WO2000002890A1

WO2000002890A1 - Hydroformylation process

Info

Publication number: WO2000002890A1
Application number: PCT/FI1999/000600
Authority: WO
Inventors: Riitta Laitinen; Jouni Pursiainen; Pekka Knuuttila; Sirpa JÄÄSKELÄINEN; Ari Koskinen; Outi Krause; Tapani Pakkanen; Heidi Reinius; Pekka Suomalainen
Original assignee: Neste Chemicals Oy
Priority date: 1998-07-08
Filing date: 1999-07-06
Publication date: 2000-01-20
Also published as: DE19983354T1; DE19964298C2; AU5041099A; DE19983354C2

Abstract

The present invention concerns a process for preparing substituted arylhalophosphines and derivatives thereof. According to the invention a substituted haloaryl is lithiated to form a substituted lithiumaryl which is subjected to metal exchange to provide a metal exchanged organometal compound. After reaction with a halophosphine compound a substituted aryl halophosphine is obtained. The present invention also provides a novel process for hydroformylation of olefinic compounds. The hydroformylation is carried out in the presence of a catalyst system based on a rhodium precursor and heterodonor ligands of the formula (I): YX1X2X3, wherein Y is phosphorus or arsenic and X1, X2 and X3 are each independently selected from aromatic groups comprising substituted phenyl and pyridyl groups, the substituents being hydrocarbyl groups attached to the aromatic ring at ortho-position via a heteroatom. With the various ligands of the present invention, i/n-ratios in range of 5 to 30 are obtainable. In the case of hydroformylation of methyl methacrylate, the selectivity of the methyl α-formylisobutyrate is 80 - 90 % and the amount of byproducts, such as methyl isobutyrate, is small.

Description

Hydroformylation process

The present invention relates to a hydroformylation process. In particular the invention concerns a process for hydroformylation of olefinic compounds in the presence of rhodium catalyst complexes. The invention also discloses new types of phosphine ligands and their metal complexes. Further, the present invention concerns the production of substituted arylhalophosphines, in particular ortho-anisyl and ortho-thioanisyl substituted arylchlorophosphines and derivatives thereof.

Hydroformylation is the general term applied to the reaction of an olefinic substrate with carbon monoxide and hydrogen to form aldehyde isomers with one more carbon atom than in the original olefinic reactant (Scheme 1).

CHO

_/^ CO/H₂

Scheme 1. Hydroformylation reaction

In Scheme 1 , R stands for a hydrocarbyl residue optionally containing functional groups, such as carboxy, hydroxy or ester groups.

If the olefin chain contains more than two carbon atoms, hydroformylation results in a mixture of linear and branched aldehydes, and a key issue in the hydroformylation reaction is how to control the ratio of normal to branched products. In case of linear olefins the normal product is usually the desired one, while in functional or asymmetric hydroformylation the end application determines the desired product form. Branched (iso-form) hydroformulation compounds of (meth)acrylic acid esters and similar olefinic compounds containing at least one other functional group are of particular interest as starting materials for fine chemicals, e.g., sterically hindered polyols and lactones, which contain no hydrogen in β-position. Generally, the reaction conditions and the specific catalyst-ligand combination used have a great effect on the chemical structure of the hydroformylation product and product distribution.

The ratio of branched compounds to linear compounds (i/n-ratio) can be influenced by the specific ligand used. In the late 70's, Tanaka et al. (Bull. Chem. Soc. Jpn., 50 (1979) 9, 2351-2357) studied the effect of shorter methylene-chained diphosphines in combination with Rh₂Cl₂(CO)₄ catalyst on product selectivity in hydroformylation of .β-unsaturated esters. The use of triphenylphosphine ligands suppressed the hydrogenation and increased the content of the -isomer, but the branched to normal ratio (i/n-ratio) still remained unsatisfactorily low.

Various regioselective hydroformylation processes have been suggested since Tanaka published his work. WO 93/14057 discloses a process wherein an olefin is reacted with carbon monoxide in the presence of a soluble catalyst comprising a rhodium complex and a bidentate phosphine ligand. Using unsaturated olefins as reactant olefins, branched aldehydic esters are produced in good yields and high selectivities. GB Patent Application 2 275 457 suggest using a catalyst system based on sources of rhodium cations and various alkylphosphino ligands for raising the selectivity and reaction rates of the desired alpha- formyl isomers of hydroformylation of methyl methacrylate.

In spite of prior efforts there still exists a need for further improving catalyst activity, regioselectivity and chemoselectivity.

Surprisingly it has now been found out that by using a catalyst system based on rhodium and specific stabilizing and coordinating heterodonor ligands, the selectivity of the reaction can easily be controlled. Thus, ligand design is the major part of developing hydroformylation catalysts at this moment. The only classes of ligands used in industrial hydroformylation processes are phosphines, triphenylphosphine oxide and in some special cases phosphites.

The number of commercially available alkyl- and arylchlorophosphines is, however, limited, which reflects difficulties in the preparation of these compounds. By this reason, the research into the preparation of new arylchlorophosphines is important in itself, and it is particularly important for the development of new catalyst systems which can be used in hydroformylation.

Aryldichlorophosphines have been prepared for over 100 years, mostly by using aluminium, stannic, ferric or titanium chloride catalysis. Thus, Michaelis described in 1896 the preparation of/?-anisyldichlorophosphine by an aluminiumtrichloride catalyzed Friedel- Crafts reaction. Modifications of this original method have been used in the preparation of aryldichlorophosphines in the majority of the reported works since then. This method typically leads to a mixture of ortho and para isomers of substituted aromatic chloro- phosphines, the para isomer being the main product. Deactivating, meta directing groups prevent the substitution.

Several other methods have also been devised for the preparation of dichlorophosphines. In For preparing aryldichlorophosphines containing large aromatic groups, such as anthracene, lithiation of the corresponding brominated reagent and subsequent use of an excess of PC1₃ has been recommended for the formation of dichlorophosphine. The use of chloro bis(diethylamino)phosphine as an intermediate and the transmetallation with ZnCl₂ of a Grignard reagent of an ortho or meta substituted aryl group which then is reacted with PC1₃ are examples of further methods which have been employed for producing substituted dichlorophosphines. However, these methods do not provide high selectivity for ortho substituted anisyl derivatives, nor are they generally applicable to any anisyl dichlorophosphine structures.

It is an aim of the present invention to eliminate the problems of the prior art and to provide a new route for preparing a large range of substituted arylhalophosphines which then easily can be converted to the desired tertiary phosphines.

It is a further aim of the present invention to provide a novel process for selectively preparing σrt/jo-substituted arylhalophosphines.

It is a third object of the invention for providing novel phosphine ligands.

It is a fourth object of the invention to provide a novel olefin hydroformylation process.

The present invention is based on the concept of transmetalling a lithiated aromatic starting compound before reacting it with a halophosphine. Surprisingly it has been found that the desired arylhalophosphines will then be formed with high selectivity. The transmetallation is preferably performed with a metal halide. The present process therefore comprises the steps of lithiating a suitable starting compound, such as ort/iø-bromothioanisole or ortho- bromoanisole, then changing the organolithium reagent of the starting compound into an organometal halide reagent which is then reacted with an appropriate halophosphine producing the desired product. In connection with the present invention it has been found that prior art methods discussed above cannot be used for preparing potentially interesting thioanisyl or aminoanisyl derivatives. The new process disclosed herein allows for the production of a large group of compounds, including novel compounds useful as starting reagents for tertiary phosphines.

More specifically, the process according to the present invention is characterized by what is stated in the characterizing part of claim 1.

The novel heterodonor ligands are characterized by what is stated in claims 20 and 21.

According to the present invention, olefm hydroformylation is carried out in the presence of a catalyst system based on a rhodium precursor and heterodonor ligands of the formula I

YX,X₂X₃, (I)

wherein

Y is phosphorus or arsenic, and

X,, X₂ and X₃ are each independently selected from aromatic residues substituted with one to four donor groups in ortho position.

heterodonor ligands containing a hetero atom group, such as an alkoxy, alkylthio or alkylamine group, in ortho position will provide high selectivity and a high i/n ratio for α,β-unsaturated esters

The hydroformylation process according to the invention is characterized by what is stated in the characterizing part of claim 22.

A great number of considerable advantages are obtained by the present invention. Thus, the selectivity of the method for preparing the substituted arylhalophosphines is good, it becomes possible to incorporate into the arylhalophosphine the very structure, e.g. the specific configuration (ortho), of the starting compound. The desired product can easily be separated from the reaction mixture e.g. by direct distillation.

The selectivity of the preparation process can be further improved by selecting a solvent which is inert and which does not form any side products in the reaction mixture. To mention an example, when the reaction is performed in diethylether e.g. 2-thioanisyl dichloro-phosphine, an interesting intermediate in the preparation of tertiary phosphine ligands, can be formed without significant side products. Said phosphine is obtained at high yield with no evidence of the formation of meta or para isomers, or tris(o-thiomethyl- phenyl)phosphine.

The present preparation process is generally applicable to a various arylhalophosphines.

The tailored ligands according to the present invention, comprising a hetero atom substituent in ortho-position of the aromatic ring, constitute a significant step towards controlled properties of hydroformylation catalysts. With the various ligands of the present invention, i/n-ratios in range of over 1, preferably over 1.5 and in particular 5 to 30 are obtainable. In the case of hydroformylation of methyl methacrylate, the selectivity of the methyl α-formylisobutyrate is 80 - 90 % and the amount of byproducts, such as methyl isobutyrate, is small. The ratio between the branched and linear chain aldehydes does not essentially change during the reaction.

Next the invention will be examined more closely with the aid of a detailed description and a number of working examples.

In the attached drawing

Figures 1 to 3 shows the structure of 82 preferred ligands;

Figure 4 is a simplified process scheme of a liquid circulation one-phase hydroformylation process for methyl methacrylate;

Figure 5 indicates the yield of aldehydes and by-products for three different phosphine ligands according to the invention;

Figure 6 is a graphical presentation of the selectivity vs. process pressure for some of the hydroformylated products; and

Figure 7 indicates the i/n ratio vs. time of products hydroformylated in the presence of catalyst containing various ligands.

As noted above, the present invention concerns a process for preparing substituted arylhalophosphines from the corresponding reactants comprising substituted haloaryl compound and halophosphines. The following description discloses in more detail the preparation of some specific ørtΛo-substituted compounds (ort zø-anisyl and ortho- thioanisyl substituted arylchloro-phosphines and derivatives thereof, such as tertiary phosphine ligands). However, it should be noted that the invention can also be applied to corresponding (and other) meta and para substituted aryl compounds.

The preferred ortho compounds comprise phenylchlorophosphines, in particular: o- thioanisyldichlorophosphine, o-thioanisylchlorophenylphosphine, o-anisyldichloro- phosphine and o-anisylchlorophenylphosphine. In connection with the present invention it has been found that these compounds can be prepared selectively and at high yield by using organolithium and zinc halide as reagents for preparing an organozinc halide reagent, which is then reacted with PC1₃. Importantly, the ørt/jo-thioanisyl or ørtΛo-anisyl group, which is of particular interest for the use of the corresponding tertiary phosphine ligand in catalysis, can maintained during the synthesis and thus incorporated into the end product from the starting reactant, the o-substituted haloaryl compound.

Scheme 2 shows the three basic steps of the synthesis using the preparation of o- thioanisyldichlorophosphine as an example.

(1)

Scheme 2. Schematic representation of the synthesis of o-thioanisyldichlorophosphine

The process comprises first providing an ortho-anisyl or ortho-thioanisyl substituted lithiumaryl by reacting the corresponding ortho-anisyl or ortho-thioanisyl substituted haloaryl with a lithium-containing reagent. The halosubstituent can be any of fluoro, chloro, bromo and iodo, bromo being particularly preferred. Useful lithium reagents include elemental lithium and organolithium compounds, such as n-butyllithium, isobutyl- lithium and phenyllithium. The first reaction steps is illustrated in the scheme by the reaction of o-bromothioanisole with n-butyllithium.

The reaction between the substituted haloaryl and the lithiating reagent is preferably carried out in a non-polar solvent, such as an aliphatic ether, e.g. diethyl ether. The reaction temperature is typically about - 10 to +50 °C, preferably about -5 to +20 °C, in particular about 0 °C, and the reaction time about 1 min to 24 hours, preferably about 10 min. to 5 hours. After the completion of the reaction, the substituted lithiumaryl obtained is subjected in situ, i.e. without prior separation from the reaction mixture, to metal exchange to provide an ørt/70-substituted organometal compound. The metal exchange can be carried out by adding the salt of a suitable metal, such as zinc, aluminium, iron or copper, into the reaction mixture containing the substituted lithiumaryl and contacting the reagents in the mixture under stirring. It is preferred to use metal halides, and zinc chloride is particularly preferred. Scheme 1 illustrates the transmetallation by showing the reaction of o-lithium thioanisole with zinc chloride. The reaction conditions of the metal exchange are roughly the same as for the lithiation: reaction temperature - 10 to +50 °C, preferably about -5 to +20 °C, and reaction time about 1 min to 24 hours, preferably about 10 min. to 5 hours.

The organometal halide thus obtained is then reacted with a chlorophosphine compound to produce the desired, e.g. ørt/zø-anisyl or ørt/rø-thioanisyl substituted, aryl chlorophosphine. The chlorophosphine reagent comprises e.g. trichlorophosphine or dichlorophenyl- phosphine. Scheme 2 shows the reaction between an organozinc chloride and trichlorophosphine, which gives ørt zo-thioanisyldichlorophenylphosphine (compound 1).

The reaction is conducted e.g. by feeding the reaction mixture containing the halide into a solution of the phosphine compound and contacting the reactants under stirring. During the addition of the organometal reagent, the temperature is kept at about - 10 to +20 °C. The actual reaction is, however, carried out under refluxing conditions at about 30 to 100 °C, depending on the reaction medium. When diethyl ether is used the reaction temperature is about 36 °C. The reaction time is about 1 to 100 hours.

The above reaction steps are preferably carried out at normal (i.e. atmospheric) pressure in an inert atmosphere and, on laboratory scale, e.g. in combination with standard Schlenk techniques. Any suitable inert gas such as nitrogen, argon, xenon, krypton and helium can be employed; argon is preferred.

After the reaction, the reaction mixture is cooled to room temperature and the solvent removed by distilling. The o-substituted chlorophosphine compound is then recovered and separated from the reaction mixture by fractional distillation at reduced pressure.

All the above reaction steps can be carried out in the same solvent. It is particularly preferred to carry out the reaction between the ørt 10-substituted organozinc halide and the chlorophosphine compound in a solvent which is essentially inert at the reaction conditions, i.e. which does not react with the reactant. Examples of such solvents are the above mentioned aliphatic ethers, such as dialkyl ethers, in particular diethyl eter. The refluxing of the aryllithium compound in THF with ZnCl₂ is to be avoided.

As mentioned above, by means of the present invention it is possible to prepare a large group of compounds, including both known and novel compounds. Of the novel compounds, the following can be mentioned: o-thioanisyldichlorophosphine, o- thioanisylchlorophenylphosphine, m-thioanisyldichlorophosphine and p-(dimethyl- aminoanisyl)-dichlorophosphine. The following known compounds can also be prepared: o-anisyldichlorophosphine, o-anisylchlorophenylphosphine, m-anisyldichlorophosphine, p- anisyldichlorophosphine and p-(dimethylaminoanisyl) dichlorophosphine.

The substituted arylchlorophosphines can be converted into their derivatives, in particular into tertiary phosphines. The reaction can be performed by lithiating (as described above) suitable aromatic reagents and reacting the lithiated aromatic reagents with the substituted arylchlorophosphines to form the desired phosphine ligands. In particular the aromatic components comprise halo aryl or halo pyridyl rings which can contain substituents in ortho-, meta- or αr -position relative to the halo atom. The substituents include alkoxy, alkylthio, alkylamine and alkylphosphoro groups. The aryl rings include phenyl and fused aryl rings, such as naphthyl and anthracyl.

The conversion of the present substituted arylchlorophosphines to tertiary phosphines is discussed in Example 4 with reference to the reaction of ort/zø-anisyl and ørt/zø-thioanisyl substituted arylchloro-phosphines with substituted lithiated phenyls, in which the aromatic residue comprises a thioanisyl, anisyl, naphthyl or anthracenyl group. Generally, the present heterodonor ligands can be synthetized from corresponding arylhalophosphines by methods known in the art for metallating alkoxy, alkylthio, alkylamine or alkylphosphoro substituted phenyl and/or pyridyl rings containing bromine in ortho, meta or para position with n-butyllithium, after which an appropriate halogenated phosphine is added. These reactions can be made in argon atmosphere.

The structures of 82 preferred, but no means limiting, examples of heterodonor ligands suitable for being converted into hydroformylation catalysts and which all can be prepared by the present invention are shown in the attached drawings (Figs. 1 -3). Of these specific embodiments, at least the following compounds are novel: compounds having the Formulas

8 to 36, 38, 40 to 45, 62, and 64 to 81. As discussed above, the hydroformylation process according to the present invention, and made possible by the provision of a large number of ligands, is based on using a catalyst system made from a source of rhodium and a source of ligands, the latter primarily comprising a trisubstituted phosphorus or arsenic atom. Generally, the substituents can be selected from aromatic groups substituted by alkoxy, alkylthio and alkylamine groups in which the alkyl groups are linear or branched and comprise 1 to 20, preferably about 1 to 6 carbon atoms.

According to a particularly preferred embodiment, the substituents are constituted by aromatic groups selected from substituted and unsubstituted phenyl and pyridyl groups, the substituents being hydrocarbyl groups attached to the aromatic ring in ortho position via a heteroatom, such as oxygen, nitrogen, sulphur or phosphorus. These kinds of ligands will also be called "heterodonor ligands" in the following, and the group containing a heteroatom is called a "donor group". The heteroatom or donor atom can also be located in the cyclic structure attached to phosphorus or arsenic atom. Thus, the structure of Formula

82, wherein there are two phenyl rings and one pyridyl ring attached to the phosphorus atom, is also included in the scope of the present ligands and is considered a heterodonor ligand.

The hydrocarbyl groups of the substituents may comprise aryl, aralkyl, or cyclic or branched or linear alkyl groups, the alkyl groups being particularly preferred. Lower alkyl groups, such as alkoxy, alkylthio, alkylamino and alkylphosphoro groups, wherein the alkyl residue is derived from methyl, ethyl, a propyl or a butyl group, are particularly interesting.

In principle, the substituents can be located in ortho-, meta- or para-position relative to the phosphorus atom of the phosphine group (or the corresponding arsenic atom). Particular benefits will, however, be achieved with substituents located in ortho-position, as will be explained below. As regards the various heteroatom substituents, it should be noticed that o-thio substituted ligands provide exceptionally high selectivity, typically 80 % or more towards the form, during hydroformylation of methyl methacrylate.

The ligands are used in the hydroformylation process either in a solution with metal precursors or as solutions of complexes made of the ligands and metal precursors. The other ligands in the complexes are for example halides, carbon monoxide, nitrogen trioxide. According to a preferred embodiment, the homogeneous catalysts used in the hydroformylation reaction according to the present invention are prepared by reacting a Rh compound with an organic ligand of the above-identified kind to form a reactive complex at suitable reaction conditions so that transesterification required by the activation of the catalyst takes place. The amount of ligand can vary substantially depending on the application, but molar ratio of ligand to rhodium is generally in the range of 0.5 to 1000, preferably 1 to 100. The ligand-to-rhodium ratio is crucial in controlling the selectivity of the reaction and, thus, the i/n ratio of the products.

The rhodium precursors used are either rhodium salts or metallorganic compounds, including halogenides, nitrates, carbonyl compounds, sulphates, acetates, dicarbonyl acetylacetonate, or rhodium complexes. Specific examples of suitable precursors are rhodium(III)nitrate, rhodium(I)acetate, rhodium dicarbonyl-acetylacetonate, dirhodium- tetracarbonyl dichloride, dodecacarbonyltetrarhodium, and hexadecacarbonylhexarhodium.

Although we do not wish to be bound by any specific theory, it would appear that the present ligands stabilize the catalyst complex and are therefore capable of tuning the activity and selectivity of the catalyst via electronic and steric mechanisms. Variation of the donor atoms and the substitution sites allows versatile modification of the complexes. One possible mechanism of the heterodonor ligands is the "arm-off mechanism, where partial dissociation of the catalyst generates a free coordination site for an incoming carbon monoxide or olefin molecule. The variation of the substitution in the phenyl groups allows the control of the ligand stereochemistry and gives an easy route to optically active ligands. Scheme 3 below indicates one possible mechanism:

X = Heteroatom (O, S, P, ..)

Scheme 3. The proposed arm-off mechanism of rhodium activation Ligands containing nitrogen donors may be used in both one and two phase processes. Their rhodium complexes have an amphiphilic property, which means that they are water soluble in acidic conditions. During the hydroformylation the system is homogeneous. After the catalytic reaction the catalyst can be extracted by water of a certain pH, when the separation of products and catalyst is easily carried out. The aqueuos phase containing the water-soluble catalyst is then neutralised and the catalyst is extracted into a fresh organic reaction mixture.

The olefinic compound used as a reactant may be any compound comprising an olefinic double bond between the alpha and beta carbon atoms. Thus, the olefinic reactant includes simple alpha-olefins and functionalized olefins. The reactant can be any aliphatic or cyclic compound, wherein there is another functional group, such as an ester, another double bond, acid anhydride, acid, phenyl, alcohol, epoxy etc. at the end of the carbon chain. The compound can be cyclic or fused or it may contain mono or fused cyclic parts.

The simple alpha-olefins are exemplified by ethylene, propylene, the butenes, the pentenes and the hexenes. Preferred functionalized aliphatic olefins comprise those functionalized with at least one ester group. Thus, there may be employed alkyl esters of unsaturated acids, such as acrylic acid, methacrylic acid, crotonic acid and allylic acid. Suitable examples are methyl acrylate, ethyl acrylate, sec-butyl acrylate, methyl methacrylate, alpha- methylene-gamma-butyrolactone, cis- or trans-ethyl crotonate and allyl acetate.

In particular, the substrates used according to the present invention in the hydroformylation reaction are simple longer chain olefins, e.g. 1 -hexene, or functional olefins, such as methyl methacrylate, or olefinic substrates leading to asymmetric hydroformylation products, e.g. styrene or cyclopentadiene. The field of application of the present invention is not, however, limited to these substrates.

Branched products (with a high iso/n-ratio) are obtained with the present catalyst using esters having a carbonyl group adjacent to the olefinic double bond. Ethyl acrylate, methyl methacrylate and ethyl crotonate are examples of such esters. The iso/n-ratio is generally above 1, in particular 1.3 or more, preferably in excess of 3 and suitably 5 to 30.

The structure of the reactant, the reaction conditions and the catalyst are selected so that the reaction is not directed to the other functional group of the compound but primarily only towards the alpha-double bond. The amount of rhodium in the catalyst system may vary, but the molar ratio of substrate to rhodium is generally between 500 to 30 000. Amounts between 2500 to 10 000 on the same basis are preferred.

The actual hydroformylation can, in principle, be carried out by methods known per se. Thus, the olefin is reacted with either a mixture of carbon monoxide and hydrogen or carbon monoxide alone or carbon monoxide and another reducing agent in the presence of the catalyst system, which is dissolved in the reaction medium. However, it should be pointed out that the influence of solvents on the rate of the hydroformylation reaction is significant. The overall rate measured for aldehyde formation is strongly dependent on the polarity of these solvents. Alcohols like methanol and ethanol increase the rate up tenfold compared with nonpolar solvents such as n-hexane or toluene. This suggests that cationic and anionic catalyst species may be responsible for this solvent effect. In addition, it has surprisingly been found that nitrogen containg solvents, such as acetonitrile or N- methylpyrrolidone, accelerate the reaction. Therefore, in an embodiment of the invention, the reaction is carried out in N-methylpyrrolidone or in acetonitrile.

According to the present invention, the hydroformylation reaction is carried out at remarkably mild conditions. Typically the temperature varies between 30 to 200 °C, preferably in the range of 50 to 130 °C. The total reaction pressure is between 1 to 150 bar, preferably between 40 to 100 bar. The hydrogen-to-carbon monoxide ratio can vary from 0.1 to 2.5, preferably 0.8 to 1.2

It has turned out that an increase of the reaction pressure, i.e. the molar ratio of gas being

CO:H₂ = 1:1, does not change the selectivity of the reaction.

Turning now to Figure 4, which represents a basic configuration of a methyl methacrylate hydroformylation process, it can be noted that the processing equipment comprises three sections, i.e. a hydroformylation reactor 1, a stripping section 2 and a product separation section 3. The reactor 1 typically comprises a reaction vessel provided with an agitator 4. The reactor depicted in the drawing can be operated batch-wise or semi batch-wise. Methyl methacrylate is fed into the mixing reactor 1 together with catalyst and solvents. The other reactants, viz. carbon monoxide and hydrogen are fed into the stripping column in gaseous form. The gases are absorbed into the solvent separated from the product phase and conducted to the reactor 1 together with the recycled solvent and unreacted methyl methacrylate. The separation of the products, the byproducts and the reactant methyl methacrylate is based on the differences in densities. Thus, the byproducts, such as isobutyric acid metyl ester, are separated in the stripping column as a side draw-off and recovered. The reactant is removed as the overhead product, whereas the aldehydes, being the heaviest component, are removed together with the catalyst phase as bottoms. The aldehyde mixture is fed into a distillation column operated at reduced pressure ("vacuum distillation column"). Catalyst is removed from the bottom of the fractionator/distillator, whereas the - and β-isomers are taken out as side draw-offs. The overhead product comprises light hydrocarbons and solvent fraction, such as toluene.

The following non-limiting examples illustrate the invention:

Example 1 o-Thioanisyldichlorophosphine

o-Bromothioanisole (3.0 ml, 5 g, 25 mmol) was lithiated in diethylether (40 ml) at 0 °C with n-butyllithium (10 ml, 2.5 M in hexane, 25 mmol). The reaction mixture was stirred for two hours at 0°C, after which an etheral solution (40 ml) of ZnCl₂ (3.3 g, 25 mmol) was added. Stirring was continued for two hours at room temperature to ensure the formation of the organozinc halide reagent. The organozinc halide was added to a solution of PC1₃ (6.6 ml, 75 mmol) in diethylether (30 ml) at 0°C. The reaction mixture was then refluxed for 40 hours, cooled to room temperature and the solvent was distilled at the normal pressure. The raw product was distilled under reduced pressure. The product (1.5 g, 6.6 mmol, 26.3 %) was obtained as a colorless liquid with the boiling point of 99-100°C / 0.1 torr.

Anal, calcd. for C₇H₇C1₂PS: C 37.4; H 3.1; S 14.2 %. Found: C 38.0; H 3.5; S 14.8 %. Η- NMR (400 MHz, CDC1₃) 2.5 ppm (s, H₇, 3H), 7.4-7.6 (m, H₄-H₆, 3H), 8.1 (d, ³J„.„ 8.0 Hz, H₃, 1H). ^,3C{Η}-NMR (100 MHz, CDC1₃) 20.5 (d, J_C._P 4.1 Hz, C₇, IC), 128.4 (s, C₅, IC), 130.4 (d, ³J_c.p 3.9 Hz, C₃, IC), 132.5 (s, C₄, IC), 132.9 (s, C₆, IC), 140.6 (d, 'J^ 38.2 Hz, C„ IC), 142.1 (d, ²J_C._P 52.6 Hz, C₂, IC). ³¹P{Η}-NMR (162 MHz, CDC1₃) 150.5 ppm (s).

Example 2 o-Thioanisylphenylchlorophosphine The title compound was prepared using the method of Example 1 with the exception that the organozinc halide reagent was not added to tri chlorophosphine but to an etheral (30 ml) solution of phenyldichlorophosphine (PphCl₂, 75 mmol) at 0 °C. After refluxing four 40 hours, the solvent was distilled from the slightly orange mixture. The product (5.4 g, 20.3 mmol, 81.3 %) was obtained as a colorless liquid with a boiling point of 51 to 52 °C at 0.1 torr.

Example 3 o-Anisyldichlorophosphine

o-Anisyldichlorophosphine was prepared using the method described in Example 1 with the difference that o-bromoanisole was used as a starting material. The refluxing time was 20 hours. The 2-anisyldichlorophosphine (3,9 g, 18.7 mmol, 37.4 %) was obtained as a colorless liquid with a boiling point of 86 to 89 °C at 0.1 torr.

Example 4

Syntheses of phosphine ligands

Eight different phosphine ligands were prepared as follows:

An organic reagent containing bromine group was lithiated with n-butyllithium in sodium- dried diethyl ether at 0 °C. The reaction mixture was stirred for 1 to 2 hours at 0 °C, after which 2-aryldichlorophosphine was added in diethyl ether. The mixture was stirred an additional 1 to 2 hours at 0 °C. The precipitation was filtered and dried in vacuum. The product was recrystallized from ethanol or a mixed ethanol-toluene solution.

In the above way, the following compounds were obtained:

(2-thiomethylphenyl)bis(9-anthracenyl)phosphine, yield 0.7 g, 1.3 mmol, 64.3 %.

Mp. 231-232 °C. (2-thiomethylphenyl)bis(l-naphthyl)phosphine, yield 0.2 g, 0.5 mmol, 53.4 %.

Mp. 204-205 °C.

(2-thiomethylphenyl)bis(4-thiomethylphenyl)phosphine, yield 0.2 g, 0.5 mmol, 40.4 %.

Mp. 113-115 °C.

(2-thiomethylphenyl)bis(2-methoxyphenyl)phosphine, yield 0.3 g, 0.8 mmol, 62.2 %. Mp. 180-182 °C.

(2-methoxyphenyl)bis(9-anthracenyl)phosphine, yield 0.2 g, 0.4 mmol, 17.1 %. Mp. 232-233 °C.

(2-methoxyphenyl)bis(l-naphthyl)phosphine, yield 0.3 g, 0.8 mmol, 32.3 %. Mp. 222-224 °C.

(2-methoxyphenyl)bis(4-thiomethylphenyl)phosphine, yield 0.4 g, 1.0 mmol, 71.6 %. Mp. 103-106 °C.

(2-methoxyphenyl)bis(2-thiomethylphenyl)phosphine, yield 0.4 g, 1.1 mmol, 47.0 %. Mp. 156-159 °C.

The prepared ligands are potentially multidentate. Experimental results show that the phosphine ligands containing 2-thiomethyl groups behave typically as bidentate ligands in metal complexes, independent of the number of substituent groups. Behaviour of 2- methoxyphenyl phosphine ligands depends on nature of the metal center of the complexes. With Cr, Mo, W, Rh and Ir centers 2-methoxyphenyl substituted ligands behave mainly as monodentate ligands. With molybdenum the coordination can also be fluxional. In this kind of hemilable complexes the phosphorus atom is strongly bound to a transition metal while the oxygen may be coordinatively labile. The oxygen can dissociate from the metal allowing the formation of a free coordination site, which may be important in homogeneous catalysis.

Example 5

Preparation of (p-Metoxyphenyl)di-3-pyridyl

The compound of Formula 65 in Figure 2, (p-metoxyphenyl)di-3-pyridyl, was prepared as follows: A solution of n-BuLi (10.0 ml, 25.0 mmol, 2.5M in hexane) in Et₂O (30 ml) was cooled to -80 °C using ethanol-liquid nitrogen bath. 3-BrC₅H₄N (2.5 ml, 25.0 mmol) in

Et₂O (30 ml) was added quickly. The yellow solution was stirred at -80 °C for one hour. A solution of p-anisyldichlorophosphine (2.6 g, 12.5 mmol) in Et₂O (30 ml) was added drop wise and the stirring was continued at -80 °C (1 h) before warming slowly to room temperature. The p-anisyldichlorophosphine was prepared as described by Davies and Mann, J Chem Soc 1944 p. 276. The brown mixture was extracted with H₂SO₄ (2 M) and the aqueous layer was made alkaline with NaOH. The oily raw product was extracted from the aqueous phase with diethylether and purified by column chromatography (silica gel, MeOH/CH₂Cl₂, 1 :1). The (p-metoxyphenyl)di-3 -pyridyl (1.4 g, 4.9 mmol, 39 %) was stored under argon. Example 6 Preparation of 3-PyPPh₂

The compound of formula 82 in Figure 3, 3-PyPPh₂, was prepared as follows: A solution of n-BuLi (6.0 ml, 15.0 mmol, 2.5M in hexane) in absolute Et₂O (40 ml) was cooled to 100

°C using ethanol-liquid nitrogen bath. 3-BrC₅H₄N (1.5 ml, 15.0 mmol) in Et₂O (30 ml) was added quickly. The yellow solution was stirred at 100 °C for one hour. The solution of PPh₂Cl (2.8 ml, 15.0 mmol) in Et₂O (30 ml) was added dropwise and the stirring was continued at 100 °C (1 h) before warming slowly to room temperature. The light yellow mixture was extracted with H₂SO₄ (2M) and the aqueous layer was made alkaline with

NaOH. The brownish oily raw product was extracted from the aqueous phase with tetrahydrofuran and purified by column chromatography (silica gel, 5 % MeOH in CH_jCLJ. The 3-pyridyldiphenylphosphine product obtained (2.48 g, 9.4 mmol, 63 %) was stored under argon, (synthesis modified as described in Inorg.Chem. 25,1986, 3926-3932 and J.C.S. Dalton 1980, 55-58).

³¹P{¹H}-NMR (162 MHz; CDCl₃): 11.2 ppm s.

Example 7

Rh(CO)(Cl)([o-(Methoxy)phenyl]diphenylphosphine)₂. 50 mg (0.1286 mol) of Rh₂(CO)₄Cl₂), 110 mg (0.3763 mmol) of [o-methoxyphenyl]diphenylphosphine) and 10 ml of toluene were fed into a Berghof s 100 ml autoclave. The autoclave was pressurized to 20 bar of CO/H₂ and heated to 100 °C. After four hours of reaction the autoclave was rapidly cooled and brought to normal atmosphere. The yellow precipitate obtained was filtered, washed with toluene and dried under vacuo. Single crystals for crystallographic determination were obtained from n-pentane/dichloromethane. Elemental analysis for C₃₉H₃₄P₂O₃ClRh: calcd % C: 62.37; H: 4.56; found % C: 62.07; H: 4.54; IR: v(CO) (CH₂Cl₂) = 1974 cm-' (s)

Preparation of Rh(CO)Cl(3-PyPPh₂)₂ A yellow solution of Rh₂(CO)₄Cl₂ (0.40 g, 1.0 mol) in tetrahydrofuran (40 ml) was stirred for h and the ligand, 3-PyPPh, (1.07 g, 4.0 mmol), in tetrahydrofuran (5 ml) was added dropwise. The yellow solution was stirred V h at room temperature. Tetrahydrofuran was evaporated and the solid raw product washed with acetone. The product was filtered and dried in vacuo (0.93 g, 1.3 mmol, 65

%). Single crystals for crystallographic measurements were crystallized from methylenechloride.

3 lD P{f 1Η}-NMR (162 MHz; CDC1₃): 26.3 ppm d, J_Rh._P 117Hz

Example 8 p-O-o-SSP

The compound of formula 20 in Figure 1 was prepared as follows: o-bromothioanisole (1 g, 0.66 ml, 4.9 mmol) was lithiated with n-BuLi (1.96 ml 2.5M in hexane, 4.9 mmol) in sodium-dried diethylether (20 ml) at 0°C. The mixture was stirred for 1 hour at 0°C, p- anisyldichlorophosphine (0.51 g, 2.45 mmol) was added in 20 ml E^O, and the mixture formed was stirred additional 1 hour at 0°C. The precipitate was filtered off and the solvent was evaporated from the filtrate. The formed raw product was washed with hexane. The product was recrystallized for x-ray crystallographic analysis from hexane/chloroform mixture (or hexane/dichloromethane) .

³¹P{^!H}-NMR (162 MHz; CDC1₃): -27.7 ppm [s].

Example 9 Hydroformylation of 1-hexene

An autoclave was charged in nitrogen atmosphere with 1 ml 1-hexene, 0.259 mmol of Rh(NO₃)₃ or 0.155 mol Rh₂(CO)₄Cl₂, 0.0159 mmol of (o-methoxyphenyl)diphenyl- phosphine and 5 ml of solvent (toluene). The autoclave was pressurised with hydrogen and carbon monoxide (1 : 1) up to a total pressure of 20 bar. The autoclave was then heated to the reaction temperature 100 °C. After four hours the autoclave was rapidly cooled to room temperature and the pressure was realesed. The conversion and the selectivities of the obtained products are presented below in Table 1 :

Table 1. Conversion and selectivities of hydroformylation of 1-hexene

OP: [o-(Methoxy)phenyl] diphenylphosphine

Example 10 Hydroformylation of 1-hexene

In a similar manner as described in Example 9, [o-(Methylthio)phenyl]diphenylphosphine, [o-(N,N-dimethylamino)phenyl] diphenylphosphine and [o-(Methoxy)phenyl] diphenylphosphine were tested as ligands in situ with Rh(NO₃)₃. The results obtained are presented in Figure 5.

It will appear from Figure 5 that in the presence of a catalyst system according to the present invention hydroformylation of 1-hexene provides aldehydes at good selectivity and with a minimum of hydrogenation.

As described above, but at a higher pressure (40 bar), the first complex described in

Example 3 was tested. Reaction yielded a total aldehyde conversion of 60 %.

Example 11

Hydroformylation of methyl methacrylate

An autocalve was charged with 5 ml methylmethacrylate, 0.0064 mg Rh(NO)₃, 0.025 mg (o-thio-methylphenyl)diphenylphosphine and 20 ml solvent, toluene. The autoclave was flushed with nitrogen and then the autoclave was pressurised with nitrogen up to 80 bar. The pressure was released and the autoclave was heated to 100 °C. At 100 °C the autoclave was pressurised with hydrogen and carbon monoxide (1 : 1) up to 60 bar. After five hours a sample was taken of the reaction mixture. The conversion was 44 % and selectivity to the α-form was 85 %.

Example 12 Hydroformylation of methyl methacrylate

In a similar manner as described in Example 11, the effect of ligand (o-N,N-dimethyl- aminophenyl)diphenyl-phosphine was tested. The conversion was 65 % and selectivity toward α-form was 37 %. Example 13

Hydroformylation of methyl methacrylate

An autocalve was charged with 5 ml methylmethacrylate, 0.0064 mg Rh(NO)₃, 0.030 mg (o-thiomethyl)bis(o-methoxyphenyl) phosphine and 20 ml solvent, toluene. The autoclave was flushed with nitrogen and then the autoclave was pressurised with nitrogen up to 80 bar. The pressure was released and the autoclave was heated to 100 °C. At 100 °C the autoclave was pressurised with hydrogen and carbon monoxide (1 : 1) up to 60 bar. After one hour a sample was taken of the reaction mixture. The selectivity towards the α-form was 82 %.

Example 14

Hydroformylation of methyl methacrylate

An autocalve was charged with 5 ml methylmethacrylate, 0.0064 mg Rh(NO)₃, 0.032 mg

(o-thiomethyl)bis(p-thiomethylphenyl) phosphine and 20 ml solvent, toluene. The autoclave was flushed with nitrogen and then the autoclave was pressurised with nitrogen up to 80 bar. The pressure was released and the autoclave was heated to 100 °C. At 100 °C the autoclave was pressurised with hydrogen and carbon monoxide (1 :1) up to 60 bar. After one hour a sample was taken of the reaction mixture. The selectivity towards the α- form was 92 %.

Example 15

Hydroformylation of methyl methacrylate

The tests were performed in a similar manner and with the same ligand as described in the Example 11 , but changing the pressure from 20 to 80 bar. Figure 6 shows the effect of pressure.

As apparent from Figure 6, the selectivity increases when the pressure is raised from 20 to

80 bar, reaching about 90 %. Irrespective of the selectivity, the ratio of metyl-α-formyl- isobutyrate to metyl-β-formylisobutyrate is high.

In a similar manner as described in the previous examples, the effect of reaction time on the ratio of branch products to normal products (i/n ratio) was studied using ligands according to the present invention. The results are shown in Figure 7, which indicates that i/n ratios in the range of 10 to 30 can be obtained with the present catalysts containing heterodonor groups.

Example 16 Hydroformylation of cyclopentadiene

An autoclave was charged with 2.53 g dicyclopentadiene, 9.1 mg Rh(NO)₃, and 29.3 mg triphenylphosphine. The autoclave was flushed with nitrogen and then the autoclave was pressurised with nitrogen up to 25 bar. The pressure was released and the autoclave was heated to 100 °C. At 100 °C the autoclave was pressurised several times with hydrogen and carbon monoxide (1 : 1) up to 20 bar. After four hours a sample was taken of the reaction mixture. The conversion was 100 % and selectivity to monoformyl-DCPD was 84 %.

In another test run an autoclave was charged with 2.75 g dicyclopentadiene, 10.1 mg Rh(NO)₃, and 41.1 mg (o-methylphenyl)diphenylphosphine. The autoclave was flushed with nitrogen and then the autoclave was pressurised with nitrogen up to 25 bar. The pressure was released and the autoclave was heated to 91 - 97 °C. At 91 °C the autoclave was pressurised with hydrogen and carbon monoxide (1 :1) up to 20 bar. After four hours a sample was taken of the reaction mixture. A pressure drop of about 4 bar was noticed. The conversion was 23 % and selectivity to monoformyl-DCPD was 92 %.

Claims

Claims:

1. Process for preparing substituted arylhalophosphines and derivatives thereof, comprising the steps of - lithiating a substituted haloaryl to form a substituted lithiumaryl;

- subjecting the substituted lithiumaryl to metal exchange to provide a metal exchanged organometal compound;

- reacting the organometal compound with a halophosphine compound in a reaction mixture to produce a substituted aryl halophosphine; and optionally - recovering the substituted aryl halophosphine from the reaction mixture.

2. The process according to claim 1 for preparing ørt/20-anisyl and ørt/20-thioanisyl substituted arylchlorophosphines and derivatives thereof, comprising the steps of

- reacting an ørt/zø-anisyl or ort/zø-thioanisyl substituted bromoaryl with a lithium- containing reactant to form an organolithium;

- subjecting the organolithium to metal exchange by reacting it with a metal halide to provide an ortho substituted organometal halide;

- reacting the organometal halide with a chlorophosphine compound to produce a reaction mixture containing ørt 20-anisyl or ort/20-thioanisyl substituted aryl chlorophosphine; and optionally

- recovering the substituted aryl chlorophosphine from the reaction mixture.

3. The process according to claims 1 or 2, wherein the reaction between the organozinc halide and the chlorophosphine compound is carried out in a solvent which is inert under the reaction conditions.

4. The process according to claim 3, wherein the reaction is carried out in diethyl ether.

5. The process according to any of claims 1 to 4, wherein each reaction step of the process is carried out in the same solvent.

6. The process according to any of claims 1 to 5, wherein the substituted lithiumaryl is subjected to metal exchange at a temperature in the range of - 10 to +50 °C.

7. The process according to any of claims 1 to 6, wherein the reaction between the metal exchanged organometal compound and the halophosphine compound is carried out at reflux.

8. The process according to any of claims 1 to 7, wherein the substituted lithiumaryl is subjected to metal exchange without prior separation from the reaction medium.

9. The process according to any of claims 1 to 8, wherein the substituted haloaryl is lithiated with elemental lithium or with an organolithium compound, such as n- butyllithium.

10. The process according to any of claims 1 to 9, wherein the metal halide is reacted with the chlorophosphine compound by feeding the halide into a solution of the phosphine compound.

11. The process according to any of the preceding claims, wherein the metal halide is zinc chloride.

12. The process according to any of the preceding claims, wherein the process is carried out in inert atmosphere.

13. The process according to any of the preceding claims, wherein the reaction product is recovered and separated from the reaction mixture by fractional distillation at reduced pressure.

14. The process according to any of the preceding claims, which comprises using ortho- thioanisyl or ørt/20-anisyl bromophenyl as substituted haloaryl.

15. The process according to any of the preceding claims, wherein the chlorophosphine compound comprises trichlorophosphine or dichlorophenylphosphine.

16. The process according to any of the preceding claims, comprising preparing o- thioanisyldichlorophosphine, o-thioanisylchlorophenylphosphine, o- anisyldichlorophosphine or o-anisylchlorophenylphosphine.

17. The process according to any of the preceding claims, comprising reacting the ortho- anisyl or ortho-thioanisyl substituted arylchloro-phosphines with a lithiated aromatic group in order to form a phosphine ligand.

18. The process according to claim 17, wherein the substituted aromatic group is selected from aryl and pyridyl rings comprising at least one substituent selected from alkoxy, alkylthio, alkylamine and alkyphosphoro.

19. The process according to claim 18, comprising reacting the ortho-anisyl or ortho- thioanisyl substituted arylchloro-phosphines with a lithiated aromatic group, in which the aromatic residue comprises a thioanisyl, anisyl, naphthyl or anthracenyl group.

20. Compound selected from the group consisting of o-thioanisyldichlorophosphine, o- thioanisylchlorophenylphosphine, m-thioanisyldichlorophosphine and p-dimethylanisyl- dichlorophosphine.

21. Heterodonor ligands according to any of Formulas 8 to 36, 38, 40 - 45, 62, and 64 - 81.

22. A process for the hydroformylation of olefinic compounds in the presence of a catalyst system based on a rhodium precursor and heterodonor ligands of the formula I

YX]X₂X₃,

wherein

Y is phosphorus or arsenic, and

X,,X₂ and X₃ are each independently selected from aromatic groups comprising substituted phenyl and pyridyl groups, the substituents being hydrocarbyl groups attached to the aromatic ring at ortho-position via a heteroatom.

23. The process according to claim 22, wherein the heteroatoms are selected from the group of oxygen, nitrogen, sulphur and phosphorus, and the hydrocarbyl groups are selected from aryl, aralkyl, or cyclic or branched or linear alkyl groups, the alkyl groups being particularly preferred.

24. The process according to claim 23, wherein the donor groups are selected from alkoxy, alkylthio, alkylamino and alkylphosphino groups.

25. The process according to any of claim 22 to 24, wherein the donor group is capable of coordination with rhodium and of thus forming a chelate complex.

26. The process according to any of claims 22 to 25, wherein the phosphorous atom is capable of coordination with rhodium.

27. The process according to any of claims 22 to 26, wherein the ligand forms a complex with rhodium via the phosphorus atom and/or the hetero donor atom, the structure being capable of opening during the reaction, in the bond either beween phosphorus and rhodium or between the hetero donor atom and rhodium.

28. The process according to any of the preceding claims, wherein the ligand is a mono- dentate or bi-dentate ligand.

29. The process according to any of the preceding claims, wherein the ligand is present in an excess amount in relation to the stoichiometric amount, the ratio of Rh to ligand being 0.5 to 1000, preferably 1 to 100.

30. The process according to any of the preceding claims, wherein the hydroformylation reaction is carried out at a temperature in the range of 30 to 200 °C, preferably in the range of 50 to 130 °C, the total reaction pressure being between 1 to 150 bar, preferably between 40 to 100 bar and the hydrogen to carbon monoxide ratio being from 0.1 to 2.5, preferably 0.8 to 1.2.

31. The process according to any of the preceding claims, wherein the ligand is selected from the groups shown in Figures 1 - 3.

32. The process according to any of the preceding claims, wherein the olefinic compounds are selected from group consisting of C_2.16 olefins optionally containing at least one functional group.

33. The process according to claim 32, wherein the olefins are selected from ethylene, propylene, 1-hexene, styrene and cyclopentadiene.

34. The process according to claim 32, wherein the olefins are selected from esters having a carbonyl group adjacent to an olefinic double bond, such as methyl methacrylate, ethyl acrylate, and ethyl crotonate.

35. The process according to claim 34, wherein methyl methacrylate is hydroformylated in the presence of a catalyst system comprising a heterodonor ligands of formula I wherein at least one of X,,X₂ and X₃ comprises a hydrocarbyl groups attached to the aromatic ring at ortho-position via a sulphur atom.

36. The process according to claim 34 or claim 35, wherein the alpha-double bond of the olefins is primarily subjected to hydroformylation to yield a product containing iso- and normal-isomers of the hydroformylated compound at a ratio of iso-to-normal of at least 1, preferably 1.3 or more, in particular 5 to 30.