Oxidants heterocycle formation with

Thus, a rare one-pot reaction for assembling pyrrolo[l,2-fl]quinoxalines from 1-(2-nitrophenyl)pyrroles and various alcohols. The nitro reduction, alcohol oxidation, heterocycle formation, and heterocycle oxidation were realized in a cascade. A wide range of these fused heterocycles bearing different alkyl and aryl groups in position 4 have been elaborated from suitable substrates thereby 3-nitro-2-pyrrolopyridine was also compatible with this process, giving the corresponding fused tricyclic compounds. 

As 1,2,5-thiadiazole analogues, potent HlV-1 reverse transcriptase inhibitors, some simple 1,2,5-oxadiazoles, compounds 4-6 (Fig. 9), have been synthesized using the traditional Wieland procedure as key for the heterocycle formation [121]. Such as thiadiazole parent compounds, derivative with chlorine atoms on the phenyl ring, i.e., 5, showed the best anti-viral activity. Selectivity index (ratio of cytotoxic concentration to effective concentration) ranked in the order of 5 > 6 > 4. The activity of Fz derivative 6 proved the N-oxide lack of relevance in the studied bioactivity. These products have been claimed in an invention patent [122]. On the other hand, compound 7 (Fig. 9) was evaluated for its nitric oxide (NO)-releasing property (see below) as modulator of the catalytic activity of HlV-1 reverse transcriptase. It was found that NO inhibited dose-dependently the enzyme activity, which is hkely due to oxidation of Cys residues [123]. 

Small radicals such as tert-butylperoxy and ethylperoxy can, however, react via 1,4 H-transfer only the strain energy involved in O-heterocycle formation is 28 kcal. per mole. In this case, k.4(x — 106 sec."1 whereas krta = 10r> 4 sec. 1 and when [02] = 200 mm. of Hg, ko[02] = 105,3 sec. 1, so that k.4ct < < (tkr,a + k [02]). The result is that in the oxidation of small alkyl radicals, the route via alkylperoxy radicals will be blocked because reverse Reaction —4 competes successfully with Reaction 5. Reaction 2 will thus be a more effective mode of reaction of alkyl radicals with oxygen and the conjugate alkene will be a major product. 

When an oxidation with Mn02 leads to an enone containing a properly positioned amine, an intramolecular conjugated addition of the amine to the enone can occur, resulting in a useful one-pot oxidation followed by heterocycle formation.63... 

The deselelenation reaction of heterocycle 202 with triphenylphosphine followed by addition of mesitonitrile oxide results in the formation of product 203 in 83% yield (Scheme 12) <1995JOM43>. This compound is thermally very stable and does not decompose even at 200 °C in toluene. This reaction has been extended to the use of Tbt(Ditp)Sn=E, Tbt(Dmtp)Sn=S, and Tbt(Tcp)Sn=E precursors (E = S, Se) in the reaction with mesytonitrile oxide (Ditp = 2,2"-diisopropyl-/ -terphenyl-2 -yl Dmtp = 2,2"-dimethyl- z-terphenyl-2 -yl Tcp = 2,4,6-tricyclohexyl-phenyl) <2004JA15572>. 

The synthesis of heterocyclic compounds with aryl->o3-iodanes extends to oxidative-condensation reactions. This approach has recently been employed for the synthesis of 1,2,4-thiadiazoles 82 by the treatment of thioamides with DAIB or its polystyrene variant (Scheme 24) (02SC2155). The production of 82 in these reactions is accompanied by the formation of elemental sulfur. 

Like other heterocyclic iV-oxides, imidazole 3-oxides 1063 react with AC2O to give the corresponding imidazolones 1064 and 1065 (Scheme 257). TMSCN transforms 1063 into imidazole 2-carbonitriles 1066, whereas alkyl thiones convert 1063 to 1067 <2000HCA728, 1998HCA1585, 2002AGE2290>. The 2-aminoimidazoles 1068, formed from the reactions with either isocyanate or isothiocyanate, react further with isocyanates to form ureas but are inert toward thiourea formation. In contrast to nonaromatic imidazole A -oxides (nitrones), oxides 1063 react with DMAD to form butanedioates 1069, rather than the (putative) [3-1-2] adduct <2000T5405>. 

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