Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
1999-11-01
2001-02-06
Geist, Gary (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C562S605000
Reexamination Certificate
active
06184415
ABSTRACT:
This invention relates, inter alia, to the discovery that it is possible to produce enantioselectively a chiral 2-haloalkanoic acid or salt thereof, e.g., a chiral 2-halopropionic acid or salt thereof, by subjecting a 2-halo-&agr;,&bgr;-alkenoic acid or salt, e.g., a 2-haloacrylic acid or salt, to asymmetric hydrogenation in the presence of an enantiometrically-enriched (BINAP)Ru(II) catalyst. In contrast to asymmetric hydrogenation of olefinic compounds having an electron rich, electropositive substituent in the 2-position such as in U.S. Pat. Nos. 4,994,607; 5,198,561; and 5,202,473, the present invention involves use as the substrate reactant of a 2-haloacrylic acid or salt thereof wherein the substituent in the 2-position is an electronegative, electron-withdrawing halide substituent.
It is fortuitous that pursuant to this invention a 2-halo-&agr;,&bgr;-alkenoic acid or salt such as a 2-haloacrylic acid or salt can be converted to a non-racemic 2-halopropionic acid in good yield and with high enantiomeric selectivity. Enantiometrically-enriched 2-haloalkanoic acids or their salts such as 2-halopropionic acids or their salts are useful as intermediates in the synthesis of aryloxyalkanoic acid herbicides having chiral carbon centers, and the need is growing for herbicidal formulations based on non-racemic rather than racemic acids. This in turn has created a need for effective and efficient process technology for producing enantiomerically-enriched 2-haloalkanoic acid intermediates that can be used in producing the desired enantiomerically-enriched aryloxyalkanoic acid herbicidal compounds. Thus the present invention can fulfill these needs most expeditiously.
In accordance with one of its embodiments, this invention provides a process wherein at least one 2-halo-&agr;,&bgr;-alkenoic acid or salt thereof is subjected to asymmetric hydrogenation in the presence of a catalyst formed by the inclusion in the reaction mixture of at least one enantiomerically-enriched (BINAP)Ru(II) catalyst, such that at least one chiral 2-haloalkanoic acid or salt thereof is enantioselectively produced. In preferred embodiments the 2-halo-&agr;,&bgr;-alkenoic acid or salt used is at least one 2-chloro-&agr;,&bgr;-alkenoic acid or salt, or at least one 2-bromo-&agr;,&bgr;-alkenoic acid or salt. Of the 2-halo-&agr;,&bgr;-alkenoic acids or salts thereof, 2-chloroacrylic acid, 2-bromoacrylic acid, 2-chlorocrotonic acid, 2-bromocrotonic acid, or salts of these acids are particularly preferred. Most preferred is 2-chloroacrylic acid.
Another preferred embodiment involves the discovery that certain halide salts are able to accelerate the rate of the foregoing reactions in which the corresponding chiral 2-haloalkanoic acids or salts thereof are enantioselectively produced. Among suitable halide salts are alkali metal halides, ammonium halides, and quaternary ammonium halides in which the halogen atom has an atomic number greater than 9. Thus pursuant to this embodiment there is provided a process wherein at least one 2-halo-&agr;,&bgr;-alkenoic acid or salt thereof is subjected to asymmetric hydrogenation in the presence of a catalytic system formed by the inclusion in the reaction mixture of at least one enantiomerically-enriched (BINAP)Ru(II) catalyst and at least one alkali metal halide in which the halogen atom is a chlorine, bromine or iodine atom, or at least one ammonium halide, or quaternary ammonium halide in which the halogen atom is a chlorine, bromine or iodine atom, such that at least one chiral 2-haloalkanoic acid or salt thereof is enantioselectively produced.
It is to be clearly understood that in the practice of this invention a single 2-halo-&agr;,&bgr;-alkenoic acid or salt thereof or a mixture of a single 2-halo-&agr;,&bgr;-alkenoic acid and a single salt thereof can be used as the initial reactant. Likewise in the practice of this invention a mixture of two or more 2-halo-&agr;,&bgr;-alkenoic acids, or a mixture of two or more 2-halo-&agr;,&bgr;-alkenoic acid salts, or a mixture of two or more 2-halo-&agr;,&bgr;-alkenoic acids with two or more 2-halo-&agr;,&bgr;-alkenoic acid salts can be used as the initial reactants. Similarly a mixture of a single 2-halo-&agr;,&bgr;-alkenoic acid with two or more 2-halo-&agr;,&bgr;-alkenoic acid salts or a mixture of two or more 2-halo-&agr;,&bgr;-alkenoic acids with a single 2-halo-&agr;,&bgr;-alkenoic acid salt can be used as the initial reactants. The acid salt(s) when used can be preformed or formed in situ.
In addition, it is to be clearly understood that this invention is not to be limited in any way to any specific composition of the catalyst(s) or catalyst system(s) once the ingredient(s) thereof has/have been included in the initial reaction mixture. At least one enantiomerically-enriched (BINAP)Ru(II) catalyst is included among the components charged to the reaction vessel. It is possible that such catalyst remains completely unchanged during the reaction. On the other hand it is possible that one or more catalytic species are formed in situ before and/or during the reaction. Thus this invention is intended to cover the catalyst(s) and/or catalyst system(s) in whatever form(s) and composition(s) such catalyst(s) and/or catalyst system(s) exist(s) in the reaction mixture during the course of carrying out the asymmetric hydrogenation reaction.
Typically the hydrogenation pursuant to this invention is performed in a liquid medium comprised at least of (i) at least one alcohol, and, at least when the initial reactant(s) comprise one or more 2-halo-&agr;,&bgr;-alkenoic acids, (ii) at least one base capable of deprotonating the 2-halo-&agr;,&bgr;-alkenoic acid(s) to form one or more salts that is/are soluble in said medium. Other suitable co-solvents can be employed such as a halogen-containing solvent, e.g., methylene chloride, methylene bromide, chloroform, chloroethane, 1,1- and 1,2-dichloroethane. Other co-solvents may also be used including diethyl ether, tetrahydrofuran, 1,2-dimethoxyethane, acetone, water and like solvents. The role of the co-solvent, if present, is at least partially to increase the solubility of the catalyst and/or precatalyst in the reaction medium. The substrate 2-halo-&agr;,&bgr;-alkenoic acids or salts must have sufficient solubility in the medium for the reaction to proceed but they need not be miscible, that is, a slurry of partially dissolved substrate may be used.
In accordance with this invention, at least a substantial portion of the hydrogenation is typically performed at least at one pressure in the range of about 100 to about 3000 psig, and preferably is performed at least at one pressure in the range of about 500 to about 2000 psig. Likewise, at least a substantial portion of the hydrogenation is typically performed at least at one temperature in the range of about −20 to about 100° C., and preferably is performed at least at one temperature in the range of about 0 to about 30° C. It is not critical how much of the hydrogenation reaction is performed under the foregoing temperature and pressure conditions, as long as at least most of the hydrogenation is performed under such conditions. Thus as in most chemical processes, the assertion of exact numerical values is meaningless since things do not behave that way in the real world. In short, given a guideline, anyone of ordinary skill in the art can determine what portion of the total reaction period should be conducted under these temperature and pressure conditions in order to achieve satisfactory results when using a particular set of components in the reaction mixture.
Particularly preferred embodiments of this invention involve operating the above process utilizing the materials and operating conditions set forth in Table 1.
Enantiomerically-enriched (BINAP)Ru(II) catalysts are complexes in which a chiral phosphine ligand is complexed with a divalent ruthenium cation, the phosphine ligand being a BINAP ligand, i.e., a 2,2′-bis(diarylphosphino)-1,1′-binaphthyl ligand such as an enantiomerically-enriched 2,2′-bis(diphenylphosphi
Bedell Christi R.
Samsel Edward G.
Albemarle Corporation
Geist Gary
Maier Leigh C.
Pippenger Philip M.
LandOfFree
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