2-Substituted-l,2,3-triazoles

Regiospecific synthesis of 2-substituted-l,2,3-triazoles are rare. 5-Carbomethoxy-2-carbomethoxymethyl-4-trinitromethyl-l,2,3-triazole (84a) was prepared by 1,3-dipolar cycloaddition/ alkylation of NCC(N02)3 with Me02CCHN2. X-ray crystallographic data shows the trinitromethyl substituent of 83a is a strained sp center which infers chemical reactivity comparable to that observed for polynitrometnanes thus, 84a with ethanolic KOH afforded potassium 4-dinitromethyl-l,2,3-triazole salt (84b) [93ZOR(29)1231]. Copper-catalyzed oxidative cyclizations of arylhydrazones, while sensitive to substituent effects, provides 2-aryl-l,2,3-triazoles (85) [94H(38)739]. 

Treatment of 2- or 4-(p-formylphenyl)-2/f-l,2,3-triazoles with p-tolyl-substituted heterocycles such as benzo[6]furans,58,63 benzol-thiophenes,56,63 benzoxazoles,63,64 benzisoxazoles,54 oxazoles,63 isoxa-zoles,63 oxadiazoles,63,65 benzotriazoles,63 and y-triazolo [ 1,5-a]-pyri-dines19 has led to the formation of a number of new stilbene derivatives some of which are shown in Table XI. 

The aromatic 2-substituted 1,2,3-triazole 1-oxides are represented by the structure 341. The parent compound 342 is one of the three possible tautomeric forms of 1-hydroxy-l,2,3-triazole 343. 1-Hydroxy-l,2,3-triazoles 343 constitute a separate group of compounds, which are not included in the present review (Scheme 101). 

The resonance structures of the 2-substituted 1,2,3-triazole 1-oxides 341 are discussed in Section 1.1.1. According to IUPAC nomenclature, structure 341 is a 2-substituted 2H-l,2,3-triazole 1-oxide. Other names found in the literature are 2-substituted 1,2,3-triazole 1-oxides. In the present review the most commonly used naming, which is accepted by IUPAC, Chem. Abstr. Autonom., has been adopted calling structure 341 a 2-substituted 1,2,3-triazole 1-oxide. 

Leaving groups at C5 of 2-substituted 1,2,3-triazoles are predicted to be the most reactive in nucleophilic aromatic substitution reactions following an AE mechanism (see Section 1.4.2). Accordingly, chlorine at C5 of 360 could be replaced by strong nucleophiles like methanethiolate or methoxide to give 377 or 378. The unactivated 2-phenyl-4-chloro-l,2,3-triazole 380 (R=Ph) was inert toward these nucleophiles (1981JCS(P1)503) (Scheme 115). 

Unhke hydrazoic acid, trimethylsilyl azide is thermally quite stable. Even at 200° it decomposes slowly and without explosive violence. Accordingly it is a very convenient and safe substitute for hydrazoic acid in many reactions. A notable example is the cycloaddition of hydrazoic acid to acetylenes which is a general route to substituted triazoles. The reaction of trimethylsilyl azide with acetylenes is also a general reaction from which the 2-trimethylsilyl-l,2,3-triazoles may be obtained in good yield. On hydrolysis these adducts are converted under mild conditions to the parent alkyl 1,2,3-triazoles. ... 

In an extension of these reactions, 4-amino-2-methyl-l,2,3-triazole-5-aldehyde was refluxed with tetraethyl orthocarbonate. The isolated intermediate (86), stirred with cold ethanolic ammonia, provided 2-ethoxy-8-methyl-8-azapurine in good yield.87 This reaction seems to be unique for producing a 2-alkoxy-substituted pyrimidine ring. 

Substituted thiazolo[3,2-c][l,2,3]triazoles (50) react with alkyl halides at 2-N affording the corresponding quaternary 2,3-disubstituted thiazolo[3,2-c][l,2,3]triazolium salts (52) (Equation (4)) <91X2851, <94H2017>. 

Triazoles have been obtained via microwave-assisted [3 -i- 2] cycloaddition, under solvent-free conditions [54], starting from organic azides and acetylenic amides at 55 °C for 30 min (Scheme 23). The complete conversion of the reagents into hT-substituted-l,2,3-triazoles 69 was achieved without decomposition and side products. A control reaction carried out at the same temperature in an oil bath did not give the cycUc products, not even after 24 h of reaction time. 

The Raines group published an elegant paper on the replacement of an amide bond with a 1,5-substituted [l,2,3]-triazole 22 and incorporation of this dipeptide into bovine pancreatic ribonuclease (RNase A) by semisynthetic methods and showed that the melting temperature (T ) and catalytic activity of the resulting RNase A variants were retained. The triazolyl dipeptide was prepared by a Ru(ll)-catalyzed alkyne-azide cycloaddition which afforded 1,5-substituted triazoles, selectively (see Scheme 10.6). 

The D-g/wco-pentitol-l-yl substituted uracil 96 and its D-galacto-isomer were synthesized from tri-O-benzyl-D-glucal and -o-galactal, respectively, by [2+2]cy-cloaddition of trichloroacetyl or chlorosulfonyl isocyanate, cleavage of the p-lactam rings in the products with methanol after AT-carbamoylation, and cycliza-tion of resulting glycosylureas. Tosylation of 4-(D-ga/acro-pentitol-l-yl)-2-phenyl-2/f-l,2,3-triazole led to the 3,6-anhydride 97 and two partially tosylated derivatives. ... 

Copper catalyzed azide-alkyne cycloaddition (CuAAC reaction) is the well-known Huisgen [3+2] cycloaddition reaction of an azide with a terminal alkyne. The CuAAC gives a mild efficient reaction, which requires no protection groups, and no purification in many cases. Appukuttan et al. (2004) reported a one pot, three-component synthesis of various 1,4-substituted-l,2,3-triazoles using the corresponding... 

Halogeno-l-methyl-l,2,3-triazoles undergo substitution reactions with amines, but the 4-halogeno analogs do not. 5-Chloro-l,4-diphenyl-l,2,3-triazole with sodium cyanide in DMSO gives the cyano derivative (63JCS2032). 1-Substituted 3-chloro- and 5-chloro-l,2,4-triazoles both react with amines. 

A combination of the preceding type of synthesis and of cyclization of 4-amino-5-arylazopyrimidine can be seen in the novel procedure of Richter and Taylor. Proceeding from phenylazomalonamide-amidine hydrochloride (180), they actually close both rings in this synthesis. The pyrimidine ring (183) is closed by formamide, the triazole (181) one by oxidative cyclization in the presence of cupric sulfate. Both possible sequences of cyclization were used. The synthetic possibilities of this procedure follow from the combination of the two parts. The synthesis was used for 7-substituted 2-phenyl-l,2,3-triazolo[4,5-d]-pyrimidines (184, 185). An analogous procedure was employed to prepare the 7-amino derivatives (188) from phenylazomalondiamidine (186). 

In a 1-substituted 1,2,3-triazole (79), both the 2- and 3-nitrogen atoms possess lone pairs of electrons that are available for quaternary salt formation, and quatemization is known to occur at the 3-nitrogen atom to give the symmetrical cation (80). Thus, the reaction between 1-methyl-l,2,3-triazole and benzyl iodide yields the same salt as is obtained from the interaction of 1-benzyl-1,2,3-triazole and methyl iodide the salt must therefore be 80 (R = Me, R = PhCH2,... 

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>. 

Substitution of the 4-nitro group in 3,4-dinitrofuroxan 1176 by ammonia occurs readily, even at low temperature. Subsequent treatment of the obtained amine, product 1177, with r-butylamine results in formation of 4-amino-2-(/-butyl)-5-nitro-l,2,3-triazole 1-oxide 1178. However, there must be some additional side products in the reaction mixture, as the isolated yield of compound 1178 is only 17%. Upon treatment with trifluoroperacetic acid, the r-butyl group is removed. The obtained triazole system can exist in two tautomeric forms, 1179 and 1180 however, the 1-oxide form 1179 is strongly favored (Scheme 195) <2003CHE608>. 

Scheme 203 provides a methodology for the conversion of aryl bromides onto 4-aryl-l,2,3-triazoles. In the given example, palladium-copper catalyzed substitution of the bromine atom in indole 1226 by trimethylsilylacetylene provides intermediate 1227. Hydrolysis of the trimethylsilyl protecting group releases terminal alkyne 1228, isolated... 

Pyrazol-3-yl)pyridine 4-(2 -Pyridyl)l,2,4-triazole Room temperature R-substituted triazole in 4-position Spin crossover... 

Bromination of 2-aryl-thiazolo[3,2-A [l,2,4]triazoles 164 gives the corresponding 5-substituted 6-bromo thia-zolo[3,2-/ ][1,2,4]triazoles 165 (Equation 5) <2000FAR71>. 

Analogs of strobilurine, such as substituted thiazolo[3,2-A][l,2,4]triazoles at C-2, -5, and -6 positions of the heterocyclic skeleton, have been investigated as agrochemical fungicides <1999ELJP909760>. 

Two structurally related arylazides were also transformed similarly. Porter et al. described <1997S773> that ketone 486 can conveniently be transformed into 487 when treated with a substituted acetonitrile containing an active methylene group under basic conditions. The products were obtained in most cases in excellent yields. Cyclization to 489 proceeds in a similar manner as described by an Italian team <1996FA131, 2000EJM333> the n-azidobenzoic acid 488 yielded the fused [l,2,3]triazole 489. 

Lithium Salts Based on Heterocyclic Anions. Lithium salts based on organic anions where the formal charge is delocalized throughout substituted heterocyclic moieties were also reported sporadically, which included, for example, lithium 4,5-dicyano-l,2,3-triazolate ° and lithium bis(trifluoro-borane)imidazolide (Lild). ° The former was developed as a salt to be used for polymer electrolytes such as PEO, and no detailed data with respect to electrochemistry were provided, while the latter, which could be viewed as a Lewis acid—base adduct between LiBp4 and a weak organic base, was intended for lithium ion applications (Table 13). 

---