Synthesis of partly-fluorinated heterocycles: reaction of perfluoro-2-methyl-2-pentene or perfluoro-5-aza-4-nonene with aniline or its derivatives

Abstract

Fluorine-containing aromatic compounds have drawn much attention because of their biological activities. [l-31 Many of them are used as new medicine or pesticide as themselves or as precursors for the synthesis of biologically active compounds. For example, some azoles and pyrimidines with perfluoroalkyl substituents have shown interesting biological activities. This fact substantially triggers the development of effective methods for the synthesis of various heterocyclic systems with a fluorinated moiety, especially a perfluoroalkyl group. Among the known methods for the production of 5-and 6membered heterocycles, hetero-cyclization by the reaction of binucleophilic reagents with available intemal perfluoroolefins has been focused as a useful methodology [4-71.The azetine derivatives are also the prospective intermehates for new antibiotics [8,9]. Synthesis of 4-membered heterocycles has been performed by the reaction of some intemal perfluoroolefins with ammonia or p r i m amines [ 10-161. Thus, reaction of tetrafluoroethylene trimer with cyclohexylamine led to l-cyclohexyl-2-trifluoromethyl-3(2,2,2-trifluoroethylidene)-cyclohexyl~o-4-N~yclohexylimino-2-azetine [lo]. Treatment of perfluor0-3,4-&methylhex-3-ene with butylamine or methylamine respectively gave N-butylaminoperfluoru-2,3,4-trimethyl-4-ethyl-2-azetine or 3-( 1 -methylamino-1trifluoromethyl-perfluoropropyl) -4-methyl-imino-N-methyl-2-trifluoromethyl-2 -azetine [ 1 31. Moreover, perfluoro-2-methylpent-2-ene is known to react with ferf-butylamine, iso-pqylamine and n-propylamine to yeld azetine derivatives [12,14-161. On the other hand, reaction of internal perfluoroolefin with aniline has been noticed to provide quinoline derivatives [ 10,17,18]. Thus, treament of aniline with 2H-heptafluorobut-2-ene produced the phenyl-(2-tnfluoromethyl-quinoline-4-yl)amine [ 131 and reaction of aniline with tetrafluoroethylene trimer provided 2-trifluoromethyl-3(1-N-phenylimino-2,2,2-~fluoroethyl)-4-(N-phenylamino)quinoline [lo]. The presence of electron-donating substituents in aromatic amines is supposed to facilitate the formation of quinoline derivatives. As a matter of fact, reaction of perfluoro-2-methylpent-2-ene with 2,4dimethoxyaniline gave 4(2,4dimethoxyanilino)-6,8-dimethoxy-2-pentafluoroethyl-3-trifluoromethylquinoline [17]. However, that kind question remains unclear yet since reaction of aniline with octafluoro-3,4-bis(tnfluoromethyl)hexa-2,4-diene yielded 1-phenyltetrakis(trifluoromethy1)-1H-pyrrole instead of 2,3,4,5-tetrakis(tnfluoromethyl)-1 H-benzo @] -azetine [ 191. To continue our research on the new methodology for the synthesis of heterocycles starting with 0-7803-6486-4/oO/$10.000 2000 IEEE.-159 -intemal perfluoro-olefins, we have investigated in detail the reactions of perfluoro-2-methylpent-2-ene (1) and perfluoro-5-azanon-4-ene (2) with aniline and its derivatives: 4-fluoroaniline, 2,6-dimethylaNline, 2,6-dichloroaniline, 4-methoxyaniline, 2-and 4-nitroaniline and pentafluoroaniline. All reactions were carried out in the presence of tri...