On the Nucleophilic Reactivity of 4,6-Dichloro-5-nitrobenzofuroxan with Some Aliphatic and Aromatic Amines: Selective Nucleophilic Substitution

Abstract

The reaction rates for the nucleophilic aromatic substitution of 4,6-dichloro-5-nitrobenzofuroxan 1 with eight aliphatic amines (characterized by very different basicities/nucleophilicities) and three anilines have been measured in both methanol and toluene. The obtained rates have been related to the basicity (pK aH in water and K b in benzene) or nucleophilicity (N Mayr constants) of the tested amines. The whole of the obtained kinetic data has furnished useful information on the high nucleophilic reactivity of benzofuroxan derivatives, which has been related essentially to two factors: the high electron-drawing ability/power of the condensed furoxan ring and the low aromatic character of the benzofuroxan system.

The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study

“…At the same time, the more electron-rich phenylazide undergoes cycloaddition with 1,3-dicarbonyl compounds under the same conditions [31,32]. Asnitro-substituted benzofuroxans are known for their superelectrophilic nature [7,21,[33][34][35][36], we attribute the difference between azidonitrobenzofuroxan 2 and azidofuroxan derivatives [27] to the strong electron-withdrawing effect of the former. Scheme 2.…”

“…Moreover, benzofuroxans exhibit anunusual chemical behavior due to the specificity of the electronic structure of the 1,2,5-oxadiazole-N-oxide cycle. Benzofuroxans are capable of entering not only substitution reactions [20,21], but also nucleophilic addition and cycloaddition reactions both as a dienophile and as a diene [22][23][24]. Additionally, they are characterized by the phenomenon of tautomerism (benzo[c] [1,2,5]oxadiazole 1-oxide quickly rearranging into benzo[c] [1,2,5]oxadiazole 3oxideviathe open dinitroso form) [25], which often complicates the determination of the structure of asymmetrically substituted benzofuroxans [26] and makes their derivatization a challenging task.…”

Recent Advances in the Synthesis and Biomedical Applications of Heterocyclic NO-Donors

“…Benzofuroxans bearing additional electron-withdrawing groups are also considered as super-electrophiles which is convenient for rapid and straightforward installation of various pharmacophoric moieties to the benzofuroxan core. Recently, a thorough investigation of the reactivity of 4,6-dichloro-5-nitrobenzofuroxan with aliphatic and aromatic amines was performed [ 109 ]. Using a super-electrophilic nature of the benzofuroxan ring system, a series of promising anticancer drug candidates 65 bearing 2-aminothiazole moiety was synthesized ( Scheme 33 ).…”

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

“…In line with our interest in the study of the reactivity/activity of heterocyclic compounds, we thoroughly investigated the chemical/biological behavior of several classes of heterocycles containing nitrogen, oxygen, and sulphur atoms. Thus, we examined ring-into-ring rearrangements [1][2][3][4], reactivity with nucleophiles [5][6][7], ring-opening [8,9], and so on [10][11][12]. Moreover, considering that in the last few decades, the interest of chemists has been deeply focused on the pharmaceutical/pharmacological activities of several heterocyclic compounds [13][14][15], we evaluated some of their cardiovascular [16], antitumor [17], or anti-MDR1 [18] effects.…”

“…Accordingly, some of us are conducting a long-term study of new syntheses of benzofuroxan derivatives, their chemical reactivity, biological activity, and the possibility of their use in the biological/pharmacological fields [7,23,27,28,51]. Among the benzofuroxans used in our previous works, 4,6-dichloro-5-nitro-benzofuroxan (1) (Figure 1) is one of the most interesting chemical platforms because it easily reacts with various nucleophiles, leading to the formation of products with very interesting antimicrobial activity.…”