JP2005047864A - New method for synthesizing aromatic olefin - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To apply a recoverable and reusable catalyst having high activities to a Heck reaction to form an aromatic olefin. <P>SOLUTION: The method for synthesizing the aromatic olefin utilizes the transition metal complex catalyst which is a network-shaped supermolecule obtained by associating a polyacrylamide derivative having a diphenylphosphino group at a proper interval, with a transition metal in an aqueous solution. The recovery and the reuse of the catalyst are made possible by using the transition metal complex catalyst for the Heck reaction, and a high number of turnovers are achieved. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to the Heck reaction using a polymer-supported transition metal catalyst, and is used for the synthesis of aromatic olefins required in the fields to which organic synthesis belongs and other fields.

  Aromatic olefins are extremely important compounds in the chemical industry. For example, cinnamic acid, styrene, and stilbene derivatives are widely used as starting materials for polymers, ultraviolet absorbers, and precursors for bioactive substances. And since this aromatic olefin is a very important compound, its synthesis method has been actively studied.

  In 1979, RF Heck reported an innovative method for synthesizing aromatic olefins in high yield from aromatic halides and olefins in the presence of palladium catalyst and base [RF Heck, Acc. Chem. Res. , 12, 146 (1979)]. In this method, aromatic olefins can be obtained with high selectivity and high yield under mild conditions, and there are few restrictions due to functional groups. For this reason, it is used in many fields and is called the Heck reaction in the name of the developer.

  In general, a homogeneous palladium catalyst is advantageous in order to make the Heck reaction proceed smoothly, and various homogeneous palladium catalysts have been reported. However, the presence of this homogeneous palladium catalyst may interfere with the purification of the target product. In particular, in the fields to which pharmaceuticals, cosmetics, foods, etc. belong, the palladium catalyst must be strictly removed. In recent years, “environmentally friendly chemical synthesis” has been demanded, and from this viewpoint, a reaction system capable of completely removing the palladium catalyst has been actively developed.

  Various attempts have been made to solve the palladium catalyst removal. For example, P.P. W. The method of Wang et al. A bidentate 1,2-bis (diisopropylphosphino) benzene was chemically bonded to polystyrene, and palladium was coordinated to synthesize a polystyrene-supported palladium catalyst, which was used as a catalyst for the Heck reaction of methyl acrylate and iodobenzene. Used. It has been reported that the use of a polystyrene-supported palladium catalyst makes it easy to recover the catalyst and can be used repeatedly without impairing the catalyst efficiency [J. Org. Chem., 59, 5358 (1994)]. In addition, M. as a use of dendrimer. T. The method of Reetz et al. M. T. Reetz et al. Synthesized a dendrimer-supported palladium catalyst in which a diphenylphosphinomethyl group was introduced into the surface amino group of a dendrimer composed of 1,4-diamine and palladium was coordinated therewith. This is used as a catalyst for the Heck reaction of styrene and bromobenzene. The reaction proceeds in DMF, and after completion of the reaction, ether is added to precipitate and recover the dendrimer-supported palladium catalyst. The recovered dendrimer-supported palladium catalyst can be reused without impairing the catalyst efficiency [Angew. Chem. Int. Ed. Engl., 36, 1526 (1997)]. In recent years, the recovery and reuse of palladium catalysts have been studied using ionic liquids for the Heck reaction. A. J. Carmichael et al. Conduct the Heck reaction using several ionic liquids. For example, palladium acetate and triphenylphosphine are added to 1-butyl-3-methylimidazolium hexafluorophosphate to prepare an ionic liquid solution of palladium catalyst, and ethyl acrylate and iodobenzene are added to this to perform the Heck reaction. ing. After completion of the reaction, the product is extracted from the reaction mixture with hexane. It has been reported that an ionic liquid solution of palladium catalyst can be used repeatedly [Org. Lett., 1, 997 (1999)].

  As described above, many methods for improving the Heck reaction have been reported. The number has increased in recent years. P. W. The method of supporting palladium on polystyrene resin reported by Wang et al. Is a very useful method because it can recover and reuse the palladium catalyst. However, P.I. W. The method of Wang et al. Has a low catalyst turnover number of 780, which is not satisfactory. M. T. The method of loading palladium on dendrimers reported by Reetz et al. Requires reaction in a polar solvent such as DMF. In addition, the amount of the dendrimer-supported palladium catalyst is 2 mol%, which is not satisfactory. A. J. The method using an ionic liquid reported by Carmichael et al. Is a very useful method because the preparation of a palladium catalyst is simple and can be recovered and reused. However, the ionic liquid is relatively unsatisfactory because it is relatively expensive and requires about 20 mol% of palladium catalyst. There is a strong demand for a Heck reaction that uses a catalyst that can be easily separated, shows high catalytic activity, and can be reused.

  Thus, the inventors have conducted extensive research and have completed the present invention. That is, the present invention has the following structural formula:

(Wherein k, L and n are each independently an integer of 1 or more, m is an integer of 0 or more, M is selected from transition metals such as palladium, nickel, ruthenium, rhodium, indyllium and platinum, R ¹ and R ² are each independently selected from hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, hexyl group, cyclohexyl group, phenyl group, and benzyl group; Selected from chlorine, acetate, carbon monoxide, acetonitrile, benzonitrile, acetylacetone, triphenylphosphine, Ar ¹ and Ar ² are each independently methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t A transition metal catalyst represented by -phenyl group or naphthyl group which may have a butyl group) The present invention relates to a method for synthesizing an aromatic olefin. The above catalyst was developed by the inventors, and has already been reported for application to the Suzuki-Miyaura reaction [Org. Lett., 4, 3371 (2002)].

  This catalyst can be synthesized very easily according to the above document. A typical example of this catalyst is a palladium supramolecular palladium complex obtained by reacting a chain copolymer of N-substituted amido-4-styryl (diphenyl) phosphine with palladium. Since this supramolecular palladium complex is amphiphilic, it incorporates a hydrophilic or hydrophobic substrate or reagent in the vicinity of palladium and functions as a catalyst for the reaction between the substrate and the reagent. And since it is a network-like supramolecule, it is insoluble in water and organic solvents and can be easily recovered from the reaction system. Palladium is strongly supported on the phosphino group of the copolymer. Therefore, there is no elution of palladium during the reaction, and it can be used repeatedly. The synthesis method of the palladium catalyst shown by the following structural formula used for this invention as a reference example below is shown.

Reference Example 1 Synthesis of palladium catalyst
Dissolve 1 mol of 4-styryl (diphenyl) phosphine and 6 mol of N-isopropylacrylamide in t-butanol. Add 0.0215 mol of azoisobutyronitrile to this solution, stir at 75 ° C for 41 hours, and precipitate by methylene chloride-diethyl ether precipitation. Purification and drying yielded a chain copolymer in 85% yield. An aqueous solution in which 2562 mg of this linear copolymer was dissolved in 588 ml of THF and then 284 mg of ammonia tetrachloropalladium was dissolved in 236 ml of water was added, stirred at room temperature for 62 hours, further added with 235 ml of water, and refluxed at 80 ° C. for 4 hours. The precipitate was collected by filtration, washed and dried, and THF was added and reflux washing was repeated. The precipitate was collected by filtration, washed, and dried to quantitatively obtain 2789 mg of palladium catalyst as a network supramolecular complex.

IR absorption of the obtained palladium catalyst is shown.
IR: 3285, 3061, 2971, 2973, 2874, 1651, 1460, 1387, 1366, 1175, 1119, 1096, 694, 523 (cm ⁻¹ )

  This catalyst can be recovered very easily. Moreover, as shown in Example 8 below, it can be reused, and even if it is repeatedly used at least 5 times continuously, its catalytic activity does not decrease. In addition, as shown in Examples 1 to 7 below, the yield of the product is as high as 90% or more, and the turnover number of the catalyst is extremely high. Thus, since the method according to the present invention uses a catalyst that is a network-like supramolecule that is insoluble in the reaction solvent, the catalyst can be completely recovered after the reaction is completed and can be reused. In addition, it has a high catalytic activity and realizes a high yield with a very small amount of catalyst, so it can be said to be an extremely useful catalyst for Heck reaction.

  Hereinafter, preferred embodiments of the present invention will be described, but these are exemplifications and do not limit the present invention. It will be apparent to those skilled in the art that variations are possible within the scope of the invention.

Example 1 Synthesis of t-butyl cinnamate 36.5 mmol of iodobenzene, 54.7 mmol of t-butyl acrylate, 54.7 mmol of triethylamine, and 1.82 μmol of the palladium catalyst synthesized in Reference Example were added to toluene and refluxed at 100 ° C. for 15 hours. Methanol was added to the reaction mixture and filtered to recover the palladium catalyst. From the filtrate, t-butyl cinnamate was recovered and purified to obtain 6859 mg of an oily product of t-butyl cinnamate. The yield was 92%.

Example 2 Synthesis of ethyl 3-ethoxycarbonylcinnamate Similar to Example 1 except that ethyl 3-iodobenzoate was used instead of iodobenzene of Example 1 and ethyl acrylate was used instead of t-butyl acrylate. The operation was performed to obtain 8130 mg of crystals of ethyl 3-ethoxycarbonylcinnamate. The yield was 95%.

Example 3 Synthesis of methyl 4-acetoxycinnamate Using 4-acetoxyiodobenzene in place of iodobenzene in Example 1 and methyl acrylate in place of t-butyl acrylate, the same procedure as in Example 1 was performed. Then, 7395 mg of methyl 4-acetoxycinnamate was obtained. The yield was 95%.

Example 4 Synthesis of methyl 4-chlorocinnamate The same procedure as in Example 1 was carried out using 4-chloroiodobenzene in place of iodobenzene in Example 1 and methyl acrylate in place of t-butyl acrylate. Then, 6818 mg of crystals of methyl 4-chlorocinnamate were obtained. The yield was 95%.

Example 5 Synthesis of methyl 4-methoxycinnamate Using 4-methoxyiodobenzene in place of iodobenzene in Example 1 and methyl acrylate in place of t-butyl acrylate, the same procedure as in Example 1 was performed. As a result, 6454 mg of methyl 4-methoxycinnamate was obtained. The yield was 92%.

Example 6 Synthesis of stilbene The same procedure as in Example 1 was carried out using styrene instead of t-butyl acrylate in Example 1 to obtain 5921 mg of stilbene crystals. The yield was 90%.

Example 7 Synthesis of resveratrol Similar to Example 1 except that 4-benzoyloxyiodobenzene was used in place of iodobenzene and 3,5-dibenzoyloxystyrene was used in place of t-butyl acrylate. The operation was performed to obtain 18350 mg of (E) -3,5,4′-tribenzoyloxystyrene. This yield was 93%.
(E) -3 mmol of 5,5,4′-tribenzoyloxystyrene and 1.5 mmol of sodium methoxide were added to a tetrahydrofuran-methanol mixed solvent and heated at 50 ° C. for 5 hours. The crude product was separated and purified to obtain 224 mg of crystals of (E) -3,5,4′-hydroxystyrene (resveratrol).

Example 8 Reuse of Catalyst The operation of Example 1 was repeated by reusing the palladium catalyst recovered in Example 1. The number of repetitions and the yield of t-butyl cinnamate at that time are shown.
Second time: 93%
Third time: 95%
Fourth time: 94%
5th: 95%

Claims (2)

The following structural formula

(Wherein k, L and n are each independently an integer of 1 or more, m is an integer of 0 or more, M is selected from transition metals such as palladium, nickel, ruthenium, rhodium, indyllium and platinum, R ¹ and R ² are each independently selected from hydrogen, methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, hexyl group, cyclohexyl group, phenyl group, and benzyl group; Selected from chlorine, acetate, carbon monoxide, acetonitrile, benzonitrile, acetylacetone, triphenylphosphine, Ar ¹ and Ar ² are each independently methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t In the presence of a transition metal catalyst represented by -phenyl group or naphthyl group optionally having butyl group) Synthesis of aromatic olefins, characterized in that reacting the ride and olefins. The aromatic olefin synthesis according to claim ¹ , wherein n is 10, L is 2, m is 2, M is palladium, X is chlorine, R ¹ is isopropyl, R ² is hydrogen, and Ar ¹ and Ar ² are phenyl groups. Law.