FIELD OF THE INVENTION

The present invention relates to a process for the direct production of aromatic olefins, starting with aryl chlorides.

The process is based on the reaction of aryl chlorides with olefins and a base in the presence of a catalyst system comprising a palladium complex with a biphosphine ligand.

BACKGROUND OF THE INVENTION

Palladium-catalyzed vinylation of aryl halides, also known as the "Heck reaction", is a known synthetic method for the production of aromatic olefins. Palladium catalyzed vinylation of aryl iodides and bromides has been described by T. Mizoroki, K. Mori and A. Ozaki, Bull Chem. Soc. Jpn. (1971) 4, 581 and by R.F. Heck and J.P. Nolley, Jr., J. Org. Chem. (1972) 37, 2320.

A serious limitation of the Heck reaction is that aryl chlorides are usually unreactive. Various efforts to directly vinylate aryl chlorides have resulted in low yields and low catalyst stability.

A. Spencer, J. Organometal. Chem. (1984) 270, 115, reported vinylation of aryl chlorides catalyzed by palladium acetate in the presence of triphenylphosphine. Moderate yields of a maximum of 51% were obtained only when electron- withdrawing substituents were present on the aromatic ring. Chlorobenzene itself was essentially unreactive, leading to a poor 4% yield. In addition, only activated olefins were reported to undergo this reaction and a low catalyst turnover (a maXpiraum of 51) was obtained because of catalyst decomposition to unreactive palladium metal.

J.B. Davidson et. al., J. Mol. Catal. (1984) 22, 349, described vinylation of chlorobenzene with styrene to form stilbene catalyzed by palladium acetate in the presence of triphenylphosphine and water. Once again, only a moderate yield (a maximum of 56%) was obtained and the catalyst decomposed to palladium metal, resulting in a low catalyst turnover (maximum 25 turnover) . Benzene and biphenyl also formed in this reaction as undesirable by-products.

European Patent No. 103544 discloses the reaction of chlorobenzenes with an olefin in the presence of a palladium catalyst, a base and an arsenic or phosphorous ligand. Yields up to 61% were obtained with substituted chlorobenzenes, but only 4% with unsubstituted chlorobenzene.

United States Patent No. 4,814,489 and J.J. Bozell et al.,J. Am. Chem. Soc. (1988) 110, 2655, disclose the halide exchange reaction of aryl chlorides with iodide or bromide ions in the presence of a nickel catalyst to obtain aryl iodides or bromides, which are then reacted in a second reaction with an olefin in the presence of a palladium catalyst. However, stoichiometric amounts of the bromide or iodide salts are required. Also, the need to perform two separate reactions - the nickel catalyzed halide exchange reaction followed by the palladium vinylation reaction complicates the process. In addition, this process is completely ineffective in the presence of nitro substituents and the only exemplified olefins are ethyl acrylate and acrylonitrile.

European Patent Application EP 406 848 describes a process of catalytic formylation of aryl chlorides to produce aromatic aldehydes in the presence of a palladium complex of the formula [RιR_*-P(CH2)»χPR3R.4].*2Pd, wherein n is 3 or 4 and Ra. to R ₄ are hydrogen, alkyl, cycloalkyl or aryl, at least one of them being alkyl or cycloalkyl. DESCRIPTION OF THE INVENTION It has now been found according to the present invention that vinylation of aryl chlorides by reacting same with an

olefin and a base in the presence of a catalyst system comprising a palladium compound and a chelating biphosphine ligand leads to the production of aromatic olefins in high yields. The invention thus relates to a process for the production of aromatic olefins of the formula

wherein Ar is a radical selected from the group consisting of unsubstituted carbocyclic and heterocyclic aryl and carbocyclic and heterocyclic aryl substituted by one or more radicals selected from the group consisting of alkyl, carbocyclic aryl or aralkyl, fluoro, chloro, cyano, nitro, OR.*, S-alkyl, COR-*, CO2R- _* and SO3R-*, wherein R ₄ is hydrogen, alkyl, carbocyclic aryl or aralkyl; and Rx,R ₂ ,R ₃ are the same or different and each represent hydrogen, alkyl, carbocyclic aryl or aralkyl, chloro, fluoro, cyano, nitro, ORs, COaRs, CORs and wherein R _s is hydrogen, alkyl, carbocyclic aryl or aralkyl, which comprises catalytic vinylation of an aryl chloride of the formula ArCl with an olefinic compound of the formula wherein Ar, Rx, Rz and R3 are as defined above, in the presence of a base and of a palladium complex catalyst of the formula:

[RβR-P(CH _a )»PRβR93*2 Pd wherein n is 3 or 4 and R _s to Rs are selected from hydrogen, alkyl, cycloalkyl, unsubstituted carbocyclic aryl or aralkyl and carbocyclic aryl or aralkyl substituted by alkyl, alkoxy or phenoxy.

The term "alkyl" as employed herein by itself or as part of another group includes both straight and branched chain radicals of up to 12 carbon atoms, preferably from 1 to 8 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl and isobutyl. The term "carbocyclic aryl" as employed herein

by itself or as part of another group includes monocyclic or bicyclic Cs-Cxo aryl groups, such as phenyl and naphthyl, preferably phenyl. The term "heterocyclic aryl" as employed herein includes 5-6 membered heteroaromatic ring radicals containing one or more 0, S or N atoms, such as furyl, thienyl and pyridyl. The term "cycloalkyl" as employed herein includes saturated cyclic hydrocarbon groups containing from 3 to 7 carbon atoms, preferably cyclohexyl.

The radical Ar is preferably phenyl optionally substituted by one or more radicals selected from the group consisting of alkyl, phenyl, fluoro, nitro, pyridyl, OR _* ,

C0R ₄ and C0aR ₄ , wherein R ₄ is hydrogen, alkyl or phenyl.

Rx and R**. are preferably hydrogen or alkyl and R3 is preferably hydrogen, alkyl, COaR _* , unsubstituted phenyl or phenyl substituted by alkyl or ORs, wherein Rs is hydrogen, alkyl or phenyl.

R ₃ to Rs are preferably alkyl, such as isopropyl, phenyl or cyclohexyl. The reaction takes place according to the following reaction scheme:

The base used in the reaction may be an organic or inorganic base that is soluble, at least partially, in the reaction mixture. Suitable bases are exemplified by, but not limited to, sodium acetate, potassium acetate, potassium propionate, sodium carbonate and calcium carbonate. The reaction is advantageously carried out in a solvent that is inert to the reactants and products, preferably a polar solvent, such as dimethylformamide (DMF), dioxane, dimethylacetamide, sulfolane and N-methylpyrrolidone. The temperature of the reaction is generally between about 100- 250°C, the optimum temperature being about 150°C. The palladium compound used for the preparation of the palladium complex catalyst is any palladium salt or complex,

such as palladium chloride, palladium acetate and palladium dibenzylideneacetone.

Among the biphosphine ligands of the type

RβR*7P(CH2) _n PR ₈ Rs, used to prepare the complex catalyst, the prefered compounds are:

(i-Pr) ₂ P(CHa) ₃ P(i-Pr)a(dippp) ; Cy ₂ P(CHa)*PPha;

(i-Pr)aP(CHa) ₄ P(i-Pr)a(dippb); CyaP(CH ₂ ) ₃ PCya;

PhaP(CHa) ₃ PPha(dppp); wherein i-Pr - isopropyl; Ph = phenyl; Cy = cyclohexyl. The molar ratio of the palladium compound to the biphosphine is in the range of 1:0.5 to 1:100 Pd to biphosphine, the optimum being about 1:2.

The palladium complex catalyst may be generated in situ under the catalytic reaction conditions from a palladium salt or complex and the biphosphine ligand. Alternatively, a palladium compound already containing the biphosphine ligand as part of its molecular structure may be utilized, in the presence or absence of additional biphosphine. Examples for suitable such complexes include Pd[(i-Pr)aP(CH ₂ ) ₄ P(i-Pr)a]a and

Pd[PhaP(CHa) ₃ PPha]a.

The complex Pd[PhaP(CHa) ₃ PPha]Cla is a precursor to the active catalyst and will be used in the presence of additional biphosphine.

The invention will now be illustrated by the following non-limiting examples.

Example 1. Preparation of trans-4-benzoylstilbene. A solution containing 23 mg of palladium acetate and 58 mg of dippb in 5 ml of DMF was stirred at room temperature under nitrogen for 1 hr. 2.17g of p-chlorobenzophenone were added, followed by 1.6g of sodium acetate and 1.3 g of styrene and the closed reaction vessel was heated under nitrogen and stirred at 150°C for 20 hrs. The reaction mixture was poured over a slurry of water and ice and the

product was extracted with 800 ml of ether containing 20% methylene chloride. The organic layer was washed once with water and dried over anhydrous sodium sulfate. The solvent was removed under vacuum to yield a solid residue which was washed with pentane containing 20% of ether. 2.556g (90% yield) of pure crystalline trans-4-benzoylstilbene were obtained, characterized by IR, ¹ H-NMR and MS.

Example 2. Preparation of stilbene A solution containing 45 mg of palladium acetate and 116 mg of dippb in 4 ml of DMF was stirred at room temperature under nitrogen for 1 hr. 1.016 ml of chlorobenzene was added, followed by 1.3 ml of styrene and 840 mg of sodium acetate. The resulting mixture was heated and stirred in a closed vessel under nitrogen at 150°C for 24 hrs. After cooling to room temperature, the reaction mixture was poured over a water-ice slurry and extracted with ether containing 10% methylene chloride. The organic layer was separated and washed once with water, dried over anhydrous sodium sulfate and the solvent was removed under vacuum. The residue was purified on a silica column to give an 80% yield of trans-stilbene and 4.4% yield of cis-stilbene, characterized by ^X HNMR, IR and GC in comparison to authentic samples.

Example 3. Preparation of trans-4-benzoyl-4'-methoxystilbene

4-Chlorobenzophenone was reacted with 4-methoxystyrene under the same conditions of Example 1, except for using ether containing 30% of methylene chloride to completely dissolve the product. 2.897g (92.3% yield) of pure crystalline trans-4-benzoyl-4'-methoxystilbene was obtained, characterized by IR, ^X H-NMR and MS.

Example 4. Preparation of trans-4-formyl-4'-methoxystilbene 4-Chlorobenzaldehyde was reacted with 4-methoxystyrene under the conditions of Example 1, to yield 1.9g(80% yield)

of pure product.

Example 5. Preparation of styrene

A solution containing 45 mg of palladium acetate and 165 mg of dppp in 10 ml of DMF was stirred for 1 hr at room temperature under nitrogen in a 500 ml glass pressure vessel.

2.12 g of sodium carbonate and 1.016 ml of chlorobenzene were added, followed by addition of ethylene to a pressure of 20 psi. The reaction mixture was heated at 140°C for 24 hrs, after which it was cooled to room temperature and the gas was vented off. GC analysis of the reaction mixture showed formation of styrene in 70% yield.

Using other starting materials, the following products were produced according to the process of the present invention:

Aryl Chloride Olefin Product 4-chlorotoluene styrene 4-methylstilbene 3-chloroanisole styrene 3-methoxystilbene 4-chloroni robenzene styrene 4-nitrostilbene 4-fluorochlorobenzene styrene 4-fluorostilbene chlorobenzene 4-methoxy styrene 4-methoxystilbene chlorobenzene methyl acrylate methyl cinnamate 4-chlorobiphenyl methyl acrylate methyl 4-phenyl- cinnamate methyl 4-chloro- benzoate ethylene 4-carbomethoxy- styrene

3-chloropyridine styrene β-(3-pyridyl)- styrene

The invention will now be defined by the following non- limiting claims.