Solid-liquid Phase Transfer Catalysis Research Articles

Experimental and theoretical investigations for novel 6-nitroquinoxaline-2,3‑dione derivatives: Synthesis, characterization, DFT calculations, ADME analysis, hirshfeld surface calculations, molecular docking studies, and antiproliferation evaluation

This work describes the synthesis of eight different 6-nitro-1,4-disubstituted-quinoxaline-2,3‑dione derivatives (4a-h). The starting material, 6-nitroquinoxaline-2,3‑dione 3 was prepared by reacting 4-nitro-o-phenylenediamine 1 with oxalic acid 2 at reflux in hydrochloric acid. Compound 3 was alkylated with various alkyl halides under solid-liquid phase transfer catalysis (PTC) to give the dialkyl quinoxalines (4a-h). The structures of all compounds obtained were elucidated based on spectroscopic measurements: 1H, 13C NMR, MS and UV spectroscopy and confirmed by single-crystal X-ray diffraction studies in the case of 4a, 4b, 4f, and 4h. The geometrical parameters and spectral data were also compared with those of a DFT geometry optimization and molecular orbital calculation at the B3LYP/6–311++G (d, p) level of theory. The closest contacts between the molecules of the four structures were investigated by analyzing their Hirshfeld surfaces and docking investigations in the protein EGFR (pdbid: 4HJO). Moreover, the experimental results are correlated to the calculated ones and showed great compatibility. Cell proliferation was used to measure the immunomodulatory activity of 4a-h compared to a control consisting only of normal cells cultured alone to determine their antiproliferative screening which concluded that the quinoxaline derivatives 4c, 4d, 4f and 4g showed immunomodulatory potential.

Synthesis of 3,4-Dihydropyridin-2-ones via Domino Reaction under Phase Transfer Catalysis Conditions

3,4-dihydropyridin-2-ones are of considerable importance due to the large number of these core structures exhibiting a diverse array of biological and pharmacological activities. The Michael-type addition of 1,3-dithiane-2-carbothioates to α,β-unsaturated N-tosyl imines, followed by intramolecular annulation driven by a sulfur leaving group, provides a practical reaction cascade for the synthesis of a variety of substituted 3,4-dihydropyridin-2-ones. In this work, the reaction was carried out under solid–liquid phase transfer catalysis (SL-PTC) conditions at room temperature, in short reaction times in the presence of cheap Bu4N+HSO4– and solid KOH. The new PTC method exhibited adequate functional group tolerance, proving to be a green and reliable method and easy to scale up to furnish rapid access to 3,4-dihydropyridin-2-ones after desulfurization from simple, readily available starting materials.

Reactions of Sodium Diisopropylamide: Liquid-Phase and Solid-Liquid Phase-Transfer Catalysis by N,N,N',N″,N″-Pentamethyldiethylenetriamine.

Sodium diisopropylamide (NaDA) in N,N-dimethylethylamine (DMEA) and DMEA-hydrocarbon mixtures with added N,N,N',N″,N″-pentamethyldiethylenetriamine (PMDTA) reacts with alkyl halides, epoxides, hydrazones, arenes, alkenes, and allyl ethers. Comparisons of PMDTA with N,N,N',N'-tetramethylethylenediamine (TMEDA) accompanied by detailed rate and computational studies reveal the importance of the trifunctionality and κ2-κ3 hemilability. Rate studies show exclusively monomer-based reactions of 2-bromooctane, cyclooctene oxide, and dimethylresorcinol. Catalysis with 10 mol % PMDTA shows up to >30-fold accelerations (kcat > 300) with no evidence of inhibition over 10 turnovers. Solid-liquid phase-transfer catalysis (SLPTC) is explored as a means to optimize the catalysis as well as explore the merits of heterogeneous reaction conditions.

Fiber-Supported Poly(quaternaryammonium Bromide)s as Supported-Phase Transfer Catalysts in the Spinning Basket Reactor

In this paper, a newly developed fiber-supported poly(quaternaryammonium bromide)s, which served as an efficient and recyclable supported phase-transfer catalyst in the spinning basket reactor for a series of nucleophilic substitutions, is reported. The fiber catalysts were designed and synthesized systematically from commercially available polyacrylonitrile fiber, and the properties of fiber samples at different stages were characterized in detail by sorts of technologies. Moreover, the nucleophilic substitutions mediated with fiber-supported phase-transfer catalyst exhibited high efficiency to afford a range of substituted products in excellent yields (91–98%) under mild conditions, and on this basis, a solid–liquid phase-transfer catalysis mechanism was proposed. Markedly, the spinning basket reactor with fiber catalyst in its impellers revealed prominent recyclability at least for 15 cycles, and the concise method of operation also exerted a good perspective application in chemical industry.

Insight into solid-liquid phase transfer catalyzed synthesis of Mecoprop ester using $$\hbox {K}_{2}\hbox {CO}_{3}$$ K 2 CO 3 as base and development of new kinetic model involving liquid product and two solid co-products

2-Methyl-4-chlorophenoxy propionic acid (Mecoprop) is a widely used household herbicide. In the current work, a simple synthetic method is developed for Mecoprop methyl ester using solid-liquid phase transfer catalysis (S-L PTC) with $$\hbox {K}_{2}\hbox {CO}_{3}$$ as mild base and toluene as solvent. Conversion of 95% was achieved with 100% selectivity for Mecoprop ester at $$100\,{^{\circ }}\hbox {C}$$ . Simple isolation process was employed to recover the product from the reaction mixture. A reaction mechanism was proposed and new kinetic model developed involving one liquid and two solid co-products. The activation energy for the reaction was calculated. This is the first example of its kind being reported vis-a-vis kinetics and mechanism. Solid-liquid phase transfer catalyzed (S-L PTC) O-alkylation of 4-chloro-2-methyl phenol is done at relatively mild conditions to form methyl 2-(4-chloro-2-methylphenoxy) propionate (Mecoprop methyl ester). New insight on reaction mechanism and kinetics is presented.

Regioselective O-Sulfonylation of N,N-Bis(2-hydroxyalkyl)tosylamides as a Synthetic Key Step to Enantiopure Morpholines.

The synthesis of enantiopure 2,6-disubstituted morpholines was realized through sequential ring opening of two different optically pure oxiranes by a tosylamide, under solid-liquid phase-transfer catalysis (SL-PTC) conditions, mono-O-sulfonylation of the resulting tosylamido-2,2'-diol, and cyclization to the morpholine. The crucial step, the regioselective formation of the monosulfonate, was controlled by taking advantage of the different stereo, electronic, and coordination properties of the oxirane-derived side chains in the diol backbone. As an application of this protocol, a new morpholine-3-carboxamide was synthesized starting from threonine.

Selective synthesis of 1-(1-naphthyloxy)-2,3-epoxypropane from 1-naphthol and epichlorohydrin under solid–liquid phase transfer catalysis: a waste minimization strategy

Selective organic transformation is a basic theme which needs to be followed to have a waste free, clean and green process. Phase transfer catalysis (PTC) is a synthetic technique that satisfies this criterion very well in which reaction rates and selectivities are enhanced by several folds, thereby decreasing processing costs and hazardous conditions. Solid–liquid (S–L) PTC is better than liquid–liquid (L–L) PTC since the rates of reactions are intensified by order(s) of magnitude and total selectivity can be obtained due to suppression of aqueous-phase reactions. 1-(1-Naphthyloxy)-2,3-epoxypropane is an intermediate in the synthesis of β-blocker drugs propranolol and nadolol. In the current work, synthesis of 1-(1-naphthyloxy)-2,3-epoxypropane was carried out by the reaction of 1-naphthol and epichlorohydrin by using a variety of phase transfer catalysts among which tetra-n-butyl ammonium bromide (TBAB) was the best catalyst at 70 °C under S–L PTC. The effects of various parameters affecting the conversion and initial rates of O-alkylation were studied to establish kinetics and mechanism. Selectivity of 100% for 1-(1-naphthyloxy)-2,3-epoxypropane was observed. The reaction followed pseudo-first-order kinetics. S–L PTC is a waste minimization strategy since no by-products are formed and the process is intensified reducing reactor volume and processing time.

Synthesis and kinetic study of N-(1-methyl-3-phenyl-propane)-phthalimide (NP) by phase-transfer catalysis assisted by ultrasound irradiation

Synthesis of N-(1-methyl-3-phenyl-propane)-phthalimide (NP) was successfully carried out by reacting the potassium phthalimide (PPK) with 2-bromo-1-phenyl propane by using solid–liquid phase-transfer catalysis under nitrogen atmosphere. The effects of agitation rate, reactant concentrations, solvents, catalysts and temperature on the conversion are investigated in the sequence to find the optimum operating environments for this NP formation. It has been found that agitation speed does not affect the reaction once it exceeds 1000 rpm. The apparent reaction rate was first order for the selected reaction.

CHARACTERIZATION AND ANTIMICROBIAL STUDIES OF FIVE SUBSTITUTED BIS-THIOUREAS

Thioureas play an important role in medicinal chemistry and agricultures due to their biological activity such as antibacterial, antifungal, antiviral, herbicides, rodenticides, phenoloxidase enzymatic inhibitors, anti-HIV and anti-tumor agents. In this study, five substituted bis-thioureas have been synthesized. The isophataloyl chloride and 2,6pyridinedicarbonyl dichloride were easily converted to bis-isothiocyanate compound via the reaction with ammonium thiocyanate by solid–liquid phase transfer catalysis of polyethylene glycol-400 (PEG-400). Bis-isothiocyanate compound was reacted with aniline derivatives to produce substituted bis-thioureas in good yield at room temperature. All the novel compounds were obtained as yellow solid after recrystallization using DMF/EtOH/H2O. Their c h e m i c a l structures were confirmed by Infrared spectrosopy (IR), Nuclear Magnetic Resonance (NMR) H and C and mass spectrometry. The five synthesized compounds were screened for antimicrobial activities using disc diffusion method for antimicrobial activity against Gram-positive bacteria (Bacillus Subtilis and Staphylococcus Aureus), Gram-negative bacteria (Escherichia Coli and Salmonella Typhi) and a mold (Aspergillus Niger). All tested compounds showed low antimicrobial activity since the diameter of inhibition zone (IZ) measure was less than positive control inhibition zone.

The novel synthetic route of 3,5-dimethyl-1-(3-phenylpropyl)-1H-pyrazole under solid–liquid phase transfer catalysis conditions assisted by an ultrasound application—A study of some kinetic parameters

The kinetic study for synthesis of 3,5-dimethyl-1-(3-phenylpropyl)-1H-pyrazole was studied successfully by reacting the 3,5-dimethyl pyrazole with 1-bromo-3-phenyl propane under phase transfer catalysis and ultrasonic irradiation conditions using aqueous solution of NaOH (5 g or 0.25 g/ml), excess amount of bromobenzene and tetrahexyl ammonium bromide as a phase transfer catalyst. The reaction was carried out at 40 °C under pseudo-first order conditions and was monitored by gas chromatography (GC). Kinetic reaction found to follow ‘pseudo first order’ rate law. From the experimental data, a rate expression had been developed to explain the kinetic behavior of the reaction from which the apparent rate constant (kapp) of the organic phase was attained. The effects of agitation speed, amount of sodium hydroxide, effect of quaternary ammonium salts, amount of catalyst and temperature on the reaction were also studied.

ChemInform Abstract: A New Approach to 4,6‐Disubstituted‐3,4‐dihydropyran‐2‐ones by Domino Michael Addition‐Cyclization Reaction under PTC Conditions.

AbstractThe new domino process allows the preparation of dithioacetals (III).

A new approach to 4,6-disubstituted-3,4-dihydropyran-2-ones by Domino Michael addition-cyclization reaction under PTC conditions

Domino Michael addition-cyclization reactions of α,β-unsaturated carbonyl compounds with activated 1,3-dithiane-2-carbothioate esters under solid-liquid phase transfer catalysis conditions provide 4,6-disubstituted-3,4-dihydropyran-2-one-3,3-dithioacetals in good chemical yield. Desulfurization proceeds chemoselectively under mild conditions affording 3,4-dihydropyran-2-ones in high yields.

Synthesis of 3,5-dimethyl-1-prop-2-enylpyrazole under solid–liquid phase transfer catalytic conditions assisted by ultrasonic irradiation—A kinetic study

The synthesis of 3,5-dimethyl-1-prop-2-enylpyrazole was successfully carried out by reacting the 3,5-di-methyl pyrazole with 3-bromoprop-1-ene in small amount of KOH and organic solvent solid–liquid phase medium under phase transfer catalysis (PTC) and almost anhydrous conditions assisted by the ultrasonic irradiation in the 5h at 50°C. The main target of this carried work was to provide evidence that the reaction conditions by investigation of the kinetic behaviour, activation energy, reaction mechanism and the related parameters in the solid–liquid PTC reaction besides on to reduce time and temperature of reaction. A rational mechanism for the reaction has been derived base on the experimental result. This kinetic reaction follows pseudo first order rate law. A rate expression had developed to explain the kinetic behaviours from which the apparent rate constant (kapp) of the organic-phase reaction was obtained via investigated data. Kinetics of the reaction, including the effects of agitation speed, quantity of potassium hydroxide, quantity of water, temperature, quantity of tetraoctylammonium bromide (TOAB), volume of cyclohexanone, quarternary ammonium salts and organic solvents on the conversion of RBr and the apparent rate constant (kapp) were investigated in full length. Rational explanations for the resulting phenomena are also provided.

ChemInform Abstract: 1,2,3‐Trimethoxypropane and Glycerol Ethers as Bio‐Sourced Solvents from Glycerol. Synthesis by Solvent‐Free Phase‐Transfer Catalysis and Utilization as an Alternative Solvent in Chemical Transformations.

Byline: Marc Sutter, Wissam Dayoub, Estelle Metay, Yann Raoul, Marc Lemaire Keywords: alkylation; Ci[pounds sterling] C coupling; glycerol; green chemistry; phase-transfer catalysis; transesterification Abstract 1,2,3-Trimethoxypropane (2), 1-alkoxy-2,3-dimethoxy-propanes, and 1-aryloxy-2,3-dimethoxypropanes were prepared in good yields and selectivity by solid-liquid phase-transfer catalysis in the presence of an inorganic base and an ammonium salt as the phase-transfer catalyst with no additional solvent. No heating was required, and the synthesis was easily performed under atmospheric pressure on a 150ag scale. For the preparation of 2, the conversion of glycerol was complete and the selectivity for the expected glycerol trimethylether was above 95%. This product was utilized as a solvent in organic reactions such as transesterifications between glycerol and vegetable oil, organometallic reactions (Grignard- and Barbier-type reactions), carbon-carbon coupling reactions (Suzuki, Sonogashira, Heck), and in etherification reactions by dehydrogenative alkylation. The solvent showed interesting properties for the solubilization of polymers. Author Affiliation: Laboratoire de Catalyse, Synthese et Environnement (CASYEN), Groupe Lemaire, Institut de Chimie et Biochimie Moleculaires et Supramoleculaires (ICBMS), CNRS. UMR5246, Universite Lyon 1, Batiment Curien-CPE, 3[degrees] etage 43 Bd du 11 Novembre 1918, 69622, Villeurbanne Cedex (France), Fax: (+33)472431408 Sofiproteol, 11, rue de Monceau, CS 60003, 75378 Paris Cedex 08 (France) Laboratoire de Catalyse, Synthese et Environnement (CASYEN), Groupe Lemaire, Institut de Chimie et Biochimie Moleculaires et Supramoleculaires (ICBMS), CNRS. UMR5246, Universite Lyon 1, Batiment Curien-CPE, 3[degrees] etage 43 Bd du 11 Novembre 1918, 69622, Villeurbanne Cedex (France), Fax: (+33)472431408 Supporting information: Additional Supporting Information may be found in the online version of this article As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. CAPTION(S): miscellaneous_information

Synthesis and Bioactivity of Some Novel 5-Arylmethylideneamino-1,3,4-Thiadiazole-2- Ylthioacetanilide Derivatives

Some novel of 5-arylmethylideneamino-1,3,4-thiadiazole-2-ylsulfanyl acetamide derivatives were synthesized by the S-alkylation of 5-arylmethylideneamino-2-mercapto-1,3,4-thiadiazoles with chloroacetyl anilide under solid–liquid phase transfer catalysis using polyethylene glycol-400 (PEG-400) catalyst in the presence of potassium carbonate. Some of the title compounds were investigated for plant growth-regulating activity. They were found to enhance root elongation remarkably at a low concentration. [Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the following free supplemental files: Additional figures and tables].

Esterification of sodium 4-hydroxybenzoate by ultrasound-assisted solid–liquid phase-transfer catalysis using dual-site phase-transfer catalyst

The catalytic esterification of sodium 4-hydroxybenzoate with benzyl bromide by ultrasound-assisted solid–liquid phase-transfer catalysis (U-SLPTC) was investigated using the novel dual-site phase-transfer catalyst 4,4′-bis(tributylammoniomethyl)-1,1′-biphenyl dichloride (BTBAMBC), which was synthesized from the reaction of 4,4′-bis(chloromethyl)-1,1′-biphenyl and tributylamine. Without catalyst and in the absence of water, the product yield at 60°C was only 0.36% in 30min of reaction even under ultrasound irradiation (28kHz/300W) and 250rpm of stirring speed. When 1cm3 of water and 0.5mmol of BTBAMBC were added, the yield increased to 84.3%. The catalytic intermediate 4,4′-bis(tributylammoniomethyl)-1,1′-biphenyl di-4-hydroxybenzoate was also synthesized to verify the intrinsic reaction which was mainly conducted in the quasi-aqueous phase locating between solid and organic phases. Pseudo-first-order kinetic equation was used to correlate the overall reaction, and the apparent rate coefficient with ultrasound (28kHz/300W) was 0.1057min−1, with 88% higher than that (0.0563min−1) without ultrasound. The esterification under ultrasonic irradiation using BTBAMBC by solid–liquid phase-transfer catalysis was developed.

Kinetics and mechanism of Horner–Wadsworth–Emmons reaction of weakly acidic phosphonate in solid–liquid phase-transfer catalysis system

Homer–Wadsworth–Emmons (HWE) reaction of diethyl benzylphosphonate (DEBP, pKa = 27.55) with aldehyde was performed in a solid–liquid phase-transfer catalysis (SL–PTC) system using sodium hydroxide as the solid phase. Various parameters that influenced the pseudo-first-order rate constant including stirring speed, catalysts, salt, water and temperature were investigated to explore the process of the generation and transfer of the active intermediate. A reasonable interfacial mechanism of the PTC reaction of the weakly acidic substrate was proved for the first time. HWE reactions under SL–PTC conditions showed high activity and geometric selectivity. It is anticipated that this simple and controllable synthesis method should provide a new idea for HWE reaction in chemical industry. • HWE reaction of weakly acidic phosphate was developed in SL-PTC system. • The reaction kinetics was investigated under the pseudo-first-order conditions. • The interfacial mechanism for SL-PTC reaction of weakly acidic substrate was proved. • This reaction showed high activity and geometric selectivity at low temperatures.

Design, synthesis and antiproliferative properties of some new 5-substituted-2-iminobenzimidazole derivatives

Some new 1,3,5-substituted-2,3-dihydro-2-imino-benzimidazoles were synthesized under solid–liquid phase transfer catalysis conditions using 5-substituted-2-aminobenzimidazoles as precursors in order to assess their cytotoxicity respectively proliferative activity. The structures of the compounds were confirmed by IR, 1H NMR, 13C NMR and elemental analysis.Compounds 9–10, 12 and 16–17 were evaluated for their cytotoxical effect on four cancer cell lines: HT-29, breast cancer cells MDA-MB-231, HeLa, HepG2 and as well as human diploid cell line Lep-3.Significant cytotoxicity of hydrazone 16 against MDA-MB-231 was established by biologically study, the IC50 was 6.2 nM while the EC50 value to Lep 3 is 0.21 nM. Relative high antiproliferative effects of the acetate 12 and compound 16 against HT-29 were ascertained and the calculated IC50 values were IC50 – 0.85 nM and IC50 – 2.83 nM respectively. Cytotoxic activity against HeLa and HepG2 cells was demonstrated by hydrazone 17, IC50 was 7.2 nM and 117 nM respectively. All tested compounds revealed proliferative activities to human diploid cell line Lep-3. The EC50 values were in the range from 0.05 to 16.91 nM. The obtained results prove the selective cytotoxicity of the tested compounds and are promising for further evaluation of the investigated compounds in vivo experiments using experimentally induced tumors in laboratory animals.

ChemInform Abstract: Use of Diethoxymethane as a Solvent for Phase‐Transfer Esterification of Carboxylic Acids.

Abstract The esterification of carboxylic acids with selected primary alkyl halides in diethoxymethane (DEM) utilizing solid–liquid phase-transfer catalysis has been studied. The use of DEM as the solvent simplifies the process in that a single solvent can be used for both reaction and workup.

Synthesis of New Phosphorus-Containing (Co)Polyesters Using Solid-Liquid Phase Transfer Catalysis and Product Characterization

This paper is directed towards the development of safe, and thermally stable solid polymer electrolytes. Linear phosphorus-containing (co)polyesters are described, including their synthesis, thermal analysis, conductivity, and non-flammability. Polycondensation of phenylphosphonic dichloride (PPD) with poly(ethylene glycol) (PEG 12000) with and without bisphenol A (BA) was carried out using solid-liquid phase transfer catalysis. Potassium phosphate is used as base. Yields in the range of 85.0–88.0%, and inherent viscosities in the range of 0.32–0.58 dL/g were obtained. The polymers were characterized by gel permeation chromatography, FT-IR, 1H- and 31P-NMR spectroscopy and thermal analysis. Their flammability was investigated by measuring limiting oxygen index values. The polymers are flame retardants and begin to lose weight in the 190 °C–231 °C range. Solid phosphorus- containing (co)polyesters were complexed with lithium triflate and the resulting ionic conductivity was determined. Conductivities in the range of 10−7–10−8 S cm−1 were obtained.