Aryl Oximes Research Articles

A Convenient Practical Synthesis of Alkyl and Aryl Oxime Esters

A facile access to the synthesis of alkyl and aryl oxime esters of ketoximes and aldoximes in high yields (90–97%) is reported. The reactions were performed using N-[3-(methylamino)propyl]-N′-ethylcarbodiimide hydrochloride (EDCI) reagent in the presence of 4-(dimethylamino)pyridine (DMAP) as a catalyst at room temperature. The isolation and purification of products is very simple and in cases where product is solid, column chromatography is avoided.

Regioselective Synthesis of 2,6‐Dimethyl‐3,5‐bis[(3‐aryl‐5‐trifluoromethyl)‐isoxazol‐4‐carbonyl]‐pyridine Derivatives

AbstractEthyl 4,4,4‐trifluoro‐3‐oxo‐butyrate reacted with 2,6‐dimethyl‐3,5‐diacetyl‐pyridine 1 in the presence of NaOC2H5 at 0°C to give 2,6‐dimethyl‐3,5‐bis(4,4,4‐trifluoro‐1,3‐oxo‐butyl)‐pyridine (2a) in good yield. Cyclization reaction of 2a and aryl imidoyl chlorides 5a–5i, obtained from chlorination of aryl oximes with N‐chlorosuccimide, afforded 2,6‐dimethyl‐3,5‐bis[(3‐aryl‐5‐trifluoromethyl)‐isoxazol‐4‐carbonyl]‐pyridine derivatives 6a–6i.

Synthesis, characterization and X-ray structure of glycosyl-1,2-isoxazoles and glycosyl-1,2-isoxazolines prepared via 1,3-dipolar cycloaddition

A convenient preparative method of a series of glycosyl-1,2-isoxazoles (6–11) and glycosyl-1,2-isoxazolines (15–20) by a simple and efficient 1,3-dipolar cycloaddition of a series of aryl nitrile oxide, generated in situ from aryl oximes (4–5), with a variety of O-propargyl glycosyles (1–3) or O-allyl glycosyles (12–14) respectively, is reported. The carbohydrate-containing 1,2-isoxazoles and 1,2-isoxazolines compounds were isolated in excellent yields (81–91%) and they were fully characterized by 1H, 13C NMR and mass spectrometry. The relative stereochemistry of the glycosyl-1,2-isoxazole 10 was confirmed by single crystal X-ray analysis. The molecular structure of 10 confirms the retention of both, the anomeric stereochemistry of the D-fructose as well as the placement of the acetal groups.

ChemInform Abstract: Efficient Synthesis of Oxazoles by Dirhodium(II)‐Catalyzed Reactions of Styryl Diazoacetate with Oximes.

AbstractA series of 4‐styryl‐5‐methoxyoxazoles (III) is readily prepared by reaction of styryl diazoacetate (I) with aryl oximes (II).

Synthesis of some novel 1-(2-naphthyl)-2-(imidazol-1-yl)ethanone oxime ester derivatives and evaluation of their anticonvulsant activity

Twenty-three new oxime ester derivatives of nafimidone were synthesized with the prospect of potential anticonvulsant activities. MES and ScM tests were employed for their anticonvulsant activities and rotorod test for neurological deficits. Eighteen compounds were found to be protective against MES seizures. Alkyl (1–8) and arylalkyl (9, 10) oxime ester derivatives were found to be more active than aryl oxime ester derivatives (11–23). Five compounds (2, 3, 7, 9, 10), which were protective at 0.5 h at the doses of 30 mg/kg and higher in MES test, showed the highest activity. Compound 17 was the most active one in ScM test at all dose levels at 4 h.

ChemInform Abstract: One‐Pot Synthesis of Aryl Oxime Analogues from Methyl Arenes Using NBS and Hydroxyl Amine Hydrochloride.

AbstractThe reaction is advantageous with regard to functional group tolerance, high yield, and simple experimental procedure.

One-pot synthesis of aryl oxime analogues from methyl arenes using NBS and hydroxyl amine hydrochloride

The one-pot synthesis of aryl oximes is reported by the reaction of methyl arenes with NBS using hydroxyl amine hydrochloride. The direct conversion of methyl group into oxime group has been achieved under mild reaction conditions in the presence of sensitive functional groups including chloro, bromo, cyano, hydroxy, fluoro, dioxaborolane, esters, and trifluoro methyl substituents with excellent yields. The simple experimental procedure and easy purification make this protocol advantageous.

Efficient synthesis of oxazoles by dirhodium(II)-catalyzed reactions of styryl diazoacetate with oximes.

An efficient one-step synthesis of multi-functionalized oxazole derivatives is achieved in high yield by dirhodium(II)-catalyzed reactions of styryl diazoacetate with aryl oximes.

Investigation of collision‐induced dissociations involving odd‐electron ion formation under positive electrospray ionization conditions using accurate mass

Collision induced dissociation (CID) has been extensively used for structure elucidation. CID in the electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) modes has been found to generate mostly even-electron fragment ions while it has been occasionally reported to form odd-electron free radical ions. However, the structural requirements and the fragmentation mechanisms for free-radical CIDs have not been well characterized in the literature. For this purpose, we studied a series of aromatic and non-aromatic compounds such as sulfonamides, N-aryl amides, tert-butyl-substituted aromatic compounds, aryl alkyl ethers, and O-alkyl aryl oximes using the LTQ and LTQ Orbitrap linear ion trap mass spectrometers. The accurate measurement of the fragment ion masses established the unambiguous assignment of the fragment structures resulting from the test compounds. Our results showed that free radical fragmentation is structure dependent and is to a large extent correlated with the neighboring groups in the structures that stabilize the newly formed free radical ions.

Manipulating cytochrome P450 enzymes: new perspectives for cancer treatment

Manipulating cytochrome P450 enzymes: new perspectives for cancer treatment

Preparation of a Spiroisoxazolinopiperidinylbenzamide-Based Scaffold

A route to spiroisoxazolinopiperidinylbenzamides has been developed. N-Boc-4-piperidone underwent a Wittig olefination and Boc-deprotection followed by a nucleophilic substitution reaction with 4-fluoro-3-nitrobenzoic acid to yield the starting scaffold 3 in excellent yields. Diversification of the acid with primary amines, followed nitrile oxide formation in situ (aryl oximes treated with bleach) and subsequent 1,3-dipolar cycloaddition to the exomethylene moiety delivered the spiroisoxazolinopiperdines. Reduction of the arylnitro group followed by acylation with acid chlorides or reductive amination with aldehydes yielded the spiroisoxazolinopiperidinylbenzamide library.

Synthesis and biological activity of 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles

Acid hydrazides were coupled with acrylic acid derivatives and cyclodehydration gave 1,3,4-oxadiazoles. Lastly, in-situ nitrile oxide formation from aryl oximes treated with sodium hypochlorite, and subsequent 1,3-dipolar cycloaddition to the exomethylene moiety delivered 2-(4,5-dihydroisoxazol-5-yl)-1,3,4-oxadiazoles. This library was evaluated in a high-throughput screen at Dow AgroSciences. Several compounds were active against fungal pathogens and pest insects.

DFT‐Verified Crystallographic Mechanism of Cycloplatination

AbstractTwo key intermediates in the mechanistic cycle of cycloplatination of aryl oximes by PtII complexes were crystallographically characterized. trans‐[PtCl2(SOMe2)(N‐acetophenone oxime)] is an active precursor on the C–H cleavage reaction coordinate. The formation of trans‐[PtCl2(N‐benzaldehyde oxime)2] accounts for the rate retardation by excess oxime. DFT calculations support the crystallographic evidence that provides unequivocal proof for the electrophilic nature of cycloplatination. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Methyltrioxorhenium‐Catalyzed Oxidation of Aromatic Aldoximes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Methyltrioxorhenium-Catalyzed Oxidation of Aromatic Aldoximes

The first catalytic oxidation of aryl oximes to nitro compounds by means of methyltrioxorhenium and urea hydroperoxide is reported. The formation of carbamates, probably occurring through formation of nitrile oxide intermediates, has been observed from 2,6-disubstituted aryl oximes.

Stoichiometric reactions of methylparathion with a palladium aryl oxime metallacycle.

The reaction of [Pd(3)(OAc)(6)] with (E)-acetophenone oxime and pyridine in CHCl(3) under reflux affords the metallacycle [Pd(OAc)[C,N-(C(6)H(4)C(CH(3))=NOH)-2](py)] (1) as a yellow air-stable complex. The same reaction carried out at room temperature in the absence of pyridine affords the trinuclear oximato complex [Pd(mu-(E)-ON=C(CH(3))Ph)(mu-OAc)](3) (2), which can be converted into 1 upon heating in the presence of pyridine. As indicated by (1)H and (31)P NMR spectroscopy, complex 1 reacts with methylparathion in acetone-d(6)-D(2)O solutions to afford [Pd(SP(=O)(OCH(3))(2))[C,N-(C(6)H(4)C(CH(3))=NOH)-2](py)] (3) and [Pd(mu-SP(=O)(OCH(3))(2))[C,N-(C(6)H(4)C(CH(3))=NOH)-2]](2) (4) as well as free p-nitrophenol. Compounds 1-4 have been characterized by single-crystal X-ray analysis, NMR and EA. Compounds 1 and 3 are mononuclear complexes with the acetate and dimethylthiophosphate ligand, respectively, trans from the phenyl group. Compound 2 is a trinuclear complex whose structure can be derived from that of [Pd(3)(OAc)(6)] by replacing three of the acetate ligands on one side of Pd(3) plane by three N,O-coordinated oximate ligands. Complex 4 is a dinuclear complex in which the two square-planar palladium moieties are linked by the sulfur atoms of the bridging dimethylthiophosphate ligands.

Saturated N‐Heterocyclic Carbene Oxime and Amine Palladacycle Catalysis of the Mizoroki—Heck and the Suzuki Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Saturated N-Heterocyclic CarbeneOxime and Amine Palladacycle Catalysis of the Mizoroki-Heckand the Suzuki Reactions

ortho-Palladated aryl oxime and amines with a N-heterocyclic carbene ligand show increased thermal stability and catalyze the Mizoroki-Heck and Suzuki reaction with high yields, and moderate TON (2,000-92,000) and TOF (200-4,300 h - 1 ). Homo coupling of the aryl halides gave low yields of the biaryls in the presence of these catalysts.

Structural and mechanistic look at the orthoplatination of aryl oximes by dichlorobis(sulfoxide or sulfide)platinum(II) complexes.

Structural and mechanistic aspects of orthoplatination of acetophenone and benzaldehyde oximes by the platinum(II) sulfoxide and sulfide complexes [PtCl(2)L(2)] (2, L = SOMe(2) (a), rac-SOMePh (b), R-SOMe(C(6)H(4)Me-4) (c), and SMe(2) (d)) to afford the corresponding platinacycles cis-(C,S)-[Pt(II)(C(6)H(3)-2-CR'=NOH-5-R)Cl(L)] (3, R, R' = H, Me) have been investigated. The reaction of acetophenone oxime with sulfoxide complex 2a in methanol solvent occurs noticeably faster than with sulfide complex 2d due to the fact that the sulfoxide is a much better platinum(II) leaving ligand than the sulfide. Evidence is presented that the orthoplatination is a multistep process. The formation of unreactive dichlorobis(N-oxime)platinum(II) cations accounts for the rate retardation by excess acetophenone oxime and suggests the importance of pseudocoordinatively unsaturated species for the C-H bond activation by Pt(II). A comparative X-ray structural study of dimethyl sulfoxide platinacycle 3b (R = R' = Me) and its sulfide analogue 3e (R = H, R' = Me), as well as of SOMePh complex 3c (R = H, R' = Me), indicated that they are structurally similar and a sulfur ligand is coordinated in the cis position with respect to the sigma-bound phenyl carbon. The differences concern the Pt-S bond distance, which is notably longer in the sulfide complex 3e (2.2677(11) A) as compared to that in sulfoxide complexes 3b (2.201(2)-2.215(2) A) and 3c (2.2196(12) A). Whereas the metal plane is practically a plane of symmetry in 3b due to the H-bonding between the sulfoxide oxygen and the proton at carbon ortho to the Pt-C bond, an S-bonded methyl of SOMePh and SMe(2) is basically in the platinum(II) plane in complexes 3c and 3e, respectively. There are intra- and intermolecular hydrogen bond networks in complex 3b. An interesting structural feature of complex 3c is that the two independent molecules in the asymmetric unit of the crystal reveal an extremely short Pt-Pt contact of 3.337 A.

Conformational Studies by Dynamic NMR. 89.1 Stereomutation and Cryogenic Enantioseparation of Conformational Antipodes of Hindered Aryl Oximes

Aryl benzyl oximes having the configuration Z give rise to stereolabile atropisomers when a halogen atom is present in the ortho position of the aryl moiety, as a consequence of the restricted aryl-CN bond rotation. By means of dynamic (1)H NMR spectroscopy it has been possible to determine the corresponding rotation barrier, hence the lifetime of the atropisomers that, in the case of the iodine derivative, was found sufficiently long as to allow a physical separation to be achieved on an appropriately cooled enantioselective HPLC column. Comparison of the barriers determined by dynamic NMR and dynamic HPLC proved the equivalence of the two techniques. When the iodine atom was substituted by an alpha-naphthyl group, two dynamic processes were observed. That with the lower barrier could be determined by NMR and that with the higher barrier by HPLC, thus outlining the complementarity of these two techniques.