Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acids and salts thereof
Reexamination Certificate
1998-12-16
2001-07-31
Killos, Paul J. (Department: 1623)
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acids and salts thereof
C560S103000, C560S105000, C560S114000
Reexamination Certificate
active
06268526
ABSTRACT:
TECHNICAL FIELD
This invention relates to palladium catalyzed carbonylation reactions that yield aromatic substituted aliphatic acids starting from aromatic substituted alcohols and/or aromatic substituted alkyl halides.
BACKGROUND
Processes for producing aromatic substituted aliphatic acids and their derivatives via palladium catalyzed carbonylation reactions are of great interest. Several palladium catalyzed processes for producing aromatic substituted aliphatic acids from olefins have been described, including those disclosed in GB 1 565 235 (1980), U.S. Pat. No. 5,315,026 (1994), U.S. Pat. No. 5,315,028 (1994), U.S. Pat. No. 5,482,596 (1996), U.S. Pat. No. 5,536,870 (1996), and WO 98/30529 (1998). Another convenient route to aromatic substituted aliphatic acids and their derivatives is a palladium catalyzed carbonylation utilizing aromatic substituted alcohols or aromatic substituted all halides. Such processes have been the subject of previous studies, including those reported in JP Kokoku 56-35659 (1981), JP Kokai 59-95238 (1984), JP Kokai 59-95239 (1984), E.P. 338852A1 (1989), U.S. Pat. No. 4,981,995 (1991), and U.S. Pat. No. 5,322,959 (1994).
Two possible isomers may result from the palladium catalyzed carbonylation reaction, one in which the carboxyl group is bound to the alpha carbon, and one in which the carboxyl group is bound to the beta carbon. When the desired carbonylation product is one isomer, formation of mixtures containing both isomers becomes a problem because they are difficult to separate.
THE INVENTION
The processes provided by this invention convert aromatic substituted alcohols and/or aromatic substituted alkyl halides to carboxylic acids and their derivatives, including esters, salts, racemates, and individual optical isomers. In the processes described herein, formation of the beta-substituted isomer is reduced, such that the product is essentially pure after the initial reaction workup. This exceptionally high reaction regioselectivity is brought about by use as the carbonylation catalyst of a palladium catalyst comprising a cycloalkyldiarylphosphine ligand.
Accordingly, an embodiment of this invention entails forming a mixture from ingredients comprising (i) an aromatic substituted alcohol and/or an aromatic substituted alkyl halide, (ii) a copper-free palladium catalyst comprising a palladium compound in which palladium has a valence of zero to two and a phosphine ligand wherein the ligand is a cycloalkyldiarylphosphine, and (ii) an optional halogen acid. The mixture is heated with CO at a pressure of at least about 1 atmosphere and a temperature from about 25° C. to about 300° C. to form an aromatic substituted aliphatic acid or ester. In other words, this embodiment comprises carbonylating with carbon monoxide a mixture formed from an aromatic substituted alcohol and/or an aromatic substituted alkyl halide, and a palladium catalyst comprising a palladium compound in which palladium has a valence of zero to two and a phosphine ligand wherein the ligand is a cycloalkyldiarylphosphine, optionally with a halogen acid such as aqueous hydrochloric acid or aqueous hydrobromic acid. When an aromatic substituted alcohol is used, the halogen acid is necessary, and at least a major portion of the aromatic substituted alcohol is rapidly converted in situ into an aromatic substituted allyl halide by reaction with the halogen acid. The resultant aromatic substituted alkyl halide is then carbonylated. The product of the reaction is a carboxylic ester or a mixte of a carboxylic acid and its ester when an alcohol is incorporated in the reaction; the ester can be hydrolyzed to give the desired carboxylic acid.
A feature of this invention is that the palladium catalyst used is either a single component (i.e., a cycloalkyldiarylphosphine-ligated palladium compound), or is a composition made from two components, viz. (a) one or a mixture of palladium compounds with a valence from zero to two and (b) cycloalkyldiarylphosphine ligand. The catalyst is thus copper-free. Further, when conducted under aqueous conditions, the product of the reaction is a carboxylic acid, which thus can be produced directly in the process when the desired product is a high purity, alpha-substituted carboxylic acid. In short, the acid can be produced directly without need for further reactions.
Another feature ofthis invention is that it makes possible the formation of the alpha-substituted isomer in extremely high yields, even though the amount of catalyst can be, and preferably is, extremely small. For example, it is possible to achieve yields of the alpha-substituted isomer of at least about ninety percent in reactions periods of six hours or less, using the foregoing palladium catalyst in amounts corresponding to a ratio of 0.01 mole of palladium compound per mole of aromatic substituted alcohol and/or aromatic substituted halide, or less. Moreover, this invention makes it possible to obtain the product with very high ratios of the alpha-substituted isomer, generally with ratios of alpha to beta isomer of at least about 100:1, and, in preferred cases, in ratios of about 500:1, or more.
The aromatic substituted alcohols and/or aromatic substituted halides in this invention are alkyl halides and alcohols substituted with an aromatic group; preferably, the aromatic group is bound to the 1-position of the alcohol. Typically these compounds have a general formula (1), in which X is a halogen atom or preferably a hydroxy group. When X is a halogen atom, it is an iodine, a bromine, or most preferably, a chlorine atom. The carboxylic compounds produced by the practice of this invention have the formula (II).
In both formula (I) and formula (II), R
1
and R
2
are the same or different and are selected from hydrogen atoms, hydrocayl groups, functionaly-substituted hydrocarbyl groups, substituted or unsubstituted aryl groups, and halogen atoms. Examples include compounds of formula (I) wherein R
1
and R
2
are hydrogen atoms, substituted or unsubstituted phenyl, C
1
to C
6
alkyl, and/or trifluoromethyl. The preferred compounds of formula (I) are those in which R
1
and R
2
are hydrogen atoms andlor C
1
to C
6
alkyl groups. Compounds in which R
1
is a hydrogen atom are more preferred; compounds in which R
1
is a hydrogen atom and R
2
is a C
1
to C
6
alkyl group are highly preferred. The preferred alkl halide moiety is ethyl halide, and the preferred alcohol moiety is ethanol, which requires in formula (I) that R
1
is a hydrogen atom and R
2
is a methyl group in the most highly preferred compounds. Aromatic substituted alcohols are the preferred starting materials for the carbonylation reaction.
In formula (II), Z is an alkali metal atom (preferably Na or K) when the acid is neutralized with a suitable base such as NaOH or KOK a hydrocawbyl group (preferably C
1
-C
6
alkyl), a fiictionally-substituted hydrocarbyl group, or, most preferably, a hydrogen atom. By suitable modifications of or additions to the procedures described herein, compounds of formula (II) can be produced in which Z can be any of a wide variety of other groups, nonlimiting exemplifications of which include ammonium, quaternamy ammonium, one-half equivalent of a divalent metal atom, one-third equivalent of a trivalent metal cation, and so forth.
The aromatic group [Ar of formula (I) and formula (II)] is aryl, substituted aryl, heteroaryl, substituted heteroaryl, aralkyl, or substituted aralkyl, encompassing phenyl, naphthyl, biphenyl, carbazolyl, or substituted phenyl, naphthyl, biphenyl, or carbazolyl, with at least one substituent which may be benzoyl, naphthoyl, halogen, amino, nitro, hydroxy, alkyl or alkoxy, the preferred aromatic group depends on the product desired. Examples of substituted aryl groups include isobutylphenyl, methoxynaphthyl, phenoxyphenyl, fluorobiphenylyl, benzoylphenyl, and chlorocarbazolyl.
In highly preferred embodiments, the aromatic substituted alcohols and/or aromatic substituted alkyl halides of choice are 1-(4-isobutylphenyl)ethanol or 1-(4-isobutylphenyl)-ethyl chloride
Albemarle Corporation
Deemie Robert W.
Killos Paul J.
Pippenger Philip M.
LandOfFree
Palladium catalyzed carbonylation process utilizing aromatic... does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Palladium catalyzed carbonylation process utilizing aromatic..., we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Palladium catalyzed carbonylation process utilizing aromatic... will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2470252