1,2,3 triazole regioselective synthesis

Oxidative processes using mild oxidants (e.g., HgO or Mn02) leading to NN bond formation convert /k-hydrazones 538 into the 1-amino-l,2,3-triazole derivatives 539 (Scheme 242) <1967TL3295, 1971JPR882>. A regioselective synthesis of 2,4-disubstituted 1,2,3-triazoles is based on a reaction of aminoacetophenones 540 with hydrazines (Scheme 243) . The reaction with methylhydrazine proceeds well without any catalysis, but that with phenylhydrazine requires cupric chloride as a catalyst. It is assumed that hydrazone 541 that forms in the first step is in a tautomeric equilibrium with its azo form 542 <2003SC3513>. 

Dandia A, Singh R, Khaturia S et al (2006) Efficient microwave enhanced regioselective synthesis of a series of benzimidazolyl/triazolyl spiro [indole-thiazolidinones] as potent antifungal agents and crystal structure of spiro[3H-indole-3, 20-thiazolidine]-30(l, 2, 4-triazol-3-yl)- 2, 40(lH)-dione. Bioorg Med Chem 14 2409-2417... 

Other examples of the same type include the regioselective synthesis of 1-substituted 1,2,4-triazoles from either 4-aminotriazole (1) [Eq. (70)]... 

Palacios, R, Ochoa de Retana, A.M., Pagalday, J., and Sanchez, J.M., Cycloadditions of azidoalkyl-carboxylates to acetylenes and enamines. Regioselective synthesis of substituted triazoles, Org. Prep. Proc. Int., 27, 603, 1995. 

Other metal-mediated reactions of azide reagents to terminal alkynes have also been reported. Indium(ll) triflate catalyzed tandem azidation/l,3-dipolar cycloaddition of various (o,(o-dialkoxyalkynes 134 with trimethylsilyl azide yielded fused 1,2,3-triazoles 135 <05TL8639>. A new ruthenium-catalyzed process for the regioselective synthesis of 1,5-disubstituted-1,2,3-triazoles has been developed <05JA15998>. 

Palladium-eatalyzed reaction of bicyclic hydrazines 175 with allyltributylstannane 176 in ionic liquid provided a facile method for the synthesis of substituted l,2,4-triazole-3,5-dionecyclopentenes 177 <05SL2273>. Sonogashira coupling of 3-mercaptopropargy 1-1,2,4-triazoles 178 with various aryl iodides led to the regioselective synthesis of 6-benzylthiazolo[3,2-()] 1,2,4-triazoles 179 <05TL1607>. 

L. Barr, S. F. Lincoln, C. J. Easton, A cyclodextrin molecular reactor for the regioselective synthesis of 1,5-disubstituted-l,2,3-triazoles, Supramol. Chem., 2005, 17, 547-555. 

As 1,4-disubstituted 1,2,3-triazoles are usually prepared through copper-catalyzed 1,3-dipolar cycloadditions of terminal alkynes with organic azides, the use of a single copper complex for a direct arylation-based sequential catalysis was probed. Thereby, a modular chemo- and regioselective synthesis of fully-substituted 1,2,3-triazoles was achieved (Scheme 9.43). Notably, the overall reaction involved the selective coupUng of four components through the formation of one C—C- and three C—N-bonds [58]. 

Miao, T. and Wang, L. 2008. Regioselective synthesis of 1,2,3-triazoles by use of a sUica-supported copper(I) catalyst. Synthesis. (3) 363-368. 

XiongZ, QiuX-L, Huang Y, Qing F-L (2011) Regioselectivity synthesis of 5-trifluoromethyl-1,2,3-triazole nucleoside analogues via TBS-directed 1,3-dipolar cycloaddition reaction. J Fluorine Chem 132 166-174... 

Wu Y-M, Deng J, Fang X, Chen Q-Y (2004) Regioselective synthesis of fluoroalkylated-1,2,3-triazoles by Huisgen cycloaddition. J Fluorine Chem 125 1415—1423... 

Rozin YA, Leban J, Dehaen W, Nenaidenko VG, Muzalevskiy VM, Eltsov OS, Bakulev VA (2012) Regioselective synthesis of 5-trifluoromethyl-l,2,3-triazoles via CF3- directed cycUzation of 1-trifluoromethyl-1,3-dicarbonyl compounds with azides. Tetrahedron 68 614-618... 

A three-component regioselective synthesis of -hydroxy-1,2,3-triazole 23 uses the epoxide 22, phenylacetylene and sodium azide in water at room temperature. ... 

Spiteri C, Moses JE (2010) Copper-catalyzed azide-alkyne cycloaddition regioselective synthesis of 1,4,5-trisubstituted 1,2,3-triazoles. Angew Chem Int Ed 49(l) 31-33 Agalave SG, Maujan SR, Pore VS (2011) Click chemistry 1,2,3-triazoles as pharmacophores. Chem Asian J 6(10) 2696-2718... 

Scheme 13 Regioselective synthesis of l-arylsulfonyl-5-hydroxy-triazoles [46]...

The thermally induced 1,3-dipolar cycloaddition of alkynes with azides to obtain 1,2,3-triazoles is well known and further developed by Huisgen [1]. A Cu(I)- and Ru(I)-catalyzed variation of this cycloaddition to a regioselective synthesis of 1,4-and 1,5-substituted (Scheme 2.1) and functionalized 1,2,3-triazoles, respectively (Scheme 2.2), termed as click reaction, was developed independently by Sharpless et al. [2] and Meldal et al. [3] as delineated. 

Scheme 4.13 Regioselective synthesis of 5-trifluoromethyl-l,2,3-triazoles via CFj-directed...

Scheme 4.23 Organocatalytic azide-aldehyde D-t-2]-cycloaddition for regioselective synthesis of 1,4-disubstituted 1,2,3-triazoles.

Recently, in 2014, Wang et al. reported a regioselective synthesis of trisubsti-tuted triazoles 100 starting from allyl ketones 99 using a 2 1 mixture of aryl azide 2 and allyl ketone 99 in the presence of 10 mol% of diethylamine as the catalyst in DMSO at 80 "C (Scheme 4.36) [39]. The reaction worked well with aliphatic, aromatic, and heteroaromatic allyl ketones. Further, both aliphatic and... 

In conclusion, we have been successful in developing a new method for the synthesis of [ 1,2,3]-triazoles by regioselective 1,3-dipolar cycloaddition of 2-diazopropane with imidates 60 in good yields. 

Process development of the synthesis of iodoaniline 28 began with an improved synthesis of l-(4 -aminobenzyl)-l,2,4-triazole (6) (Scheme 4.7), which was prepared in the medicinal chemistry synthesis, albeit with poor regioselectivity (Scheme 4.1). We found that this aniline intermediate 6 could be readily prepared in three steps in >90% overall yield from 4-amino-l,2,4-triazole (30) and 4-nitrobenzyl bromide (4) based on a modified literature procedure [9]. The condensation of 30 and 4 in isopropyl alcohol followed by deamination gave the nitro... 

Tandem azidination- and hydroazidination-Hiiisgen [3 +2] cycloadditions of ynamides are regioselective and chemoselective, leading to the synthesis of chiral amide-substituted 1,2,3-triazoles <06OBC2679>. A series of diversely l-substituted-4-amino-l,2,3-triazoles 132 were synthesized by the copper-catalyzed [3+2] cycloaddition between azides 130 and ynamides 131 <06T3837>. 

---