Short Articles
Bull. Chem. Soc. Jpn., 78, 1371–1372 (2005) 1371
drogenation of the substrate. The in-situ modification was car-
ried out in the reactor during the initial stage of the hydroge-
nation.6 Here, tartaric acid (and if necessary, NaBr) was added
to the reaction media. It was demonstrated that the tartaric
acid-NaBr-in-situ-modified reduced nickel catalyst maintained
about an 80% e.d.a. during 20 runs,6 whereas the pre-modified
nickel catalyst lost most of the virgin e.d.a. after only a few
runs.
For both methods, many variables need to be optimized for
attaining a high e.d.a. For example, the type of nickel catalyst
and the method of activation, the type and amount of the modi-
fier and co-modifier, the pH and temperature of the modifica-
tion solution (for the pre-modification), and the reaction tem-
perature and the additive to the reaction media.
During studies for optimizing the variables affecting the
e.d.a., it was demonstrated that the addition of carboxylic acid
to the reaction media increased the e.d.a. of the pre-modified
catalyst.2,7 During the hydrogenation of ꢀ-ketoesters, a small
amount of acetic acid increased the e.d.a. by 10–20%. Harada
et al. demonstrated that the added acetic acid converted the so-
dium nickel tartrate adsorbed on the ‘‘enantio-differentiating
site’’ to nickel hydrogen tartrate, and that this increased the
e.d.a. of the tartaric acid-NaBr-pre-modified nickel catalyst.8
In the present paper, we describe the effects of acetic acid
added to the reaction media on the rate of the hydrogenation
of methyl acetoacetate over the in-situ modified and unmodi-
fied nickel catalysts and on the e.d.a. of the in-situ modified
catalyst.
Specific Acceleration of the
Hydrogenation of Methyl
Acetoacetate on Enantio-
Differentiating Sites of a Tartaric
Acid-Modified Nickel Catalyst
by the Addition of Acetic Acid
to the Reaction Media
ꢀ
Tsutomu Osawa, Masashi Ando,
Tadao Harada,1 and Osamu Takayasu
Faculty of Science, Toyama University,
Gofuku, Toyama 930-8555
1Faculty of Science and Technology, Ryukoku University,
Seta, Otsu 520-2194
Received January 25, 2005; E-mail: osawa@sci.toyama-u.ac.jp
The hydrogenation of methyl acetoacetate on enantio-
differentiating sites of a tartaric acid-modified nickel catalyst
was specifically accelerated by the addition of acetic acid to
the reaction media to increase the enantio-differentiating
ability of the catalyst.
A typical experimental procedure is as follows. Nickel
oxide (Wako Pure Chemical Industries, Ltd., lot LDQ3413)
was calcined in air at 1373 K for 6 h. The resultant nickel
oxide was reduced at 623 K in a hydrogen stream for 1 h (40
cm3 minꢁ1) to produce a reduced nickel catalyst. Methyl ace-
toacetate (5 g) was hydrogenated with the reduced nickel cat-
alyst (0.5 g) in a mixture of THF (10 cm3) and acetic acid. For
hydrogenation over an in-situ modified catalyst, (R,R)-tartaric
acid (1.7 mg) was added to the reaction mixture. Hydrogena-
tion was carried out in a stirred autoclave at an initial hydrogen
pressure of 9 MPa and at 373 K. To avoid mass diffusion con-
trol, the stirring rate and the amount of the catalyst were exam-
ined. A stirring rate of 1370 rpm and a catalyst amount of 0.5 g
were the optimum conditions, which avoided mass diffusion
control, and the apparent hydrogenation rate would represent
the intrinsic rate of hydrogenation. The hydrogen pressure in
the reactor was automatically recorded by a PC every one min-
ute. The hydrogenation rate was expressed by the amount of
hydrogen consumption during the reaction after the tempera-
ture of the autoclave reached the reaction temperature (373
K). After the reaction was completed, the reaction solution
was separated by decantation from the catalyst, and then sub-
jected to distillation. The e.d.a. of the catalyst was expressed
by the optical purity of the methyl 3-hydroxylbutyrate deter-
mined by polarimetry.
The production of optically active compounds is an impor-
tant issue in synthetic organic chemistry, especially in the
fields of pharmaceutical, flavor- and aroma-chemicals, and
agro-chemicals.1 Enantio-differentiating solid catalysts for this
purpose have attracted much attention because of their easy
handling, that is, easy preparation, easy separation, easy recov-
ery and reuse, and ease to scale up, compared with the homo-
geneous ones.
The tartaric acid-modified nickel catalyst is one of the most
successful enantio-differentiating solid catalysts. The hydroge-
nation of ꢀ-ketoesters attained an enantio-differentiating abil-
ity (e.d.a.) of 90–98%,2–4 and that of 2-alkanones attained an
e.d.a. of 80–85%4 over a tartaric acid-NaBr-modified nickel
catalyst (Chart 1).
Modified catalyst can be prepared by two methods, one is a
pre-modification and the other is an in-situ modification. The
pre-modification method has been typically studied for many
years.5 An activated nickel catalyst is soaked in an aqueous so-
lution of tartaric acid (modifier) and NaBr (co-modifier, if nec-
essary) at pH 3.2 and 373 K. A pre-modified nickel catalyst
was prepared in a different vessel from the reactor before hy-
20
Optical purity/% = (½ꢁꢂD of methyl 3-hydroxybutyrate/
20
½ꢁꢂD of pure enantiomer) ꢃ 100. It was calculated using the
(R,R)-tartaric acid-modified Ni
H3C
OCH3
H3C
OCH3
20
value of ½ꢁꢂD ¼ ꢁ22:95 (neat) for the optically pure (R)-
H2
THF, acetic acid
OH
O
methyl 3-hydroxylbutyrate.5
O
O
main product
Figure 1 shows the effect of the addition of acetic acid to the
reaction media on the hydrogenation rate. In the absence of
Chart 1.
Published on the web July 1, 2005; DOI 10.1246/bcsj.78.1371