Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
1999-11-22
2002-04-16
Owens, Amelia (Department: 1612)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C558S388000, C568S811000, C568S812000
Reexamination Certificate
active
06372921
ABSTRACT:
TECHNICAL FIELD
The present invention relates to methods for producing isochromanone compounds useful as raw materials for drugs and agricultural chemicals and to methods for producing intermediate compounds for the production of isochromanone compounds. More particularly, the present invention relates to (1) methods for producing isochromanone compounds from o-xylene compounds as starting compounds through &agr;-halogeno-o-xylene derivatives, &agr;-cyano-o-xylene derivatives, and &agr;-halogeno-&agr;′-cyano-o-xylene derivatives, and (2) methods for producing isochromanone compounds from o-xylene compounds as starting compounds through &agr;,&agr;′-dihalogeno-o-xylene derivatives, &agr;,&agr;′-dihydroxy-o-xylene derivatives, &agr;-halogeno-&agr;′-hydroxy-o-xylene derivatives and &agr;-cyano-&agr;′-hydroxy-o-xylene derivatives, and (3) methods for producing these intermediates for the production of isochromanone compounds.
BACKGROUND ART
(1) As a general method for producing &agr;-halogeno-o-xylene compounds, various methods have heretofore been known. For example, in the case of &agr;-chloro-o-xylene, there have been known a reaction of o-xylene as a starting compound with N-halogenated succinimide and a reaction of o-xylene as a starting compound with sulfuryl chloride or chlorine in the presence of azobisisobutyronitrile (AIBN).
Also, a method for selectively producing of &agr;-chloro-o-xylene by reaction of 2-methylbenzyl alcohol (&agr;-hydroxy-o-xylene) with thionyl chloride has been known (J. Am. Chem. Soc., 62, 2295 (1940)).
Of these methods, the method in which o-xylene and chlorine are reacted tends to give di- or tri-substituted perchlorides and it is difficult to obtain only &agr;-chloro-o-xylene selectively.
The method in which 2-methylbenzyl alcohol and thionyl chloride are reacted by-produces highly toxic sulfurous acid gas and hence is undesirable as a commercial method.
Thus, conventional production methods for &agr;-halogeno-o-xylene compounds produce highly toxic by-products or the target product, &agr;-halogeno-o-xylene, has low selectivity so that they are not always satisfactory methods for practicing on an industrial scale.
(2) Production methods for &agr;,&agr;′-dihydroxy-o-xylene compounds include a method in which &agr;,&agr;′-dibromo-o-xylene is heated in the presence of sodium hydroxide to obtain &agr;,&agr;′-dihydroxy-o-xylene (Ber., 17, 123 (1884)). &agr;,&agr;′-Dihydroxy-o-xylene is under alkaline condition and when heated, an intermediate &agr;-hydroxy-&agr;′-halogeno-o-xylene undergoes intramolecular dehalogenohydrogenation to produce phthalan of formula (XI) and the yield of objective &agr;,&agr;′-dihydroxy-o-xylene decreases so that the method is not suitable for industrial application.
Similarly, a method has been reported in which &agr;,&agr;′-dibromo-o-xylene is hydrolyzed in the presence of potassium hydroxide to obtain &agr;,&agr;′-dihydroxy-o-xylene (Ann. Chim. Phys., [6]6, 106 (1885)). Similarly, phthalan is produced and is not advantageous for industrial application.
Further, a method in which o-phthaloyl dichloride is converted to &agr;,&agr;′-dihydroxy-o-xylene with sodium amalgam (Ber., 12, 646 (1879)), a method in which phthalic anhydride or o-phthaloyl dichloride is reduced with lithium aluminum hydride (LiAlH
4
)to synthesize &agr;,&agr;′-dihydroxy-o-xylene (Nystrom et al., J. Am. Chem. Soc., 69, 1197-9 (1947)), a method in which o-phthaloyl dichloride is reacted with sodium borohydride (NaBH
4
) in dioxane to obtain &agr;,&agr;′-dihydroxy-o-xylene (Chaikin et al., J. Am. Chem. Soc., 71, 122-5 (1949)) are known. In each case, starting compounds are not available industrially so that they are not industrially advantageous.
Further, there is disclosed a method for producing a, &agr;′-dihydroxy-o-xylene in which &agr;,&agr;′-dichloro-o-xylene is reacted with water in the presence of an alkali metal formate or alkaline earth metal formate (JP-A-64-26528). Addition of formate necessitates disposal of formic acid after ultimately recovering &agr;,&agr;′-dihydroxy-o-xylene. That is, there occurs mixing of formic acid, which is a BOD source, into wastewater so that treatment of wastewater becomes necessary, making the process complicated.
(3) There have been few report on the production method for &agr;-halogeno-&agr;′-cyano-o-xylenes. An example of reports is Research Disclosure (RD) 409066, p.581-584. This discloses synthesis of &agr;-chloro-&agr;′-cyano-o-xylene by reacting &agr;-cyano-o-xylene with sulfuryl chloride in fluorobenzene as a solvent. However, the method uses sulfuryl chloride, which is expensive, as a chlorinating agent and is unsatisfactory as an industrial method.
(4) The production method for &agr;-halogeno-&agr;′-hydroxy-xylenes is reported in J. Org. Chem., 57, 4074-4079 (1992). In this production method, &agr;,&agr;′-dihydroxy-xylene is reacted with thionyl chloride using benzene as a solvent and pyridine as a catalyst. However, this method requires overnight reaction time and yield of the reaction is as low as 59.5% so that it is not advantageous for industrial application.
(5) &agr;-Carboxy-&agr;′-hydroxy-xylenes and salts thereof are industrially useful compounds. However, there are few industrial production methods.
On the production method for &agr;-carboxy-&agr;′-hydroxy-xylenes and salts thereof, JP-A-9-67364 describes that trial to synthesize them through &agr;-carboxy-&agr;′-hydroxy-o-xylene by reacting &agr;,&agr;′-dihalogeno-o-xylene with carbon monoxide and water in the presence of a catalyst such as palladium failed since &agr;-carboxy-&agr;′-hydroxy-o-xylene was not synthesized.
Regarding &agr;,&agr;′-dihalogeno-m-xylene or &agr;,&agr;′-dihalogeno-p-xylene, it is considered that &agr;-carboxy-&agr;′-hydroxy-xylenes can be synthesized therefrom similarly to the method described in JP-A-9-67364. However, use of expensive catalysts is required so that such a method is not an industrially advantageous method.
(6) Regarding 3-isochromanone, there is a report that it can be synthesized by reacting o-bromomethylbenzyl alcohol (&agr;-bromo-o-xylene) with carbon monoxide in the presence of palladium complex catalyst (J. Am. Chem. Soc., 102, 4191 (1908)). However, use of expensive catalysts does not make the method industrially advantageous.
Further, Research Disclosure (RD) 409066, p.581-584 discloses a method in which 3-isochromanone is produced using &agr;-chloro-&agr;′-cyano-o-xylenes as raw material and large excess sulfuric acid and tetrabutylammonium bromide. This method uses a large amount of sulfuric acid and hence produces a large amount of wastewater, thus raising the problems of imposing a large load on the environment and low yields.
Further, as another method, a method has been known in which &agr;-halogeno-&agr;′-cyano-o-xylenes are subjected to alkali hydrolysis in an aqueous solution of sodium hydroxide or potassium hydroxide, and the reaction mixture is rendered acidic by addition of acid to cyclize them. This method requires two reaction processes, i.e., the alkali hydrolysis of &agr;-halogeno-&agr;′-cyano-o-xylenes (hydrolysis reaction step) and then acidification with acid (cyclizing step), resulting in that yield is too low for the method to be adopted industrially.
PROBLEMS WHICH THE INVENTION IS TO SOLVE
A main object of the present invention is to provide an industrially advantageous production method that can efficiently give 3-isochromanone compounds from o-xylene compounds as raw materials.
More particularly, an object of the present invention is to use o-xylene compounds as raw materials and provide:
(1) an industrially advantageous production method for isochromanone compounds through &agr;-halogeno-o-xylene derivatives, &agr;-cyano-o-xylene derivatives, and &agr;-halogeno-&agr;′-cyano-o-xylene derivatives.
Also, an object of the present invention is to use o-xylen
Miyota Yoshiaki
Ohshiro Kimitaka
Saito Makoto
Shibuya Akira
Yasuda Masaru
Owens Amelia
Showa Denko K.K.
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