5-(4,6-Diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole-2-thione with Some C-Electrophiles and N-Nucleophiles

5-(4,6-Diphenyl-2-pyrimidinyl)-1,3,4-oxadiazole-2-thione reacted with haloalkanes or their derivatives containing side chain oxo group to give S-alkylated compounds. Aminomethylation and acylation of the thione yielded N₍₃₎-derivatives. Treatment of the title compound with hydrazine hydrate in butanol resulted in 4-amino-5-(4,6-diphenyl-2-pyrimidinyl)-1,2,4-triazole-3-thione via a recyclization reaction. Reaction of the title compound with hydrazine hydrate or phenylhydrazine in dioxane led to formation of the corresponding thiocarbohydrazides. The latter in the presence of a base were cyclized to 4-amino-1,2,4-triazole-3-thiones.     

Reaction of 5-aryl-1,3,4-oxadiazole-2(3H)-thiones with chloromethyl alkyl ethers

3-Alkoxymethyl-5-aryl-1,3,4-oxadiazole-2(3H)-thiones were synthesized. The direction of alkylation of 5-aryl-1,3,4-oxadiazoline-2-thiones and their potassium salts was studied relative to the substrate, alkylating agent, solvent, and reaction conditions.Institute of Plant Chemistry, Academy of Sciences of the Republic of Uzbekistan, 7001 70 Tashkent, Uzbekistan. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1249–1252, September, 1999.     

Reactions of α-Halo Ketones with 5-Benzyl- and 5-Phenoxymethyl-2H,3H-1,3,4-oxadiazole-2-thiones

Alkylation of 5-substituted 2H,3H-1,3,4-oxadiazole-3-thiones with -bromo ketones in alkaline solutions yields 5-substituted 2-aroylmethylthio-1,3,4-oxadiazoles; in acidic solutions these compounds re- arrange into 4-aryl-3-arylacetamido-2H,3H-1,3-thiazol-2-ones.     

2-aryl-5-arylsulfanyl-1,3-oxazole-4-carboxylic acids and their derivatives

A convenient preparative procedure has been developed for the synthesis of previously unknown 2-aryl-5-arylsulfanyl-1,3-oxazole-4-carboxylic acids and their functional derivatives from accessible multicenter substrates of the general formula Cl₂C=C(NHCOR)C(O)OMe. The products turned out to be suitable for various subsequent transformations. Some oxazole-4-carboxylic acid hydrazide derivatives containing a substituted oxazol-5-yl fragment at the N² atom in the hydrazine moiety underwent recyclization on heating in acetic acid; as a result, one oxazole ring was converted into 1,3,4-oxadiazole.     

Manganese(II) complexes of 5-(4-pyridyl), 5-phenyl and 5-(4-methoxy-phenyl)-1,3,4-oxadiazole-2-thione containing 2, 2′-bipyridyl/ethylenediamine: synthesis,spectral, and X-ray characterization

Three new mixed ligand complexes [Mn(4-pytone)₂(bipy)₂]bipy (1), [Mn(pot)₂(en)₂] (2) and [Mn(4-mot)₂(en)₂] (3) (4-pytone = 5-(4-pyridyl)-1,3,4-oxadiazole-2-thione, pot = 5-phenyl-1,3,4-oxadiazole-2-thione, 4-mot = 5-(4-methoxy-phenyl)-1,3,4-oxadiazole-2-thione) have been prepared containing bipy/en as coligands. The starting material potassium N-(aryl-carbonyl)-hydrazinecarbodithioates (RCONHNHCSSK) underwent cyclization during complexation in the presence of bipy or en to give the corresponding 5-aryl-1,3,4-oxadiazole-2-thiones. The complexes have been characterized by physicochemical techniques and single crystal X-ray structure determination. In all cases, the manganese has a six coordinate octahedral arrangement coordinated by 4N atoms of two bipy/en and two covalently bonded N atoms of the oxadiazole-2-thione anions.     

Synthesis and Transformations of 2-R-5-Aryl-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-b][1,3]thiazin-7-ones

A new procedure for preparation of 2-R-5-aryl-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones by condensation of 5-R-1,2,4-triazole-3-thiones with 3-arylacryloyl chlorides was developed. The thiazine ring of the [1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones is easily cleaved by treating with ammonia and hydrazine affording amides and hydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids. The latter react with isothiocyanates furnishing carbamoyl thiohydrazides of 3-aryl-3-(1H-1,2,4-triazol-5-ylsulfanyl)propanoic acids that in alkaline media undergo cyclization into 4-aryl-5-[2-(4H-1,2,4-triazol-5-ylsulfanyl)-2-phenylethyl]-2,4-dihydro-3H-1,2,4-triazole-5-thiones.     

Recyclization reactions of heterocyles. XVII. Hydrazination of 1, 3, 4-oxadiazolium salts

2, 5-Diaryl-3-alkyl-1, 3, 4-oxadiazolium salts react with hydrazine to give acyclic hydrazinolysis products or products of recyclization with participation of the carbon atom in the 2 position of the oxadiazole ring, i.e., dihydro-sym-tetrazines and N-amino-sym-triazoles (with hydrazine) and 2-phenyl-5-aryl-1, 3, 4-oxadiazoles (with benzoylhydrazine) or formazans (with phenylhydrazine).See [1] for communication XVI.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 629–634, May, 1976.     

Synthesis of polyamides from active 4,4′-diacylbis-2-aryl-1,3,4-oxadiazoline-5-thiones and -ones and diamines under mild conditions

New active bisamides, 4,4′ -diacylbis-2-aryl-1,3,4-oxadiazoline-5-thiones and -ones having various electron accepting groups in the oxadiazoline units were synthesized, and their reactivities toward diamines were investigated. The polycondensation reactions of the bisamides derived from 2-aryl-1,3,4-oxadiazoline-5-thiones with both aliphatic and aromatic diamines occurred rapidly even at room temperature to form high-molecular-weight polyamides in quantitative yields. The reactivities of the bisamides having electron accepting groups such as p-chloro and p-nitro groups, particularly p-nitro groups, toward diamines were much higher than that of the corresponding bisamide having no such group. It was also found that reaction conditions such as solvent, monomer concentration, and temperature had a strong influence on the molecular weight of the resulting polyamides. Aminolysis of several benzoyl derivatives of 2-aryl-1,3,4-oxadiazoline-5-thiones and -ones was also carried out as a model reaction, and the effect of electron accepting groups on the reactivity of these compounds was discussed.     

Recyclization of 2-Aryl-4-cyano-5-hydrazinooxazoles

The available 2-benzoylamino-3,3-dichloroacrylonitrile and its analogs when treated with excess hydrazine hydrate convert to 2-aryl-4-cyano-5-hydrazinooxazoles. The products are fairly stable in usual conditions but undergo recyclization on heating in acetic acid to give previously unknown derivatives of 2-methyl-1,3,4-oxadiazole with a 5-acylamino(carbamoyl)methyl substituent, whose structure was established by spectroscopy and X-ray diffraction. An important role in this complex transformation is probably played by prototropic forms of 4-cyano-5-hydrazinooxazoles, viz. hydrazones of substituted 2-oxazolin-5-ones which are not aromatic and thus can be cleaved with acetic acid and then recyclize.     

Synthesis of 3,5-disubstituted 1,3,4-oxadiazole-2-thiones as potential fungicidal agents

Sixteen new 3-arylaminomethyl-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole-2-thione and six 3-alkyl aryl alkyl-5-(2,4-dichlorophenyl)-1,3,4-oxadiazole-2-thiones were synthesised and characterised by their sharp melting points, elemental analysis, ir, ¹H nmr and mass spectra. These substituted oxadiazolethiones were screened for their fungitoxic properties. Most of the compounds showed toxicity against two test organisms, Curvularia verruciformis and Alternaria tenuis. The degree of inhibition ranged from 38--100% for a few compounds.     

Synthesis, characterization and antifungal evaluation of 5-substituted-4-amino-1,2,4-triazole-3-thioesters

A series of 5-substituted-4-amino-1,2,4-triazole-3-thioesters was synthesized by converting variously substituted organic acids successively into the corresponding esters, hydrazides, 5-substituted-1,3,4-oxadiazole-2-thiols, 5-substituted-1,2,4-triazole-2-thiols and 5-substituted-1,3,4-oxadiazole-2-thioesters. Finally the target compounds were obtained by refluxing 5-substituted-1,3,4-oxadiazole-2-thioesters in the presence of hydrazine hydrate and absolute alcohol. The structures of the synthesized compounds were established by physicochemical and spectroscopic methods. The synthesized compounds were evaluated for their in vitro antifungal activity. Some of the evaluated compounds possessed significant antifungal activity as compared to a terbinafine standard.     

1,3,4-Oxadiazole N-Mannich Bases: Synthesis,Antimicrobial, and Anti-Proliferative Activities

The reaction of 5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thione 3 with formaldehyde solution and primary aromatic amines or 1-substituted piperazines, in ethanol at room temperature yielded the corresponding N-Mannich bases 3-arylaminomethyl-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 4a–l or 3-[(4-substituted piperazin-1-yl)methyl]-5-(3,4-dimethoxyphenyl)-1,3,4-oxadiazole-2(3H)-thiones 5a–d, respectively. The in vitro inhibitory activity of compounds 4a–l and 5a–d was assessed against pathogenic Gram-positive, Gram-negative bacteria, and the yeast-like pathogenic fungus Candida albicans. The piperazinomethyl derivatives 5c and 5d displayed broad-spectrum antibacterial activities the minimal inhibitory concentration (MIC) 0.5–8 μg/mL) and compounds 4j, 4l, 5a, and 5b showed potent activity against the tested Gram-positive bacteria. In addition, the anti-proliferative activity of the compounds was evaluated against prostate cancer (PC3), human colorectal cancer (HCT-116), human hepatocellular carcinoma (HePG-2), human epithelioid carcinoma (HeLa), and human breast cancer (MCF7) cell lines. The optimum anti-proliferative activity was attained by compounds 4l, 5a, 5c, and 5d.     

Rearrangements 1,3 en Serie Heterocyclique. VI—Fragmentation,en Spectrometrie de Masse,des Aryl-2 Alkyl-4 Oxadiazol-1,3,4 Ones-5 et des Aryl-2 Alcoxy-5 Oxadiazoles-1,3,4

The mass spectra of 2-aryl-4-alkyl-1,3,4-oxadiazole-5-ones and their 2-aryl-5-alkoxy 1,3,4-oxadiazole isomers have been studied. Unimolecular electron impact-induced isomerization does not seem to occur during the fragmentation of these compounds. For each type of heterocycle, the hydrogen transfers, during the cleavage of the alkyl chain, are mainly caused by the nitrogen in position 4.     

Synthesis of heterocycles. Part VI. Synthesis and antimicrobial activity of some 4-amino-5-aryl-1,2,4-triazole-3-thiones and their derivatives

4-Amino-5-aryi-1,2,4-triazole-3-thiones I react with acid chlorides to yield 4-acylamino-5-aryl-1,2,4-triazole-3-thiones II. Compounds I also react with methylene iodide, chloroacetonitrile and methyl bromoacetate to give bis-(4-amino-5-aryl-1,2,4-triazol-3-ylthio)methanes III, 4-amino-5-aryl-3-cyanomethylthio-1,2,4-triazoles IV and 4-amino-5-aryl-3-carbomethoxymethylthio-1,2,4-triazoles V, respectively. Compounds V react with hydrazine hydrate to give the corresponding acid hydrazides VI which in turn condenses with acid chlorides and aldehydes to afford respectively 1-[(4-amino-5-aryl-1,2,4-triazol-3-ylthio)acetyl]-2-aroylhydrazines VII and aryl methylene (4-amino-5-aryl-1,2,4-triazol-3-ylthio)acethydrazones VIII. The antimicrobial activities of the above compounds were screened against different strains of bacteria and fungi.     

Synthesis of 3-acylamino-2-oxazolidinone derivatives through cyclic transformations of 5-aryl (or benzyl)-1,3,4-oxadiazol-2(3H)-one derivatives

New 3-acylamino-2-oxazolidinone derivatives 3 were obtained in good yields by reaction of 5-aryl (or benzyl)3-(2-hydroxyethyl)1,3,4-oxadiazol-2(3H)ones 1 with sodium ethylate. Treatment of ethyl 5-aryl-2-oxo-1,3,4-oxadiazole-3(2H)-acetates 7 with aromatic aldehydes in the presence of sodium ethylate or sodium hydride afforded 3-acylamino-5-aryl-4-ethoxycarbonyl-2-oxazolidinone derivatives as two trans- 5 and cis- 6 racemics. Only RS,SR-racemates were obtained with acetophenone under the same conditions.     

Synthesis of substituted N-(2,4-dioxo-1,2,3,4-tetrahydroquinazolinyl)benzamides and N-(2-thiono-4-oxo-1,2,3,4-tetrahydroquinazolinyl)benzamides

Substituted N-(2,4-Dioxo-1,2,3,4-tetrahydroquinazolinyl)benzamides ( 3a-g ) and substituted N-(2-Thiono-4-oxo-1,2,3,4-tetrahydroquinazolinyl)benzamides ( 4a-g ) were synthesized in one step from the reaction of methyl anthranilate with 2-aryl-1,3,4-oxadiazolin-5-ones ( 1a-g ) and 2-aryl-1,3,4-oxadiazoline-5-thiones ( 2a-g ), respectively, in m-cresol at 150–160°. Alternative routes leading to the formation of 3a and 4a are also reported.     

含嘧啶环的1,3,4-噁二唑Mannich碱的合成及生物活性

以芳香酸为原料, 通过酯化、 肼解及环化反应制得中间体5-芳基取代-1,3,4-噁二唑-2-硫酮(C1~C3), 然后中间体与甲醛和取代氨基嘧啶(D1~D5)发生Mannich反应得到一系列新型含有嘧啶环的1,3,4-噁二唑类衍生物(E1~E15). 所得目标化合物的结构经元素分析、 IR及 ¹H NMR确认. 初步的生物活性测定结果表明, 大部分目标化合物对植物病原菌有很好的抑制作用, 其中化合物E3和E8的抑菌效果优于对照药三唑酮.     

Electron ionization induced fragmentation of some oxadiazole and thiadiazole derivatives

The mass spectrometric behaviour under electron ionization of several 3,4-(alkyl/aryl)-disubstituted 1,2,4-oxadiazole-5(4H)-ones (1-13) and 1,2,4-thiadiazole-5(4H)-thiones (14-17), and that of 3-aryl-5-alkyl- or arylthio-1,2,4-thiadiazoles (18-24), was studied. These five-membered rings split similarly to the corresponding 1,2,4-thiadiazole-5(4H)-ones, although substitution has also a clear effect on the routes of fragmentation and the magnitude of secondary processes. In particular, the fragmentation of 1,2,4-oxadiazole-5(4H)-ones (1-6), which do not bear aromatic substituents, was, in addition to the ring ruptures, fairly complicated. The other compounds fragmented more systematically and relatively few unpredictable fragmentations occurred.     

Synthesis and Fungicidal Activity of 1,3,4-Oxadiazole Substituted Acylthioureas

A series of N′-(5-aryl-1,3,4-oxadiazole-2-yl) actylthioureas have been synthesized from p-chlorophenoxyacetic acid, and then substituted 2-amino-5-aryl-1,3,4-oxadiazoles reacting with acylthiocyanoester, which are derived from the second step, are used. Their structures are confirmed by Infrared, ¹H nuclear magnetic resonance, and elementary analysis. From biological testing, it is found that some of these compounds have good fungicidal activity. Translated from Chemical Research and Application, 2005, 17(2) (in Chinese)     

Syntheses and antibacterial studies of some 2-[5-(Aryl)-[1,3,4]oxadiazole-2-ylsulfanyl] alkanoic Acids

Some new 2-[5-(aryl)-[1,3,4]oxadiazole-2-ylsulfanyl]alkanoic acids were synthesized and studied for their antibacterial activity. These compounds were prepared from aromatic carboxylic acid hydrazides. Aromatic carboxylic acid hydrazides 1 on refluxing with carbon disulfide and methanolic potassium hydroxide and then on subsequent acidification with hydrochloric acid furnish 5-aryl-1,3,4-oxadiazole-2-thiones 2. 2-Chloro alkanoic acids react with 2 in alkaline media and on acidification yield the title compounds 3. These compounds were characterised by CHN analyses, IR, mass and ¹H NMR spectral data. All the compounds were evaluated for their in vitro antibacterial activity against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa) and two Gram positive strains (Bacillus subtilis and Staphylococcus aureus) and their minimum inhibitory concentration (MIC) were determined.