Phase-Transfer Catalysts and Their Applications

D.D.U. GORAKHPUR UNIVERSITY A PROJECT WORK ON PHASE-TRANSFER CATALYST by Prof. O.P. PANDEY

ACKNOWLEDGEMENT I bow before the electric, divine and bl essing forces (parents and teachers). Who made me worthy of doing this sac red job to completion . I sincerely thank all my friends and the humane for their kind support and en couragement.

Introduction In heterogeneous system of immiscible liquids, reactants can not react eaisly because of no collision between reactants as system is heterogeneous. Based on the assumption that a reaction between lipophilic and hydrophilic reactants is facilitated by enhancement of mutual solubility, the transfer of a solute between phases is crucial for the establishment of liquid- liquid distribution equilibria. Consider the following reaction: "The 1-chlorooctane and sodium cyanide solution form two separate layers. Heating of this two phase mixture under reflux and vigorous stirring for 1-2 days gives no reaction. The easy way to overcome these prolemems is the use of phase-transfer catalyst (PTC). They are ammonium, sulphonium, phosphonium salts in which alkyl groups are long chain(not less than 4 carbon-atoms). In 1971, C.M. Stars introduced the term phase-transfer catalysis to explain the critical role of tetraalkylammonium or phosphonium salts in the reactions between two substances located in different immiscible phases.

Definition of a phase transfer catalyst: " A phase transfer catalyst is a catalyst which facilitates the migration of a reactant in a heterogeneous system from one phase into another phase where reaction can take place. Ionic reactants are often soluble in an aqueous phase but are insoluble in an organic phase unless the phase transfer catalyst is present . Phase-transfer agents promote the solubility of ionic substances in non-polar solvents. They transfer the ionic substance from an aqueous phase to a non-aqueous one. Phase-transfer agents increase the rates of reactions involving anions. The anion is relatively unsolvated and very reactive in non-polar media compared to water or alcohols. Consider the following reactions: In the above reaction, a tetraalkylammonium chloride (benzyltriethylammonium chloride (BnEt3N+Cl-) is needed as a phase transfer catalyst to allow sufficient hydroxide to enter the organic layer to deprotonate the nitrile.

PRINCIPLE OF PHASE-TRANSFER CATALYSIS The principle of PTC is based on the ability of certain phase-transfer agents (the PT catalysts) to facilitate the transport of one reagent from one phase into another (immiscible) phase wherein the other reagent exists. Thus, reaction is made possible by bringing together the reagents which are originally in different phases. The following salt is an effective phase-transfer catalysts for the transport of anions, tetrabutylammonium chloride

TYPES OF PHASE-TRANSFER CATALYSTS There are many types of phase transfer catalysts, such as quaternary ammonium and phosphonium salts, crown ethers, cryptands, etc. Among these, the quaternary ammonium salts are the cheapest and hence the most widely used in the industry. Typical phase-transfer catalysts Ammonium salts 1-4 and phosphonium salts 5,6 Crown ethers 7-9 and acryptand10 Complexes with potassium cation are shown for 7and 10

Mechanism of action of PTC When an appropriate quaternary ammonium salt is added, tetrahexylammonium chloride, the displacement occurs rapidly in near 100% in 2-3h. 1) Transfers the cyanide into the organic phase. 2) Activates the transferred cyanide for the reaction with the alkyl halide. 3) Transfers the displaced chloride anions back to the aqueous phase to start a new catalytic Cycle.

Advantage of PTC Elimination of organic solvents Use of simple and inexpensive reactants(NaOH,KOH,K2CO3etc. Instead of NaH,KHMDS t-BuOK,etc) High yields and purity of products Simplicity of the procedure Highly scalable Low energy consumption and low investment cost Minimization of industrial waste Since the catalyst is often a quaternary ammonium salt is a much loose ion pair than say Na+X-. This loose ness of the ion pair is a key reason for enhanced reactivity,which will ultimately lead to increased productivity(reduce cycle time ) in commercial processes. Increase quality : improve selectivity ,reduce variability Enhance safety ;control exothermic reactions ,use less hazardous raw materials Reduce other manufacturing costs:eliminate workup unit operations,use alternate less expensive or easier to handle raw materials. Undoubtedly, PTC offers many substantial advantages for the practical execution of numerous reactions

Chiral Phase-Transfer Catalysis The growing importance of enantiomerically pure compounds for life-science applications has fueled a wealth of research in asymmetric synthesis. Asymmetric Phase transfer catalysts:

Cyclopropanation Figure : Chiral PTC C-Alkylation Using Allyl Acetate (not Allyl Halide)

Applications of PTC Sulfenylation Cyanation Fluorination Alkylation Reduction Michael Addition Oxidation phase transfer catalysts Aldol and Related Reactions Aziridination Darzens Reaction Epoxidation Neber Rearrangement Cyclopropanation Horner C Wadsworth C Emmons Reaction

CONCLUSION The present paper has concentrated on the methods of modelling PTC reactions, using both soluble and immobilized forms of the catalyst After the breakthrough made by the Merck research group, large numbers of naturally occurring alkaloid derivatives have been elaborated as powerful and readily available chiral phase-transfer catalysts. Purely synthetic chiral quaternary onium salts and chiral crown ethers, with their characteristic advantages, have also been developed. This catalyst manifold has certainly benefited not only in attaining considerably higher reactivity and stereoselectivity but also expanding the applicability of asymmetric phase-transfer catalysis in modern organic synthesis