4-Amino-1,2,3-triazoles acylation

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

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>. 

Treatment of 4-amino-3-phenyl-5-thio-477-[l,2,4]triazole 83 with bromoacylacetylenes gives the corresponding 6-(acyl-methylene)-5,6-dihydro-3-phenyl[l,2,4]triazolo[3,4- ][l,3,4]thiadiazohydrobromides 88 (Equation 23) <1988ZOR2151>. 

A-acylation of the triazole nucleus results in a bathochromic shift whereas acylation of substituent amino groups has little effect on the spectrum (55CR(24l)l049>. 

Halotriazoles can act as halogenating agents and A-acyltriazoles can act as acyl transfer reagents. Triazole can be used for the synthesis of peptide bonds and is superior to imidazole in that less racemization is observed. It can also be used to transfer the t-butyloxycarbonyl (t-Boc) protecting group to the nitrogen of amino acids. For details see Polya <84CHEC-I(5)733, p. 786). 

The parent 2(3/i/)-oxazolone moiety functions as a bifunctional leaving group when carboxyl groups are activated for acylations and condensations, similar to other five- and six-membered heterocycles such as imidazole, triazole, and 2-pyridinethiol. The excellent leaving ability of a 2(3//)-oxazolone moiety has led to the development of versatile reagents. Thus, 3-acyl- and 3-alkoxycarbonyl-2(3//)-oxazolones serve as ready-to-use -type agents for the regioselective and chemoselective N-protection of amino alcohols, amino phenols and polyamines. 

Uber eine Relais-Synthese lassen sich aus 4-(a-Amino-benzy]idenamino)-4H-l,2,4-triazolcn mit Carbonsaureanhydriden oder Carbonsaure-chloriden in Dimethylformamid 2-substi-tuierte 1,3,4-Oxadiazole im Eintopfverfahren herstellen552,553. Diese Reaktion verlauft iiber Acyl-hydrazone von 1-Formyl-3-phenyl-l,2,4-triazol, dessen Pyrolyse ebenfalls gute Aus-beuten liefert552. Mit dieser Methode konnten einige 1,3,4-Oxadiazole in besseren Ausbeuten und groBerer Reinheit als nach anderen Verfahren synthetisiert werden. 

The presence of a basic amino group affords a compound that also shows some degree of antidepressant activity. Acylation of the hydrazine (16-3) with chloroacetyl chloride proceeds on the more basic nitrogen to give the hydrazide (17-1). Heating that intermediate in acetic acid closes the triazole ring to give the chloromethylated product (17-2). The displacement of chlorine by means of dimethylamine then affords adinazolam (17-3) [21]. 

Other 7- substituents that have been introduced include the dialkylamino, acetamido, hydroxy, alkoxy and alkylthio groups (B-71MI11209). Acylation of the 7-amino group by heterocycles such as cyanuric chloride and its derivatives was inevitable, as was incorporation of a 7-triazole substitution pattern by diazotization of the 7-amino group and o-coupling with 2-naphthylamine followed by triazolization (94). 

Diazotiation 3-amino-5-acetamido-l,2,4-triazole and following substitution diazo group on nitro group on the method [392] leads to corresponding nitrotriazole [445], which on the acyl protection relieving gives 5-amino-3-nitro-l,2,4-triazole [262, 446] (Scheme 57). 

Nitro-l,2,4-triazole (45%) [451] and l-methyl-4-cyano-5-nitropyrazole (42%) [452] were isolated during the oxidation of corresponding aminoazole derivatives by a solution of hydrogen peroxide in trifluoroacetic acid. One of the amino groups in l-acyl-3,5-diamino-l,2,4-triazole is oxidized by hydrogen peroxide in the presence of sodium tungstate [453] (Scheme 59). 

Reaction with phenylhydrazine hydrochloride141 produces the isolable, ring-opened l-acyl-5-phenyl-diaminoguanidine hydrochloride (58), the free base of which is partly oxidized even by atmospheric oxygen to l-acyl-3-amino-5-phenylformazane. Cyclization of 58 with alkali produces arylhydrazino- or arylazo-1,2,4-triazoles (59) heating 58 in butanol produces 3,4-diamino-l,2,4-triazole (60). 

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