WO2001044147A1

WO2001044147A1 - Process for the preparation of 2-methylbiphenyl and of 2-phenylbenzyl bromide

Info

Publication number: WO2001044147A1
Application number: PCT/US2000/033686
Authority: WO
Inventors: Ronny W. Lin
Original assignee: Albemarle Corporation
Priority date: 1999-12-14
Filing date: 2000-12-12
Publication date: 2001-06-21

Abstract

An o-tolylmagnesium Grignard reagent, and chlorobenzene are brought together in a liquid medium comprised predominately of tetrahydrofuran and/or liquid alkyl-substituted tetrahydrofuran to which is added a triarylphosphine, and an anhydrous nickel(II) halide in which the halogen atom has an atomic number above 9. 2-Methylbiphenyl is produced. This can be selectively brominated on the methyl side chain to produce 2-phenylbenzyl bromide, an important starting material for the preparation of 7-phenyl-2-methylindene, or other indene derivatives. These in turn are useful in the preparation of metallocene olefin polymerization catalysts.

Description

NOVEL CROSS-COUPLING REACTION AND USE THEREOF

BACKGROUND

Nickel-phosphine catalyzed cross-coupling reactions between Grignard reagents and aryl halides were first reported in 1972 by Corriu et al., J. Chem. Soc, Chem. Comnn ., 1972, 144; and

Tamao et al, J. Am. Chem. Soc, 1972, 94, 4374. Subsequent papers on such reactions include Tamao et al., J. Chem. Soc. Jpn., 1976, 49, 1958; Negishi et al., J. Org. Chem., 1977, 1821 , Ibuki et al., Bull. Chem. Soc. Jpn., 1980, 53, 821 ; and Ikoma et al., Synthesis, 1990, 147.

In Synthesis, 1990, 147, Ikoma et al., report results on reactions in tetrahydrofuran between aryl Grignard reagents and aryl halides in the presence of non-ligated nickel(II) chloride as well as reactions conducted in the presence of other catalysts including certain nickel-phosphine catalysts. Their results indicate that the highest yields were obtained when reacting bromobenzene or chlorobenzene with an aryl Grignard reagent having a methyl group in the ortho-pos\ on using non- ligated NiCl₂ as the catalyst.

In their 1976 paper, Tamao et al. (J. Chem. Soc. Jpn., 1976, 49, 1958) indicate on the basis of reactions conducted in diethyl ether that bromobenzene is more reactive than chlorobenzene in reactions catalyzed by nickel-phosphine catalyst systems.

THE INVENTION

It has been found, surprisingly, that if the reaction between chlorobenzene and an o- tolylmagnesium Grignard reagent is carried out in tetrahydrofuran (THF) to which is added triphenylphosphine and anhydrous nickel(II) bromide, the yield and purity of 2-methylbiphenyl were higher than when the same Grignard reagent is reacted with the more highly reactive bromobenzene in THF to which was added non-ligated anhydrous nickel(II) bromide.

Pursuant to this invention (a) an o-tolylmagnesium Grignard reagent, and (b) chlorobenzene are mixed together in a liquid medium comprised predominately (>50% by volume, exclusive of the chlorobenzene) of tetrahydrofuran and/or at least one liquid alkyl-substituted tetrahydrofuran to which is added (c) a triarylphosphine, and (d) an anhydrous nickel(II) halide in which the halogen atom has an atomic number above 9, such that 2-methylbiphenyl is produced. It is possible to form a reaction mass having a normalized GC area % of at least 95% 2-methylbiphenyl.

In this process (a) is preferably o-tolylmagnesium chloride or bromide, and most preferably is the chloride. Any liquid alkyl-substituted tetrahydrofuran or mixture thereof with or without THF itself can be used as the liquid medium. Also minor amounts (<50 % by volume) of other liquid ether or hydrocarbon solvents can be present in the liquid medium. Preferably, however, the liquid medium is comprised of >90% by volume of tetrahydrofuran (exclusive of the chlorobenzene) The triaryl phosphine, (c), can contain up to 36 carbon atoms or more in the molecule as phenyl, naphthyl, biphenylyl, dihydronaphthyl, tetrahydronaphthyl, or related aryl groups, including alkyl- and/or cycloalkyl-substituted derivatives thereof Preferred is triphenyl phosphine Of the nickel halides, (d) is preferably NiCl₂ or NiBr₂, with the latter being most preferred

In a preferred embodiment, the process is conducted by adding (i) a solution of (a) in a liquid medium comprised predominately of tetrahydrofuran and/or at least one liquid alkyl-substituted tetrahydrofuran, to (ii) a mixture formed from (b), (c), (d), and a liquid medium comprised predominately of tetrahydrofuran and/or at least one liquid alkyl-substituted tetrahydrofuran Reactants (a) and (b) are proportioned such that the mole ratio of (a) (b) is 0 1-1 1, and preferably 0.2-0.8 1 The mole ratio of (c) (d) is typically 1 - 12 1 , and preferably 2-6 1 The mole ratio of (d).(a) is typically 0 001-0 06 1, and preferably 0 005-0 03 1 The amount of the liquid medium is of little significance as long as there is a sufficient amount present to dissolve the reactants, (a) and (b), and to provide a readily-stirrable reaction mass This cross-coupling reaction is performed under the usual anhydrous Grignard reaction conditions Normally the reaction will be initiated at ambient room temperature (e g , 23-25 °C) with the reactants being brought together at a rate such that the temperature does not exceed 120°C Naturally, if the temperature exceeds the boiling temperature of the liquid medium, the reaction should be conducted under reflux. In another aspect of this invention, any of the embodiments of this invention such as each embodiment of claims 1 through 13 as filed is further characterized by selectively brominating the methyl group of at least a portion of the 2-methylbiphenyl produced pursuant to the particular embodiment. This results in the production of 2-phenylbenzyl bromide, an important starting material for the preparation of 7-phenyl-2-methylindene, or other indene derivatives These in turn are useful in the preparation of metallocene olefin polymerization catalysts The side chain bromination of 2- methylbiphenyl can be conducted in the presence of water and a free radical initiator as catalyst

Elemental bromine is the preferred bromine source for use in such side chain bromination of 2-methylbiphenyl. However, other known brominating agents can be used Examples include N- bromosuccinimide, l,3-dibromo-5,5-dimethylhydantoin, and pyridinium tribromide The amount of brominating agent used should not materially exceed the amount required to monobrominate the methyl side chain of the 2-methylbiphenyl Moderate reaction temperatures, e.g. , in the range of 50 to 150°C, will usually be employed in such side-chain bromination Any of a wide variety of free radical initiators can be used as catalyst for such side chain bromination Thus use can be made of well-known peroxide or hydroperoxide free radical catalysts, as well as other known types, such as percarbonates or persulfates The literature is replete with information about free radical catalysts and their use, and thus anyone who may be unfamiliar with such subject matter is referred to the literature on the subject See, for example, Kirk-Othmer, Encyclopedia of Chemical Technology, Third Edition, 1981, John Wiley & Sons, Inc , Volume 13, pages 356-370 A preferred free radical generator for use as the catalyst is 2,2'-azobisisobutyronitrile, often referred to as AIBN

In lieu of a free radical catalyst, the side chain bromination can be conducted thermally or photochemically, if desired If conducted thermally, temperatures in the range of 100 to 1 50° C can be used. If conducted photochemically, a light source of short wavelength should be used, such as a quartz mercury-vapor lamp

The following Examples are presented for purposes of illustration and not limitation

EXAMPLE 1 o-TolylMgCl (430 cc of 1 M in THF) was fed to a mixture of Ph,P (4 2 g), NiBr₂ anhydrous

(0.87 g), THF solvent (65 g) and chlorobenzene ( 135 g) for 4 hours The temperature increased from 25 °C to 40-48 °C due to the heat of reaction The reaction mass was then stirred at ambient temperature overnight A sample had normalized GC area%, 97% 2-methylbiphenyl, 1 3% biphenyl and 1.7% bi(2-methylphenyl) After workup with aqueous HC1 (approx 1 7 wt%, 210 g) and washing with water (200 g), the organic phase (518 5 g) was heated up to 160 ° C to strip off solvent and residual water (405 g) The product was vacuum-stripped, yielding 95 9 g of product which had 23.7 GC area% chlorobenzene, 1 00% biphenyl, 70 46% 2-methylbiphenyl and 1 24% bι(2- methylphenyl).

COMPARATIVE EXAMPLE

For comparison with the "high yield" recipe of Ikoma et al., loc. cit , o-tolylMgCl (400 cc of

1 M in THF) was coupled with bromobenzene (78 5 g) and as per the recipe, no ligand (e.g., Ph₃P) was used. The same molar amount of NiBr₂ (0 9 g) was used instead of NiCl₂, to enable direct comparison with Example 1 The reaction mass had 5 4 normalized GC area% biphenyl, 88 1% 2- methylbiphenyl and 6 5% bi(2-methylphenyl)

EXAMPLE 2 A portion (49 g) of the 2-methylbiphenyl cut produced in Example 1, water (20 g) and AIBN (0.5g) were stirred and heated up to 70°C Bromine (32 g) was fed dropwise and the temperature was allowed to increase up to 80 °C After 40 minutes, more AIBN (0 2 g) was added and the remaining Br₂ was fed with the reaction mass at 82-87° C The total feed time was 1 8 hours The reaction mass was further stirred at 87 °C for 20 minutes Concentrated aqueous HBr solution was separated and the organic phase was washed 3 times with water (70 cc each time) The organic phase (63 g) had 79 4 normalized NMR mole % 2-phenylbenzyl bromide, 16 9% 2-methylbiphenyl, 3 7% 2-phenylbenzal bromide (and no detectable quantity of 2-phenylbenzaldehyde)

Compounds referred to by chemical name or formula anywhere in this document, whether referred to in the singular or plural, are identified as they exist prior to coming into contact with another substance referred to by chemical name or chemical type (e.g., another component or a solvent). It matters not what preliminary chemical changes, if any, take place in the resulting mixture or solution, as such changes are the natural result of bringing the specified substances together under the conditions called for pursuant to this disclosure Also, even though the claims may refer to substances in the present tense (e.g., "comprises" or "is"), the reference is to the substance as it exists at the time just before it is first contacted, blended or mixed with one or more other substances in accordance with the present disclosure

Except as may be expressly otherwise indicated, the article "a" or "an" if and as used herein is not intended to limit, and should not be construed as limiting, a claim to a single element to which the article refers Rather, the article "a" or "an" if and as used herein is intended to cover one or more such elements, unless the text expressly indicates otherwise

Claims

1. A process which comprises mixing together an o-tolylmagnesium Grignard reagent, and (b) chlorobenzene in a liquid medium comprised predominately of tetrahydrofuran and/ or at least one liquid alkyl-substituted tetrahydrofuran to which is added (c) a triarylphosphine, and (d) an anhydrous nickel(II) halide in which the halogen atom has an atomic number above 9, such that 2- methylbiphenyl is produced.

2. A process according to Claim 1 wherein (a) is o-tolylmagnesium chloride or o- tolylmagnesium bromide or both.

3. A process according to Claim 1 wherein the liquid medium consists essentially of tetrahydrofuran.

4. A process according to Claim 1 wherein (c) is triphenylphosphine.

5. A process according to Claim 1 wherein (d) is nickel(II) bromide or nickel(II) chloride, or both.

6. A process according to Claim 1 wherein (a) is o-tolylmagnesium chloride, wherein the liquid medium consists essentially of tetrahydrofuran, wherein (c) is triphenylphosphine, and wherein

(d) is nickel(II) bromide or nickel(II) chloride, or both.

7. A process according to Claim 1 wherein the process is conducted by adding (i) a solution of (a) in a liquid medium comprised predominately of tetrahydrofuran and/or at least one liquid alkyl-substituted tetrahydrofuran, to (ii) a mixture formed from (b), (c), (d), and a liquid medium comprised predominately of tetrahydrofuran and/or at least one liquid alkyl-substituted tetrahydrofuran.

8. A process according to Claim 7 wherein (a) is o-tolylmagnesium chloride or o- tolylmagnesium bromide or both.

9. A process according to Claim 7 wherein (c) is triphenylphosphine.

10. A process according to Claim 7 wherein (d) is nickel(II) bromide or nickel(II) chloride, or both.

11. A process according to Claim 7 wherein the liquid medium in (i) and in (ii) consists essentially of tetrahydrofuran.

12. A process according to Claim 7 wherein (a) is o-tolylmagnesium chloride, wherein the liquid medium consists essentially of tetrahydrofuran, wherein (c) is triphenylphosphine, and wherein

(d) is nickel(II) bromide or nickel(II) chloride, or both.

13. A process according to any of Claims 1 , 6, 7, or 12 wherein the components are proportioned such that the mole ratio of (a) (b) is 0 1 - 1 1 , the mole ratio of (c) (d) is 1 - 12 1 , and the mole ratio of (d):(a) is 0 001-0.06 1

14. A process according to any of Claims 1, 6, 7, or 12 wherein the components are proportioned such that the mole ratio of (a) (b) is 0 2-0.8: 1, the mole ratio of (c):(d) is 2-6 1 , and the mole ratio of (d):(a) is 0 005-0 03 : 1

15. A process according to any of Claims 1. 6, 7, or 12 further comprising brominating at least a portion of the 2-methylbiphenyl such that 2-phenylbenzyl bromide is produced