Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-05-16
2002-11-19
Trinh, Ba K. (Department: 1625)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C549S546000
Reexamination Certificate
active
06482964
ABSTRACT:
INTRODUCTION AND BACKGROUND
The present invention relates to a process for the preparation of &bgr;-isophorone epoxide (&bgr;-IPO, 1,5,5-trimethyl-7-oxa-bicyclo-[4,1,0]-heptan-3-one) by epoxidation of &bgr;-isophorone (&bgr;-IP, 3,5,5-trimethylcyclohex-3-en-1-one), wherein there is used as the oxidizing agent an organic per-acid in the form of its solution in an inert organic solvent.
The &bgr;-isophorone epoxide obtained in that process can be converted directly to hydroxyisophorone (HIP) by isomerization in the presence of suitable catalysts. 3,5,5-Trimethyl-4-hydroxy-cyclohex-2-en-1-one (HIP) is described in the literature as an aromatic substance and a fragrance (JP-OS 81 35 990; CH-PS 549 961; DE-OS 22 02 066). Its use as a flavouring auxiliary for foodstuffs is also known (CH-PS 549 956; M. Ishikara et al., J. Org. Chem. 1986, 51, 491 ff). Hydroxyisophorone is also a widely usable synthesis component for natural substances and pharmaceuticals (N.S. Zarghami et al., Phytochemistry 1971, 10, 2755 ff; J.N. Marx and F. Sondheimer, Tetrahedron Lett., Suppl. No. 8, Pt 1, 1-7, 1966).
In particular, &bgr;-IPO is an important intermediate for the synthesis of 2,6,6-trimethylcyclohexane-1,4-dione and hence for vitamin E. The synthesis sequence that is conventionally followed proceeds according to the following scheme:
The known processes for the preparation of &bgr;-IPO produce only unsatisfactory yields. It has been found that the oxidation of &bgr;-isophorone usually proceeds to 4-oxo-isophorone, hydroxyisophorone being formed in concentrations of from 1 to 50% depending on the oxidizing agent used. According to the described processes, the formation of hydroxyisophorone appears to be a secondary reaction. When the progress of the reaction is monitored, it is found that hydroxyisophorone is not the intermediate of 4-oxo-isophorone, since hydroxyisophorone is virtually inert under the oxidizing conditions.
The epoxidation of &bgr;-isophorone goes back to Isler et al. (Helv. Chim. Acta 39, 1956, 2041 ff), who carries out the epoxidation with peracetic acid as the oxidizing agent in acetic acid as the solvent and, after adjusting the pH value to from 8 to 9 using aqueous sodium hydroxide solution, isolates only HIP in unsatisfactory yields. Nor do Zarghami et al. (Phytochemistry 10, 1971, 2755 ff) disclose any yields of &bgr;-IP epoxide in their reaction with peracetic acid. A further description of the epoxidation of &bgr;-isophorone is to be found in Tetrahedron Lett. Suppl. No. 8, Pt. 1, 1966, 1-7. There are described organic solvents such as chloroform with the use of meta-chlorobenzoic acid as the oxidizing agent, m-chlorobenzoic acid precipitating from the solution after completion of the redox reaction and a product pattern being obtained that is composed of &bgr;-IP epoxide and HIP in a ratio of 1:1, and alpha-isophorone. It is evident that, according to that process, neither the undesired back-isomerization to alpha-IP nor the consecutive reaction to HIP can be suppressed. After hydrolysis at basic pH, 87% HIP are isolated.
A common feature of all those processes is that &bgr;-isophorone epoxide is obtained in unsatisfactory yields, which can be attributed to the fact that the reaction is carried out non-selectively, or to unsuitable oxidizing agents, or to the presence of water in the reaction medium, which both catalyses the back reaction of &bgr;-isophorone and destabilises the epoxide. From the &bgr;-IP epoxide, the diol that forms can also be demonstrated by addition of water.
A further reaction that is observed when there is inadequate monitoring of the reaction is the epoxidation of alpha-IP (which is formed in situ from &bgr;-IP by isomerization) to alpha-IP epoxide, and the consecutive reaction thereof, with isomerization, to 2-hydroxy-isophorone. Those basic secondary reactions are also observed in the case of epoxidation with other substrates, wherein diols and hydroxy esters in particular are obtained (see W. M. Weigert, Wasserstoffperoxid und seine Derivate, Hythig Verlag Heidelberg 1978, page 79 ff).
The possible secondary and consecutive reactions in the case of &bgr;-IP epoxidation are shown diagrammatically in the following scheme:
The epoxidation of &bgr;-isophorone is also described in the presence of anhydrous peroxidation reagents such as alkyl hydroperoxides (Hutter, Baiker et al., Journal Mol. Cat. 172, 427-435, 1997). A heterogeneous SiO
2
—TiO
2
mixed oxide contact mass activates the peroxide, wherein, in order to achieve high selectivities, inter alia in order to suppress the formation of HIP, expensive pretreatment of the catalyst is necessary or, alternatively, additional auxiliary substances such as bases must be added. Although the best epoxide selectivities hitherto have been achieved by that process, the use of alkyl hydroperoxides, which are consumed stoichiometrically, for carrying out an industrial process is disadvantageous. Furthermore, it is not desirable to use a heterogeneous contact mass which must be prepared in an expensive manner.
DP 38 06 835 describes the oxidation of &bgr;-IP by reaction with aqueous hydrogen peroxide in the presence of formic acid to form HIP. &bgr;-IP epoxide is obtained as an intermediate in that process, but a rate of back-isomerization of the order of from 20 to 35% makes the process less attractive from an industrial point of view.
No process has hitherto been known that permits the preparation of &bgr;-IP epoxide using inexpensive oxidizing agents that are obtainable efficiently industrially, and with a high product selectivity. The objects to be achieved by the invention are derived therefrom.
An object of the present invention is to prepare &bgr;-isophorone with high selectivity and in a high yield starting from &bgr;-isophorone, wherein, especially, the back-isomerization of the starting material to alpha-isophorone is to be suppressed, in order to prevent alpha-IP having to be separated from the product solution in an expensive manner, the consecutive reaction to the diol in the presence of water is to be suppressed, and industrially inexpensive oxidizing agents, especially hydrogen peroxide or a per-acid, are to be used as the epoxidizing agent.
A further object of the invention is to find a process for the conversion of &bgr;-isophorone, wherein the per-acid is prepared in a preliminary step by the reaction between the corresponding organic carboxylic acid, water-containing hydrogen peroxide and sulfuric acid, and, by means of suitable process-related measures, in preparing the resulting per-acid solution so that it is suitable for the selective epoxidation of &bgr;-isophorone.
SUMMARY OF THE INVENTION
The above and other objects of the invention can be achieved by bringing &bgr;-isophorone into contact, at moderate temperatures, with an anhydrous organic per-acid dissolved in an organic solvent, the organic solvent at the same time also being the extracting agent for the extraction of the organic per-acid during its preparation. According to the understanding of the person skilled in the art, the percarboxylic acid designated anhydrous may generally still contain up to 5 wt. %, especially from 0.01 to 5 wt. %, water.
According to the process it is possible to work with inexpensive raw materials such as aqueous hydrogen peroxide on the one hand and organic carboxylic acid and a solvent on the other hand, only the starting material substrate &bgr;-isophorone and hydrogen peroxide being consumed in the epoxidation process and it being possible to recirculate most of the other raw materials.
A further aspect of the process according to the invention relates to the safe handling of the substances used or the peroxide mixtures formed in situ, especially the per-acid dissolved in the solvent together with hydrogen peroxide. According to the prior art (DP 38 06 835), high temperatures of about 60° C. must be ensured for the reaction in order to achieve at least adequate reaction velocities, which is harmful in terms of safety when working with performic acid. Furthermore, in that process hy
Huthmacher Klaus
Krill Steffen
Möller Alexander
Degussa - AG
Smith , Gambrell & Russell, LLP
Trinh Ba K.
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