ORGANIC
LETTERS
2008
Vol. 10, No. 11
2187-2190
Zwitterionic Salts as Mild
Organocatalysts for Transesterification
Kazuaki Ishihara,* Masatoshi Niwa, and Yuji Kosugi
Graduate School of Engineering, Nagoya UniVersity, Furo-cho, Chikusa,
Nagoya 464-8603, Japan
Received March 14, 2008
ABSTRACT
The exothermic reaction of 3,5-bis(trifluoromethyl)phenyl or 4-nitrophenyl isothiocyanate with 4-pyrrolidinopyridine (PPY) gave the corresponding
arylaminothiocarbonylpyridinium salts in quantitative yields. These novel zwitterionic salts were effective as organocatalysts for the
transesterification reaction of an equimolar mixture of methyl carboxylates and alcohols in hydrocarbons such as heptane and octane under
azeotropic reflux conditions with the removal of methanol. In sharp contrast, PPY was inert as a catalyst under the same reaction conditions.
The transesterification reaction is one of the most popular
methods for synthesizing carboxylic esters. Although several
procedures catalyzed by a variety of protic and Lewis acids,
organic and inorganic bases, enzymes, and antibodies have
been developed,1,2 a more efficient and more generally
applicable transesterification procedure involving simple
preparations and a nontoxic catalyst is still needed. We report
nothiocarbonylpyridinium salt (2) are mild organocatalysts
for the transesterification reaction of an equimolar mixture
of methyl carboxylates and alcohols.
Initially, we envisaged the possibility of dual activation
of the transesterification reaction based on acid-base
combination chemistry.3,4 N,N′-[3,5-Bis(trifluoromethyl)phe-
nyl]thiourea (3)5 and 4-pyrroridinopyridine (PPY)6 were
examined as a Brønsted acid catalyst and a nucleophilic base
catalyst, respectively, for the dual activation of methyl
phenylacetate for transesterification between methyl pheny-
lacetate and benzyl alcohol. As shown in entries 1 and 2 of
Table 1, transesterification in heptane under azeotropic reflux
conditions with the removal of methanol proceeded smoothly
in the presence of 2 mol % each of 3 and PPY. Methanol
here
that
[3,5-bis(trifluoromethyl)phenyl]ami-
nothiocarbonylpyridinium salt (1) and (4-nitrophenyl)ami-
(1) For reviews of (trans)esterifications, see: (a) Otera, J. Chem. ReV.
1993, 93, 1449–1470. (b) Otera, J. Esterification; Wiley-VCH Verlag
GmbH: Weinheim, Germany, 2003. (c) Otera, J. Acc. Chem. Res. 2004,
37, 288–296. (d) Grasa, G. A.; Singh, R.; Nolan, S. P. Synthesis 2004,
971, 985. (e) Hoydonckx, H. E.; De Vos, D. E.; Chavan, S. A.; Jacobs,
P. A. Top. Catal. 2004, 27, 83–06. (f) Enders, D.; Niemeier, O.; Henseler,
A. Chem. ReV. 2007, 107, 5606–5655
.
(2) For recent contributions regarding catalytic transesterifications, see:
(a) de Sairre, M. I.; Bronze-Uhle, E. S.; Donate, P. M. Tetrahedron Lett.
2005, 46, 2705–2708. (b) Jiang, P.; Zhang, D.; Li, Q.; Lu, Y. Catal. Lett.
2006, 110, 101–106. (c) Remme, N.; Koschek, K.; Schneider, C. Synlett
2007, 491, 493. (d) Kondaiah, G. C. M.; Reddy, L. A.; Babu, K. S.; Gurav,
V. M.; Huge, K. G.; Bandichhor, R.; Reddy, P. P.; Bhattacharya, A.; Anand,
R. V. Tetrahedron Lett. 2008, 49, 106–109. (e) Ohshima, T.; Iwasaki, T.;
Maegawa, Y.; Yoshiyama, A.; Mashima, K. J. Am. Chem. Soc. 2008, 130,
(3) For our account article, see: Ishihara, K.; Sakakura, A.; Hatano, M.
Synlett 2007, 686, 703
(4) For a recent review of bifunctional acid-base catalysts, see: Kanai,
M.; Kato, N.; Ichikawa, E.; Shibasaki, M. Synlett 2005, 1491, 1508
.
.
(5) (a) Schreiner, P. R. Chem. Soc. ReV. 2003, 32, 289–296. (b)
Wittkopp, A.; Schreiner, P. R. Chem. Eur. J. 2003, 9, 407–414.
(6) (a) Hassner, A.; Krepski, L. R.; Alexanilan, V. Tetrahedron 1978,
34, 2069–2076. (b) Held, I.; Xu, S.; Zipse, H. Synthesis 2007, 1185–1196,
and references cited therein.
2944–2945. (f) Inahashi, N.; Fujiwara, T.; Sato, T. Synlett 2008, 605–607
.
10.1021/ol8005979 CCC: $40.75
Published on Web 04/29/2008
2008 American Chemical Society