Synthesis of D,L-α-tocopherol using strong solid acids as catalysts

Article abstract of DOI:10.1006/jcat.1998.2351

The synthesis of D,L-α-tocopherol starting from trimethylhydroquinone and isophytol using a heterogeneous solid acid catalyst, e.g., Nafion NR 50, is described. Advantages of this new procedure are high yield and selectivity, facile recovery of the catalyst, no waste problems, and mild reaction conditions.

Full text of DOI:10.1006/jcat.1998.2351

Journal of Catalysis 182, 282–284 (1999)
Article ID jcat.1998.2351, available online at http://www.idealibrary.com on
RESEARCH NOTE
Synthesis of D,L-�-Tocopherol Using Strong Solid Acids as Catalysts
1
Frank Schager and Werner Bonrath
Vitamin Research and Technology Development, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, CH-4070 Basel, Switzerland
Received September 9, 1998; revised October 28, 1998; accepted November 8, 1998
(
7), the tertiary alcohol 2 was not dehydrated under these
The synthesis of D,L-�-tocopherol starting from trimethylhydro- conditions. As outlined in Scheme 1, the acid-catalyzed con-
quinone and isophytol using a heterogeneous solid acid catalyst, densation consists of a Friedel–Crafts reaction followed by
e.g., Nafion NR 50, is described. Advantages of this new procedure
are high yield and selectivity, facile recovery of the catalyst, no waste
a condensation reaction. The aim of our work was to find a
good solvent system, to study the reproducibility catalysts
problems, and mild reaction conditions.
�c 1999 Academic Press
used, and to test the property of the recycled catalyst.
The reactions were carried out in batch reactors under ar-
gon atmosphere. The catalyst, reactants, and solvents were
used without purification. Yields and purity were deter-
mined by GLC analysis.
Key Words: D,L-�-tocopherol; Friedel–Crafts reaction; solid acids.
Industrial syntheses of
condensation of trimethylhydroquinone (1) with isophytol
2) or phytol halides (1). Lewis acids and Brønsted acids,
D,
L
-�-tocopherol are based on the
The reactions were carried out on a 200 mmol scale, 1 h
(
�
heating at 100–140 C, and ambient pressure. The reaction
e.g., zinc chloride and a mineral acid, serve as catalysts for
this reaction (2). BF3, AlCl3, Fe/HCl, or the combination
boric acid and carboxylic acids are good catalysts (1). The
reaction can be carried out in various solvents, e.g., ethyl
acetate or hydrocarbons. Disadvantages of all the known
methods are corrosion problems and/or a potential con-
tamination of waste water with zinc ions.
solution consists of 33 wt% solvent, 21 wt% 1, 40 wt% 2, and
5
wt% catalyst. The conversions are around 95% and the
yields of tocopherol are in the range of 75–92% . In Table 1
the results of the condensation reaction between 1 and 2
are summarized.
A first remarkable observation is that the
D
, -�-toco-
L
pherol yields are maximized in polar aprotic solvents. A
second observation is, surprisingly, that Nafion NR 50 is
the most efficient catalyst for this reaction (8). Other het-
erogeneous polysulfonic acid catalysts, e.g., Dowex 50WX8
To overcome the disadvantages of the known synthe-
ses of
D
, -�-tocopherol we used for mineral acids the
L
strongly acidic sulfonic acid Nafion NR 50 as replace-
ment. The acidity of this acid perfluorosulfonic acid resin,
which isa copolymer oftetrafluoroethene and a perfluorsul-
fonylether, has been suggested to be similar to concentrated
sulfuric acid (3). A considerable number of reactions cata-
lyzed by Nafion have already been described (4–6). Olah
and co-workers demonstrated that alcohols are efficiently
dehydrated in the presence of Nafion. The ease of dehydra-
tion is in the order tertiary > secondary > primary alcohol.
At higher temperature the alcohols are dehydrated nearly
quantitative yield (7). We also used Amberlyst 15, a strongly
acidic cation exchange resin with a SO3H functional struc-
ture.
(
20% ) or Amberlite 200 (60% ), are less active.
The main by-products in this reaction are phytadi-
enes and the furan derivative 4 (Scheme 2), which has
already been found by Yamamoto and co-workers in the
In this paper, we show that the condensation of 1 and 2
can be carried out using strong solid acids in various sol-
vents. Contrary to our expectations and to the literature
1
To whom correspondence should be addressed. E-mail: Werner.
Bonrath@Roche.com.
SCHEME 1
282
0021-9517/99 $30.00
Copyright �c 1999 by Academic Press
All rights of reproduction in any form reserved.

SYNTHESIS OF
D,
L
-�-TOCOPHEROL
283
TABLE 1
Condensation of 1 and 2 in Different Solvents
Using Strong Solid Acids
Catalyst
Solventa
Yield (% )b
Nafionc
Nafion
Nafion
Nafion
Toluene
Diethyl ketone
Isobutylmethyl ketone
Propylene carbonate
� -Butyrolactone
Toluene
Diethyl ketone
Isobutylmethyl ketone
Propylene carbonate
� -Butyrolactone
75
84
83
92
80
83
82
79
90
77
d
SCHEME 2
Nafion
e
Amberlyst
Amberlyst
Amberlyst
Amberlyst
Amberlyst
scandium(III) trifluoromethanesulfonate catalyzed con-
densation of 1 and 2 (9).
d
In further experiments, the reproducibility of the Nafion
NR 50 results was examined. The results are summarized in
Table 2. The reactions are carried out under the aforemen-
tioned conditions with Nafion NR 50 as catalyst in propy-
lene carbonate as solvent.
The conversions are around 95% . The yield is in the range
of 90.5–92.5% . The reproducibility of these experiments is
remarkably good (Table 2): the average yield is higher than
a
5
0 ml solvent.
b
Yield is based on 2, determined by GLC analysis of the crude reaction
products; in some cases all products were isolated and the yields compare
well with that optained by GC analysis.
c
d
e
+
Nafion, Nafion NR 50 (H -Form, 7–9 mesh).
Two-phase system with heptane (one to one mixture).
Amberlyst, Amberlyst 15 (H -Form, 20–50 mesh).
+
9
1% .
Figure 1 represents the results we obtained by reusing the
TABLE 2
catalyst under the aforementioned conditions with Nafion
NR 50 in propylene carbonate as solvent.
Reproducible Synthesis of D,L-�-Tocopherol Using
Nafion NR 50 in Propylene Carbonate
We found that the yield of
D
, -�-tocopherol decreases
L
after a few experiments. This is explained by deactivation
of the catalyst, because unchanged starting material and
a higher amount of phytadienes are detected. However,
the catalyst can be reactivated (10). The yields for reusing
Amberlyst 15 are in the range of 50–60% .
Run
Yield (% )a
1
2
3
4
5
92.3
91.3
90.5
91.4
91.0
In comparison with the results of zinc chloride/Brønsted
acid or BF3-catalyzed reactions, we found good yields and
a
Yield is based on 2, determined by GLC analysis of
selectivities. Using ZnCl2/HCl or BF3 as catalyst
D
, -�-toco-
L
the crude reaction products.
pherol yields of approximately 80% could be achieved (11).
In contrast to our results, Amberlyst 15 in combination with
the metal ions Sn(IV), Sn(II), or Zn(II) decreases the yield
of
D
, -�-tocopherol (12). Another advantage of the new
L
procedure is the low amount of catalyst.
The described procedure has advantages over the known
processes for the synthesis of
D
, -�-tocopherol, i.e., high
L
yield conversion and selectivity. Therefore, it can be em-
phasized that the strong solid acid catalyst Nafion NR 50
shows a better catalytic performance. It has to be pointed
out that the heterogenously catalyzed synthesis of
D
, -�-
L
tocopherol is improved by using a polar aprotic solvent,
such as propylene carbonate.
ACKNOWLEDGMENTS
FIG. 1. Synthesis of
propylene carbonate.
D,L
-�-tocopherol with reused Nafion NR 50 in
The authors are grateful to Mr. F. Aquino for technical assistance and
to Dr. D. Burdick for valuable advice and discussion.

2
84
SCHAGER AND BONRATH
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