5-Amino-4,5-dihydroisoxazoles. Part I. 5-Amino-3-aryl-4-methylene-4,5-dihydroisoxazoles and 4-aminomethyl-3-arylisoxazoles from 5-amino-4-aminomethyl-3-aryl-4,5-dihydroisoxazoles

5-Amino-4-aminomethyl-3-aryl-4,5-dihydroisoxazoles 2 were obtained by cycloaddition of nitrile oxides to 1,3-diaminopropenes 1. On reaction with methyl iodide the corresponding 4-(quaternary)-ammoniomethyl iodides 3 were formed. These compounds, on reaction with bases, afforded 5-amino-3-aryl-4-methylene-4,5-dihydroisoxazoles 4. The acid-catalyzed deamination of compounds 2 afforded 4-aminomethyl-3-arylisoxa-zoles 5 and 3-arylisoxazoles as retro-Mannich products. The deamination of 2 to yield 5 was also obtained by base catalysis.     

5-Bromomethyl-4,5-dihydroisoxazoles

The preparation of substituted 4,5-dihydroisoxazoles can be accomplished via the treatment of β,γ-unsaturated oximes with liquid bromine. The reaction provides a convenient route to the highly functionalized title compounds.     

Synthesis and Structure of 3-Aryl-5-cyano-6-methylthio pyrimidine2,4-diones

Polarizedketenedithioacetalsl,(XY)C=C(SR)2(X,Y=CN,NO2,COOEt,CONH=,R=alkyl,benzyl).havebeenextensivelyusedasbuildingblocksinorganicsynthesisespeciallyinthepreparationofheterocycliccompounds''.Inanextensionofourrecentstudies'intheapplicationofketokete...     

5-Amino-4,5-dihydroisoxazoles. Part II . Reactions of 5-amino-3-aryl-4-methylene-4,5-dihydroisoxazoles with Nucleophiles

Several 5-amino-3-aryl-4-methylene-4,5-dihydroisoxazoles were reacted with methoxide, benzenethiolate, benzenethiol, carboxylic acids and secondary amines. Addition and/or addition-elimination products were obtained. Reaction mechanisms are discussed.     

Synthesis in Water and Antimicrobial Activity of 5-Trichloromethyl-4,5-dihydroisoxazoles

Two series of 5-trichloromethylisoxazoles were synthesized from the cyclocondensation of 1,1,1-trichloro-4-methoxy-3-alken-2-ones [Cl₃CC(O)C(R²) = C(R¹)OMe, where R¹ = H, Me, Et, Pr, iso-Pr, cyclo-Pr, Bu, terc-Bu, CH₂Br, CHBr₂, CH(Me)SMe, (CH₂)₂Ph, and Ph, and R² = H; R¹ = H and R² = Me and Et; R¹ and R² = -(CH₂)₄- and -(CH₂)₅-; and R¹ = Et and Ph and R² = Me] with hydroxylamine hydrochloride through a rapid one-pot reaction in water. The 5-trichloromethyl-4,5-dihydroisoxazoles were aromatized by reaction with concentrated sulfuric acid to obtain the respective 5-trichloromethylisoxazoles. Their structures were confirmed by elemental analysis, ¹H/¹³C nuclear magnetic resonance, and electron impact mass spectroscopy. Crystal structure analysis for 5-triclhoromethyl-5-hydroxy-3-propyl-4,5-dihydroisoxazole (2d) and 5-trichloromethyl-5-hydroxy-3,4-hexamethylene-4,5-dihydroisoxazole (2o) is presented. The antimicrobial activities of the 5-trichloromethyl-4,5-dihydroisoxazole derivatives were examined using the standard twofold dilution method against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and yeasts (Candida spp. and Cryptococcus neoformans). All of the tested 5-trichloromethyldihydroisoxazoles exhibited antibacterial and antifungal activities at the tested concentrations.

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Haloacetylated enol ethers. 6 [5]. Synthesis of 4,5-trimethylene-4,5-dihydroisoxazoles

The investigation of the effect of the cyclopentane ring on the regiochemistry of the reactions of 2-acetylcyclopentanones 1a-d and β-methoxyvinyl trifluoromethyl ketone derivative 2a with hydroxylamine hydrochloride is reported. The reactions give regiospecifically the 4,5-trimethylene-4,5-dihydroisoxazoles 3a-d in good yields.     

Synthesis of 5-(thiazol-5-yl)-4,5-dihydroisoxazoles from 3-chloropentane-2,4-dione

Condensation of 3-chloropentane-2,4-dione with thioamides gives 1-(thiazol-5-yl)ethanones and subsequent Wittig olefination, followed by nitrile oxide 1,3-dipolar cycloaddition to the resulting prop-1-en-2-yl moiety, delivers racemic 5-(thiazol-5-yl)-4,5-dihydroisoxazoles. When this thiazole and isoxazoline diheterocyclic scaffold has a carboethoxy substituent at C2 of the thiazole ring, aminolysis provides for effective diversification. A 50-member library of various 5-(thiazol-5-yl)-4,5-dihydroisoxazoles is reported.     

Haloacetylated enol ethers. 7 . Synthesis of 3-aryl-5-trihalomethylisoxazoles and 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles

β-Aryl-β-methoxyvinyl trihalomethyl ketones 1a-g, 2a-g [aryl = p-YC₆H₄ where Y= H, Me, OMe, F, Cl, Br, NO₂] are cyclocondensed with hydroxylamine hydrochloride to afford the 3-aryl-5-hydroxy-5-trihalomethyl-4,5-dihydroisoxazoles 3a-g, 4a-f in good yield. The dehydratation of compounds 3a-g with concentrated sulfuric acid, led the corresponding 3-aryl-5-trichloromethylisoxazoles 5a-g . An alternative one-pot procedure yields 3-aryl-5-trihalomethylisoxazoles 5,6a-g directly by cyclocondesation of 1,2a-g with hydroxylamine hydrochloride in the presence of an excess of concentrated hydrochloric acid.     

Synthesis of 2-amino-4-aryl-3-cyano-5-hydroxyimino-4,5-dihydrothiophenes

The Michael addition of cyanothioacetamide to nitrostyrenes was investigated. Previously unknown 2-amino-4-aryl-3-cyano-5-hydroxyimino-4,5-dihydrothiophenes were obtained. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1472–1477, October, 2007.     

Solid base-catalyzed synthesis of 5-substituted 4,5-dihydroisoxazoles

We present a new synthetic route for the preparation of 5-substituted 4,5-dihydroisoxazole derivatives starting from ethyl nitroacetate and alkenes in the presence of modified Mg:Al 3:1 hydrotalcite.     

Some acylations of 3-phenyl and 3-mesityl-4,5-dihydroisoxazoles

A study on the acetylation and benzoylation of title compounds by quenching the corresponding 4-carbanions with acyl chlorides or esters is reported. The obtained ketones are formed as minor regioisomeric adducts in the cycloadditions of benzo and mesitonitrile oxide to methyl and phenyl vinyl ketone. The quenching with methyl chloroformate was also examined as a possible convenient route to 4-methoxycarbonyl-3-aryl-4,5-dihydroisoxazoles.     

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.     

New synthesis of 2-amino-3-cyano-4,5-tetramethylenethiophene

We have shown that 2-amino-3-cyano-4,5-tetramethylenethiophene (IV) is formed in the reaction of cyclohexanethione (I) with malononitrile (II) and sulfur in the presence of triethylamine. The reaction proceeds through a step involving the formation of cyclohexylidenemalononitrile (III) and occurs via attack by the malononitrile anion on the sulfur atom of the thiocarbonyl group of I. Δ^2,α-Bornanylmalononitrile (V) was similarly obtained from thiocamphor and II; the latter reaction cannot be realized with camphor because of the steric hindrance of the carbonyl carbon atom.     

Synthesis and Properties of 4,5-trans-2-Alkylthio-3-cyano-6-hydroxy-6-methyl-4-phenyl-5-pyridinio-1,4,5,6-tetrahydropyridine Iodides

Alkylation of 4,5-trans-4-aryl-3-cyano-6-hydroxy-6-methyl-5-pyridinio-1,4,5,6-tetrahydropyridine-2-thiolates 1, 2 was carried out. The presence of 5-pyridinio cation in thiolates 1, 2 as a strong electron-withdrawing group leads to a pronounced enhancement of their stability to dehydration but decreases their reactivity with electrophilic reagents. Steric structures of 2-alkylthio-6-hydroxytetrahydropyridines 3-5 are discussed in the light of ¹H NMR spectra and crystal X-ray diffraction data.     

Synthesis,Phosphonylation, and Anti-Viral Activity of Some 6-Aryl-5-cyano-2-thiouracils

Russian Journal of General Chemistry - A series of 6-aryl-5-cyano-2-thiouracils was synthesized, the reaction of which with diethyl chloroethynylphosphonate leads to the selective formation of new...     

A New Facile Synthesis of 5-Alkyl-2-Aryl-3H-Pyrazol-3-Ones

The title compounds widely used in construction of pigments and antimaterials are most usually prepared by condensation of arylhydrazines and β-keto esters ^1,2. Although a number of 5-methyl and aryl derivatives have been obtained, other 5-alkyl-3-pyrazolones are rarely mentioned in literature ³ because of the lack of a convenient method to prepare the approperate β-keto esters used in condensation.     

A New Synthesis of 3-Aryl-5-Arylmethylene-2(5H)-Furanones

A recent report about the synthesis of di and tri-substituted 2 (5H)-furanones starting from bromoaldehydes and potassium phenyl-acetate¹ prompts us to report our own studies on the preparation of 3-aryl-5-arylmethylene-2 (5H)-furanones (or butenolides) 1. We have earlier reported² a general method for the synthesis of 1 from phenylpropargyl aldehyde, 2 and arylacetic acids. Although several methods have been reported for the synthesis of the parent compound 1 (R = R₁ = Ph)^3–6, these methods have not been extended to other substituted furanones. Saikachi and Taniguchi⁷ prepared 1 (R = 5-nitro-2-thenyl, R₁ = 2-thenyl and 2-furyl) in 16–17% yields.