Phase Transfer Catalyzed Reactions Research Articles

Ultrasound and Two Active Site Phase-Transfer Catalyst Effect in Asymmetry Synthesis: A Kinetic Study

The phase transfer catalyst 1-benzyl-1,4-diazoniabicyclo[2.2.1]hepta-2,4(7)-dienedichloride (BDHDC) in organic chiral synthesis was used in this study. Kinetic parameters such as ultrasonication effect, phase transfer catalyst dose, solvents, butyl chloride volume, stirring speed and weight of KOH were examined for the phase transfer catalytic reactions. The reaction between phenyl acetonitrile and butyl chloride was carried out under basic conditions and ultrasonic irradiation (300 W, 40 kHz) using BDHDC as a phase transfer catalyst. The introduction of BDHDC catalyst significantly improved the overall reaction, resulting in a high yield of the chiral combination. The product formation has been optimized by modifying the kinetic parameters.

Ionic Liquids: Advances and Applications in Phase Transfer Catalysis

Ionic liquids are a family of liquids that are composed entirely of ions and usually have melting points lower than 100 °C. Extensive research, along with the ever-growing interest of the scientific community, allowed for the development of a multitude of ionic liquids with low melting points. Such compounds are considered neoteric materials as well as ideal, custom-made solvents for a variety of different chemical transformations. In this regard, the importance of phase transfer catalysis is evident in a diversity of substrates and reactions. The use of phase transfer catalysts allows the reaction to proceed, facilitating the transfer of otherwise insoluble reactants to the desired phase. Recent scientific advances led to the emergence of ionic liquids, which are excellent candidates as phase transfer catalysts. The inherent fine-tuning capability of these molecules, along with the potential of phase transfer catalytic reactions, epitomize the sustainable aspect of this field of research. Herein, a cohesive report of such applications will be presented, including the period from the last decade of the 20th century up to date.

Chemical modification of edible sodium caseinate: A new grafting method of oleic acid. Characterization and thermal properties of the conjugate

Sodium caseinate is a well-known amphiphilic protein derived from natural products currently used for the preparation of edible films. To improve some properties, especially to decrease the hydrophilicity and water solubility of the caseinate, the covalent grafting of a hydrophobic edible fatty acid, namely oleic acid, onto caseinate, appears to be a solution. We describe a new synthesis method for the chemical modification of sodium caseinate involving the synthesis of an acid chloride derivative from oleic acid and a phase transfer catalysis reaction in a biphasic medium. Under these conditions, free amine and alcohol groups of the caseinate are likely to be grafted with a fairly high (>50 %) substitution degree. The caseinate derivative is finely characterized, in particular by DOSY NMR, to assess the formation of a casein/oleic acid grafted compound as well as the absence of residual oleic acid.

Quaternary ammonium salt functionalized polyetheretherketone fiber: A novel fibrous material for phase-transfer catalysis

Herein, the commercially available ultra-high-strength textile fiber polyetheretherketone (PEEK) was directionally functionalized by afterward immobilization procedures to graft quaternary ammonium salts into its surface layer, and the resulted fibrous materials were capable of acting as the heterogeneous-supported phase-transfer catalysts were presented in the etherification of halogenated nitrobenzenes for the synthesis of nitroanisoles. The acquiring fiber samples from different processes were observed and characterized detailedly by diversified technologies of morphologies, mechanical properties, elemental analysis, FTIR spectroscopy, X-ray diffraction, and thermogravimetric analysis to confirm the reliability of this methodology. Moreover, the effect of functionalized degree on the PEEK fiber was inspected, and the phase-transfer catalytic system mediated by the fibrous material showed superior performance in terms of simple procedures, high yields of nitroanisoles (up to 99%), and excellent recyclability (over 30 cycles). Additionally, the newly developed fibrous catalyst exhibited superior stability (at least for 4 months) and effectively gram-scale operation in a concise spinning basket reactor, which is very attractive for various phase-transfer catalysis reactions in chemical productions.

Synthesis of Galectin Inhibitors by Regioselective 3'-O-Sulfation of Vanillin Lactosides Obtained under Phase Transfer Catalysis.

Vanillin-based lactoside derivatives were synthetized using phase-transfer catalyzed reactions from per-O-acetylated lactosyl bromide. The aldehyde group of the vanillin moiety was then modified to generate a series of related analogs having variable functionalities in the para- position of the aromatic residue. The corresponding unprotected lactosides, obtained by Zemplén transesterification, were regioselectively 3′-O-sulfated using tin chemistry activation followed by treatment with sulfur trioxide-trimethylamine complex (Men3N-SO3). Additional derivatives were also prepared from the vanillin’s aldehyde using a Knoevenagel reaction to provide extended α, β-unsaturated carboxylic acid which was next reduced to the saturated counterpart.

Interfacial Processes—The Key Steps of Phase Transfer Catalyzed Reactions

After short historical introduction, interfacial mechanism of phase transfer catalyzed (PTC) reactions of organic anions, induced by aqueous NaOH or KOH in two-phase systems is formulated. Subsequently experimental evidence that supports the interfacial deprotonation as the key initial step of these reactions is presented.

Design and Development of Novel Continuous Flow Stirred Multiphase Reactor: Liquid–Liquid–Liquid Phase Transfer Catalysed Synthesis of Guaiacol Glycidyl Ether

Phase transfer catalysed (PTC) reactions are used in several pharmaceutical and fine chemical industrial processes. We have developed a novel stirred tank reactor (Yadav reactor) to conduct batch and continuous liquid–liquid–liquid (L-L-L) PTC reactions. The reactor had a provision of using three independent stirrers for each phase, thereby having complete control over the rate of mass transfer across the two interfaces. In the continuous mode of operation, the top and bottom phases were continuously fed into the reactor while the middle phase was used as a batch. All three stirrers were used independently, thereby having independent control of mass transfer resistances. The reactor in a batch mode showed higher conversion and selectivity compared to a conventional batch reactor. L-L-L PTC reaction in the continuous mode was successfully performed without loss of the middle catalyst phase and with steady conversion and selectivity. The reaction of guaiacol with epichlorohydrin was conducted as a model reaction, with a 76% conversion of epichlorohydrin, 85% selectivity of guaiacol glycidyl ether, and the middle catalyst phase was stable throughout the process.

Understanding phase-transfer catalytic synthesis of fullerenol and its interference from carbon dioxide and ozone

Phase-transfer catalytic reaction involving the use of tetrabutylammonium hydroxide (TBAH) as catalyst and sodium hydroxide (NaOH) solution as the source of hydroxide ions is among the popular choices for synthesis of fullerenol, the polyhydroxylated fullerene. To further understand the process, two experiments were conducted to preliminarily explore the influences of the amount of TBAH and NaOH, respectively, in terms of the achieved level of hydroxylation (i.e. number of hydroxyl groups per fullerenol molecule). The process responded to the variation of the amount of TBAH (over a twofold series of 3–192 drops, average volume 0.0223 ± 0.0004 ml per drop) in a nonlinear manner with a local maximum achieved from 24 drops TBAH (giving 13 OH groups) and a local minimum from 48 drops (giving 8 groups). To the variation of the amount of NaOH (over the range of 0.5–8.0 ml NaOH), the fitted function of the process response resembled Freundlich adsorption isotherm, with an initially increasing trend before levelling off at 4.0 ml NaOH (giving 15 OH groups). It is therefore suggested that fullerene hydroxylation could be explained by liquid–solid adsorption. In addition, it was found that ambient carbon dioxide led to the existence of sodium carbonate in the bulk of the collected product (although not chemically bound). It was also discovered that ambient ozone adversely affected fullerenol synthesis by converting C60 fullerene into fullerene epoxide (C60O). The affected syntheses thus produced epoxide-containing fullerenol instead.

Accelerating Biphasic Biocatalysis through New Process Windows.

Process intensification through continuous flow reactions has increased the production rates of fine chemicals and pharmaceuticals. Catalytic reactions are accelerated through an unconventional and unprecedented use of a high‐performance liquid/liquid counter current chromatography system. Product generation is significantly faster than in traditional batch reactors or in segmented flow systems, which is exemplified through stereoselective phase‐transfer catalyzed reactions. This methodology also enables the intensification of biocatalysis as demonstrated in high yield esterifications and in the sesquiterpene cyclase‐catalyzed synthesis of sesquiterpenes from farnesyl diphosphate as high‐value natural products with applications in medicine, agriculture and the fragrance industry. Product release in sesquiterpene synthases is rate limiting due to the hydrophobic nature of sesquiterpenes, but a biphasic system exposed to centrifugal forces allows for highly efficient reactions.

Synthesis and Antimicrobial Activity of Some New Coumarin and Dicoumarol Derivatives

Phase transfer catalysis reaction of 4-hydroxy-6-methyl-2H-chromen-2-one with alkyl halides afforded C4 oxygen alkylation products of 2H-chromen-2-one derivatives in appreciative yield, whereas with phenyl isothiocyanate gives the C3 addition product of 4-hydroxy-6-methyl-2-oxo-N-phenyl-2H-chromene-3-carbothioamide, also one pot three component phase transfer reaction was investigated. Treatment of 4-hydroxy-6-methyl-2H-chromen-2-one with aromatic aldehydes in different molar ratios gives 3‑arylidine and the dicoumarol derivatives. However pyrano chromene and pyrano pyridine were obtained by reaction of arylidine with ethyl acetoacetate through Michael cycloaddition reaction. The stability of pyrone ring in 3-arylidine and dicoumarol towards different nucleophilic reagents under reflux and/or fusion conditions has been studied by the action of, hydrazine hydrate, ammonium acetate, methyl amine and p-toluidine afforded compounds 1,2-bis(benzo[d][1,3]dioxol-5-ylmethylene)hydrazine, 1,2-bis(4-methoxybenzylidene)hydrazine and 2,6-bis((2,6-dihydroxy-3-methylphenyl)(hydroxy)methylene)-1-(4-methoxyphenyl)-4-(p-tolyl) piperidine-3,5-dione derivatives. The antimicrobial activity of some synthesized compounds has been investigated.

Benzophenone Schiff bases of glycine derivatives: Versatile starting materials for the synthesis of amino acids and their derivatives

This review focuses on the introduction and early development, in solution, of phase-transfer catalyzed (PTC) reactions to afford racemic or enantioenriched natural and unnatural amino acids. To form monosubstituted amino acids alkylation reactions are performed on the benzophenone Schiff base of glycine. For α,α-disubstituted amino acids the activated intermediate is an aldimine derivative of the monosubstituted amino acid. Enantioenriched products are produced by organocatalysis using derivatives of Cinchona alkaloids as the phase-transfer catalyst. Selectivity for monoalkylatation and lack of product racemization depend on the acidities of the glycine imines, and dialkylated products are formed from aldimine esters of monoalkyl amino acids. The racemic and catalytic enantioselective reactions of a cationic glycine equivalent with organoboranes, organometallics and malonate anion are discussed as are other reactions of these versatile Schiff bases derivatives.

Synthesis of α-CF3-proline derivatives by means of a formal (3 + 2)-cyclisation between trifluoropyruvate imines and Michael acceptors.

We herein report the first formal (3 + 2)-cyclisation between 3,3,3-trifluoropyruvate-derived imines and indandione-based Michael acceptors. This reaction gives access to a novel class of spirocyclic α-CF3-α-proline derivatives with complete control of the diastereoselectivity under phase transfer-catalysed reaction conditions.

Macrocyclic Hosts in Asymmetric Phase-Transfer Catalyzed Reactions

The introduction and development of neutral macrocyclic hosts capable of complexing ions within their pre-organized cavity, has been of utmost importance in supramolecular chemistry. Their ability to form stable organic-soluble metal–macrocycle complexes opened up the way to their application in phase-transfer catalysis (PTC) as a viable alternative to quaternary onium salts. In particular, their conformationally rigid preorganized backbone, accommodating organic substrates in defined orientations, promotes highly efficient stereoselective reactions. This short review summarizes the applications of neutral macrocyclic hosts in stereoselective PTC, highlighting the difference and possible complementarity with quaternary ammonium salts.1 Introduction2 Crown Ethers and Related Coronands2.1 Enantioselective PTC with Chiral Macrocyclic Coronands2.2 Enantioselective PTC Reactions Catalyzed by Chiral Quaternary Ammonium Salts with Achiral Crown Ether Co-catalysts3 Cyclic Peptoids4 Miscellaneous Chiral Macrocyclic Hosts5 Summary and Outlook

Interfacial Generation of a Carbanion: The Key Step of PTC Reaction Directly Observed by Second Harmonic Generation.

We present the first unambiguous evidence of the interfacial mechanism of phase-transfer catalysis (PTC) by direct observation of the formation of carbanions in the interfacial region between the aqueous and the organic phase by using a surface-sensitive spectroscopic method known as second harmonic generation (SHG). Ion exchange of carbanions adsorbed at the surface after addition of lipophilic tetraalkylammonium salts (TAA) to organic phase and transport of the lipophilic ion-pairs to the organic phase is observed. Results allow for the formulation of a more detailed mechanism of PTC.

Experimental validation of equilibrium based mathematical modelling of liquid‐liquid phase transfer catalysis

The reaction between two compounds which reside in immiscible phases can be accelerated using a phase transfer catalyst. The catalyst helps to transfer a species ion from one phase to the other phase, thus promoting its reaction. Several mechanisms have been proposed to describe phase transfer catalyzed reactions. In this work, we have carried out an experimental and theoretical study of phase transfer catalysis in batch mode. A mathematical model is developed which helps to predict the progress of the reaction under different operating conditions. Here the different species in the aqueous phase are assumed to be in equilibrium and these react with the species in the organic phase. The effect of diffusional resistance inside the dispersed organic phase is shown to be negligible. The two reaction systems studied are the phase transfer catalyzed (i) thioetherification and (ii) benzyl alcohol oxidation using sodium hypochlorite. Batch experiments were performed to determine the effect of catalyst loading, solvent dilution, and pH. The experimental results show that with an increase in catalyst loading, the phase transfer catalyzed reactions were accelerated. The use of a minimal amount of solvent results in a better performance. Benzyl alcohol oxidation is favoured under low pH conditions. The developed model is able to capture the performance of the system over a wide range of operating conditions accurately.

Synthesis of allyl acrylpimarate by microwave irradiation and phase-transfer catalytic reaction and its UV-curing reactions as a new monomer

The rosin molecules can improve the adhesion and mechanical properties of polymers. It may be introduced either directly or via active functional groups. The focus of this work has been to develop a new method for creating such active functional groups connected to the acrylpimarate molecule by a microwave irradiation and phase-transfer catalytic reaction with allyl chloride. The synthesized monomer was then polymerized under ultraviolet (UV) irradiation. A new polymerization monomer with two functional groups (two allyl groups) has been synthesized through Diels-Alder reaction using levopimaric acid (an important component of rosin) as raw material under microwave irradiation. The yield and gas chromatography on content of the allyl acrylpimarate monomer were 92.2% and 98.6%, respectively. Due to the steric hindrance in the original rosin molecules, two major allyl acrylpimarate isomers in a 1:4 ratio were observed in the monomeric products, as confirmed by two-dimensional nuclear magnetic resonance spectroscopy (2D NMR). UV-curing reaction of the synthesized monomer confirmed that its two functional groups led to a novel polymerization pathway compared with that of the monomer bearing only one allyl group. Conversion of the monomer reached 90% by using Michlers ketone as a photoinitiator. The cured film was composed of a three-dimensional cross-linked polymer due to the bifunctional monomer, and showed good performance in terms of thermal stability, hardness, and chemical resistance.

Recent developments on phase-transfer catalytic reactions under ultrasound irradiation

Abstract The kinetics for various reaction systems were reviewed under the phase-transfer catalysis assisted by ultrasound irradiation conditions. The different factors on the kinetics of the reaction were reviewed. Advantages of chemical reaction under ultrasound irradiation conditions are highlighted. Chemical conversions under phase-transfer catalytic conditions improved the yields. These reactions avoid longer reaction times, enhance the yields of the products and reduce the organic solvent. Development of this methodology and selectivity of various reactions were presented.

A comprehensive theoretical investigation of the transition states and a proposed kinetic model for the cinchoninium ion asymmetric phase-transfer catalyzed alkylation reaction

The discovered that the cinchoninium ion could promote a highly enantioselective alkylation of an indanone enolate via phase-transfer catalysis was a breakthrough in the area asymmetric organocatalysis. However, only recently the mechanism of asymmetric induction was unraveled by theoretical calculations. It was found the process takes place through cooperative catalysis with a key role of the cinchoninum hydroxyl group. In this work, we have done a more detailed investigation of the possible transition states, reporting twenty-four structures. More reliable calculations at MP2 level was applied to the most important species and we have observed that dispersion forces play a very important role to selectively stabilize the critical transition state leading to the main enantiomer. The possible partition equilibria of several species have also been considered and a kinetic model was proposed. We have found the formation of a dimer of the cinchoninium ion takes place and this behavior leads to fractional kinetic order in the catalyst concentration. The theoretical overall kinetics is in very good agreement with the experimental data, with an effective activation free energy barrier deviating by only 1.2kcalmol−1 from the experimentally observed value. This study provides a very detailed picture at molecular level for this reaction system at first time.

Study of Solid–Liquid Phase Transfer Catalysed Reaction to Produce P-Nitroanisole Using 18-Crown-6 as Catalyst

Anisoles and substituted anisoles are the main precursors in the process industries which prepare important pharmaceuticals and these can be produced from various reactants in liquid–liquid or solid–liquid phase transfer catalytic reaction mechanisms. The solid–liquid phase transfer catalysed reaction between p-chloronitrobenzene and potassium methoxide (CH3OK) using 18-crown-6 as a phase transfer catalyst for the production p-nitroanisole was investigated. Potassium methoxide was present as the solid phase and the PCNB which was dissolved in Benzene taken as the liquid phase and the catalyst was also in the liquid phase. Experiments were conducted to observe the effect of various process parameters such as degree of agitation, temperature, catalyst concentration, and different solvents on the conversion of PCNB. A kinetic model has been developed for the above-mentioned reaction to predict the reaction rate. From the results it has been observed that the reaction was found to follow the first order at a low catalyst concentration and initial reaction period. Apparent activation energy was also determined from the Arrhenius plot.

Novel 5-functionalized-pyrazoles: Synthesis, characterization and pharmacological screening.

In the present study a series of O-substituted pyrazoles 7(a-f) and N-substituted pyrazoles 9(a-f) were synthesized via phase-transfer catalyzed reaction of ethyl 5-(bromomethyl)-1,3-diphenyl-1H-pyrazole-4-carboxylate 5 with various oxygen and nitrogen containing compounds in presence of tetrabutylammonium bromide (TBAB) in THF. The compound 5 was obtained by the efficient bromination with N-bromosuccinimide (NBS) in presence of a catalytic amount of azoiso-bis-butyro nitrile (AIBN) in refluxing CCl4. The synthesized compounds were evaluated for their in vitro antimicrobial and antidiabetic activity and were compared with standard drugs. Among the synthesized compounds, compound 9b emerged as an excellent antimicrobial and antidiabetic agent. Newly synthesized compounds were characterized by analytical and spectral (IR, (1)H NMR, (13)C NMR and LC-MS) methods.