1.2.3- Triazoles from azides

Sharpless, W. D., Wu, P., Hansen, T. V. and Lindberg, J. G. (2005) Just click it undergraduate procedures for the copper(I)-catalyzed formation of 1,2,3-triazoles from azides and terminal acetylenes. J Chem Educ., 82, 1833-1836. 

Triazoles from azides and enamines via 5-amino-J -1,2,3-triazolines... 

S.2.2.4. Triazoles from Azides. Cycloadditions of this type constitute a valuable synthetic route to the triazole ring system. This is shown in Scheme 5.30. This combination dates back to the early work of Huis-gen, but in more recent times it was discovered to be subject to catalysis by Cu(I) compounds. The reactions are fast under mild conditions, have high regiospecificity, and occur in a variety of solvents including water. In addition, reaction products are easily isolated. Reactions with these characteristics have become known as comprising click chemistry this term was coined by K. B. Sharpless. The first and most commonly used reaction referred to by this name is indeed the azide-alkyne cycloaddition, and new interest has developed in triazole hemistry since the discoveiy of the copper catalysis. In addition to its use in organic... 

In 2005, ruthenium cyclopentadienyl complexes were found to catalyze the formation ofthe complementary 1,5-disubstituted triazole from azides and terminal... 

Nitrogen nucleophiles used to diplace the 3 -acetoxy group include substituted pyridines, quinolines, pyrimidines, triazoles, pyrazoles, azide, and even aniline and methylaniline if the pH is controlled at 7.5. Sulfur nucleophiles include aLkylthiols, thiosulfate, thio and dithio acids, carbamates and carbonates, thioureas, thioamides, and most importandy, from a biological viewpoint, heterocycHc thiols. The yields of the displacement reactions vary widely. Two general approaches for improving 3 -acetoxy displacement have been reported. One approach involves initial, or in situ conversion of the acetoxy moiety to a more facile leaving group. The other approach utilizes Lewis or Brmnsted acid activation (87). 

Esters of a-diazoalkylphosphonic acids (95) show considerable thermal stability but react with acids, dienophiles, and triphenylphosphine to give the expected products. With olefinic compounds in the presence of copper they give cyclopropane derivatives (96), but with no such compounds present vinylphosphonic esters are formed by 1,2-hydrogen shift, or, when this route is not available, products such as (97) or (98) are formed, resulting from insertion of a carbenoid intermediate into C—C or C—H bonds. The related phosphonyl (and phosphoryl) azides (99) add to electron-rich alkynes to give 1,2,3-triazoles, from which the phosphoryl group is readily removed by hydrolysis. 

After the optimization of these conditions, by adding an azide to the input stream it was possible to synthesize a range of substituted triazoles in a heterogeneously catalysed three-component reaction (Scheme 18). After the CFC, the stream was passed through a column containing a resin-immobilized copper-based catalyst, which was used in a previous work by the same authors to successfully catalyze the formation of triazoles from alkynes and azides [44]. An immobilized thiourea-containing cartridge was subsequently used to remove any leached Cu catalyst. In a similar way as for the alkynes production, the series of resins was used to purify the product. 

The synthesis of triazoles from organic azides and active methylene compounds under basic conditions is well known. Although the condensation is stepwise, the reaction is usually regiospecific,... 

Amino-1,2,3-triazoles with a substituent at the 4-position have been prepared (i) from azides and active methylene nitriles (ii) from azides and ynamines (iii) from diazomethane and carbo-diimides (iv) from azides and 1,1-diaminoethenes and (v) from the rearrangement of 3-hydrazono-1,2,4-oxadiazoles. Among these, the first method, a regiospecific process, is the most versatile and convenient although it is suitable only for 5-NH2-substituted triazoles. Other methods are used to prepare 5-NHR , 5-NR R - and 5-NHCOR-substituted triazoles. Intramolecular cyclization of suitable precursors also gives 5-aminotriazoles. For example, a-imino-a-piperidyl phenylhydrazones (838), in the presence of copper acetate, give 5-piperidyl-triazoles (839) (Equation (85)) <94H(38)739>. 

Hydroxy-1,2,3-triazoles with an aryl or carbonyl function at C(4) are similarly synthesized from azides and 1,3-dicarbonyl compounds. 

The intermediate methylenetriazolines from azide-allene reactions also give isomeric methyltriazoles.185,186,254,301 The triazole formed in the... 

Imidazolines are well known and certain derivatives, such as efaroxan 27, stimulate insulin secretion by binding to imidazoline I3 receptors <1999ANY(881)217>. Stability decreases as the number of heteroatoms increases 1,2,3-triazolines 28 are formed from azides as 1,3-dipolar cycloadducts but readily form the aromatic 1,2,3-triazole by oxidation or elimination. 

It is possible to synthesize 1,2,3-triazoles from acetylenes and hydrazoic acid, but the instability of hydrazoic acid has limited this application. Sodium azide is sdylated readdy with trimethylchlorosdane to produce ttimethylsdyl azide [4648-54-8]y (CH3)3SiN3, which reacts with acetjdenes to produce... 

Intramolecular cycloaddition of (263) in the presence of potassium and AI2O3 leads to 4-phenyl-l,2,3-triazole (70CB1908). For the synthesis of 1-aryl-l,2,3-triazoles from aryl azides and sodium ethoxide see (68JCS(C)i329). 

Aryloxy- and alkyloxy-l,2,3,4-thiatriazoles have been prepared from azide ion and aryl chlorothionofbrmates " or alkyl chloro-thionoformates , respectively. Alkyloxythiatriazoles are also made from alkyl thionocarbazates and nitrous acid ° °. The subject has been reviewed by Martin . The 5-aryloxy- or 5-alkyloxy-l,2,3,4-thiatriazoles decompose thermolytically in a manner analogous to the decomposition of the other triazoles mentioned above they give nitrogen, sulphur and cyanates. This is the most used route to alkyl and aryl cyanates, R—OGN. The mechanism of this decomposition could be concerted, or it could involve a thioacyl azide ... 

Triple bonds add azides to give 1,2,3-triazoles (from carbon-carbon triple bonds) and tetrazoles (from nitriles or isonitriles). The reactions are of very wide scope, but there are few examples involving acyl azides. The formation of triazoles from acetylenes and azides in general has been reviewedand the scope of these reactions has been expanded by more recent work, a few examples of which are found in the references 255-25s triazole formation from acetylenes... 

Triazoles can also be prepared from in situ formation of azides from halo compormds. For example, 1,4-disubstituted-1,2,3-triazoles 138 were obtained in excellent yields by a convenient one-pot procedure from a variety of aryl and alkyl iodides 136 and terminal alkynes 137 without isolation of potentially unstable organic azide intermediates 05SL2941>. Efficient one-pot synthesis of 1,2,3-triazoles from in situ formation of azides from benzyl and alkyl halides with alkynes has also been reported <05SL943>. 

A one-pot, copper-catalyzed formation of fully decorated triazoles was recently demonstrated by Ackermann. In the first step, a copper-catalyzed click reaction produces triazoles from alkynes and azides. In the second step, a direct, copper-catalyzed... 

A convenient synthesis, which leads toA-hydrogen-l,2,3-triazoles, utilises the stable (and relatively safe) trimethylsilyl azide. Alternatively, by conducting a cycloaddition in the presence of formaldehyde, A-hydroxymethyl-triazoles are formed (mainly the 2-isomer from isomerisation of initially formed 1-hydroxymethyl-triazole) from which AT-unsubstituted heterocycles can be easily obtained using base azidomethanol is formed in situ and is the entity that adds to the alkyne. ... 

Synthesis of 1,2,3-triazoles from alkyl or aryl azides and active methylene compounds. 

Alkyl-1,2,4-triazole 4-imines can be also prepared from azides and 1-alkyl-1,2,4-triazoles.87 For instance, the IV-imine 53 is produced when acetyl azide, which under these conditions gives acetyl nitrene,89 is irradiated in the presence of 1-benzyl-s-triazole. 

The synthesis of alkoxy-1,2,3-triazoles by azide addition to acetylenes appears to be highly regiospeciftc, but the yields vary widely with the nature of the azide (Eq. 1). There are also some serious conflicting reports to be found. For examples, Huisgen and his collaborators have reported the addition of 4-nitrophenylazide (Eq. 1) to give an 83% yield. Furthermore, Daeniker and Druey have found 4-ethoxy-1-phenyl-1,2,3-triazole (the isomer of 8.1-1) from this same reaction (Eq. 2). Clearly, these discrepancies must be cleared up before the full utility of the method can be properly assessed. 

M. T. Garcia-Lopez, G. Garcia-Munoz, J. Iglesias, and R. Madronero, Heterocyclic JV-glyco-sides. III. Synthesis of A-glycosyl-v-triazoles from glycosyl azides and phenylacetylene, J. Heterocycl. Chem., 6 (1969) 639-642. 

R. E. Harmon, R. A. Earl, and S. K. Gupta, Synthesis of 1-JV-glycosyl-triazoles from glycosyl azides and substituted acetylenes, J. Org. Chem., 36 (1971) 2553-2556. 

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