Process for the preparation of unsaturated ketones

Organic compounds -- part of the class 532-570 series – Organic compounds – Oxygen containing

Reexamination Certificate

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C568S361000, C568S405000, C568S409000, C568S415000

Reexamination Certificate

active

06586635

ABSTRACT:

BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to an improved process for the preparation of &bgr;,&ggr;,&dgr;-allenic and/or &agr;,&bgr;,&ggr;,&dgr;-conjugated di-unsaturated ketones by the reaction of propargyl alcohols with enol ethers in the presence of an acid catalyst at elevated temperature.
2. Discussion of the Background
A range of &bgr;,&ggr;,&dgr;- and &agr;,&bgr;,&ggr;,&dgr;-unsaturated ketones constitute valuable intermediate products for the preparation of vitamins E, A, K
1
and carotinoids.
Reaction of an unsaturated alcohol and an enol ether was described for the first time by Marbet and Saucy in Chimia 14 (1960), pages 362 to 363. Methyl or ethyl is isopropenyl ether, which have boiling points of 34° C. and 61° C. respectively, are often utilized in the Saucy-Marbet reaction. The reaction temperature of the Saucy-Marbet reaction is, however, higher than the boiling points of the ethers. In order to reach the reaction temperature necessary for achieving high conversions and adequate space-time yields, the reaction is carried out either in the presence of a solvent or in solvent-free manner under pressure.
DE 1 230 783 describes a process for the preparation of polyene ketones and their isomerization products from secondary alcohols in the presence of acid catalysts such as, for example, sulfuric or phosphoric acid.
U.S. Pat. No. 3,029,287 and the publication by R. Marbet and G. Saucy, Helv. Chim. Acta (1967) 50, 1158-1167 describe a process for the preparation of &bgr;,&ggr;,&dgr;-unsaturated ketones by the reaction of propargyl alcohols with enol ethers in the presence of an acid catalyst. The reaction times required in order to achieve complete conversion of the tertiary propargyl alcohol are, however, in excess of 15 hours according to this publication. These long reaction times necessitate high reaction volumes when the process is translated to the industrial scale, hence giving rise to high capital costs.
The reaction of dehydrolinalool with isopropenyl methyl ether catalyzed by p-toluenesulfonic acid to obtain a mixture of 6,10-dimethyl-4,5,9-undecatrien-2-one and pseudoionone isomers is disclosed in CS 235228. The reaction times required in order to achieve complete conversion of the dehydrolinalool are 17 hours at 100° C. The long reaction times are disadvantageous in this process.
It was described in DE 199 49 796.6 that the Saucy-Marbet reaction is catalyzed efficiently by aliphatic sulfonic acids or sulfonic acid salts, with markedly shortened reaction times in comparison to prior art processes. The reaction times are from 6 to 8 hours. In accordance with this process the reaction is carried out in the presence of a suitable solvent so that the necessary reaction temperature can be reached. However, yields decrease when working under pressure in the absence of the solvent. Carrying it out the process in the presence of a solvent moreover gives rise to an increased plant cost for isolating and working up the product.
SUMMARY OF THE INVENTION
Accordingly, an object of the invention is to improve the reaction between an unsaturated alcohol and an enol ether in a Saucy-Marbet reaction to obtain unsaturated ketones so as to enable the reaction to be carried out in highly selective manner and with markedly reduced reaction times. A further object of the invention is the achievement of the aforementioned aims without the need to work with additional reaction solvents.
DETAILED DESCRIPTION OF THE INVENTION
The invention provides a process for the preparation of &bgr;,&ggr;,&dgr;-unsaturated ketones and/or &agr;,&bgr;,&ggr;,&dgr;-unsaturated ketones by the reaction of an unsaturated alcohol with an enol ether or mixture of enol ethers, with formation of ketals as a by-product, at temperatures of from 50° C. to 200° C., in the presence of an acid catalyst.
The process according to the invention is characterized in that one or all of the reagents is/are heated to reaction temperatures of from 50° C. to 200° C. before the acid catalyst is added.
One aspect of the invention is a process for the preparation of &bgr;, &ggr;, &dgr; unsaturated ketones corresponding to the general Formula (IA) and/or &agr;, &bgr;, &ggr;, &dgr;-unsaturated ketones corresponding to the general Formula (IB)
in which
R
1
and R
2
are hydrogen, a C
1
-C
20
alkyl radical which is optionally substituted with oxygen-containing groups and may be saturated or unsaturated, branched or unbranched, or a C
1
-C
20
alkylaryl radical, whereby the radicals R
1
and R
2
may also together form a 5- or 6-membered ring;
R
3
and R
5
are hydrogen or a C
1
to C
4
-alkyl radical, preferably hydrogen, and
R
4
is a hydrogen or a C
1
to C
4
-alkyl radical;
or mixture thereof,
by the reaction of an unsaturated alcohol corresponding to the general Formula II
in which
R
1
, R
2
and R
3
denote the same as indicated above, with an enol ether corresponding to the general Formula III
in which
R
4
is hydrogen or a C
1
- to C
4
-alkyl radical, preferably a methyl radical;
R
5
denotes the same as indicated above, and
R
6
is a C
1
- to C
4
-alkyl radical, preferably a methyl radical;
with formation, as a by-product, of ketals corresponding to the Formula IV in which R
4
, R
5
and R
6
denote the same as indicated above
 at temperatures of from 50° C. to 200° C., in the presence of an acid catalyst.
The process according to the invention may, for example, be carried out in the following variants:
A. an unsaturated alcohol corresponding to the Formula II is introduced into a pressure vessel as an initial charge, and heated in the absence of the acid catalyst to a temperature of between 50° C. and 200° C., preferably between 60° C. and 170° C., particularly preferably between 80° C. and 130° C. When the desired reaction temperature is reached, with the pressure having risen in the vessel, an enol ether corresponding to the Formula III or a mixture of enol ethers corresponding to the Formula III, an acid catalyst, are dispensed-in, in mixed or separate manner, in continuous manner or portion-wise; or
B. an unsaturated alcohol corresponding to the Formula II as a mixture with an enol ether corresponding to the Formula III or a mixture of enol ethers corresponding to the Formula III is introduced into a pressure vessel as an initial charge, and heated in the absence of the acid catalyst to a temperature of between 50° C. and 200° C., preferably between 60° C. and 170° C., particularly preferably between 80° C. and 130° C. When the desired reaction temperature is reached, with the pressure having risen in the vessel, the acid catalyst is then dispensed-in in a continuous manner or portion-wise; or
C. the enol ether corresponding to the Formula III or a mixture of enol ethers corresponding to the Formula III is introduced into a pressure vessel as an initial charge, and heated in the absence of the acid catalyst and the unsaturated alcohol to a temperature of between 50° C. and 200° C., preferably between 60° C. and 170° C., particularly preferably between 80° C. and 130° C. When the desired reaction temperature is reached, and the pressure within the vessel has increased, an acid catalyst and an unsaturated alcohol corresponding to the Formula II, are then added, in mixed or separate manner, in continuous manner or portion-wise,
In each of A, B and C described above, it is possible to introduce as an initial charge, and then to heat to a temperature of between 50° C. and 200° C., a portion of the reagent or reagents in the absence of the acid catalyst, and then to add thereto the remainder of the reagent or reagents and the acid catalyst in continuous manner or portion-wise.
In a farther aspect of the invention, a liquid base or a basic solution which is able to form a salt which has acid properties “in situ” with the acid catalyst, may be added into the initial reaction mixture, in addition to the dispensing-in portion-wise or in continuous manner of the acid catalyst, at the necessary reaction temperature.
When the reaction is carried out under the conditions accor

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