MARCEL DEKKER, INC.

• 270 MADISON AVENUE • NEW YORK, NY 10016

©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

SYNTHETIC COMMUNICATIONSÕ
Vol. 33, No. 11, pp. 1867–1872, 2003

Improvement of the Synthesis of Vitamin E

Catalyzed by Montmorillonite

Hui-Yun Duan,* Zhen-Hua Wang, Ji-Tai Li, Sheng-Hui Li,

Li-Jun Li, and Tong-Shuang Li

College of Chemistry and Environmental Science of

Hebei University, Baoding, Hebei Province, P.R. China

ABSTRACT

Montmorillonite K 10 or montmorillonite K 10-supported metal salt

as catalysts to synthesize VE (yield 21.0–64.4%) with 2,3,5-trimethyl-
hydroquinone and isophytol. The catalysts can be reused.

Key Words: Vitamin E; Synthesis; Montmorillonite; Supported

catalyst.

*Correspondence: Hui-Yun Duan, College of Chemistry and Environmental

Science of Hebei University, Department of Chemistry, Hezuo Road No. 88,
Baoding 071002, Hebei Province, P.R. China; Fax: þ86-312-5079628;
E-mail: orgsyn@mail.hbu.edu.cn.

1867

DOI: 10.1081/SCC-120020197 0039-7911 (Print); 1532-2432 (Online)

Copyright & 2003 by Marcel Dekker, Inc. www.dekker.com
 MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

1868 Duan et al.

Since scientist began to research Vitamin E (VE) from 1930s, the

mainly synthetic method was the condensation of 2,3,5-trimethylhydro-
quinone (TMHQ, 1) and isophytol (IPL, 2) catalyzed by anhydrous
zinc chloride.[1,2] From then on, similar technological process catalyzed
by Lewis acid was continued to use in the industrial production.
However, the drawback of the traditional catalyst from the practical
and environmental viewpoints was exposed with the development of
science. Then some new catalysts were found, such as scandium(III)
trifluoromethanesulfonate,[3] trifluoromethanesulfonimide,[4] trimethyl-
hydroquinone-ZnBr2,[5] trimethylhydroquinone-NafionNR 50[6] andsoon.
The reaction catalyzed by these new catalysts is not acceptable because of
high cost, low yield, or environmental problem. Besides, by-products,
such as benzofurans type by-products (4) and dehydrated by-products
of isophytol, also obstruct the application of these new catalysts to
industrial. Therefore, the technological process catalyzed by zinc chloride
has been continuing to use in most present industrial production.
For the past few years, we have searched the application of
montmorillonite type catalysts and found that it can catalyze lots of
reactions successfully, including alkylation and condensation. Besides,
the catalysts are convenient, economical, and environmentally friendly.[7]
Up to now, no reports are found in which VE is synthesized catalyzed by
montmorillonite. In this article, we have applied montmorillonite or
montmorillonite-supported metal salt as catalysts to synthesize VE with
1 and 2 (Sch. 1).
Catalyzed by Mont. K 10-supported Lewis acid, VE can be synthesized.
Different catalyst, different yield of VE was given. The crude products
was separated on GLC and identified to the contents of VE, benzofurans
type by-products and the dehydrated by-products of isophytol. The
contents were used as the index to weight the performance of catalysts.

Scheme 1.
 MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

Vitamin E Catalyzed by Montmorillonite 1869

Table 1. Synthesis of vitamin E catalyzed by montmorillonite K 10.

Yields (%)
Reaction
a
Entry Catalyst time/min 3 4 5

1 Mont. K 10 5 56.3 0 28.3

b
2 ZnCl2-M 30 61.6 0 26.7
c
3 Ce3þ-M 240 21.0 31.2 27.0
4 CoCl2-M 40 61.1 0 32.3
5 SnCl2-M 35 61.8 0 30.4
6 SnI4-M 180 57.6 0 34.7
7 FeCl3-M 5 39.1 10.7 39.1
8 CuCl2-M 8 43.0 4.6 37.6
9 SbCl3-M 90 64.4 3.7 23.2
10 MnSO4-M 15 54.5 0 20.6
c
11 MnSO4-M 60 58.2 0 23.6
12 NiCl2-M 60 60.7 0 22.3

Yield data is based on GLC. Benzene as solvent. Metal salt/Mont. K 10 ¼ 1 mmol/g.

TMHQ/Cat. ¼ 1:0.5 (mol), IPL/TMHQ ¼ 1.5–1.7.
a
5 indicates dehydrated by-products of isophytol.
b
M stands for Mont. K 10.
c
TMHQ/Cat. ¼ 1:0.25.

Then some more efficient catalysts, the suitable ratio of catalyst to

substrate and the suitable ratio of 2 to 1 can be sought.
Exchanging proton by metallic cations modified Mont. K 10.
The initial result is summarized in the Table 1. It seems that there is no
obvious regularity from the table. Most of the catalysts have excellent
selectivity for VE and benzofurans type by-products, but poor for
dehydrated by-product of isophytol. Strong acid can convert isophytol
into olefin easily through dehydration, so this kind of catalyst has poor
selectivity for dehydrated by-products of which the yields are 15–40%.
The water, which produced during dehydration and was not removed,
can reduce the activity of catalyst. Consequently, a volume of isophytol
and catalyst was used. Although some of solid acid, like Ce3þ, Cu2þ,
Fe3þ-Mont. K 10, etc. are not good catalysts for synthesizing VE, several
kinds of catalysts that can be studied more were screened out, such as
Mn2þ, Ni2þ, Sb3þ, etc. In the reactions catalyzed by these solid acids,
the contents of VE are above 60%. The isomer by-products (4) and
dehydrated by-products are less.
The reaction can still be performed on a multigram scale under the
same condition. The product VE can be separated from the colature by
 MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

1870 Duan et al.

Table 2. Results of reaction on multigram scale.

Catalyst Reaction time Yields of VE

MnSO4-M 40 min 89%

MnSO4-M (recovered) 40 min 88%

TMHQ: 3.04 g (0.02 mol), IPL: 8.88 g (0.03 mol).

column chromatography on silica gel and the yields are above 85%.
A more excellent result is the used catalyst can be reused and the yields
are also above 85%. Two groups of data are listed in Table 2.
The catalysts of solid acid have some special characters. It is
convenient, economic, and environmentally friendly. In our experiment,
some kinds of worthwhile solid acid catalysts are found. Therefore, to
study these catalysts deeply may lead a new idea for the synthesis of VE.

EXPERIMENTAL

Preparation of Catalyst

To a solution of MnSO4 (0.602 g, 4 mmol) in ethanol (30 mL) was

added montmorillonite K 10 (4 g) at room temperature. Using a rotary
evaporator under reduced pressure evaporated the solvent. The resulting
reagent was then dried at 120 C for 2 h.

Typical Procedure

A dry three-necked flask fitted with a stir bar and a reflux condenser
was charged with benzene 5 mL, 1, 19 mg and Mont. K 10-SbCl3 63 mg.
Under a nitrogen atmosphere, the solution was soon brought to reflux.
After a solution of 2, (65 mg) in benzene (2 mL) was added in drops over
10 min, the reaction mixture was refluxed with stirring for 1 h. When the
resulting solution was cooled, the catalyst was removed by filtration and
the solvent was evaporated to give yellow oil (93 mg). Analytical GLC for
the yellow oil was performed on Gaskuro Kogyo Model 370 instrument
with a flame-ionization detector and a capillary column of HP-1 (20 m)
using nitrogen as the carrier gas: column temp. ¼ 280 C, tR ¼ 13.0 min
(64.4%) for 3, tR ¼ 11.8 min (3.7%) for 4, tR ¼ 3.8–4.9 min (23.2%) for
dehydrated by-products.
 MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

Vitamin E Catalyzed by Montmorillonite 1871

The Recovery of Catalyst

After the reaction, the filter catalyst was oven dried at 120 C for 1 h
to be reused.

ACKNOWLEDGMENTS

We thank the helpful discussion with Dr. Susumu Akutagawa,

TNI, Japan.

REFERENCES

1. Bergel, F.; Copping, A.M.; Jacob, A.; Diwoky, A. Synthesis of race-

mic a-tocopherol and of a lower homolog. J. Chem. Soc. 1938, 1382.
2. Irvin, L.; Ungnade, H.E. The chemistry of vitamin E. IV. the synth-
esis of tocopherols. J. Org. Chem. 1939, 4, 298.
3. Matsui, M.; Karibe, N.; Hayashi, K.; Yamamoto, H. Synthesis of a-
tocopherol: scandium (III) trifluoromethanesulfonate as an efficient
catalyst in the reaction of hydroquinone with allylic alcohol. Bull.
Chem. Soc. Jpn. 1995, 68, 3569.
4. Ishihara, K.; Kubota, M.; Yamamoto, H. Practical synthesis of ()-
a-tocopherol trifluromethanesulfonimide as an extremely active
brønsted acid catalyst for the condensation of trimethylhydroqui-
none with isophytol. Synlett 1996, 11, 1045.
5. Norio, K.; Kenji, H.; Norio, M. Jpn. Kokai Tokkyo Koho JP,
07291958 [95291958], 1995 (CA, 1995, 124: P87429x).
6. Werner, B. Eur. Pat. Appl. EP, 782993, 1997 (CA, 1997, 127:
P109079z).
7. (a) Li, T.S.; Li, H.Z.; Guo, J.L.; Jin, T.S. Montmorillonite clay
catalysis I: an efficient and convenient preparation of 5(6), 50 (60 )-
unsaturated 3b,3b0 -disteryl ethers. Synth. Commun. 1996, 26 (13),
2497; (b) Li, T.S.; Li, S.H.; Li, J.T.; Li, H.Z. Montmorillonite clay
catalysis part 2: an efficient and convenient procedure for prepara-
tion of acetals catalyzed by montmorillonite K 10. J. Chem. Research
(S) 1997, 17 (1), 26; (c) Li, T.S.; Zhang, Z.H.; Yang, F.; Fu, C.G.
Montmorillonite clay catalysis part 7: an efficient and environmen-
tally friendly procedure for the synthesis of coumarins via Pechmann
condensation of phenols with acetoacetate. J. Chem. Research (S)
 MARCEL DEKKER, INC. • 270 MADISON AVENUE • NEW YORK, NY 10016
©2003 Marcel Dekker, Inc. All rights reserved. This material may not be used or reproduced in any form without the express written permission of Marcel Dekker, Inc.

1872 Duan et al.

1998, 18 (1), 38; (d) Li, T.S.; Zhang, Z.H.; Jin, T.S. Montmorillonite
clay catalysis part 9: a mild and efficient method for removal of
tetrahydropyranyl. Synth. Commun. 1999, 29 (2), 181.

Received in Japan June 16, 2002