Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-11-13
2002-08-27
Solola, T. A. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06441200
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to a preparation method of DL-alpha-tocopherol of high purity through the condensation between isophytol or phytol derivatives and trimethylhydroquinone (TMHQ). More particularly, the present invention relates to a combined catalyst system which includes a divalent halogen compound MX
2
(wherein M is a divalent metal ion and X is halogen) as a main catalyst component, silica gel and/or silica-alumina as a co-catalyst and a Brönsted acid as an additional catalyst component and a regenerating component for the co-catalyst, thereby enabling the preparation of DL-&agr;-tocopherol with a high purity at a high yield on a commercial scale.
2. Description of the Prior Art
For the past few decades, extensive effort has been made to effectively prepare DL-&agr;-tocopherol by use of Zn(II) ions as metallic catalysts (Lewis acid catalyst). Conventionally, the DL-&agr;-tocopherol is prepared through the condensation of a isophytol and trimethylhydroquinone (TMHQ) represented by the following reaction formula 1:
For example, U.S. Pat. No. 4,217,285(hereinafter referred to as '285 patent), which is assigned to Nisshin, discloses the synthesis of DL-&agr;-tocopherol in toluene or n-hexane solvent with ZnCl
2
and silica-alumina (or silica-gel) in the presence of acid, especially HCl, asserting that tocopherol can be obtained with a purity of 95 to 96% at a production yield of 99% or higher. Also, U.S. Pat. Nos. 4,634,781 and 4,639,533, both assigned to BASF, disclose processes for producing DL-&agr;-tocopherol in which isophytol is reacted with amines such as tridecylamine or octadecylamine and thereafter with TMHQ in the presence of ZnCl
2
and HCl, which are somewhat complicated and inefficient. In those techniques, the tocopherol is described to be produced with a purity of 94 to 95% at a yield of 95 to 98%. Other preparation methods of DL-&agr;-tocopherol can be found in U.S. Pat. Nos. 5,663,376 and 5,886,197, both assigned to Eisai Co., Ltd, in which isophytol is reacted with TMHQ in a mixed solvent system comprising a non-polar solvent and an alcohol or carbonate ester. It is described that DL-&agr;-tocopherol can be produced at a yield of 94 to 98% with a purity of 92 to 97%.
However, the conventional techniques leave room for improving purity because their DL-&agr;-tocopherol is as low as 95% on average purity. Particularly, the BASF and the Eisai patents are inefficient in that they do not satisfy the desired yield of DL-&agr;-tocopherol. Such a disadvantage is attributed to the fact that, in the case that a Brönsted acid, such as hydrochloric acid, serving as a co-catalyst, is present from the early stage of the reaction, loss of the reactant isophytol occurs owing to the dehydration by the Brönsted acid, giving rise to a decrease in the total yield.
Being used as a solvent in the '285 patent, toluene or hexane brings about a poor total yield of DL-&agr;-tocopherol. When used, toluene itself is partially reacted with isophytol to be produced undesired by-products. Hexane, although not reacting with isophytol, lengthens the reaction time owing to its low boiling point (approximately 69° C.) such that the catalyst induces the dehydration of isophytol. Furthermore, when the synthesis of DL-&agr;-tocopherol is carried out under such a reaction procedure, by-products analogous in structure to DL-&agr;-tocopherol are found in relatively large quantities, decreasing the purity of the DL-&agr;-tocopherol separated. In addition, the total yield of DL-&agr;-tocopherol is lowered when purifying it to a very high purity.
The '285 patent has an advantage over the above other patents in that it is high in the production yield of DL-&agr;-tocopherol because of the use of silica gel or silica-alumina as a solid catalyst, however suffers from the disadvantage of being unable to recycle the silica catalyst because of the adsorptivity of silica for certain organic materials. For instance, in the case that the reactant TMHQ, reaction intermediates (the condensation may provide two intermediates owing to the reaction mechanism), and the required product DL-&agr;-tocopherol are adsorbed onto the surface of the silica gel catalyst to prevent active functional sites of the catalyst such that the activity of the catalyst drops sharply. That is, it is impossible to reuse the silica gel catalyst. Furthermore, when the DL-&agr;-tocopherol adsorbed onto the surface of the silica gel is not recovered, the total yield of DL-&agr;-tocopherol becomes poor.
Another problem with the '285 patent resides in the existence of hydrochloric acid from the early stage of the reaction. As aforementioned, hydrochloric acid decomposes isophytol through dehydration to decrease the total yield, as well as causes other side-reactions which may occur between isophytol and TMHQ, to generate by-products which are similar in molecular weight to vitamin E, thereby lowering the purity thereof.
SUMMARY OF THE INVENTION
Knowledge of a catalytic reaction allows modification and adaptation leading to the present invention.
The intensive and extensive research on the preparation of DL-&agr;-tocopherol from isophytol or phytol derivatives and TMHQ, conducted by the present inventors, resulted in the finding the preparation method of DL-&agr;-tocopherol capable of minimizing the self-decomposition of isophytol or phytol derivatives and the generation of by-products by employing MX
2
as a main catalyst and silica gel and/or silica-alumina as a co-catalyst to form intermediates in the reaction mixture and thereafter adding a Brönsted acid as an additional catalyst to the reaction for obtaining a final product when the intermediates formation has been completed.
Therefore, it is an object of the present invention to provide a method for preparing DL-&agr;-tocopherol with a high purity at a high yield.
It is another object of the present invention to provide a method for preparing DL-&agr;-tocopherol from a minimum amount of isophytol or phytol derivatives relatively while generating substantially no by-products, whereby a great economical benefit can be brought about in terms of production cost.
It is a further object of the present invention to provide a method for preparing DL-&agr;-tocopherol by use of a catalyst system which is highly effective even for application on a commercial scale and can be regenerated continually.
In accordance with the present invention, the above objects could be accomplished by a provision of a method for preparing DL-&agr;-tocopherol with a high purity at a high yield, comprising:
a) adding isophytol or phytol derivatives to trimethylhydroquinone for the condensation thereof at 80 to 135° C. over 30 to 60 min in the presence of a catalyst system comprising main catalyst component and a co-catalyst in a reaction solvent to form intermediates, said main catalyst consisting of a divalent metal halogen compound represented by MX
2
wherein M is Zn
2+
, Fe
2+
or Sn
2+
and X is F, Cl or I, said co-catalyst consisting of silica gel and/or silica-alumina;
b) adding a Brönsted acid to the resultant mixture of said a) step, thereafter to obtain a product through the separation; and
c) washing the remaining co-catalyst with a polar solvent for recovery after said b) step, whereby the recovered co-catalyst can be reused for the preparation of DL-&agr;-tocopherol.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the present invention, DL-&agr;-tocopherol is prepared through the condensation between isophytol or phytol derivatives and TMHQ in the presence of a catalyst system comprising a main catalyst, a co-catalyst and an additional catalyst in a solvent selected from the group consisting of aliphatic saturated hydrocarbons, aromatic hydrocarbons, appropriate polar solvents and mixtures thereof. The main catalyst is represented by the general formula MX
2
wherein M is a divalent metal ion such as Zn
2+
, Fe
2+
or Sn
2+
and X represents halogen such as F, Cl, Br or I. The co-cat
Choi Jun-Tae
Kim Jeong-Soo
Kim Myung-Jun
Kwak Byong-Sung
Lee Sijoon
Abelman ,Frayne & Schwab
Sk Corporation
Solola T. A.
LandOfFree
Method for preparing DL-&agr;-tocopherol with a high yield... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for preparing DL-&agr;-tocopherol with a high yield..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for preparing DL-&agr;-tocopherol with a high yield... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2893600