1.2.4- Triazoles 3-hydrazino- from

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 ... 

The reaction of 2-anilino-l,4-naphthoquinone 374 with benzoylacetic acid hydrazide gives 3-hydrazino-pyrazolyl derivative 375, that is acetylated to produce 5-[[l,4-dihydro-l,4-dioxo-3-(phenylamino)-2-naphthalenyl]sulfonyl]-3-methyl-6-phenyl-5/7-pyrazolo[5,l-c][l,2,4]triazole 51. This latter derivative is also obtained in 51% yield from reaction of 374 with benzoylacetic acid hydrazide in the presence of a mixture of acetic acid-sodium acetate <2004PS(179)1907> (Scheme 39). 

Qualitative spot tests for aldehydes, in the presence of ketones, are generally only reliable for water-soluble compounds. This problem can be overcome by the use of 4-amino-3-hydrazino-5-mercapto-1,2,4-triazole (Purpald , Aldrich Chemical Company) in the presence of Aliquat (Scheme 5.27). Under aerial oxidation, the initially formed colourless cyclic adduct changes colour through red to purple. The colourless cyclic aminal can also be formed by ketones, but only the adducts derived from the aldehydes are oxidized to the purple bicyclic aromatic system [28]. Weakly electrophilic aldehydes, e.g., 4-methoxybenzaldehyde, reacts slowly, but will give the positive coloration upon gentle heating to ca. 70°C for one or two minutes. 

As part of their study on aza-transfer reactions, Tisler and co-work-ers289 290 reacted 2-hydrazino-4-oxo-4//-pyrido[l,2-u]pyrimidine with various diazo derivatives and obtained 2-azido- and 2-amino-4-oxo-4/f-pyrido[l,2-u]pyrimidines. From 2-azido-4-oxo-4/f-pyrido[l,2-u]pyrimi-dines various derivatives of 2-(l,2,3-triazol-l-yl)-4-oxo-4//-pyrido[1.2- ]-pyrimidine (221) were prepared by reaction with acetylene,287 1,3-dioxo compounds,166 ordiethylamine.291 For further ring transformation reactions of the 2-azido-4-oxo-4//-pyrido[l,2- ]pyrimidine (102), see Section lll.C.lO. 

The hydrazino compound (63) (from nucleophilic displacement of chlorine with hydrazine) reacts with triethyl orthoformate under mild conditions to give the fused triazole (64). Heating in a neutral solvent gives the thermodynamically more stable, isomeric fused triazole (65) which can also be obtained from (63) directly. The 5-amino derivative (29 see Section 4.05.3.1) is readily converted into (65 Scheme 25) (81JCS(Pl)2387). 

The dual nature of 4-aminotriazoles as aromatic amines and unsymmetric hydrazines gives rise to many interesting reactions (81HC(37)1, p. 161, 483, 607, 611) some of which are shown in Schemes 55-57. Although nitrous acid normally reacts with both amino and hydrazino groups, examples of selective reactivity are shown in Scheme 58. The nitrosamine from 4-benzylamino-1,2,4-triazole is cleaved by sodium hydroxide to triazole. 

Tetrahydro-[l,2,4]triazolo[4,3-h]cinnolines have been prepared from 3-hydrazino-5,6,7,8-tetrahydrocinnolines and the reagents just described for (17) (71BSF3043), and also by condensing 2-hydroxymethylenecyclohexanone with 4-amino-1,2,4-triazole (79JCS(P1)3085). 

As with the [4,3-c(] series of the previous section, derivatives of (40) are available by ring closure of various 6-hydrazino-l,2,4-triazines (74JPR667,79JHC555). There is also a report whereby these compounds have been prepared from 1,2,4-triazoles (70JPR669). 

Triazolo[3,4-6] 1,3-benzoxazole-3-thione (85) has been prepared by cyclizing 2-hydrazino-l,3-benzoxazole (83) with carbon disulfide (58USP2861076) or phenyl isothiocyanate (59JOC1478). The alternative approach (62TL1193) of fusing the 1,3-benzoxazole onto a 1,2,4-triazole was also used in the synthesis of 3-phenyl-1,2,4-triazolo[3,4- ]-benzoxazole (88) from 3-hydroxy-5-phenyl-4-(2-methoxyphenyl)-1,2,4-triazole (86). 

Treatment of 4-aroylamino-5-thiol[l,2,4]triazoles (90) with POCI3 induces cyclization to [l,2,4]triazolo[3,4-6][l,3,4]thiadiazoles (55) (Equation (20) and Table 8). The same fused heterocycles (55) can be obtained from the cyclization of 5-substituted 2-acetyl- or 2-benzoyl-hydrazino[l,3,4]thiadiazoles (54) (cf. 8.07.8.1.1(i)). 

Ring closure reactions of a 4-hydrazino[l]benzofuro[2,3- /]pyridazine, derived from naturally occurring rotenone, yielded [l]benzofuro[2,3-d]pyridazines fused with 1,2,4-triazole, 1,2,4-triazine, and 1,2,4-triazepine derivatives <01JHC1097>. 

Amination of nitroarenes with hydroxylamine, known for over 100 years [43], proceeds undoubtedly according to the VNS mechanism. Modem aminating agents, such as 4-amino-1,2,4-triazole [44—46], sulfenamides [47, 48], and 0-methyl hydroxylamine [49, 50], are more versatile and efficient than hydroxylamine. 1,1,1-Trimethyl hydrazinium iodide proved to be particularly useful for this purpose [51-53]. Amination with this reagent proceeds via addition of the hydrazino moiety followed by a base-induced p-elimination of trimethylamine from the corresponding adducts. 

---