto acid derivatives <1995H(41)2203,... 

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