Syntheses and degradations of fluorinated heterocyclics. IV. Imidoylamidoximes, 1,2,4-oxadiazole precursors

Perfluoroalkylether amidoximes free from amide-contamination were prepared from imidate esters. The amidoximes were stable at 110°C; at ～170°C partial decomposition to 1,2,4-oxadiazoles, admixed with other compounds, took place. Interactions between nitriles and amidoximes at 50°C resulted in the formation of imidoylamidoximes; these dissociated readily into their constituents when subjected to higher temperatures. At 70°C and above, in the presence of excess nitrile or other ammonia acceptors, the imidoylamidoximes afforded high yields of the corresponding 1,2,4- oxadiazoles.     

Hetaryl- and heteroarylvinyl-substituted nitrofurans identified as non-cytotoxic selective antitubercular agents

New (E)-5-[2-(5-nitrofuran-2-yl)vinyl]-1,2,4-oxadiazoles and 5-(5-nitrofuran-2-yl)-1,2,4-oxadiazoles were synthesized via the base-promoted condensation of nitrofuran-containing acyl chlorides with amidoximes. Testing these compounds against Gram-negative E. coli, Gram-positive B. subtilis and S. aureus as well as M. tuberculosis HRv37 strain revealed three compounds being selectively antimycobacterial. None of these compounds displayed any cytotoxicity towards human pancreatic epithelioid carcinoma cell line, PANC-1.     

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.     

15N NMR study of the mechanism of the reaction of amidoximes with nitrites in the presence of ZnCl2 and HCl

The structures of complexes formed during the transformation of amidoximes into 1,2,4-oxadiazoles by the action of nitriles in the presence of zinc chloride and HCl were studied by¹⁵N NMR spectroscopy.Translated fromIzyestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 676–678, April, 1994.     

The reaction of amidoximes with carboxylic acids or their esters under high-pressure conditions

Russian Chemical Bulletin - 3,5-Disubstituted 1,2,4-oxadiazoles were synthesized by the reaction of amidoximes with carboxylic acids or their esters under high-pressure conditions (10 kbar). The...     

A convenient synthesis of 3-substituted 5-guanidino-1,2,4-oxadiazoles

The reaction of amidoximes with cyanoguanidine in the presence of Lewis acids affords 3-substituted 5-guanidino-1,2,4-oxadiazoles. A study of the reaction of¹⁵N-labeled chloroacetamidoxime with cyanoguanidine showed that the formation of the oxadiazole ring occursvia the elimination of the amino group from the amidoxime fragment. 1,2,4-Oxadiazoles bearing the imidazole or pyrimidine moiety were synthesized.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 118–121, January, 1994.     

Syntheses and properties of related polyoxadiazoles and polytriazoles

New aromatic poly-1,2,4-triazoles and poly-1,3,4-oxadiazoles are studied as thermally stable membrane materials. Various groups were introduced onto the pendant phenyl groups of poly-1,2,4-triazoles. Glass transition temperature, degradation temperature, and cold crystallization behavior were studied as a function of these groups. Cold crystallization appeared to be highly sensitive to macromolecular regularity. The solubility of poly-1,3,4-oxadiazoles was highly improved upon incorporation of 5-t-butylisophthalic, 1,1,3-trimethyl-3-phenylindane, 4,4′-(2,2′-diphenyl) hexafluoro propane, and diphenyl ether groups into the polymeric main chain, whereas the high glass transition temperatures and degradation temperatures typical for aromatic poly-1,3,4-oxadiazoles were maintained. © 1994 John Wiley & Sons, Inc.     

A novel synthesis of 1,2,4-oxadiazoles and isoxazoles

A novel synthesis of 1,2,4-oxadiazoles and isoxazoles is described by utilizing the reactions between amidoximes and α,β-alkynic aldehydes and/or ketones. Conjugate addition products, obtained from amidoximes and α,β-alkynic aldehydes and/or ketones, afford 1,2,4-oxadiazoles and isoxazoles when treated with bases and acids, respectively. 1,2,4-Oxadiazoles can also be synthesized directly from amidoximes and α,β-alkynic aldehydes in a one-pot manner under basic conditions. The reactions are general for a variety of starting compounds and tolerate the presence of aryl, heteroaryl and alkyl groups.     

Chromatography-free synthesis of 1,2,4-oxadiazoles using ROMPGEL-supported acylating reagents

1,2,4-Oxadiazoles were synthesized in solution from aromatic amidoximes and acylating agents supported on a ring opening metathesis polymer (ROMPGEL) backbone. High yields and purities of the 1,2,4-oxadiazoles were obtained with minimal purification.     

One-Pot Synthesis of 3,5-Disubstituted 1,2,4-Oxadiazoles Using Catalytic System NaOH‒DMSO

Russian Journal of Organic Chemistry - One-pot convenient process was developed for the production of 3,5-disubstituted 1,2,4-oxadiazoles by reaction of amidoximes with anhydrides or acyl chlorides...     

Synthesis of 3,5-Disubstituted 1,2,4-Oxadiazoles from Amidoximes and Aldehydes in the Superbasic System NaOH/DMSO

Russian Journal of Organic Chemistry - A new procedure has been proposed for the synthesis of 3,5-disubstituted 1,2,4-oxadiazoles by reaction of amidoximes with aldehydes in the superbasic system...     

1,3-Dipolare Cycloaddition aromatischer Nitril-ylide und Nitril-oxide an Dicyan und Diazocyanide

1,3 Dipolar Cycloaddition of Aromatic Nitrile Ylides and Nitrile Oxides with Cyanogen and Diazocyanides Nitril ylides 2 generated from the imidoyl chlorides 1 react with cyanogen and aryldiazocyanides to 2,5(4)-dia-ryl-1H-imidazole-4(5)-carbonitriles 3a , b or 5(4)-(arylazo)-2,4(5)-diaryl-1H-imidazoles 4a and 2,3,5-triaryl-2,3-dihydro-1H-1,2,4-triazole-1-carbonitriles 5a – f , respectively (Scheme 1). Reactions of benzonitrile oxides 7 with these dipolarophiles lead to 3,3′-diaryl-5,5′-bi[1,2,4]oxadiazoles 8a – c or 3-aryl-5-(arylazo)-1,2,4-oxadiazoles 9a – j (Scheme 2).     

Recyclization of 1,3,4-Oxadiazoles and Bis-1,3,4-oxadiazoles into 1,2,4-Triazole Derivatives. Synthesis of 5-Unsubstituted 1,2,4-Triazoles

Efficient methods have been developed for obtaining precursors of stable carbenes, viz. 5-unsubstituted 3,4-diaryl-1,2,4-triazoles and 3,3′- or 4,4′-bridge linked bis-1,2,4-triazoles, by the recyclization of 5-unsubstituted 1,3,4-oxadiazoles or p-phenylenebis-1,3,4-oxadiazole with anilines or aromatic diamines in the presence of trifluoroacetic acid or with aniline hydrochlorides in pyridine. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 1026–1032, July, 2005.     

Synthesis of (pyridinyl)-1,2,4-triazolo[4,3-a]pyridines

Methods for the synthesis of (pyridinyl)-1,2,4-triazolo[4,3-a]pyridines were developed. The principal route to the required intermediate 2-chloropyridines was based on rearrangements of mono N-oxides of 2,2′-bipyridine, 2,3′-bipyridine, 3,3′-bipyridine, 2,4′-bipyridine and 4,4′-bipyridine with phosphorus oxychloride. Reaction of 3,3′-bipyridine 1-oxide or 2,2′-bipyridine 1-oxide with phosphorus oxychloride gave mixtures of chloro isomers. Reaction with acetic anhydride, 3,3′-bipyridine 1-oxide and 2,2′-bipyridine 1-oxide gave exclusively [3,3′-bipyridine]-2(1H)-one and [2,2′-bipyridine]-6(1H)-one, respectively. 1,2,4-Triazolo[4,3-a]pyridines with pyridinyl groups at the 5,6,7 and 8 positions were synthesized.     

3,5-Disubstituted-1,2,4-oxadiazoles and 4,5-dihydro-3,5-disubstituted-1,2,4-oxadiazoles

A series of 3,5-disubstituted-1,2,4-oxadiazoles ( 2 ) were prepared from a mono- or dichlorophenyl-substituted amidoxime and (i) an acid chloride, (ii) an isatoic anhydride, or (iii) a β-keto ester. Although cyclizations of the same amidoximes with acetaldehyde gave 4,5-dihydro-5-methyl-substituted derivatives ( 5 ), that annulation procedure either failed or gave low yields with other aldehydes. A novel alternative method, the diborane reduction of 2 , has been found to be a generally applicable procedure for preparing 5 . The reduction is regioselective, i.e., only the 4,5-(C=N) linkage is reduced even when a large excess of diborane is present.     

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.     

Manganese oxide nanoparticles supported on graphene oxide as an efficient nanocatalyst for the synthesis of 1,2,4-oxadiazoles from aldehydes

The easy synthesis of graphene oxide (GO)-supported manganese dioxide (MnO₂) nanoparticles as a stable heterogeneous nanocatalyst (MnO₂@GO) is described. This catalyst was investigated in the synthesis of 1,2,4-oxadiazoles from amidoximes and aldehydes via a cyclization and oxidation process. The nanocomposite was prepared and characterized using various techniques. The catalytic application of the nanocomposite was examined in the reaction of a variety of aldehydes with aliphatic and aromatic amidoximes. The stable and robust catalyst was recycled for seven consecutive runs without a significant decrease in the catalytic activity.     

Room-temperature synthesis of pharmaceutically important carboxylic acids bearing the 1,2,4-oxadiazole moiety

An efficient and mild one-pot protocol has been developed for the synthesis of 1,2,4-oxadiazoles via the reaction of amidoximes with dicarboxylic acid anhydrides in a NaOH/DMSO medium. The method allows the synthesis of diversely substituted carboxylic acids bearing the 1,2,4-oxadiazole motif, – a popular building block for pharmaceutical research, in moderate to excellent yields. The reaction scope includes aromatic and heteroaromatic amidoximes as well as five-, six- and seven-membered anhydrides. The advantages of this procedure are proven gram-scalability and the use of inexpensive starting materials, which from a process chemistry point of view are essential for future industrial applications.     

Facile room-temperature assembly of the 1,2,4-oxadiazole core from readily available amidoximes and carboxylic acids

A one-pot ambient-temperature procedure for the synthesis of 3,5-disubstituted-1,2,4-oxadiazoles from amidoximes and carboxylic acids under superbase-promoted conditions is reported.     

Anil-Synthese. 20. Mitteilung. Über die Herstellung von Stilbenyl-Derivaten des 1,2,4,-Oxadiazols

Preparation of Stilbenyl Derivatives of 1,2,4-Oxadiazoles Schiffs bases derived from 3- and 5-(p-formylphenyl)-phenyl-1,2,4-oxadiazoles and chloroanilines are reacted with various p-tolyl substituted aromatic heterocycles in the presence of dimethylformamide and potassium hydroxide to yield the corresponding heterocyclic substituted stilbenes (‘Anil synthesis’). The reactivity of 5-[4-(chlorophenylimino-methyl)phenyl]-3-phenyl-1,2,4-oxadiazoles is very low and side reactions will predominate.