Beirut Reaction Mechanism

There is some debate in the literature as to the actual mechanism of the Beirut reaction. It is not clear which of the electrophilic nitrogens of BFO is the site of nucleophilic attack or if the reactive species is the dinitroso compound 10. In the case of the unsubstituted benzofurazan oxide (R = H), the product is the same regardless of which nitrogen undergoes the initial condensation step. When R 7 H, the nucleophilic addition step determines the structure of the product and, in fact, isomeric mixtures of quinoxaline-1,4-dioxides are often observed. One report suggests that N-3 of the more stable tautomer is the site of nucleophilic attack in accord with observed reaction products. However, a later study concludes that the product distribution can be best rationalized by invoking the ortho-dinitrosobenzene form 10 as the reactive intermediate. 

With unsymmctrically substituted benzofuroxans, a mixture of products might be expected in cyclization reactions, however, considerable regioselectivity has been observed in cycliza-tions. For mechanisms of the Beirut reaction see references 215 and 216. 

In basic medium and under mild conditions, phenazine-5,10-dioxides 35 are formed. However, from 1,2,3-benzoxadiazol-l-oxide and enolates or enamines quinoxaline-1,4-dioxides arise. The Beirut reaction possesses considerable preparative scope, but its mechanism has not yet been fully elucidated. 

In 1965 researchers at the American University of Beirut observed that combining benzofurazan oxides with morpholine-cyclohexene in methanol afforded quinoxaline-1,4-dioxide in 48% yield. There is some debate in the literature as to the exact mechanism of the Beirut reaction. In the case of benzofurazan oxides reacting with an enamine, the following mechanism is generally accepted in the literature. The first step is nucleophilic addition of the enamine to the electrophilic benzofurazan oxide to form the ammonium zwitterion. Ring closure occurs via condensation of... 

Scheme 6. Beirut Reaction (a) General Reaction and (b) General Mechanism...

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