Phase transfer catalysis

Phase transfer catalysis, introduction types, theories, examples, mechanisms, application.

1. Phase Transfer Catalysis Presented By: Rohit pal ( M.Pharmacy 2 nd Semester)

2. CONTENTS Introduction Principle of PTC reaction Features of PTC Mechanisms of phase transfer catalyst Theories of phase transfer catalyst Types of phase transfer catalyst Advantages of phase transfer reaction Choice of phase transfer reaction Factors influences phase transfer reaction Application of phase transfer catalysis References

3. introduction Catalysis :- Catalysis is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst. A phase-transfer catalyst or PTC is a catalyst  that facilitates the migration of a reactant from one phase into another phase where reaction occurs. Phase-transfer catalysis is a special form of heterogeneous catalysis. Ionic reactants are often soluble in an aqueous phase but insoluble in an organic phase in the absence of the phase-transfer catalyst. The catalyst functions like a detergent for solubilizing the salts into the organic phase. Phase-transfer catalysis refers to the acceleration of the reaction upon the addition of the phase-transfer catalyst.

4. By using a PTC process, one can achieve faster reactions, obtain higher conversions or yields, make fewer by products, eliminate the need for expensive or dangerous solvents that will dissolve all the reactants in one phase, eliminate the need for expensive raw materials and/or minimize waste problems. Phase-transfer catalysts are especially useful in green chemistry—by allowing the use of water, the need for organic solvents is reduced. Contrary to common perception, PTC is not limited to systems with hydrophilic and hydrophobic reactants. PTC is sometimes employed in liquid/solid and liquid/gas reactions. As the name implies, one or more of the reactants are transported into a second phase which contains both reactants .

5. PRINCIPLE 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. Reaction is made possible by bringing together the reagents which are originally in different phases It is also necessary that the transferred species is in an active state for effective PT catalytic action, and that it is regenerated during the organic reaction

6. In 1971, Starks introduced Phase Transfer Catalysis (PTC) to explain the role of tetraalkylammonium or phosphonium salts in the reactions between two substances located in different immiscible phases. e.g. the displacement reaction of 1-chlorooctane with aqueous sodium cyanide is accelerated > 1000x by the addition of hexadecyltributylphosphonium bromide as a PTC.

7. Features of PTC PTC achieve steady growth as a practical methodology for organic synthesis. This main features of PTC are such as:  simple experimental operations  mild reaction conditions  inexpensive  environmentally benign reagents and solvents, and  the possibility to conduct large-scale preparations

8. MECHANISMS OF PTC A quaternary ammonium halide dissolved in the aqueous phase (Q + X - ) undergoes anion exchange with the anion of the reactant dissolved in the aqueous solution The ion-pair formed (Q + X - ) can cross the liquid-liquid interface due to its lipophilic nature and diffuses from the interface into the organic phase, this step being the phase-transfer In the organic phase, the anion of the ion-pair being quite nucleophilic undergoes a nucleophilic substitution reaction with the organic reagent forming the desired product (RY) The catalyst subsequently returns to the aqueous phase and the cycle continues.

9. An overview of PTC reactions is given in the scheme bellow:

10. Theories of catalysis Intermediate Compound formation theory (Homogenous catalyst reaction ) Adsorption theory ( Heterogenous catalyst reaction ) 1) Intermediate compound formulation theory: According to this theory one of the reactants combines with catalyst to form intermediate product, which carries out the reaction, E.g. A + C = AC AC + B =AB + C A + B + C = AB + C where A and B are reactants, C is the catalyst and AC is the intermediate product.

11. 2) Adsorption Theory: In general adsorption theory applies to heterogeneous catalytic reactions. The catalyst functions by the adsorption of the reacting molecules on its surface. The adsorption reaction undergoes four types of steps. I ) Adsorption of reactant molecule: The reactant molecules A and B strike the surface of the catalyst. The reaction molecules held up by the partial chemical bond. II ) Formation of intermediate complex : The reactant molecule adjacent one another join to form an intermediate complex ( A-B ). The intermediate complex is unstable.

12. ( III ) Decomposition of intermediate complex: The intermediate complex breaks to form the products C and D. The product molecules hold to the catalyst surface by partial chemical bond. ( IV ) Release of product: The product particles are released from the surface .

13. Types of phase transfer catalyst Quaternary ‘Onium’ salts such as ammonium, phosphonium , antimonium and tertiary sulphonium salts. Some of the PTC’s normally used are:- Aliquat 336 : N+CH3(C8H17)3 Cl Methyl trioctylammonium chloride Benzyl trimethylammonium chloride or bromide (TMBA) N+(CH3)3 CH2 C6H5 X- Benzyl triethylammonium chloride N+(C2H5)3 CH2 C6H5 X- Cetyl trimethylammonium chloride or bromide (CTMAB) N+ (CH3)3 (CH2)15 CH3 X-

14. Types of phase transfer catalysed reactions Liquid-Liquid phase transfer reaction Solid-Liquid phase transfer reaction Solid-gas phase transfer reaction Triphase catalyst Insolubilized ammonium and phosphonium salts Insolubilized crown ethers and cryptands Insolubilized cosolvents 15

15. Advantages of PTC Do not require vigorous conditions and the reaction are fast. Do not require expensive aprotic solvents. Do not require high temperature ; the reaction usually occur at low temperature. There is no need for anhydrous conditions since water is used as one of the phases. With the help of PTC , the anion is available in organic solvent and so its nucleophilicity increases.

16. Phase Transfer Catalysts Crown Ether Linear Crown Ether

17. High-molecular-weight PEG (e.g. PEG 8000, PEG 2000 )

18. Typical phase-transfer catalysts ammonium salts 1-4 and phosphonium salts 5,6 N R R Me Cl P Br 6 n Bu n Bu n Bu n Bu P Br 5 n Bu n Bu n Bu n Bu X Et Et Cl Me Me OH X = ( T B A B ) (TBAF) (TBAH) a Br b F c OH d HSO 4 e BH 3 CN f ClCrO 3 1 N R 2 N Et 3 ( T E B A) N Me 4 (Triton B) a R = n -C 8 H 17 (Aliquat 336) b R = n -C 8 -C 10 (Adogen)

19. Choice of phase transfer catalyst To use depend on factors such as reaction type , solvent , temperature , base strength and ease of catalyst recovery and removal . Polyethelene glycols ( PEGs): the cheapest and are stable in basic media and at elevated temperatures. Crown ethers and cryptands: the most expensive. Crown ethers and cryptands, besides their high costs, are also toxic, and are to be avoided whenever possible. Crown ethers Cryptand

20. FACTORS Following three factors plays important role in the successful use of phase transfer catalyst reaction :- Influence of solvent :- Solvent should be aprotic and immiscible with water to avoid strong interaction with ion pairs. Influence of cation :- The large number of carbon atom around the central N atom in the PTC. Salt effect :- Addition of sodium hydroxide and potassium carbonate increases the extraction coefficient many times and thus increases the rate of reaction.

21. PTC: Reaction Category Reactions to which PTC is applicable can be divided into two major categories: 1. Reactions of anions that are available as salts e.g. sodium cyanide, sodium azide , sodium acetate, etc. 2. Reactions of anions that should be generated in situ e.g. alkoxides, phenolates, and carbanions.

22.  In the former case the salts are used as aqueous solutions or in the form of powdered solids , whereas the organic phase contain organic reactants neat (when liquid) or in appropriate solvents.  Since the phases are mutually immiscible the reaction does not proceed unless the catalyst , usually a tetraalkylammonium salt , Q + X – , is present.

23. PTC-Examples PTC for anions reactant are often quaternary ammonium or phosphonium salts Eg . benzyltrimethylammonium chloride and hexadecyl tributylphosphonium bromide. PTC for cations are often crown ethers

24. PTC-Nucleophilic substitution  The catalyst transfers continuously reacting anions into the organic phase in the form of lipophilic ion-pairs produced according to the ion-exchange equilibrium.  They react further, for example, with alkyl halides affording nucleophilic substitution . Cat. regenerated

25. Applications of phase transfer Catalysis 1 ) Nitriles From Alkyl Halides :- 2 ) Benzoyl Cyanides from Benzoyl Chloride:- PTC R-X + NaCN Organic Aqueous O Cl + N a N N O + N a Cl Bu4 N +X- Benz o yl cyani d e Benzoyl chl o l r i d e Sodium cyani d e RC N + NaX Nitrile

26. 3 ) Aryl Ethers/Thioethers :- 4 ) Benzoin Condensation :- A r O H + RX A rOR N a OH P he n o l Aryl ether Benzaldehyde

27. 4) Esterification :- Carboxylic acids can be esterified with alkyl halides in the Presence of triethylamine. RCO 2 Na + RX In the field of Pharmaceuticals like Synthesis of various drugs like dicyclomine, phenoperidine ,oxaladine ,ritaline ,etc. Williamson Ether Synthesis :- C 8 H 17 OH + C 4 H 9 Cl C 8 H 17 OC 4 H 9 + C 8 H 17 OC 8 H 17 PTC Alcohol Alkyl halide E t her By-product Carboxylic acid as sod. salt Alkyl hali d e RCO 2 R + Na X Ester

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