The synthesis and stability of some perfluoroalkl- and perfluoroalkylene-1,2,4- and 1,3,4-oxadiazoles

5-Perfluoroalkyl-3-phenyl-1,2,4-oxadiazoles have been synthesised directly from benzamidoxime and perfluoromonoacyl chlorides. However, a more complex pattern of products was observed in the reaction between arylamidoximes and perfluorodiacyl chlorides. Depending on the conditions, the products were O, O′-perfluorodiacyl di(arylamidoximes), α, ω-bis(3-aryl-1,2,4-oxadiazol-5-yl) perfluoroalkanes and arylamidoxime (3-aryl-1,2,4-oxadiazol-5-yl)perfluorocarboxylates.     

Synthesis of 1,2,4- and 1,3,4-oxadiazoles from 1-aryl-5-methyl-1<Emphasis Type="Italic">H</Emphasis>-1,2,3-triazole-4-carbonyl chlorides

5-Substituted 2-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-1,3,4-oxadiazoles were synthesized by reaction of 1-aryl-5-methyl-1H-1,2,3-triazole-4-carbonyl chlorides with the corresponding 5-substituted 1H-tetrazoles. 5-Methyl-1-phenyl-1H-1,2,3-triazole-4-carbonyl chloride reacted with N′-hydroxybenzimidamides to give 3-aryl-5-(5-methyl-1-phenyl-1H-1,2,3-triazol-4-yl)-1,2,4-oxadiazoles. Reactions of 4-(5-methyl-1H-1,2,3-triazol-1-yl)benzoic acid with N′-hydroxybenzimidamides resulted in the formation of 3-aryl-5-[4-(5-methyl-1H-1,2,3-triazol-1-yl)phenyl]-1,2,4-oxadiazoles.     

Rearrangement reactions of aziridinylbenzaldoximes

Reactions of 2,2-dimethylaziridine with benzohydroximoyl chlorides [ArC(Cl)?NOH] give aziridinylbenzaldoximes 1 . It has been found that the aziridine ring in these compounds undergoes ring opening in hydrogen chloride-dioxane solution to give (Z)-N-hydroxy-N′-(2-chloro-2-methylpropyl)benzenecarboximidamides [ArC(NHCH₂CR¹R²Cl)?NOH, 4 ]. Treatment of 1 with hydrochloric acid followed by neutralization with aqueous sodium hydroxide gave 6,6-dimethyl-3-aryl-1,2,4-oxadiazines 2. Reaction of 4 with sodium hydride in dioxane gave 5-isopropyl-3-aryl-4,5-dihydro-1,2,4-oxadiazoles 5. Reaction of the 4,5-dihydro-1,2,4-oxadiazoles 5 with N-chlorosuccinimide gave the heteroaromatic 1,2,4-oxadiazoles 6 . It is suggested that reactions of 4 with sodium hydride in dioxane solution involve the conjugate base of 4 which undergoes a 1,2-hydride shift that is concerted with loss of chloride ion. In aqueous sodium hydroxide solution it is suggested that the conjugate base of 4 undergoes ionization of the chlorine atom followed by nucleophilic attack by the oximate anion.     

1,2,4-Oxadiazoles from cycloreversions of oxadiazabicyclo[3.2.0]heptenes: 1-azetines as thiocyanate equivalents

1,3-Dipolar cycloaddition of nitrile oxides to 4-aryl-2-alkylthio-1-azetines gave a series of oxadiazabicyclo[3.2.0]heptenes as single diastereoisomers. Heating these cycloadducts in toluene resulted in an overall [2+2]-cycloreversion to give 5-alkylthio-3-aryl-1,2,4-oxadiazoles. In this process, the 1-azetine behaves as a thiocyanate equivalent. When the nitrile oxide substituent was 2-azidobenzene, the azide could be converted into a 1,2,3-triazole giving a (1,2,4-oxadiazolo)-(1,2,3-triazolo)-1,2-disubstituted benzene. 1,2,4-Oxadiazoles are sought after in medicinal chemistry and materials sciences.     

One-potCuAAC synthesis of (1H-1,2,3-triazol-1-yl)methyl-1,3,4/1,2,4-oxadiazoles starting from available chloromethyl-1,3,4/1,2,4-oxadiazoles

The one-pot CuAAC synthesis of (1H-1,2,3-triazol-1-yl)methyl-1,3,4-oxadiazole and (1H-1,2,3-triazol-1-yl)methyl-1,2,4-oxadiazole derivatives via three-component reaction of consequent nucleophilic substitution of chlorine, with azide, and its further “click” reaction, with alkynes, in the presence of CuI was studied. The utility of newly synthesized 2-(azidomethyl)-1,3,4/1,2,4-oxadiazoles and chloromethyl-1,3,4/1,2,4-oxadiazole derivatives was explored, and their limitations were determined. Novel 5-([4-aryl-1H-1,2,3-triazol-1-yl]methyl)-3-(aryl)-1,2,4-oxadiazoles, 2-([4-aryl-1H-1,2,3-triazol-1-yl]methyl)-5-(aryl)-1,3,4-oxadiazoles were obtained in good yields.     

3,3-Dinitrobutyl-1,2,4-oxadiazoles

The syntheses of 3,5-bis(3,3-dinitrobutyl)-1,2,4-oxadiazole and a series of 3-aryl-5-(3,3-dinitrobutyl)-1,2,4-oxadiazoles were accomplished by treating 4,4-dinitropentanoyl chloride with the appropriate amidoximes to yield the intermediate O-(4,4-dinitropentanoyl)amidoximes, which were dehydrated to the 1,2,4-oxadiazoles.     

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. 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.     

Unprecedented stereoselective synthesis of 3-methylisoxazolidine-5-aryl-1,2,4-oxadiazoles via 1,3-dipolar cycloaddition and study of their in vitro antioxidant activity

The stereoselective 1,3-dipolar cycloaddition between allyl cyanide and a menthone-derived nitrone led to the desired isoxazolidine in good yield. Once the nitrile group transformed to an amidoxime group, the cyclocondensation of various aldehydes with chiral amidoxime led to unprecedented enantiopure 3-methylisoxazolidine-5-aryl-1,2,4-oxadiazoles. The menthone chiral auxiliary was then removed with acid hydrolysis. The new compounds were also screened for their in vitro antioxidant activity using DPPH and FRAP assays. Some of the compounds showed promising antioxidant activity.     

One-Step Protection-Free Synthesis of 3-Aryl-5-hydroxyalkyl-1,2,4-oxadiazoles as Building Blocks

A simple and straightforward synthesis of 3-aryl-5-hydroxyalkyl-1,2,4-oxadiazoles is described. The reaction among arylamidoximes, ethyl glycolate or ethyl lactate, and potassium carbonate in refluxing toluene afforded the desired 1,2,4-oxadiazoles in moderate to good yields. The synthesis has been accomplished in a single step, avoiding protection–deprotection protocols.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

Regioselectivity in the 1,3-dipolar cycloaddition of nitrile oxides to 3,3-methylene-5,5-dimethyl-2-pyrrolidinone

Summary Nitrile oxides add regioselectively to the carbon-carbon double bond of 3,3-methylene-5,5-dimethyl-2-pyrrolidinone (1), giving exclusively spiro-isoxazolines: 3-aryl-6-oxo-8,8-dimethyl-1-oxa-2,7-diazaspiro[4.4]non-2-enes3 a–l. The regiochemistry of the 1,3-dipolar cycloaddition to 1 seems to be controlled by the steric effect of the methyl groups at the ring junction and by frontier orbital interactions.Part XXV in the series 1,3-Dipolar Cycloaddition on Heterocycles. Part XXIV Ref. [10]     

Oxidative addition of <Emphasis Type="Italic">N</Emphasis>-aminophthalimide to styryl-1,2,4-oxadiazoles

The oxidation of N-aminophthalimide with lead tetraacetate in the presence of 5-[(E)-2-arylethenyl]-3-(4-methylphenyl)-1,2,4-oxadiazoles and 5-(4-methylphenyl)-3-[E)-2-phenyl-ethenyl]-1,2,4-oxadiazole led to the formation of the corresponding (3-aryl-1-phthalimidoaziridin-2-yl)-(4-methylphenyl)-1,2,4-oxadiazoles. In the reaction with 3,5-distyryl-1,2,4-oxadiazole a mixture was obtained of two regioisomeric monoadducts and a diadduct in the ratio 80 : 15: 5; at the use of 3 equiv of the aziridinating reagents only diadduct was isolated as a mixture of two diastereoisomers in the ∼3 : 2 ratio that were separated by recrystallization.     

Synthesis of 2-(2-methyltetrazol-5-yl)-2,2-dinitroacetonitrile and its reaction with substituted nitrile N-oxides

A procedure of synthesis of 2-(2-methyltetrazol-5-yl)-2,2-dinitroacetonitrile has been developed and its reaction with substituted nitrile N-oxides has been investigated, proceeding by the mechanism of 1,3-dipolar cycloaddition and affording 2-methyl-5-[(1,2,4-oxadiazol-5-yl)(dinitro)methyl]-2H-tetrazoles. The latter react with KOH in ethanol forming the potassium salt of 2-methyltetrazol-5-yldinitromethane and substituted 5-hydroxy-1,2,4-oxadiazoles.     

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.     

Microwave-assisted synthesis and crystal structure of some novel 1,2,4-oxadiazol-5-ylmethyl-1,2,3-triazoles

Microwave-assisted 1,3-dipolar cycloaddition of 5-azidomethyl 3-aryl-substituted 1,2,4-oxadiazoles to electron-deficient alkyne; phenyl propiolic acid affords a series of 1,2,3-triazole derivatives carrying 3-p-substitutedphenyl-1,2,4-oxadiazolyl methyl unit. The structures of all the cycloadducts were elucidated by IR, NMR (¹H, ¹³C, 2D), MASS (low and high resolution) spectra, X-ray diffraction data, and physical characteristics (melting points and R_f values).     

A convenient synthesis of 2-aryl substituted benzo[f] [1,2,4]triazolo[1,5-a]azepine derivatives

A convenient synthetic pathway to 2-aryl-5,6-dihydro-4H-benzo[f][1,2,4]triazolo[1,5-α]azepine derivatives 7 was developed. The synthesis was based on the cycloaddition of the 1,2,3,4-tetrahydronaphthalene a-acetoxy azo compounds 3 with Ar-CN in the presence of AlCl3 and the consecutive ring enlargement.     

Tandem reactions of 1,2,4-oxadiazoles with allylamines

A reaction of 3-chloro-1,2,4-oxadiazoles with allylamine and diallylamine has been investigated. 3,3a,4,5-Tetrahydroisoxazolo[3,4-d]pyrimidines are produced through a tandem ANRORC/[3 + 2]cycloaddition pathway consisting of the addition of allylamine to the 1,2,4-oxadiazole, followed by ring opening, nitrone formation, and finally cycloaddition. 3-N-Allylamino-1,2,4-oxadiazoles were also obtained as minor products through a classical SNAr. Conversely, a reaction with diallylamine produces 3-N,N-diallylamino-1,2,4-oxadiazole and imidazoline through tandem SNAr/aziridination and nucleophilic ring opening.     

Synthesis of new 1,2,4-oxadiazolidin-3-ones by cycloaddition of 2-alkyl-3-aryloxaziridines with chlorosulfonylisocyanate

2-Alkyl-4-chlorosulfonyl-5-aryl-1,2,4-oxadiazolidin-3-ones 5 were prepared via cycloaddition of 2-alkyl-3-aryloxaziridines 3 with chlorosulfonylisocyanate. The structure of 5 was proved by a crystal X-ray analysis. Hydrolysis of 5 in the presence of triethylamine afforded 2-alkyl-5-aryl-1,2,4-oxadiazolidin-3-ones 6.     

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.