Synthesis and Some Chemical Behaviour of Certain Substituted Thiosemicarbazides

Three new thiosemicarbazides (1 a-c ) were prepared from N-[4-phenyl-5-(2-thienyl)-1,2,4-triazol-3-yl]mercaptoacetohydrazide. Reaction of (1 a-c) with the appropriate phenacyl bromide afforded thiazoline derivatives (2 a-i) whereas their reaction with chloroacetic acid or maleic anhydride gave the corresponding thiazolidine derivatives (3 a,b) and (4 a,b) . Cyclodesulfurization of (1 a-c) with DCCD in toluene yielded 5-substituted-amino-1,3,4-oxadiazoles (5 a,b) , while their dehydration with PPA gave the corresponding 5-substituted-amino-1,3,4-thiadiazoles (6 a-c) . Six representative compounds were tested for their in-vitro antimicrobial activity against some pathogenic microorganisms, some of them were proved to be active.     

Competing ring-photoisomerization pathways in the 1,2,4-oxadiazole series. An unprecedented ring-degenerate photoisomerization

The irradiation of some 5-alkyl-3-amino-1,2,4-oxadiazoles at lambda = 254 nm in methanol in the presence of triethylamine (TEA) gave ring-photoisomerization both into 2-alkyl-5-amino-1,3,4-oxadiazoles and, unprecedently, into the ring-degenerate 3-alkyl-5-amino-1,2,4-oxadiazoles. The competing ring contraction-ring expansion route and the internal cyclization-isomerization mechanism explain the results.     

Fluorinated heterocyclic compounds: an assay on the photochemistry of some fluorinated 1-oxa-2-azoles: an expedient route to fluorinated heterocycles

Photoinduced heterocyclic rearrangements of ON bond-containing azoles have been claimed in the synthesis of target fluorinated heterocyclic compounds. In this context, the photochemical behavior of some fluorinated 1,2,4-oxadiazoles has been investigated. Irradiations of 3-amino-5-perfluoroalkyl-1,2,4-oxadiazoles at λ=313 nm in methanol gave open-chain products arising from a reaction of the nucleophilic solvent with either the first formed ring-photolytic species or with a nitrilimine moiety generated from it. Differently, irradiations in methanol with the presence of triethylamine (TEA) followed competing phototransposition pathways leading to the ring-isomers 2-amino-5-perfluoroalkyl-1,3,4-oxadiazoles (major component) and the ring degenerate isomers 5-amino-3-perfluoroalkyl-1,2,4-oxadiazoles (minor component). On the other hand, 3-amino-5-polyfluorophenyl-1,2,4-oxadiazoles underwent ring-photoisomerization into 1,3,4-oxadiazoles when irradiations were carried out at λ=254 nm. In turn, the irradiation of the 3-phenyl-5-perfluoroheptyl-1,2,4-oxadiazole at λ=254 nm in methanol gave the solvolysis product, but no ring-isomerization was observed. Some mechanistic considerations are reported, and some applications in the synthesis of target fluorinated 1,3,4-oxadiazoles are claimed.     

Theoretical study of photoinduced ring-isomerization in the 1,2,4-oxadiazole series

A theoretical study of photoinduced ring-isomerization of 3-amino-5-methyl- and 3-amino-5-phenyl-1,2,4-oxadiazoles is reported. The results well agree with the reported experimental data: in particular, they explain the ring-photoisomerization into the corresponding 2-amino-1,3,4-oxadiazoles through a ring contraction-ring expansion route; moreover, the occurrence of competing pathways involving both the ring contraction and the internal cyclization-isomerization mechanism during irradiation of the 5-alkyl substituted substrates in the presence of a base has been also substantiated.     

Ring transformations of heterocycles. Part 1. Transformation of 4-amino-Δ2-1,2,4-oxadiazolines into 1,3,4-oxadiazoles

3-Aryl-4-amino-δ²-1,2,4-oxadiazolines 3 and their N-chloroacetyl derivatives 4 , upon treatment with chloroacetic anhydride in refluxing toluene, afford 2-chloromethyl-5-aryl-1,3,4-oxadiazoles 5 , suggesting the conversion sequence 3 → 4 → 5 . The generality of the new ring transformation 4 → 5 is supported similar conversion of other 4-(acylamino)-1,2,4-oxadiazolines 8 to 1,3,4-oxadiazoles 9 .     

Synthesis and properties of azoles and their derivatives. 36. Synthesis of 2-amino-1,3,4-oxadiazoles, 2-amino-1,3,4-thiadiazoles,and 1,2,4-triazoline-3-thiones containing indolyl radicals

On the heterocyclization of 1-(indol-3-ylcarbonyl)thiosemicarbazides, depending on the conditions of performing the reaction, either 1,2,4-triazoline-3-thiones, 2-amino-1,3,4-thiadiazoles, or 2-amino-1,3,4-oxadiazoles containing an indolyl residue in position 5 are obtained. 1,2,4-Triazoline-3-thiones and 2-amino-1,3, 4-thiadazoles have also been synthesized by the reaction of the hydrochloride of ethyl indol-3-carboximidate with thiosemicarbazides.For communication 35, see [1].Translated from Khimiya Geterotsilicheskikh Soedinenii, No. 9, pp. 1271–1276, September, 1984.     

Synthesis of new modified aza heterocycles on the basis of 5-(2-chloro-1-nitroalkyl)-3-phenyl-and 5-(2-chloro-1-nitroalkyl)-3-methyl-1,2,4-oxadiazoles

3-Phenyl-and 3-methyl-5-(2-chloro-1-nitroalkyl)-1,2,4-oxadiazoles reacted with piperidine, pyrrolidine, and morpholine to give the corresponding 5-(2-amino-1-nitroalkyl) derivatives, while their reactions with sodium p-toluenesulfinate led to the formation of 2-[3-methyl(or phenyl)-1,2,4-oxadiazol-5-yl]-2-nitroethyl p-tolyl sulfones.     

Rapid acid hydrolysis of 5-aryl-3-(β-thiomorpholinoethyl)-1,2,4-oxadiazoles

The acid hydrolysis of a series of 5-aryl-3-(β-thiomorpholinoethyl)-1,2,4-oxadiazoles gave substituted benzoic acids and 2-amino-8-thia-1-aza-5-azoniaspiro[4.5]dec-1-ene chloride hydrate, whose structure was demonstrated by spectral methods and X-ray diffraction structural analysis.     

A facile synthesis of 3-trifluoromethyl-1,2,4-oxadiazoles from cyanamides

A safe and facile method for the formation of 3-trifluoromethyl-5-amino-1,2,4-oxadiazoles, via a reversed addition of hydroxylamine to cyanamides, is reported. This two-pot procedure is suitable to scale-up and avoids the hazards associated with trifluoromethyl amidoxime synthesis.     

Synthesis of 4(5)-substituted 2-amino-5(4)-hydroxyimino-5(4)H-imidazoles and their transformation into the corresponding 3-substituted 5-amino-1,2,4-oxadiazoles

Treatment of 4(5)-phenyl(or alkyl)-2-aminoimidazoles with isoamyl nitrite in acetic acid afforded the corresponding 4(5)-substituted 2-amino-5(4)-hydroxyimino-5(4)H-imidazoles which by heating in water were transformed into 3-benzoyl(or acyl)-5-amino-1,2,4-oxadiazoles.     

Oxydation d'hydrazones par le bioxyde de plomb: Nouvelles synthèses d'oxadiazoles-1,3,4 et de dérivés de l'amino-4 triazol-1,2,4 one-5

Aromatic aldehyde aroylhydrazones when oxidizen with lead dioxide, in acetic acid, gave quickly the corresponding 1,2,4-oxadiazoles in good yields. Aromatic aldehyde carbodihydrazones on the other hand, gave derivatives of 4-amino-3-aryl-1m,2,4-triazol-5-ones, in dimethylformamide as solvent. To explane these results, some radical mechanisms are proposed.     

Synthesis and properties of azoles and their derivatives

Thermal condensation of 1-cyanoadamantane with arylhydroxamic acid chlorides gave 5-(1′-adamantyl)-1,2,4-oxadiazoles containing aromatic groupings in the 3 position. The same 1,2,4-oxadiazoles were synthesized by reaction of the N-oxides of the appropriate nitriles with adamantane-1-carboxylic acid methyl imino ester obtained from 1-cyanoadamantane. The corresponding 5-(1′-adamantyl)-3-substituted 1,2,4-oxadiazoles were obtained by condensation of the latter with amidoxines.     

Cyclization of protected N-acylhydroxyguanidine to 3-amino-1,2,4-oxadiazole

The acid mediated cyclization of a protected N-acylhydroxyguanidine into the corresponding 3-amino-1,2,4-oxadiazole and confirmation of its structure by single crystal X-ray crystallography is reported herein. The yield of the cyclization is comparable to literature reports utilizing alternative procedures. Importantly, these new conditions provide complementary chemoselectivity to current synthetic procedures which may be useful for the synthesis of 3-amino-1,2,4-oxadiazoles in general.     

Synthesis of 2-amino-5-(5R-1,2,4-oxadiazolyl-3)-1,3,4-oxadiazoles

The interaction of 2-amino-1,3,4-oxadiazole-5-carboxamidoxime with nitriles in the presence of ZnCl₂ and HCl or with trichloroacetic anhydride affords 2-amino-5-(5R-1,2,4-oxadiazolyl-3)-1,3,4-oxadiazoles. Their reactions with N-nucleophiles have been studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2100–2103, December, 1993.     

Synthesis of 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one. Derivatives and their ring transformation into 5-benzamido-1,2,4-triazolidine-3,5-dione derivatives

Some 5-aryl-3-carbazoyl-1,3,4-oxadiazol-2(3H)-one derivatives 6 and 9 have been synthesized in two ways. The expected thermal ring transformation into 2,5-disubstituted 1,3,4-oxadiazoles did not occur but, by acid hydrolysis of 5-aryl-3-[3-benzylidene-2-methyl(or phenyl)carbazoyl]-1,3,4-oxadiazol-2(3H)-ones 6 , a new ring transformation took place and the corresponding 4-benzamido-1-methyl(or phenyl)-1,2,4-triazolidine-3,5-dione derivatives 11 were formed. The 4-amino-1-phenyl-1,2,4-triazolidine-3,5-dione ( 19 ) has been prepared and its structure was confirmed by some reactions.     

Syntheses with nitrile oxides. 2. Reaction of aromatic nitrile oxides with bis(trimethylsilylcarbodiimide)

The reaction of aromatic nitrile oxides with bis(trimethylsilylcarbodiimide) gives 5-amino-3-aryl-1,2,4-oxadiazoles.For previous communication, see [1].N. D. Zelinskii Institute of Organic Chemistry, Russian Academy of Sciences, 117334 Moscow. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 10, pp. 2430–2432, October, 1992.     

Synthèse et propriétés des aroylhydrazones du benzoate d'éthyle. Synthèses d'hétéroscycles azotes

The aroylhydrazones of ethyl benzoate have been prepared in fair yield by the action of aroylhydrazines on ethyl benzimidate hydrochloride. These products give rise, quantitatively, at their melting point, to 5-aryl-2-phenyl-1,3,4-oxadiazoles, and, in the presence of hydrazine hydrate, in boiling 1-propanol to 4-amino-5-aryl-3-phenyl(4H)-1,2,4-triazoles (Yields 50%). The addition of methylmagnesium iodide to these products give aroylhydrazones of acetophenone.     

Improved syntheses of 5-substituted-4-amino-3-mercapto-(4H)-1,2,4-triazoles

Two improved methods have been developed for the synthesis of 5-substiluted-4-amino-3-mercapto-(4H)-1,2,4-triazoles. One of these involves the direct hydrazinolysis of potassium 3-aroyldithiocarbazates and the other involves ring-opening and reclosure of 5-substituted-2-mereapto-1,3,4-oxadiazoles to the aminomercaptotriazoles. Both of these methods offer advantages over the classic Hoggarth synthesis.     

Synthèse d'amino-oxadiazoles - 1, 2, 4

Two new syntheses of 5-amino-1,2,4-oxadiazoles are described. The first one is based on the reaction of guanidine on benzhydroxamyl chloride. The second is more general and consists in allowing primary or secondary amines, hydrazine or guanidine to react with 5-trichloromethyloxadiazoles.     

Synthesis and properties of azoles and their derivatives. 37. Synthesis of 3,5-disubstituted 1,2,4-oxadiazoles containing indole radicals

The 1,3-dipolar cycloaddition of nitrile N-oxides to indole nitriles yields 3,5-di-substituted 1,2,4-oxadiazoles containing an indole radical at the 5 position. Condensation of amidoximes with indole iminoester hydrochlorides yields 1,2,4-oxadiazoles having an indole segment at the 3 and/or 5 position of the oxadiazole ring. Pyrolysis of O-acyl derivatives of indole amidoximes yields 1,2,4-oxadiazoles with an indole residue at the 3 position.For Communication 36, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1609–1615, December, 1984.