2-Arylhydrazononitriles in heterocyclic synthesis: a novel route to 1,3-diaryl-1,2,4-triazol-5-amines via a Tiemann rearrangement of arylhydrazonoamidoximes

2-Arylhydrazononitriles react with hydroxylamine hydrochloride in refluxing ethanolic sodium acetate to yield amidoximes that cyclized into 1,2,3-triazol-5-amines or 1,2,4-triazol-5-amines depending on the nature of the substituents on hydrazone linkage. NOE difference experiments could successfully be utilized to distinguish 1,2,3-triazoles from isomeric 1,2,4-triazoles


3
H H

Scheme 2
In an attempt to accelerate cyclization, amidoximes 6a-c were refluxed in acetic anhydride.The obtained products could be assigned the oxadiazolylarylhydrazone structure 8a-c or acetylamino-1,2,3-triazoles 9a-c.Structure 9 could be confirmed for these products based on their identity with acetylamino-1,2,3-triazole 9, prepared via acylating 7a-c with acetic anhydride.Interestingly 9a-c, could be converted into 7a-c upon reflux in ethanolic sodium ethoxide.To verify whether or not an oxadiazole 8 is formed initially, amidoximes 6 were acylated with acetyl chloride at room temperature, and even under such conditions the only products formed were acetylamino-1,2,3-triazoles 9 (cf.Scheme 2).Thus the intermediacy of oxadiazoles and subsequent Boulton-Katritzky 17,18 rearrangement, as has recently been assumed, seems least likely.In contrast to the behavior of 6a-c amidoxime 6d cyclized upon reflux in DMF in presence of piperidine to yield the 1,2,4-triazol-5-amine 11d as was established by Xray crystal structure (cf.Fig. 1).
ARKAT USA, Inc.It is believed that amidoxime 6d in this case has initially undergone a Tiemann rearrangment [19][20][21][22][23][24] to yield intermediate 10d that then further cyclized into 11d.It became now clear that we have two competing modes of cyclization that may lead either to 1,2,4-triazole or 1,2,3-triazole amines.It seemed thus mandatory to develop a way to establish, spectroscopically, structure for product of cyclization.An easy way could be achieved through NOE difference experiments.Thus irradiating NH 2 protons in 11d at δ 6.64 ppm enhanced ortho-aromatic protons at δ 7.65 ppm while in the 1,2,3-triazole irradiating amino protons did not effect such enhancement.

Conclusions
Arylhydrazonoamidoximes are readily obtainable compounds that can be easily cyclized to afford in good yields either 1,2,3-triazolamines or 1,2,4-triazolamines depending on the nature of substituent on the hydrazone carbon.A simple spectroscopic method that allows a reliable structure determination of the cyclization product is also suggested.
The support of this work was received from University of Kuwait through research grant (SC04/06) and the facilities of Analab/SAF (GS01/01) and (GS03/01) are gratefully acknowledged.

Crystallographic analysis
The crystals were mounted on a glass fiber.All measurements were performed on an ENRAF NONIUS FR 590.The data were collected at a temperature of 25 o C using the ω scanning technique to a maximum of a 2θ of 24.108 o .The structure was solved by direct method using SIR 92 and refined by full-matrix least squares.Non-hydrogen atoms were refined anisotropically.Hydrogen atoms were located geometrically and were refined isotropically.reflection 690 measured, θ max = 24.09o , ωR factor = 0.278.Figure 1 illustrates the structure as determined.Full data can be obtained on request from the CCDC. 25

Synthesis of 2-substituted-2-(2-arylhydrazono) acetonitriles (2d-h)
A cold solution of aryldiazonium salts (10 mmol) was prepared by adding a solution of sodium nitrite (1.4 g dissolved in 10 mL water) to cold solution of arylamine hydrochloride (10 mmol of arylamine in 6 mL, 6M HCl) with stirring.The resulting solution of aryldiazonium salts were then added to a cold solution of either enaminonitrile (4) or acetonitrile derivatives (1) in ethanol (50 mL) in the presence of sodium acetate trihydrate (2.8 g, 20 mmol).The mixture was stirred at room temperature for 1 h and the solid product was collected by filtration, washed with water and recrystallized from the appropriate solvent.
Method B. Compound (6) (1 mmol) was treated with acetyl chloride (0.079 g, 1 mmol) in piperidin (10 mL) and the reaction mixture was stirred for 4 h at room temperature and triturated as in method A.