Mononuclear heterocyclic rearrangements. Part 4 Synthesis and characterization of the E-isomer phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole

3-Benzoyl-5-phenyl-1,2,4-oxadiazole (I) with phenylhydrazine in acetic acid gives the two geometrical isomers, phenylhydrazones II-Z and II-E, which have been characterized by uv-visible, ir, and nmr spectra. The possible II-E ? II-Z isomerization as well as the rearrangement of II-Z and of II-E into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole (III) has been pointed out.     

Mononuclear isoheterocyclic rearrangements. Note I. Interconversion of 3-benzoylamino-5-methyl-1,2,4-oxadiazole and 3-acetylamino-5-phenyl-1,2,4-oxadiazole

The first example of mononuclear isoheterocyclic rearrangement is reported. The 3-benzoylamino-5-methyl-1,2,4-oxadiazole ( 5 ) furnishes through a reversible process (slowly at room temperature in methanol, acetone or dioxane, fast in DMSO or in methanol in the presence of strong bases) a mixture of 5 and 3-acethylamino-5-phenyl-1,2,4-oxadiazole ( 6 ). The equilibrium process can be achieved also by heating 5 at 181° and the same reaction mixture can be obtained using 6 as the starting material. 3-Trichloroacetylamino-5-methyl-1,2,4-oxadiazole ( 7 ) was unaffected by similar treatment. The results obtained are discussed.     

Mononuclear heterocyclic rearrangements 5. Kinetic Investigation of the behaviour of (e)- and (z)-phenylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole in benzene. Isomerization and rearrangement

The kinetic behaviour of the geometrical isomers I-E and I-Z of the title compound in the presence of piperidine in benzene has been investigated. The kinetic results suggest that I-Z rearranges directly into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole (II), whereas I-E probably rearranges only through the intermediate I-Z formed by isomerization. All the reactions studied are piperidine-catalyzed.     

On the application of the extended Fujita-Nishioka equation to polysubstituted systems. A kinetic study of the rearrangement of several poly-substituted Z-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into 2-aryl-4-benzoylamino-5-phenyl-1,2,3-triazoles in dioxane/water

The rearrangement rates of several di-, tri-, tetra- or penta-substituted Z-arylhydrazones of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (1a-18a) into the relevant 2-aryl-4-benzoylamino-5-phenyl-1,2,3-triazoles (1b-18b) have been determined in 1:1 (v:v) dioxane/water in a wide range of pS⁺ (3.80-12.50) at different temperatures. The kinetic data obtained have been correlated with those previously collected for the rearrangement of ortho-, meta- and para-substituted Z-arylhydrazones (19a-38a) by means of an extension of the linear free-energy relationship (LFER) proposed by Fujita and Nishioka, thus considering steric (E_s) and field (F_o) proximity effects in addition to the normal electronic effects (σ_o,m,p). Excellent correlation coefficients have been calculated (R≥0.999), with susceptibility constants (ρ, δ and f) close to those previously obtained for 19a-38a, when only excluding data for the 2,6-bis-ortho-substituted Z-arylhydrazones 11a and 16-18a, which show a reactivity much higher than foreseeable, evidencing the first case of ‘steric acceleration’ in mononuclear rearrangements of heterocycles. A rationale for such a behaviour is proposed.     

Mononuclear heterocyclic rearrangement. Part 6 . Studies on base catalysis of the rearrangement of the (Z)-p-nitrophenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole in benzene: Effect of piperidine,triethylamine and of some secondary amines

The kinetics of the title reaction catalyzed by various secondary and tertiary amines have been measured at 40° in benzene. The catalysis laws which were observed confirm the previous hypothesis about the mechanism of the mononuclear heterocyclic rearrangements.     

The first kinetic evidence for acid catalysis in a monocyclic rearrangement of heterocycles: conversion of the Z-phenylhydrazone of 5-amino-3-benzoyl-1,2,4-oxadiazole into N,5-diphenyl-2H-1,2,3-triazol-4-ylurea

The title reaction has been studied in dioxane/water in a large (0.1-14.9) pS+ range, evidencing, together with an uncatalyzed process at intermediate (3.5-8.0) pS+ values, the occurrence of a catalyzed pathway both in the acidic (pS+ 0.1-3.5) and in the basic region (pS+ 8.0-14.9): specific-acid catalysis and general-base catalysis, respectively, have been found to take place by means of kinetic investigations at different buffer concentrations. Mechanisms for the three pathways have been advanced on the grounds of structural features. In a comparison with previous data particular attention has been paid to the acid-catalyzed pathway, herein observed for the first time in an azole-to-azole interconversion. The mechanistic hypotheses seem well supported by ab initio calculations.     

Heterocyclic rearrangements. N,N-diphenylhydrazones,oximes and O-methyloximes of 3-benzoyl-5-phenyl-1,2,4-oxadiazole

The behaviour of (E)- and (Z)-N,N-diphenylhydrazones and O-Methyloximes of 3-benzoyl-5-phenyl-1,2,4-oxadiazole has been studied. When refluxed in benzene, or in dioxane-water (1:1), the (Z)-N,N-diphenylhydrazone 8Z gave the indazole 11 or the substituted semicarbazide 12 , respectively. The O-methyloxime 14Z did not give any rearrangement. A criticism of the oximation reaction of 3-benzoyl-5-phenyl-1,2,4-oxadiazole is also reported.     

On the rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole into (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas: substituent effects on the different reaction pathways

We have recently evidenced an interesting differential behavior in the reactivity in dioxane/water between the (Z)-2,4-dinitrophenylhydrazone (1a) and the (Z)-phenylhydrazone (1b) of 5-amino-3-benzoyl-1,2,4-oxadiazole. The former rearranges into the relevant triazole 2a only at pS+ > 4.5 while undergoing hydrolysis at high proton concentration (pS+ < 3.5); on the contrary, the latter rearranges into 2b in the whole pS+ range examined (0.1 < or = pS+ < or = 14.9). Thus, for a deeper understanding of these differences we have now collected kinetic data on the rearrangement in dioxane/water of a series of 3- or 4-substituted (Z)-phenylhydrazones (1c-l) of 5-amino-3-benzoyl-1,2,4-oxadiazole in a wide range of proton concentrations (pS+ 0.1-12.3) with the aim of gaining information about the effect of the substituent on the course of the reaction. All of the (Z)-arylhydrazones studied rearrange via three different reaction routes (specific-acid-catalyzed, uncatalyzed, and general-base-catalyzed), and the relevant results have been examined by means of free energy relationships.     

On the use of multi-parameter free energy relationships: the rearrangement of (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole into (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas

By using a multi-parameter approach (a combination of Hammett/Ingold-Yukawa-Tsuno/Fujita-Nishioka free energy relationships) the mononuclear rearrangements of heterocycles (MRH) rates for five new ortho-substituted and ten new di-, tri-, or tetra-substituted (Z)-arylhydrazones of 5-amino-3-benzoyl-1,2,4-oxadiazole into the relevant (2-aryl-5-phenyl-2H-1,2,3-triazol-4-yl)ureas (in dioxane/water and in a large range of pS⁺ values) have been related to the electronic and proximity effects exerted by the present substituents, also considering previous results on some mono meta- and para-substituted (Z)-arylhydrazones. In every case, excellent correlation coefficients have been calculated (r² or R²≥0.996). Once more the study of MRH has furnished an interesting panel of different reactivity (three pathways of reaction have been evidenced: general-base-catalyzed, uncatalyzed, and specific-acid-catalyzed) and this has been useful in enlightening how polysubstitution can differently affect the MRH rates. Moreover 2,6-disubstitution on the (Z)-arylhydrazono moiety causes a significant increase of the reactivity in all of the three studied pathways. All of the collected data appear useful for understanding structure-reactivity/activity relationships in polysubstituted compounds.     

Mononuclear heterocyclic rearrangements. Part III. Rearrangement of the P-methoxyphenylhydrazone and the m-nitrophenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole in dioxane/water in the pS+ range 3.8–11.5

The rates of the mononuclear heterocyclic rearrangement of the p-methoxyphenylhydrazone (Ib) and the m-nitrophenylhydrazone (1c) of 3-benzoyl-5-phenyl-1,2,4-oxadiazole have been measured in the range of pS⁺ 3.8–11.5 (solvent: dioxane/water 1:1, v:v) and compared with those of the unsubstituted phenylhydrazone (Ia). The obtained results show that in the base-catalyzed range, electron-repelling as well as electron-withdrawing substituents accelerate the rearrangement rates.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

Studies in the 1,2,4-triazole series. III. Aminomethylation of 4-phenyl-1,2,4-triazolinethione-3

In a study of the aminomethylation of 4-phenyl-1,2,4-triazolinethione-3 (TRIT) it is ascertained that the reaction involves the nitrogen atom of the thioamide group. Salts of TRIT with secondary amines are obtained. It is shown that replacement of N (2) in 1-phenyltetrazolinethione-5 by the=CH- of TRIT leads to a decrease in the acidity of the thione and an increase in the stability of the hydroxymethyl and chloromethyl derivatives.For preceding papers see [1] and [2].     

Conversion of 3-Azido-5-phenyl-1,2,4-oxadiazole into benzoyl cyanide; a new thermal fragmentation

Flash vacuum pyrolysis of 3-azido-5-phenyl-1,2,4-oxadiazole ($\text{1a}$) gives benzoyl cyanide for which a mechanism involving the formation and fragmentation of $\text{N}$-benzoylpentaazafulvene ($\text{3}$) is proposed.     

A survey of the lone pair effect on the ring geometry of 1,2,4-triazoles and analogous 1,2,3-triazoles and imidazoles : The structures of 1-methyl-5-amino-3-methylthio-1,2,4-triazole, 1-phenyl-5-amino-3-methylthio-1,2,4-triazole and 1-(4-methylbenzyl)-3-amino-5-methylthio-1,2,4-triazole

The structures of the title compounds have been established by X-ray crystallography from diffractometer data. Crystals of the first (I), C₄H₈N₄S, are monoclinic, space group P2₁/c, with a = 8.166(2), b = 10.481(1), c = 8.585(1) Å, β = 109.33(2)°, Z = 4, D_c = 1.381 g cm⁻³. Crystals of the second (II), C₉H₁₀N₄S, are monoclinic, space group P2₁/c, with a = 11.850(4), b = 7.898(1), c = 23.981 (6) Å, β = 117.23(2)°, Z = 8, D_c = 1.373 g cm⁻³. Crystals of the third (III), C₁₁H₁₄N₄S₁ are also monoclinic, space group P2₁/c with a = 12.829(3), b = 8.348(1), c = 11.088(4) Å, β = 94.40(4)°, Z = 4, D_c = 1.314 g cm⁻³. The structures, determined by direct methods (I, III) and Patterson synthesis (II) were refined to R = 0.039 for 1070 reflections of I, R = 0.040 for 2792 reflections of II and R = 0.041 for 1900 reflections of III. The characteristic features of the planar five-membered rings are studied in comparison with the analogous 1,2,3-triazoles and imidazoles. It is shown that these planar rings exhibit only two patterns of the endocyclic bond angles induced dominantly by the number and relative position of the N-lone pairs. A similar effect of the double bonds (attached to C atoms) is also discussed.     

On the synthesis and reactivity of the Z-2,4-dinitrophenylhydrazone of 5-amino-3-benzoyl-1,2,4-oxadiazole

The synthesis of the title compound (4b) has been completed: its rearrangement (in dioxane/water; 1:1, v/v) into N-(2,4-dinitrophenyl)-5-phenyl-2H-1,2,3-triazol-4-ylurea (7) has been quantitatively studied in a wide reactivity (at 293 K, k(A) 10(-8) -4 s(-1)) and pS+ (4.5-14.1) range and compared with that of the Z-2,4-dinitrophenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (10), of the 3-(p-nitro)phenylureine of 5-phenyl-1,2,4-oxadiazole (13), and of N-(5-phenyl-1,2,4-oxadiazol-3-yl)-N'-p-nitrophenylformamidine (14). The results (reactivity, occurrence of specific or general base-catalysis, evidence for or absence of rate-limiting constants) have been well interpreted considering the structure of the side-chains involved and the stability of the final rings obtained in the rearrangements.     

Synthesis of 3-substituted 4-imino-4,5-dihydro-1,2,3-triazole 1-oxides and 4-amino-1,2,3-triazole 1-oxides. Crystal and molecular structure of 4-imino-5,5-dimethyl-3-phenyl-4,5-dihydro-1,2,3-triazole 1-oxide

A new procedure for the synthesis of triazole N-oxides, based on base-induced intramolecular cyclization of 1-(-cyanoalkyl)-3-aryl(hetaryl)triazen-1-oxides, is proposed. An X-ray study of 4-imino-5,5-dimethyl-3-phenyl-4,5-dihydro-1,2,3-triazole 1-oxide was carried out.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 746–751, April, 1993.     

Reductive ring cleavage of 1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones with raney-nickel alloy. Synthesis of N-benzoyl-3-alkylamino-3-phenylalanine amides from rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone

rel-(4R,5R)-4-Benzoylamino-5-phenyl-3-pyrazolidinone ( 1 ) was alkylated at position 1 with carbonyl compounds 2a-g . The corresponding rel-(4R,5R)-4-benzoylamino-5-phenyl-3-pyrazolidinone-1-azomethine imines 3a-g , were treated with sodium borohydride to give rel-(4R,5R)-1-alkyl-4-benzoylamino-5-phenyl-3-pyrazolidinones 4a-g . Reduction of pyrazolidinones 4a-g with Raney-nickel alloy in methanolic potassium hydroxide furnished rel-(4R,5R)-N-benzoyl-3-alkylamino-3-phenylalanine amides 5a-f .     

Mass spectrometry of heterocyclic compounds. XV—The mechanism of the fragmentation under electron impact of 3-p-NH2-phenyl-5-phenyl-1,2,4-oxadiazole. A CNDO/2 treatment

Molecular orbital calculations using the semi-empirical CNDO/2 method were carried out on the molecular ion of 3-p-NH₂-phenyl-5-phenyl-1,2,4-oxadiazole, whose structure had been determined by X-ray diffraction. The calculated diatomic interaction energy values are consistent with the mechanistic proposals made previously in terms of the quasi-equilibrium theory concerning the cleavage of the heterocycle ring after electron impact.