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.     

Thermolysis of 3-phenyl-5-arylamino-1,2,4-oxadiazole and thiadiazole derivatives

Thermal reactions of 3-phenyl-5-arylamino-1,2,4-oxadiazoles I and II were investigated. Neat heating at ca. 250°C for 6 hours afforded H₂O, benzonitrile, arylcyanamides, arylamines, azobenzene, benzimidazole derivatives, and 3,3′-diphenyl-5,5′-bis[1,2,4-oxadiazolyl]. Analogous results were obtained by the thermolysis of 3-phenyl-5-anilino-1,2,4-thiadiazole III at ca. 200°C for 2 hours. In addition to H₂S, NH₃, and HNCS, phenyl isothiocyanate and thiocarbanilide were obtained. Thermolysis of III in quinoline as a radical trap gave analogous resuLts but also 2-anilinoquinoline. A free-radical mechanism has been suggested to account for the identified products. © 1997 John Wiley & Sons, Inc.     

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.     

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.     

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.     

Reaction of 3-azido-5-phenyl-1,2,4-oxadiazole with dimethylformamide,a new deoxygenative coupling reaction

When 3-bromo-5-phenyl-1,2,4-oxadiazole (1b) is heated with sodium azide in anhydrous dimethylformamide at 130°, 3-dimethylamino-($\text{1c}$) and 3-dimethylaminomethyleneamino-5-phenyl-1,2,4-oxadiazole ($\text{1d}$) are formed, the latter by a new deoxygenative coupling of the azide ($\text{1a}$), or the nitrene derived from it, with the solvent.     

Mononuclear heterocyclic rearrangement. Note I. Kinetic study of the rearrangement of the phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole

The rates of the mononuclear heterocyclic rearrangement of the phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (1) into 2,5-diphenyl-4-benzoylamino-1,2,3-triazole (II) have heen measured in dioxane/water (50:50, v:v) in the range of pS⁺ 3.8–12.2 at various temperatures and the activation parameters determined. On the basis of the results obtained, we present evidence for the occurrence of two different types of reaction: the first, base-catalyzed; the second, pS⁺ -independent. In the base-catalyzed range the catalysis is of the general type.     

Neue acetonylsubstituierte Azole II. 3-Acetonyl-1,2,4-oxadiazole, 2-Acetonyl-1,3,4-oxadiazole und 5-Acetonyl-1,2,4-thiadiazole

3-Acetonyl-1,2,4-oxadiazoles and 2-acetonyl-1,3,4-oxadiazoles are accessible starting with the ketal of acetoacetamide oxime and the ketal of acetoacetic acid hydrazide, respectively. 5-Acetonyl-1,2,4-thiadiazoles are obtained from 5-chloro-1,2,4-thiadiazoles andtert.-butyl acetoacetate. These Acetonyl-azoles are starting materials for three series of azolylvinyl phosphates and phosphonates.

Herrn Prof. Dr.Klaus Weissermel zu seinem 60. Geburtstag.     

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.     

Heterocyclic rearrangements in constrained media. A zeolite-directed photorearrangement of 1,2,4-oxadiazoles

[reaction: see text] The first intrazeolite-photoinduced rearrangement of a five-membered heterocycle is reported. A completely different behavior compared to solution irradiations has been observed. The zeolite's role in directing the photoreaction of 3-phenyl-1,2,4-oxadiazoles toward the formation of the corresponding 1,3,4-oxadiazoles in a ring contraction-ringexpansion route is discussed.     

Tautomerism in 3-ethoxy-5-phenyl-1,2,4-triazole

The cmr spectrum of the title compound was observed at several temperatures and assigned based on a tautomeric exchange requiring that the N(1)-H compound be present to the extent of 70%.     

Host-guest interactions between beta-cyclodextrin and the (Z)-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole: the first kinetic study of a ring-ring interconversion in a "confined environment"

The effect of beta-cyclodextrin (beta-CD) on the mononuclear heterocyclic rearrangement of the (Z)-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (1) in aqueous borate buffer at pH = 9.6 has been analyzed at temperatures ranging from 293.15 to 313.15 K. The trend of the absorption spectra of 1 as a function of time has been accounted for with the formation of two different 1:1 complexes between beta-CD and 1, the first, "unreactive" complex being formed faster than the "reactive" one. The occurrence of negative activation enthalpy values for the studied interconversion evidences the kinetic relevance of inclusion processes. Computational models elaborated using the MM2 molecular mechanics force field give an idea of the relative importance of the different complexes, additionally helping us to formulate a suitable reaction scheme.     

5-Ethoxy-3-(trichloromethyl)-1,2,4-oxadiazole

5-Ethoxy-3-(trichloromethyl)-1, 2, 4-oxadiazole (V) was synthesized to elucidate the chemistry involved in the preparation of the hitherto unreported alkoxy-1, 2, 4-oxadiazoles and to determine the effect of the isosteric replacement of sulfur by oxygen on antifungal activity. Heating the “amino-oxime” tautomer II of trichloroacetamidoxime with ethyl chloroformate furnished exclusively the O-acylated product III. The trans configuration of III accounts for its resistance to cyclize under a variety of conditions, in contrast to the general behaviour of acylated amidoximes. Pyrolysis of III at 160° yielded IV which exists in the keto form. Refluxing IV with ethyl iodide in the presence of silver oxide gave an isomeric mixture which was separated by v.p.c. to give V and VI. Compound V retained 60% of the overall activity of the corresponding sulfur analog.     

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.     

Neue acetonylsubstituierte Azole I. 5-Acetonyl-1,2,4-oxadiazole

Aliphatic amidoximesR—C (NH₂)=NOH react with diketene to yield 5-acetonyl-3-alkyl-1,2,4-oxadiazoles, which are susceptible to a wide variety of reactions at the keto-group as well as at the methylene-group. Their transformations into 1-methyl-2-oxadiazolyl-vinylN,N-dimethylcarbamates, 2-chloro-1-oxadiazolylpropenes, 1-oxadiazolyl-2-(1,2,4-triazol-1-yl)propenes, 1,1-dichloro-1-oxadiazolylacetones and 3-hydroxy-2-oxadiazolyl-crotonic amides are described as well as their reactions with diazonium salts, with sodium nitrite and with carbon disulfide. Further products obtained are carbamates of of 1-oxadiazolyl-2-oxo-propane-1-oximes, 2-chloro-2-oxadiazolylvinyl phosphates and an oxadiazolyl pyrimidine.

Herrn Prof. Dr.Klaus Weissermel zu seinem 60. Geburtstag.     

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.     

Synthesis of trifluoromethylated 2-benzoyl- and 2-aminoimidazoles from ring rearrangement of 1,2,4-oxadiazole derivatives

Fluoroalkylated 2-ylamino-imidazoles have been synthesized by reaction of 3-amino-5-phenyl-1,2,4-oxadiazole with fluorinated β-dicarbonyl compounds and subsequent base-induced Boulton-Katritzky Rearrangement (BKR) of the isolated β-enaminocarbonyl intermediate. Alternatively, one-pot reactions performed in the presence of Montmorillonite K10 favoured the condensation at the 3-amino moiety of the oxadiazole and, in some cases, allowed the direct synthesis of 2-benzoylamino-imidazoles. Hydrolysis of 2-benzoylamino-imidazoles easily yielded fluorinated 2-amino-imidazoles targets.