1

PHASE
TRANSFER
CATALYST

Submitted by
T.Thulasiraman
M.Pharm 2nd Semester
Department of Pharmaceutical Chemistry
 CONTENTS
2
1. INTRODUCTION
2. THEORIES OF PTC
3. MECHANISM OF PTC REACTION
4. CLASSIFICATION OF PTC
5. TYPES OF CATALYST USED
Onium salts
Macro cyclic polyether’s
Aza – macro bicyclic ethers
Open chain polyether’s
6. STABILITY OF PHASE TRANSFER CATALYST
7. APPLICATION OF PTC
8. PTC IN GREEN CHEMISTRY
9. CONCLUSION
1O. REFERENCES
 INTRODUCTION
3

Catalyst:

Catalyst is an agent used Not consumed throughout

to enhance the rate of the reaction process and act
chemical reaction continuously.

Works by lowering the

activation energy or altering
the mechanism of reaction.
 Phase transfer catalyst
4
 Exchanging of the chemical reactions between the two non-miscible, heterogeneous
systems.
 Both functional sites to get solubilized in both system and allow transferring
substance from one system to another.

PT catalysis uses
• Catalytic amount and it allows to react the reactants of two different phases
• Via facilitating transfer of reactants from interface,
Which are not miscible and itself regenerated again and the cycle is repeated.

• It accelerates the reaction, decreases reaction time, needs less solvents, obtains
higher yield, has less side reaction, and eliminate hazardous waste etc,

• Green Chemistry which allows reaction in water and the use of organic solvents is
dramatically decreased.
5
General understanding
PTC is not limited to
hydrophilic and lipophilic
system but in some cases, it
is highly useful and utilized
in liquid/gas and
liquid/solid reaction
conditions.
Diversified application
PTC is also combined with
other rate enhancing
techniques - microwave,
electro-organic synthesis,
sono-chemistry,
photochemistry and many
more are exploring.
6 THEORIES OF PTC

 Intermediate compound formation theory or Homogenous

catalyst reaction

 Adsorption theory or Heterogenous catalyst reaction.

INTERMEDIATE COMPOUND FORMATION THEORY OR HOMOGENOUS
7 CATALYST REACTION
 The catalyst first forms an intermediate compound with one of the reactants.

 The intermediate compound being unstable combines with other reactant to

form the desired product and the catalyst is regenerated.

Example
8 EXAMPLE

The catalytic oxidation of SO2 to SO3 in the lead chamber process

probably takes place as;

 2 NO (Catalyst) + O2   ------- > 2NO2  (Intermediate Compound)

NO2 + SO2   ------ >   SO3 (Product) + NO (Catalyst)

9 ADSORPTION THEORY
 The catalyst functions by the adsorption of the reacting molecule on
it’s surface.
 The adsorption reaction undergoes four type of steps.
They are,
1. Adsorption of reactant molecule
2. Formation of intermediate complex
3. Decomposition of intermediate complex
4. Release of product
10
ADSORPTION OF REACTANT MOLECULE

FORMATION OF INTERMEDIATE COMPLEX

11
DECOMPOSITION OF INTERMEDIATE COMPLEX

DESORPTION OF PRODUCTS
12 HETEROGENEOUS CATALYSIS
13 MECHANISM OF PTC REACTION
 In 1971, Starks proposed ‘Ion Pair Mechanism” for the phase transfer catalysis, where
a quaternary ammonium halide(QX) undergoes dissolution in aqueous phase followed
by phase transfer and nucleophilic substitution reaction in organic phase to forms
subsequent desired product (RY).

 Again, the catalyst returns back to the aqueous phase and the cycle is repeated
continuously.
14 AN EXAMPLE IN PHASE TRANSFER CATALYSIS

 Cyanide displacement for alkyl halide :-1-chlorootane with sodium cyanide yields
1-cyanooctane

Step-1: Anion transfer from aqueous to organic phase.

Step-2: The intrinsic reaction or organic phase displacement reaction.
 Other mechanisms that can be considered as phase-
15
transfer catalytic are,

PTC of uncharged species: complexation and transfer of uncharged

protic species or metal salts into the organic medium as complexes of the
phase -transfer agent.

Electron-transfer catalysis for Redox systems.

Metal ion-transfer from aqueous solutions into water-immiscible ionic

liquids containing neutral complexing agents.

Pyrolytic alkylation process.

16 CLASSIFICATION OF PTC
17 LIQUID-LIQUID PHASE TRANSFER CATALYSIS (LL-PTC)

 The PTC reactions were performed using an aqueous phase and an organic phase.
This technique is called liquid-liquid phase transfer reaction.

 The nucleophile is dissolved in an aqueous phase.

 higher selectivities and yields are sometimes obtained by operating in the solid-
liquid mode as compared to operation in the liquid-liquid mode.
18 MECHANISMS UNDER LIQUID-LIQUID PHASE
TRANSFER CONDITIONS

There are 2 mechanisms involved,

1) Starks extraction mechanism

2) Makosza Interfacial Mechanism

19 EXTRACTION MECHANISM 
20 INTERFACIAL MECHANISM
21 SOLID-LIQUID PTC (SL-PTC)
 SLPTC it is a solid suspended in the organic phase.
 Liquid-liquid and solid-liquid systems are the main classes of reactions where
PTC finds its most applications, and future discussion and analysis of PTC
systems concentrates on LLPTC and SLPTC reactions.
22 GAS-LIQUID PTC (GL-PTC)

 GLPTC involves the use of PTC in gas-liquid-solid systems.

 Advantages of GLPTC include ease of adaptation to continuous flow operation.

absence of organic solvent since the organic substrate is present in gaseous
form, ease of recovery of the PT catalyst as it is directly loaded onto the solid
bed, and better selectivity than LLPTC in some cases.

methylation of aroxylacetonitriles and methyl-2- aroxyacetates using DMC

(dimethyl carbonate) gives up to 99% of the monomethylated derivatives,
which are widely used in the synthesis of biologically active compounds and
plant growth regulators.
23 TYPES OF CATALYST USED

1. Onium Salts (Ammonium And Phosphonium Salts),

2. Macrocyclic Polyethers (Crown Ethers),

3. Aza - Macro Bicyclic Ethers (Cryptands),

4. Open chain polyethers (polyethylene glycols and their

dimethyl ethers).
 QUATERNARY ONIUM SALTS
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Moderately stable
under basic conditions
Widely used.
and upto 1000C.
Recovery is
Ammonium salts Cheap Decomposition by
relatively
Hofmann elimination
difficulty.
under basic conditions.
Moderately active.

More stable
thermally than Widely used.
Costlier than ammonium salts, Recovery is
Phosphonium salts
ammonium salts although relatively
less stable under difficult.
basic conditions.
25  The most frequently used quaternary onium catalysts are depicted in table.

o Many quaternary
ammonium
(R4N+X-),
phosphonium
(R4P+X-) and
arsonium are
able to transfer
anions from an
aqueous to an
organic phase.
26
 Mostly frequently used phosphonium salts is,
TETRA PHENYL PHOSPHONIUM BROMIDE.
 MACROCYCLIC POLYETHERS
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    SOLUBILITY& USE & RECOVERY

CATALYST COST ACTIVITY OF CATALYST

   
    Often used. Recovery
Stable and highly
    active catalysts both is difficult and poses
Crown Expensive under basic environmental issues
conditions and at
ethers higher temperatures due to their toxicity.
up to even 150-
2OO0C
 AZA - MACRO BICYCLIC ETHERS
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    SOLUBILITY& USE & RECOVERY

CATALYST COST ACTIVITY OF CATALYST
     
Used sometimes
    Stable and highly
despite high costs and
Cryptands Expensive reactive, except in the
toxicity, due to higher
presence of strong
reactivity.
acids.
29 Most widely used crown ethers and cryptands are,
 OPEN CHAIN POLYETHERS
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    SOLUBILITY& USE & RECOVERY

CATALYST COST ACTIVITY OF CATALYST
    Often used. Can be
    More stable than used when larger
PEG Very cheap quaternary ammonium quantities of catalyst
salts, but lower cause no problems.
activity. Relatively easy to
recover.
31  A list of most frequently used podands or poly ethylene glycol as phase
transfer catalyst,
 STABILITY OF PHASE TRANSFER CATALYST
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Phosphonium salts
Tetra-n-butylammonium
salts usually stable enough
More stable than ammonium
Salts, less stable in others.

Sufficiently well partitioned

Less prone to intramolecular Into the organic phase
Displacement when associated

Being reasonable stable Good catalyst for

Catalysts up to a temperature Many reactions.
Of 150-170°C, ammonium
Salts lost their activity rather
Rapidly at temperature greater
Than about 110-120 °C.
33

 Quaternary ammonium salts have a low thermal stability at elevated temperatures.

 Highly reactive alkyl groups, such as benzyl and allyl and to a lesser extent methyl,
undergo intramolecular displacement much more rapidly than N-alkyl groups.

 The macro polyether such as crown ethers, cryptands and podands are thermally
more stable than quaternary ammonium and phosphonium salts.
 ADVANTAGES OF PHASE TRANSFER CATALYST
34 OVER CONVENTIONAL CATALYST
1. Faster reactions can be achieved.

2. Higher conversions or yields are obtained.

3. There are fewer byproducts.

4. There is no need for expensive or dangerous solvents which dissolve all the reactants in one
phase.

5. Expensive raw materials are not required.

6. Waste problems are minimized.

7. They are especially useful in green chemistry. They allow the use of water so there is less
need for organic solvents.

8. It is not limited to systems with hydrophobic and hydrophilic reactants. It is used in liquid /
solid and liquid / gas reactions as well.
35 DISADVANTAGES

 The high concentration of catalyst in PTC reactions can inhibit substitution. This
phenomenon is observed in various nucleophilic reactions where the formation of
lipophilic ion-pair or similar complexes take place.

 Another problem is the degradation of catalysts under PTC conditions. Ammonium

and phosphonium salts may be subject to destruction that proceeds mainly in the
presence of aqueous alkali.

 The separation of the catalyst from the product in the purification process is difficult.
36 APPLICATIONS OF PTC

I. SYNTHETIC APPLICATION:

1. Phase transfer catalysis in anhydride synthesis:

37 2. FORMATION OF ESTER BY USING PTC
General reaction:

EXAMPLE
38
3. FORMATION OF NITRILE:
General reaction:

Example:

1.

2.
39 4. SULPHIDE FORMATION:
General reaction:
2 RX + Na2S -------- > R ----- S ----- R

Example:
RX + R'S Na --------- > R-S-R'

5. REDUCTION BY USING PTC:

Example:
40 II. INDUSTRIAL APPLICATION

 Applications involving the use of a co-catalyst include co- catalysis by surfactants,

alcohols and other weak acids in hydroxide transfer reactions, use of iodide, or
reactions carried out with dual PT catalysts; have been also reported.

 In nucleophilic substitution reactions and in reactions in the presence of bases

involving the deprotonation of moderately and weakly acidic organic compounds.

 PTC has made possible the use of cheaper and easily available alternative raw
materials like potassium carbonate and aqueous NaOH solution, thereby obviating the
need of severe anhydrous conditions, expensive solvents, and dangerous bases such
as metal hydrides and organometallic reagents.
  When any kind of chemical reactions are carried out in the presence of a PT catalyst in
41 biphasic systems, simple, cheap and mild bases like NaOH and K2CO3 can be used
instead of toxic alkali metal alkoxides, amides, and hydrides.

 PTC can also be used for the synthesis process for fine chemicals manufacture industries.

 Perfumery and Fragrance Industry like Synthesis of phenylacetic acid, an intermediate in

the perfumery industry.

 In the field of Pharmaceuticals like Synthesis of various drugs like dicyclonine,

phenoperidine, ritaline, etc.

 Polymeric bonded PTC for the determination of cyanide, iodide, nitrite, sulphide and
thiocyanate, led to easy layer separation and PTC-free injection of the sample into the
chromatograph.
42 PTC IN GREEN CHEMISTRY
Examples:

1. Replacement of halogen, sulfonate, or sulphate substituents

2. Sonication of ethyl cyanoacetate and ethylene dibromide with

potassium carbonate and poly(ethylene glycol) in ethylene dichloride
43
3. Displacement reaction of Na2S with benzyl chloride and p-chlorobenzyl
chloride to produce the corresponding dialkyl sulfides

4. Reduction of conjugated double bonds in aldehydes and ketones.

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5. Other pharmaceutical heterocycles including phenothiazine,

dibenzazepine, dihydrodibenzazepine, phenothiazine and derivatives
were N-alkylated.
45 CONCLUSION

 From past 4 decades, the PTC popularity is increasing, and many significant
reactions are performed as desired with employing PTC.
 Nowadays more diversified chemical structure with ammonium, phosphonium,
crown and the non-ionic PTC are developed and available commercially which
allows us to select the specificity to the certain reaction nature.
 Moreover, the chiral PTC are playing great role in asymmetric synthesis. So, we
hope this concise review will provide information regarding PTC as widely
accepted synthetic tool for organic reactions due to its unique phenomenon,
efficiency, simplicity, and economical viability.
46 REFERENCE
 Sanjeev D.Naik and L. K. Doraiswamy. Reactors, Kinetics and Catalysis. Journal
review of Phase Transfer Catalysis: Chemistry and Engineering. 1998; 44(3) : 612 –
615.
 Senthamizh selvi , Nanthini and suganya. The basic principle of phase transfer
catalysis, some mechanistic aspects and important application. International journal of
scientific and technology research. 2012; 01(3): 61 – 62.
 Tesfaye Tebeka and Atitegebe Abera. Review on Asymmetric Transformations with
Chiral Phase-Transfer Catalysts. International Research Journal of Science and
Technology. 2006; 01(3): 6 – 12.
 Dirgha Raj Joshi and Nisha Adhikari. Phase transfer catalyst in organic synthesis.
World Journal of Pharmaceutical Research. 2019; 08(8): 508 – 515.
 Jerry march .Advanced organic chemistry.4th edition. 1992: 378-379,392,482,780,974-
975.
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