D,L-α-tocopherol synthesis catalyzed by the Bronsted acidic ionic liquids

Article abstract of DOI:10.1080/00397910600781166

The synthesis of D,L-α-tocopherol from trimethylhydroquinone and isophytol using the Bronsted acidic SO₃H-functionalized ionic liquids as catalysts was explored. The catalytic activities of the SO ₃H-functionalized ionic liquids were dependent on their anions. The yield of D,L-α-tocopherol also depended on the solvent, which was the reaction medium. A yield of 94.3% was obtained using the SO₃H- functionalized ionic liquid with [BF₄^-] anion as catalyst in propylene carbonate/heptane. The reaction mixture exhibited good biphasic behaviors, so that the produced D,L-α-tocopherol could be separated by decantation. The SO₃H-functionalized ionic liquids could be reused after the removal of water. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910600781166

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D,L‐α‐Tocopherol Synthesis Catalyzed by the
Brønsted Acidic Ionic Liquids
a
a
a
a
Huabing Xing , Tao Wang , Zhenhuan Zhou & Youyuan Dai
a
State Key Laboratory of Chemical Engineering, Department of Chemical
Engineering , Tsinghua University , Beijing, China
Published online: 27 Oct 2006.
To cite this article: Huabing Xing , Tao Wang , Zhenhuan Zhou & Youyuan Dai (2006) D,L‐α‐Tocopherol
Synthesis Catalyzed by the Brønsted Acidic Ionic Liquids, Synthetic Communications: An International
Journal for Rapid Communication of Synthetic Organic Chemistry, 36:17, 2433-2439, DOI:
10.1080/00397910600781166
To link to this article: http://dx.doi.org/10.1080/00397910600781166
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Synthetic Communications , 36: 2433–2439, 2006
Copyright # Taylor & Francis Group, LLC
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910600781166
D,L-a-Tocopherol Synthesis Catalyzed by
the Brønsted Acidic Ionic Liquids
Huabing Xing, Tao Wang, Zhenhuan Zhou, and Youyuan Dai
State Key Laboratory of Chemical Engineering, Department of Chemical
Engineering, Tsinghua University, Beijing, China
Abstract: The synthesis of D,L-a-tocopherol from trimethylhydroquinone and
3
isophytol using the Brønsted acidic SO H-functionalized ionic liquids as catalysts
was explored. The catalytic activities of the SO H-functionalized ionic liquids were
3
dependent on their anions. The yield of D,L-a-tocopherol also depended on the
solvent, which was the reaction medium. A yield of 94.3% was obtained using the
2
4
SO H-functionalized ionic liquid with [BF ] anion as catalyst in propylene
3
carbonate/heptane. The reaction mixture exhibited good biphasic behaviors, so
that the produced D,L-a-tocopherol could be separated by decantation. The SO H-
3
functionalized ionic liquids could be reused after the removal of water.
Keywords: Brønsted acidic ionic liquid, D-L-a-tocopherol, synthesis
INTRODUCTION
D,L-a-Tocopherol is the most economically valuable form of vitamin
E, which is the most important fat-soluble antioxidant in biological
[
1]
systems. Industrial synthetic processes of D,L-a-tocopherol are based on
the condensation of trimethylhydroquinone (TMHQ) with isophytol (IP) or
phytyl halides. Lewis or Brønsted acids, such as zinc chloride with a
[
2–4]
mineral acid, are usually used as the catalysts for this condensation
reaction. The main problems in the synthesis of D,L-a-tocopherol with the
Received in Japan October 24, 2005
Address correspondence to Tao Wang, State Key Laboratory of Chemical Engineer-
ing, Department of Chemical Engineering, Tsinghua University, Beijing 100084,
China. E-mail: taowang@tsinghua.edu.cn
2
433

2
434
H. Xing et al.
conventional catalysts are the corrosion due to the acidic media, the
contamination of water with acids, and the difficulty of recycling the acid
catalysts.
Many efforts have been made to improve the synthesis of D,L-a-
tocopherol. The heterogeneous acids (e.g., Nafion
[
5–7]
), microencapsulated
[
scandium tris-triflate, fluorinated NH-acidic catalyst, and Amberlyst
8]
[9]
[10]
were explored as alternatives to replace the mineral acids. However, there is
still one or more disadvantages in the synthetic procedure with those
catalysts, such as expensive reagents, complicated catalyst preparation pro-
cedures, low yields, large amounts of solid supports, and large amounts of
toxic wastes. Furthermore, the solid acids are fraught with drawbacks of
their own, including heterogeneous kinetics and the susceptibility to ready
[
6,8]
deactivation.
Recently, ionic liquids are gaining increasing attentions as alternative
solvents or catalysts for many organic reactions, especially in acid-
[
11–15]
catalyzed reactions.
It is well known that ionic liquids with metal
halide anions present Lewis acidity, especially those based upon chloroalumi-
nate anions. However, these ionic liquids are sensitive to moisture and
[
11,12]
unstable in water,
so the preparation and application of such kinds of
ionic liquids often need extreme operational conditions. Recently, Brønsted
acidic ionic liquids with an alkyl sulfonic acid group in the cations were
[
16]
developed. Cole et al.
with an alkyl sufonic acid group in imidazole cation and triphenylphosphine
first synthesized the Brørnsted acidic ionic liquids
cation. In a previous work, we developed the SO H-functionalized ionic
3
liquids that were composed of an alkyl sulfonic acid group modified with
The structures of the SO H-
3
[17]
pyridinium cation and different anions.
functionalized ionic liquids are shown in Fig. 1, where [PSPy] ¼ N-propyl
sulfonic acid pyridinium. The sulfonic acid group in pyridinium cation is
the ionic liquids’ functional group.
These SO H-functionalized ionic liquids are water stable, nonvolatile,
3
noncorrosive, and immiscible with many organic solvents. In our previous
work, these SO H-functionalized ionic liquids were used as acidic catalysts
3
for the esterification of benzoic acid with alcohols under solvent-free con-
[
17]
ditions.
In this work, the synthesis of D,L-a-tocopherol from TMHQ and
3
Figure 1. Structures of the SO H-functionalized ionic liquids with a pyridinium
cation.

D,L-a-Tocopherol Synthesis
2435
IP was conducted in these SO H-functionalized ionic liquids. The catalytic
3
activities of these SO H-functionalized ionic liquids were explored.
3
EXPERIMENTAL
Materials and Reagents
3
-Propyl sulfonic pyridinium (PSPy, purity: 97.5%) was purchased from
Wuhan Fengfan Chemical Co., China. TMHQ (purity: 99.5%) and IP
purity: 97%) were obtained from Zhejiang Xinhecheng Co., China. D,L-a-
(
Tocopherol (purity: 98.5%) was from Aldrich. All other chemicals (analytical
grade) were commercially available and used without further purification
unless otherwise stated.
Preparation of the SO H-Functionalized Ionic Liquids
3
The SO H-functionalized ionic liquids, [PSPy][BF ], [PSPy][HSO ], [PSPy]
4
3
4
[pTSA], and [PSPy][H PO ], were prepared according the procedures
reported in our previous paper.
2 4
[
17]
In the synthesis of [PSPy][BF ], the
4
reaction time was prolonged to 10 days to ensure the complete reaction. The
water contents of the SO H-functionalized ionic liquids were determined by
Karl Fisher titration with a Mitsubishi moisture meter (model CA-05).
3
Synthesis of D,L-a-Tocopherol
D,L-a-Tocopherol was synthesized using TMHQ and IP as reactants (Fig. 2).
The reaction was conducted in a three-necked glass flask equipped with a
reflux condenser at atmospheric pressure. IP was dropped into the mixture of
TMHQ and the SO H-functionalized ionic liquid in different solvents, which
3
was stirred at the boiling temperature. After adding IP, the reaction mixture
was stirred continuously for the desired time. The reaction mixture formed a
biphasic system when the reaction completed. The upper phase that contained
D,L-a-tocopherol was isolated by decantation. D,L-a-Tocopherol was
analyzed by HPLC (C18). TMHQ and IP were analyzed by GC (HP-1).
Figure 2. Synthesis reaction of trimethylhydroquinone with isophytol.

2
436
H. Xing et al.
The ionic liquid was confined in the lower phase and directly reused for
the next reaction run. For recycling [PSPy][BF ] in propylene carbonate/
4
heptane as the catalyst, the biphasic reaction mixture of the previous
reaction run was separated into two phases by decantation. The lower phase,
without any further treatment, which mainly consisted of [PSPy][BF ] and
4
propylene carbonate, was directly poured in the three-necked flask and
mixed with fresh heptane and THMQ. Then, IP was dropped into the three-
necked flask. The mixture was stirred at the boiling temperature for the
desired time. After that, the formed two-phase mixture was again separated
by decantation. The lower phase was reused for the next run. For the
seventh and eighth runs, the [PSPy][BF ] in propylene carbonate was regener-
4
ated by distillation in vacuum at 80 8C for 2 h to remove the excess water.
RESULTS AND DISCUSSION
The synthesis of D,L-a-tocopherol was initially carried out under the organic
solvent-free condition, in which the SO H-functionalized ionic liquid serves
3
as the dual solvent–catalyst. As listed in Table 1, although the conversion
of IP was around 99%, the yield of D,L-a-tocopherol was poor under the
solvent-free conditions. It was mainly because IP, a tertiary and allylic
alcohol, could be easily dehydrated to form phytadines in the presence of
[
6,9]
acid catalysts.
pure SO H-functionalized ionic liquids, which resulted in the ionic liquid
Moreover, TMHQ could be partially decomposed in the
3
phase gradually becoming dark as the reaction progressed. IP (99%) was
decomposed in pure [PSPy][BF ] at 120 8C for 2 h. TMHQ (36%) would be
4
degraded at the same condition.
As shown in Table 1, [PSPy][BF ] showed the best catalytic activity for
4
the synthesis of D,L-a-tocopherol. [PSPy][HSO ] could also be used as the
4
catalyst for the reaction with a slightly weaker activity as compared with
a
Table 1. Synthesis of D,L-a-tocopherol in different ionic liquids
Temperature
(8C)
Conversion
of IP (%)
Yield
c
(%)
b
Entry
Ionic liquid
1
2
3
4
[PSPy][BF
[PSPy][HSO
[PSPy][pTSA]
[PSPy][H PO
4
]
110
110
110
110
99
99
99
99
62.6
52.6
9.5
4
]
2
4
]
,1
a
Reaction condition: TMHQ–IP–ionic liquid 1 : 1 : 1.6; reaction temperature 110 8C;
reaction time 3 h.
b
Water content in ionic liquids: [PSPy][BF
PSPy][pTSA] 3.1%; [PSPy][H PO ] 2.6%.
4 4
] 6.8%; [PSPy][HSO ] 4.5%;
[
2
4
c
Yield based on IP.

D,L-a-Tocopherol Synthesis
2437
that of [PSPy][BF ]. The yield of D,L-a-tocopherol in [PSPy][pTSA] was
4
poor, only 9.5%. The synthesis reaction couldn’t be catalyzed by [PSPy]
[H PO ].
2
4
To avoid the decompositions of IP and TMHQ in the pure SO H-functio-
3
nalized ionic liquid, the reaction was carried out in toluene or propylene
carbonate (PC)/heptane (Hep) with [PSPy][BF ] or [PSPy][HSO ] as the
4
4
catalysts. As shown in Table 2, the yield of D,L-a-tocopherol was obviously
enhanced in these organic solvents. The yield of D,L-a-tocopherol increased
as the ratio of TMHQ–IP increased (compare Entries 6 and 7). The highest
yield of D,L-a-tocopherol (Entry 7, 94.3%) was obtained with [PSPy][BF4]
as the catalyst in propylene carbonate/heptane. With either toluene or
propylene carbonate/heptane as the solvent, the reaction systems exhibited
good biphasic behaviors. No appreciable amount of [PSPy][BF ] was
4
dissolved in the toluene phase. The reaction mixture was a biphasic system
when toluene was used as solvent. The SO H-functionalized ionic liquids
3
were easily dissolved in propylene carbonate and formed a biphasic system
with heptane. Furthermore, the D,L-a-tocopherol was hardly dissolved
in the ionic liquids or ionic liquids/propylene carbonate mixture, so the
produced D,L-a-tocopherol could be easily separated by decantation.
The feasibility of reusing [PSPy][BF ] with both toluene and propylene
4
carbonate/heptane as the solvents was checked. With toluene as the solvent,
the lower phase of the biphasic reaction mixture, in which [PSPy][BF ] was
4
conserved, could not be reused for catalyzing the synthesis reaction. The
yield of D,L-a-tocopherol with this [PSPy][BF ] phase as the catalyst was
4
only 26%. However, [PSPy][BF ] could be well reused in a simple way
4
when propylene carbonate/heptane was used. As shown in Fig. 3, without
any regeneration after the phase separation of the reaction mixture, the
catalytic activity of the [PSPy][BF ] in propylene carbonate was only a
4
slight decrease after being repeatedly used for six runs. For the seventh and
Table 2. Synthesis of D,L-a-tocopherol using ionic liquids in different solvents
TMHQ–IP–
ionic liquid
(molar ratio) Solvent
Reaction
temperature Reaction Yield
a
d
Entry
Ionic liquid
(8C)
time (h)
(%)
b
5
6
7
8
[PSPy][BF
[PSPy][BF
4
]
]
1.2 : 1 : 0.8 Toluene
1.2 : 1 : 0.8 PC/Hep
2:1 : 1 : 0.8 PC/Hep
2:1 : 1 : 0.8 PC/Hep
110
98
2
1
1
1
86.6
86.0
94.3
84.6
c
c
c
4
[PSPy][BF4]
[PSPy][HSO
98
98
4
]
a
4 4
Water content in ionic liquids: [PSPy][BF ] 4.8%; [PSPy][HSO ] 4.5%.
b
1
0 mmol of TMHQ in 20 ml of toluene.
c
1
0 mmol of TMHQ in 8 ml of PC/12 ml of Hep biphasic system; PC ¼ propylene
carbonate; Hep ¼ heptane.
d
Yield based on IP.

2
438
H. Xing et al.
Figure 3. Performance of reusing [PSPy][BF
4
] in the synthesis of D,L-a-tocopherol.
TMHQ–IP–ionic liquid 1.2 : 1 : 0.8, 10 mmol of TMHQ in 12 ml of PC and 8 ml of
Hep; reaction temperature 98 8C; reaction time 2 h; IP was dropped into the reaction
system within 0.5 h.
eighth runs, the [PSPy][BF ]/propylene carbonate was regenerated by distilla-
4
tion in vacuum at 80 8C for 2 h to remove water, and the catalytic activity was
totally recovered.
CONCLUSIONS
D,L-a-Tocopherol can be synthesized from TMHQ and IP using the SO H-
3
functionalized ionic liquids as catalysts. The catalytic activity of the
SO H-functionalized ionic liquid is dependent on its anion. The yield of
3
D,L,a-tocopherol can be as high as 94.3% with [PSPy][BF ] as the catalyst
4
in propylene carbonate/heptane. The produced D,L-a-tocopherol can be
easily separated from the reaction mixture by decantation. The catalyst/
solvent, [PSPy][BF ]/propylene carbonate, can be reused without or with
4
the regeneration by distillation in a vacuum.
REFERENCES
1
2
3
. Isler, O.; Brubacher, G.; Ghisla, S.; Kr a¨ utler, B.; In Vitamine II; Thieme: Stuttgart,
1
998; pp. 126–115.
. Yoshino, Y.; Kazuko, K. Process for the preparation of D,L-a-tocopherol of high
purity. US patent 4217285, 1980.
. Baldenius, K.-U.; von dem Bussche-H u¨ nnefeld, L.; Hilgemann, E.; Hoppe, P.;
St u¨ rmer, R. In Ullmann’s Encyclopedia of Industrial Chemistry; VCH:
Weinheim, 1996; Vol. A27, pp. 478–488.
4
. Finnan, J. L. Alpha tocopherol process. US Patent 4634781, 1987.

D,L-a-Tocopherol Synthesis
2439
5
6
7
. Schager, F.; Bonrath, W. Synthesis of D,L-a-tocopherol using strong solid acids as
catalysts. J. Catal. 1999, 182, 282–284.
. Wang, H.; Xu, B. Q. Catalytic performance of Nafion/SiO2 nanocomposites for
the synthesis of a-tocopherol. Appl. Catal. A 2004, 275, 247–255.
. Schneider, M.; Zimmermann, K.; Aquino, F.; Bonrath, W. Industrial application of
Nafion systems in rearrangement–aromatisation, transesterification, alkylation,
and ring-closure reactions. Appl. Catal. A 2001, 220, 51–58.
8. Schager, F.; Bonrath, W. Synthesis of D,L-a-tocopherol using “microencapsu-
lated” catalysts. Appl. Catal. A 2000, 202, 117–120.
9
. Bonrath, W.; Hass, A.; Hoppmann, E.; Netscher, T.; Pauling, H.; Schager, F.;
Wildermann, A. Synthesis of (all-rac)-a-tocopherol using fluorinated NH-acidic
catalysts. Adv. Synth. Catal. 2002, 344, 37–39.
1
0. Kokubo, Y.; Hasegawa, A.; Kuwata, S.; Ishihara, K.; Yamamoto, H.; Ikariyaa, T.
Synthesis of (all-rac)-a-tocopherol in supercritical carbon dioxide: Tuning of the
product selectivity in batch and continuous-flow reactors. Adv. Synth. Catal.
2005, 347, 220–224.
1
1
1
1
1
1
1. Welton, T. Room-temperature ionic liquids: Solvents for synthesis and catalysis.
Chem. Rev. 1999, 99, 2071–2083.
2. Wassercheid, P.; Keim, W. Ionic liquid—new “solution” for transition metal
catalysis. Angew. Chem., Int. Ed. 2000, 39, 3772–3783.
3. Davis, J. H., Jr.; Fox, P. A. From curiosities to commodities: Ionic liquids begin the
transition. Chem. Commun. 2003, 1209–1213.
4. Sheldon, R. Catalytic reactions in ionic liquids. Chem. Commun. 2001,
2399–2407.
5. Zhao, D. B.; Wu, M.; Kou, Y.; Min, E. Z. Ionic liquid: Application in catalysis.
Catal. Today 2002, 74, 157–189.
6. Cole, A. C.; Jensen, J. L.; Ntai, I.; Tran, K. L. T.; Weaver, K. J.; Forbes, D. C.;
Davis, J. H., Jr. Novel Brønsted acidic ionic liquids and their use as dual
solvent–catalysts. J. Am. Chem. Soc. 2002, 124, 5962–5963.
17. Xing, H. B.; Wang, T.; Zhou, Z. H.; Dai, Y. Y. Novel Bronsted-acidic ionic liquids
for esterifications. Ind. Eng. Chem. Res. 2005, 44, 4147–4150.