Organic compounds -- part of the class 532-570 series – Organic compounds – Carboxylic acid esters
Patent
1998-03-18
1999-03-23
Barts, Samuel
Organic compounds -- part of the class 532-570 series
Organic compounds
Carboxylic acid esters
549290, C07C 6976
Patent
active
058862110
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/JP96/01677 filed Jun. 19, 1996.
1. Field of the Invention
This invention relates to a process for producing 2-(halomethyl)phenylacetic acid esters which are intermediates for synthesizing cephalosporin antibiotics and are also expected to be intermediates for synthesizing fungicides for agricultural use, and relates to a process for producing 3-isochromanones which are starting materials for producing the 2-(halomethyl)phenylacetic acid esters.
2. Background of the Art
Among the known processes for synthesizing 2-(halomethyl)phenylacetic acid esters is a process starting with xylene (Japan Kokai Tokkyo Koho, JP 59-193370), but it is not deemed useful because of involvement of many steps and poor selectivity.
A process comprising reacting 3-isochromanone with .alpha.,.alpha.,.alpha.'-trichlorodimethyl ether into 2-(chloromethyl)phenylacyl chloride is also known (J. Prakt. Chem., 12 (1966)). However, the yield is low, and a further reaction with an alcohol is required for producing 2-(chloromethyl)phenylacetic acid esters. There is no report on synthesis of 2-(halomethyl)pehnylacetic acid esters using 3-isochromanone as a starting material.
Known processes for producing 3-isochromanones referred to above as a starting material include (1) chloromethylation of a substituted phenylacetic acid (J. Chem. Soc., 178 (1927)), (2) reaction between o-bromomethylbenzyl alcohol and carbon monoxide in the presence of a palladium catalyst (J. Amer. Chem. Soc., 4193 (1980)), (3) oxidation of 2-indanone with a peroxide, such as metachloroperbenzoic acid, in a solvent in accordance with Bayer-Villiger rearrangement (Synthesis, 818 (1981)), (4) cyclization of .alpha.-methoxy-.alpha.'-cyano-o-xylene with sulfuric acid (J. Chem. Soc., 2819 (1954)), (5) cyclization of ethyl o-ethoxycarbonylphenylacetate with diisobutylaluminum hydride followed by oxidation (Tetrahydron Letters, 2359 (1973)), and (6) reaction between o-methylbenzyl alcohol and butyl lithium followed by reaction with carbon dioxide (Tetrahydron Letters, 1233 (1983)).
The process (1) has a poor yield and is not necessarily regarded advantageous for industrial production. The processes (2) to (6) involve difficulties in preparing the starting materials used so that the synthesis of 3-isochromanones must begin with purification of the starting material. These processes therefore comprise an increased number of steps, which is disadvantageous for cost and yield, and none of them can be a useful process for industrially producing 3-isochromanones.
DISCLOSURE OF THE INVENTION
The inventors have conducted various studies for providing industrial and economical processes for producing 2-(halomethyl)phenylacetic acid esters and 3-isochromanones that are starting materials of the 2-(halomethyl)phenylacetic acid esters. As a result, it has now been found that 2-(halomethyl)phenylacetic acid esters can be prepared selectively and in good yield under mild conditions by (1) reacting a 3-isochromanone with a hydrogen halide and an alcohol or (2) reacting a 3-isochromanone with a dihalomethyl alkyl ether and reacting the reactant with an alcohol. It has also been found that the starting 3-isochromanones can be prepared in a short time with good selectivity and yield by reacting an o-xylene dihalide derivative, which is an industrially economical material, with carbon monoxide and water in an organic solvent in the presence of a hydrogen halide capturing agent and a catalyst.
That is, the present invention relates to a process for producing 2-(halomethyl)phenylacetic acid esters represented by the following formula (3): ##STR2## wherein R.sup.1 represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, or an alkyloxy group having 1 to 6 carbon atoms; R.sup.2 represents an alkyl group having 1 to 6 carbon atoms; and X represents a halogen atom, formula (1): ##STR3## wherein R.sup.1 has the same meaning as defined above, with a hydrogen halide and an alcohol represented by the following formula (2):
Furthermore, the pr
REFERENCES:
Chem Abstracts online printout; 1981:103198, Pandey et al.
Journal of the American Chemical Society, vol. 102, No. 12, (1980), A. Cowell and J.K. Stille "Synthesis of Lactones by the Palladium-Catalyzed Carbonylation of Halo Alcohols", pp. 4193-4198.
Hirai Kenji
Masuda Katsuyuki
Matsuzawa Masahumi
Ono Yukio
Sugiyama Masahide
Barts Samuel
Iharanikkei Chemical Industry Co., Ltd
Sagami Chemical Research Center
LandOfFree
Process for producing 2-(halomethyl)phenylacetic acid esters 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 producing 2-(halomethyl)phenylacetic acid esters, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for producing 2-(halomethyl)phenylacetic acid esters will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2127230