Deoximation Reaction in Room Temperature Ionic Liquids under Mild Conditions

Deoximation in metal chloride ionic liquids based on 1‐alkyl‐3‐methylimidazolium and triethylene ammonium cations, such as AmimBr(Cl)‐MCl_x(A=ethyl, butyl, benzyl; M=Al, Fe, Cu, Sn and Zn; x=2, 3) and Et₃NHCl‐FeCl₃ were investigated under mild conditions. Ferrate chloride ionic liquid was proved to be an effective catalyst for deoximation of cyclohexanone oxime, exhibiting high conversion of oximes and selectivity to cyclohexanone. Good performance for the deoximation of other oximes such as salicylald oxime, acetone oxime, benzophenone oxime, 4‐nitrobenzald oxime, acetophenone oxime, 2‐chlorobenzaldehyde oxime, Acetald oxime, 2‐butanone oxime and (1R)‐camphor oxime was also achieved with bmimBr‐FeCl₃ as catalyst and solvent. The deoximation was determined to carry out via acid‐catalytic hydrolysis and the reaction mechanism was proposed.     

Novel enantioselective synthesis of trans-α-(2-carboxycycloprop-1-yl)glycines: conformationally constrained l-glutamate analogues

d- and l-α-(2-carboxycycloprop-1-yl)glycines were synthesized from trans-1,3-di(2-furyl)propenone. Conversion of the double bond to a cyclopropane is followed by the formation of an oxime ether. Enantioselective reduction of the oxime ether, separation of diastereomers and oxidation of the furane rings gave enantiomerically pure d- and l-CCG I and CCG II. The structure of oxime 7b was determined by X-ray crystal structure analysis. The key step is the oxazaborolidine catalyzed enantioselective conversion of oxime ethers to amines.     

,β-unsaturated oximes Isoxazoline formation by thermal cyclisation of compounds related to benzalacetophenone oxime and isoxazoline thermal cycloreversion reactions

At about 300° the title compounds yield fragments attributed to cyclisation to isoxazolines and subsequent cycloreversion. Isoxazolines are formed at about 200° and can usually be isolated. At 300° they yield the same products as the oximes.

Thus benzalacetophenone oxime gives 3,5-diphenylisoxazoline which then largely undergoes two distinct cycloreversions: (a) 1,3-cleavage (numbers refer to isoxazoline bonds) yielding benzonitrile and acetophenone and (b) reductive 1,4-cleavage yielding benzaldehyde and 1-phenylethylimine hydrolysis products. By-products are 2,4,6-triphenylpyridine, water and ammonium benzoate. With -methylchalcone oxime reductive 1,4-cleavage is suppressed and with β-methylchalcone oxime both modes of cleavage are suppressed and 5-methyl-3,5-diphenylisoxazole is the stable product. An analogue of -methylchalcone oxime, 2-methyl-1-phenyl-3-(2-thienyl)prop-2-ene-1-one oxime gives fragments attributed to both cleavage modes of an unisolatable and hitherto unknown isoxazoline.

Possible mechanisms for the cyclisation and cycloreversions are discussed and the reductive 1,4-cleavage is believed to be a cycloreversion of a vinyl-nitrene.     

α,β-unsaturated oximes : Isoxazoline formation by thermal cyclisation of compounds related to benzalacetophenone oxime and isoxazoline thermal cycloreversion reactions

At about 300° the title compounds yield fragments attributed to cyclisation to isoxazolines and subsequent cycloreversion. Isoxazolines are formed at about 200° and can usually be isolated. At 300° they yield the same products as the oximes.Thus benzalacetophenone oxime gives 3,5-diphenylisoxazoline which then largely undergoes two distinct cycloreversions: (a) 1,3-cleavage (numbers refer to isoxazoline bonds) yielding benzonitrile and acetophenone and (b) reductive 1,4-cleavage yielding benzaldehyde and 1-phenylethylimine hydrolysis products. By-products are 2,4,6-triphenylpyridine, water and ammonium benzoate. With α-methylchalcone oxime reductive 1,4-cleavage is suppressed and with β-methylchalcone oxime both modes of cleavage are suppressed and 5-methyl-3,5-diphenylisoxazole is the stable product. An analogue of α-methylchalcone oxime, 2-methyl-1-phenyl-3-(2-thienyl)prop-2-ene-1-one oxime gives fragments attributed to both cleavage modes of an unisolatable and hitherto unknown isoxazoline.Possible mechanisms for the cyclisation and cycloreversions are discussed and the reductive 1,4-cleavage is believed to be a cycloreversion of a vinyl-nitrene.     

Formaldehyde oxime <--> nitrosomethane tautomerism

Formaldehyde oxime <--> nitrosomethane tautomerism, isomeric nitrone, and their common cations and anions are studied with Gaussian-2 theory using MP2(full)/6-31G geometries and with density functional theory using B3LYP/6-311+G**. Geometrical parameters, harmonic vibrational frequencies, relative stabilities, conformational stabilities, and ionization energies are compared with experimental gas-phase data when available. The formaldehyde oxime <--> nitrosomethane tautomerism is compared with the amide <--> imidol, imine <--> enamine, keto <--> enol, and nitro <--> aci-nitro tautomeric processes. Solvent effects are estimated by the self-consistent isodensity polarizable continuum model (SCIPCM). The influence of hydrogen bonding interactions with the solvent is addressed by including two water molecules. In the final evaluation, formaldehyde oxime is 15.8 kcal/mol more stable than nitrosomethane when the aqueous solvation correction of 3.8 kcal/mol is applied to the G2 energies. Unsolvated formaldehyde oxime is estimated to be 11.1 kcal/mol more stable than nitrone. The estimated gas-phase ionization energies (G2) are 362.5 kcal/mol for formaldehyde oxime, 350.6 kcal/mol for nitrosomethane, and 351.4 kcal/mol for nitrone.     

A Direct Spectrophotometric Assay for Pyruvic Oxime Hydrolase

Abstract

A sensitive spectrophotometric method, which directly measures the formation of pyruvic oxime from pyruvate and NH₂OH in the UV, is described for the detection of pyruvic oxime hydrolase activity in biochemical systems. The method was used in an attempt to detect pyruvic oxime hydrolase activity in cell-free extracts from an Alcaligenes sp. which can grow on pyruvic oxime. Although substantial pyruvic oxime + nitrite oxidative activity was detected in cells and cell-free extract of this bacterium, catalysis of pyruvic oxime formation was not observed within the error of the method (～20% of the uncatalyzed rate constant of 1.9x10^?3 s^?1 at pH 7, 22°C). The rate of pyruvic oxime oxidation by cells and cell-free extract was at least 10⁵?10⁶ times greater than the rate of its hydrolysis, thus implying that oxidation of pyruvic oxime need not require prior hydrolysis. The method would appear to be applicable to hydrolases directed toward a variety of oximes.     

The Oxime Ethers with Heterocyclic,Alicyclic and Aromatic Moiety as Potential Anti-Cancer Agents

Chemotherapy is one of the most commonly used methods of cancer disease treatment. Due to the acquisition of drug resistance and the possibility of cancer recurrence, there is an urgent need to search for new molecules that would be more effective in destroying cancer cells. In this study, 1-(benzofuran-2-yl)ethan-1-one oxime and 26 oxime ethers containing heterocyclic, alicyclic or aromatic moiety were screened for their cytotoxicity against HeLa cancer cell line. The most promising derivatives with potential antitumor activity were 2-(cyclohexylideneaminoxy)acetic acid (18) and (E)-acetophenone O-2-morpholinoethyl oxime (22), which reduced the viability of HeLa cells below 20% of control at concentrations of 100–250 μg/mL. Some oxime ethers, namely thiazole and benzothiophene derivatives (24–27), also reduced HeLa cell viability at similar concentrations but with lower efficiency. Further cytotoxicity evaluation confirmed the specific toxicity of (E)-acetophenone O-2-morpholinoethyl oxime (22) against A-549, Caco-2, and HeLa cancer cells, with an EC50 around 7 μg/mL (30 μM). The most potent and specific compound was (E)-1-(benzothiophene-2-yl)ethanone O-4-methoxybenzyl oxime (27), which was selective for Caco-2 (with EC50 116 μg/mL) and HeLa (with EC50 28 μg/mL) cells. Considering the bioavailability parameters, the tested derivatives meet the criteria for good absorption and permeation. The presented results allow us to conclude that oxime ethers deserve more scientific attention and further research on their chemotherapeutic activity.     

铜(Ⅱ)-羟肟络合物的电子自旋共振谱研究

本文报导芳香族羟肟铜(Ⅱ)络合物的电子自旋共振(ESR)谱的研究。讨论了这类配位体上取代基的电子效应对络合物中铜(Ⅱ)的超精细分裂常数A_(Cu)值的影响,以及A_(Cu)值与这些配位体萃取铜的分配系数的关系。     

Enhanced reactivity of an α-nucleophile in water-dimethyl sulfoxide mixtures. A transition state effect.

The reactivity of the anion of α,α,α-trifluoroacetophenone oxime towards p-nitrophenylacetate is considerably enhanced relative to that of the similarly basic p-chlorophenoxide anion on addition of Me₂ SO to aqueous solutions. This is shown to be due to an enhanced stabilization of the transition state for the oxime reaction.     

Reaction of hexafluoropropylene and its oligomers with acetone oxime

Reactions of perfluoropropylene and its oligomers with acetone oxime in the presence of a base afford perfluoroalkyl and/or perfluoroalkenyl ethers of acetone oxime. When heated to 100 °C, the 3-perfluoro-2-methyl-2-pentenyl ether of acetone oxime (3) is quantitatively converted to 4-hydroxy-3-methyl-5,5-bistrifluoromethyl-4-pentafluoroethyl-1-pyrroline (4), the structure of which was established by X-ray diffraction analysis. A convenient one-stage synthesis of perfluoro-3-isopropyl-4-methyl-3-penten-2-one (7) was proposed.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1068–1072, June, 1994.     

Unusually Facile Pyrrolization of 2-Acetylcoumarone Oxime with Acetylene

The oxime of 2-acetylcoumarone reacts with acetylene under pressure in the system KOH-DMSO unusually readily forming 2-(2-pyrrolyl)coumarone and the corresponding O-vinyl oxime. Under more rigid conditions 2-(1-vinyl-2-pyrrolyl)coumarone is formed. The possibility of a two-stage transformation of 2-acylcoumarones into 2-pyrrolylcoumarones has therefore been demonstrated for the first time.__________Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 524–529, April, 2005.     

SYNTHESIS AND CHARACTERIZATION OF DIAQUA(3-pTOLYLIMINO-2-BUTANONE OXIMATO)(3-p-TOLYLIMINO-2-BUTANONE OXIME)NICKEL(II) PERCHLORATE

Abstract

[Ni(L^?1)(HL)(H₂O)₂].ClO₄ with a Schiff base ligand L (HL = 3-p-tolylimino-2-butanone oxime) was prepared and structurally characterized by IR, cyclic voltammetry and X-ray diffraction methods. The nickel atom has distorted octahedral coordination consisting of four nitrogen atoms and two oxygen atoms. The equatorial plane is formed by two oxime nitrogen atoms and two imine nitrogen atoms of two Schiff base ligand (L^?1 and HL) with Ni‐ N bond distances between 2.01(1) and 2.11(1)Å. Water oxygen atoms occupy axial positions with Ni‐ O bond distances of 2.06(1) and 2.15(1) Å. The oxime groups in the Schiff base ligands are coordinated to Ni atom through their nitrogen atoms. One asymmetric intramolecular hydrogen bridge between the two oxime groups is found in the title complex.     

New Estrone Oxime Derivatives: Synthesis,Cytotoxic Evaluation and Docking Studies

The interest in the introduction of the oxime group in molecules aiming to improve their biological effects is increasing. This work aimed to develop new steroidal oximes of the estrane series with potential antitumor interest. For this, several oximes were synthesized by reaction of hydroxylamine with the 17-ketone of estrone derivatives. Then, their cytotoxicity was evaluated in six cell lines. An estrogenicity assay, a cell cycle distribution analysis and a fluorescence microscopy study with Hoechst 3358 staining were performed with the most promising compound. In addition, molecular docking studies against estrogen receptor α, steroid sulfatase, 17β-hydroxysteroid dehydrogenase type 1 and β-tubulin were also accomplished. The 2-nitroestrone oxime showed higher cytotoxicity than the parent compound on MCF-7 cancer cells. Furthermore, the oximes bearing halogen groups in A-ring evidenced selectivity for HepaRG cells. Remarkably, the Δ^9,11-estrone oxime was the most cytotoxic and arrested LNCaP cells in the G₂/M phase. Fluorescence microscopy studies showed the presence of condensed DNA typical of prophase and condensed and fragmented nuclei characteristic of apoptosis. However, this oxime promoted the proliferation of T47-D cells. Interestingly, molecular docking studies estimated a strong interaction between Δ^9,11-estrone oxime and estrogen receptor α and β-tubulin, which may account for the described effects.     

Photochemical reactions of high polymers. XIV. Syntheses and photochemical reactions of copolymers bearing O-acyloxime groups

Copolymers bearing pendant O-acyloxime groups were synthesized by two methods: copolymerizations of oxime acrylate (methyl β-naphthyl ketone oxime acrylate or benzophenone oxime acrylate) and styrene, condensation of acrylic acid—styrene copolymer with oximes (benzophenone oxime, p-nitrobenzophenone oxime, methyl β-naphthyl ketone oxime, benzalacetone oxime or 9-fluorenone oxime). The photochemical behavior of the O-acyloxime copolymers changed markedly with the irradiation conditions: irradiation of benzene solutions led to degradation in air and crosslinking under nitrogen, while irradiation of solid films in air resulted in simultaneous degradation and crosslinking. Photolysis of methyl β-naphthyl ketone oxime acetate, a model for the O-acyloxime copolymer, in benzene solution under nitrogen resulted in scission of the N? O bond. The same reaction was observed in the irradiation of the O-acyloxime copolymers. It is suggested that formation of free radicals on the polymer chains via scission of the N? O bond is followed by decarboxylation. In the absence of oxygen, crosslinking of the polymer by recombination of the free radicals competes with degradation via β-scission. In the presence of oxygen, autoxidative degradation predominates.     

Polarographic investigation of syn-phenyl 2-pyridyl ketone oxime

The polarographic reduction of syn-phenyl 2-pyridyl ketone oxime to -(2-pyridyl)benzylamine over the pH range 0.78–12.88 is reported. Two waves are observed, both of which are pH-dependent. The complex electrode reaction is discussed and a mechanism advanced to describe the reduction of the oxime group over the pH range considered.     

Syntyhesis of 1,2,4,5-Tetrazino[1,6-a: 4,3-a′]diquinoxaline

A new one-step synthesis of 2 (1H)-quinoxalinone oxime ( 3 ) from (1,2-benzenediamine ( 1 ) and s-trans-chloroethanedial dioxime ( 2 ) is described. This oxime is converted into a new heterocyclic compound, 1,2,4,5,-tetrazino)[1,6-a: 4,3-a′]diquinoxaline ( 4 ), by the template effect of Co(II) and Ni(II) ions.     

The beckmann rearrangement of cyclohex-2-enone oximes. Synthesis of 4,5-diphenyl-2,3,4,5-tetrahydro-1H-azepin-2-one

The Beckmann rearrangement of either syn or anti 3,4-diphenyl-cyclohexenone oxime 2a,b in polyphosphoric acid produces only one of the two possible isomeric unsaturated caprolactams 1 . Under neutral conditions, only the syn oxime tosylate 9b rearranges to lactam 1 , the anti oxime tosylate 9a remains unchanged. These results support earlier reports that alkyl migration is preferred over vinyl migration in the Beckmann rearrangement of unsaturated cyclic ketoximes. Structure proof of the lactam was made using deuterium exchange and HMQC nmr experiments.     

Polymerization and copolymerization of an isocyanate blocking agent. N-(1,1′-dimethyl-3-oxobutyl) acrylamide oxime. Mechanical and thermal properties

The bulk polymerization and copolymerization of N-(1,1′-dimethyl-3-oxobutyl) acrylamide oxime have been studied. Polymerization of diacetone acrylamide oxime was carried out with different initiating systems. The rate of polymerization of diacetone acrylamide oxime with azoisobutyronitrile as the initiating system was much higher than with peroxides. However, in the case of perester initiating systems (t-butyl perbenzoate and t-butyl per ethyl-2-hexanoate), cobalt salt promoted the polymerization rate markedly. Diacetone acrylamide oxime readily formed copolymers with a variety of comonomers (crosslinking agents and reactive diluents). Gel permeation chromatography has shown a higher reactivity of diacetone acrylamide oxime with trimethylol propane trimethacrylate as crosslinking agent and N-vinyl-pyrrolidone as reactive diluent. Therefore, the dynamic mechanical analyses presented an increase in T_g with trimethylolpropane trimethacrylate and N-vinyl-pyrrolidone as comonomers. The terpolymer formed with diacetone acrylamide oxime, trinethylolpropane trimethacrylate, and N-vinyl-pyrrolidone exhibited interesting mechanical properties and high temperature behavior.     

Crystal and molecular structure of 7,7-dimethyl-2,3-di(4-methoxyphenyl)-5-oxo-5,6,7,8-tetrahydroquinoline

An x-ray crystallographic investigation of 7,7-dimethyl-2,3-di(4-methoxyphenyl)-5-oxo-5,6,7,8-tetrahydroquinoline, obtained by the hydrolysis of its oxime, was undertaken. The oxime, together with the isomeric oxime of 7,7-dimethyl-2,4-di(4-methoxyphenyl)-5-oxo-5,6,7,8-tetrahydroquinoline, is formed in the reaction of 5,5-dimethyl-2-[1,3-di(4-methoxyphenyl)-3-oxopropyl]cyclohexane-1,3-dione with hydroxylamine hydrochloride.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1085–1088, August, 1987.     

Control of chain ends of polyesters in polycondensation of AA and BB monomers by use of solid‐phase reagent

For selective synthesis of linear polyester having a functional group at one end, polycondensation between 1,4‐butanediol ( 1a ) and sebacoyl chloride ( 2a ) and between 1,12‐dodecanediol ( 1b ) and isophthaloyl chloride ( 2b ) was conducted in the presence of oxime resin or oxime silica gel, followed by cleavage of the formed polyester from the solid‐phase support with aniline. Matrix‐assisted laser desorption ionization time‐of‐flight mass spectra and ¹H NMR spectra of the cleaved polyester showed that the products contained not only polyester with anilide at one end ( poly 1 ), but also polyester with anilides at both ends ( poly 2 ). The product ratio of poly 1 to poly 2 ( poly 1 / poly 2 ) was dependent on monomers, monomer concentration, feed ratio of monomer to oxime moiety in the support, oxime content in the support, reaction solvent, and the nature of the support. Polyester with a high poly 1 / poly 2 ratio of 81/21 and moderate molecular weight (M_n = 1430 g/mol) was obtained by polycondensation of 1b and 2b in the presence of oxime silica gel in dichloromethane. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 1379–1386