1.2.3.4- Tetramethyl-5,6-dinitrobenzene

Nitronium tetrafluoroborate used in large excess (>6 equiv.) is able to transform hexamethylbenzene and its derivatives to dinitroprehnitene (1,2,3,4-tetramethyl-5,6-dinitrobenzene) in a highly selective nitration process486 [Eq. (5.180)]. Scheme 5.47 summarizes the key steps of the mechanistic proposal, including the ipso - n i tro are n iu m ion 123, the formation of benzyl nitrite 124, and the complexation of the N02+ ion to form the mononitro intermediate (125) facilitating the attack to the ortho position resulting in the formation of the 1,2-dinitro product. 

Preparation of 4,5,6,7-tetrabromobenzotriazole and its tetrachloro analog by direct bromination or chlorination of benzotriazole is described in Section 5.01.7. However, other tetra-substituted benzotriazoles have to be constmcted from a suitably substituted benzene ring. Thus, treatment of pentamethylbenzene 1293 with fuming nitric acid in concentrated sulfuric acid provides 3,4,5,6-tetramethyl-l,2-dinitrobenzene 1294 in 66% yield. Using routine procedures, derivative 1294 is reduced with SnCl2 in aqueous HC1, and the obtained diamine 1295 is subsequently treated with NaNOz (in aq. HC1) to provide 4,5,6,7-tetramcthyl-l //-benzotriazole 1296 (Scheme 216) <2004BMC2617>. 

In an attempt to elucidate the mechanism, the reaction was performed in the presence of a radical trap (TEMPO=2,2,6,6-tetramethyl-l-piperidinoxyl), a reversible electron acceptor (dinitrobenzene), or a radical sensitizer (dimethoxybenzene). In all cases the proportion of coupled product was increased, suggesting that both radical and polar mechanisms contribute to the outcome of this reaction. 

Experimental evidence for the presence of radical intermediates is provided by the identification of expected products from radical rearrangements, by the use of appropriate radical probes and by direct detection by electron spin resonance (ESR). Other mechanistic evidence includes inhibition by radical traps, such as di-t-butylnitroxide (DTBN), TEMPO (2,2,6,6-tetramethyl-l-piperidinyloxy), galvinoxyl and oxygen, and by radical anion scavengers such as p-dinitrobenzene (p-DNB). 

Inhibition by radical traps or radical anion scavengers has been extensively used in providing evidence for the mechanism with both aliphatic and aromatic substrates. The most commonly employed inhibitors are compounds that add irreversibly to radicals butylnitroxide (DTBN), 2,2,6,6-tetramethyl-l-piperidinyloxy (TEMPO), galvinoxyl, etc.] and good reversible electron acceptors such as dinitrobenzenes (DNB) which intercept the radical anions38. 

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