Imidazole, 1-methyl-, positional reactivities

The substitution by imidazole (4) of pentafluorobenzenes 5 occurs mainly at the position para to the R moiety and, correspondingly, substituted imidazoles 6 are obtained in good yields." The reactivity varies markedly with the substituents nitro- or cyanopentafluorobenzene react readily at room temperature without the need for any bases however, methyl- or methoxypen-tafluorobenzene fail to react even at lOO C and in the presence of a strong basc. ... 

Imidazole is much less reactive to nitration than heterocycles like furan and thiophene. Nitration of l-methyl-2-(2 -furyl)imidazole (and the thienyl analogue) in acetic anhydride occurs at the 5 -position in polyphosphoric acid the imidazole ring is also 5-nitrated <89CHE1168, 91CHE1140>. Imidazole is, however, more reactive than thiazole imidazole substituted at C-2 by 2-methyl-4-thiazolyl nitrates at both 4- and 5-positions without affecting the thiazole moiety <89JHC1627>. 

TMS ethers are too labile to acid-catalysed hydrolysis to be preparatively useful, but tert-butyldimethylsilyl (TBDMS) ethers are around 10 times less susceptible to acid hydrolysis.The steric restriction about the central silicon atom presumably is the cause of the reduced reactivity, which also makes their introduction with tert-butyldimethylsilyl chloride (TBDMSCl) in pyridine selective for the primary position, but very slow. With the more basic imidazole 1 rather than 5.2 for pyridine) in DMF as base catalyst, the reaction is readier but loses its absolute selectivity for primary positions (Figure 6.25). Reaction of methyl a-o-glucopyranoside with two equivalents of TBDMS... 

Imidazole is much more reactive towards nitration than thiazole, snbstitution taking place via the salt, as does nitration of alkyl-thiazoles. Thiazole itself is nntonched by nitric acid/oleum at 160 °C, but methyl-thiazoles are sufficiently activated to undergo substitntion, the typical regioselectivity being for formation of more 5-nitro than 4-nitro derivatives the 2-position is not attacked 4,5-dimethylimidazole is resistant to nitration. The much less reactive oxazoles do not nndergo nitration. 

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