Isoxazole Ring Research Articles

3-Chloromethyl-6,7-dimethyl-1,2-benzoxazole

In the title compound, C10H10ClNO, the benzoisoxazole ring is almost planar (r.m.s. deviation = 0.0121 Å) and the chloro substituent in the side chain is anti­clinal relative to the N—C bond of the isoxazole ring. In the crystal, adjacent mol­ecules are linked via a pair of weak C—H⋯N hydrogen bonds, forming dimers through a cyclic R 2 2(8) association.

3-Benzyl-5-methyl-1,2-benzoxazole 2-oxide

In the title compound, C15H13NO2, the isoxazole unit and the attached benzene ring are almost coplanar, making a dihedral angle of 1.42 (8)°. The benzyl ring is inclined to the isoxazole ring by 74.19 (8)° and is in a +sc conformation with respect to the benzisoxazole unit. In the crystal, C—H⋯O hydrogen bonds link the mol­ecules, forming zigzag chains propagating along the b axis. There are also π–π inter­actions present involving the isoxazole and benzyl rings [centroid–centroid distance = 3.5209 (10) Å], and C—H⋯π inter­actions involving the benzene ring of the benzoisoxazole unit and the methyl­ene bridging group.

4-[4-(4-Chlorobenzoyl)-2,3-diphenylisoxazolidin-5-yl]-1-(4-methoxyphenyl)-3-phenylazetidin-2-one

In the title compound, C38H31ClN2O4, the isoxazole ring adopts an envelope conformation with the N atom as the flap. The crystal packing is stabilized by C—H⋯O hydrogen bonds, forming chains running along the c-axis direction.

5-Amino-3-methyl-1,2-oxazole-4-carbonitrile

In the title compound, C5H5N3O, the isoxazole ring is essentially planar, with a maximum deviation of 0.007 (1) Å from the least-squares plane. The N atom of the amine group exhibits sp 2 character (sum of bond angles around this atom = 358°). In the crystal, mol­ecules are aggregated by two kinds of N—H⋯N hydrogen bonds into fused R 2 2(12) and R 6 6(26) rings, forming a slightly puckered two-dimensional array lying parallel to (101).

Synthesis and evaluation of 4-(substituted styryl/alkenyl)-3,5-bis(4-hydroxyphenyl)-isoxazoles as ligands for the estrogen receptor

A series of 3,5-bis (4-hydroxyphenyl) isoxazoles bearing a styryl/alkyl vinyl group at the 4-position were prepared and evaluated as ligands for the estrogen receptor-alpha (ERα). The target compounds were prepared using the Suzuki reaction to couple an iodo-isoxazole intermediate with a series of styryl/alkenyl boronic acids, followed by O-demethylation. The products were evaluated for their estrogen receptor-α ligand binding domain (ERα-LBD) binding affinity using a competitive binding assay. The 4-(4-hydroxystyryl) derivative 4h displays binding properties similar to those of the previously described pyrazole class of ER ligands, indicating that the ERα-LBD tolerates the presence of the added vinyl group at the 4-position of the isoxazole ring.

N-(2,4-Difluoro-phen-yl)-5-methyl-1,2-oxazole-4-carboxamide hemihydrate.

In the title compound, C11H8F2N2O2·0.5H2O, the dihedral angle between the benzene and isoxazole rings is 8.08 (3)°. In the crystal, the components are linked by O—H⋯N and N—H⋯O hydrogen bonds, in which the water mol­ecule acts as both a donor and an acceptor, into a tape with an R 4 4(16) graph-set motif along the a axis. The water mol­ecule is located on a twofold rotation axis. The methyl H atoms were treated as disordered groups over two sites with a refined site-occupancy ratio of 0.48 (6):0.52 (6).

ChemInform Abstract: Synthesis and Antimicrobial Evaluation of Some New Cyclooctanones and Cyclooctane‐Based Heterocycles.

AbstractA variety of new aminomethylenecyclooctane derivatives and cyclooctane‐based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine, and imidazopyrimidine rings is synthesized via reactions of cyclooctanone (III) with appropriate nitrogen nucleophiles.

Rac-Methyl 3-(2-methoxyphenyl)-1-phenyl-3,3a,4,9b-tetrahydro-1H-chromeno[4,3-c]isoxazole-3a-carboxylate

The title compound, C25H23NO5, comprising two stereogenic carbon atoms of the same configuration, crystallizes in a centrosymmetric space group as a racemate. The six-membered pyran ring and the five-membered isoxazole ring adopt sofa and twisted conformations, respectively. The dihedral angle between the benzene ring and the mean plane through the near coplanar atoms of the pyran ring is 10.73 (7)°. The crystal structure features C—H⋯O hydrogen bonds.

3,5-Bis(4-fluorophenyl)isoxazole

In the crystal structure of the title compound, C15H9F2NO, the complete mol­ecule is generated by a crystallographic twofold rotation axis and the O and N atoms of the central isoxazole ring are statistically disordered with equal site occupancies. The terminal benzene rings form a dihedral angle of 24.23 (3)° with the isoxazole ring. The dihedral angle between the benzene rings is 47.39 (2)°. No significant inter­molecular inter­actions are observed.

Rac-6-Ethoxy-3,3a,4,9b-tetrahydro-1,3-diphenyl-1H-chromeno[4,3-c]isoxazole-3a-carbonitrile

The title compound, C25H22N2O3, with three stereogenic centres, crystallizes in a centrosymmetric space group as a racemate. The pyran ring adopts a sofa conformation and the five-membered isoxazole ring exhibits an envelope conformation. The dihedral angle between the benzene ring and the mean plane through the near coplanar atoms of the pyran ring is 10.54 (9)°. In the crystal, no significant intermolecular interactions are observed.

5-Methyl-N-[2-(trifluoro-meth-yl)phen-yl]isoxazole-4-carboxamide.

In the title compound, C12H9F3N2O2, the benzene ring is nearly perpendicular to the isoxazole ring, making a dihedral angle of 82.97 (2)°. In the crystal, mol­ecules are linked by N—H⋯O hydrogen bonds into a supra­molecular chain running along the c axis.

Intramolecular Iodine‐Mediated Oxygen Transfer from Nitro Groups to C≡C Bonds

AbstractHighly regioselective oxygen transfer from nitro groups to C≡C bonds has been achieved by employment of iodine monochloride or molecular iodine. The precursors are heterocyclic, aromatic or acyclic compounds, each bearing a nitro group ortho to an internal alkyne. The developed methodology is general for the preparation of a wide range of fused isoxazoles, each bearing a carbonyl function in the fifth position in the isoxazole ring. It is very important to note that the outcomes of the cycloisomerizations are not dictated by the natures of the heterocycle or alkyne substituents. Moreover, this is a unique example of iodine‐mediated ring closure of internal alkynes without introduction of halogen into the newly formed rings.

Ethyl 5-(4-aminophenyl)isoxazole-3-carboxylate

The asymmetric unit of the title compound, C12H12N2O3, contains two mol­ecules in which the benzene and isoxazole rings are almost coplanar, the dihedral angles between their mean planes being 1.76 (9) and 5.85 (8)°. The two mol­ecules inter­act with each other via N—H⋯N and N—H⋯O hydrogen bonds, which link the mol­ecules into layers parallel to the ac plane. The layers stack in a parallel mode with an inter­layer distance of 3.36 (7) Å.

Identification of imine or enamine drug metabolites using online hydrogen/deuterium exchange and exact mass measurements

Drug metabolites that have imine or enamine partial structures cause extra mass-to-charge (m/z) increases in online hydrogen/deuterium exchange (HDX) in addition to hydroxyl or amine protons. Online HDX and exact mass measurement were used herein to characterize this extra increase property, and to further confirm proposed metabolite structures. Metabolites of two proprietary compounds as well as two commercially available compounds were analyzed using aqueous and HDX liquid chromatography coupled with an LTQ-Orbitrap. The exact mass measurements of both the precursor ions and product ions were acquired through data-dependent acquisition and compared with theoretical values of proposed fragment ions. Analysis of exact mass measurements of metabolite product ions under both normal aqueous and HDX conditions led to the identification of the isoxazole ring opening of compound C-1, and a double-bond formation on the methylpyrrolidine ring of compound C-2 during biotransformation. In both cases, imine or enamine structures formed in the metabolites caused extra m/z increases upon HDX that contributed confirmatory information to the structure identification. The compound 3,3-diphenyl-2-ethyl-1-pyrroline also demonstrated that the methylene protons adjacent to the imine were exchanged during online HDX. The exchangeability of methylene protons adjacent to imine or enamine moieties proved to be useful to narrow down or even pinpoint the metabolism sites of parent drugs when high-resolution exact mass measurement and online HDX were used.

Diarylheterocycle Core Ring Features Effect in Selective COX‐1 Inhibition

The COX-1 isoenzyme plays a significant role in a variety of diseases, as it catalyzes the bioprocesses behind many health problems. Among the diarylheterocycle class of COX inhibitors, the isoxazole ring has been widely used as a central heterocycle for the preparation of potent and selective COX-1 inhibitors such as P6 [3-(5-chlorofuran-2-yl)-5-methyl-4-phenylisoxazole]. The role of the isoxazole nucleus in COX-1 inhibitor selectivity has been clarified by preparing a set of new diarylheterocycles with various heterocycle cores. Replacement of isoxazole with isothiazole or pyrazole gave a drastic decrease in COX-1 inhibitory activity, whereas the introduction of an electron-donating group (EDG) on the N-aryl pyrazole allowed recovery of COX-1 inhibitory activity and selectivity. The EDG-equipped 5-(furan-2-yl)-1-(4-methoxyphenyl)-3-(trifluoromethyl)-1H-pyrazole (17) selectively inhibits COX-1 activity (IC(50) =3.4 μM; 28% COX-2 inhibition at 50 μM), in contrast to its inactive analogue, 3-(furan-2-yl)-1-phenyl-5-(trifluoromethyl)-1H-pyrazole, which does not bear the methoxy EDG. Molecular docking studies of compound 17 into the binding site of COX-1 shed light on its binding mode.

4-Hydroxy-3,5-dimethoxy-N-{4-[(5-methyl-1,2-oxazol-3-yl)sulfamoyl]phenyl}benzamide methanol monosolvate

The title compound, C19H19N3O7S·CH3OH, was synthesized from syringic acid and sulfamethoxazole. The benzene rings make a dihedral angle of 41.8 (1)° and the isoxazole ring is twisted by 74.3 (1)° from the central benzene ring. The crystal packing features O—H⋯O and O—H⋯N hydrogen bonds in which the hy­droxy groups from the main mol­ecule and methanol solvent mol­ecules serve as donor groups.

(2S,5S,6R)-5-(4-Methylphenyl)-3-phenyl-4,8-dioxa-3-azatricyclo[7.4.0.02,6]trideca-1(13),9,11-triene-6-carbonitrile

In the title compound, C24H20N2O2, the six-membered pyran ring adopts a half-chair conformation with one C atom deviating from the mean plane of the remaining ring atoms by 0.654 (6) Å. The five-membered isoxazole ring adopts an N-envelope conformation with the N atom displaced by 0.742 (5) Å from the mean plane formed by the remaining ring atoms. The carbonitrile side chain is almost linear, with a C—C—N angle of 178.6 (5)°. The crystal packing is stabilized by inter­molecular C—H⋯N inter­actions, through bifurcated acceptor hydrogen bonds formed between the carbonitrile N atom and two alternate C atoms in the unsubstituted benzene ring. The mol­ecular structure and crystal packing are further stabilized by intra­molecular and inter­molecular C—H⋯π inter­actions.

Carbohydrate nitrone and nitrile oxide cycloaddition approach to chiral sulfur heterocycles and nucleosides

S-Alkenyl and -alkynyl carbohydrate derivatives were prepared from 1,2:5,6-O-diisopropylidene-α-D-allofuranose. Nitrones and nitrile oxides generated from these derivatives led to the formation of 6, 7, and 11-membered chiral sulfur heterocycles fused to isoxazolidine, isoxazoline and isoxazole rings. Some of these sulfur heterocycles were converted to nucleosides. The 11-memebered sulfur compound was found to gelate hydrocarbon solvents.

An Efficient One-Pot Synthesis of Highly Fanctionalized Isoxazoles

Triphenylphosphine and dialkyl acethylenedicarboxylates in the presence of 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine react in one-pot to afford novel highly functionalized Isoxazoles in fairly good yields at room temperature. When 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-triazine were employed in these reactions, related isoxazole rings were obtained in good yields.

Synthesis of New 3, 5-Diaryl-4, 5-Dihydroisoxazole-4- Carbonitriles via 1, 3-Dipolar Cycloaddition Reaction

Abstract : Aromatic aldoximes 1a-i undergo oxidative dehydrogenation with CrO 2 to give nitrile oxides, which are trapped in situ by 4-methoxycinnamonitrile 2 to afford of ethyl 3,5-diaryl-4,5-dihydroisoxazole-4-carbonitriles 3a-i in good yield . Key words : Isoxazoles, isoxazolines, magtreive TM , antimicrobial, antioxidant. I. Introduction Isoxazoles and isoxazolines are very useful heterocycles in organic and heterocyclic chemistry [1]. Isoxazolines also serves as important building blocks for the synthesis of various biologically active molecules [2]. The isoxazoles are known to exhibit significant number of biological applications such as hypoglycemic, analgesic, anti-inflammatory and HIV-inhibitory activity [3], also found to exhibit antibacterial [4], antifungal [5], antioxidant [6], potent selective agonists at human cloned dopamine D4 receptors [7], COX-2 inhibitory [8], antinociceptive [9], anticancer [10], and antibiotic, antitumour, insecticidal activities [1,2]. They serve as prodrug for the anti-arithretic agent [11]. Vijay V. Dabholkar and co-workers [12] reported the synthesis and their antimicrobial activity of fused isoxazolines. Joshi and et al [13] reported that isoxazoles acts as potential antitubercular agents. The most convenient synthesis of isoxazoline and isoxazole ring system has been executed in the literature via 1, 3-dipolar cycloaddition reactions of alkenes and alkynes with nitrile oxides generated