This application is a 371 of PCT/EP98/04319, which was filed on Jul. 11, 1998.
The present invention relates to processes for the preparation of oxo products by the hydroformylation of substrates having Cxe2x95x90C double bonds using unmodified rhodium catalysts in a reaction mixture essentially consisting of the substrates, the catalyst and carbon dioxide in a supercritical state (scCO2). In particular, the invention relates to such processes for the preparation of products which contain substantial proportions of branched i-oxo products. Further, the invention relates to such processes for the hydroformylation of substrates which do not correspond to the general formula CnH2n. The invention further relates to such processes in which the separation of product and catalyst is effected using the special solvent properties of scCO2.
The transition metal catalyzed reaction of substrates containing Cxe2x95x90C double bonds with a mixture of hydrogen (H2) and carbon monoxide (CO) is referred to as hydroformylation or oxo reaction; it is a technically important method for the preparation of aldehydes and alcohols (oxo products). More than 6 million tons per year of oxo products are produced by catalytic hydroformylation worldwide. These products are employed as plasticizers and modifiers for PVC and other polymers, in detergent production, and as fine chemicals and as intermediates for the production of agrochemicals, food additives and pharmaceuticals (C. D. Frohning, C. W. Kohlpaintner, in Applied Homogeneous Catalysis with Organometallic Compounds (editors: B. Cornils, W. A. Herrmann), VCH, Weinheim, 1996, Vol. 1, Section 2.1.1).
Depending on the reaction parameters, the catalysts and the substitution pattern at the Cxe2x95x90C double bond of the substrate, linear (normal, n-) or branched (iso, i-) oxo products are produced more or less selectively in the hydroformylation. Of the oxo products of simple short-chain olefins of general formula CnH2n (n=2, 3), it is mainly the n-products which are economically important. Of the long-chain olefins CnH2n (nxe2x89xa74), the branched i-oxo products are also economically important and are discussed, for example, as starting materials for the preparation of plasticizers in pure form or as mixtures with the n-oxo products. Above all, the i-oxo products are also particularly important for substrates with functionalized Cxe2x95x90C double bonds, i.e., substrates which do not correspond to the general formula CnH2n. In particular, reference may be made herein to the technical synthesis of vitamin A described in U.S. Pat. No. 3,840,589, DE 2 03 078 and U.S. Pat. No. 4,124,619, which involves the formation of an i-aldehyde by the hydroformylation of substrates comprising allyl ester moieties. The formation of branched products in the hydroformylation of vinyl aromatics (e.g., styrene) is discussed as a possible route to xcex1-aryl-carboxylic acids, which are employed, inter alia, as analgetics and antirheumatics (e.g., Ibuprofen(copyright), Naproxen(copyright), Suprofen(copyright)).
The catalysts for hydroformylation can be classified into so-called xe2x80x9cunmodifiedxe2x80x9d and xe2x80x9cmodifiedxe2x80x9d catalysts which are respectively preferred for particular processes or particular substrates according to the prior art (C. D. Frohning, C. W. Kohlpaintner, supra, p. 33ff). xe2x80x9cModifiedxe2x80x9d systems means catalysts in which the catalytically active metal component contains additional ligands, usually phosphorus compounds, in addition to H and CO for increasing the useful life and for controlling activity or selectivity. The term xe2x80x9cunmodified catalystsxe2x80x9d denotes all other metal compounds which are capable of forming catalytically active hydrido-carbonyl compounds under the reaction conditions. Technical importance has been achieved to date mainly by catalysts based on the metals cobalt (Co) and rhodium (Rh). The separation of the products and recovery of the catalysts is an important factor in the technical realization of hydroformylation reactions.
Supercritical (xe2x80x9cfluidxe2x80x9d) carbon dioxide (scCO2), i.e., compressed carbon dioxide at temperatures and pressures beyond the critical point (Tc=31.0xc2x0 C., pc=73.75 atm, dc=0.467 gxc2x7mlxe2x88x921) is employed as a reaction medium for hydroformylation in U.S. Pat. No. 5,198,589 and in German Application DE-A-197 02 025.9 (Jan. 23, 1997). Carbon dioxide in a supercritical state is an interesting solvent for performing catalytic reactions because it is toxicologically and ecologically safe, in contrast to conventional organic solvents. Further, scCO2 has the property of being completely miscible with many gaseous reaction partners within wide limits, whereby limitation of the reaction rate by diffusion processes, which frequently occurs in gas/liquid phase reactions, is totally avoided. Further, due to the solvent properties of scCO2 which vary as a function of pressure and temperature, separation of main or side products from the reaction mixture is possible in favorable cases when the external parameters are appropriately selected. A survey of catalytic reactions in scCO2 is found in Science 1995, 269, 1065.
In DE-A-197 02 025.9, modified rhodium catalysts are employed for the hydroformylation in scCO2, specially developed phosphorus compounds ensuring high solubility of the catalysts in scCO2. Thus, the stated advantageous properties of scCO2 can be fully utilized with modified rhodium catalysts, but the preparation of the phosphorus ligands is an additional cost factor in possible technical applications. In U.S. Pat. No. 5,198,589, unmodified cobalt catalysts are employed for the hydroformylation of simple olefins CnH2n in scCO2. As compared to conventional solvents, similar reaction rates are obtained with significantly higher selectivities in favor of the linear n-oxo products. This increase in selectivity in favor of the n-oxo products is attributed to the use of scCO2 as the reaction medium.
We have now found that unmodified rhodium catalysts can be efficiently used for hydroformylation in scCO2 to obtain, surprisingly, not only significantly higher reaction rates, but also significantly higher selectivities in favor of the branched i-oxo products than are obtained in conventional solvents.
Rhodium catalyzed hydroformylations in scCO2 are conveniently performed by charging the catalyst or catalyst precursor and the substrate into a high-pressure reactor and then pressurizing with H2 and CO, either as a mixture or successively, at room temperature up to the desired partial pressure. Then, the amount of CO2 required to reach the desired density of the reaction medium is filled into the reactor. Then, heating to the desired reaction temperature is performed with stirring. After said temperature has been reached, the stirrer can be turned off due to the fast diffusion within the homogeneous supercritical phase. After the desired reaction time, the pressure is released from the reactor, during which the products can be isolated from the supercritical phase using appropriate known methods (K. Zosel, Angew. Chem. 1978, 90, 748; M. A. McHugh, V. J. Krukonis, Supercritical Fluid Extraction: Principle and Practice, Butterworths, Stoneham, 1994). Due to the fact that the solubilities of the metal species and the products are clearly different, the catalysts can be easily separated from the products and recycled.
As catalysts or catalyst precursors for the formation of unmodified Rh systems in scCO2, salts, complexes or cluster compounds of rhodium in any oxidation state can be employed. Compounds 1-8 are preferred examples of such catalysts or catalyst precursors, without intending to limit the choice of the catalyst to the structures shown. Particularly preferred catalysts are complex compounds of rhodium, 4-8, containing carbonyl ligands (CO) or ligands which can be readily replaced by CO under the reaction conditions. The amount of catalyst can be freely selected within a broad range depending on the reaction conditions and the reactivity of the substrates. Typical amounts of catalysts, based on the amount of substrate employed, range from 0.001 to 10 mole percent, preferably from 0.01 to 1 mole percent, more preferably from 0.05 to 0.5 mole percent. 
R1-R5 are residues independently selected from hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, aryl, C1-C20 perfluoroalkyl, C1-C20 carboxylate, C1-C20 alkoxy, C2-C20 alkenyloxy, C2-C20 alkynyloxy, aryloxy, C2-C20 alkoxycarbonyl, C1-C20 alkylthio, arylthio, C1-C20 alkylsilyl, arylsilyl, C1-C20 alkyloxysilyl or aryloxysilyl, each of which may optionally be substituted with C1-C12 alkyl, C1-C12 perfluoroalkyl, halo, C1-C5 alkoxy, C1-C12 carboxylate, C2-C12 alkoxycarbonyl or aryl. Residues R1-R5 may be connected with one another in cyclic compounds.
L1-L4 are neutral ligands independently selected from the group consisting of CO, R1R2Cxe2x95x90CR3R4, R1Cxe2x89xa1CR2, NR1R2R3, wherein R1-R4 are as defined above. L1-L4 may be connected with one another in cyclic compounds.
X, Y are anions or ligands with one negative charge, independently selected from the group consisting of Rxe2x88x92, Fxe2x88x92, Clxe2x88x92, Brxe2x88x92, Ixe2x88x92, ROxe2x88x92, RCO2xe2x88x92, p-C6H4SO3xe2x88x92, PF6xe2x88x92, BF4xe2x88x92, BR4xe2x88x92, wherein R is defined as mentioned for R1-R5.
Possible substrates for the rhodium catalyzed hydroformylation in scCO2 are compounds containing at least one Cxe2x95x90C double bond which, on one hand, allow a hydroformylation reaction due to their substitution pattern, and on the other hand, are sufficiently soluble in scCO2 so that homogeneous solutions are obtained during the reaction. Preferred are substrates with a Cxe2x95x90C double bond as represented by general formula 9. Mixtures of such compounds may also be used as substrates. The amount of substrate employed is not critical as long as complete solubility in the supercritical medium is achieved. Based on the reactor volume, typical substrate quantities are 0.05-5 mol/l, preferably 0.1-2 mol/l. 
R6-R9 are residues independently selected from hydrogen, C1-C20 alkyl, C2-C20 alkenyl, C2-C20 alkynyl, aryl, C1-C20 perfluoroalkyl, C1-C20 carboxylate, C1-C20 alkoxy, C2-C20 alkenyloxy, C2-C20 alkynyloxy, aryloxy, C2-C20 alkoxycarbonyl, C1-C20 alkylthio, arylthio, C1-C20 alkylsilyl, arylsilyl, C1-C20 alkyloxysilyl, aryloxysilyl, C1-C20 alkylsilyloxy, C1-C20 alkyloxysilyloxy, C1-C20 alkylsulfonyl, C1-C20 alkylsulfinyl or halo, each of which may optionally be substituted with additional residues corresponding to the same definition as R6-R9. Residues R6-R9 may be connected with one another in cyclic compounds.
The partial pressure of H2 and CO can be widely varied. Typical pressures at room temperature are between 0.1 bar and 100 bar for each of H2 and CO, preferably between 1 bar and 30 bar. The influence of the H2 and CO partial pressure on the reaction rate and selectivity is largely identical with the trends found in conventional solvents (C. D. Frohning, C. W. Kohlpaintner, supra, p. 55ff). Much the same applies to the reaction temperature the lower limit of which is determined by the critical temperature of CO2 (Tc=31xc2x0 C.). Typical reaction temperatures for hydroformylation with unmodified rhodium catalysts in scCO2 are between 31xc2x0 C. and 150xc2x0 C., preferably between 35xc2x0 C. and 100xc2x0 C. When the H2/CO pressure and the reactor volume are given, the total pressure prevailing at the reaction temperature is determined by the amount of CO2. The minimum amount thereof is determined by the critical density of CO2 (dc=0,467 gxc2x7mlxe2x88x921), while the upper limit depends on the maximum admissible system test pressure of the reactors employed. For standard V2A high pressure reactors with inspection glasses, this results in a typical range for the amount of CO2 employed, based on the reactor volume, of from 0.46 gxc2x7mlxe2x88x921 to 0.90 gxc2x7mlxe2x88x921, preferably from 0.5 gxc2x7mlxe2x88x921 to 0.75 gxc2x7mlxe2x88x921.
Reactions according to the present invention may also be performed in the presence of one or more additives to provide, for example, an easier handling of the substrates or catalysts, or an improvement of the solvent properties of the reaction medium, or an increase of the reaction rate, or an improvement of the yield. Such additives may be independently selected, for example, from water, amines, perfluorinated compounds, organic solvents (e.g., dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichloroethene, benzene, toluene, xylene, cumene, hexane, cyclohexane, halobenzenes, tetrahydrofuran, tert-butyl methyl ether, diethyl ether, dimethoxyethane, dimethylformamide, ethyl acetoacetate, acetone, dimethyl carbonate, alcohols).
In order to ensure that the reaction will start only after the supercritical state is reached, it may be convenient, depending on the reactivity of the substrate, to supply the catalyst and the substrate in a spatially separated way. Thus, for example, either the substrate or the catalyst may be supplied to the reactor in a separate storage vessel open at the top. One component may also be supplied in a second pressure vessel which is connected with the reactor through a valve. It is also possible to supply the catalyst in glas ampoules which can be cracked under the reaction conditions. Another alternative is the continuous or discontinuous metering of a component by means of a pump system.
Example 1 describes the typical procedure adopted in the hydroformylation in scCO2 with unmodified rhodium catalysts and illustrates the increased reaction rate and the unexpected change of selectivity when scCO2 is used as compared to a conventional solvent. The Examples summarized in Table 1 describe the hydroformylation of some prototypical compounds in scCO2 under typical conditions, but are not intended to limit the scope, the application range or the advantages of the present invention in any way.