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Title:
PROCESS FOR PREPARING A (HETERO)AROMATIC OLEFIN
Document Type and Number:
WIPO Patent Application WO/1998/049128
Kind Code:
A1
Abstract:
The invention relates to a process for preparing a (hetero)aromatic olefin, in which an optionally substituted olefin is arylated in the presence of a metal (compound) containing a metal from any one of groups 8, 9 or 10 of the Periodic System, a compound being chosen as the arylating agent that has the formula (1): Ar-CO-YCOA where Ar stands for an optionally substituted (hetero)aromatic group; A stands for an optionally substituted (hetero)aromatic or aliphatic group, an optionally substituted alkoxy or aryloxy group or a bond with Ar; Y stands for an optionally substituted heteroatom, and the arylation is carried out in the presence of a halide. As the arylating agent use is preferably made of an aromatic carboxylic anhydride, for example benzoic anhydride. Suitable for use as the (metal) compound containing a metal from any one of groups 8, 9 or 10 of the Periodic System is a compound from the group comprising PdCl�2?, PdBr�2?, PdI�2?, Na�2?PdCl�4?, Na�2?PdCl�6?, Pd�2?(dibenzylidene acetone)�3?, (Ph�3?P)�4?Pd, (PhCN)�2?PdCl�2?, Pd(OAc)�2? and PdSO�4?. Suitable for use as the halide is a compound from the group comprising halides of alkali metals, quaternary ammonium halides and quaternary phosphonium halides.

Inventors:
DE VRIES JOHANNES GERARDUS (NL)
STEPHAN MASSOUD (NL)
Application Number:
PCT/NL1998/000231
Publication Date:
November 05, 1998
Filing Date:
April 24, 1998
Export Citation:
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Assignee:
DSM NV (NL)
VRIES JOHANNES GERARDUS DE (NL)
STEPHAN MASSOUD (NL)
International Classes:
C07B37/04; C07C2/86; C07C41/30; C07C67/343; C07C231/12; C07C253/30; C07D207/267; C07D213/127; C07D307/54; C07C255/34; C07D207/26; C07D213/06; (IPC1-7): C07C67/343; C07C2/86; C07C13/28; C07C15/02; C07C15/52; C07C41/30; C07C43/188; C07C69/618; C07C231/12; C07C233/11; C07C253/30; C07C255/34; C07D207/267; C07D213/127
Other References:
HANS-ULRICH BLASER ET AL.: "The Palladium-catalyzed Arylation of Activated Alkenes with Aroyl Chlorides", JOURNAL OF ORGANOMETALLIC CHEMISTRY., vol. 233, no. 2, 20 July 1982 (1982-07-20), LAUSANNE CH, pages 267 - 274, XP002048799
Attorney, Agent or Firm:
Jacobs, Monique Sophie Nicole (P.O. Box 9, MA Geleen, NL)
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Claims:
CLAIMS
1. Process for preparing a (hetero)aromatic olefin, in which an aliphatic unsaturated compound is arylated using a (hetero)aromatic carbonyl compound as the arylating agent, in the presence of a metal (compound) containing a metal from any one of groups 8, 9 or 10 of the Periodic System, characterised in that a compound is chosen as the arylating agent that has the formula (1) ArCOYCOA (1) where Ar stands for an optionally substituted (hetero) aromatic group, A stands for an optionally substituted (hetero) aromatic or aliphatic group, an optionally substituted alkoxy or aryloxy group or a bond with Ar, Y stands for an optionally substituted heteroatom, and the arylation is carried out in the presence of a halide.
2. Process according to Claim 1, a symmetrical aromatic carboxylic anhydride being used as the arylating agent.
3. Process according to Claim 2, benzoic anhydride being used as the arylating agent.
4. Process according to any one of Claims 13, an aromatic or aliphatic alkene or an acrylate being used as the optionally substituted olefin.
5. Process according to any one of Claims 14, characterised in that the metal is Pd.
6. Process according to Claim 5, characterised in that use is made of a Pd compound from the group <BR> <BR> <BR> <BR> comprising PdCl2, PdBr2, Pud121 Na2PdCl4, Na2PdCl61 <BR> <BR> <BR> <BR> <BR> Pd2(dibenzylidene acetone) 3, (Ph3P)4Pd, (PhCN)2PdCl2, Pd(OAc)2, PdSO4, Pd clusters and Pd metal.
7. Process according to Claim 6, characterised in that use is made of PdCl2.
8. Process according to any one of Claims 17, characterised in that as the halide use is made of a compound from the group comprising halides of alkali metals, quaternary ammonium halides and quaternary phosphonium halides.
9. Process according to Claim 8, characterised in that NaBr is used as the halide.
10. Process according to any one of Claims 17, characterised in that the metal from any one of groups 8, 9 or 10 of the Periodic System and the halide are used in a single compound.
Description:
PROCESS FOR PREPARING A (HETERO)AROMATIC OLEFIN The invention relates to a process for preparing a (hetero)aromatic olefin, in which an alipahtic unsaturated compound is arylated using a (hetero)aromatic carbonyl compound as the arylating agent, in the presence of a metal (compound) containing a metal from any one of groups 8, 9 or 10 of the Periodic System.

Such a process is known from Blaser and Spencer, Journal of Organometallic Chemistry, 233, pp.

267-274 (1982), as a variant of the "Heck reaction" for the arylation of olefins, in which an aroyl chloride as the arylating agent is brought into contact with a substituted vinyl compound in the presence of a Pd catalyst.

A drawback of the known process is that the arylation is effected in the presence of an at least equimolar amount of a base, which results in the formation of an at least equimolar amount of a salt.

The formation of this salt as a by-product is, especially if it is a halide salt, undesirable from an economic and ecological viewpoint.

The invention's aim is to provide a process <BR> <BR> <BR> <BR> for the preparation of (hetero) aromatic olefins in which salt formation is avoided.

This aim is achieved according to the invention by choosing as the arylating agent a compound having formula (1) Ar-CO-YCOA (1) where - Ar stands for an optionally substituted (hetero) aromatic group, - A stands for an optionally substituted (hetero)- aromatic or aliphatic group, an optionally substituted alkoxy or aryloxy group or a bond with above mentioned Ar, - Y stands for an optionally substituted heteroatom, and carrying out the arylation in the presence of a halide.

A '(hetero)aromatic olefin' is in the context of the invention understood to be a compound with a (hetero)aromatic group and an aliphatic unsaturated group in which a (hetero)aromatic group has been conjugated with the aliphatic unsaturated (olefinic) bond, and also an aliphatic unsaturated compound in which the olefinic bond has subsequently been deconjugated, for example through isomerisation.

Examples of (hetero)aromatic olefins that can be prepared with the process according to the invention are styrene compounds, for example non-

substituted styrene, a-fluorostyrene, p-cyanostyrene, p-isobutyl styrene and m-chlorostyrene; cinnamates, for example methyl cinnamate, 2-ethylhexyl-p- methoxycinnamate, methyl-p-methoxycinnamate and isopentyl-p-methoxycinnamate; a-hexyl cinnamaldehyde, 6-methoxy-2-vinyl naphthalene, stilbene, 4,4'- dicyanostilbene, 2-vinyl pyridine, methyl-3-(2- quinolyl)acrylate and cinnamic acid nitrile.

Suitable examples of optionally substituted (hetero)aromatic groups are phenyl, naphthyl, quinolyl, isoquinolyl, pyrrolyl, furyl, thienyl, benzofuryl, indenyl, pyrimidinyl, pyrazolyl, imidazolyl, p- methoxyphenyl, p-isobutylphenyl and 6-methoxy-naphthyl.

An 'aliphatic group' is in the context of the invention understood to be an optionally substitu- ted saturated or unsaturated hydrocarbon group with preferably between 1 and 50 carbon atoms. Suitable examples of aliphatic groups are alkyl and alkenyl groups, for example methyl, ethyl, n-propyl, isopropyl, n-butyl, tert-butyl, isobutyl, benzyl, allyl, chloromethyl, dichloromethyl, trichloromethyl, trifluoromethyl, nonafluorobutyl, methoxycarbonylmethyl and cyanomethyl.

The (hetero)aromatic and aliphatic groups may optionally be substituted with one or more substi- tuents, for example with substituents that are inert under the given reaction conditions. Suitable examples of such substituents are a methoxy, cyano, methylcarbonyl, carbamoyl or halogen, preferably chlorine or fluorine, group.

Suitable examples of alkoxy groups are groups with preferably between 1 and 20 carbon atoms, for example methoxy, ethoxy, n-propoxy, isopropoxy, n- butoxy, tert-butoxy, isobutoxy, benzyloxy, allyloxy and hexafluorobenzyloxy.

Suitable examples of an aryloxy group are groups with preferably between 6 and 50 carbon atoms, for example phenoxy, naphthyloxy, chlorophenoxy, dichlorophenoxy, pentachlorophenoxy and pentafluorophenoxy.

The (hetero)aromatic group may also be substituted with one or more groups of the YCOA type, in which Y and A are defined as in formula (1). This makes it possible to cause the arylating agent to react with several optionally substituted olefin molecules.

The optionally substituted heteroatom Y is for example 0, S or NR, in which R corresponds to hydrogen, an alkyl or an aryl group with between 1 and 20 carbon atoms. Preferably Y stands for 0.

Suitable examples of the arylating agent are optionally substituted benzoic anhydride, for example p-methoxybenzoic anhydride and p- isobutylbenzoic anhydride; optionally substituted benzoic-thio-anhydride, for example p-methoxybenzoic- thio-anhydride; optionally substituted di- and triacylamines, for example bis(2-furancarbonyl)amine and tris(phenylcarbonyl)amine; optionally substituted N-acyl-substituted derivatives of amides, for example N-acetylbenzamide and N-methyldibenzamide; 6- methoxynaphthalene-2-carboxylic anhydride, 2-

furancarboxylic anhydride, 2-picolinic anhydride, 2,3- pyridine dicarboxylic anhydride, 2-thiophene carboxylic anhydride and a mixed anhydride of for example benzoic acid and other carboxylic acids, for example acetic acid, pivalic acid and trifluoroacetic acid.

Preferably a symmetrical aromatic carboxylic anhydride is used as the arylating agent, for example an optionally substituted benzoic anhydride. By using a symmetrical aromatic carboxylic - anhydride as a starting product it was found that not only is no salt formed, but also the carboxylic acid formed as a by-product in the process according to the invention can be converted back into the arylating agent.

The choice of for example benzoic anhydride as a starting product in the process according to the invention yields an economically attractive route for the arylation of olefins.

A may also represent a bond with the (hetero)aromatic group Ar from formula (1), as a result of which a (hetero)aromatic cyclic compound is formed.

Examples of such aromatic cyclic compounds are phthalic anhydride, phthalic-thio-anhydride and phthalimide.

It may also be advantageous to use an arylating agent that is prepared in situ, for example from an aromatic carboxylic acid, for example benzoic acid, and a carboxylic anhydride, for example acetic anhydride or trifluoroacetic anhydride. This may be advantageous if the compound HYCOA, which is formed as a by-product in the process according to the invention,

can be easily removed through distillation, preferably at atmospheric pressure.

As the aliphatic unsaturated compound, in the framework of this invention also briefly indicated as olefin, use is preferably made of a compound having formula (2) R1R2C=CHR3 (2) where R1, R2 and R3 can each be independently of one another chosen as a function of the desired end product and may represent electron-repelling, electron- attracting or electron-neutral groups. Suitable choices for R11 R2 and R3 are: hydrogen; alkyl groups with for example between 1 and 20 carbon atoms; alkenyl groups with for example between 2 and 20 carbon atoms; (hetero)aryl groups with for example between 6 and 50 carbon atoms; a carboxyl group; alkyl and arylcarboxylate groups with for example between 2 and 50 carbon atoms; alkyl and arylacyl groups with for example between 2 and 50 carbon atoms; a carbamoyl group or N-substituted alkyl and arylcarbamoyl groups with for example between 2 and 50 carbon atoms; an amino group or N-substituted alkyl and arylamino groups with for example between 1 and 50 carbon atoms; alkyl and arylamido groups with for example between 2 and 50 carbon atoms; alkoxy and aryloxy group with for example between 1 and 50 carbon atoms; cyano; nitro; a halogen and alkyl and arylthio groups with for example between 1 and 50 carbon atoms.

Preferably one of the three R1, R2, R3 substituents is hydrogen, the other two substituents preferably being in the cis position relative to one another; more preferably two of the three substituents are hydrogen.

Suitable examples of olefins having formula (2) are aromatic and aliphatic alkenes, for example ethylene, 1,3-butadiene, l-decene and styrene; acrylates, for example methyl methacrylate, n-butyl acrylate, n-butyl methacrylate and benzyl acrylate; olefinic nitriles, for example acrylonitrile and methacrylonitrile; olefinic amides, for example acrylamide and N,N-dimethylacrylamide; maleates, for example di-n-butylmaleate; pyridines, for example 4- vinyl pyridine; olefinic ethers, for example cyclohexyl vinyl ether and l-vinyl-2-pyrrolidone. Optionally substituted cyclic olefins, for example cyclohexene, indene and cyclooctene, with R1 and R3 from formula (2) forming an annular structure together with the carbon atoms to which they are bound, are also olefins that are suitable for use in the process according to the invention.

Preferably use is made of aliphatic and aromatic alkenes and acrylates.

The process according to the invention is carried out in the presence of a (metal) compound containing a metal from any one of groups 8, 9 or 10 of the Periodic System (new IUPAC version, Handbook of Chemistry and Physics, 70th Edition, CRC Press, 1989- 1990). Preferably the metal is Rh, Pd, Pt or Ni, most

preferably Pd. Pd can be used as Pd(IV), Pd(II) or as Pd(0). As the Pd compound a compound is preferably chosen from the group comprising PdCl2 (Pd-acetate), PdBr2, PdI2, Na2PdCl4, Na2PdCl61 Pd(OAc)2, PdSO4, Pd clusters and Pd metal, optionally on a carrier.

Alumina, titanium dioxide, carbon, zirconium oxide or silica can for example be chosen as the carrier material. Most preferably use is made of PdCl2 (Ph represents phenyl). Optionally use may also be made of a Pd compound containing ligands. Examples of such a Pd complex are Pd2(dibenzylidene acetone)3, (Ph3P) 4Pd, (PhCN)2PdCl2 and (Ph3P)2PdCl2. Such a Pd complex can also be prepared in situ from a mixture of a Pd compound and a ligand. Use is for example made of PdCl2 combined with 4,4'-dimethyl-2,2'-bipyridine, phosphines, for example triphenylphosphine, or bidentates, for example 1,3-bis- diphenylphosphinopropane.

The process according to the invention can optionally also be carried out in a sealed reactor in an inert atmosphere. An advantage of the process according to the invention is that Pd compounds can be chosen that are not particularly sensitive to oxygen, preferably compounds that contain no phosphine ligands, as a result of which the process can be carried out in the presence of oxygen, in particular air, without the Pd compound employed losing activity to a substantial extent.

The process according to the invention is carried out in the presence of a halide. The compound containing the halide is preferably chosen from the

group comprising halides of alkali metals, quaternary ammonium halides and quaternary phosphonium halides.

Suitable choices are alkyl chlorides and alkyl <BR> <BR> <BR> <BR> bromides, for example LiCl, LiBr, Nail, NaBr, KCl, KBr, CsC1, CsBr, quaternary alkyl ammonium halides and quaternary alkyl phosphonium halides, in which the alkyl groups each independently of one another preferably contain between 1 and 20, in particular between 1 and 5, carbon atoms, for example methyl, ethyl or n-butyl-substituted ammonium halides and phosphonium halides. <BR> <BR> <BR> <BR> <P>Very good results were obtained with NaBr, LiBr, LiCl, (n-C4H8)4NBr, (n-C4H8)4PBr, (n-C4H8)4NCl and (n-C4H8)4PCl.

Most preferably NaBr is chosen. NaBr is a very easily obtainable halide.

In the process according to the invention the element from any one of groups 8, 9 or 10 of the Periodic System and the halide can also be used in a single compound, for example PdCl2, PdBr2, PdI2, Na2PdCl4 or Na2PdCl6. Preferably PdCl2 is chosen.

Very high yields and degrees of conversion were obtained with a combination of PdCl2 and NaBr.

If use is made of a Pd compound and a halide compound, then both compounds may be used either separately or as a mixture. Good results were obtained when the two aforementioned compounds are each separately added to a solution of the optionally substituted (hetero)aromatic compound of formula (1) and the optionally substituted olefin, the order of the additions being random.

The amount of metal from any one of groups 8, 9 or 10 of the Periodic System to be used is not critical: preferably an amount of 0.01 - 5 mol.%, more preferably of 0.05 - 1 mol.%, most preferably 0.05 - 0.5 mol.%, is used, relative to the amount of arylating agent used.

Preferably the molar ratio of the metal and halide lies between 1:10 and 2:1, in particular between 1:6 and 1:1, a ratio of between 1:3 and 1:5 appearing optimum.

The solvent used can in principle be any solvent which dissolves the starting and reaction products, the (metal) compound and halide-containing compound to a reasonable extent and which - if so desired - remains inert under the given reaction conditions. Preferably use is made of a polar solvent.

Suitable solvents are for example N-methyl-2- pyrrolidone (NMP), dimethylacetamide (DMA) and dimethylsulphoxide (DMSO).

An additional advantage of the process according to the invention is that it can be carried out in a system in which the solvent, the (metal) compound containing the metal from any one of groups 8, 9 or 10, the halide-containing compound and the reaction products form a substantially homogeneous mixture. As a result, for example no surfactants need be used as in the known process, in which a non- homogeneous system is used.

The temperature at which the reaction is carried out depends on the stability of the reaction

products and the solvent. Preferably the process according to the invention is carried out at <BR> <BR> <BR> <BR> temperature of between 80 and 220"C, more in particular between 130 and 1700C.

The process according to the invention can be used to prepare agrochemical intermediates, for example methyl cinnamate, an intermediate for the phytotoxic product Karphos(TM), to prepare pharmacological intermediates, for example 2-vinyl-6- methoxynaphthalene, an intermediate for naproxene, p- isobutylstyrene, an intermediate for ibuprofen and p- methoxycinnamate esters, for example 2-ethylhexyl-p- methoxycinnamate and isoamyl-p-methoxycinnamate, which are for example used as W-absorption agents in preparations for protecting the skin against sunlight.

The invention will now be elucidated with reference to examples, without being limited as a result.

Examples Definitions Yield = Cend/Do * 100 % Degree of conversion = (Do~De)Do * 100 % Selectivity = (yield/degree of conversion) * 100 where: Cend = number of mol of (hetero)aromatic olefin formed at the end of the reaction.

Do = number of mol of arylating agent according to formula (1) at the beginning of the reaction.

De = number of mol of arylating agent according to formula (1) at the end of the reaction.

Example I: preparation of n-butyl-trans-cinnamate n-Butyl-trans-cinnamate was prepared from n- butylacrylate and benzoic anhydride in the presence of PdCl2 according to the following reaction: Benzoic anhydride (BZA) (1.15 g; 5.0 mmol), PdCl2 (2.2 mg; 0.0124 mmol; 0.25 mol.% relative to BZA) and NaBr (5.2 mg; 0.05 mmol) were weighed into a 10-ml Schlenk vessel. A magnetic stirring bar was added, the Schlenk vessel was sealed with a rubber septum, which was followed by evacuation and rinsing with argon. Next the following were added via a syringe: n-hexyl ether (93.2 mg; 0.5 mmol) as an internal standard for the GC analysis, n-butyl acrylate (0.85 ml; 6.0 mmol) and N- methyl pyrrolidone (NMP) (S ml). After 75 minutes' react ion at 1600C according to the GC analysis all the benzoic anhydride had been converted and the experiment was stopped (degree of conversion = 100 %). n-Butyl-trans-cinnamate was formed with a 90% yield and was isolated through distillation.

The same experiment but without sealing and rinsing the Schlenk vessel, so in the presence of air, led to the same result.

Examples II-VIII The process according to Example I was repeated, using different Pd compounds and/or halide compounds. The reaction conditions and the results are summarised in Table 1.

Table 1 : Examples II - VIII<BR> BZA = benzoic anhydride; NMP = N-methyl pyrrolidone; DMA = dimethyl acetamide.<BR> dba = dibenzylidene acetone Example Pd compound Halide Solvent Temp. Time Yield Degree of [mol. % rel. to compound or (°C) (min) (%) conversion BZA] ligand (%) [mol. % rel. to BZA] II PdBr2 [0.25%] NaBr [1%] NMP 160 60 44.5 52.6 III (PhCN)2PdCl2 (n-Bu)4PBr NMP 160 60 91.4 100 [0.25%] [1%] IV (Ph3P)2PdCl2 none NMP 160 90 40.5 54.3 [0.25%] V Na2PdCl4 [0.25%] NaBr [0.5%] NMP 155 90 62.8 76.5 VI Na2PdCl6 [0.25%] (n-Bu)4NBr NMP 160 90 81.0 100 [1%] VII Pd2(dba)3 [1%] (n-Bu)4NBr DMA 155 90 58.7 72.0 [5%] VIII (Ph3P)4Pd [0.25%] (n-Bu)4NBr NMP 160 90 10.9 29.0 [1%]

Examples IX - XI Example I was repeated using different amounts of the halide compound (n-Bu)4NCl at a reaction time of 60 minutes. The results are summarised in Table 2. The amount of Pd compound used is 0.25 mol.% relative to the benzoic anhydride.

Table 2: Examples IX-XI Example Concentra- Pd:halide Yield Degree of tion (mol.% molar ratio (%) conversion rel. to (%) BZA) IX 0.5 % 1:2 70.5 86.0 X 1 % 1:4 83.0 100 XI 2.5 % 1:10 76.5 100 Examples XII - XXIII Example I was repeated using different olefins. The reaction conditions and the results are summarised in Table 3.

Table 3: Examples XII - XXIII Ex. Olefin Temp. Time Degree of Products formed (°C) (min.) conversion (% selectivity) (%) XII 1-decene 160 90 85 mixture of monoarylated decenes (95) XIII styrene 160 120 90 trans-stilbene (85) 1,1'-diphenylethylene (11) XIV 4-vinyl pyridine 178 450 20 trans-4-aza-stilbene (80) XV cyclooctene 160 120 100 phenylcyclooctene (85) diphenylcyclooctene (10) XVI cyclohexyl vinyl ether 160 120 80 a-cyclohexyloxystyrene (25) XVII N,N-dimethyl 160 60 100 trans-N,N-dimethylcinnamic amide acrylamide (60) XVIII acrylonitrile 140 180 90 trans-cinnamic nitrile (75) cis-cinnamic nitrile (20) Ex. Olefin Temp. Time Degree of Products formed (°C) (min.) conversion (% selectivity) (%) XIX acrylamide 140 120 90 cinnamic amide (10) XX n-butyl methacrylate 160 90 100 n-butyl-trans-a-methyl cinnamate (55) XXI di-n-butylmaleate 190 90 100 di-n-butyl phenyl fumarate (85) di-n-butyl phenyl maleate (10) XXII 1-vinyl-2-pyrrolidone 160 90 100 1-(1-styryl)-2-pyrrolidone (30) 1-(2-trans-styryl)-2-pyrrolidone (10) XXIII benzylacrylate 160 90 100 benzyl-trans-cinnamate (90) Examples XXIV - XXVI Example I was repeated using different anhydrides. The reaction conditions and the results are represented in Table 4.

Table 4: Examples XXIV - XXVI Ex. Anhydride Temp. Time Degree of Products formed (°C) (min.) conversion (selectivity %) (%) XXIV p-methoxybenzoic 190 60 100 n-butyl-trans-p-methoxycinnamate (80) acid XXV phthalic acid 160 75 100 n-butyl-2-(3-phthalido) acetate (5) XXVI 2-furancarboxylic 160 90 100 n-butyl-trans-2-furylacrylate (85) acid