Claims
- 1. A method for coupling aryl and heteroaryl monohalides having 4 to 20 carbon atoms to produce biaryl or hetero-biaryl compounds, said method comprising contacting said monohalide with a catalytic combination comprising:
- (I) an anhydrous nickel compound, wherein the ratio of gram atoms of nickel to moles of monohalide is in the range of about 0.0001 up to 0.5;
- (II) at least one bidentate phosphorus-containing ligand selected from the group consisting of ##STR19## wherein each Ar is independently selected from aromatic ring compounds having 4 up to 20 carbon atoms;
- the x bonds and the y bonds are attached to adjacent carbon atoms on the ring structures;
- each R, when present as a substituent, is independently selected from alkyl, aryl, --F, --NR'.sub.2, --CN, --CHO, --OR', --OCO--R', --COO--R', ##STR20## --SO.sub.2 --R', --SO.sub.3 R', or --NR'COR': wherein R' is a hydrocarbyl or heteroaryl radical having up to 20 carbon atoms;
- n is an integer in the range of 0-4 where Ar is phenyl; 0-6 where Ar is naphthyl; and 0-8 where Ar is phenanthryl or anthracenyl;
- each R.sub.1 and R.sub.2 is independently selected from alkyl, aryl, aralkyl, alkaryl or cycloaliphatic radicals, or substituted derivatives thereof wherein substituted derivatives include ethers, amines, amides, sulfonic acids, esters, hydroxyl groups and alkoxy groups;
- each R.sub.3 and R.sub.4 is independently selected from hydrogen and the R.sub.1 substituents;
- each of the above alkyl groups or moieties is straight or branched chain of 1-20 carbon atoms;
- each aryl group contains 4-20 ring carbon atoms; and
- each cycloaliphatic group contains from 4-8 ring carbons; ##STR21## wherein Ar, x, y, R, n, R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are each as defined above, and each of z and z' can independently vary between 0 and 4, with the proviso that z+z' is at least 2; ##STR22## wherein R, R.sub.1 and R.sub.2 are as defined above; and ##STR23## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined above; and m is a whole number which can vary from 4 up to 8;
- as well as mixtures of any two or more thereof; wherein the amount of ligand is in the range of about 0.5 up to 20 moles per gram atom of nickel; and
- (III) at least one reducing metal selected from the group consisting of zinc, magnesium and manganese; wherein the molar ratio of reducing metal to reactant monohalide falls in the range of about 0.01 up to 20:1;
- wherein said contacting is carried out in the presence of a polar, aprotic solvent at a temperature in the range of 0.degree. up to 250.degree. C. for a time sufficient to form said biaryl or heterobiaryl compounds.
- 2. The method in accordance with claim 1 wherein said bidentate ligand has the structural formula: ##STR24## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and n are as defined above.
- 3. The method in accordance with claim 2 wherein said bidentate ligand is selected from the group consisting of:
- 2,2'-bis(diphenylphosphinomethyl)-1,1'-biphenyl;
- 2,2'-bis(dibenzylphosphinomethyl)-1,1'-biphenyl;
- 2,2'-phenylbenzylphosphinomethyl)-1,1'-biphenyl; and
- 2. 2'-bis(diisobutylphosphinomethyl)-1,1'-biphenyl.
- 4. The method in accordance with claim 1 wherein said bidentate ligand has the structural formula: ##STR25## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, x and y are as defined above.
- 5. The method in accordance with claim 4 wherein said bidentate ligand is 2-(diphenylphosphinomethyl)-1-[2-(diphenylphosphinomethyl)phenyl]-naphthalene.
- 6. The method in accordance with claim 1 wherein said bidentate ligand has the structural formula: ##STR26## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, x and y are as defined above.
- 7. The method in accordance with claim 6 wherein said bidentate ligand is 2,2'-bis(diphenylphosphinomethyl)-1,1'-binaphthyl.
- 8. The method in accordance with claim 1 wherein said bidentate ligand has the structural formula: ##STR27## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and n are as defined above.
- 9. The method in accordance with claim 8 wherein said bidentate ligand is .alpha.,.alpha.'-bis(diphenylphosphino)ortho-xylene.
- 10. The method in accordance with claim 1 wherein said bidentate ligand has the structural formula: ##STR28## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and n are as defined above.
- 11. The method in accordance with claim 10 wherein said bidentate ligand is .alpha.,.beta.'-bis(diphenylphosphino)-2-ethyltoluene.
- 12. The method in accordance with claim 1 wherein said bidentate ligand has the structural formula: ##STR29## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and n are as defined above.
- 13. The method in accordance with claim 12 wherein said bidentate ligand is 1,2-bis[2-(diphenylphosphino)ethyl]benzene.
- 14. The method in accordance with claim 1 wherein said bidentate ligand is 1,1'-bis(diphenylphosphino)ferrocene.
- 15. The method in accordance with claim 1 wherein said bidentate ligand has the structural formula: ##STR30## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 are as defined above; and wherein m is a whole number which can vary from 4 up to 8.
- 16. The method in accordance with claim 15 wherein said bidentate ligand is selected from the group consisting of:
- 1,4-bis(diphenylphosphino)butane,
- 1,5-bis(diphenylphosphino)pentane,
- 1,6-bis(diphenylphosphino)hexane,
- as well as mixtures of two or more thereof.
- 17. The method in accordance with claim 1 wherein said catalytic combination further comprises at least one bidentate ligand containing at least one nitrogen atom as part of an aromatic ring structure.
- 18. The method in accordance with claim 17 wherein said bidentate ligand containing at least one nitrogen atom is selected from 2,2'-bipyridine, a C.sub.1 up to C.sub.6 dialkylamino pyridine, phenanthroline or 2-picolinic acid.
- 19. The method in accordance with claim 1 wherein said reducing metal is zinc.
- 20. The method in accordance with claim 1 wherein the nickel compound is nickel chloride.
- 21. The method in accordance with claim 1 wherein at least 0.1 moles per gram atom of nickel of an inorganic salt is added as a promoter.
- 22. The method in accordance with claim 21 wherein the inorganic salt is selected from the group consisting of: an alkali metal iodide, an alkali metal bromide, an alkali metal chloride, as well as mixtures of any two or more thereof.
- 23. The method in accordance with claim 1 wherein the aprotic solvent is N,N-dimethylacetamide.
- 24. The method in accordance with claim 1 wherein the aprotic solvent is N,N-dimethylformamide.
- 25. The method in accordance with claim 1 wherein the aprotic solvent is 1-methyl-2-pyrrolidinone.
- 26. The method in accordance with claim 1 wherein the monohalide has the formula: ##STR31## wherein one or more of the carbon atoms of the benzene ring in formula (I) is optionally replaced by N;
- wherein X is a halogen selected from the group consisting of Cl, Br and I;
- R is a monovalent radical selected from alkyl, aryl, --F, --NR'.sub.2, --CN, --CHO, --OR', --OCO--R', --COO--R', ##STR32## --SO.sub.2 --R', --SO.sub.3 --R', or --NR'COR': wherein R' is a hydrocarbyl or heteroaryl radical having up to 20 carbon atoms, and x is an integer having values of 0 to 4 with the proviso that no more than one R is in a position ortho to the X-containing ring carbon atom.
- 27. The method according to claim 26 wherein X is Cl.
- 28. The method according to claim 27 wherein said monohalide is selected from the group consisting of:
- 2-chlorotoluene,
- 2-chloropyridine,
- 4-fluoro-2-chlorotoluene,
- 2-chlorobenzyl methyl ether,
- 2-chlorobenzyl ethyl ether,
- 4-(N-ethyl-N-acetyl)-2-chlorotoluene,
- 6-(N-ethyl-N-acetyl)-2-chlorotoluene,
- 4-chlorotoluene,
- 4-chloroanisole,
- 2-chlorobenzyl(2-methoxy)ethyl ether,
- as well as mixtures of any two or more thereof.
- 29. A method as claimed in claim 26 wherein R is methyl and x is 1.
- 30. A method as claimed in claim 1 wherein the temperature is from about 25.degree. C. to about 120.degree. C.
- 31. The method in accordance with claim 30 wherein the ratio of gram atoms of nickel to moles of monohalide falls in the range of about 0.01 up to 0.2:1; the amount of bidentate phosphorus-containing ligand falls in the range of about 1 up to 10 moles per gram atom of nickel; and the molar ratio of reducing metal to reactant monohalide falls in the range of about 0.2 up to 10:1.
- 32. The method in accordance with claim 30 wherein the ratio of gram atoms of nickel to moles of monohalide falls in the range of about 0.03 up to 0.1:1; the amount of bidentate phosphorus-containing ligand falls in the range of about 1 up to 5 moles per gram atom of nickel; and the molar ratio of reducing metal to reactant monohalide falls in the range of about 0.4 up to 5:1.
BACKGROUND OF THE INVENTION
This application is a continuation-in-part of Ser. No. 227,826, filed November 30, 1988, now abandoned.
The present invention relates to the preparation of biaryl compounds from aryl halides. In a particular aspect, the present invention relates to the reductive coupling of aryl halides.
It is known that biphenyl compounds can be produced by the reductive coupling of aryl halides. For example, Chao, et al., in the Journal of Organic Chemistry, Volume 48, at pages 4904-4907 (1983), disclose the reaction of aryl halides with an equivalent amount of a highly activated metal such as nickel powder.
An alternative approach is to activate an aryl halide by a chemical transformation, and then allow the activated aryl halides to couple to form biaryl species. For example, Gilman, et al., in the Journal of the American Chemical Society, Volume 61, at pages 957-959 (1939), demonstrated this approach by the reaction of two equivalents of aryl Grignard reagents with one equivalent of nickel(II) salts to give biaryl compounds. This reaction is believed to proceed through the bis(aryl)nickel(0) species which then decomposes to give the desired biaryl product.
Kumada, et al., in Bulletin of the Chemical Society of Japan, Volume 49, at pages 1958-1969 (1976), have demonstrated that aryl halides can be reacted with a variety of aliphatic Grignard reagents to give alka-aryl products. However, attempts to couple aryl Grignard reagents with aryl halides were successful only with aryl bromides. Attempts to use aryl chlorides gave less than a ten percent yield of desired biaryl products.
Aryl chlorides are frequently more readily available than are the corresponding bromides and iodides. The chlorides are also typically less reactive and are less expensive materials as well. It would, therefore, be desirable to find a means to promote the coupling of aryl chlorides to produce high yields of biaryl compounds.
Such coupling of aryl chlorides has been disclosed by Colon, et al., in U.S. Pat. No. 4,263,466. The authors disclose the use of a metallic reducing agent such as zinc, magnesium, or manganese in a dipolar, aprotic solvent such as dimethylformamide with a catalyst containing a nickel compound in combination with triaryl organphosphines and alkali metal halide promoters. The reducing metal converts the nickel salts into highly reactive zerovalent nickel compounds which promote the coupling of the aryl halides and regenerate the nickel salts which can be reduced again to the zerovalent state, thereby maintaining the catalytic cycle.
In later publications by the same authors (see Colon, et al., in Journal of Organic Chemistry, Vol. 51 at pages 2627-2637 (1986), it is indicated that bidentate ligands (as opposed to the monodentate triaryl organophosphines disclosed in '466) are not effective for the nickel/reducing metal-promoted reductive coupling reaction. Takagi, et al., in the Bulletin of the Chemical Society of Japan, at pages 1887-1890 (1984) have made similar observations. See especially Run Number 14 reported at page 1888.
In accordance with the present invention, it has surprisingly been found that aryl chlorides can be reductively coupled employing bidentate ligands to produce biaryl compounds in high yield. By contacting aryl halides with a catalyst comprising a nickel compound, at least one bidentate phosphorus-containing ligand selected from a specified group and a reducing metal, high yields of biaryl compounds are obtained.
The practice of the present invention allows for the ready preparation of biaryl derivatives from aryl chloride starting materials. Aryl chlorides are generally preferred starting materials as they are more accessible on a commercial basis and are generally less expensive than the corresponding aryl bromides or aryl iodides.
In accordance with the present invention, there is provided a method for the preparation of biaryl compounds of the structure: ##STR1## wherein Ar is an aromatic moiety having in the range of 4 up to 20 carbon atoms, each R is independently selected from alkyl, aryl, --F, --NR'.sub.2, --CN, --CHO, --OR', --OCO--R', --COO--R', ##STR2## --SO.sub.2 --R', --SO.sub.3 R', or --NR'COR': wherein R' is a hydrocarbyl or heteroaryl radical having up to 20 carbon atoms, and x is an integer falling in the range of 0 up to 8, depending on the size of the aromatic ring, Ar, and with the proviso that there be no more than one substituent ortho to the Ar--Ar bond.
The invention method comprises contacting an aromatic halide having the structure: ##STR3## wherein Ar, R and x are as defined above and X is a halogen; under conditions suitable for the formation of the desired biaryl compound in the presence of at least 0.001 equivalents of a nickel catalyst comprising:
Reaction temperatures employed in the practice of the present invention can vary widely. Typically, reaction temperatures fall in the range of about 0.degree. up to 250.degree. C., with reaction temperatures in the range of about 25.degree. up to 120.degree. C. being preferred.
Reaction times contemplated for the practice of the present invention can vary widely. One of skill in the art can readily determine that amount of time which is sufficient to allow formation of the desired biaryl or heterobiaryl compounds. Typically, reaction times will fall in the range of about 0.1 up to 24 hours or longer, with reaction times in the range of about 0.5 up to 16 hours being preferred.
Aryl halides contemplated for use in the practice of the present invention are compounds have the general structure: ##STR9## wherein Ar is an aromatic moiety having in the range of 4 up to 20 carbon atoms, each R is independently selected from alkyl, aryl, --F, --NR'.sub.2, --CN, --CHO, --OR', --OCO--R', ##STR10## --SO.sub.2 R', SO.sub.3 R', or NR'COR': wherein R' is a hydrocarbyl or heteroaryl radical having up to 20 carbon atoms; X is a halogen and x is an integer falling in the range of 0 up to 8, depending on the size of the aromatic ring, Ar, and with the further proviso that there be no more than one substituent ortho to the halogen moiety. Exemplary aryl halides contemplated for use in the practice of the present invention include:
Presently preferred monohalides contemplated for use in the practice of the present invention include compounds having the structural formula: ##STR11## wherein one or more of the carbon atoms of the benzene ring in formula (I) is optionally replaced by N;
Additional compounds contemplated by the above structural formula are those wherein one or more of the carbon atoms of the benzene ring is replaced by N. Especially preferred compounds contemplated by the above formula are those wherein X is Cl.
Examples of preferred monohalides which satisfy structural formula (I) include:
A wide range of nickel compounds are suitable for use in the practice of the present invention, so long as the nickel compounds employed are essentially water-free. The nickel(II) halide salts are a convenient source of nickel as such compounds are readily available in anhydrous form. Alternatively, hydrates of such compounds can be employed if an appropriate means of water removal, e.g., azeotropic distillation, is employed prior to contacting the nickel species with the reducing metal and aryl halide. Those of skill in the art recognize that a wide variety of nickel compounds can be used in addition to the nickel(II) halides, e.g., nickel nitrates, sulfates, phosphates, oxides, carbonates, carboxylates, acetylacetonate and the like, as well as Ni(O) complexes such as, for example, bis(1,5-cyclooctadienyl)nickel(O), nickel(O) tetracarbonyl, and the like.
The nickel(II) halides are presently preferred because of their ready availability in anhydrous form (or, alternatively, the ease with which the hydrates forms such compounds can be dehydrated), and because the presence of halides in the reaction mixture appears to promote the coupling reaction. Especially preferred are nickel chloride and nickel bromide.
Suitable ratios of nickel to aryl halides can vary widely. Molar ratios in the range of 0.0001 up to 0.5:1 are generally suitable. Ratios in the range of about 0.01 up to 0.2:1 are preferred, with molar ratios in the range of about 0.03 up to 0.1 being most preferred because good conversions are obtained at reasonable reaction rates.
Optionally added to the catalyst composition are inorganic salt promoters. When used, preferred promoters include alkali, alkaline earth, zinc, magnesium, manganese and aluminum halides, or mixtures thereof. Bromides are particularly preferred. The amount of promoter, when used, can range from about 0.1 to about 1000 moles per gram atom of nickel with about 1 to about 100 moles of promoter being preferred.
The presently most preferred promoters include alkali metal iodides, alkali metal bromides and alkali metal chlorides.
Organophosphines contemplated for use in the practice of the present invention are compounds having the structures set forth above as (i), (ii), (iii), or (iv).
Exemplary compounds contemplated by structure (i) include compounds having the structural formula: ##STR13##
wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, and n are as defined above; including such compounds as
Exemplary compounds contemplated by structure (i) also include compounds having the structural formula: ##STR14## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, x and y are defined above; such as, for example
Exemplary compounds contemplated by structure (i) also include compounds having the structural formula: ##STR15## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4, x and y are as defined above; such as, for example
Exemplary compounds contemplated by structure (ii) include compounds having the structural formula: ##STR16## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and n are as defined above; such as, for example
Exemplary compounds contemplated by structure (ii) also include compounds having the structural formula: ##STR17## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and n are as defined above; such as, for example
Exemplary compounds contemplated by structure (ii) also include compounds having ##STR18## wherein R, R.sub.1, R.sub.2, R.sub.3, R.sub.4 and n are as defined above; such as, for example
Exemplary compounds contemplated by structure (iii) include: 1,1'-bis(diphenylphosphino)ferrocene, and the like.
Exemplary compounds contemplated by structure (iv) include:
The molar ratio of organophosphine to nickel compound employed in the practice of the present invention can vary widely. Typically, such molar ratio will fall within the range of 0.5:1 up to 20:1, with ratios in the range of 1:1 up to 10:1 preferred. Ratios in the range of about 1:1 up to 3:1 are presently most preferred because little added benefit is seen in the use of large excesses of organophosphine(s).
Optional coordinating ligands employed in combination with the above-described bidentate organophosphines are bidentate ligands containing at least one nitrogen atom as part of an aromatic ring structure. Such bidentate ligands include bipyridine, a C.sub.1 up to C.sub.6 dialkylamino pyridine, phenanthroline or 2-picolinic acid, and the like.
When the optional use of mixtures of bidentate organophosphine and bidentate ligand containing at least one nitrogen atom as part of an aromatic ring structure are employed as the coordinating ligand, molar ratios of the bidentate organophosphine to the bidentate ligand containing at least one nitrogen atom as part of an aromatic ring structure can vary widely, for example, in the range of about 0.1:1 up to 20:1, with ratios in the range of 0.5 up to 10 preferred. Ratios in the range of about 1:1 up to 2:1 are presently most preferred because little added benefit is observed when large excesses of the bidentate ligand containing at least one nitrogen atom as part of an aromatic ring structure are employed.
Solvents suitable for use in the practice of the present invention include dipolar, aprotic solvents such as solvents, such as N,N-dimethylacetamide, N,N-dimethylformamide, 1-methyl-2-pyrrolidinone, tetramethylurea, dimethylsulfoxide, sulfolane, and the like. If desired these dipolar, aprotic solvents can be mixed with lower polarity inert solvents, such as saturated aliphatic hydrocarbons, including pentanes, hexanes, dodecanes and the like; aromatic hydrocarbons, such as benzene, toluene, xylenes and the like; and saturated aliphatic and cycloaliphatic ethers, such as, diethyl ether, diglyme, tetrahydrofuran and the like.
It is preferred that all solvents use in the practice of this invention be anhydrous.
Although magnesium and manganese metals can be used, zinc metal is the presently preferred reducing metal for use in the invention process for coupling aryl monochlorides.
The molar ratio of reducing metal to aryl halide employed in the practice of the present invention can vary widely. Typically, such molar ratio will fall within the range of about 0.01:1 up to 20:1, with ratios in the range of about 0.2:1 up to 10:1 preferred. Ratios in the range of about 0.4:1 up to 5:1 are presently most preferred because it is desired to minimize the quantity of reducing metal which must be removed from the reaction mixture and little added benefit is obtained when large excesses of reducing metal are employed.
The molar ratio of reducing metal to nickel employed in the practice of the present invention can vary widely. Typically, such molar ratios will fall within the range of about 1 up to 1000:1, with ratios in the range of about 10 up to 500:1 being preferred. Ratios in the range of about 40 up to 100:1 are presently preferred for the same reasons as stated in the preceding paragraph.
Preparation of the novel catalyst composition is carried out conveniently by mixing the aforementioned nickel compound, ligand(s), promoter, and reducing metal(s) in the dipolar, aprotic solvent under an inert atmosphere and heating to a temperature in the range of about 25.degree. to about 80.degree. C.
The present invention will now be described in greater detail by reference to the following non-limiting examples.
US Referenced Citations (1)
| Number |
Name |
Date |
Kind |
|
4263466 |
Colon et al. |
Apr 1981 |
|
Non-Patent Literature Citations (2)
| Entry |
| "Nickel-Phosphine Complex Catalyzed Homocoupling of Aryl Halides in the Presence of Zinc Copper", Zembayashi et al., Tet. Lett. 47: 4089-4092 (1977). |
| "Coupling of Aryl Chlorides by Nickel and Reducing Metals", Colon et al., J. Org. Chem. 51: 2627-2637 (1986). |
Patent Grant
4916227
