392
Chemistry Letters 2001
Highly Durable Enantio-Differentiating Nickel Catalyst for Repeated Use
for the Hydrogenation of Methyl Acetoacetate
Tsutomu Osawa,* Saori Sakai, Tadao Harada,† and Osamu Takayasu
Faculty of Science, Toyama University, Gofuku, Toyama 930-8555
†Faculty of Science and Technology, Ryukoku University, Seta, Otsu 520-2194
(Received February 5, 2001; CL-010100)
The enantio-differentiating hydrogenation of methyl ace-
situ modification.
The typical experimental procedure is as follows. Fine Ni
toacetate was repeated 30 times over a fine Ni powder catalyst
while modifiers (optically active tartaric acid and NaBr) were
directly added to the reaction media only in the first run. Over
80% optical yields were attained for the repeated runs. The
addition of sodium 2-ethylhexanoate increased the optical
yields in the subsequent runs. The very simple and highly
durable enantio-differentiating nickel catalyst for repeated use
was developed by an in situ modification.
powder (0.5 g) (Vacuum Metallurgical Co., Ltd., Chiba, Japan)
was treated in a hydrogen stream at 280 °C for 0.5 h. Methyl
acetoacetate (5 g) was hydrogenated with the activated fine Ni
powder in a mixture of THF (10 mL) and acetic acid (0.1 g).
(R,R)-TA (0.1 g) and NaBr (2 mg) were added to the reaction
mixture only in the first run. NaBr was added as an aqueous
solution of 50 µL distilled water. The hydrogenation was car-
ried out in a 30 mL glass tube in a 100 mL stainless steel auto-
clave at the initial hydrogen pressure of 9 MPa and at 100 °C.
After the reaction was completed, the reaction media was sepa-
rated by decantation from the catalyst and then subjected to dis-
tillation. The optical purity of the methyl 3-hydroxylbutyrate
was determined by polarimetry. It was calculated using the
value of [α]D20 = -22.95 (neat) for the optically pure (R)-methyl
3-hydroxylbutyrate. For the repeated use of the catalyst, the
catalyst remaining in the glass tube was washed three times
with THF (3 × 10 mL) and then used for the next run under the
same reaction conditions except for TA and NaBr. In the pres-
ent study, sodium 2-ethylhexanoate (5 mg in 50 µL THF) was
added to the reaction media (methyl acetoacetate, THF, and
acetic acid) in the 5th and 26th runs. The hydrogenation was
completed within 5 h for the first run, and within 2 h for the
runs from 2 to 30. No decrease in the hydrogenation activity
was observed under the present experimental conditions during
the repeated runs.
Figure 1 shows the results on the optical yield in the
repeated runs of the catalyst. In the runs from the first to the
4th, the optical yields were maintained at about 70%. When
racemic sodium 2-ethylhexanoate was added to the reaction
media in the 5th run, the optical yield increased to 80%. In runs
6 to 23, 80 to 85% optical yields were obtained. In runs 24 to
26, 76 to 78% optical yields were attained. The addition of
sodium 2-ethylhexanoate to the reaction media in the 26th run
recovered the optical yield of 80% for the 27th run. These runs
show a remarkable durability of the catalyst for the enantio-dif-
ferentiating hydrogenation. The addition of only 0.1 g of (R,R)-
TA to the reaction media involving the fine Ni powder (0.5 g)
in the first run gave optically active methyl 3-hydroxybutyrate
for 30 runs. The addition of sodium 2-ethylhexanoate increased
the optical yield of the reaction. As we demonstrated that sodi-
um ions were important for the effective enantio-
differentiation,8 the effect of the sodium ions on the optical
yield was confirmed again in the repeated runs of the catalyst
prepared by the in situ modification. For the practical proce-
dure of the enantio-differentiating hydrogenation of methyl ace-
toacetate, the addition of TA, NaBr, and sodium 2-ethylhexa-
noate in the first run would be more appropriate for attaining
high optical yields from the first run.
The tartaric acid-NaBr-modified Raney Ni catalyst (TA-
NaBr-MRNi) is one of the most successful heterogeneous
enantio-selective catalysts for producing optically active com-
pounds. TA-NaBr-MRNi can be prepared by pre-modifica-
tion before hydrogenation, that is, immersing RNi in an aque-
ous solution of TA and NaBr at pH 3.2. The resulting MRNi
hydrogenates β-ketoesters in the high optical yields of
80–98%.1,2 The heterogeneous enantio-selective catalyst can
produce large amounts of optically active compounds using a
small amount of an optically active modifier. Repeated use of
the modified Ni catalyst would have a great advantage in fur-
ther minimizing the starting optically active modifiers and
waste of the modification solution.
The studies of the repeated use of the enantio-differentiat-
ing heterogeneous catalysts were performed with cinchona-
modified Pt catalysts and with TA-modified Ni catalysts.
Böhmer et al. reported that Pt/zeolite modified with cinchoni-
dine was an effective catalyst for long-term use with the addi-
tion of the modifier during each run of the hydrogenation.
However, the decrease in the enantiomer excess of the product
and, especially, the decrease in the hydrogenation rate were
inevitable.3 Tai et al. demonstrated that the repeated use of the
conventional TA-NaBr-MRNi resulted in a drastic decrease in
the enantio-differentiating ability and hydrogenation activity
after the second run of the catalyst while the silicone-embed-
ded catalyst kept its initial enantio-differentiating ability and
hydrogenation ability even after the 27th repeated uses.4
However, the enantio-differentiating ability of the silicone
embedded catalyst was about 10% lower than that of TA-
NaBr-MRNi. Tai et al. also demonstrated that the amine-treat-
ed TA-NaBr-MRNi maintained about 80% of the initial optical
yield after the 10th run in the repeated trials.5,6
Recently, we reported that the in situ modification (TA and
NaBr were directly added to the reaction media) was applied to
the enantio-differentiating hydrogenation of methyl acetoac-
etate with about an 80% optical yield using the fine Ni powder
catalyst.7 In the present communication, we show a highly
durable catalyst for the enantio-differentiating hydrogenation of
methyl acetoacetate using a fine Ni powder prepared by an in
Copyright © 2001 The Chemical Society of Japan
Osawa, Tsutomu
