The Role of Methoxy Group in the Nazarov Cyclization of 1,5-bis-(2-Methoxyphenyl)-1,4-Pentadien-3-one in the Gas Phase and Condensed Phase

ESI-protonated 1,5-bis-(2-methoxyphenyl)-1,4-pentadien-3-one (1) undergoes a gas-phase Nazarov cyclization and dissociates via expulsions of ketene and anisole. The dissociations of the [M + D]⁺ ions are accompanied by limited HD scrambling that supports the proposed cyclization. Solution cyclization of 1 was effected to yield the cyclic ketone, 2,3-bis-(2-methoxyphenyl)-cyclopent-2-ene-1-one, (2) on a time scale that is significantly shorter than the time for cyclization of dibenzalacetone. The dissociation characteristics of the ESI-generated [M + H]⁺ ion of the synthetic cyclic ketone closely resemble those of 1, suggesting that gas-phase and solution cyclization products are the same. Additional mechanistic studies by density functional theory (DFT) methods of the gas-phase reaction reveals that the initial cyclization is followed by two sequential 1,2-aryl migrations that account for the observed structure of the cyclic product in the gas phase and solution. Furthermore, the DFT calculations show that the methoxy group serves as a catalyst for the proton migrations necessary for both cyclization and fragmentation after aryl migration. An isomer formed by moving the 2-methoxy to the 4-position requires relatively higher collision energy for the elimination of anisole, as is consistent with DFT calculations. Replacement of the 2-methoxy group with an OH shows that the cyclization followed by aryl migration and elimination of phenol occurs from the [M + H]⁺ ion at low energy similar to that for 1.

Reactivities of osmium (VIII) towards some aldoses,amino sugars,and methylated sugars in alkaline medium

The kinetics of oxidation of some aldoses, amino sugars and methylated sugars by osmium (VIII) have been studied spectrophotometrically in alkaline medium. The reactions are first‐order with respect to both [sugar]≤9.0×10⁻³ mol dm⁻³ and [OH⁻]≤10.0×10⁻² mol dm⁻³ but tends toward zero order with respect to each at higher concentration. Activation parameters of the reactions have been calculated and plausible reaction mechanisms have been suggested. © 1999 John Wiley & Sons, Inc. Int J Chem Kinet 31: 477–483, 1999     

Reactions of titanium(IV) isopropoxide with aliphatic and aromatic hydroxy esters,part I. 5-, 6-, 7- and 8-coordinate titanium(IV) complexes

Summary Reactions of titanium(IV) isopropoxide with ethyl 1-hydroxycyclohexylacetate, ethyl 2-hydroxy-2-arylpropionate, ethyl 2-hydroxy-2-arylbutyrate and ethyl 2-hydroxy-2-arylhydrocinnamate have been studied in dry benzene in different molar ratios under strictly anhydrous conditions. The Ti(OPr-i)₄-_nL_n type compounds, where L = hydroxy ester and n = 1 to 4, have been isolated and characterised by elemental analysis, molecular weight, i.r. and n.m.r. spectral studies. These products may be distilled unchanged under reduced pressure.Reprints of this are not available.     

Differentiation of electrophilic and ambiphilic carbenes

Comparative selectivities toward alkenes of CH₃CCl, CCl₂, and CH₃OCCl establish the former two carbenes as electrophiles; the latter is an ambiphile.     

Structural features of some small carbonyls in the 1,3nπ states: An mcscf study

Structural features of a series of tetraatomic carbonyls in the ^1,3nπ* states are studied by using a recently proposed MCSCF algorithm at the INDO/2 level. The computed geometrical parameters and the inversion barrier heights agree quite well with the available experimental or ab initio theoretical data. The calculated transition energies turn out to be somewhat lower than the experimental counterparts. The specific MCSCF algorithm used is found to have excellent convergence properties.     

Binuclear iron(III) compounds with bidentate bases

Summary Binuclear iron(III) derivatives, Fe₂Cl(anth)₅, Fe₂Cl(salH)₅, Fe₂Cl(acac)₅ and Fe₂Cl(quin)₅ · quinH have been prepared by reacting Fe₂Cl(OH)₂(AcO)₃ · 2AcOH with anthranilic acid (anthH), salicylic acid (salH₂), acetylacetone (acacH) and 8-hydroxyquinoline (quinH), respectively. These compounds have been characterised by molecular weight, conductance, i.r. spectral, magnetic susceptibility and Mössbauer measurements.     

Validated LC–MS/MS method for quantitation of a selective JAK1 inhibitor,filgotinib in rat plasma,and its application to a pharmacokinetic study in rats

Filgotinib is a selective JAK1 (Janus kinase) inhibitor, filed in Japan for the treatment of rheumatoid arthritis. In this paper, we report a validated liquid chromatography coupled with tandem mass spectrometry for the quantification of filgotinib in rat plasma using tofacitinib as an internal standard (IS) as per the Food and Drug Administration regulatory guidelines. Filgotinib and the IS were extracted from rat plasma using ethyl acetate as an extraction solvent and chromatographed using an isocratic mobile phase (0.2% formic acid:acetonitrile; 20:80, v/v) at a flow rate of 0.9 mL/min on a Gemini C₁₈ column. Filgotinib and the IS were eluted at ~1.31 and 0.89 min, respectively. The MS/MS ion transitions monitored were m/z 426.3 → 291.3 and m/z 313.2 → 149.2 for filgotinib and the IS, respectively. The calibration range was 0.78–1924 ng/mL. No matrix effect and carryover were observed. Intra- and inter-day accuracies and precisions were within the acceptance range. Filgotinib was stable for three freeze–thaw cycles: on bench-top up to 6 h, in an autosampler up to 21 h, and at −80 ° C for 1 month. This novel method has been applied to a pharmacokinetic study in rats.     

Enantioselective LC–ESI–MS/MS method for quantitation of (−)-lumefantrine and (+)-lumefantrine in mice plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective, and reliable LC–MS/MS–ESI method for the direct quantitation of lumefantrine (LFN) enantiomers [(−)-LFN and (+)-LFN] in mice plasma as per regulatory guideline. LFN enantiomers and carbamazepine (internal standard) were extracted from mice plasma using Strata X SPE (solid-phase extraction) cartridges. Good resolution between enantiomers was achieved on a Chiralpak IA-3 column using an isocratic mobile phase (0.1% of diethyl amine in methanol), which was delivered at a flow rate of 0.8 mL/min. Detection and quantitation were performed using multiple reaction monitoring mode following the transitions m/z 530.27 → 512.30 and 237.00 → 194.00 for LFN enantiomers and the internal standard, respectively, in the positive-ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 2.39–895 ng/mL for each enantiomer. The intra- and inter-day precisions were in the range of 1.03–6.14 and 6.36–8.70 and 2.03–4.88 and 5.82–11.5 for (−)-LFN and (+)-LFN, respectively. Both (−)-LFN and (+)-LFN were found to be stable under different stability conditions. The method was successfully used to delineate stereoselective pharmacokinetics of LFN enantiomers in mice after an oral administration of rac-LFN (20 mg/kg). The pharmacokinetic results indicated that the disposition of LFN enantiomers was stereoselective in mice.