Hydrazines 1,2,4-triazoles

Nitric acid may be precipitated by nitron [2218-94-2] (4,5-dihydro-l,4-diphenyl-3,5-phenylimino-l,2,4-triazole). The yellow precipitate maybe seen at dilutions as low as 1 60,000 at 25°C or 1 80,000 at 0°C. To prevent nitrous acid from interfering with the test results, it may be removed by treating the solution with hydrazine sulfate, sodium azide, or sulfamic acid. 

The pyrazole ring is particularly difficult to cleave and, amongst the azoles, pyrazoles together with the 1,2,4-triazoles are the most stable and easiest to work with. This qualitative description of pyrazole stability covers the neutral, anionic and cationic aromatic species. On the other hand, the saturated or partially saturated derivatives can be considered as hydrazine derivatives their ring opening reactions usually involve cleavage of the N—C bond and seldom cleavage of the N—N bond. It should be noted, however, that upon irradiation or electron impact the N—N bond of pyrazoles can be broken. 

EINHORN - BRUNNER Tria2ole Synthesis Condensation of hydrazines with diacyctamines (imidea) to triazoles... 

Methyl>1,5-dlphsnyl-1,2,4-triazole (3), A mixture of phenyl hydrazine hydrochlonde 1 (14 5 g, 0.11 moQ, N-acetytbenzamide 2 (16.5 g, 0.1 moQ and NaOAc (10 g, 0.12 mol) in AcOH (30 mL) was refluxed for 10 h. The product was made elkaline wNaOH solution and extracted with Et20 Evaporation gave a pale yellow oil which slowly sofidiTied, mp 80-61 0. Recrystallization from 90% EtOH and petroleum ether afforded IS 4 g of 3 (76%). 

Triazole has been prepared by the oxidation of substituted 1,2,4-triazoles, by the treatment of urazole with phosphorus pentasulfide, by heating equimolar quantities of formyl-hydrazine and formamide, by removal of the amino function of 4-amino-l,2,4-triazole, by oxidation of l,2,4-triazole-3(5)-thiol with hydrogen peroxide, by decarboxylation of 1,2,4-triazole-3(5)-carboxylic acid, by heating hydrazine salts with form-amide,by rapidly distilling hydrazine hydrate mixed with two molar equivalents of formamide, i by heating N,N -diformyl-hydrazine with excess ammonia in an autoclave at 200° for 24 hours, and by the reaction of 1,3,5-triazine and hydrazine monohydrochloride. ... 

Three skeleton atoms of a hetero-l,3-diene are incorporated into a five-membered ring system on reaction with 1,2 [n,n] compounds (e.g., hydrazines, reaction type 4, equation 10). On further heating in the presence of azobisiso-butyronitrile (AIBN), the bis(trifluoromethyl)-substituted 1,2,4-triazolines are transformed into 5-tnfluoromethyl-l,2,4-triazoles in high yield [t02 (equation 22). 

Triazolopyrimidines and their derivatives are relatively stable toward alkaline and acid hydrolysis. However, the action of aqueous sodium hydroxide, ammonia, or hydrazine under pressure converts them to derivatives of 1,2,3-triazole. ... 

The action of hydrazine on l-acetonyl-5-chloro[l,2,4]triazole 777 or 778 gave (77JOC1018 82KGS1113) 779 and 780, respectively. Dehydrogenation of 779 gave 781. Condensation of 3-hydrazino[l,2,4]triazole 782 with... 

Regarding the series of hetero aromatic pentacyclic compounds with three heteroatoms, an accelerated synthesis of 3,5-disubstituted 4-amino-1,2,4-triazoles 66 under microwave irradiation has been reported by thermic rearrangement of dihydro-1,2,4,5 tetrazine 65 (Scheme 22). This product was obtained by reaction of aromatic nitriles with hydrazine under microwave irradiation [53]. The main limitation of the method is that exclusively symmetrically 3,5-disubstituted (aromatic) triazoles can be obtained. 

Simple 1,2,4-triazole derivatives played a key role in both the synthesis of functionalized triazoles and in asymmetric synthesis. l-(a-Aminomethyl)-1,2,4-triazoles 4 could be converted into 5 by treatment with enol ethers <96SC357>. The novel C2-symmetric triazole-containing chiral auxiliary (S,S)-4-amino-3,5-bis(l-hydroxyethyl)-l,2,4-triazole, SAT, (6) was prepared firmn (S)-lactic acid and hydrazine hydrate <96TA1621>. This chiral auxiliary was employed to mediate the diastereoselective 1,2-addition of Grignard reagents to the C=N bond of hydrazones. The diastereoselective-alkylation of enolates derived from ethyl ester 7 was mediated by a related auxiliary <96TA1631>. 

Formaldehyde hydrazones react with N,AT -thiocarbonyldi-1,2,-4-triazole to give hydra-zones of thioglyoxalyl-1,2,4-triazoles, which react readily under displacement of 1,2,4-triazole with nucleophilic reagents such as amines and hydrazines but also with less nucleophilic compounds, including hydrazones, sulfonylhydrazides, thiosemicarbazides, and hydrazides.[10]... 

Amino-1,2,4-triazole has been obtained from orthoformic ester and hydrazine hydrate in a sealed tube at 120° 1 by heating formylhydrazine at 150-210° 2-3-4 by heating N,N -diformyl-hydrazine at 160° 5 by decarboxylation of 4-amino-1,2,4-tria-zoldicarboxylic acid 6 by fusion of l,2-dihydro-l,2,4,5-tetrazine 6 and by heating l,2-dihydro-l,2,4,5-tetrazinedicarboxylic add above its melting point.4-6-7... 

Thiadiazinotriazolopyrimidines can be prepared in several ways from the hydrazine-substituted thiadiazino-pyrimidine 186. Reaction with carbon disulfide gives the thione 187 reaction with either anhydrides or orthoformates with sulfuric acid gives the substituted triazoles 188, and reaction with cyanogen iodide gives the aminotriazole 189 (Scheme 47) <2004HC0335>. 

Cyclic ADC compounds are similarly prepared by oxidation of the corresponding cyclic hydrazine derivatives. The most commonly encountered compounds are the 3//-l,2,4-triazole-3,5(4//)-diones (5), and in particular the 4-phenyl derivative (5, R = Ph), usually abbreviated as PTAD. Similarly, the abbreviation MTAD is used for the 4-methyl derivative. First prepared by Thiele,18 PTAD remained unused in organic synthesis until Cookson reported its powerful dienophilic properties some 70 years later.19 PTAD is an isolable, red, crystalline compound, prepared by r-butyl hypochlorite oxidation of 4-phenylurazole.20 Other oxidants which have been successfully... 

Conversion of other heterocyclic systems into pyridazines has also been used, for example the reaction of 3-aminopyrone 9 with hydrazine, followed by oxidative aromatisation <06T9718> and the more unusual utilisation of a 1,2,4-triazole 10 as the source of the N-N unit <06T8966>. In this latter transformation, the intermediate quaternary salt 11 was isolable. An even more unusual example was the reaction of the diazetidine 12 with enolates <06S2885>. 

Alkylation of 1,2,3-triazole with Ar-(2-bromocthyl)phthalimidc in the presence of Cs2C03 followed by cleavage of the phthalyl moiety with hydrazine provides l-(2-aminoethyl)-l,2,3-triazole 94 in 51% yield <2003JME1116>. A reaction of 4-nitro-l,2,3-triazole with propargyl bromide in the presence of KOH gives a mixture of isomeric 1-propargyl-l,2,3-triazoles 95 and 96 in the equimolar ratio <2003RJ01792>. However, in acidic media, when N-l... 

Gyclocondensation of diazomalonaldehyde 336 with 4-fluoroaniline carried out in methanol-acetic acid provides l-(4-fluorophenyl)-l,2,3-triazole-l-carbaldehyde 337 in 78% yield. Oxidation with MnOz in the presence of sodium cyanide in methanol converts aldehyde 337 into methyl ester 338 with 79% yield. Hydrazide 339 (84% yield) is obtained in a reaction of ester 338 with hydrazine. Product 339 reacts with various aromatic aldehydes to give hydrazones possessing interesting antiplatelet activity (Scheme 53) <2003BMC2051>. 

Disubstituted 1,2,3-triazoles are usually minor components in the product mixtures obtained from reactions of triazole with electrophiles (see Section 5.01.5). The few regioselective syntheses of such compounds include a reaction of aminoacetophenones 1235 with hydrazines. The reaction with methylhydrazine proceeds well without any catalysis, but that with phenylhydrazine requires cupric chloride as a catalyst. It is assumed that hydrazone 1236 that forms in the first step is in a tautomeric equilibrium with its azo form 1237. However, it is not clear how bond formation between the nitrogen atoms and oxidation to the triazole system occurs. 4-Aryltriazoles 1238 are obtained in 50-66% yield (Scheme 205) <2003SC3513>. 

The synthesis of a series of 2-pyridyl-substituted 1,2,4-triazoles was achieved from methyl 4-cyanobenzimidate 88 by reaction with the appropriate acid chloride and hydrazine via the unstable iV-aroyliruidatc intermediate. For example, reaction of 88 with 4-methoxybenzoyl chloride gave the imidate 89, subsequent reaction of which with pyridylhy-drazines 90a and 90b gave 1,2,4-triazoles 91a and 91b (Equation 33) <2004BMC2013>. 

Microwave irradiation of a reaction mixture containing aromatic nitriles, hydrazine hydrate, hydrazine dihydrochloride, and ethylene glycol as solvent in a one-pot process gave 3,5-disubstituted 4-amino-l,2,4-triazoles 98a-i in excellent yields (Equation 35 and Table 14) <2000TL1539>. 

Fluorinated triazole derivatives have been prepared by a somewhat deceptive route that starts with imine perfluoro(5-aza-4-nonene) 140 reaction of 140 with aromatic hydrazines gives 1,2,4-triazoles 141a-g in good yields (Equation 44 and Table 27) <2001RJ01621, 2001ZOR1693>. 

The reaction of perfluoro(5-aza-4-nonene) 140 with propionyl hydrazine under the conditions outlined above gives the parent 1//-1,2,4-triazole 142 in 42% yield via spontaneous loss of the propionyl group (Equation 45) <2001RJ01621, 2001ZOR1693>. 

Table 42 Reaction of fluorinated 1,2,4-oxadiazoles with hydrazine to give 1,2,4-triazole derivatives...

Oxadiazole 220 bearing a ferrocenyl substituent was reacted with ammonium ethanoate and hydrazine to yield the corresponding 1,2,4-triazoles 221 and 222 in reasonable yield (Scheme 19) <2003JOM(675)1>. 

This time using hydrazine hydrate as the amine donor, reaction with l,3,4-oxadiazole-2-(3//)-thiones 223a-e under heating in ethanol yielded the corresponding l,2,4-triazole-2-(3//)thiones 224a-e (Equation 69 and Table 46) <2005EJM1156>. 

Reaction of iminooxazolidinone 229 with hydrazine gave the 1,2,4-triazole 230 in an overall yield of 62% (Equation 72) <2002JHC319>. 

Unlike the 3-position, the 5-position is very susceptible to nucleophilic substitutions and additions. Thus, a series of publications report that 5-fluoroalkyl-l,2,4-oxadiazoles 94 undergo reaction with hydrazine or hydroxylamine to furnish 3-fluoroalkyl-l,2,4-triazoles 95 (X = NH) and 3-fluoroalkyl-1,2,4-oxadiazoles 95 (X = 0), a reaction that proceeds via addition of the nitrogen nucleophile to the 5-position (Scheme 9) <2005JOC3288, 2004EJ0974, 2003JOC605>. 

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