Dehydrative Esterification of Carboxylic Acids with Alcohols Catalyzed by Polymer-Supported Sulfonic Acids in Water

Article abstract of DOI:10.1002/1615-4169(200206)344:3/4<270::AID-ADSC270>3.0.CO;2-7

Dehydrative esterification of carboxylic acids with alcohols in water was efficiently catalyzed by hydrophobic polystyrene-supported sulfonic acids as recoverable and reusable catalysts. In these reactions, esters were obtained in high yields without using any dehydrating agents or apparatus. The sulfonic acid contents of the catalysts and the presence of long alkyl chains on the benzene rings of polystyrene significantly affected the catalytic activity.

Full text of DOI:10.1002/1615-4169(200206)344:3/4<270::AID-ADSC270>3.0.CO;2-7

COMMUNICATIONS
Dehydrative Esterification of Carboxylic Acids with Alcohols
Catalyzed by Polymer-Supported Sulfonic Acids in Water
Kei Manabe, Shu≈ Kobayashi*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, CREST, Japan Science and Technology Corporation
(JST), Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax: ( ‡ 81)-35684-0634, e-mail: skobayas@mol.f.u-tokyo.ac.jp
Received: October 29, 2001; Accepted: February 5, 2002
catalyst. Therefore, we aimed to develop a catalyst that
Abstract: Dehydrative esterification of carboxylic
can be recovered and reused, and envisioned use of
acids with alcohols in water was efficiently catalyzed
polymer-supported catalysts for this purpose.[6,7] Al-
by hydrophobic polystyrene-supported sulfonic acids
though polymer-supported sulfonic acids have been
as recoverable and reusable catalysts. In these
used for Br˘nsted acid-catalyzed reactions including
reactions, esters were obtained in high yields without
ester hydrolysis in water,[8] there is no example of their
using any dehydrating agents or apparatus. The
use for esterification in the medium. Herein we report
sulfonic acid contents of the catalysts and the
that the dehydrative esterification in water was effec-
presence of long alkyl chains on the benzene rings
tively catalyzed by hydrophobic polystyrene-supported
of polystyrene significantly affected the catalytic
sulfonic acids as recoverable and reusable catalysts.
activity.
In our search for effective polymer catalysts for
dehydration reactions in water, the esterification of
lauric acid with 3-phenyl-1-propanol was chosen as a
model, which was catalyzed by DBSA to give the
Keywords: aqueous reactions; Br˘nsted acids; dehy-
dration; esterification; polymer catalysts
corresponding ester in 60% yield after 24 h (Table 1,
¾
entry 1).[3] First, a commercially available DOWEX
50W-X2 (H form, 1)[9] was tested as a representative
Organic reactions in water have been a subject of much polystyrene-supported sulfonic acid. Unexpectedly, it
recent research.[1] Although various efficient synthetic turned out to be totally ineffective even when used in
reactions in aqueous media have been developed so far, large excess (entries 2 and 3). This resin swells signifi-
there are still some problems to be solved. One of the cantly in water due to its high sulfonic acid content.[9] On
most serious problems is that large amounts of water as a the other hand, it has been reported that, in hydrolysis of
solvent have detrimental effects on reactions in which esters, hydrophobic polystyrene-supported sulfonic
water molecules must be removed during the reaction. acids are more active compared with less hydrophobic
An example is acid-catalyzed direct esterification of ones.[8c, d] Therefore, we expected that more hydro-
carboxylic acids with alcohols. Usually in this dehydra- phobic resins would be more effective also in the present
tion reaction, water molecules have to be removed dehydration reaction.
(azeotropically or using a dehydrating agent) to shift the
Thus, we prepared polystyrene-supported sulfonic
equilibrium to the ester formation.[2] On the other hand, acids 2 and 3 whose sulfonic acid contents (0.879 and
we have recently developed surfactant-type Br˘nsted 0.352 mmol/g, respectively) were less than that of 1
acid-catalyzed dehydration reactions such as esterifica- (Scheme 1). As shown in Table 1 (entries 4 and 5), 2 and
tion,[3] etherification, thioetherification, and dithioace- 3 did indeed catalyze the esterification, and the more
talization[4] in water. In these reactions, a surfactant-type hydrophobic 3 was found to be superior to 2. We also
Br˘nsted
acid,
p-dodecylbenzenesulfonic
acid prepared another polymer-supported sulfonic acid 4
(DBSA),[5] and hydrophobic substrates assemble to- (1.01 mmol/g) having a long alkyl group (Scheme 1).
gether through hydrophobic interaction to form emul- With this hydrophobic catalyst 4, the esterification also
sion droplets whose interior is hydrophobic enough to proceeded smoothly (Table 1, entry 6). Most polymer
remove water molecules from the droplets. In addition, catalysts reported for aqueous reactions significantly
DBSA is concentrated onto the surface of the droplets at swell or dissolve in water.[7] On the other hand, both 3
which the reaction takes place, thus enhancing the rate and 4 scarcely swelled in water but worked as efficient
to reach equilibrium.
catalysts. This result indicates that the highly hydro-
Although DBSA catalyzes the dehydration reaction phobic nature of polymer-supported catalysts plays a
to afford the corresponding products in high yields, it very important role for activity in the dehydration
was still difficult to achieve recovery and reuse of the reaction in water.[10]
270
¹ VCH Verlagsgesellschaft mbH, 69451 Weinheim, Germany, 1615-4150/02/3443+4-270 273 $ 17.50-.50/0
Adv. Synth. Catal. 2002, 344, No. 3+4

Dehydrative Esterification of Carboxylic Acids with Alcohols
COMMUNICATIONS
C11H23COOH + HO(CH2)3Ph
SO3H
(1 : 2)
ClSO3H
3 (0.10 equiv.)
H2O
CH2Cl2
C11H23COO(CH2)3Ph
2 (0.879 mmol/g)
3 (0.352 mmol/g)
40 °C, 48 h
1st: 91%
2nd: 91%
3rd: 89%
4th: 92%
5th: 91%
CH3(CH2)16COCl
CO(CH2)16CH3
AlCl3
CS2
Scheme 2.
Table 2. Dehydrative esterification of other substrates in
water.
LiAlH4
(CH2)17CH3
AlCl3
ClSO3H
catalyst (0.10 equiv)
Et2O
reflux
CH2Cl2
RCO2H
+
HOR'
RCO2R'
H2O
40 °C, 48 h
(1 : 2)
Entry
R
R'
Catalyst Yield [%][a]
(CH2)17CH3
1
2
3
4
5
6
Ph(CH2)4-
CH3(CH2)10
CH3(CH2)10
-(CH2)11CH3
-(CH2)11CH3
-(CH2)11CH3
-(CH2)11CH3
-(CH2)11CH3
-(CH2)12Br
3
3
4
3
4
3
92
71
96
45
94
93
SO3H
4 (1.01 mmol/g)
-
-
Scheme 1.
(CH2)7-
(CH2)7-
CH3(CH2)7
CH3(CH2)7
Ph(CH2)4-
The equilibrium position between the ester and the
starting materials restricts the maximum yield of the
ester. From the result of the longer reaction time (120 h,
Table 1, entry 5), the position was found to be almost
identical with that of the DBSA-catalyzed reaction
(entry 1).
[a] Isolated yield.
As expected, the catalysts were recoverable and
reusable. For example, resin 3 was easily recovered by
filtration after the esterification was completed, and the
catalyst was repeatedly reused at least 4 times without
loss of the catalytic activity (Scheme 2).
These polymer-supported catalysts were applied to
other substrates as shown in Table 2. For some sub-
strates having simple aliphatic chains, the reactions with
catalyst 3 proceeded slowly (entries 2 and 4). However,
4 catalyzed the reactions more rapidly (entries 3 and 5).
It should be noted that the presence of long alkyl chains
on the benzene rings in 4 alters the catalytic activity for
these substrates.
In conclusion, dehydrative esterification of carboxylic
acids with alcohols in water was successfully carried out
in the presence of hydrophobic polymer-supported
sulfonic acids as recoverable and reusable catalysts.
The hydrophobic nature and alkyl chains of the catalysts
were found to play important roles in the present
system. This work will not only lead to a practical
synthetic method but also expand the versatility of
catalytic organic reactions in water.
Table 1. Effect of catalysts on dehydrative esterification in
water.
catalyst
C11H23COO(CH2)3Ph
C
11H23COOH + HO(CH2)3Ph
H2O
40 °C, 24 h
(1 : 1)
Yield (%)[a]
Entry
Catalyst (equiv.)
DBSA (0.10)
60 (83, 85[b] [c]
)
1
2
3
4
5
6
1 (0.10)
1 (6.45)
2 (0.10)
3 (0.10)
4 (0.10)
0
2
41
74 (81, 84[b] [c]
)
72
[a] Isolated yield.
[b] NMR yield.
[c] For 120 h.
Adv. Synth. Catal. 2002, 344, 270 273
271

Kei Manabe, Shu≈ Kobayashi
COMMUNICATIONS
carboxylic acid) in water (1.5 mL) was stirred at 40 8C for 24
48 h. Water (5 mL) and ether (for Table 2, entries 1 and 6) or
toluene (for entries 2 5) (2 mL) were added, and the polymer
was filtered and rinsed with ether. The organic layer was
washed with saturated NaHCO3 solution, dried over Na2SO4,
and concentrated. The product was purified by chromatog-
raphy on silica gel.
Experimental Section
Preparation of Polymer-Supported Catalyst 3
To a suspension of polystyrene (3.03 g, 1% DVB cross-linked,
200 400 mesh) in dichloromethane (60 mL) was slowly added
chlorosulfonic acid (0.10 mL) at 0 8C, and the whole was stirred
for 6 h. Acetic acid (30 mL) was added and, after 1 h, the resin
was collected on a glass filter, rinsed with water (50 mL Â 3),
water/THF (1/1, 50 mLÂ3), and dichloromethane (50 mLÂ3),
and dried under vacuum to give resin 3. From the result of
elemental analysis (found: S 1.13%), the sulfonic acid content
was estimated as 0.352 mmol/g. Resin 2 was similarly prepared
by increasing the amount of chlorosulfonic acid used.
Acknowledgements
This work was partially supported by a Grant-in-Aid for
Scientific Research from Japan Society of the Promotion of
Science.
Preparation of Polymer-Supported Catalyst 4
References and Notes
To a mixture of AlCl3 (4.43 g) in carbon disulfide (50 mL) were
added polystyrene (2.31 g, 1% DVB cross-linked, 200 400
mesh) and stearoyl chloride (10.1 g) successively at room
temperature. After stirring for 32 h, 1 N aqueous HCl
(150 mL) was added. After stirring for 12 h, the carbon
disulfide was evaporated, and 1 N aqueous HCl (100 mL)
was added. The resin was collected on a glass filter, rinsed with
water (300 mL), water/THF (1/1, 300 mL), THF (300 mL), and
dichloromethane (300 mL), and dried under vacuum at 60 8C.
According to the result of elemental analysis, the acylation
proceeded quantitatively. Anal. calcd: C 84.26, H 11.42; found:
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[2] a) R. C. Larock, Comprehensive Organic Transforma-
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1
C 84.13, H 11.42; IR (KBr): n ˆ 1686 cm .
The resin was reduced in the following step. AlCl3 (3.91 g)
was added to a mixture of LiAlH4 (1.13 g) in ether (60 mL) in
several portions at 0 8C. After warming to room temperature,
the resin (5.00 g) was added in several portions, and the whole
was heated under reflux for 24 h. After cooling to 0 8C, 1 N
aqueous HCl (180 mL) was added. The mixture was stirred for
13 h, evaporated to remove the ether, and filtered. The
resultant resin was rinsed with 1 N aqueous HCl (100 mL),
water (200 mL), water/THF (1/1, 200 mL), THF (200 mL),
dichloromethane/methanol (5/2, 70 mL), and dichlorome-
thane (150 mL) and dried under vacuum at 60 8C. According
to the result of elemental analysis, the reduction proceeded
quantitatively. Anal. calcd: C 87.56, H 12.44; found: C 87.30, H
12.44. IR and swollen resin-magic angle spinning 13C NMR[11]
(CDCl3) also confirmed disappearance of the carbonyl group.
The resin was then sulfonated as follows. To a suspension of
the resin (724 mg) in dichloromethane (4.0 mL) was added
chlorosulfonic acid (0.080 mL) at 0 8C, and the whole was
stirred for 12 h. Acetic acid (2 mL) was added, and, after
stirring at room temperature for 30 min, water (1 mL) was
added. After further stirring for 30 min, the resultant resin was
collected on a glass filter, rinsed with water/THF (1/1, 100 mL),
THF (50 mL), and dichloromethane (50 mL), and dried under
vacuum at 60 8C. From the result of elemental analysis (found:
S 3.23%), the sulfonic acid content was estimated as
1.01 mmol/g.
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General Procedure for Esterification in Water
[8] a) G. G. Thomas, C. W. Davies, Nature 1947, 159, 372;
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A mixture of a carboxylic acid (0.25 mmol), an alcohol (0.25
0.50 mmol), and a polymer-supportedcatalyst (0.1 equiv. to the
272
Adv. Synth. Catal. 2002, 344, 270 273

Dehydrative Esterification of Carboxylic Acids with Alcohols
COMMUNICATIONS
Makromol. Chem. 1966, 91, 243; d) S. Yoshikawa, O.-K.
Kim, Bull. Chem. Soc. Jpn. 1966, 39, 1515.
[9] The sulfonic acid content of 1 was determined to be
4.41 mmol/g by acid-base titration.
[10] The relationship between catalytic activity and hydro-
phobicity of polymer-supported catalysts has been dis-
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R. Neumann), Chapman & Hall, London, 1997, pp. 424
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Adv. Synth. Catal. 2002, 344, 270 273
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