Acylations 1,2,4-triazole

In pyrazolo[4,3-c]pyrazoles and pyrazolo[3,4-d]-t>-triazoles, acyl derivatives of the type 383, analogs of the stable NH tautomer (Section IV,A, 1) are formed.65,66b-66c-367... 

Triazole acyl-tripeptides, (HI), prepared by McComsey (4) and aminomethyl-pyrroloquinazoline derivatives, (IV), prepared by Maryanoff (5) were effective as PAR-1 antagonists and used for treating PAR-1-mediated disorders. 

In peptide syntheses, where partial racemization of the chiral a-carbon centers is a serious problem, the application of 1-hydroxy-1 H-benzotriazole ( HBT") and DCC has been very successful in increasing yields and decreasing racemization (W. Kdnig, 1970 G.C. Windridge, 1971 H.R. Bosshard, 1973), l-(Acyloxy)-lif-benzotriazoles or l-acyl-17f-benzo-triazole 3-oxides are formed as reactive intermediates. If carboxylic or phosphoric esters are to be formed from the acids and alcohols using DCC, 4-(pyrrolidin-l -yl)pyridine ( PPY A. Hassner, 1978 K.M. Patel, 1979) and HBT are efficient catalysts even with tert-alkyl, choles-teryl, aryl, and other unreactive alcohols as well as with highly bulky or labile acids. 

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). 

H- Pyrro lo[l,2-c][l,2,4]triazol-3-ones synthesis, 6, 991 Pyrroloyl azides Curtius rearrangement, 4, 288 Pyrrolyl anions acylation, 4, 232 alkylation, 4, 235 solvent effects, 4, 236 C-alkylation... 

Triazole, 5-amino-acetylation, 5, 696 acylation, 5, 696 diazotization, 5, 97 4-substituted... 

The triazoles previously obtained from jS-keto-ylides and acyl azides or ethyl azidoformate are the 2-acyltriazoles (80) formed by isomerization under the basic conditions of the initially formed 1-substituted triazoles (79). The latter can be isolated in some cases if the reactions are interrupted. Aryl mono- and bis-azides have also been used in the preparation of the triazolcs (81). 

Hydroxyenones have also been used in catalytic amide formation, although 1,2,4-triazole is required as a co-catalyst. Assumed protonation of the Breslow intermediate and tautomerisation generates an acylazolium intermediate, which is trapped by triazole, releasing the NHC and generating the acyltriazole 60 that is the active acylating agent for the amine (Scheme 12.11) [16]. 

The mass spectra of azolides are not very specific, since they depend to a large extent on the structures of the respective acyl groups. Flash vacuum pyrolyses of azolides has been studied for 1-acyl-1,2,4-triazoles and benzotriazolides by tandem mass spectrometry (MS/MS). 461 Rearrangements of triazolides resulted in the formation of oxazoles. 471... 

Irradiation of 1-acyl-1,2,4-triazoles, contrary to A-acylimidazoles affords no photo-Fries products, but instead forms aldehydes and other products via the corresponding acyl radicals.t9]... 

Acyl hydrazides are useful precursors for the synthesis of 1,2,4-triazoles. Reaction of acyl hydrazides 149 with imidoylbenzotriazoles 148 in the presence of catalytic amounts of acetic acid under microwave irradiation afforded 3,4,5-trisubstituted triazoles 150 <06JOC9051>. Treatment of A-substituted acetamides with oxalyl chloride generated imidoyl chlorides, which reacted readily with aryl hydrazides to give 3-aryl-5-methyl-4-substituted[ 1,2,4]triazoles <06SC2217>. 5-Methyl triazoles could be further functionalized through a-lithiation and subsequent reaction with electrophiles. ( )-A -(Ethoxymethylene)hydrazinecarboxylic acid methyl ester 152 was applied to the one-pot synthesis of 4-substituted-2,4-dihydro-3//-1,2,4-triazolin-3-ones 153 from readily available primary alkyl and aryl amines 151 <06TL6743>. An efficient synthesis of substituted 1,2,4-triazoles involved condensation of benzoylhydrazides with thioamides under microwave irradiation <06JCR293>. 

The regioselective alkylation and acylation of 3,5-diamino-l,2,4-triazole 19 using a simple protecting group strategy has been described in detail <2006RJA624, 2006ZPK632>. 

Phenyl-1,2-dihydro-3//-l,2,4-triazole-3-selenones 130a-d were delivered as minor products from the reaction of a range of acyl chlorides with potassium isoselenocyanate (Equation 40 and Table 23) <2006H(68)1191>. 

---