HADDADIN-ISSIDORIDES Quinoxaline Synthesis

HADDADIN ISSIDORIDES Ouinoxalinesynthesis Synthesis of quinoxaline dioxides from benzofurazan oxide and ketone enolates or enamines (also known as Beirut reaction). 

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,... 

M. J. Haddadin, A. Yavrouian, and C. H. Issidorides, Tetrahedron Lett., 1409(1970). Routes in the synthesis of furo[3,4-6]quinoxalines have been explored M. M. Roland, Ph.D. Dissertation, Utah State University, Salt Lake City (1975) [Dui. Abstr. B 36, 244 (1975)]. 

Haddadin and Issidorides first reported an elegant method for the synthesis of quinoxaline 1,4-dioxides (47) from the reaction of benzofurazan 1-oxide (46) and an enamine or an active methylene compound, such as a /J-diketone or a /J-ketoester, in the presence of base.46 47 Quinoxaline 1,4-dioxide formation formally involves loss of secondary amine in the enamine reaction and loss of water when an active methylene compound of the type R CH2CORJ is used. This reaction is now commonly referred to as the Beirut reaction. The isolation of the dihydroquinoxaline 1,4-dioxide 48 from the reaction of 46 and NJV-dimethylisobutenylamine (Me2C=CHNMe2), which is unable to aromatize by amine loss, suggests that 2,3-dihydroquinoxalines are likely intermediates in all these reactions.48... 

Quinoxaline and phenazine bis-jV-oxides, synthesis from benzofuroxan M. J. Haddadin and C. H. Issidorides, Heterocycles 4, 767-816 (1976). 

Habibi D, Nematollahi D, Meshldnghalam S, Varmaghani E (2014) An unexpected oxidative decarboxylation reaction of 2,3-dihydroxybenzoic acid in the synthesis of new dibenzylte-trahydroquinoxalinediones. Tetrahedron 70 4361-4366. doi 10.1016/j.teL2014.04.077 Haddadin MJ, Issidorides CH (1976) Application of benzolurazan oxide to the synthesis of heteroaromatic A-oxides. Heterocycles 4(4) 767-816. doi 10.3987/R-1976-04-0767 Haddadin MJ, Agopian G, Issidorides CH (1971) Synthesis and photolysis of some substituted quinoxaline di-A-oxides. J Org Chem 36(4) 514-518. doi 10.1021/jo00803a005 Haddadin MJ, Bitar H, Issidorides CH (1979) Synthesis and some reactions of o-nitrosoaniline. 

Haddadin MJ, Issidorides CH (1967) Photolysis of a quinoxaline-di-A-oxide. Tetrahedron Lett 8 (8) 753-756. doi 10.1016/S0040 039(00)90589-6 Hakan G, Tuncbilek M, Ayhan G, Altanlar N (1998) Synthesis of some new benzimidazolecar-boxamides and evaluation of their antimicrobial activity. Farmaco 53(6) 415-420. doi 10.1016/ S0014-827X(98)00045-7... 

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