Organic compounds -- part of the class 532-570 series – Organic compounds – Nitriles
Reexamination Certificate
1997-04-08
2001-02-27
Ambrose, Michael G. (Department: 1613)
Organic compounds -- part of the class 532-570 series
Organic compounds
Nitriles
C546S311000, C546S348000, C548S560000, C549S080000, C549S506000, C560S102000, C568S323000, C585S025000
Reexamination Certificate
active
06194599
ABSTRACT:
FIELD OF THE INVENTION
This invention relates generally to preparing biaryl compounds by arylaryl coupling reactions. More specifically, it relates to preparing biaryl compounds by reacting an arylmetal reagent with an aryl halide. It further relates to preparing biaryl compounds by reacting an arylmetal reagent with an arylchloride and to preparing biaryl compounds by reacting an arylzinc reagent with an aryl halide. Biaryl compounds are valuable as fine chemicals for liquid crystals and related applications and as precursors to pharmaceutically active compounds. In particular, 2-(4′-methylphenyl)benzonitrile (also known as 4-methyl-2′-cyanobiphenyl) can be used as an intermediate in the preparation of various angiotensin II antagonists.
BACKGROUND OF THE INVENTION
The following references give reviews of methods of preparing biaryl compounds: Sainsbury,
Tetrahedron,
vol. 36 (1980), pp. 3327-3359 and Bringman et al.,
Angew. Chem. Int. Ed. Engl.,
vol. 29, (1990), 977-991.
In the Meyers oxazoline method to make unsymmetrical biaryl 2-carboxylic acid derivatives, disclosed in Meyers et al,
J. Org. Chem.,
vol. 43 (1978), pp. 1372-1379, the carboxyl group in 2-methoxybenzoic acids is converted into an oxazoline to activate the 2-methoxy group for nucleophilic substitution by arylmagnesium halide or aryllithium reagent and to protect the carboxyl group in a form that is not subject to nucleophilic attack by the aryl carbanion species.
Carini et al.,
J. Med. Chem.,
vol. 34 (1991), 2525-2547 disclose the application of the Meyers oxazoline method to the preparation of 2-(4′-methylphenyl)benzonitrile by the following steps: 1) 2-methoxybenzoic acid is reacted with thionyl chloride; 2) the acyl chloride formed is treated with 2-amino-2-methyl-1-propanol, which provides an amide in the crude form; 3) this amide is subjected to the action of thionyl chloride, forming 4,4-dimethyl-2-(2-methoxyphenyl)-oxazoline (yield 88% from the acid chloride); 4) this oxazoline derivative is reacted with p-tolyl-magnesium bromide and the complex formed is hydrolyzed, which gives 4,4-dimethyl-2-(4′-methylbiphenyl-2′-yl)-oxazoline (yield 91%); and 5) the oxazoline derivative formed is then treated with phosphorus oxychloride, which finally provides 2-(4′-methylphenyl)benzonitrile (yield 96%). The overall yield is 77% but this process has the disadvantage of requiring the use of 5 steps, starting from commercially available products, due to the prior formation of the dimethyloxazolinyl group and its subsequent conversion to the cyano group. U.S. Pat. No. 5,128,355 (to Carini et al.) similarly exemplifies the application of the multistep Meyers oxazoline method to the preparation of 2-(4′-methylphenyl)benzoic acid (example 85), and the conversion of this benzoic acid to the benzonitrile Example 89). Implicitly, these references illustrate that when an aryl magnesium reagent (in this case, p-tolyl magnesium bromide) is used directly to provide the aryl group in an arylbenzonitrile (in this case, 2-(4′-methyl-phenyl)benzonitrile) the nitrile group cannot be present in the substrate that is treated with the aryl magnesium reagent. It must be in a protected precursor form during the coupling process (in this case, as the dimethyloxazolinyl group).
Tamao et al.,
Bull. Chem. Soc. Japan,
vol. 49 (1976), pp. 1958-1969, discloses that arylbromides can be reacted with arylmagnesium halides (aryl Grignard reagents) in the presence of dihalodiphophinenickel complexes to give biaryl compounds. A sole disclosed attempt to react an aryl chloride (chlorobenzene) with an arylmagnesium halide (mesityl) was reported to give only a 6% yield of the desired biaryl. Similar reactions of the bromobenzene with mesitylmagnesium bromide gave yields of 78-96%. This reference states, “The most serious limitation is that the substituents on the organic halides and on the Grignard reagents are restricted to those which cannot react with Grignard reagents.”
In a review article titled “Transformations of Chloroarenes, Catalyzed by Transition-Metal Complexes”,
Chem. Rev.,
vol 94 (1994), pp. 1047-1062, Grushin et al. state, “Unfortunately, the most reactive iodo- and bromoarenes are the most expensive ones, whereas aryl fluorides are both costly and unreactive. Chloroarenes are certainly the most attractive aryl halides for synthetic applications on an industrial scale, because they are inexpensive and readily available in bulk quantities. The main drawback here is the exceedingly high stability of the aromatic carbon-chlorine bond whose inertness remains the major obstacle on the way to wide utilization of chloroarenes.”
Clough et al.,
J. Org. Chem.,
vol. 41 (1976), pp. 2252-2255 discloses that 1,8-dihalonapthalenes can be reacted with arylmagnesium halides in the presence of certain soluble nickel catalysts to give 1,8-diarylnaphthalenes. The reactivities of the 1,8-dihalonaphthalenes in this system was found to be I>Br>>Cl.
U.S. Pat. No. 4,912,276 discloses that aryl chlorides can be reacted with arylmagnesium halides in the presence of a nickel-triorganophosphine catalyst to give biaryl compounds. The disclosed scope of the aryl groups in the arylchlorides, the arylmagnesium reagents, and the biaryl compounds consists of phenyl and substituted phenyl with hydrocarbyl or hydrocarbyloxy substituents or protected carbonyl-containing derivatives thereof. These are all substituents that are unreactive to arylmagnesium halides. The only biaryl whose preparation is exemplified by working examples is the symmetrical biaryl 2,2′dimethylbiphenyl, prepared from 2-chlorotoluene and o-tolylmagnesium chloride (derived from 2-chlorotoluene).
Pridgen,
J. Org. Chem.,
vol. 47 (1982), pp. 4319-4323 discloses two examples in which 2-(chlorophenyl)-2-oxazolines are reacted with arylmagnesium halides in the presence of a diphosphine-chelated nickel catalyst to give the corresponding 2-(biaryl)-2-oxazoline compounds. The oxazoline group activates the aryl chloride and provides a form of the carboxyl group that is protected from reaction with the arylmagnesium halide.
U.S. Pat. No. 5,288,895 discloses a process for the preparation of 4-methyl-2′-cyanobiphenyl (a.k.a. 2-(4′-methylphenyl)benzonitrile) wherein a 2-halobenzonitrile is reacted with a 4-methylphenyl magnesium halide in the presence of manganous salt. The Examples of this patent, which describe reactions of 2-chlorobenzonitrile, report analyzed chemical yields of 60-75% of 2-(4′-methylphenyl)benzonitrile) in a recovered “brown viscous liquid”. Recrystallizations (plural) give the product as a beige solid, but the yields of these purified solids are not reported.
This patent also discloses tests showing that the direct reaction of 4-methylphenyl magnesium bromide with 2-chlorobenzonitrile, in the absence of manganese salt, “proves incapable of giving 4-methyl-2′-cyanobiphenyl”. Analysis showed unreacted 2-chlorobenzonitrile and the addition product of the reagent to the nitrile group, 2-chloro-1-phenyl(4-tolyl)ketone, but no trace of 2-(4′-methylphenyl)benzonitrile.
This patent also discloses attempted reactions of several equivalents of 4-methylphenyl magnesium bromide with 1 equivalent of 2-bromobenzonitrile and 0.3 equivalents of either PdCl
2
or NiCl
2
in tetrahydrofuran at 0° C. Yields of 22% and 27%, respectively, of 2-(4′-methylphenyl)benzonitrile were analyzed in recovered crude residue. Similar reactions with 0.003 equivalents tetrakis(triphenylphosphine)palladium(0) at 0 and 65° C. gave only a 1% yield in the residue.
Negishi et al,
J. Org. Chem.,
vol. 42 (1977), pp. 1821-1823 discloses reactions of arylzinc derivatives (arylzinc chloride or diarylzinc) with aryl bromides or iodides in the presence of nickel or palladium complexes as catalysts to produce unsymmetrical biaryls. The arylzinc derivatives were prepared by a metathesis reaction between the corresponding aryllithium and zinc dichloride. The reference does not report any attempt to react an arylzinc derivative with
Farrell Robert P.
Miller Joseph A.
Ambrose Michael G.
Catalytica Inc.
Grate John H.
Iecminek Al A.
LandOfFree
Process for preparing biaryl compounds does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for preparing biaryl compounds, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for preparing biaryl compounds will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2614688