Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1990-11-06
1992-01-14
Killos, Paul J.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
562460, 562406, C07C 6976
Patent
active
050812793
DESCRIPTION:
BRIEF SUMMARY
DESCRIPTION
1. Technical Field
This invention relates to a method of producing .alpha.-(3-benzoylphenyl)propionic acid derivatives. More particularly, the invention relates to an efficient and economical method of producing highly pure .alpha.-(3-benzoylphenyl)propionic acid derivatives.
Incidentally, the .alpha.-(3-benzoylphenyl)propionic acid is excellent in the relief of fever, pain and inflammation and it is a useful substance which is known by a trade name of Ketoprofen.
2. Background Art
In the class of substituted arylpropionic acids, there are many compounds which can be used intact as medicines and various kinds of preparation methods have been hitherto proposed. Among them, .alpha.-(3-benzoylphenyl)propionic acid is excellent in the relief of fever, pain and inflammation and it is a useful substance as a trade name of Ketoprofen.
The .alpha.-(3-benzoylphenyl)propionic acid derivatives as the subject materials in the present invention are represented by the following general formula (C). In the formula, when X is a hydroxyl group, the formula represents Ketoprofen. When X is hydrogen or X is an alkoxyl group, the compound is easily converted into Ketoprofen by being oxidized or by being hydrolyzed through ordinary methods, respectively. ##STR1## wherein X is hydrogen, a hydroxyl group or an alkoxyl group.
With regard to the preparation of Ketoprofen, several kinds of methods have been proposed. The following methods are typical ones.
(1) 3-Benzoylpropiophenone is reacted with methyl orthoformate in the presence of thallium nitrate to obtain methyl ester of Ketoprofen. This is hydrolyzed by a conventional method to obtain Ketoprofen (British Patent No. 2,019,393).
(2) 3-Acetylbenzophenone and chloroform are reacted in a basic condition in the presence of a quaternary ammonium salt to obtain .alpha.-arylpropenoic acid, which is then subjected to catalytic reductive hydrogenation with a catalyst of palladium-carbon to obtain Ketoprofen (Japanese Laid-Open Patent Publication No. 55-7225).
Both the above methods are, however, not satisfactory as industrial production methods because toxic thallium is used, the preparation of starting materials themselves is difficult, and the processes are not efficient due to their low yields.
In addition, with regard to the dehydrogenation of benzophenone, it is known that, in the presence of a hydrogen donor, the carbonyl group of benzophenone is easily hydrocracked in the reaction system by the hydrogen which is generated from the hydrogen donor and it is converted into diphenylmethane (Fuel, Vol. 57, p. 650 (1978)). In other words, the carbonyl group connected between the adjacent two phenyl groups is highly activated, and as a result, the carbonyl group is liable to suffer hydrocracking, which is different from methyl ethyl ketone or else. Accordingly, it is supposed that, when ethylbenzophenone is dehydrogenated, a compound having a diphenylmethane structure, rather than ethenylbenzophenone, is produced.
According to the results of investigation carried out by the present inventors with regard to the catalytic dehydrogenation of ethylbenzophenone, however, the initially expected compound having diphenylmethane structure is hardly produced by a specific method, and to their surprise, it was found out that ethenylbenzophenone is produced in a high yield.
Accordingly, the object of the present invention is to produce efficiently highly pure .alpha.-(3-benzoylphenyl)propionic acid derivatives by dehydrogenating 3-ethylbenzophenone and then carbonylating.
DISCLOSURE OF INVENTION
The present invention provides a method for producing .alpha.-(3-benzoylphenyl)propionic acid derivative characterized in the following step (I) and step (II).
Step (I)
A step of vapor phase dehydrogenation by bringing 3-ethylbenzophenone represented by a formula (A) into contact with a dehydrogenation catalyst in the coexistence of an inert gas through a fixed bed flow method to obtain 3-ethenylbenzophenone represented by a formula (B), and
Step (II)
A step to obtain .alpha.-(3-ben
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Inomata Yoshihisa
Matsumura Yasuo
Shimizu Isoo
Killos Paul J.
Nippon Petrochemicals Company Limited
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