Acylation 1,2,3-triazole derivatives

FIGURE 7.14 Acylation of N-nucleophiles using polymer supported 1-hydroxybenzo-triazole derivative. 

Notwithstanding controversies on O- against AT-acylation of triazolinones, modern views favour the former. The substantial number of 1,2,4-triazole derivatives of phosphorus acids (8iHC(37)i, p. 241, 247, 316, 357) are acylated on oxygen even when alternative N-acylation would have been possible. 

The use of 6-membered ring systems as sources of amidrazones to be converted into triazoles is relatively rare the case of 1-aminoadenine (Scheme 91) has already been mentioned. Transformations of 4,6-dihydrazinopyrimidine, hydrazines formed from haloaminopyridazine (81 HC(37)l, p. 8) and 1,2,4-triazines (8lHC(37)i, pp.409,424,488) all involve amidrazone intermediates cyclized to triazoles with the acyl function derived from the original ring. For instructive examples of preparative links between tetrahydrotetrazine, formazans and 1,2,4-triazoles, see Scheme 120 (81KGS694). 

Ohler, E., Kang, H.-S., and Zbiral, E., Regioselective cyclisation reactions of acyl-substituted epoxyphosphonates with 2-mercaptoazoles. Syntheses of thiazolo[3,2-fii]benzimidazole, imidazo[2,l-fc]thi-azole, and thiazolo[3,2-fc]-[l,2,4]triazole derivatives, Chem. Ber, 121, 977, 1988. 

This reaction was first reported by Pellizzari in 1894. It is the preparation of 1,2,4-triazole derivatives by baking the mixture of amide and acyl hydrazide. Therefore, it is generally known as the Pellizzari reaction. This reaction is usually carried out at temperatures > 250°C, but very reactive substrates can proceed at relatively lower temperatures, such as the coupling between diphenylformamidine and formhydrazide at 150°C. This reaction is very useful for the preparation of monosubstituted-, disubstituted-, and 1,3,5-trisubstituted-l,2,4-l/f-triazoles. However, at such a high temperature, transamination may occur between amide and acyl hydrazide, especially for the aliphatic acid hydrazides," resulting in a mixture of triazoles and a lower yield of the expected triazole. It has been found that co-heating the mixture of formamide and hydrazine hydrochloride with two equivalents of pulverized KOH can improve the yield of 1,2,4-triazole to almost 17%. ... 

The action of formic acid on 6-phenylhydrazinouracil (628) causes ring contraction to the triazole derivative (629). Treatment of acyl-hydrazines R C0NHNH2 with alkyl isothiocyanates R NCS gives triazolinethiones (630), if... 

Triazoles are acylated with acyl halides, usually initially at the 1-position, but the acyl group may migrate to the 2-position on heating or on treatment with base. Thus acetylation with acetyl chloride often gives 1-acetyl derivatives, which rearrange to the 2-isomers above 120 °C (74AHCil6)33). 

Acyl derivatives of azoles containing two different environments of nitrogen atoms can rearrange. For example, 1-acyl-1,2,3-triazoles are readily isomerized to the 2H-isomers in the presence of triethylamine or other bases the reaction is intermolecular and probably involves nucleophilic attack by N-2 of one triazole on the carbonyl group attached to another (74AHC(16)33). 

Azido derivatives of furazans have proved to be particularly useful for the synthesis of heterocyclic systems. Thus, by 1,3-dipolar addition of l-azido(4-amino-l,2,5-oxadiazol-3-yl)aldoxime 186 to propargyl alcohol and phenylacetyl-ene, bicyclic 4-amino-l,2,5-oxadiazol-3-yl(4-R-l,2,3-triazol-l-yl)ketoximes 187 were obtained (Equation 34) which in reaction with acetic anhydride afforded the corresponding 0-acyl derivatives <2003RJ0574>. 

Alkylation or acylation takes place at the nitrogen in position 1 when l/7-[l,2,4]triazolo[4,3-A][l,2,4]triazole 9 is treated with methyl iodide or acetyl chloride, furnishing compound 10 or 11, respectively <1983S415>. The 7-methyl isomers 13 are obtained after conversion of compounds 9 into the 1-acetyl derivatives 11 followed by methylation with methyl trifluoromethanesulfonate to give the l-acetyl-6-aryl-7-methyl-3-methylthio-17/-[l,2,4]triazolo[4,3-A]-[l,2,4]triazol-7-ium-trifluoromethanesulfonates 12, which upon treatment with aqueous sodium carbonate afford the 7-methyl derivatives 13 <1985BCJ735>. 

In the reactions with phosphonio-a-methoxycarbonyl-alkanides, the products of type 261 derived from 1,3-cycloaddition can rearrange to the tautomeric lif-pyrazolo-triazole (87MI2). The reaction of 3-diazopyra-zoles and 3-diazoindazole with acyl-substituted phosphonium ylides led to pyrazolo-triazine and indazolo-triazine derivatives 266 instead of the expected triazole compounds (8IJHC675). In this case, the ylides, which can exist as phosphonium enolates, possess nucleophilic and electrophilic centers in a /8-relationship, giving [7 + 2] or [11 -I- 2]cycloaddition reactions. With dimethylsulfonio-a-aroyl-methanides, very complex, temperature-dependent mixtures were obtained, in some cases with sulfur retention (87MI3). 

Acyl substituents at the 3- and/or 4-positions result in decreased hydrolytic stability compared with the alkyl and aryl derivatives described above. Despite this constraint most of the usual reactions of the carbonyl group are possible. Aldehydes <9ILA1211> and ketones are oxidized to the carboxylic acid, borohydride reduction affords the expected alcohols, and epoxides are formed on reaction with diazomethane. Oximes and arylhydrazones are formed with hydroxylamine and arylhydrazines, and the products may subsequently undergo monocyclic rearrangement involving the oxadiazole to give the corresponding isomeric furazans and 1,2,3-triazoles (Section 4.05.5.1.4). 

Meso-ionic 3-acyl-1-phenyl-1,2,3-triazol-4-ones (190, R = Ph or Me, = H) have been postulated as intermediates in the interesting base-catalyzed transformation of IV-acylsydnone imines (191, R = Ph or Me, R = H) into 4-hydroxy-1-phenyl-1,2,3-triazole (192, R = A similar photochemical transformation (191 190, R = Me or Ph, R = Ph) has also been reported. " A different base-catalyzed transformation of sydnone imine derivatives into pyrazolones has been recently reported. ... 

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