Intriguing enigma of nitrobenzofuroxan's ‘Sphinx’: Boulton–Katritzky rearrangement or unusual evidence of the N-1/N-3-oxide rearrangement?

Abstract

The first attempt to compare Boulton–Katritzky rearrangement with N-1/N-3-oxide tautomerism: formation of isomeric products in the reaction between 2-aminothiazoles and 7-chloro-4,6-dinitrobenzofuroxan.

Novel Hybrid Compounds Containing Benzofuroxan and Aminothiazole Scaffolds: Synthesis and Evaluation of Their Anticancer Activity

“…Among possible isomers, which can be formed through Pathways 1 and 2 ( Scheme 2 ) both due to the N-1/N-3-oxide equilibrium and/or prototropic tautomerism in the molecule [ 25 , 26 , 27 , 28 ], the most stable one is 3aC ; however, the energy difference between models with different locations of hydrogen (at amine/thiazole N: 3aA / 3aC and 3aB / 3aD ) is less than 1 kcal/mole, suggesting the possible coexistence of both structures ( Table 1 ). The preferable location of the benzofuroxan oxygen moiety is at the N1 atom that is almost by 4 kcal/mol more advantageous compared to the tautomers with an oxygen atom located at N3.…”

“…On the example of the simplest representative of benzofuroxan and aminothiazole hybrids with R=R 2 =R 3 =H 3a, three possible ways have been considered for aromatic nucleophilic substitution reaction: Pathway 1-attack of electrophile on the exocyclic NH 2 , Pathway 2-attack of an electrophile on the endocyclic nitrogen atom and Pathway 3-attack on the carbon atom in Position 5 (Scheme 1). Among possible isomers, which can be formed through Pathways 1 and 2 (Scheme 2) both due to the N-1/N-3-oxide equilibrium and/or prototropic tautomerism in the molecule [25][26][27][28], the most stable one is 3aC; however, the energy difference between models with different locations of hydrogen (at amine/thiazole N: 3aA/3aC and 3aB/3aD) is less than 1 kcal/mole, suggesting the possible coexistence of both structures (Table 1). The preferable location of the benzofuroxan oxygen moiety is at the N1 atom that is almost by 4 kcal/mol more advantageous compared to the tautomers with an oxygen atom located at N3.…”

4,6-Dinitro-7-(thiazol-2-ylamino)benzo[c][1,2,5]oxadiazole 1-oxide

“…The presence of the two doublets permitted us to exclude the formation of compound C, where only one signal should be present for the thiazole moiety. In this context, it has to be noted that, when N,N-disubstituted 2-aminothiazole is used, only the product derived from this kind of attack was detected [11].…”

“…Other interesting nucleophiles we used are thiazole derivatives, which we combined with different electrophiles, mainly 4,6-dinitrobenzofuroxan and 7-chloro-4,6-dinitrobenzofuroxan (1) [9][10][11][12].…”

4,6-Dichloro-5-Nitrobenzofuroxan: Different Polymorphisms and DFT Investigation of Its Reactivity with Nucleophiles

“…Benzofuroxans (benzo[c][1,2,5]oxadiazole 1-oxides) occupy a relevant place in the variety of synthetic biological active compounds and are also of interest from a mechanistic point of view [23][24][25][26][27]. Benzofuroxans exhibit a wide spectrum of biological activities: they behave as UV-protective [28], antituberculosis [29], antileukemic, immunosuppressive [30], anti-infective [31], antibacterial [32], antifungal [33], insecticidal [34], and antiparasitic (antiplasmodial and trypanocidal) agents [35], calcium channel modulators [36], and monoamine oxidase inhibitors [37].…”