T. Kawabata et al. / Tetrahedron Letters 44 (2003) 9205–9208
9207
The transformation of a carboxylic acid to the corre-
sponding methyl ester is also important synthetic
sequence, especially as protecting groups for the car-
boxylic functions.1a The present Ti4+-mont can
efficiently catalyze the esterifications of various car-
boxylic acids with methanol, and the results are sum-
marized in Table 3.
protocol’ to replace homogeneous acids for the above
versatile reactions as a strong solid acid catalyst.
Acknowledgements
This work is financially supported by the center of
excellence (21COE) program ‘Creation of Integrated
EcoChemistry’ of Osaka University. We are also grate-
ful to the Department of Chemical Science and Engi-
neering, Graduate School of Engineering Science,
Osaka University, for scientific support with the gas-
hydrate analyzing system (GHAS) and lend-lease labo-
ratory system.
Several primary carboxylic acids were readily esterified
to the corresponding methyl esters (entries 1, 5, and 6).
Suberic acid afforded the dimethyl ester in a 99% yield
(entry 7). Notably, the esterification of homophthalic
acid occurred chemoselectively at the non-conjugated
carboxylic group to yield methyl 2-carboxyphenyl-
acetate without formation of the diester; similar results
were also observed for itaconic acid (entries 8 and
9).2c,2g,15 It is noteworthy that the hydrolysis of the
methyl esters, even in the presence of both Ti4+-mont
and large amounts of water, was not observed under
the reflux conditions of methanol.16
References
1. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis; John Wiley and Sons: New York,
1999; (b) Larock, R. C. Comprehensive Organic Transfor-
mations; VCH: New York, 1989; p. 966.
Presumably, the prominent catalytic activity of the
Ti4+-mont might arise from the strong acid sites associ-
ated with the chain-like Ti domains within the interlay-
ers.7 In polar organic molecules, the interlayer space is
effectively expanded, allowing access of the substrates
to the catalytic site of the Ti species.17 Vide supra,
water molecules adsorbed on the interlamellar surfaces
expel the hydrophobic esters from the Ti species, which
prevents hydrolysis of the product esters.
2. For representative examples of homogeneous catalytic
esterifications, see: (a) iodine: Ramalinga, K.; Vijayalak-
shmi, P.; Kaimal, T. N. B. Tetrahedron Lett. 2002, 43,
879; (b) polyaniline salt: Palaniappan, S.; Ram, M. S.
Green Chem. 2002, 4, 53; (c) CBr4/hw: Lee, A. S.-Y.;
Yang, H.-C.; Su, F.-Y. Tetrahedron Lett. 2001, 42, 301;
(d) hafnium salt: Ishihara, K.; Ohara, S.; Yamamoto, H.
Science 2000, 290, 1140; (e) diphenyl ammonium triflate:
Wakasugi, K.; Misaki, T.; Yamada, K.; Tanabe, Y.
Tetrahedron Lett. 2000, 41, 5249; (f) ceric ammonium
nitrate: Goswani, P.; Chowdhury, P. New J. Chem. 2000,
24, 955; (g) 2,2-dimethoxypropane/TMSCl: Rodr´ıguez,
A.; Nomen, M.; Spur, B. W. Tetrahedron Lett. 1998, 39,
8563; (h) distannoxane: Otera, J.; Dan-oh, N.; Nozaki,
H. J. Org. Chem. 1991, 56, 5307.
In conclusion, esterification of equimolar amount of
carboxylic acids and alcohols was successfully carried
out using the Ti4+-exchanged montmorillonite as a
strong solid acid catalyst under solvent-free conditions.
Furthermore, the catalyst was reusable without any
appreciable losses of its high activity and selectivity. We
strongly believe that the Ti4+-mont can provide a ‘green
3. Pioneering works for the esterification using heteroge-
neous catalysts, (a) silica-supported sulphonic acid:
Bossaert, W. D.; De Vos, D. E.; Van Rhijn, W. M.;
Bullen, J.; Grobet, P. J.; Jacobs, P. A. J. Catal. 1999, 182,
156; (b) graphite bisulfite: Bertine, J.; Kagan, H. B.;
Luche, J.-L. J. Am. Chem. Soc. 1974, 96, 8113.
Table 3. Esterification of carboxylic acids with MeOH
using the Ti4+-mont-catalysta
4. (a) Clark, J. H. Green Chem. 1999, 1, 1; (b) Anastas, P.
T.; Warner, J. C. Green Chemistry: Theory and Practice;
Oxford University Press, 1998; (c) Sheldon, R. A.
Chemtech 1994, 38; (d) Trost, B. M. Science 1991, 254,
1471.
5. Excellent reviews of the mont-catalyzed organic synthe-
ses: (a) Clark, J. H.; Macquarrie, D. J. Chem. Soc. Rev.
1996, 303; (b) Izumi, Y.; Onaka, M. Adv. Catal. 1992, 38,
245; (c) Laszlo, P. Acc. Chem. Res. 1986, 19, 121; (d)
Pinnavaia, T. J. Science 1983, 220, 365.
6. Alkylation and acetalization using metal-modified mont-
morillonite catalysts have been reported, for example, see:
(a) Ce3+-mont: Tateiwa, J.; Horiuchi, H.; Uemura, S. J.
Org. Chem. 1995, 60, 4039; (b) Zr4+-mont: Tateiwa, J.;
Horiuchi, H.; Hashimoto, K.; Yamauchi, T.; Uemura, S.
J. Org. Chem. 1994, 59, 5901.
7. (a) Kawabata, T.; Kato, M.; Mizugaki, T.; Ebitani, K.;
Kaneda, K. Chem. Lett. 2003, 32, 648; (b) Kawabata, T.;
Mizugaki, T.; Ebitani, K.; Kaneda, K. Tetrahedron Lett.
a
Reaction conditions: Ti4+-mont (0.15 g, Ti: 0.1 mmol), carboxylic
acid (1 mmol), MeOH (10 mL), 70°C.
b All products were characterized by 1H NMR and mass spectra.
c Yields of products were determined by GLC analysis using internal
standards based on carboxylic acid.