1.2.4- Triazoles carboxylic acid hydrazide

Amino-S-hy droxy-1,2,3-triazole-4-carboxylic acid hydrazide 1 A218... 

Ami no-5-hydroxy-1,2,3-triazole- 4 carboxylic acid hydrazide or 1-Amino-4-hydrazido-carbon-5-hydroxytri azole,(Called 1-Amino-4-hydrazidocarbon-5 oxytriazoI in Ref 2), HO-C-N(NH ) N, mw 158.13, N... 

Triazole ring synthesis Carboxylic acid hydrazides f carboxylic acid esters... 

Periluoroalkyl-1,2,4-triazoles are often formed by rearrangement of other heterocycles or by cyclization of carboxylic acid hydrazides or their analogues. In 1962 Brown and Cheng described for the first time the synthesis of 3,5-bis(perfluoroaIkyl)-l,2,4-triazoles 70 by treatment of bis(perfluoroaIkyl)-1,3,4-oxadiazoles with methylamine [71], The method for the synthesis of NH-unsubstituted 3,4-bis(perfluoropropyl)-l,2,4-triazole by the action of P2O5 on the corresponding hydrazine was also reported in this paper. Thirty years later Threadgill et al. [72] prepared 3,5-bis(trifluoromethyl)-4-(3-benzyloxypropyl)-4H-1,2,4-triazole by the reaction of 2,5-bis(trifluoromethyl)-l,3,4-oxadiazole with 3-benzyloxypropylamine in methanol (reflux, 9 days). 

Diaryl-1,2,4-triazoles from carboxylic acid hydrazide sulfonates and nitriles s. 11, 469 o... 

More recently, Somfai and coworkers have reported on the efficient coupling of a set of carboxylic acids suitable as potential scaffolds for peptide synthesis to a polymer-bound hydrazide linker [24]. Indole-like scaffolds were selected for this small library synthesis as these structures are found in numerous natural products showing interesting activities. The best results were obtained using 2-(7-aza-l H-benzo-triazol-l-yl)-l,l,3,3-tetramethyluronium hexafluoride (HATU) and N,N-diisopropyl-ethylamine (DIEA) in N,N-dimethylformamide as a solvent. Heating the reaction mixtures at 180 °C for 10 min furnished the desired products in high yields (Scheme 7.4). In this application, no Fmoc protection of the indole nitrogen is required. 

The carboxylic acids of triazoles are readily decarboxylated on heating but are otherwise stable. Esters, amides, nitriles, and hydrazides react normally. This is illustrated in Scheme 18 for the amide and nitrile functions (88JMC330). 

Hydrolysis of 2-phenyl-[l. 2.3]triazolo[4,5-d]pyrimidine-5,7-dione N-oxides 463 in basic solution gives rise to 4-amino- and 4-ureido-2-phenyl-l,2,3-triazole-5-carboxylic acid 1-oxides 464, as well as their hydrazides and methylamide (2005JGU636) (Scheme 134). 

A different synthetic strategy for the preparation of triazoles with a carboxylic acid or related functional sidechain starts from oxazolinones or thiazolinones, i.e. cyclic amides, to provide the carboxylic function. An ArNj or ArNHN= functional group is attached to the reactive position to obtain amidrazones with endocyclic amide and exocyclic hydrazide moieties. Note that in the examples, which are not intended to exhaust variations of this approach, 4-ones as well as 5-ones may be used. 

A variety of one-carbon cyclizing agents have been used (71JOC10) to prepare 3-substituted l,3-thiazolo[2,3-c] 1,2,4-triazoles (111) from 2-hydrazino-l,3-thiazoles (110). The acid hydrazides (113) of these hydrazines, prepared either directly from 110 and carboxylic acid derivatives or indirectly from 1-acylthiosemicarbazides (112) and a-haloketones, also undergo facile dehydrative cydization to 111. [71JOC10 78JHC401 ... 

Several Curtius reactions have been employed to produce a primary amino group. Triazole-4-carboxylic acid [from acetylene-1-carboxylic acid and hydrazoic acid in chloroform (46% yield)] was esterified (70%), then converted to the hydrazide (71%) and on to the urethane (52%) and 4-aminotriazole (20%) (57YZ452). The final stage went better for 4-amino-5-methyltriazole, which achieved a 53% throughput from the urethane (76JHC589). 4-Amino-1 -methyltriazole was obtained in 64% yield from 4-ethoxycarbonyl-l-methyltriazole in this way (59ACS888). 

Recently, Demirba reported preparation of 3,6-di[(4,5-dihydro-l,2,4-triazol-l-yl)methyl]-l,4-dihydro-l,2,4,5-tet-razines 2a-e by heating of equimolar mixtures of ([l,2,4]triazol-l-yl)acetohydrazides 65a-e and carboxylic acids 66 at 130-140 °C. Formation of 1,2,4,5-tetrazines 2a-e was quite unexpected, since more stable 1,3,4-oxadiazoles or 1-amino-l,2,4-triazoles could also be formed. However, the hydrazides 65a-e did not react with the carboxylic acid 66 and underwent cyclocondensation with another molecule of hydrazide 65a-e, respectively, to furnish the corresponding tetrazines 2a-e (Scheme 16) <2004MI311>. 

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