Synergism of microwaves and immobilized enzyme catalysis in synthesis of adipic acid esters in nonaqueous media

Article abstract of DOI:10.1081/SCC-200061687

Low-energy microwave irradiation leads to enhancement by a factor of up to 2.63 in comparison with conventional heating in immobilized lipase-catalyzed esterification of adipic acid with various alcohols and this effect is due to the greater frequency of collision, without any change in activation energy of the two modes of heating. Copyright Taylor & Francis, Inc.

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Synergism of Microwaves and
Immobilized Enzyme Catalysis
in Synthesis of Adipic Acid
Esters in Nonaqueous Media
a
a
Ganapati D. Yadav & Piyush S. Lathi
a
Department of Chemical Engineering , University
Institute of Chemical Technology, University of
Mumbai , Matunga, Mumbai, India
Published online: 16 Aug 2006.
To cite this article: Ganapati D. Yadav & Piyush S. Lathi (2005) Synergism of
Microwaves and Immobilized Enzyme Catalysis in Synthesis of Adipic Acid Esters in
Nonaqueous Media, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 35:12, 1699-1705, DOI: 10.1081/
SCC-200061687
To link to this article: http://dx.doi.org/10.1081/SCC-200061687
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Synthetic Communications , 35: 1699–1705, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1081/SCC-200061687
Synergism of Microwaves and Immobilized
Enzyme Catalysis in Synthesis of Adipic
Acid Esters in Nonaqueous Media
Ganapati D. Yadav and Piyush S. Lathi
Department of Chemical Engineering, University Institute of Chemical
Technology, University of Mumbai, Matunga, Mumbai, India
Abstract: Low-energy microwave irradiation leads to enhancement by a factor of up to
2
.63 in comparison with conventional heating in immobilized lipase-catalyzed esterifi-
cation of adipic acid with various alcohols and this effect is due to the greater frequency
of collision, without any change in activation energy of the two modes of heating.
Keywords: Adipic acid, esterification, diester, immobilized lipase catalysis,
monoester, microwave irradiation, synergism
INTRODUCTION
One of the most important classes of synthetic lubricants comprises esters
of dicarboxylic acids. Monoesterification and diesterification of aliphatic
[
dicarboxylic acids are both very important. Monoesters of adipic acid are
1]
[
2,3]
particularly used in Kolbe’s synthesis
and in regioselective transfor-
[4]
mations, and also as synthons for chiral building block, whereas diesters
are extensively used as precursors in the synthesis of biodegradable
[
5]
polymers and as lubricants.
Normally esters are prepared by reaction of an alcohol and a dibasic car-
boxylic acid in the presence of an acid catalyst. The reaction temperature for
adipic acid esters is usually in the range of 100 to 1808C. Several
Received in India February 8, 2005
Address correspondence to Ganapati D. Yadav, Department of Chemical Engineer-
ing, University Institute of Chemical Technology, University of Mumbai, Matunga,
Mumbai 400 019, India. Fax: Tel: þþ 91-22-2410 2121 (D); þþ 91-22-2414 5616
Ext: 291; þþ 91-22-2414 5614; E-mail: gdyadav@yahoo.com, gdyadav@udct.org
1
699

1700
G. D. Yadav and P. S. Lathi
homogeneous catalysts, such as sulfuric acid, hydrochloric acid, p-toluene
sulfonic acid, and methanesulfonic acid, are still used but these are being
replaced by heterogeneous catalysts such as cation-exchange resins,
[
6–9]
activated clay, zeolites, and modified heteropoly acids.
reports on enzymatic synthesis of esters of adipic acid.
There are some
10,11]
Mostly all
[
above-mentioned reactions have been carried out using reactors accompanied
with traditional heat-transfer equipment. Immobilized lipases have been
widely used for esterification in nonaqueous media and our group has
[12–20]
studied several industrially relevant reactions.
Microwave irradiation
is being extensively applied to augment rates of chemical reactions. Hence,
it was thought worthwhile to combine these two different ways of green
chemistry, namely biocatalysis and microwave irradiation, in the current work.
RESULTS AND DISCUSSION
A number of alcohols were reacted with adipic acid with Novozym 435 using
both microwave irradiation and conventional heating at a controlled tempera-
ture of 608C. The microwave energy input was below 40 W. The initial rates of
reaction of the alcohols with the acid were compared for both modes of
operation as shown in Table 1 and Scheme 1. It was found that there was
an enhancement in the initial rates of reaction in the presence of microwaves.
The overall conversion was higher under microwave irradiation vis- a` -vis con-
ventional heating. This shows that the effect may not be purely thermal.
Control experiments in the absence of Novozym 435 did not initiate the
reaction. Furthermore, microwave irradiation without the enzyme also did
not initiate the reaction. Thus, there is a synergistic effect. In the case of non-
aqueous enzymology using immobilized enzymes, it is known that the enzyme
particle is always surrounded by a thin aqueous layer and all pores of the
support are filled with water, and hence the enzyme is not denatured.
Because there are no intraparticle diffusion limitations for the reactants,
which was studied independently with the most reactive substrate, micro-
waves affect the rate of reaction on the enzyme surface because of more col-
lisions of the reactant molecules, without affecting the activation energy
values. This has been witnessed in chemical catalysis in conjunction with
[21]
29
microwaves. Microwaves transfer energy in 10 s with each cycle of elec-
tromagnetic energy. The kinetic molecular relaxation time from this energy is
2
5
approximately 10 s. This means that the energy transfers faster than the
molecules can relax, which results in nonequilibrium conditions and high
instantaneous temperatures that affect the kinetics of the system. Furthermore,
microwaves do not influence the orientation of those collisions nor the acti-
[
22]
vation energy.
An increase in temperature causes greater movement of
molecules, which leads to a greater number of energetic collisions. This
leads to enhancement in reaction rates and product yields. The quality of
products is better than those obtained with conventional heating.

Table 1. Esterification of adipic acid with different alcohols
Microwave irradiation
Conventional heating
f
Enhancement
factor
Alcohol
r
o
% C
% SM
% SD
r
o
% C
% SM
% SD
n-Propanol
n-Butanol
n-Petanol
0.96
0.98
0.83
0.64
0.29
0.29
0.89
0.85
0.58
0.75
0.59
0.61
77.12
75.64
70.98
51.41
27.98
16.98
70.83
68.73
42.85
70.64
70.33
57.90
7.5
70
30
0.71
0.62
0.64
0.43
0.13
0.11
0.76
0.61
0.54
0.59
0.43
0.48
73.34
72.35
64.92
48.12
21.03
12.69
64.94
66.15
38.59
64.48
68.00
48.70
4.5
74
26
1.35
1.58
1.29
1.49
2.23
2.63
1.17
1.39
1.07
1.27
1.37
1.27
1.66
69.39
70
91
30.61
30
09
71.56
70.92
93
25.04
29.08
07
n-Hexanol
n-Octanol
n-Decanol
Iso-propanol
Iso-butanol
100
100
—
—
100
100
—
—
79.41
83.77
100
20.59
16.23
—
79.36
81.35
100
20.63
18.65
—
2-Ethylhexan-1-ol
Amyl alcohol
80.40
67.64
100
19.59
32.36
—
83.24
65.15
100
16.76
34.85
—
Benzyl alcohol
p-Chlorobenzyl alcohol
Cyclohexanol
100
—
100
—
r
o
¼ Initial rate (mol/l-min), C ¼ Conversion, SM ¼ Selectivity toward monoester, SD ¼ selectivity toward diester, f ¼ enhancement of rate.
Reaction Conditions: Adipic acid: 0.01 mol, alcohol: 0.01 mol, speed of agitation: 300 rpm, temperature: 608C, catalysts loading: 0.0035 g/cc,
catalysts: novozym 435, solvent: 1,4-dioxane up to 20 ml, reaction time: 3 h.

1702
G. D. Yadav and P. S. Lathi
Scheme 1.
In the case of linear alcohols such as n-alcohols and iso-alcohols, it
was found that as the chain length of alcohol increases for n-alcohols from
n-propanol to n-decanol and for iso-alcohols from iso-propanol to
2
-ethylhexan-1-ol, the selectivity toward monoester increases and the
overall conversion in microwave is more than in conventional heating. The
selectivity toward the monoester is more in conventional heating than in
microwave irradiation because the consecutive reaction to the disaster
formation consumes the monoester. (Table 1 and Scheme 1).
CONCLUSION
The use of low-energy microwaves in the enzyme-catalyzed synthesis of
adipic acid mono and diesters in nonaqueous media was studied for the first
time. There is significant enhancement in rates of reactions (enhancement
factors in the range of 1.07 to 2.63) under microwave irradiation in compari-
son with conventional heating. The catalyst-reusability studies showed that
the catalyst is reusable.
SUPPLEMENTARY DATA
Materials and Methods
Enzymes and Chemicals
The enzymes Novozym 435 (Candida Antarctica lipase immobilized on a
macroporous polyacrylic resin with an activity 10 PLU/g) was procured as
a gift sample from Novo Nordisk, Denmark.
All chemicals were procured from firms of repute and were used without
any further purification: adipic acid (Merck India), 1,4- dixoane, n-propanol,
n-butanol, n-pentanol, n-hexanol, n-octanol, n-decanol, iso-butnaol, amyl
alcohol, iso-propanol, benzyl alcohol, 2-ethyl hexan-1-ol, p-chloro benzyl
alcohol, cyclohexanol (all from s.d. Fine Chemicals Pvt. Ltd, Mumbai). All
chemicals were AR grade.

Microwaves and Immobilized Enzyme Catalysis
Experimental Setup
1703
Conventional Heating
The experimental setup consisted of a 3 cm i.d. fully baffled mechanically
3
agitated glass reactor of 50 cm capacity, which was equipped with four
baffles and a six-bladed pitched-turbine impeller. The entire reactor
assembly was immersed in a thermostatic water bath maintained at the
desired temperature with an accuracy of+18C.
In a typical experiment, the reaction mixture consisted of 0.01 mol of
adipic acid and 0.01 mol alcohol, diluted to 20 ml with 1, 4-dioxane as a
solvent. The reaction mixture was agitated at 608C for 15 min at a speed of
3
00 rpm and a known quantity of immobilized enzyme was then added to
3
initiate the reaction typically (0.0035 g/cm ). Clean samples were
withdrawn periodically and analyzed by HPLC.
Microwave Reactor
The experimental setup consisted of the “Discover” system (CEM Corpor-
ation, USA). This system consists of a circular single-mode cavity design
which directs the microwave energy into a defined area, resulting in a homo-
genous field pattern surrounding the sample. The Discover System incorpor-
ates temperature and pressure feedback systems for complete control on
reaction conditions. The same reaction conditions as used for experiments
with conventional heating were used.
Analysis
The concentration of the reactants and products were determined on HPLC
equipped with a UV detector using the following conditions:
Column ¼ Merck 50938 column with a stationary phase of Lichrosphere 100
RP-8 particle size 5 mm, prepacked on a 125 ꢀ 4 mm ID. Mobile phase ¼
2
1
Acetonitrile: Water (60:40 by vol.) Flow rate ¼ 0.8 ml min . Detector ¼
Knauer K-2501 UV detector set at 214 nm.
ACKNOWLEDGMENT
PSL thanks University Grant Commission (UGC) for SRF, which enabled this
work to be carried out. GDY acknowledges support from the Darbari Set
Professor Endowment for personal chair.

1704
G. D. Yadav and P. S. Lathi
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