NR 2(R=H)(Route 1) was formed by conventional with hydroxylamine and deprotection.'A route to metrically 3, 5-disubsti- tuted isoxazoles, outlined in Sc of regiocontrol inherent in reactions of 1, 3-diketones with HR2 Scheme 45 Anthranils can be prepared by dehydration of 2-nitrobenzyl erivatives and this method has been used as a route to the sulfones 90 from the readily available nitro compounds 89 MNR2 CH2l2 Zn-Cu 3-Alkylaminoanthranils have been obtained by cyclisation of the nitrobenzylphosphonates 91.48 SMe MesH NHR Scheme 46 SOpH P(O)OEth2 isocyanide(TosMiC) to N-tosyl- or N-(dimethylsulfamoyl)- aldimines 97. 5 The N-substituent is easily removed from the imidazoles, either spontaneously or by reaction with aqueous HBr. Tetrasubstituted imidazoles 99 have been prepared by NR2 heating the amides 98 with ammonium trifluoroacetate. The reaction of methyl isothiocyanate with LDA can take different courses that are dependent on the reaction conditions(Scheme 47). The thiazole 100 is isolated after methylation of the reac- tion mixture with dimethyl sulfate, but the imidazole 101 is 93 obtained if the reaction mixture is quenched with water before methylation. 57 Further experimental and mechanistic details have appeared of the unusual conversion of 2, 5-diarylfurans into 3, 5-disubsti tuted isothiazoles which was described in the report. 49, 150 The dithiazole 92, which is easily prepared from Appels salt and malononitrile, has been converted in high yield into the isothiazole 93 by heating with benzyltriethyl- ammonium chloride.s3-Dialkylamino-1, 2-benzisothiazoles 95 are formed in excellent yields from the disulfide 94 by nucleo- philic addition of the amide r,NMg Br to the nitrile followed by oxidative cyclisation with copper()chloride. 5I 2MeN·=s 8 midazoles and benzimidazoles MeHN SMe A compilation of methods of synthesis of imidazoles and benz- nidazoles is available. 52 Several new routes to tri-and tetrasubstituted imidazoles are based on the cyclisation of amino( thiocarbonyl)amidines and related species. Two of these routes are outlined in Scheme 45. 3 Oxidative cyclisation followed by treatment with base 5% es N (Route I)resulted in the extrusion of sulfur, probably by way of the thiadiazine shown. alternatively the imidazole could be formed by S-methylation followed by the elimination of methanethiol ( Route 2). This second route is related mech Scheme 47 nistically to a different synthesis of imidazoles of this type which is shown in Scheme 46. In this synthesis the carbenoid attacks the nitrogen and the reaction then follows the same described that is a refinement of a method first published 80 course as in Route 2 above years ago by Pellizzari. Arylhydrazines were converted by suc- In a new application of their isocyanide methodology, van cessive cyanation and acylation into the hydrazides 102 monosubstituted imidazoles by the addition of tosylmethyl ether at 190C. This method was earlier shown to go by 2858 Chem. Soc. Perkin Trans. I.1999. 2849-28662858 J. Chem. Soc., Perkin Trans. 1, 1999, 2849–2866 was formed by conventional reaction with hydroxylamine and deprotection.145 A route to unsymmetrically 3,5-disubsti￾tuted isoxazoles, outlined in Scheme 44, avoids the problems of regiocontrol inherent in reactions of 1,3-diketones with hydroxylamine.146 Anthranils can be prepared by dehydration of 2-nitrobenzyl derivatives and this method has been used as a route to the sulfones 90 from the readily available nitro compounds 89. 147 3-Alkylaminoanthranils have been obtained by cyclisation of the nitrobenzylphosphonates 91. 148 Further experimental and mechanistic details have appeared of the unusual conversion of 2,5-diarylfurans into 3,5-disubsti￾tuted isothiazoles which was described in the previous report.149,150 The dithiazole 92, which is easily prepared from Appel’s salt and malononitrile, has been converted in high yield into the isothiazole 93 by heating with benzyltriethyl￾ammonium chloride.45 3-Dialkylamino-1,2-benzisothiazoles 95 are formed in excellent yields from the disulfide 94 by nucleo￾philic addition of the amide R2NMgBr to the nitrile followed by oxidative cyclisation with copper() chloride.151 8 Imidazoles and benzimidazoles A compilation of methods of synthesis of imidazoles and benz￾imidazoles is available.152 Several new routes to tri- and tetrasubstituted imidazoles are based on the cyclisation of amino(thiocarbonyl)amidines 96 and related species. Two of these routes are outlined in Scheme 45.153 Oxidative cyclisation followed by treatment with base (Route 1) resulted in the extrusion of sulfur, probably by way of the thiadiazine shown. Alternatively the imidazole could be formed by S-methylation followed by the elimination of methanethiol (Route 2). This second route is related mech￾anistically to a different synthesis of imidazoles of this type which is shown in Scheme 46.154 In this synthesis the carbenoid attacks the nitrogen and the reaction then follows the same course as in Route 2 above. In a new application of their isocyanide methodology, van Leusen and his co-workers have prepared a series of 4(5)- monosubstituted imidazoles by the addition of tosylmethyl Scheme 44 isocyanide (TosMIC) to N-tosyl- or N-(dimethylsulfamoyl)- aldimines 97. 155 The N-substituent is easily removed from the imidazoles, either spontaneously or by reaction with aqueous HBr. Tetrasubstituted imidazoles 99 have been prepared by heating the amides 98 with ammonium trifluoroacetate.156 The reaction of methyl isothiocyanate with LDA can take different courses that are dependent on the reaction conditions (Scheme 47). The thiazole 100 is isolated after methylation of the reac￾tion mixture with dimethyl sulfate, but the imidazole 101 is obtained if the reaction mixture is quenched with water before methylation.157 A new synthesis of 2-acylaminobenzimidazoles has been described that is a refinement of a method first published 80 years ago by Pellizzari. Arylhydrazines were converted by suc￾cessive cyanation and acylation into the hydrazides 102. These rearranged cleanly to benzimidazoles when heated in diphenyl ether at 190
C.158 This method was earlier shown to go by way Scheme 45 Scheme 46 Scheme 47