A novel way to prepare n-butylparaben under microwave irradiation

Article abstract of DOI:10.1016/S0040-4039(01)02065-2

The synthesis of n-butylparaben under microwave irradiation in the presence of an inorganic salt ZnCl₂ as a catalyst is reported. Using this specific catalyst for the synthesis of the n-butylparaben under microwave irradiation, not only shortens the reaction time, but also reduces the pollution from the use of concentrated sulfuric acid and prevents the complicated after-treatment handling problems. The reason for this type of microwave-assisted reaction is also demonstrated from the temperature profiles of the reaction. The ratio of the reactants for the better microwave energy efficiency is discussed. The use of microwave irradiation for the large-scale production of this type of food preservative is therefore feasible.

Full text of DOI:10.1016/S0040-4039(01)02065-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 45–48
A novel way to prepare n-butylparaben under microwave
irradiation
a
a,
b
Xiangjun Liao, G. S. V. Raghavan * and V. A. Yaylayan
a
Department of Agricultural & Biosystems Engineering, Macdonald Campus of McGill University, 21,111 Lakeshore Road,
Ste-Anne-de-Bellevue, Canada QC H9X 3V9
b
Department of Food Science and Agricultural Chemistry, Macdonald Campus of McGill University, 21,111 Lakeshore Road,
Ste-Anne-de-Bellevue, Canada QC H9X 3V9
Received 7 September 2001; revised 30 October 2001; accepted 31 October 2001
Abstract—The synthesis of n-butylparaben under microwave irradiation in the presence of an inorganic salt ZnCl as a catalyst
2
is reported. Using this specific catalyst for the synthesis of the n-butylparaben under microwave irradiation, not only shortens the
reaction time, but also reduces the pollution from the use of concentrated sulfuric acid and prevents the complicated
after-treatment handling problems. The reason for this type of microwave-assisted reaction is also demonstrated from the
temperature profiles of the reaction. The ratio of the reactants for the better microwave energy efficiency is discussed. The use of
microwave irradiation for the large-scale production of this type of food preservative is therefore feasible. © 2001 Elsevier Science
Ltd. All rights reserved.
1
. Introduction
However, these methods have limitations of general
applicability owing to low yields, extensive by-product
formation and harsh reaction conditions. In fact, the
use of large amounts of condensing reagents and activa-
tors should be avoided in order to promote green
agricultural food engineering and efficient energy con-
sumption. The direct condensation of acids with alco-
hols using a small amount of catalyst under microwave
irradiation is the most suitable method.
p-Hydroxybenzoic acid esters (parabens) have been
widely used as antimicrobial preservative agents in
food, drugs and cosmetics for more than 50 years due
1
to their broad antimicrobial spectrum. Parabens are
very versatile in terms of food preservatives, differing
from the other preservatives such as benzoates, propi-
onates and sorbates, because they are not weak acid
compounds but have a wide pH range. The antimicro-
bial activity of parabens is directly dependent on the
chain length. For example, the ability of n-butyl-
paraben to inhibit bacteria is 4 times that of ethyl-
The use of microwave irradiation techniques has pro-
found impact on the solution of the synthesis of this
type of compound. Since the appearance of the first
papers on the application of microwaves for organic
2
,3
4
paraben. The increasing use of these types of
5,6
compounds with relatively low toxicity, good stability,
non-volatility and non-irritability in those fields has led
to the development of many techniques for the synthe-
sis and assay of these compounds. In general, most
methods of paraben synthesis involve the presence of a
catalyst such as concentrated sulfuric acid and PTSA
synthesis, numerous papers regarding the application
of this special technology in organic synthesis have
7
been published. The use of microwaves in the synthesis
results in better selectivity, rate enhancement and
reduction of thermal degradation and higher energy
consumption efficiency when compared to traditional
(
p-toluene sulfonic acid). In most cases, large excess of
either acid or alcohol is used in the condensation to
give a higher yield of the desirable esters (Scheme 1).
Keywords: n-butylparaben; esterification; microwave irradiation;
ZnCl ; temperature; ratio.
2
*
Corresponding author: Tel.: 1-514-398-7775; fax: 1-514-398-8387;
e-mail: raghavan@macdonald.mcgill.ca
Scheme 1. The synthesis of parabens (cat.=catalyst such as
PTSA, H SO ).
2
4
0
040-4039/02/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02065-2

4
6
X. Liao et al. / Tetrahedron Letters 43 (2002) 45–48
heating. In addition, microwave-assisted synthesis with-
out surplus reactant offers such advantages as the
reduction of hazardous explosions and the removal of
excess reactants or high boiling solvents from the reac-
tion mixture. Esterification of carboxylic acid in the
presence of catalysts such as concentrated sulfuric acid
and PTSA by employing microwave energy has been
0–300 W in a tubular quartz reactor (250 ml) with
irradiation being monitored by PC. The temperature of
reaction media was measured continuously with an
IR-pyrometer, which was an integral part of the Syn-
thewave 402. For the sake of comparison, reactions
were also carried out using traditional heating in the
presence of ZnCl as a catalyst and reactions were also
2
8,9
extensively investigated. Further, microwave irradia-
tion has also been utilized for the synthesis of parabens
using catalysts such as concentrated sulfuric acid,
performed using PTSA as a catalyst in the presence of
microwave or conventional heating.
10–12
PTSA and inorganic acid.
However, after checking
2.2.1. General procedure 1 (microwave-assisted synthe-
Scifinder Scholar provided by CAS (Chemical Abstract
Service), to the best of our knowledge, there is no
sis). A mixture of 8 ml of butanol, 0.18 g ZnCl and
2
1.72 g p-hydroxybenzoic acid was introduced together
in the quartz reactor of the synthewave 402 apparatus
equipped with a condenser. The irradiation was carried
out in the following sequence at 70% power (300 W×
70%): 15 s off, 30 s on; 15 s off, 30 s on; 15 s off, 30 s
on; 30 s off, 30 s on; 15 s off, 30 s on. After heating and
cooling, the mixture was diluted by ethanol and ana-
lyzed by GC. Methylparaben was used as internal
standard to calibrate the yield of reaction.
literature relevant to the use of ZnCl as a catalyst to
2
perform the esterification under microwave irradiation.
In this report we describe a fast microwave-induced
synthesis of potentially practical use in chemical engi-
neering by esterification of alcohol with p-hydroxyben-
zoic acid in the presence of an inorganic salt ZnCl as
2
a catalyst. The results are compared with the traditional
synthesis. It not only can save reaction time, but can
also reduce the pollution associated with the use of
concentrated sulfuric acid and avoid the complicated
after-treatment handling problems. Although the rea-
son for microwave-assisted chemical reaction has been
extensively investigated, most results contributed to
2.2.2. General procedure
2
(conventional heating
method). A mixture of 3.46 g of p-hydroxybenzoic acid
and 0.35 g ZnCl was introduced to 250 ml reaction
2
flask and then 16 ml of butanol was added. The mixture
was refluxed on a hotplate for 45 min. After heating
and cooling, the product was analyzed as above.
13
‘
hot spot’ or ‘localized superheating’ of the solvent. In
our paper, the reason for this microwave-assisted chem-
ical reaction is discussed by making use of temperature
data of the reaction mixture during the microwave
processing.
2.2.3. GC analysis. The GC was operated with an
injector temperature of 250°C and a helium carrier gas
flow rate of 24 ml/min. The GC column was a non-
polar general-purpose capillary column [30 m×0.25 mm
i.d., 0.25 mm thickness, Phase DB5 (Catalogue No.
2
. Materials and methods
1
22-5032, J&W Scientific Co.)]. The detector (FID) was
2
.1. Materials
operated at 250°C and oven temperature was pro-
grammed as follows: (1) initial temperature was 100°C;
(2) Level 1, 5.0°C/min, 100°C, keep 2 min; (3) Level 2,
10°C/min, 160°C, keep 5 min; (4) Level 3, 10°C/min,
250°C, keep 5 min.
The following chemicals: n-butanol, methylparaben, n-
butylparaben, p-hydroxybenzoic acid, PTSA and ZnCl2
were purchased from Sigma-Aldrich, Canada (Ontario).
All reagents and catalysts were used without further
treatment.
The products were identified by comparison of their
GC retention time with those of authentic samples. The
yields were calculated from the theoretical standard
calibration line.
2.2. Experimental procedure
Reactions have been carried out by employing a Syn-
thewave S402 with a mono-mode MW cavity from
Prolabo operating at 2450 MHz with power range of
3
. Results and discussion
3
.1. The calibration line
The responses of the yields to GC detector were found
to be linear (Fig. 1) to the ratio of the peak areas of
butylparaben (PB(A)) to the peak area of methyl-
paraben (PM(A)).
3
3
.2. Reaction under conventional heating
.2.1. PTSA or ZnCl as a catalyst. As expected, the
2
butylparaben was successfully synthesized using PTSA
as a catalyst by the conventional heating method with a
yield of 76%. However, when PTSA was replaced with
Figure 1. Theoretical calibration line of paraben (yield=num-
ber of mol for ester after reaction/number of mol for acid
before reaction).
ZnCl as catalyst under the same reaction conditions,
2

X. Liao et al. / Tetrahedron Letters 43 (2002) 45–48
47
the yield was reduced to a meager 5% of the original
reaction. The results are shown in Table 1.
as a catalyst under microwave irradiation. However,
the yield was lower than the conventional method due
to the much short reaction time. Interestingly, the yield
3
3
.3. Reactions under microwave irradiation
for the use of ZnCl was slightly higher than that of the
reaction catalyzed by PTSA. The results are also shown
in Table 1.
2
.3.1. PTSA or ZnCl as a catalyst. As expected, the
2
butylparaben was successfully synthesized using PTSA
Table 1. Esterification of p-hydroxybenzoic acid and n-
3
.3.2. Temperature profiles of the reaction. The tempera-
butanol under microwave irradiation and classic heating
ture profiles of the esterification of butanol and p-
hydroxybenzoic acid in the presence of PTSA or ZnCl2
under microwave irradiation are shown in Figs. 2 and
Entry
Catalyst
Heating mode
Yield (%)
3
, respectively.
1
2
3
4
5
6
Microwave irradiation
Conventional heating
Microwave irradiation
Microwave irradiation
Conventional heating
Conventional heating
0
0
41
43
76
3.5
As can be seen, the temperature under microwave
irradiation was slightly higher than the boiling point of
butanol (117.6°C). This is in accordance with the previ-
PTSA
ZnCl2
PTSA
ZnCl2
13i
ous report by Baghurst and Mingos and Hoopes et
13j
al. This results in reaction rate enhancement when
compared with the synthesis by using classic heating. In
classic heating, the temperature provided for the reac-
tion is usually the reflux temperature. The temperature
in the case of ZnCl as a catalyst was also slightly
2
higher than the boiling point of butanol. This cannot
only explain rate enhancement under microwave irradi-
ation, but can also give an explanation for why the
desired product could not be successfully produced
under conventional heating. According to this, it is
important to point out that each catalyst has its exact
reaction temperature whether the reaction is performed
using microwave heating or conventional heating. The
non-thermal effect claimed by some authors probably
result from difficulties relating to temperature distribu-
tion estimation and keeping the absolutely identical
reaction conditions while comparing.
Figure 2. Temperature (°C) profile of esterification under
microwave irradiation in the presence of PTSA.
3
.4. Effect of microwave parameters
In order to optimize the reaction conditions, a series of
experiments in the reactor were performed. Fig. 4
shows the effect of the irradiation power supplied and
the ratio of the reactants on the yield of esterification.
As can be seen, an increase in the irradiation power
provides an increase in the yield of butylparaben. Inter-
estingly, the yield decreases with an increase in the ratio
of the reactants. For example, the higher yield was
obtained when the reactant ratio was 1:1. This result is
different from the traditional concept that large excess
of either acid or alcohol is used in the condensation to
give a higher yield of the desirable esters.
Figure 3. Temperature (°C) profile of esterification under
microwave irradiation in the presence of ZnCl2.
4
. Conclusions
This paper describes a microwave-assisted synthesis of
butylparaben in the presence of ZnCl as a catalyst and
2
identified the reason for the difference between the
reaction performed under microwave heating and con-
ventional heating. In direct esterification, the catalytic
use of inorganic salts is practical and economical
because of its simplicity and applicability to large-sale
Figure 4. Effect of microwave irradiation power supplied (%)
and the ratio of the reactants (molar ratio=butanol/acid) on
the yield of esterification.

4
8
X. Liao et al. / Tetrahedron Letters 43 (2002) 45–48
operations and at the same time avoiding the higher
cost of PTSA or the use of concentrated sulfuric acid.
Also, this procedure gave the right ratio of reactant,
which should be 1:1. With this ratio, the microwave
energy efficiency is the highest. Further optimization of
the irradiation time and microwave power supplied will
be investigated in order to make this microwave tech-
nology applicable in the agriculture and food industries.
9. (a) Majetich, G.; Wheless, In Microwave Heating in
Organic Chemistry; Kingston, H. M.; Stephen, J. H., Eds.
Microwave-enhanced chemistry—Fundamentals, Sample
preparation, and Applications; ACS: Washington DC,
1997; Chapter 8, pp. 455–505; (b) Majetich, G.; Hicks, R.
J. Microw. Power Electromagn. Energy 1995, 30, 27–45;
(c) Majetich, G.; Hicks, R. Radiat. Phys. Chem. 1995, 45,
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Can. J. Chem. 1993, 71, 90–95; (f) Bram, G.; Loupy, A.;
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Bram, G.; Loupy, A.; Majdoub, M.; Gutierrez, E.; Ruiz-
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rez, E.; Loupy, A.; Bram, G.; Ruiz-Hitzky, E.
Tetrahedron Lett. 1989, 30, 945–948.
Acknowledgements
We are grateful for financial support from CIDA
(
Canada international development agency), NSERC
and FCAR funding.
10. Chen, X.; Hong, P.; Dai, S. Huaxue Tongbao. 1993,
38–39.
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