Organic Process Research & Development 2005, 9, 749−756
Selectivity Engineering of Phase Transfer Catalyzed Alkylation of
2
′-Hydroxyacetophenone: Enhancement in Rates and Selectivity by Creation of
a Third Liquid Phase
Ganapati D. Yadav* and Neesha M. Desai
Department of Chemical Engineering, UniVersity Institute of Chemical Technology (UICT),
UniVersity of Mumbai, Matunga, Mumbai-400 019, India
Abstract:
transfer catalysts from the reaction mixture can be achieved
1
,2
Enhancements in rate of reaction and selectivity of the desired
product in biphasic reactions are achieved by creating a third
liquid phase, under appropriate conditions, where the third
liquid phase is the locale of the main reaction, having a dramatic
effect on product distribution in complex chemical reactions.
Thus, in the case of phase transfer catalysis (PTC), conversion
of liquid-liquid (L-L) PTC into liquid-liquid-liquid (L-L-
L) PTC is of considerable techno-commercial interest resulting
in waste minimization which is a major theme of green
chemistry. Etherification of 2′-hydroxyacetophenone with 1-bro-
mopentane, under traditional liquid-liquid phase transfer
catalysis, results in loss of catalyst. However, the transformation
of two liquid phases into three liquid phases (L-L-L) PTC
leads enhancement in rates by orders of magnitude, with 100%
conversion of the limiting reactant 1-bromopentane and 100%
selectivity to 2′-pentyloxyacetophenone. This strategy eliminates
separation problems and results in high reaction rates reducing
the total reaction time. Moreover, the catalyst-rich third phase
is recycled more than 7 times without loss in activity. The
kinetics of the reaction are studied in great detail. There is a
substantial reduction in activation energy under L-L-L PTC
vis- a` -vis L-L PTC, where the locale of the reaction is shifted
from the organic phase to the third phase.
by extraction, distillation, and adsorption, which are all
energy intensive and uneconomical due to high dilutions.
Extraction needs an additional solvent that has to be distilled
off to recover the phase transfer catalyst. Distillation is
possible only if the catalyst has a lower boiling point than
the reactants, products, and the solvents. In the case of
adsorption, the catalyst must be eluted using a solvent. Since
the quantities of the catalyst used are small, they do not
contribute much to the expensive product cost. Therefore,
the catalyst is mostly not recovered but removed by washing
the organic phase with copious quantities of water which is
disposed to the effluent treatment plant as an end-of-the-
pipe approach of pollution prevention. Although milder
reaction conditions and use of cheap solvents in L-L PTC
improve the economics, PTC needs to be practised from the
green chemistry perspective such as solventless synthesis and
catalyst reuse and an overall strategy of waste reduction.
Instead of conducting reactions in homogeneous media,
it may desirable to convert the reaction into a multiphase
system and achieve the same objective most economically.3
Furthermore, a third, catalyst-rich phase can be created
between the aqueous and organic phases containing the
reactants whereby the reaction occurs in the middle phase
through a proper balance of liphophilicity, hydrophilicity,
interfacial tension, solubilities, phase equilibria, and density;
and this constitutes the so-called liquid-liquid-liquid (L-
L-L) PTC. It was observed that when the amount of catalyst
exceeds a critical value the rate of reaction increases sharply.
Indeed, we have found, in a number of reactions, not only
the rates of reaction but also the selectivity can be enhanced
dramatically thereby reducing reaction time and separation
,4
1
. Introduction
Phase transfer catalysis (PTC) has fascinated many
researchers and industries for the past three and half decades
1,2
and is a mature discipline now. The major advantages of
PTC include high yield, high reaction rate, selectivity to
desired product with less quantity of catalyst, mild conditions,
and reduction in energy consumption. PTC has been suc-
cessfully applied to economically viable synthesis of im-
portant and valuable chemicals. A large number of indus-
trially important reactions involve the use of PTC reported
under L-L phase transfer catalysis. The major disadvantage
of liquid-liquid phase transfer catalysis (L-L PTC) is that
the catalyst remains distributed between the two liquid phases
and cannot be recovered easily. The separation of phase-
5
-10
costs.
The third liquid phase is the main reaction phase
for the phase transfer catalyst to catalyze the reaction, and
the recovery and reuse of the catalyst are easier since it forms
an immiscible third liquid phase. The advantages of L-L-L
PTC over L-L PTC are (i) enhanced reaction rates and
milder reaction conditions such as lower temperature; (ii)
easier catalyst recovery and reuse; (iii) suppression of
(3) Sharma, M. M. Chem. Eng. Sci. 1988, 43 (8), 1749.
(4) Doraiswamy, L. K.; Sharma, M. M. Heterogeneous Reactions: Examples,
Analysis, Reactor Design; Wiley-Interscience: New York, 1984; Vol. 2.
*
To whom correspondence should be addressed. E-mail: gdyadav@
yahoo.com; gdyadav@udct.org.Telefax: 91-22-410 2121.
(5) Yadav, G. D.; Naik, S. S. Catal. Today 2000, 1-10, 2357.
(6) Yadav, G. D.; Reddy, C. A. Ind. Eng. Chem. Res. 1999, 38 (6), 2247.
(7) Yadav, G. D.; Jadhav, Y. B. Clean Technol. EnViron. Policy 2003, 6, 32.
(8) Yadav, G. D.; Bisht, P. M. J. Mol. Catal. 2004, 221 (1-2), 59.
(9) Yadav, G. D.; Lande, S. V. Appl. Catal. 2005, 287 (2), 267.
(10) Yadav, G. D.; Lande, S. V. AdV. Synth. Catal. 2005, 347 (9), 1235.
(
(
1) Starks, C. M.; Liotta, C. L.; Halpern, M. Phase Transfer Catalysis:
Fundamentals, Applications, and Industrial PerspectiVes; Chapman and
Hall: New York, 1994.
2) Sasson, Y., Neumann, R., Eds. Handbook of Phase Transfer Catalysis;
Blackie Academic and Professional: London, 1997.
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0.1021/op050086m CCC: $30.25 © 2005 American Chemical Society
Vol. 9, No. 6, 2005 / Organic Process Research & Development
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Published on Web 10/28/2005