Dehydration reactions in water. Surfactant-type Bronsted acid-catalyzed direct esterification of carboxylic acids with alcohols in an emulsion system [2]

Full text of DOI:10.1021/ja016338q

J. Am. Chem. Soc. 2001, 123, 10101-10102
Dehydration Reactions in Water. Surfactant-Type
10101
Brønsted Acid-Catalyzed Direct Esterification of
Carboxylic Acids with Alcohols in an Emulsion
System
Kei Manabe, Xiang-Min Sun, and Shuj Kobayashi*
Graduate School of Pharmaceutical Sciences
The UniVersity of Tokyo, CREST
Japan Science and Technology Corporation (JST)
Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Figure 1. Illustration of direct esterification by dehydration in the
ReceiVed June 4, 2001
ReVised Manuscript ReceiVed July 22, 2001
presence of a surfactant-type catalyst in water.
the products (esters) would lie at the ester side, because water
molecules would be expelled out of the droplets due to hydro-
phobic nature of their interior. As a result, the dehydration
reactions would efficiently proceed even in the presence of a large
amount of water as a solvent. Dehydration in water is really
unusual and exciting because in water usually hydrolysis occurs.
Indeed, the acid-catalyzed direct formation of esters with the aid
of surfactants in water has not been reported as far as we know,
although surfactants have been occasionally used to accelerate
the reactions to the opposite direction: hydrolysis of esters.7 Here
we show that direct esterification in water was realized using a
surfactant-type Brønsted acid and that selective esterification was
also observed in this system.
First, we carried out the esterification of carboxylic acids with
3-phenyl-1-propanol (the molar ratio of a carboxylic acid to the
alcohol ) 1:1) in the presence of 10 mol % p-dodecylbenzene-
sulfonic acid (DBSA),8 a surfactant-type Brønsted acid, at 40 °C
for 24 h in water. When acetic acid was used as a substrate, the
yield of 3-phenylpropyl acetate was only 6% (determined by 1H
NMR). To our delight, however, the reactions of more lipophilic
carboxylic acids proceeded in water to afford the corresponding
esters in acceptable yields (butyric acid: 31% yield; caprylic
acid: 61% yield; lauric acid: 63% yield).9 It should be noted
that the ester formation was realized at 40 °C in water in contrast
to high temperatures which are required for conventional azeo-
tropic removal of water in organic solvents.
Sodium p-dodecylbenzenesulfonate instead of DBSA did not
catalyze the esterification of lauric acid (1% yield), indicating
that the catalytic species is proton. It is also noteworthy to mention
that the esterification in the presence of p-toluenesulfonic acid
(TsOH) as a catalyst proceeded very slowly. According to a study
on the initial rates of the esterification of lauric acid with 3-phenyl-
1-propanol, DBSA was found to catalyze the reaction 60 times
faster than TsOH did (for DBSA, 5.41 × 10-3 M h-1; for TsOH,
9.05 × 10-5 M h-1). These results clearly demonstrate that both
the long-chain alkyl and the sulfonic acid moiety of DBSA are
crucial for efficient catalysis. In the case of using DBSA, the
reaction mixtures became white turbid emulsions, as in the case
of DBSA-catalyzed Mannich-type reactions, in which the forma-
tion of white turbid mixtures was important for good yields of
the desired Mannich adducts.3a-c Formation of emulsion droplets
in the present reaction system was confirmed by optical micros-
copy (Figure 2).10
Recently, organic reactions in water have received much
attention, because water is a cheap, safe, and environmentally
benign solvent.1 Our and others’ studies on surfactant-type Lewis2
or Brønsted acid3 catalysts revealed that carbon-carbon bond-
forming reactions proceeded in the presence of these catalysts in
water. Under the reaction conditions, emulsion droplets were
formed from catalytic amounts of these catalysts and reaction
substrates.2c,3c,4 These droplets, although dispersed in water, are
hydrophobic enough for protecting water-labile substrates such
as silyl enolates from hydrolytic decomposition. These results
prompted us to realize dehydration reactions in water.
Acid-catalyzed direct esterification5 of carboxylic acids with
alcohols was selected as a representative dehydration reaction.
Generally, direct esterification is carried out in organic solvents
and needs either of two methods to shift the equilibrium between
reactants and products.6 One is removal (azeotropically or using
dehydrating agents) of water generated as the reactions proceed,
and the other is use of large excess amounts of one of the
reactants. On the other hand, our idea is that the esterification
would be realized even in water without using a large excess of
reactants. The concept is shown in Figure 1. The surfactant-type
catalysts and organic substrates (carboxylic acids and alcohols)
in water would form the droplets whose interior is hydrophobic.
The surfactants would concentrate a catalytic species such as
proton onto the droplets’ surfaces, where the reaction takes place,
and then enhance the rate to reach equilibrium. For lipophilic
substrates, the equilibrium position between the substrates and
(1) (a) Organic Synthesis in Water; Grieco, P. A., Ed.; Blackie Academic
and Professional: London, 1998. (b) Li, C.-J.; Chan, T.-H. Organic Reactions
in Aqueous Media: John Wiley & Sons: New York, 1997.
(2) (a) Kobayashi, S.; Wakabayashi, T.; Nagayama, S.; Oyamada, H.
Tetrahedron Lett. 1997, 38, 4559. (b) Kobayashi, S.; Wakabayashi, T.
Tetrahedron Lett. 1998, 39, 5389. (c) Manabe, K.; Mori, Y.; Wakabayashi,
T.; Nagayama, S.; Kobayashi, S. J. Am. Chem. Soc. 2000, 122, 7202. (d)
Mori, Y.; Kakumoto, K.; Manabe, K.; Kobayashi, S. Tetrahedron Lett. 2000,
41, 3107. (e) Manabe, K.; Aoyama, N.; Kobayashi, S. AdV. Synth. Catal. 2001,
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Kobayashi, S. Tetrahedron 2001, 57, 2537. (d) Akiyama, T.; Takaya, J.;
Kagoshima, H. Synlett 1999, 1426. (e) Akiyama, T.; Takaya, J.; Kagoshima,
H. Tetrahedron Lett. 1999, 40, 7831.
(4) Emulsion systems have been used for organic reactions. One successful
example is emulsion polymerization. For example: Harkins, W. D. J. Am.
Chem. Soc. 1947, 69, 1428.
(5) (a) Larock, R. C. ComprehensiVe Organic Transformations; John Wiley
& Sons: New York, 1999. (b) Greene, T. W.; Wuts, P. G. M. ProtectiVe
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(b) Izumi, J.; Shiina, I.; Mukaiyama, T. Chem. Lett. 1995, 141. (c) Ishihara,
K.; Ohara, S.; Yamamoto, H. J. Org. Chem. 1996, 61, 4196. (d) Ishihara, K.;
Ohara, S.; Yamamoto, H. Science 2000, 290, 1140. (e) Masaki, Y.; Tanaka,
N.; Miura, T. Chem. Lett. 1997, 55. (f) Storck, S.; Maier, W. F.; Salvado, I.
M. M.; Ferreira, J. M. F.; Guhl, D.; Souverijins, W.; Martens, J. A. J. Catal.
1997, 172, 414. (g) Zhang, G.-S. Synth. Commun. 1999, 29, 607. Esterification
under water-toluene two-phase conditions has been reported, although the
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Nakato, T. Catal. Today 1998, 45, 73.
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(8) p-Dodecylbenzenesulfonic acid (soft type) was purchased from Tokyo
Kasei Kogyo Co., Ltd. This is a mixture of linear alkylbenzenesulfonic acids.
Its molecular weight was regarded as 326.50.
(9) The esterification of lauric acid with ethanol (a more hydrophilic
alcohol) resulted in 6% yield.
(10) Stirring (usually 1400 rpm) of the reaction mixture was not very
important to keep it an emulsion system. Without stirring, large, visible droplets
were formed, but the aqueous phase was still a white turbid solution (the
yield of 3-phenylpropyl laurate is 58% after 24 h at 40 °C without stirring).
Cf. ref 2c.
10.1021/ja016338q CCC: $20.00 © 2001 American Chemical Society
Published on Web 09/22/2001

10102 J. Am. Chem. Soc., Vol. 123, No. 41, 2001
Communications to the Editor
Table 2. Selective Esterification Catalyzed by DBSA in Water
Figure 2. Optical micrograph of the reaction mixture of DBSA (10 mol
%)-catalyzed esterification of lauric acid with 3-phenyl-1-propanol (1:1)
in water.
1
a Determined by H NMR. b 120 h.
esterification based on the difference of hydrophobicity was also
observed for other substrates (entries 2 and 3). Furthermore,
preferential esterification of nonconjugated carboxylic acids over
aromatic or conjugated carboxylic acids11 was also attained
(entries 4 and 5). These results of the selective esterification
significantly expand the utility of the DBSA-catalyzed reactions
in water.
Figure 3. Reaction profiles for esterification of lauric acid with 3-phenyl-
1-propanol (1:1) in the presence of DBSA (10 mol %) in water. (4) at
30 °C; (() at 40 °C; (O) at 60 °C.
In conclusion, dehydration reactions were conducted to yield
esters in water using DBSA as a surfactant-type Brønsted acid
catalyst, and unique selective esterification was also attained. The
reactions need neither dehydrating agents nor azeotropic removal
of water. Instead, the catalyst and substrates in the present system
assemble together through hydrophobic interactions to form
devices for dehydration reactions (“dehydrating devices”), in
which the catalyst enhances the reaction rate and hydrophobic
interior of emulsion droplets facilitates exclusion of water
molecules. Furthermore, since both of the sole byproduct and the
solvent in the esterification are water, the reactions are atom-
economical12 and may lead to a method which solves some
environmental problems. This work will not only lead to a
practical synthetic method but also provide a new aspect of
chemistry in water.
Table 1. Esterification Catalyzed by DBSA in Water
a Isolated yield.
Acknowledgment. This work was partially supported by a Grant-
in-Aid for Scientific Research from the Ministry of Education, Culture,
Sports, Science and Technology, Japan.
Figure 3 shows the profiles of the DBSA-catalyzed reaction
of lauric acid with 3-phenyl-1-propanol (1:1) at various temper-
atures. At 40 °C, the reaction reached its equilibrium position in
120 h with a maximum yield of 84%. Raising the temperature to
60 °C made the reaction faster, although its maximum yield
slightly decreased to 80%. At 30 °C, the time required to reach
the equilibrium position increased significantly.
This catalytic system was applied to other substrates as shown
in Table 1. The use of 2 equiv of alcohols improved the yields to
greater than 90% for most cases.
We next investigated selective esterification in this system.
When a 1:1 mixture of lauric acid and acetic acid was esterified
with 3-phenyl-1-propanol in the presence of DBSA in water,
3-phenylpropyl laurate was selectively obtained (Table 2, entry
1). This selectivity is attributed to the hydrophobic nature of lauric
acid and is unique to the present reaction system. Selective
Supporting Information Available: Experimental details for the
esterification and the initial rate kinetics, and characterization of the
products (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
JA016338Q
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