Reactions of 1,2,3-Triazoles

A characteristic reaction of 1,2,3-triazoles is cleavage of one nitrogen-nitrogen... 

Thermal reaction of 1,2,3-triazol derivative 125 at 130 °C led to an open-chain intermediate 126, which with 2,2,4,4-tetramethyl-l,3-cyclobutanedithione 122b gave the 1,3-thiazole derivative 127 and thietane 124 in 43% and 26% yield, respectively (Scheme 28) <2002HCA2644>. 

Recent studies on the reaction of 1,2,3-triazoles with glycosyl halides have shown promise in the preparation of glycosyltriazoles (Eq. 26). The use of 5-diazouracils (e.g., 4.2-6) has been shown to be an important approach (Eq. 27) with many examples and excellent yields. El Khadem s laboratory has provided several examples of 2-aryl- derivatives from the osatriazoles (Eq. 28). The extent of interest in this field is illustrated by the publication of an undergraduate laboratory experiment based on the conversion of sucrose to 2-phenyl-l,2,3-triazole-4-carboxylic acid. ... 

In addition to the Ru- and Ag-catalyzed cycloaddition reaction, Homeff and coworkers developed an Rh-catalyzed transannulation reaction of 1,2,3-triazoles with nitriles (Fig. 12) [128]. The CuAAC product iV-sulfonyl 1,2,3-triazoles remains reactive and can react with nitriles to form the imidazole products through an Rh-... 

The addition of phthalimidylnitrene (374) to simple alkynes affords 1-azirines in yields of 1-15% (Scheme 10). In this reaction, which is of no real preparative value, the symmetrical 2-azirines (375) were suggested as the most plausible intermediates and unequivocal proof of the existence of such species was demonstrated from a series of 1,2,3-triazole pyrolysis reactions <71CC1518). Extrusion of nitrogen from the regioisomeric 4,5-disubstituted 1,2,3-triazoles (376) during flash vacuum pyrolysis furnished identical product mixtures which included both regioisomeric 1-azirines (377). 

Alkylation of 1,2,3-triazole with Ar-(2-bromocthyl)phthalimidc in the presence of Cs2C03 followed by cleavage of the phthalyl moiety with hydrazine provides l-(2-aminoethyl)-l,2,3-triazole 94 in 51% yield <2003JME1116>. A reaction of 4-nitro-l,2,3-triazole with propargyl bromide in the presence of KOH gives a mixture of isomeric 1-propargyl-l,2,3-triazoles 95 and 96 in the equimolar ratio <2003RJ01792>. However, in acidic media, when N-l... 

Esters of acetylenedicarboxylic acid 1023 are commercially readily available, are very reactive as dipolarophiles, and the carboxylic groups in products of their reactions can be easily converted to many other functionalities. Therefore, they are often the first choice as substrates for 1,3-dipolar cycloaddition to azides 1024 (Huisgen reaction). The reactions are carried out at room or elevated temperature, and the yields of 1,2,3-triazoles 1025 are usually high to quantitative (Equation 22). Several products obtained in this way are presented as structures 1026-1034. Some details about the reactions leading to these products are given in Table 10. 

In one approach to catalytic synthesis of 1,2,3-triazoles, copper(l) is introduced to the reaction mixture as Cul. Compounds 1109-1115 are obtained this way. As can be seen in Table 12, a tertiary amine is often added as a base. The reaction conditions are mild and yields of the products are high. In some cases, the reaction can be carried out in water (compound 1115). For the synthesis of triazole 1116, addition of Cu powder is enough to generate catalytic amounts of Cu(l). 

Reactions of salts of 1,2,3-triazole with electrophiles provide an easy access to 1,2,3-triazol-jV-yl derivatives although, usually mixtures of N-l and N-2 substituted triazoles are obtained that have to be separated (see Section 5.01.5). Another simple method for synthesis of such derivatives is addition of 1,2,3-triazole to carbon-carbon multiple bonds (Section 5.01.5). N-l Substituted 1,2,3-triazoles can be selectively prepared by 1,3-dipolar cycloaddition of acetylene or (trimethylsilyl)acetylene to alkyl or aryl azides (Section 5.01.9). 

A similar reaction of 1,2,4-triazole with 2-cyano-3-fluoropyridine 33 gave 3-[l,2,4]-triazol-l-yl-pyridine-2-carboni-trile 34 in a yield of 92% after purification (Equation 7) <2004JME2995>. 

L abbe has studied the rearrangement reactions of 1,2,3-thiadiazoles to differently substituted 1,2,3-thiadiazoles <1983CC588>. He also studied many 5-azido-l,2,3-thiadiazoles 33 that rearranged to 1,2,3,4-thiatriazoles 34 (Equation 5) <1988BSB163>. He even found that l,2,3-thiadiazole-4-carboxaldehydes 35 upon treatment with amines underwent thermal rearrangement to 1,2,3-triazoles 36 (Equation 6) <1993J(P1)1719>. 

Ab initio calculations on the equilibrium between (14a) and (14b) are carried out with the 3-21G basis set. Figure 4 shows a plot of the calculated activation energy E vs. the reaction energy AE for the cyclization reactions. The plot is linear and provides a striking confirmation of Hammond s postulate. The cyclic structures (14b) are found to be planar, while the terminal =NH group in (14a) is ca. 50° out of the plane formed by the other atoms in (14a) <90CC882>. The gas phase basicity and acidity of 1,2,3-triazole have been calculated by ab initio methods (6-31G //6-31G) and compared with experimental values <89MI 401-01 >... 

Tautomerism was only treated briefly in CHEC-I <84CHEC-i(5)67l> under the section of thermal and photochemical reactions. Tremendous effort has been devoted to the study of the tautomerism, both prototropic and ring chain, of 1,2,3-triazoles and benzotriazoles. Therefore, tautomerism is described is considerably more detail in CHEC-II. For tautomerism of 1,2,3-triazolines, see Section 4.01.5. 

Substituents at the C(4) and C(5) positions of 1,2,3-triazole and at the benzene ring of benzo-triazole can undergo normal functional transformations which are independent of the triazole ring. In addition, these substituents can undergo some specialized reactions, particularly the formation of triazolo fused bi- and tricyclic systems. 

Numerous publications have been devoted to the reactions of substituents attached to the nitrogen atoms of 1,2,3-triazoles, and particularly of benzotriazoles. Several comprehensive reviews have appeared <91X2683, 94M1 401-01, 94S445>. 

The reactions of 3-diazobenzo[6]thiophene-2-one (780) with enaminones leads to the formation of 1,2,3-triazoles (781) (19-77%) as the major products along with by-products (782) (Equation (74)). The nitro derivatives (783) react with various enaminones to give generally good yields of 1,2,3-triazoles (55-82%). The mechanism for the formation of the triazoles is described <93JOC7079>. 

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