Cobalt‐Catalyzed Cyclization of N‐Methoxy Benzamides with Alkynes using an Internal Oxidant through C−H/N−O Bond Activation

The cyclization of substituted N‐methoxy benzamides with alkynes in the presence of an easily affordable cobalt complex and NaOAc provides isoquinolone derivatives in good to excellent yields. The cyclization reaction is compatible with a range of functional group‐substituted benzamides, as well as ester‐ and alcohol‐substituted alkynes. The cobalt complex [Co^IIICp*(OR)₂] (R=Me or Ac) serves as an efficient catalyst for the cyclization reaction. Later, isoquinolone derivatives were converted into 1‐chloro and 1‐bromo substituted isoquinoline derivatives in excellent yields in the presence of POCl₃ or PBr₃.     

Development and validation of a highly sensitive and robust LC‐ESI‐MS/MS method for simultaneous quantitation of simvastatin acid,amlodipine and valsartan in human plasma: application to a clinical pharmacokinetic study

A high‐throughput, simple, highly sensitive and specific LC‐MS/MS method has been developed for simultaneous estimation of simvastatin acid (SA), amlodipine (AD) and valsartan (VS) with 500 µL of human plasma using deuterated simvastatin acid as an internal standard (IS). The API‐4000 LC‐MS/MS was operated under the multiple reaction‐monitoring mode (MRM) using electrospray ionization. The assay procedure involved precipitation of SA, AD, VS and IS from plasma with acetonitrile. The total run time was 2.8 min and the elution of SA, AD, VS and IS occurred at 1.81, 1.12, 1.14 and 1.81 min, respectively; this was achieved with a mobile phase consisting of 0.02 m ammonium formate (pH 4.5):acetonitrile (20:80, v/v) at a flow rate of 0.50 mL/min on an X‐Terra C₁₈ column. A linear response function was established for the range of concentrations 0.5–50 ng/mL (r > 0.994) for VS and 0.2–50 ng/mL (r > 0.996) for SA and AD. The method validation parameters for all three analytes met the acceptance as per FDA guidelines. This novel method has been applied to human pharmacokinetic study. Copyright © 2009 John Wiley & Sons, Ltd.     

Benzonitrile extrusion from molybdenum(IV) ketimide complexes obtained via radical C-E (E = O, S, Se) bond formation: toward a new nitrogen atom transfer reaction

Beta-elimination is explored as a possible means of nitrogen-atom transfer into organic molecules. Molybdenum(IV) ketimide complexes of formula (Ar[t-Bu]N)3Mo(N=C(X)Ph), where Ar = 3,5-Me2C6H3 and X = SC6F5, SeC6F5, or O2CPh, are formally derived from addition of the carbene fragment [:C(X)Ph] to the terminal nitrido molybdenum(VI) complex (Ar[t-Bu]N)3Mo identical with N in which the nitrido nitrogen atom is installed by scission of molecular nitrogen. Herein the pivotal (Ar[t-Bu]N)3Mo(N=C(X)Ph) complexes are obtained through independent synthesis, and their propensity to undergo beta-X elimination, i.e., conversion to (Ar[t-Bu]N)3MoX + PhC identical with N, is investigated. Radical C-X bond formation reactions ensue when benzonitrile is complexed to the three-coordinate molybdenum(III) complex (Ar[t-Bu]N)3Mo and then treated with 0.5 equiv of X2, leading to facile assembly of the key (Ar[t-Bu]N)3Mo(N=C(X)Ph) molecules. Treated herein are synthetic, structural, thermochemical, and kinetic aspects of (i) the radical C-X bond formation and (ii) the ensuing beta-X elimination processes. Beta-X elimination is found to be especially facile for X = O2CPh, and the reaction represents an attractive component of an overall synthetic cycle for incorporation of dinitrogen-derived nitrogen atoms into organic nitrile (R-C identical with N) molecules.     

Effect of load in scratch experiments on soda lime silica glass

Today the technological applications of glass span from everyday life to many advanced areas. These advanced applications require very accurate grinding and polishing that involve controlled removal of glass to achieve micron or even sub-micron surface finish. The major bottleneck in this connection is that the material removal mechanisms during such processes are yet to be fully understood. Since grinding involves many single pass scratch processes happening simultaneously, to develop better understanding about the effect of the normal load in affecting the material removal mechanisms; a number of single pass scratch experiments were conducted on a commercially available soda lime silica glass as a function of various normal loads (2–15 N) at a constant scratch speed of 100 μm.s^? 1. The results showed that the tribological properties, the severity and the spatial density of damage evolution were sensitive to the applied normal loads and the resultant tensile as well as shear stresses. Extensive optical and scanning electron photomicrography of the surface and sub-surface deformation zones proved the existence of three distinct deformation zones in the immediate vicinity of the scratch grooves and led to the development of a qualitative model of the material removal mechanisms.     

Variational Formula for the Time Constant of First‐Passage Percolation

We consider first‐passage percolation with positive, stationary‐ergodic weights on the square lattice ?^d. Let T(x) be the first‐passage time from the origin to a point x in ?^d. The convergence of the scaled first‐passage time T([nx])/n to the time constant as n → ∞ can be viewed as a problem of homogenization for a discrete Hamilton‐Jacobi‐Bellman (HJB) equation. We derive an exact variational formula for the time constant and construct an explicit iteration that produces a minimizer of the variational formula (under a symmetry assumption). We explicitly identify when the iteration produces correctors.© 2016 Wiley Periodicals, Inc.     

2-Nitrobenzaldehyde Thiocarbohydrazone Assisted Precise Extraction Spectrophotometric Method for the Determination of Ruthenium(III) in Alloy and Catalysts

A simple, rapid, selective, sensitive and reliable extractive spectrophotometric method was developed for the determination of ruthenium(III) using 2-nitrobenzaldehyde thiocarbohydrazone (2-NBATCH) as a chromogenic chelating ligand. The ruthenium(III)?2-NBATCH complex is formed in aqueous acetic acid media (0.7 M) containing an organic solvent after 5 min heating on a water bath. The red colored complex is extracted into 1,2-dichloroethane and absorbance is measured at 445 nm against reagent blank. The Beer’s law is obeyed within 1?6 g/mL of ruthenium(III), the optimum concentration range was 2?5 g/mL of ruthenium(III) evaluated by Ringbom’s plot. Molar absorptivity and Sandell’s sensitivity of complex were 1.41 × 10⁴ L/mol/cm and 0.0075 μg/cm², respectively. The stoichiometry of complex was 1: 3 established from Job’s method of continuous variation, molar ratio method and logarithmic slope method. The proposed method was applied for determination of ruthenium(III) in binary and ternary, synthetic mixtures corresponding to fission product elements alloy and ruthenium(III) catalysts.     

Methods for the synthesis of chiral sulfur heterocycles and their application in the asymmetric Baylis–Hillman reactions

Enantiomerically pure (2S,6S)-2,6-diphenyltetrahydro-2H-thiopyran, (2S)-2-phenyltetrahydro thiophene, and (2S)-2-phenyltetrahydro-2H-thiopyran were prepared in 70–72% yields and with 86–99% ee via cyclization of the corresponding dimesylate in an S_N2 cyclization reaction using sodium sulfide nonahydrate. The results on the application of various chiral sulfides in asymmetric Baylis–Hillman reactions are also described.     

Reactive functionalization of poly(lactic acid), PLA: Effects of the reactive modifier,initiator and processing conditions on the final grafted maleic anhydride content and molecular weight of PLA

A response surface methodology (RSM) design was used to analyze the effects of maleic anhydride (MA) and 2,5-bis(tert-butylperoxy)-2,5-dimethyl hexane (Luperox or L101) content, and TSE screw speed on the degree of grafted MA (MA_g) and number average molecular weight (M_n) of maleated PLA (PLA-g-MA), which can be used as a reactive compatibilizer in production of PLA blends with various components. PLA-g-MA's FTIR peaks indicated that MA was grafted onto the PLA backbone and oligomeric MA was also present. A maximum of 0.52 wt% MA_g determined by titration was achieved at the expense of a 50% reduction of M_n and an increase in the polydispersity index to around 2.0. Generally, increasing L101 increased the degree of grafting and decreased M_n. L101 and MA_g had a large effect on the stability of PLA-g-MA's M_n during storage. Nominally, amounts of MA equal to 4.5 wt%, L101 between 0.45 and 0.65 wt%, and screw speed of 20 rpm provided the optimal conditions for grafting MA onto PLA.