Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing
Reexamination Certificate
2000-02-11
2002-07-09
Killos, Paul J. (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Oxygen containing
C568S763000
Reexamination Certificate
active
06417409
ABSTRACT:
CROSS-REFERENCE TO RELATED APPLICATION
This application is based on German Application DE 199 05 685.4, filed Feb. 11, 1999, the disclosure of which is incorporated in its entirety herein by reference.
FIELD OF THE INVENTION
The invention relates to an improved process for the production of 2,3,5-trimethylhydroquinone diesters by rearrangement of 2,6,6-trimethyl-2-cyclohexene-1,4-dione (4-oxoisophorone, ketoisophorone) in the presence of a dissolved, acidic catalyst and an acylating agent, such as, for example, carboxylic anhydrides or carboxylic acid halides. The 2,3,5-trimethylhydroquinone diester can thereafter, optionally, be saponified to give free 2,3,5-trimethylhydroquinone (TMHQ), which is a valuable building block in the synthesis of vitamin E.
BACKGROUND OF THE INVENTION
2,3,5-Trimethylhydroquinone diesters and the corresponding TMHQ are important intermediates which are used in the production of vitamin E and vitamin E acetate. In addition to the known production process based on aromatic starting materials, 2,3,5-trimethylhydroquinone can be produced from a non-aromatic compound, 2,6,6-trimethyl-2-cyclohexene-1,4-dione, by rearrangement under acylating conditions and subsequent hydrolysis.
In patent specification DE 26 46 172 C2, a process is described in which 2,6,6-trimethyl-2-cyclohexene-1,4-dione is rearranged directly to trimethylhydroquinone in the vapor phase at a high temperature in contact with an acidic catalyst. However, the yield in this process is only low (50% with 30% conversion). If the aromatization of 2,6,6-trimethyl-2-cyclohexene-1,4-dione is carried out in the presence of an acylating agent, trimethylhydroquinone diesters are obtained which lead to trimethylhydroquinone by subsequent hydrolysis.
According to Bull. Korean. Chem. Soc. 1991, 12, 253, for example, the rearrangement is performed in a 5% solution in acetic anhydride by adding five equivalents of concentrated sulfuric acid. However, trimethylhydroquinone diester is only obtained in a 30% yield in this process.
In another process according to DE-OS 2 149 159, 2,6,6-trimethyl-2-cyclohexene-1,4-dione can be converted in the presence of acetic anhydride in a rearrangement catalyzed by protonic or Lewis acids to trimethylhydroquinone diacetate which is then saponified to trimethylhydroquinone.
Although by this method yields and conversions of ketoisophorone are is moderate to good (maximum 66% TMHQ yield, based on ketoisophorone used), large quantities of strong acids (up to 150 mole % based on ketoisophorone) and large excesses of acetic anhydride (5-10 moles Ac
2
O/1 mole ketoisophorone) are used, which makes the process unattractive from an industrial point of view.
According to a more recent process (DE-OS 196 27 977), ketoisophorone is converted to the diester in the presence of only a double stoichiometric acetic anhydride equivalent with homogeneously dissolved super acids (H
0
<−11.9) as catalysts in the liquid phase. Particularly high selectivities are achieved with trifluoromethanesulfonic acid, chlorosulfonic acid and oleum of various SO
3
concentrations. A disadvantage of this process is the use of the above catalysts, the corrosive nature of which causes considerable material problems. The use of trifluoromethanesulfonic acid as catalyst is expensive and difficult, as this acid is complicated to handle and the reagent can only be partly recycled.
SUMMARY OF THE INVENTION
An object of the invention is to provide an improved process for the production of 2,6,6-trimethyl-2-cyclohexene-1,4-dione diesters, which, in particular, proceeds using an easily handled, economical catalyst. The corresponding hydroquinones can optionally be obtained from the esters by hydrolysis.
The invention provides a process for the production of trimethylhydroquinone diesters,
wherein R, R
1
are the same or different, by reacting 2,6,6-trimethyl-2-cyclohexene-1,4-dione(ketoisophorone or KIP)
with an acylating agent in the presence of catalytic quantities of a protonic acid, which is characterized in that orthoboric acid and/or boron oxide on the one hand and one or more carboxylic acid(s), selected from the group of hydroxycarboxylic acids, di- or tricarboxylic acids, which optionally also contain hydroxy groups, on the other hand, are used.
This combined catalyst system is extraordinarily economical and is also easy to handle.
At the same time, yields and selectivities can be regarded as equivalent to those known from the prior art.
The activity of the catalyst system is based on a catalyst species formed in situ from the boron-containing compound and the carboxylic acids, the pK
S
value of which is lower than the pK
S
value of boric acid.
This catalyst combination is preferably used in a quantity of 0.1 to 10 mole %, based on the ketoisophorone used. It is present in the reaction mixture in dissolved form.
Many different boron compounds can be used as the boric acid derivative, especially boric acid triesters, boron oxides and boric acid, boric acid being used as the particularly preferred catalyst. Various oligofunctional compounds which react with boric acid derivatives, increasing the co-ordination sphere of boron, to form stable, complex boric acids, the acidic strength of which is stronger than that of the corresponding free boric acid, can be used as co-catalyst.
The ratio of boron component to co-catalyst can be varied within ranges between 1:1 and 1:10 (molar ratio), a ratio of 1:2 being particularly preferred in the case of bifunctional co-catalysts. The active catalyst species is formed in situ by reaction of the binary catalyst system of boric acid derivative and the co-catalyst in the presence of the acylating agent.
In particular, hydroxy acids of the general formula
R
2
—CO
2
H (I),
in which:
R
2
represents aryl, especially phenylene, naphthyl, each substituted by OH, HO—(CH
2
)
q
—, CH
3
(CHOH)
n
(CH
2
)
m
—, where
m is an integer from 0 to 20, preferably 0 to 8, and
n: an integer from 1 to 5, especially 1 to 4,
q: an integer from 1 to 6
are designated as co-catalysts.
The particularly suitable hydroxycarboxylic acids include glycolic acid, lactic acid, mandelic acid, tartaric acid (regardless of the configuration), citric acid, especially salicylic acid or acetylsalicylic acid, but also hydroxyl group-containing amino acids such as serine or threonine and aldonic acid.
Dicarboxylic acids of the general formula
HO
2
C—R
3
—CO
2
H (II),
in which:
R
3
represents aryl, especially phenylene, naphthyl, (CH
2
)
m
, wherein
m
has the same meaning as above, or (CH
2
)
m
(CHX)
r
, wherein r represents an integer from 1 to 5, and X is OH,H or (CH
2
)
P
—(CX)(COOH)—(CH
2
)
P
with
P
=1 to 3 or alkenyl having C
2
to C
6
,
are also preferably used.
Oxalic acid, malonic acid, malic acid, succinic acid, glutaric acid, adipic acid, pimelic acid, suberic acid, azelaic acid, sebacic acid, especially oxalic acid, and aromatic dicarboxylic acids such as phthalic acid, isophthalic acid and terephthalic acid and 2,6-naphthalene-carboxylic acid or tricarboxylic acids such as trimesic acid or citric acid, and unsaturated dicarboxylic acids such as fumaric acid and maleic acid, but also polyhydroxydicarboxylic acids, are particularly suitable.
As acylating agent, compounds of the general formula:
are preferably used, in which:
R, R
1
, are the same or different and represent an optionally substituted, aliphatic, alicyclic C
1
to C
20
group, especially an aliphatic C
2
to C
4
group, or an aryl group, preferably phenylene.
The anhydride of acetic acid is particularly suitable.
Other suitable anhydrides are those of propionic acid, butyric acid, isobutyric acid, cyclohexane-carboxylic acid or benzoic acid.
The anhydrides of chloroacetic acid, trihaloacetic acid or trifluoromethansulfonic acid can also be used, even if they are not preferred.
The ratio between ketoisophorone and acylating agent can be varied within broad ranges, but a KIP/acylating agent ratio of 1:2 to 1:3 is particularly preferred. Other acylating reagents such as carboxylic acid halides, es
Huthmacher Klaus
Krill Steffen
Degussa-Huls AG
Killos Paul J.
Pillsbury & Winthrop LLP
Reyes Hector M
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