Alkyl- or Aryl-Disubstituted 1,2,3-Triazoles

The traditional synthetic method—addition of azides to terminal acetylenes—has been used extensively and often gives a good yield of 

A variety of other methods has been applied to the synthesis of 1,4-disubstituted 1,2,3-triazoles for example, the method developed by Sheehan has been modified by Hiittel and his collaborators (Eq. 6). This modification allows the conversion, in high yield, of the formyl group (2.1-6) into various functionally substituted side chains (Eq. 7). 

The anion of N-nitrosomethylethylamine (2.1-7) reacts with nitriles to form products of structure 2.1-8 in fair-to-good yield (Eq. 8). N-methyl-1,2,3-triazoles can be prepared by alkylation although both 1- and 2-methyl products are formed (Eq. 9). The reaction of benzonitrile with diazomethane in the presence of trialkyl-aluminum catalysts provides a modest yield of 2.1-9.  

The acid catalyzed condensation of N,N-dimethylaniline with the formyl group (Eq. 10) produces an excellent yield of the methanol derivative 2.1-10. The generality of this reaction should be examined. 

A large number of 3-propenyl derivatives (2.1-11) may be obtained in high yield from the reaction of 3-acetamidopyridine with cyanogen bromide and anilines followed by diazotization (Eq. 11). Similar results have been reported in the diazotization of N-alkylpyridinium salts (Eq. 12).  

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Recently Yi et al. also utilized 2-perfluoroaIkylethyl azides as 1,3-dipoles in the 1,3-dipolar cycloaddition to phenyl- or butylacetylenes [48]. As a result in the presence of copper(I) salt the corresponding l-fluoroalkyl-4-substituted 1,2,3-triazoles were obtained in about 60 % yield. Note that in this case only anti- isomers were obtained l-fluoroalkyl-4-aryl- or l-fluoroalkyl-4-butyl-l,2,3-triazoles. The authors do not explain the high selectivity of the process, although it may be attributed to the steric effect of the bulky substituents (aryl, butyl). Yi et al. note the relatively high efficiency of the fluoroalkyl 1,4-disubstituted-1,2,3-triazoles as catalysts of aldol condensation which may be easily recovered and reused [48]. Read et al. [49] virtually simultaneously with [48] published the results of their proper exploration of the copper salts catalyzed 1,3-dipolar cycloaddition of fiuo-rinated alkyl azides to acetylenes. This research extended the methodology... 

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