Masaya Nakayama et al.
COMMUNICATIONS
Acknowledgements
Financial support for this project has been provided by SORST,
JST and the Yamada Science Foundation.
References and Notes
[1] K. Ishihara, S. Ohara, H. Yamamoto, Science 2000, 390,
1140.
[2] K. Ishihara, M. Nakayama, S. Ohara, H. Yamamoto, Syn-
lett 2001, 1117.
Scheme 4. Application to large-scale synthesis of benzyl tet-
rahydro-2-furoate.
[3] K. Ishihara, M. Nakayama, S. Ohara, H. Yamamoto, Tet-
rahedron 2002, 58, 8179.
action (100 mmol scale) more than four times, and no
loss of activity was observed for the recovered catalyst.
This means that the turnover number (TON) is greater
than 4000 and the turnover frequency (TOF) exceeds
[4] a) T. W. Greene, P. G. M. Wuts, Protective Groups on Or-
ganic Synthesis, 3rd edn., John Wiley and Sons, New
York, 1999; b) P. Kocienski, Protecting Groups, 3rd
edn., Thieme, Stuttgart, New York, 2003; c) J. Otera, Es-
terification, Wiley-VCH, Weinheim, 2003; d) J. Otera,
Acc. Chem. Res. 2004, 37, 288.
170 hꢀ1
.
In summary, we have shown that ZrOCl2 ·8 H2O and
HfOCl2 ·8 H2O are highly effective, water-tolerant,
and reusable homogeneous catalysts for direct ester
condensation between equimolar amounts of carboxylic
acids and alcohols. Notably, zirconium(IV) salts such as
ZrOCl2 ·8 H2O and Zr(OAc)x(OH)y are potential green
catalysts due to their low toxicity, commercial availabil-
ity at low cost, ease of handling, high catalytic activity,
and reusability.[12] In addition, our new system for recy-
clingof catalysts usingwater is economically and envi-
ronmentally superior to recent biphasic systems using
fluorous solvents and ionic liquids. We believe that our
new method for ester condensation may be useful as
an environmentally and industrially ideal condensation
method in the near future. Further studies aimed at ex-
ploringmore active and recyclable catalysts are ongo-
ing.
[5] For esterification of carboxylic acids with equimolar
amounts of alcohols, see: a) K. Wakasugi, T. Misakai,
K. Yamada, Y. Tanabe, Tetrahedron Lett. 2000, 41, 5249
; b) K. Manabe, S. Iimura, X.-M. Sun, S. Kobayashi, J.
Am. Chem. Soc. 2002, #124#125, 11971; c) T. Kawabata,
T. Mizugaki, K. Ebitani, K. Kaneda, Tetrahedron Lett.
2003, 44, 9205; d) L. J. Gooben, A. Dꢁhring, Synlett
2004, 263; see also, refs.[1–3]
[6] For reusable esterification catalysts, see: a) J. Xiang, S.
Toyoshima, A. Orita, J. Otera, Angew. Chem. Int. Ed.
2001, 40, 3670; b) J. Xiang, A. Orita, J. Otera, Adv. Synth.
Catal. 2002, 344, 84; c) K. Ishihara, A. Hasegawa, H. Ya-
mamoto, Angew. Chem. Int. Ed. 2001, 40, 4077; d) K. Ish-
ihara, A. Hasegawa, H. Yamamoto, Synlett 2002, 1296;
e) K. Ishihara, A. Hasegawa, H. Yamamoto, Synlett
2002, 1299.
[7] Although HfCl4 and ZrCl4 are also good catalysts for di-
rect esterification, these salts are very sensitive to mois-
ture; see ref.[3]
[8] a) Ya. G. Goroshchenko, T. P. Spasibenko, Zhurnal Neo-
rganicheskoi Khimii 1967, 12, 302; b) V. F. Chuvaev, I. V.
Potapova, Z. N. Prozorovskaya, V. I. Spitsyn, Doklady
Akademi Nauk SSSR 1973, 208, 405.
Experimental Section
General Procedure for the Esterification Catalyzed by
Zr(OAc)x(OH)y and Catalyst Recycling (Table 4)
[9] The zirconyl group consists of a complex in which four
zirconium atoms are at the corners of a slightly distorted
square and are linked alongeach edge of the square by
two OH groups: one above and one below the plane of
the square. Four water molecules are bound to each zir-
conium in such a manner that the arrangement of the
eight oxygens about each zirconium is a distorted square
antiprism. There are no zirconium-halogen bonds in this
structure. A. Clearfield, P. A. Vaughan, Acta Crystallog-
raphica 1956, 9, 555.
[10] When neutral water was used in place of 1 M hydrochlor-
ic acid to quench the reaction mixture, zirconium(IV)
and hafnium(IV) species were not completely extracted
from the organic layers. No chloride ions were included
in the metal species that were extracted with water, but
the recovered metal species were highly active as cata-
A 5-mL, single-necked, round-bottomed flask equipped with a
Teflon-coated magnetic stirring bar and a Dean–Stark appara-
tus surmounted byareflux condenser wascharged withcarbox-
ylic acid (5 mmol) and alcohol (5 mmol) as substrates and
Zr(OAc)x(OH)y (1–3 mol %) as a catalyst in hydrocarbons
such as octane or toluene (2.5 mL). The mixture was brought
to reflux with the removal of water. After the reaction was
completed, the resultingmixture was cooled to ambient tem-
perature and 1 M hydrochloric acid (0.5–1.5 mL) was added.
After beingstirred for 0.5 h, the product was isolated from
the organic layer by simple extraction with Et2O (2 mL) twice.
On the other hand, the catalyst remained in the aqueous layer,
which was used directly in the next reaction without removing
the water. The yields of the 2nd, 3rd, and 4th runs were compa-
rable to that of the 1st run.
1278
ꢀ 2004 WILEY-VCH VerlagGmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2004, 346, 1275–1279