Benzofuroxans nucleophilic attack

In spite of the usefulness of the Beirut reaction, mechanistically it is not well understood. It has been suggested that the first step involves the nucleophilic attack by the enolate or the enamine at N-3 of the benzofuroxan to yield an intermediate iV-oxide (Scheme 50) which subsequently undergoes tautomerism to an hydroxylamino derivative. This intermediate then cyclizes to the dihydroquinoxaline 1,4-dioxide. This suggestion has not been proven, and indeed there is evidence that benzofuroxan is in equilibrium with 1,2-dinitrosobenzene... 

Most fused benzene rings are stable toward nucleophilic attack, but exceptions are known for highly electron-deficient benzazoles. Thus aniline and benzofuroxan at 150°C give the anil (354) <45HCA850). 

Nitration of benzofuroxans (Section VII, A) and decomposition of polynitrophenyl azides, provide generally satisfactory routes to nitrobenzofuroxans. The nitro groups render the ring susceptible to nucleophilic attack (see Section VII,B). 4,6-Dinitrobenzofuroxan, 5,6-dinitrobenzofuroxan, and nitrobenzodifuroxan (34) act as acceptors in change-transfer complex formation with aromatic hydrocarbons. Nitrobenzofuroxans have not been reduced to the... 

In the benzofuroxan series nucleophilic attack could in principle take place at N(l) or N(3). However reaction at N(3) is considered more likely and treatment with secondary amines yields o-nitroarylhydrazines <88JCS(p1)145>. Nucleophilic reactions take place preferentially in the homocyclic ring when it is activated by electron-withdrawing substituents (Section 4.05.7.2). 

Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, the reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 34) (88JCS(P1)145). 

Initial nucleophilic attack and ring opening are involved in the conversion of benzofuroxans into quinoxaline di-iV-oxides by treatment with imines, enamines, carbonyl compounds and active methylene compounds (354 — 355) (Section 3.4.1.10.1). 

In the benzofuroxan series nucleophilic attack occurs preferentially at the homocyclic ring if activating nitro groups are present, halides being readily displaced (see Section 4.22.3.3.2). Otherwise reaction generally takes place at N(5) of the oxadiazole thus... 

Examples include the synthesis of 3-amino-l,2,4-oxadiazoles starting from 3-acylamino-5-methyl-l,2,4-oxadiazole <2002H811> and 2-aryl-l,2,3-triazoles from l,2,4-oxadiazole-3-ketone arylhydrazones <1999T12885, 2006JOC5616>. Oximes, hydrazones, formamidines, and thioureas of the furazan series also undergo base-catalyzed mononuclear rearrangements <2004RCB1121>. Nucleophilic attack at N(3) takes place in the benzofuroxan series. For example, reaction with secondary amines leads to o-nitroarylhydrazines (Scheme 55). 

The second transformation is a version of the aforementioned Boulton-Katrizky rearrangement [522], Benzofuroxan was not isolated but appeared as an intermediate on heating 2,6-dinitro-3-azidoaryldiazenobenzene. The reaction starts with nucleophilic attack of the diazene fragment on the furoxan cycle nitrogen atom [653]. 

The main mechanistic features of the reaction are shown in Scheme 8, a key feature of which is the formation of an intermediate hydroxylamino-nitrone. However more detailed study is required as it is still not proved at which nitrogen of the benzofuroxan initM nucleophilic attack occurs. Experimental evidence has been obtained which suggests that reaction may occur via the tautomeric o-dinitrosobenzene form. ... 

The reactions of the homocyclic ring are considered in three parts attack by electrophiles attack by nucleophiles and transformations involving substituent groups, together with miscellaneous reactions. Unless otherwise stated common behaviour is assumed for benzofurazans and benzofuroxans. 

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