Patent Grant
7282618
The present invention relates to a novel oxidative coupling of arenes with olefins to yield aryl alkenes, which uses ruthenium (Ru) or osmium (Os) compounds as catalysts.
Catalytic carbon-carbon bond formation by C—H activation is a topic of much current interest. Significant progress has been made in recent years in the development of synthetically useful catalytic addition of arenes to alkenes to give the saturated alkyl arenes (Murai et al, 1993; Kakiuchi et al, 1996; Jia et al, 2000a, 2000b; Matsumoto et al, 2000a).
Catalytic oxidative coupling of arenes with alkenes to give aryl alkenes, in which the double bond is preserved, is a highly desirable goal. Such a reaction, which does not require the utilization of a reactive substituent, and does not produce waste, may have an advantage over other methods for the preparation of aromatic alkenes, such as the well-known Heck reaction for the vinylation of aryl halides. Stoichiometric coupling of olefins with arenes promoted by Pd(II) is well known (Moritani et al, 1967; U.S. Pat. No. 3,674,884, 1972).
Tsuji et al (1984) and lately Fujiwara et al (1996) and Mikami et al (1999) have demonstrated catalysis by utilizing peroxides as oxidants in their systems. While good catalytic activity was achieved with some alkenes, acrylates resulted in low activity (˜10 turnovers). The use of peroxide oxidants and acetic acid solvent in these systems is problematic from the industrial point of view. Attempts to use O2 or air resulted in low activity in intramolecular (Miura et al, 1997, 1998) and intermolecular (Fujiwara et al, 1969, 1976; Asano et al, 1970; Shue, 1972; U.S. Pat. No. 3,855,329) coupling and alkene oxidation took place in the intermolecular reaction.
Another approach utilizing Rh carbonyl clusters under high (20-30 atm) CO pressure (Hong et al, 1984) resulted in modest catalytic activity with concomitant hydrocarbonylation of the alkene. Low catalytic activity was reported for the Rh-catalyzed photochemical coupling of arenes with alkenes, in which concomitant hydrogenation of the alkene took place and biaryls were formed as by-products (Sasaki et al, 1988; JP 1193241). A very low yield Rh catalyzed oxidative phenylation of ethylene to styrene was reported (Matsumoto et al, 2000b; U.S. Pat. No. 6,127,590).
It has now been found according to the present invention that aryl alkenes can be produced by reaction of arenes with olefins in the presence of ruthenium (Ru) or osmium (Os) compounds as catalysts. The reaction can be carried out in the presence of molecular oxygen as the oxidant or in the absence of O2, in which case the alkene itself serves as the oxidant. Reasonable turnover numbers were achieved.
The present invention thus relates to a method for the production of an aryl alkene comprising reacting an arene with an olefin in the presence of a Ru or Os compound as catalyst. An advantage of the process of the present invention using Ru or Os catalysts is the absence of the necessity of an acid solvent or a peroxide. Furthermore, compared to the prior art process using Rh catalysts and CO, much lower pressure of CO may be used.
In one embodiment, the reaction is carried out in the presence of molecular oxygen. The addition of a catalytic amount of hydroquinone or of a quinone such as, but not being limited to, benzoquinone, improves the yield of the reaction. The reaction may be carried out in an inert atmosphere but it is preferably carried out in an atmosphere containing CO. CO pressures are between 0 to about 100 atm, preferably between 1 to 10 and most preferably between 6 to 8 atm.
While it is expected that any ruthenium or osmium compound could be used in accordance with the present invention, preferred examples of ruthenium compounds that may be used include, but are not limited to, RuCl3.3H2O, [Ru(CO)3Cl2]2, [(η6-C6 H6)RuCl2]2, [(η6-C6H6—Ru(H2O)3](F3CSO3)2, Ru(NO)Cl3.5H2O, Ru(F3CCOCHCOCF3)3 and Ru3(CO)12. In one preferred embodiment, the ruthenium compound is RuCl3.3H2O.
Preferred examples of osmium compounds that may be used according to the invention include, but are not limited to, OsCl3.3H2O, OsO4, [Os(CO)3Cl2]2, [(η6-C6H6)OsCl2]b 2, Os(NO)Cl3.5H2O , Os(F3CCOCHCOCF3)3 and Os3(CO)12.
Most of the Ru and Os compounds present a higher catalytic activity in a CO atmosphere but the compounds Ru(F3CCOCHCOCF3)3, Ru3(CO)12 and Os3(CO)12 exhibit catalytic activity in the absence of a CO atmosphere.
In one embodiment, the method of the invention is used for the production of an aryl alkene of the formula:
Ar—CR1═CR2—R3
wherein Ar is an aryl radical and R1, R2, R3 independently of each other represent H, alkyl, aryl, alkoxycarbonyl or aryloxycarbonyl.
As used herein, the term “aryl” includes carboaryl radicals such as, but not being limited to, phenyl and naphthyl, and heteroaryl radicals such as, but not being limited to, furyl, thienyl, the aryl radical being optionally substituted by one or more halogen atoms, alkyl optionally substituted by one or more halogen atoms or alkoxy, and the term “arene” relates to the aromatic compound from which the aryl radical is derived, e.g., benzene, naphthalene furan, thiophene, that may be substituted as indicated for the aryl radical.
As used herein, the term “alkyl” for an alkyl radical itself or part of an alkoxy radical includes straight and branched radicals having up to 25 carbon atoms, preferably up to 20, more preferably up to 10, and most preferably up to 6 carbon atoms such as methyl, ethyl, propyl, butyl, pentyl and hexyl, wherein said alkyl may be optionally substituted by halogen such as fluoro, chloro and bromo, or by alkoxy.
In one embodiment, the aromatic compound may be substituted by one or more alkyl or fluoroalkyl, preferably methyl or CF3, radicals, and may be, for example, toluene or xylene. In another embodiment, the aromatic compound may be substituted by an alkoxy, preferably methoxy, radical, and may be, for example, anisole or 2-methoxynaphthalene. In a further embodiment, the aromatic compound may be substituted by a halogen such as fluoro, chloro and bromo, and may be, for example, chlorobenzene.
When R1, R2, R3 are hydrogen the reaction is carried out with ethylene. Thus when the arene is benzene the end product is styrene and when the arene is naphthalene the end product is vinylnaphthalene. When R1, R2, R3 are alkyls, the end product will be an alkenyl arene. R1, R2, R3 may also be alkyl substituted by one or more halogen atoms such as chloro, bromo, and preferably fluor. In one example as shown herein benzene is reacted with 3,3,4,4,5,5,6,6-nonafluorohex-1-ene thus producing (3,3,4,4,5,5,6,6-nonafluorohex-1-enyl)benzene.
In one preferred embodiment of the invention R1is an alkoxycarbonyl radical such as ethoxycarbonyl and, more preferably, methoxycarbonyl and R2, R3 are hydrogen. Thus for the preparation of an alkyl cinnamate, benzene is reacted with an alkyl acrylate such as methyl or ethyl acrylate. When a substituted benzene or naphthalene compound is reacted with an alkyl acrylate, the corresponding alkyl 2-propanoate derivatives are obtained such as methyl 3-(chlorophenyl)-2propanoate, methyl 3-methoxyphenyl-2-propanoate, methyl 3tolyl-2-propanoate, methyl 3-(2,5-dimethylphenyl)-2-propanoate, methyl 3-(2-naphthyl)-2-propanoate and methyl 3-(2- or 6- or 7-methoxy-2-naphthyl)-2-propanoate, that are produced by reacting an arene selected from chlorobenzene, anisole, toluene, pxylene, naphthalene and 2-methoxynaphthalene, respectively, with methyl acrylate.
In another preferred embodiment of the invention R1 is an alkoxycarbonyl radical, preferably, methoxycarbonyl, R2 is hydrogen and R3 is a carboaryl, preferably, phenyl. Thus for the preparation of an alkyl 3,3-diaryl propanoate, an arene is reacted with an alkyl cinnamate such as methyl or ethyl cinnamate. In one example as shown herein benzene is reacted with methyl cinnamate, thus producing methyl 3,3-diphenyl propanoate.
Oxygen is preferably added to the reaction at 0-10 atmospheres, more preferably 1-2 atmospheres, and the temperature of the reaction is preferably 50-250° C., and more preferably 150-180° C. At temperatures above 250° C., the reaction will still take place, but some amount of decomposition will result. At lower than 50° C., the reaction will still take place, but the turnover will become unproductively small. Similarly, at an O2 pressure above 10 atm, the reaction will still be expected to take place, but the process would not be industrially practical.
The aryl alkenes produced by the process of the invention are useful intermediates particularly for the pharmaceutical industry.
The present invention provides a novel oxidative coupling of arenes with olefins, which may optionally use molecular oxygen as the oxidant. Good catalytic activity is exhibited by the Ru compounds RuCl3.3H2O, [Ru(CO)3Cl2]2, [(η6-C6H6)RuCl2]2, Ru(NO)Cl3.5H2O and Ru(F3CCOCHCOCF3)3 under a pressure of 2 atm of O2 and 6.1 atm of CO at 180° C. In the absence of O2, the alkene itself serves as the oxidant and the coupling is accompanied by a parallel alkene hydrogenation. The reaction is accelerated by electron donating substituents on the arene.
Notably, the dehydrogenative coupling proceeds either under O2 (Equation 1) or in an inert atmosphere (Equation 2). In absence of O2 the olefin itself serves as an oxidant and, for example, when benzene (Ar=phenyl) is reacted with methyl acrylate (R1 is —COOCH3, R2, R3 ═H) a 1:1 ratio of cinnamate: propanoate is obtained. In comparison, under 2 atm of O2 the cinnamate yield is doubled and a ratio of about 3:1 of cinnamate: 2-propanoate is obtained (see Table 1). Essentially no organic carbonylation products are observed. The product turnover number increases with CO pressure up to 6.1 atm, beyond which further pressure increase has no beneficial effect. Various arenes and alkenes are reactive (see Table 3). Alky acrylates are by far the most active of the olefins tested.
The invention will now be illustrated by the following non-limiting Examples.
1A. With Ru Complexes as Catalysts
A solution containing 8 ml of benzene, 0.02 mmol of RuCl3.3H2O (1) and 5 mmol of methyl or ethyl acrylate in a Fischer-Porter glass reactor was pressurized with 6.1 atm CO and 2 atm O2 and heated to 180° C. with stirring for 48 hours, thus producing methyl or ethyl cinnamate. The results are shown in Table 1.
Addition of a catalytic amount of hydroquinone (HQ) (Entries 6 and 7) or quinone improved the yield, the turnover number and the mass balance of the reaction. Ten or 20 eq of HQ (relative to Ru) had a similar effect. Addition of a radical trap (galvinoxyl) does not retard the reaction and it proceeds as well in the dark (Entry 3 in Table 1).
aReaction conditions: a solution containing 8 mL of benzene, 0.02 mmol of 1 and 5 mmol of acrylate ester in a Fischer-Porter glass reactor is pressurized with 6.1 atm CO and 2 atm O2 and heated to 180° C. with stirring for 48 hours.
1B. With [η6-C6H6—Ru(H2O)3](F3CSO3)2 as Catalyst with 1 atm of CO
A solution containing 8 ml of benzene, 0.02 mmol of [η6-C6H6—Ru(H2O)3](F3CSO3)2 and 5 mmol of ethyl acrylate in a Fisher-Porter glass reactor was pressurized with 1 atm CO and 7.1 atm of inert gas (e.g., Argon or N2) and heated to 180° C. with stirring for 48 hours. GC analysis revealed formation of 1.1 mmol (E)-ethyl cinnamate (22% yield, 55 TON) and 1.3 mmol ethyl propanoate (26% yield, 65 TON).
1C. With Ru(CF3COCHCOCF3)3 or OS3(CO)12 or Ru3(CO)12 as Catalysts without CO Pressure
A solution containing 8 ml of benzene, 0.02 mmol of catalyst (per metal center) and 5 mmol of ethyl acrylate in a Fischer-Porter glass reactor was pressurized with 2 atm of O2 and 6.1 atm of inert gas (e.g., Argon or N2) and heated to 180° C. with stirring for 48 hours. The results are shown in Table 2.
aReaction conditions: a solution containing 8 mL of benzene, 0.02 mmol of catalyst (per metal center) and 5 mmol of ethyl acrylate in a Fischer-Porter glass reactor is pressurized with 6.1 atm Ar and 2 atm O2 and heated to 180° C. with stirring for 48 hours. Yields are based on ethyl acrylate.
bOther catalysts mentioned above gave under this conditions about 1 TON.
1D. With Os Complexes as Catalysts
A solution containing 8 ml of benzene, 0.02 mmol of OsCl3.xH2O(2) or OsO4 (3) and 5 mmol of ethyl acrylate in a Fischer-Porter glass reactor was pressurized under 2 atm of O2 and 6.1 atm of argon and heated to 180° C. with stirring for 48 hours, thus producing ethyl cinnamate. The results are shown in Table 3.
aReaction conditions: a solution containing 8 mL of benzene, 0.02 mmol of 2 or 3 and 5 mmol of ethyl acrylate in a Fischer-Porter glass reactor is pressurized with CO and O2 and heated to 180° C. with stirring for 48 hours. Yields are based on acrylate ester.
In a typical reaction protocol, an 80 mL glass pressure tube is charged with 90 mmol of arene, 0.02 mmol of RuCl3.3H2O, 0.2 mmol HQ and 5 mmol of acrylate. The reactor is then evacuated and then pressurized with 6.1 atm CO and 2 atm O2 and heated to 180° C. with stirring for 48 hours. The liquid phase is sampled and analyzed by gas chromatography, mass spectroscopy and HNMR spectroscopy at the end of the reaction. The products are characterized by comparison with authentic samples. In this way, methyl acrylate was reacted with benzene, chlorobenzene, toluene, anisole, p-xylene, naphthalene and 2-methoxynaphthalene, and ethylene, methyl cinnamate and H2C═CH(CF2)3CF3 were reacted with benzene. The results are shown in Table 4.
aThe reaction was carried out as described above in Example 2. Entry 5 was carried out under 3.4 atm of CO and 3.4 atm of ethylene. In Entry 6, 2.63 mmol of H2C = CH(CF2)3CF3 were used.
The reaction is accelerated by electron donating substituents on the arene.
In summary, a novel Ru- and Os-catalyzed oxidative coupling of arenes with olefins to produce aryl alkenes, which can either directly utilize dioxygen or can utilize the alkene as oxidant and results in reasonable turnover numbers, has been disclosed.
Matsumoto et al, “Anti-Markovnikov Olefin Arylation Catalyzed by an Iridium Complex”,J Am Chem Soc 122:7414 (2000a)
| Number | Date | Country | Kind |
|---|---|---|---|
| 140275 | Dec 2000 | IL | national |
| Filing Document | Filing Date | Country | Kind | 371c Date |
|---|---|---|---|---|
| PCT/US01/47570 | 12/13/2001 | WO | 00 | 12/2/2003 |
| Publishing Document | Publishing Date | Country | Kind |
|---|---|---|---|
| WO02/055455 | 7/18/2002 | WO | A |
| Number | Name | Date | Kind |
|---|---|---|---|
| 3674884 | Moritani et al. | Jul 1972 | A |
| 3855329 | Shue | Dec 1974 | A |
| 6127590 | Taube et al. | Oct 2000 | A |
| 20010037044 | Matsumoto et al. | Nov 2001 | A1 |
| Number | Date | Country |
|---|---|---|
| 1193241 | Aug 1989 | JP |
| Number | Date | Country | |
|---|---|---|---|
| 20040073075 A1 | Apr 2004 | US |
