The Cu(OTf)2 catalysed microwave assisted synthesis of a new scaffold, 7-aryl-7,8-dihydropyrido[4,3-c]pyridazin-5(6H)-one

The synthesis of novel 7-aryl-7,8-dihydropyrido[4,3-c]pyridazin-5(6H)-ones is described including a one-step Mannich-type reaction followed by intramolecular ring closure of ethyl 3-methylpyridazine-4- carboxylate and aldimines, catalysed by the Lewis acid Cu(OTf)2 under microwave heating. This synthesis opens up possibilities to access this unexplored scaffold for medicinal chemistry

Synthesis of Optically Active Bifunctional Building Blocks through Enantioselective Copper-Catalyzed Allylic Alkylation Using Grignard Reagents

Enantioselective copper-catalyzed allylic alkylations were performed on allylic bromides with a protected hydroxyl or amine functional group using several Grignard reagents and Taniaphos L1 as a ligand. The terminal olefin moiety in the products was transformed into various functional groups without racemization, providing facile access to a variety of versatile bifunctional chiral building blocks.

Preparation, characterization and application of a molecularly imprinted polymer for selective recognition of Sulpiride

A novel molecular imprinting polymer (MIP) was prepared by bulk polymerization using sulpiride as the template molecule, itaconic acid (ITA) as the functional monomer and ethylene glycol dimethacrylate (EGDMA) as the crosslinker. The formation of the MIP was determined as the molar ratio of sulpiride-ITA-EGDMA of 1:4:15 by single-factor experiments. The MIP showed good adsorption property with imprinting factor α of 5.36 and maximum adsorption capacity of 61.13 μmol/g, and was characterized by scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FT-IR) and surface area analysis. With the structural analogs (amisulpride, tiapride, lidocaine and cisapride) and small molecules containing a mono-functional group (p-toluenesulfonamide, formamide and 1-methylpyrrolidine) as substrates, static adsorption, kinetic adsorption, and rebinding experiments were also performed to investigate the selective adsorption ability, kinetic characteristic, and recognition mechanism of the MIP. A serial study suggested that the highly selective recognition ability of the MIP mainly depended on binding sites provided by N-functional groups of amide and amine. Moreover, the MIP as solid-phase extractant was successfully applied to extraction of sulpiride from the mixed solution (consisted of p-toluenesulfonamide, sulfamethoxazole, sulfanilamide, p-nitroaniline, acetanilide and trimethoprim) and serum sample, and extraction recoveries ranged from 81.57% to 86.63%. The tentative tests of drug release in stimulated intestinal fluid (pH 6.8) demonstrated that the tablet with the MIP–sulpiride could obviously inhibit sulpiride release rate. Thus, ITA-based MIP is an efficient and promising alternative to solid-phase adsorbent for extraction of sulpiride and removal of interferences in biosample analysis, and could be used as a potential carrier for controlled drug releas

Kinetics of dopamine oxidation by sodium N-bromo-p-toluenesulphonamide in acid medium. A mechanistic approach

The oxidation kinetics of dopamine (DPM) by sodium N-bromo-p-toluenesulphonamide (bromamine-T or BAT) was investigated at 40°C in HClO4 medium. The rate is first order in BAT0, fractional order in DPM0 and inverse fractional in H+. Addition of reaction product, p-toluenesulphonamide, or halide ions and variation of ionic strength of the medium have no significant effect on the rate. The dielectric effect is positive. The solvent isotope effect has been studied in D2O medium. The reaction fails to induce the polymerisation of acrylonitrile. The Michaelis-Menten type of kinetics is observed. Activation parameters for the overall reaction and also for the rate-limiting step were computed. Dopa-o-quinone or 2-(3â²4â²-benzoquinone) ethylamine was identified as the oxidation product of DPM. A mechanism consistent with the observed kinetics is proposed and discussed

Oxidation of some catecholamines by sodium N-chloro-p-toluenesulfonamide in acid medium: A kinetic and mechanistic approach

The kinetics of the oxidation of five catecholamines viz., dopamine (A), L-dopa (B), methyldopa (C), epinephrine (D) and norepinephrine (E) by sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in presence of HClO 4 was studied at 30 ± 0.1 °C. The five reactions followed identical kinetics with a first-order dependence on CAT o, fractional-order in substrate o, and inverse fractional-order in H +. Under comparable experimental conditions, the rate of oxidation of catecholamines increases in the order D > E > A > B > C. The variation of ionic strength of the medium and the addition of p-toluenesulfonamide or halide ions had no significant effect on the reaction rate. The rate increased with decreasing dielectric constant of the medium. The solvent isotope effect was studied using D 2O. A Michaelis-Menten type mechanism has been suggested to explain the results. Equilibrium and decomposition constants for CAT-catecholamine complexes have been evaluated. CH 3C 6H 4SO 2NHCl of the oxidant has been postulated as the reactive oxidizing species and oxidation products were identified. An isokinetic relationship is observed with β = 361 K, indicating that enthalpy factors control the reaction rate. The mechanism proposed and the derived rate law are consistent with the observed kinetics. © Central European Science Journals. All rights reserved

Oxidation of tricyclic antidepressant drugs with chloramine-T in acidic solutions: Kinetic, mechanistic and thermodynamic studies

The kinetics of the oxidation of two tricyclic antidepressants (TCA) namely, imipramine (IMP) and clomipramine (CLM) with sodium N-chloro-p-toluenesulfonamide or chloramine-T (CAT) in HClO4 medium was studied at 300 K. The two reactions followed identical kinetics with a first-order dependence of rate on CATo and fractional order dependence on TCAo. The reaction is catalyzed by H+ ions with a fractional order dependence. The reaction was studied at different temperatures and activation parameters were evaluated. The reaction constants involved in the mechanism were computed. The solvent isotope effect was studied using D2O. Addition of p-toluenesulfonamide retards the reaction rate. The rate increased with decreasing dielectric constant of the medium. Variation of ionic strength of the medium and addition of halide ions (Cl- or Br-) showed no effect on the rate. The stoichiometry of the reaction was found to be 1:1 and the oxidation products were identified as imipramine-5-N-oxide and clomipramine-5-N-oxide. The rate of oxidation of IMP is faster than CLM. The observed results have been explained in terms of a mechanism and a relevant rate law has been deduced. © 2013 Sukhdev and Puttaswamy; licensee Springer

Oxazoline Promoted Rh-Catalyzed C-H Amidation of Benzene Derivatives with Sulfonamides and Trifluoroacetamide. A Comparative Study.

A Rh-catalyzed ortho-amidation of 2-aryloxazolines offers an efficient and direct route to a range of sulfonamides. The scope of the reaction is very broad with respect to sulfonamide substrate, but the position and electronic nature of the substituents on the aryl moiety of the oxazoline lead to a surprising modulation of reactivity. The reactivity of sulfonamides in comparison to trifluoroacetamide is compared, the latter undergoing Rh-catalyzed amidation more rapidly

Improved catalytic activity of ruthenium–arene complexes in the reduction of NAD+

A series of neutral Ru-II half-sandwich complexes of the type [(eta(6)-arene)Ru(N,N')Cl] where the arene is para-cymene (p-cym), hexamethylbenzene (hmb), biphenyl (bip), or benzene (bn) and N,N' is N-(2-aminoethyl) -4-(trifluoromethyl)benzenesulfonamide (TfEn), N-(2-aminoethyl)-4-toluenesulfonamide (TsEn), or N-(2-aminoethyl)-methylenesulfonamide (MsEn) were synthesized and characterized. X-ray crystal structures of [(p-cym)Ru(MsEn)Cl] (1), [(hmb)Ru(TsEn)Cl] (5), [(hmb)Ru(TfEn)Cl] (6), [(bip)Ru(MsEn)Cl] (7), and [(bip)Ru(TsEn)Cl] (8) have been determined. The complexes can regioselectively catalyze the transfer hydrogenation of NAD(+) to give 1,4-NADH in the presence of formate. The turnover frequencies (TOF) when the arene is varied decrease in the order bn > bip > p-cym > hmb for complexes with the same N,N' chelating ligand. The TOF decreased with variation in the N,N' chelating ligand in the order TfEn > TsEn > MsEn for a given arene. [(bn)Ru(TfEn)Cl] (12) was the most active, with a TOP of 10.4 h(-1). The effects of NAD(+) and formate concentration on the reaction rates were determined for [(p-cym)Ru(TsEn)Cl] (2). Isotope studies implicated the formation of [(arene)Ru(N,N')(H)] as the rate-limiting step. The coordination of formate and subsequent CO2 elimination to generate the hydride were modeled computationally by density functional theory (DFT). CO2 elimination occurs via a two-step process with the coordinated formate first twisting to present its hydrogen toward the metal center. The computed barriers for CO2 release for arene = benzene follow the order MsEn > TsEn > TfEn, and for the Ms En system the barrier followed bn < hmb, both consistent with the observed rates. The effect of methanol on transfer hydrogenation rates in aqueous solution was investigated. A study of pH dependence of the reaction in D2O gave the optimum pH* as 7.2 with a TOF of 1.58 h(-1) for 2. The series of compounds reported here show an improvement in the catalytic activity by an order of magnitude compared to the ethylenediamine analogues

Visible-Light Photocatalysed Cyanation of Benzylic C−H Bonds

Visible light-driven single-electron transfer-based direct cyanation of benzylic C-H bond with non-toxic N-Cyano-N-phenyl-p-toluenesulfonamide (NCTS) has been proposed using 4CzIPN, a widely used and affordable substitute for metal catalysts. The aforementioned method offers broad functional group tolerance, extensive substrate scope, excellent yields, and mild reaction conditions. This green and sustainable photocatalytic hydrogen atom transfer method can be applicable for the diversified functionalization of a variety of native C–H bonds