Y-zeolite-catalyzed cyclizations of terpenols

Article abstract of DOI:10.1002/adsc.200505146

Depending on the metal doped and the activation temperature, Y-zeolites can catalyze a diversity of reactions of geraniol (1), linalool (2) and nerol (3). Compound 1 can be transformed to α- and/or γ-cyclogeraniol (4 and 5) highly efficiently.

Full text of DOI:10.1002/adsc.200505146

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DOI: 10.1002/adsc.200505146
Y-Zeolite-Catalyzed Cyclizations of Terpenols
Wei Yu,* Fengling Bian, Yuan Gao, Li Yang, Zhong-Li Liu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, Peopleꢀs Republic of China
Fax: ( þ86)-931-862-5657, e-mail: yuwei@lzu.edu.cn
Received: April 13, 2005; Accepted: October 20, 2005
Abstract: Depending on the metal doped and the ac-
tivation temperature, Y-zeolites can catalyze a diver-
sity of reactions of geraniol (1), linalool (2) and nerol
(3). Compound 1 can be transformed to a- and/or g-
cyclogeraniol (4 and 5) highly efficiently.
MS, and NMR and EI-MS if necessary. The results are
summarized in Table 1.
The reaction of geraniol (1) in NaY gave a-cyclogera-
niol (4) and/or g-cyclogeraniol (5) as the major products.
The ratio of these two products depended sensitively on
the reaction temperature. When the reaction was con-
ducted at 108C in NaYactivated at 5008C, 5 was the pre-
dominant product, while at 608C 4 was produced almost
exclusively. Compound 5 was found to isomerize to 4
within NaY at elevated temperatures, showing that 4
was the thermodynamic product. These results are con-
sistent with those obtained by Stratakis et al.[9] The mass
Keywords: catalysis; cyclization; cyclogeraniol; gera-
niol; zeolite
Besides their great success as industrial catalysts in pe- balance was about 50% with NaY activated at 5008C
troleumchemistry and related fields, the use of zeolites and above 60% with NaY activated at 2008C. A higher
in the laboratory for selective organic synthesis has mass balance was reported at high substrate loading lev-
grown continuously in recent years.[1–5] The combina- els and with differently activated NaY.[9] In the case of
tion of Lewis acidity and/or Brønsted acidity and shape linalool (2) and nerol (3), p-cymene (6) was the major
selectivity provides an opportunity to carry out a variety product, accompanied by a small amount of 4 and a-ter-
of selective reactions by use of zeolites, such as the re- pineol (7) (Fig. 1).
duction and isomerization of alkenes,[6] the regioselec-
Cyclogeraniols are important intermediates in the
tive and diastereoselective ene reaction of singlet oxy- synthesis of many natural products.[10] It is believed
gen[7] and the enantioselective epoxidation of alkenes.[8]
We report herein the selective cyclization reactions of
geraniol (1), linalool (2) and nerol (3) in NaY and FeY
zeolites. It was found that the cyclization products de-
pended significantly on the metal doped and the activa-
tion conditions. A significant finding was that geraniol
(1) could directly cyclize to a-cyclogeraniol (4) and g-cy-
clogeraniol (5) (Scheme 1).[9]
In a typical experiment, 20 mL of a hexane solution of
the terpenol (1 mmol) was stirred at room temperature
with 1.5 g of activated NaY. After the reaction was com-
plete the zeolite was filtered, washed with hexane and
then extracted with CH2Cl2. The solvent was removed
and the reaction mixture was analyzed by GC, GC-
Scheme 1. NaY- and FeY-catalyzed cyclization of geraniol
(1).
Figure 1.
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Table 1. NaY- and FeY-catalyzed reactions of geraniol (1), linalool (2) and nerol (3).[a]
Substrate
MY
Activation temperature (time)
Reaction time
Products (yield %)
1
NaY
5008C (5 h)
48 h (108C)
1.5 h (258C)
1 h (608C)
6 h
12 h
2.5 h
0.5 h
1.5 h
1 h
0.5 h
1.5 h
1 h
0.5 h
1.5 h
12 h (08C)
2 h
1.5 h
6 h
2 h
4 (2), 5 (89)
4 (30), 5 (62)
4 (84), 5 (trace)
4 (19), 5 (70), 6 (3)
No reaction
4 (15), 5 (3), 6 (5), 7 (41), 8 (11), 9 (6), 10 (3)
4 (91), 5 (trace)
6 (76), 7 (6), 4 (4)
6 (11), 7 (47), 8 (21), 9 (8), 10 (5)
6 (85)
4 (11), 6 (72), 7 (8)
4 (3), 6 (9), 7 (52), 8 (13), 9 (7), 10 (4)
4 (8), 6 (79)
13 (92), 14 (2)
13 (23), 14 (72)
NaY
NaY
FeY
FeY
NaY
FeY
FeY
NaY
FeY
FeY
NaY
NaY
NaY
FeY
NaY
FeY
2008C (5 h)
1008C (2 h)
1008C (2 h)
2008C (5 h)
5008C (5 h)
1008C (2 h)
2008C (5 h)
5008C (5 h)
1008C (2 h)
2008C (5 h)
5008C (5 h)
5008C (5 h)
2008C (5 h)
2008C (5 h)
5008C (5 h)
2008C (5 h)
2
3
11
13 (31), 14 (65)
13 (90), 14 (trace)
12
6 (13), 13 (14), 14 (61)[b]
13 (78), 14 (14)
[a]
The reactions were run at roomtemperature except were otherwise specified. The products were identified by GC-MS and
compared with the authentic samples except 4 and 5 which were identified by 1H and 13C NMR and EI-MS. The yields were
determined by GC at 100% conversion.
[b]
The conversion is 90%.
that naturally occurring cyclogeraniols are derived bio-
synthetically fromthe acid-induced cyclization of geran-
Zeolites contain both Brønsted acid sites and Lewis
acid sites. There are many Lewis acid sites within the
yl diphosphate, the usual substrate for monoterpene cy- NaY framework due to the presence of metal ions.[3,14]
clases, followed by diphosphate hydrolysis, or directly by However, NaY is generally considered to be weakly
the enzymic cyclization of geraniol itself.[11] On the other acidic since it contains only a small number of Brønsted
hand, Brønsted acid-catalyzed cyclization of 1, 2, 3 in acid sites.[15a] As the catalyzing activity of zeolites is asso-
solution generally produced a-terpineol and monoter- ciated with their acidic character, the reactions of these
penes rather than cyclogeraniols.[12] Therefore, the di- terpenols were further explored in CaY, which has been
rect cyclization of geraniol to a- and g-cyclogeraniols proved to be a much stronger Brønsted acid catalyst
in the zeolite is interesting fromboth synthetic and
when activated at 5008C under air.[15] In this case, how-
mechanistic points of view. The transformation of gera- ever, only a small amount of mixed monoterpenes and p-
niol to a-cyclogeraniol was achieved at low temperature cymene were exacted out in CH2Cl2 as products for all
using the super acid FSO3OH,[13] but the formation of g- the three substrates, most of the substrates were proba-
cyclogeraniol has never been reported. By comparison, bly cracked inside the zeolite framework.
NaY not only can effect the reaction under mild condi-
We found recently that FeCl3 ·6 H2O could serve as a
tions, but can also simplify the procedure considerably. Lewis acid to catalyze the isomerization and cyclization
More important, both the a- and g-cyclogeraniols can of 1, 2 and 3 in acetonitrile giving a-terpineol (7) as the
be obtained with high selectivity. Therefore, NaYis a su- major product (Scheme 2),[16] similar to the mineral
perior catalyst.
acid-catalyzed reactions reported previously.[12] There-
fore, Fe3þ-exchanged Y zeolites were prepared[17] and
used to catalyze the cyclization reactions of 1, 2 and 3.
The results are also listed in Table 1. It can be seen that
the reaction products depend significantly on the activa-
tion temperature of the zeolite. When FeY was activated
at 1008C for 2 h the major product for all the three terpe-
nols was a-terpineol (7), consistent with the result of
FeCl3-catalyzed reactions.[16] In addition, mixed monoter-
penes including p-cymene (6), terpinolene (8), limonene
(9) and a-terpinene (10), and a small amount of 4 in the
case of geraniol and nerol, were also formed. With FeY
activated at higher temperature (2008C), 1 was trans-
Scheme 2.
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Y-Zeolite-Catalyzed Cyclizations of Terpenols
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formed to 4 exclusively, while 2 and 3 were transformed
predominantly to p-cymene (6), similar to the NaY-cata-
lyzed reactions mentionedabove. ActivatingFeYat high-
er temperatures (between 200 and 5008C) did not change
the composition of the products appreciably.
These results demonstrate that the catalytic behavior
of the zeolites depends remarkably on the metal doped
and on the activation temperature. The FeYactivated at
1008C acted similarly to FeCl3 ·6 H2O, giving a-terpi-
neol as the major product. By comparison, NaY heated
at 1008C for the same period of time has no catalytic ef-
fect. On the other hand, FeYactivated at 2008C behaved
similarly to the activated NaY. In fact, FeYis more pow-
erful than NaYin catalyzing the reaction. Although both
NaY and FeY activated at 2008C were effective for cat-
alyzing the reaction of geraniol, the reaction proceeded
Scheme 3.
much faster in FeY than in NaY. While the conversion have a stronger complexation with acid sites, most likely
was complete within 30 min with FeY as catalyst, the with Lewis acid sites since there are many more Lewis
conversion was only little more than 1/3 with NaY acid sites than Brønsted acid sites in NaY.[14] This inter-
over the same time span. Ammonia absorption-desorp- action would act somewhat like an “anchor” to fix the
tion chromatography measurements indicate that there molecule, thus determining the effectiveness of the in-
are more acidic sites in FeY than in NaY.
teraction between the remote double bond and the
In the case of nerol and linalool, the composition of acid sites. In the case of geraniol, the structural feature
the products was consistent with the mechanism of of the molecule would effect the protonation of the
acid-catalyzed reactions in solution. Both linalool and 6,7-carbon carbon double bond, and the conformation
nerol were transformed mainly to p-cymene in NaY of the molecule in the confined space of cages is favora-
and FeY (activated at 2008C). Obviously, p-cymene ble for cyclization to formthe carbocation A. The subse-
was derived fromthe dehydrogenation of monoterpenes
quent deprotonation from A giving the exocylic double
8, 9 and 10, which resulted fromthe dehydration of a-ter- bond seems to be kinetically favored, as with NaYat low
pineol (7) or dehydration-cyclization of linalool and ner- temperature the g isomer was formed predominantly.
ol. A relevant example was reported recentlythat mono- while at high temperature, or with FeY, the more stable
terpenes including 8, 9 and 10 incorporated in methyl vi- a isomer was almost the only product.
ologen (MV2þ)-supported NaYundertook spontaneous
In the case of nerol, however, this action leading to the
electron transfer reactions to generate p-cymene (6) in formation of carbocation A was less effective, probably
high yields.[18]
due to the Z configuration of the 2,3-double bond.
The formation of a- and g-cyclogeraniol under the Meanwhile the competitive route, the formation of a-
same conditions, in the case of geraniol, was apparently terpineol and monoterpenes, was facile for nerol and li-
via a pathway which is generally not accessible under ho- nalool under acidic conditions.[12] As a result, only a
mogenous Brønsted acidic and/or Lewis acidic condi- small amount of a-cyclogeraniol was generated.
tions. Zeolites are in nature crystalline aluminosiliates
It is interesting to note that both geraniol and nerol
with a highly ordered crystalline structure. Cavities of acetates (11, 12) could be transformed efficiently to cy-
a definite size (for Y zeolite, the cavity is about 13 Š clogeraniol acetates under same conditions (Table 1).
in diameter) are formed in the rigid, three-dimensional The mass balance was >70% in these cases. Probably af-
networks composed of SiO4 and AlO4 tetrahedra.[1] ter acetylation, the orientation of the terminal double
Therefore, zeolites exert some kind of shape selectivity bond of nerol actetate inside the cavities was adjusted
to the organic molecules inside the cavities. The unique to be such that more effective interaction with the acid
supercage structure as well as the acidity of NaY pro- sites was achieved, enabling the transformation to cyclo-
vides a favorable environment for the direct transforma- geraniol acetates to occur. Besides, as the acetate is
tion of geraniol to cyclogeraniols. It is believed that the more stable than the hydroxy group towards acid, the
superacidic cyclization of geraniol to form a-cyclogera- competitive cyclization pathway toward p-cymene was
niol involves the carbocation intermediates as the result hampered for nerol acetate.
À
À
of protonation of the 6,7-double bond.[13] It is possible
that a similar process occurred in the NaY/FeY-geraniol for the formation of cyclogeraniols from geraniol. The
system(Scheme 3). When these terpenols entered the reason for this might be that after heating FeY at
FeYactivated at 1008C for 2 h was much less effective
cavities of NaY or FeY, both the hydroxy group and 1008C for 2 h, there were still some H2O molecules re-
the carbon-carbon double bond could interact with the maining inside the zeolite, and only few Brønsted acid
acid sites. We suppose that the hydroxy group should sites were generated within the framework. Therefore,
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61

Wei Yu et al.
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(s, 3H), 1.27 (dt, J¼13.6, 4.4 Hz, 1H), 1.42 (dt, J¼13.6,
4.4 Hz, 1H), 1.59 (m, 2H), 2.04 (dd, J¼4.0, 10.8, 1H), 2.12 (t,
geraniol reacted mostly in a similar way to the FeCl3 ·
6 H2O-catalyzed reaction. It was found that if FeY was
kept at 1008C for a longer time, the yield of a-cycloger-
aniol could be remarkably improved.
¼
J¼6.8 Hz, 2H), 3.62 (t, J¼10.8 Hz, 1H), 3.72 (dd, J 4.0,
10.8 Hz, 1H), 4.76 (d, J¼2 Hz, 1H), 4.96 (d, J¼2 Hz, 1H);
13C NMR (400 MHz, CDCl3): d¼23.1 (CH2), 26.6 (CH3), 28.5
(CH3), 31.7 (CH2), 33.8 (C), 36.2 (CH2), 56.4 (CH), 59.5
(CH2), 111.8 (CH2), 147.4 (C); EI-MS: m/z (%)¼154 (2), 136
(12), 121 (31), 93 (67), 81 (54), 69 (100).
In conclusion, this work demonstrates that NaY and
FeY exhibit a diversity of catalytic activities for the iso-
merization, dehydration, dehydrogenation and cycliza-
tion reactions of terpenols 1–3. The catalytic behavior
depends significantly on the metal doped and the activa-
tion temperature and enables the selective production
of different products. A significant finding is that a-
and g-cyclogeraniols can be produced directly fromger-
aniol in the zeolites, demonstrating interesting product
selectivity and the potential of using zeolites in organic
synthesis.
Acknowledgements
We thank the National Natural Science Foundation (grant No.
20372030)and Foundation for University Key Teachers by Min-
istry of Education of China for financial support.
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Spectra Data
2,6,6-Trimethylcyclohex-2-enylmethanol (a-cyclogeraniol) (4):
1H NMR (400 MHz, CDCl3): d¼0.88 (s, 3H), 1.01 (s, 3H), 1.17
(dt, J¼12.0, 4 Hz,1H), 1.40 (br, OH), 1.60 (m, 3H), 1.72 (s, 3H),
1.98 (m, 1H), 3.72 (m, 2H), 5.58 (br, 1H); 13C NMR (400 MHz,
CDCl3): d¼22.8 (CH3), 22.9 (CH2), 27.7 (2ꢀCH3), 31.7 (C),
32.4 (CH2), 52.0 (CH), 61.4 (CH2), 124.4 (CH), 131.8 (C); EI-
MS: m/z (%)¼154 (4), 136 (10), 123 (65), 93 (38), 81 (100).
2-Methylene-6,6-dimethylcyclohexylmethanol (g-cyclogera-
´
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niol) (5): H NMR (400 MHz, CDCl3): d¼0.67 (s, 3H), 0.95
62
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Adv. Synth. Catal. 2006, 348, 59 – 62