Intramolecular carbonyl-ene reaction of citronellal to isopulegol over ZnBr2-loading mesoporous silica catalysts

Article abstract of DOI:10.1016/j.molcata.2007.03.032

We report the preparation of ZnBr₂-loading mesoporous catalysts and their application to the intramolecular carbonyl-ene reaction of (+)-citronellal to (-)-isopulegol. The mesoporous catalysts were characterized by N₂ adsorption-desorption isotherms, X-ray powder diffraction (XRD), scanning electron microscopy (SEM), and inductively coupled plasma atomic emission spectrometry (ICP-AES). Among a series of mesoporous supports, C8-HMS, which was synthesized from Si(OEt)₄ via a sol-gel process in the presence of octylamine as a templating agent, was found to be an optimal support to load ZnBr₂ without damage of inherent mesoporosity of the support. The ZnBr₂ loaded on C8-HMS (ZnBr₂/C8-HMS) showed higher catalytic activity and diastereoselectivity than ZnBr₂ on other HMS with different particle and pore sizes, MCM-41, mesoporous alumina, and Al-HMS. The amount of zinc ions eluted into the solution phase from ZnBr₂/C8-HMS was only at a less than 1 ppm level. The results suggested that clumped ZnBr₂ was no longer formed on the mesoporous silica surface. The ZnBr₂/C8-HMS catalyst which had been washed well with excess EtOH still contained zinc species, but had neither catalytic activity nor bromide ions. It was concluded that at least two different kinds of Zn sites existed on the surface of ZnBr₂/C8-HMS; one site was the crystallite ZnBr₂ which was finely dispersed on the silica surface, and the other was oxygenated zinc species such as Zn(OSi{triple bond, long})₂ and/or Zn(OH)(OSi{triple bond, long}).

Full text of DOI:10.1016/j.molcata.2007.03.032

Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
Intramolecular carbonyl-ene reaction of citronellal to isopulegol
over ZnBr2-loading mesoporous silica catalysts
Shohei Imachi1, Kisho Owada, Makoto Onaka∗
Department of Chemistry, Graduate School of Arts and Science, The University of Tokyo, Meguro, Tokyo 153-8902, Japan
Received 14 November 2006; received in revised form 6 March 2007; accepted 9 March 2007
Available online 16 March 2007
Abstract
We report the preparation of ZnBr2-loading mesoporous catalysts and their application to the intramolecular carbonyl-ene reaction of (+)-
citronellal to (−)-isopulegol. The mesoporous catalysts were characterized by N2 adsorption–desorption isotherms, X-ray powder diffraction
(XRD), scanning electron microscopy (SEM), and inductively coupled plasma atomic emission spectrometry (ICP-AES). Among a series of
mesoporous supports, C8-HMS, which was synthesized from Si(OEt)4 via a sol–gel process in the presence of octylamine as a templating agent,
was found to be an optimal support to load ZnBr2 without damage of inherent mesoporosity of the support. The ZnBr2 loaded on C8-HMS
(ZnBr2/C8-HMS) showed higher catalytic activity and diastereoselectivity than ZnBr2 on other HMS with different particle and pore sizes, MCM-
41, mesoporous alumina, and Al-HMS. The amount of zinc ions eluted into the solution phase from ZnBr2/C8-HMS was only at a less than 1 ppm
level. The results suggested that clumped ZnBr2 was no longer formed on the mesoporous silica surface. The ZnBr2/C8-HMS catalyst which had
been washed well with excess EtOH still contained zinc species, but had neither catalytic activity nor bromide ions. It was concluded that at least
two different kinds of Zn sites existed on the surface of ZnBr2/C8-HMS; one site was the crystallite ZnBr2 which was finely dispersed on the silica
surface, and the other was oxygenated zinc species such as Zn(OSi )2 and/or Zn(OH)(OSi ).
© 2007 Elsevier B.V. All rights reserved.
Keywords: (+)-Citronellal; Intramolecular carbonyl-ene reaction; HMS; ZnBr2; Mesoporous catalyst
1. Introduction
In the Takasago process, myrcene, produced by thermal
cracking of ␤-pinene, reacts with diethylamine in the presence
of a catalyst of n-BuLi to give diethylgeranylamine stereose-
lectively. Asymmetric isomerization of diehtylgeranylamine to
citronellal (R,E)-diethylamine by a chiral rhodium/(S)-BINAP
catalyst is the most remarkable step in the Takasago process.
Additionally, we should consider another step of intramolecu-
lar cyclization of (R)-(+)-citronellal to (−)-isopulegol an equally
important stage, because the cyclization of citronellal can afford
four diastereoisomers, among which (−)-isopulegol is only a
desirable precursor to (−)-menthol.
As the skeleton of a menthol molecule has three stereogenic
centers, eight diastereomers are possible. However, among
the isomers (−)-menthol is only one beneficial isomer as an
ingredient for cigarettes, chewing gums, toothpastes, pharma-
ceutical and personal-care products [1], and 4500 t a year of
the compound is consumed worldwide. In the current men-
thol industry, (−)-menthol is mainly provided by three routes
[2]: (1) extraction from natural mint in China and Brazil; (2)
synthesis of racemic menthol from m-cresol via the formation
of thymol (2-isopropyl-5-methylphenol) and its reduction with
hydrogen, followed by optical resolution; (3) chemical synthesis
from myrcene through asymmetric isomerization of diethylger-
anylamine with an Rh-BINAP catalyst and an intramolecular
carbonyl-ene reaction as key steps (the Takasago process) [3].
In the Takasago process, isomerization of (+)-citronellal
to (−)-isopulegol, which is classified as an intramolecular
carbonyl-ene reaction, was originally performed in up to 92%
diastereoselectivity in the presence of ZnBr2, which had been
discovered by Nakatani and Kawashima [4]. However, there
were some shortcomings that the reaction requires a stoichio-
metric amount of solid ZnBr2, some of which were dissolved
in organic solvents such as CH2Cl2 and benzene. Recently
Takasago patented a new homogeneous catalyst of tris(2,6-
diarylphenyloxy)aluminum for the cyclization of (+)-citronellal
∗
Corresponding author. Tel.: +81 3 5454 6595; fax: +81 3 5454 6998.
E-mail address: conaka@mail.ecc.u-tokyo.ac.jp (M. Onaka).
Research Fellow of the Japan Society for the Promotion of Science.
1
1381-1169/$ – see front matter © 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.molcata.2007.03.032

S. Imachi et al. / Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
175
[5]. Although this catalyst promotes the cyclization in over 95%
yield of (−)-isopulegol with almost 100% diastereoselectiv-
ity, the catalyst is difficult to be separated from the reaction
mixture and to be reused. Therefore, discovering a new hetero-
geneouscatalystsystemhasbeenpaidmuchattentiontobymany
chemists, and several heterogeneous catalysts for the cyclization
have been reported.
Corma et al. reported that water-tolerant and Lewis acidic
Sn-␤ zeolite in which tin ions were isomorphically substituted
into the ␤ zeolite framework worked as an efficient catalyst for
the cyclization of (+)-citronellal [6]. The catalyst recorded a
turnover number of 1350 per tin ion in 83% diastereoselectivity
without elution of tin ions.
Zirconiumion-exchangedmontmorillonitewasalsoanexcel-
lent solid catalyst for the cyclization with 90% selectivity, and
was able to be reused at least five times with the same activities
[7]. Zr-␤ zeolite, which was synthesized by the incorporation of
zirconium ions into ␤ zeolite, also showed high diastereoselec-
tivity [8].
Typical porous silica-based catalysts accelerated the cycliza-
tion of (+)-citronellal as well: the cyclization was drastically
improved by using H3PO4- or heteropolyacid-loading silica gel,
while both catalysts showed only moderate diastereoselectiv-
ities [9,10]. Galvagno et al. prepared Zn(II)-loading catalysts
by impregnation of amorphous silica with a solution of ZnBr2,
followed by drying, and the catalysts were found to show up
to 86% diastereoselectivity [11,12]. According to their inves-
tigation, the silica surface consists of both physically adsorbed
ZnBr2 and Zn(II) sites of zinc oxy-hydroxide and/or Zn(OSi )2.
The Zn(II) sites are the most active for the cyclization, but the
physically adsorbed ZnBr2 is required to attain high diastereose-
lectivity. In other words, the ZnBr2 site was less active but more
diastereoselective than the Zn(II) sites. Then, it is easy to envis-
age that more active and higher diastereoselective catalysts can
be realized if support materials are covered with well-dispersed
ZnBr2 salts on the surface.
In recent years, a lot of mesoporous materials have been
developed such as silica, aluminosilicate, and alumina. Gener-
ally, mesoporous materials which have uniform mesopores and
high specific surface areas are prepared in the presence of proper
template agents through a sol–gel process. Compared with the
use of amorphous or microporous supports, that of mesoporous
supports provides us several remarkable advantages: (1) the
nano-sized uniform pore structure prevents ZnBr2 crystal from
agglomerating, (2) the large surface area enables the support to
hold a large amount of active species on the surface, and (3) the
size of mesopore is large enough to diffuse a variety of organic
substrates and products smoothly.
Fig. 1. Four diastereoisomers from the cyclization of (+)-citronellal.
sis not only of simple olefins but also of olefins functionalized
with ester, carbonyl, and halogen groups [15].
This article describes the preparation and characterization of
ZnBr2 loading mesoporous catalysts in detail and their applica-
tion for the cyclization of (+)-citronellal to (−)-isopuregol in a
high diastereoselective way (Fig. 1).
2. Experimental
2.1. General
Commercially available (+)-citronellal (Tokyo Kasei Kogyo)
was distilled before use. CH2Cl2, EtOH and CH3CN (Kanto
Chemical) were dried over Molecular Sieves 4A. SiO2 (Fuji
Silysia Chemical, CARiACT Q-3), Si(OEt)4 (Tokyo Kasei
Kogyo), colloidal silica (Aldrich, HS-40, 40 wt% suspension
in water), n-octylamine (Tokyo Kasei Kogyo), n-dodecylamine
(Tokyo Kasei Kogyo), n-hexadecylamine (Kanto Chemical),
n-hexadecyltrimethylammonium chloride (Kanto Chemical),
Al(O-s-Bu)3 (Tokyo Kasei Kogyo), NH4OH (Kanto Chemical,
30 wt%), 1-propanol (Kanto Chemical), lauric acid (Kanto
Chemical), Al(O-i-Pr)3 (Kanto Chemical) and ZnBr2 (Kanto
Chemical) were used without further purification. Infrared (IR)
spectra were recorded on a JASCO FT550 FT-IR spectrometer.
1H NMR spectra were recorded on a JEOL JNM-GSX270
(270 MHz) or a JEOL JNM-GSX500 (500 MHz) spectrometer;
chemical shifts (δ) are reported in parts per million relative to
tetramethylsilane. Splitting patterns are designed as s, singlet;
d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. 13C
NMR spectra were recorded on a JEOL EX270 (68 MHz)
spectrometer with complete proton decoupling. Chemical shifts
were recorded in parts per million relative to tetramethylsilane
with the solvent resonance as internal standard (CDCl3; δ
77.0 ppm). N2 adsorption–desorption measurements were
performed at −196 ◦C with a Belsorp 28SA (Bel Japan, Inc.)
using static adsorption procedures. Samples were outgassed at
400 ◦C and 1.3 Pa for 12 h prior to analysis. Specific surface
area (S.A.) was determined by the BET method. Pore diameter
(P.D.) was calculated by means of the BJH method. Gas chro-
matography analysis (GC) was carried out with a Shimadzu
GC-8A equipped with an FID detector and a 25 m OV-1
chemically bonded capillary column. X-ray powder diffraction
To make the best use of these features leads to the prepara-
tion of various effective catalysts. For example, we have already
reported that MoO3 supported on HMS showed remarkable
catalysis for olefin metathesis against MoO3 on normal silica
[13]. It was also demonstrated that Re2O7 finely dispersed on
mesoporous alumina more effectively catalyzed the metathe-
sis of terminal and inner olefins than Re2O7 on ␥-alumina
[14]. More recently, we discovered that methyltrioxorhenium
on ZnCl2-modified mesoporous alumina catalyzed the metathe-

176
S. Imachi et al. / Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
(XRD) patterns were recorded on a Rigaku MULTI FLEX.
Inductively coupled plasma atomic emission spectrometry
(ICP-AES) was recorded on a Rigaku SPECTROCIROS CCD.
Scanning electron microscopy (SEM) was run using a Keyence
VE-9800 operated at 3 kV without carbon coating treatment.
flow. The dried gel was set in an electric furnace, and gradually
heated to 500 ◦C for 5 h in dry air.
2.3. Synthesis of ZnBr2-loading catalyst
A typical procedure was described for the preparation of
ZnBr2/C8-HMS: an EtOH (20 ml) solution of ZnBr2 (4.0 mmol)
was added to powder C8-HMS (8.46 g), and the mixture was
dried under an N2 flow until EtOH was dried up. Then, the fol-
lowing procedure was repeated twice: EtOH (20 ml) was added
to the sapless solid, and the mixture was stirred slowly for 1 min,
followed by being dried again in an N2 flow. The ZnBr2-loading
HMS was heated to 400 ◦C at a ramping rate of 7 ◦C/min in an
N2 flow, and calcined at 400 ◦C in air for 4 h.
2.2. Synthesis of mesoporous materials
2.2.1. HMS (C8-HMS)
Under vigorous stirring, Si(OEt)4 (100 mmol) was added to
a mixture of EtOH (650 mmol), deionized water (3 mol) and
n-octylamine (25 mmol). The resulting mixture was aged by stir-
ring for 48 h at room temperature. Then, the resulting gel was
filtered, washed with EtOH, dried in vacuo at 120 ◦C. The solid
material was heated to 600 ◦C at a ramping rate of 5 ◦C/min
in an N2 flow, and calcined at 600 ◦C in air for 4 h. When n-
dodecylamine and n-hexadecylamine for the synthesis of C12-
and C16-HMS were used as templating agents, the molar com-
positions of Si(OEt)4:amine:EtOH:H2O were 1.0:0.25:8.5:28.4
and 1.0:0.3:14:23, respectively.
2.4. Cyclization of (+)-citronellal to (−)-isopulegol
To ZnBr2/C8-HMS (activated at 400 ◦C under below 133 Pa
for 4 h) containing 0.1 mmol of ZnBr2 was added a CH2Cl2 solu-
tion (10 mL) of (+)-citronellal (1.0 mmol) at room temperature.
After the reaction was completed, the mixture was filtrated and
the filtrate was evaporated. The crude products were purified
by distillation with a Kugelrohr apparatus to afford a mixture
of (−)-isopulegol and other two diastereoisomers. Diastere-
oselectivities of (−)-isopulegol to the other diastereoisomers
were determined by GC analysis using an OV-1 capillary col-
umn at 80 ◦C [16]—retention time: (−)-isopulegol 9.63 min,
(+)-neo-isopulegol 1.08 min, (+)-iso-isopulegol 10.59 min. (−)-
Isopulegol: 1H NMR (500 MHz, CDCl3) δ 0.92–1.01 (m, 5H),
1.30–1.36 (m, 1H), 1.48–1.51 (m, 1H), 1.66–1.71 (m, 5H), 1.90
(dt, J = 1.6 and 9.8 Hz, 1H), 1.96 (m, 1H), 2.03–2.05 (m, 1H),
2.2.2. MCM-41
Thirty-weight percentage of NH4OH (0.49 g) was added to a
solution of n-hexadecyltrimethylammonium chloride (29 mmol)
and deionized water (1.45 mol), and the mixture was stirred for
1 h at ambient temperature. The resulting solution was mixed
with a solution of colloidal silica (34.3 g) and aqueous NaOH
(1 M, 105 g), and the mixture was stirred for 1 h at ambient tem-
perature. The reaction mixture was put into an oven and kept
statically for 4 days at 110 ◦C. Under the heating, pH of the
solution was checked every 24 h and adjusted with acetic acid
to 11.0. The resulting solid was filtered, washed with deionized
water, dried under an N2 flow over 12 h. The dried solid was
then heated to 500 ◦C at a ramping rate of 5 ◦C/min in an N2
flow, and calcined at 500 ◦C in air for 5 h.
3.46 (dt, J = 4.3 and 10.5 Hz, 1H), 4.87 (d, J = 2.8 Hz, 2H). 13
C
NMR (CDCl3) δ 18.1, 22.0, 24.5, 31.2, 34.1, 42.5, 53.8, 70.2,
112.5, 146.4.
3. Results and discussion
2.2.3. meso-Al2O3
In a 500 ml polypropylene bottle a mixture of Al(O-s-Bu)3
(178 mmol) and 1-propanol (6 mol) was stirred for 10 min, and
then deionized water (572 mmol) was added. The solution was
stirred for 60 min at room temperature, followed by addition of
a solution of lauric acid (54 mmol) in 1-propanol (580 mmol).
The mixture was stirred for 24 h at room temperature, and then
transferred into a 300 ml autoclave. The mixture was aged at
110 ◦C for 48 h without stirring. After filtration, the white solid
was washed with EtOH (100 ml), and dried under an N2 flow
overnight at room temperature. The solid material was heated to
600 ◦C at a ramping rate of 1 ◦C/min in air flow, and calcined at
600 ◦C in air for 4 h.
3.1. Application of mesoporous materials and zinc
salt-loading ones for the cyclization of citronellal
In the present study, we selected several mesoporous mate-
rials of silica (HMS [17,18] and MCM-41 [19]), alumina
(meso-Al2O3 [20]) and aluminosilicate (Al-HMS [21]). Sil-
ica gel (SiO2) was also used as a control. Especially, we
prepared three types of HMS with different pore sizes using
varied alkylamine templates with C8, C12, and C16 car-
bon chains, and abbreviate them to Cn-HMS (n = 8, 12, and
16). Physical properties of the materials are summarized in
Table 1.
First we applied the mesoporous materials as solid catalysts
to the cyclization of (+)-citronellal to (−)-isopulegol as shown
in Table 1. Although C16-HMS has almost the same surface
area and pore diameter as MCM-41, these materials had dif-
ferent mesoporous structures: HMS possesses wormhole-like
mesopores, thicker walls, more cross-linked silica framework
and smaller particle sizes, while MCM-41 has a hexagonally
arranged, long tunnel mesoporous structure.
2.2.4. Al-HMS (Si/Al = 6.8)
Toavigorouslystirredsolutionofn-C16H33NH2 (3.31 mmol)
in EtOH (153 mmol) and deionized water (257 mmol) was added
at a time a homogeneous mixture of Si(OEt)4 (10 mmol) and
Al(O-i-Pr)3 (143 mmol) at room temperature. The mixture was
vigorously stirred for 48 h at room temperature. The white gel
formed was collected and dried at room temperature under an N2

S. Imachi et al. / Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
177
Table 1
Mesoporous material catalyzed cyclization of citronellala
Entry
Catalyst
S.A. (m2 g−1
)
P.D. (nm)
Time (h)
Yield (%)
Selectivityb (%)
1
2
3
4
5
C16-HMS
MCM-41
SiO2
meso-Al2O3
Al-HMS
880
930
700
360
1100
2.9
2.7
3.6
3.6
2.6
18
18
18
18
5
60
10
40
Trace
77
75
–
71
–
75
a
(+)-Citronerall (1.0 mmol) reacted in CH2C12 (10 ml) in the presence of catalyst (200 mg) at room temperature.
Selectivity to (−)-isopulegol out of the three diastereomers detected.
b
Table 3
Among the four possible diastereomers ((−)-isopulegol, (+)-
Effects of zinc salts loaded on C16-HMS upon the cyclizationa
neo-isoplegol, (+)-iso-isopulegol, and (+)-neoiso-isoplegol), the
most thermodynamically unstable isomer, (+)-neoiso-isoplegol,
was not detected through all the experiments in the study. Inter-
estingly, between the two mesoporous pure silicas, HMS showed
much higher catalytic activity than MCM-41 (entries 1 and
2). Although the cyclization proceeded on SiO2, the activity
was somewhat low (entry 3). It is also interesting to find that
mesoporous aluminosilicate, Al-HMS [22], gave isopulegol in
moderate yield and diastereoselectivity, because such decent
diastereoselectivitywouldnothavebeenexpectedwiththeuseof
suchahighlyacidicaluminosilicate(entry5). Almostnocycliza-
tion proceeded with meso-Al2O3 composed of pure alumina
(entry 4).
Nakatani et al. carefully investigated the cyclization of (+)-
citronellal using various zinc salts [4], and found that ZnBr2
gave the best result concerning the yield and the diastereos-
electivity to (−)-isopulegol. Therefore, ZnBr2 was loaded on
the mesoporous materials, and physical properties of the sup-
ported catalysts and their catalytic activities for the cyclization
were investigated (Table 2). Compared with catalytic activity of
unloaded supports in Table 1, the catalysis of ZnBr2 on C16-
HMS, MCM-41 and meso-Al2O3 much improved. And more
interestingly, higher diastereoselectivity was realized with C16-
HMS, MCM-41, SiO2 and meso-Al2O3 after loading of ZnBr2.
Ontheotherhands, ZnBr2/Al-HMSdidnotimprovethediastere-
oselectivity. We suppose that the acidity of pristine Al-HMS is
high enough to show high catalytic activity even though the
ZnBr2 is not loaded on Al-HMS.
Entry
Catalyst
Time (h)
Yield (%)
Selectivityb (%)
1
2
3
4
5
ZnF2/C16-HMS
ZnCl2/C16-HMS
ZnBr2/C16-HMS
ZnI2/C16-HMS
18
12
6
18
18
23
94
94
82
36
80
86
87
86
86
Zn(NO3)2/C16-HMS
a
(+)Citronellal (1.0 mmol) was treated with ZnX2 (0.1 mmol) loading C16-
HMS (Si/Zn = 16) in CH2C12 (10 ml) at room temperature.
b
Selectivity to (−)-isopulegol out of the three diastereomers.
the best yield (94%) and the highest diastereoselectivity (87%)
(entry 3), and ZnF2/C16-HMS the lowest of 23% (entry 1).
(−)-Isopulegol was obtained in a poor yield with ZnO loaded
on HMS, which had been prepared through calcination of
Zn(NO3)2-loading HMS in air at 400 ◦C (entry 5).
Although ZnBr2/C16-HMS catalyst gave such a good result,
it was found that C16-HMS underwent partial degradation of
the mesoporosity during the loading process of ZnBr2 on the
surface, because the specific surface area and the pore volume of
the ZnBr2/C16-HMS catalyst obviously decreased as shown in
Tables 1 (entry 1), and 2 (entry 1). Therefore, it seems that part of
zinc bromide active for the reaction would be buried in the silica
networks through the collapse, which disturbed a close contact
between the zinc sites and reactants. If the loading of ZnBr2
on HMS is achieved without damage of the mesoporosity, the
catalytic activities would be improved. In the next section, we
have searched for tougher mesoporous HMS materials.
Various zinc salt-loading catalysts (designated as ZnX2/C16-
HMS) were prepared by impregnation of C16-HMS with ZnF2,
ZnCl2, ZnBr2, ZnI2 and Zn(NO3)2, and their catalytic activ-
ity is summarized in Table 3. The order of the catalysis with
ZnX2/HMS was almost the same as that of catalysis with par-
ent zinc salts [4]: among zinc halides, ZnBr2/C16-HMS showed
3.2. Preparation of ZnBr2 loading HMS catalyst without
degradation of mesoporous structure
It was reported by Tanev and Pinnavaia that the thermal sta-
bility of HMS upon calcination in air was superior to that of
Table 2
Cyclization of citronellal catalyzed by ZnBr2-loading mesoporous materiala
Entry
Catalyst
S.A. (m2 g−1
)
P.D. (nm)
Time (h)
Yield (%)
Selectivityb (%)
1
2
3
4
5
ZnBr2/C16-HMS
ZnBr2/MCM-41
ZnBr2/SiO2
ZnBr2/meso-Al2O3
ZnBr2/Al-HMS
500
500
550
240
760
2.7
2.7
–
3.4
2.6
6
12
18
18
3
94
85
60
85
88
88
85
86
84
75
a
(+)-Citronelall (1.0 mmol) reacted over ZnBr2 (0.1 mmol)-loading catalyst (Si/Zn = 16 or Al/Zn = 16) in CH2C12 (10 ml) at room temperature.
Selectivity of (−)-isopulegol to other diastereomers.
b

178
S. Imachi et al. / Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
Table 4
Physical properties of pristine HMS and ZnBr2-loading HMS
Entry
HMS and
S.A. (m2 g−1
)
P.D. (nm)
P.V. (ml g−1
)
ZnBr2/HMS
1
2
3
C8-HMS
1240
1200
1190
1.9
1.9
1.9
0.28
0.28
0.27
ZnBr2/C8-HMSa
EtOH-washed
ZnBr2/C8-HMS
C12-HMS
4
5
6
1160
720
700
2.2
2.2
2.2
0.27
0.16
0.16
ZnBr2/C12-HMSa
EtOH-washed
ZnBr2/C12-HMS
C16-HMS
ZnBr2/C16-HMSa
EtOH-washed
ZnBr2/C16-HMS
SiO2
7
8
9
880
500
490
2.9
2.7
2.7
0.20
0.11
0.11
10
11
700
550
–
–
0.20
0.11
a
ZnBr2/SiO2
a
ZnBr2 (0.1 mmol) was loaded on Cn-HMS or SiO2 with the ratio of
Si/Zn = 16.
MCM-41 due to a thicker wall structure and a more cross-linked
silica network [17]. However, in our study the thermal stability
of C16-HMS was found not satisfactorily high under calcination
in the presence of ZnBr2 as mentioned in the previous section.
In the present work, we used three kinds of HMS with differ-
ent pore diameters and surface areas as a support. Table 4 shows
the physical properties of parent C8-, C12-, and C16-HMS as
well as ZnBr2-loading HMS (Si/Zn = 16). Properties of SiO2
and the ZnBr2-loading one are also shown as a control. As the
alkyl chain length of a primary amine surfactant in preparation of
mesoporous silica gets longer from C8 to C16, the pore diameter
of the obtained mesoporous silica becomes larger with a smaller
specific surface area, which is in good agreement with the report
by Tanev and Pinnavaia [17]. It is interesting to note that those
HMS exhibit very different morphologies: SEM micrographs
of pristine HMS indicate that C8-HMS consists of very small
particles <200 nm in diameter (Fig. 2c), while C12-HMS and
C16-HMS are larger spherical aggregates (Fig. 2b and a).
With ZnBr2/C12-HMS and ZnBr2/C16-HMS, the surface
areas and the pore volumes drastically decreased after loading
ZnBr2 (Table 4, entries 4 versus 5 and 7 versus 8). After the
ZnBr2 loading supports were washed with EtOH, the surface
areas of the resulting EtOH-washed ZnBr2/Cn-HMS (n = 12 or
16) did not return to the original values (entries 5 versus 6 and 8
versus 9). The change in the HMS weight indicated that ca.70%
of zinc species were extracted out from the ZnBr2-loading HMS.
Therefore we suppose that the decrease in the surface area of
HMS upon the ZnBr2 loading comes from partial collapse of the
mesoporous structure of HMS during the ZnBr2-loading process
rather than from some blockage in mesopores with ZnBr2 crys-
tallite. Upon loading of ZnBr2 on SiO2, the surface area also
decreased. In contrast, surprisingly, ZnBr2/C8-HMS had almost
the same surface area and pore volume as parent C8-HMS, indi-
cating that C8-HMS was not degraded and could maintain the
inherent mesostructure upon loading of ZnBr2.
Fig. 2. SEM micrographs of (a) C16-HMS, (b) C12-HMS, and (c) C8-HMS
samples. Bars indicate a scale of 1 ␮m.
powder XRD patterns between parent HMS and ZnBr2-loading
HMS, as shown in Fig. 3. Although the patterns of the parent
C16-HMS and C12-HMS contained a strong [1 0 0] reflection
peak at 2θ = ca. 2.5◦, no reflection peaks were observable after
the loading of ZnBr2. In contrast, though the pattern of C8-HMS
showed a very weak reflection peak, the reflection still remained
after the ZnBr2-loading. It can be concluded that C8-HMS with
a smaller pore diameter and a particle size has an improved
The destructive changes in the mesoporous structure upon
the loading of ZnBr2 were also confirmed by the comparison of

S. Imachi et al. / Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
179
species on C8-HMS, which were not soluble in EtOH, would
be oxy-zinc species chemically bonded to the silica framework.
Actually the oxy-zinc species was found to have little catalytic
activity for the cyclization of (+)-citronellal for 3 h.
We then investigated whether or not zinc species of catalyst
can dissolve into a CH2Cl2 solution phase during the reaction:
after a suspension mixture of (+)-citronellal (1.0 mmol) and zinc
catalyst of bulk ZnBr2 or loaded ZnBr2 (0.1 mmol) in CH2Cl2
(10 ml) was stirred for 3 h, the reaction mixture was filtered and
the filtrate was directly analyzed by ICP-AES. The bulk ZnBr2
was found to be completely dissolved into 10 ml of CH2Cl2.
If ZnBr2 is loaded on C8-HMS in the form of clumps, ZnBr2
should be similarly eluted into the CH2Cl2 solution. However,
the amount of eluted zinc species from ZnBr2/C8-HMS was
very low on a less than 0.1% level, and in fact, the filtrate had
no catalysis for the carbonyl-ene reaction. In addition, we could
not observe any reflection peaks corresponding to crystalline
ZnBr2 on the ZnBr2/C8-HMS by powder XRD. These findings
lead to a conclusion that a real active site on ZnBr2/C8-HMS
catalyst is a crystallite of ZnBr2 which is finely dispersed and
well interacted with the C8-HMS surface, and that the active site
shows high catalytic activity for the cyclization with excellent
diastereoselectivity.
3.4. Catalytic activity of ZnBr2-loading C8-HMS for the
cyclization of citronellal
It is easily expected that the dispersion of active zinc sites
on C8-HMS should affect the reaction rate of the cyclization. A
seriesofZnBr2/C8-HMScatalystswithdifferentatomicratiosof
Si/Zn (i.e. varied loading amounts of ZnBr2) were prepared, and
their catalytic activities were compared by use of each catalyst
including the same amount of ZnBr2 (0.1 mmol) as summarized
in Table 6. Although the diastereoselectivities were not differ-
ent, the reaction period which was required for the complete
consumption of citronellal was heavily influenced by the atomic
ratios of Si/Zn: some unknown byproducts were produced and
hence the yields of the desired products slightly decreased prob-
ably owing to the presence of more amounts of the support in
the cases of entries 3 and 4. The optimal ratio Si/Zn was 32,
with which the ZnBr2/C8-HMS (Si/Zn = 32) catalyst showed the
best result concerning the reaction rate and the chemical yield
(entry 2).
Fig. 3. Powder XRD patterns of Cn-HMS and ZnBr2/Cn-HMS. (a) C16-HMS,
(b) C12-HMS, and (c) C8-HMS.
thermal stability and sustains its intrinsic mesoporosity during
the ZnBr2-loading process.
3.3. Characterization of zinc species loaded on HMS
The elemental analysis of ZnBr2-loading Cn-HMS
(Si/Zn = 16) catalysts was performed with ICP-AES and is
summarized in Table 5. The atomic ratios of Br/Zn of the
catalysts were found to be 1.5–1.6. This result agrees with
that reported by Galvagno and coworkers [11], indicating that
ZnBr2 was partially degraded and part of bromide ions were lost
upon the loading. Interestingly, after washing ZnBr2/C8-HMS
with a sufficient quantity of EtOH, the C8-HMS still contained
0.8 wt% of zinc species, but almost no bromide ions remained
as shown in Table 5. If ZnBr2 crystallite, which had been
physically adsorbed on C8-HMS and would be a real catalyst
site, was washed out with excess EtOH, the residual zinc
In the case of Galvagno’s catalyst [11], because Zn(II)
sites, which were considered to be zinc oxy-hydroxide and/or
Zn(O–Si )2, were more active but less diastereoselective for the
Table 6
Effects of the atomic ratio of Si/Zn in ZnBr2/C8-HMS on the reactiona
Entry
Si/Zn
Time (h)
Yield (%)
Selectivityb (%)
Table 5
Elemental analysis of ZnBr2/HMS catalysts
1
2
3
4
16
32
48
64
6
3
3
2
89
94
89
80
86
88
87
87
Catalyst
Zn (wt%)
Br/Zn
ZnBr2/C8-HMS
ZnBr2/C12-HMS
ZnBr2/C16-HMS
EtOH-washed ZnBr2/C8-HMS
2.6
2.9
2.8
0.8
1.5
1.6
1.5
a
(+)-Citronelall (1.0 mmol) reacted over ZnBr2 (0.1 mmol) loading catalysts
in CH2C12 (10 ml) at room temperature.
<0.1
b
Selectivity to (−)-isopulegol out of the three diastereomers.

180
S. Imachi et al. / Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
Fig. 5. Cyclization of 7-methyloct-6-enal.
substrate has also been conducted with a combined use of tita-
nium perchlorate and (R)-BINOL at room temperature for 48 h
to give the products in a total yield of 66% with a trans/cis ratio
of 69 (55% ee)/31 [23].
4. Conclusions
The present study demonstrated the preparation of ZnBr2-
loading mesoporous catalysts and their application to the
intramolecular carbonyl-ene reaction of (+)-citronellal to
(−)-isopulegol. The ZnBr2-loading C8-HMS showed higher
catalytic activity and diastereoselectivity than other ZnBr2-
loading supports such as mesoporous silicas, C12-HMS and
C16-HMS, mesoporous alumina, and mesoporous aluminosil-
icate. The mesoporosity of mesoporous materials except for
C8-HMS was partially damaged upon calcinations at high tem-
peratures in the presence of ZnBr2. Only C8-HMS could be
tolerated under such harsh thermal conditions. The smaller pore
diameterandsmallerparticlesizeofC8-HMSseemtoberespon-
sible for a marked improvement in the thermal stability in acidic
circumstances. ThepreservationofuniformmesoporosityofC8-
HMS enabled the ZnBr2-loading catalyst to show high catalytic
performance. The real catalyst site on the surface of ZnBr2/C8-
HMS is not oxy-zinc species directly bonded to the silica, but
well-dispersed crystallite ZnBr2 on the surface.
Fig. 4. Cyclization rate of citronellal over ZnBr2-loading HMS catalysts.
ZnBr2/C16-HMS (ꢀ), ZnBr2/C12-HMS (ꢀ), and ZnBr2/C8-HMS (᭹).
carbonyl-ene reaction than ZnBr2 sites [12], ZnBr2 had to be
loaded on normal silica with a high zinc content of >4.0 mmol/g
in order for ZnBr2 to cloak the surface of zinc oxide species and
to achieve a high diastereoselection. In contrast, although the
ZnBr2/C8-HMS catalyst (Si/Zn = 32) contained a much lower
content (0.5 mmol/g) of ZnBr2, it showed high catalytic perfor-
mance and the highest diastereoselectivity to (−)-isopulegol.
The catalytic activities of ZnBr2/C8-HMS, ZnBr2/C12-HMS
and ZnBr2/C16-HMS were compared in the cyclization of
(+)-citronellal as shown in Fig. 4. The cyclization rates are crit-
ically dependent on the kind of mesoporous silicas: among the
three HMS catalysts, ZnBr2/C8-HMS which retains the inherent
mesoporosity shows the highest rate. On C-12 and C-16 HMS
catalysts, some of active ZnBr2 would be buried in the silica
framework during the loading process of ZnBr2, leading to poor
catalysis.
References
[1] S. Akutagawa, Organic Synthesis in Japan Past, Present and Future, Kagaku
Dozin, Tokyo, 1992, pp.75–82.
[2] S. Akutagawa, Yuki Gosei Kagaku Kyokaishi 44 (1986) 513–518.
[3] K. Tani, T. Yamagata, S. Akutagawa, T. Kumobayashi, T. Taketomi, H.
Takaya, A. Miyashita, R. Noyori, S. Otsuka, J. Am. Chem. Soc. 106 (1984)
5208–5217.
[4] Y. Nakatani, K. Kawashima, Synthesis (1978) 147–148.
[5] T. Iwata, Y. Okeda, Y. Hori, Eur. Pat. Appl. A2 (2002), EP1225163.
[6] A. Corma, M. Renz, Chem. Commun. (2004) 550–551.
[7] J. Tateiwa, A. Kimura, M. Tatasuka, S. Uemura, J. Chem. Soc., Perkin
Trans. 1 (1997) 2169–2174.
All the catalysts were dried and activated at 400 ◦C under
reduced pressure prior to use. Once the catalyst was used in the
reaction, washing the catalyst with CH2Cl2 and activating it at
400 ◦C in vacuo were necessary for the catalyst to be reused at
least twice for the cyclization in 88–94% yields with 87–88%
diastereoselectivities.
3.5. Catalytic activity of ZnBr2/C8-HMS for the cyclization
of 7-methyloct-6-enal
[8] Z. Yongzhong, N. Yuntong, S. Jaenicke, G.K. Chuah, J. Catal. 229 (2005)
404–413.
The intramolecular carbonyl-ene reaction of 7-methyloct-
6-enal to racemic 2-isopropenylcyclohexanol was also inves-
tigated by use of a catalytic amount of ZnBr2/C8-HMS (Fig. 5).
It was again proved that ZnBr2 firmly loaded on C8-HMS could
catalyze the cyclization at room temperature for 16 h to afford
a trans-cyclohexanol derivative in a high yield of 90% with a
high trans/cis selectivity of 91/9. Asymmetric cyclization of the
[9] P.J. Kropp, G.W. Breton, S.L. Craig, S.D. Crawford, W.F. Durland Jr., J.E.
Jones III, J.S. Raleigh, J. Org. Chem. 60 (1995) 4146–4152.
[10] K.A. da Silva, P.A. Robles-Dutenhefner, E.M.B. Sousa, E.F. Kozhevnikova,
I.V. Kozhevnikov, E.V. Gusevskaya, Catal. Commun. 5 (2004) 425–429.
[11] C. Milone, A. Parri, A. Pistone, G. Neri, S. Galvagno, Appl. Catal. A: Gen.
233 (2002) 151–157.
[12] C. Milone, C. Gangemi, G. Neri, A. Pistone, S. Galvagno, Appl. Catal. A:
Gen. 199 (2000) 239–244.

S. Imachi et al. / Journal of Molecular Catalysis A: Chemical 272 (2007) 174–181
181
[13] T. Ookoshi, M. Onaka, Chem. Commum. (1998) 2399–2400.
[14] T. Oikawa, T. Ookoshi, T. Tanaka, T. Yamamoto, M. Onaka, Micropor.
Mesopor. Mater. 74 (2004) 93–103.
[15] T. Oikawa, Y. Masui, T. Tanaka, Y. Chujo, M. Onaka, J. Organometal.
Chem. 692 (2007) 554–561.
[19] J.S. Beck, J.C. Vartuli, W.J. Roth, M.E. Leonowicz, C.T. Kresge, J.B.
Schmitt, C.T.-W. Chu, D.H. Olson, E.W. Sheppard, S.B. McCullen, J.B.
Higgins, J.L. Schlenker, J. Am. Chem. Soc. 114 (1992) 10834–10843.
[20] F. Vaudry, S. Khodabandeh, M.E. Davis, Chem. Mater. 8 (1996)
1451–1464.
[16] P.J. Kropp, G.W. Breton, S.L. Craig, S.D. Crawford, N.F. Durland Jr., J.
Org. Chem. 60 (1995) 4146–4152.
[17] P.T. Tanev, T.J. Pinnavaia, Chem. Mater. 8 (1996) 2068–2079.
[18] T.P. Pauly, Y. Liu, T.J. Pinnavaia, S.I. Billinge, T.P. Rieker, J. Am. Chem.
Soc. 121 (1999) 8835–8842.
[21] P.T. Tanev, T.J. Pinnavia, Science 267 (1995) 865–867.
[22] M. Onaka, N. Hashimoto, Y. Kitabata, R. Yamasaki, Appl. Catal. A: Gen.
241 (2003) 307–317.
[23] K. Mikami, M. Terada, E. Sawa, T. Nakai, Tetrahedron Lett. 32 (1991)
6571–6574.