Organic compounds -- part of the class 532-570 series – Organic compounds – Halogen containing
Reexamination Certificate
2002-09-24
2004-02-03
Richter, Johann (Department: 1621)
Organic compounds -- part of the class 532-570 series
Organic compounds
Halogen containing
C570S165000, C570S166000, C570S167000, C570S168000, C570S169000
Reexamination Certificate
active
06686509
ABSTRACT:
TECHNICAL FIELD
The present invention relates to a method for producing an &agr;,&agr;-difluorocycloalkane useful as a raw material for synthesizing medicines, liquid crystal materials and the like.
BACKGROUND ART
Conventionally, as methods for producing an &agr;,&agr;-difluorocycloalkane, there are a method containing a step of reacting a cycloalkanone with sulfur tetrafluoride (e.g., U.S. Pat. No. 2,859,245), a method containing a step of reacting a cycloalkanone with molybdenum hexafluoride (Tetrahedron, (27), 3956 (1971)), a method containing a step of converting a cycloalkanone into a hydrazone derivative before reacting with a halogen fluoride (e.g., J. Am. Chem. Soc. (1987), 109(3), 896), etc. However, these methods use a fluorinating agent which is expensive and has high toxicity and explosiveness, require a special instrument for production, and additionally, show low reaction yield. Therefore, these methods are not admitted as an industrial production method. Further, there is a method containing a step of reacting anhydrous hydrogen fluoride with 1-chlorocyclohexene in the presence or absence of a catalyst (e.g., Helv. Chim. Acta, 46(1963), 1818). However, this method has problems that a complicated procedure is necessary for synthesis of raw materials, and additionally, reaction yield with hydrogen fluoride is not high.
For overcoming these problems, various methods have been recently proposed. For example, Japanese Patent Application Laid-Open (JP-A) No. 63-54331 discloses a step of reacting cyclohexanone with anhydrous trifluoroacetic acid to obtain an acylal compound, and then, reacting it with hydrogen fluoride to obtain 1,1-difluorocyclohexane in high yield under mild conditions. In this method, anhydrous trifluoroacetic acid used in the reaction can be recycled by removing it as trifluoroacetic acid, and then, dehydrating the trifluoroacetic acid with phosphorus pentaoxide and the like. Therefore, the method has a merit of suppressing production cost low. However, the reaction time of the acylal process is very long, and additionally, it is necessary to extract the acylal compound, and then to conduct a fluorinating process. Further, it is necessary to use hydrogen fluoride in large amount ranging from 30 to 50 equivalent, and to use an equipment for recovering hydrogen fluoride. Therefore, the method needs to use a complicated process, and cannot avoid a large equipment load. These points may be large demerits for an industrial method.
As a de-oxygen fluorinating agent for directly obtaining a desired substance from a cycloalkanone, there are methods using aminosulfur trifluoride obtained by deriving from sulfur tetrafluoride (e.g., J. Org. Chem., 40(1975) 574, and JP-A Nos. 11-171858, 9-508646 and 11-505271). In these methods, &agr;,&agr;-difluorocycloalkanes can be synthesized under mild conditions without requiring a special equipment. However, a de-oxygen fluorinating agent used in the methods is expensive. Further, as a large problem, a by-product having a fluorocycloalkene skeleton is produced, and it is extremely difficult to remove the by-product from the desired substance. Therefore, the methods need an enormous labor for the removal.
For example, JP-A No. 11-505271 discloses a method wherein diethylaminosulfur trifluoride (hereinafter, abbreviated as “DAST”) is reacted with ethyl 4-cyclohexanonecarboxylate, and then, hydrolysis, neutralization, extraction, drying, de-solvent and distillation under reduced pressure are conducted to obtain ethyl 4,4-difluorocyclohexanecarboxylate in a yield of about 70 to 80% containing ethyl 4-fluoro-3-cyclohexenecarboxylate as an impurity. Further, it discloses a complicated purification procedure as a next step wherein the ethyl 4-fluoro-3-cyclohexenecarboxylate which is a by-product is treated with “OXONE®” and the like. However, such treating process has a problem that it deteriorates the yield of ethyl 4,4-difluorocyclohexanecarboxylate.
JP-A No. 11-171858 discloses a method wherein various aminosulfur trifluorides are reacted with 4-t-butyl-cyclohexanone to obtain 4-t-butyl-1,1-difluorocyclohexane and 4-t-butyl-1-fluorocyclohexene in a production ratio of from 67/33 to 96/4. However, it discloses no specific method for isolating 4-t-butyl-1,1-difluorocyclohexane at a high purity from the mixture thereof.
DISCLOSURE OF INVENTION
The present invention has been accomplished to solve the above-mentioned problems of the prior technologies. Therefore, the object of the present invention is to provide a method capable of producing an &agr;,&agr;-difluorocycloalkane at a higher purity in higher efficiency as compared with conventional methods.
In the prior arts stated above, the by-product having a fluorocycloalkene skeleton has been defined as a merely useless product which should be removed for obtaining an &agr;,&agr;-difluorocycloalkane. However, in variously investigation by the present inventors about a method for efficiently producing an &agr;,&agr;-difluorocycloalkane, they treated a mixture with hydrogen fluoride wherein the mixture contained 1,1-difluorocyclohexane and 1-fluorocyclohexene which was obtained by reacting cyclohexanone with a de-oxygen fluorinating agent such as DAST, and they found that the 1-fluorocyclohexene was easily converted into 1,1-difluorocyclohexane by the treatment. They have further intensively studied based on this knowledge, and resultantly found that 1,1-difluorocyclohexane at a high purity was obtained by directly adding hydrogen fluoride to such reaction mixture, and they completed the present invention.
Namely, the present invention relates to a method for producing an &agr;,&agr;-difluorocycloalkane which comprises a step of treating a fluorocycloalkene with hydrogen fluoride wherein the fluorocycloalkene has one fluorine atom directly bonded to a carbon atom of carbon—carbon unsaturated double bond.
Further, the present invention relates to a method for producing an &agr;,&agr;-difluorocycloalkane which comprises a step of treating a cycloalkanone with a de-oxygen fluorinating agent, and then treating it with hydrogen fluoride.
BEST MODES FOR CARRYING OUT THE INVENTION
In the present invention, the fluorocycloalkene means a cycloalkene having one fluorine atom directly bonded to a carbon atom of carbon—carbon unsaturated double bond.
Listed as the fluorocycloalkenes are, for example, compounds having a 4-membered to 8-membered monocyclic structure, compounds having a condensed ring structure in which adjacent carbon atoms forming a 4-membered to 8-membered monocyclic structure are cross-linked by an alkylene group, compounds having a cyclic structure in which non-adjacent carbon atoms forming a 4-membered to 8-membered monocyclic structure are cross-linked by an alkylene group. Specific examples thereof include fluorocyclobutene, fluorocyclopentene, fluorocyclohexene, fluorocycloheptene, fluorocyclooctene. These fluorocycloalkenes may have a substituent inactive to hydrogen fluoride, at a carbon atom forming a cyclic structure except a carbon atom bonded with fluorine atom. Examples of the substituent, which is inactive to hydrogen fluoride, include alkyl groups such as methyl, ethyl, propyl and butyl; aryl groups, alkoxy groups, halogen atoms, trifluoromethyl group, carboxyl group, alkoxycarbonyl groups, cyano group and nitro group.
Some specific examples of the compounds belonging to fluorocycloalkenes include, 1-fluorocyclobutene, 1-fluoro-2-methylcyclopentene, 1-fluoro-4-methylcycloheptene, 4-t-butyl-1-fluorocyclooctene, 1-fluorocyclohexene, 1-fluoro-2-methylcyclohexene, 1-fluoro-4-methylcyclohexene, 4-t-butyl-1-fluorocyclohexene, ethyl 4-fluoro-3-cyclohexenecarboxylate, 4-fluoro-3-cyclohexenecarboxylic acid, 4-cyano-1-fluorocyclohexene, 4-chloro-1-fluorocyclohexene, 1-fluoro-4-phenylcyclohexene, 1-fluoro-3-phenylcyclohexene, 1-fluoro-4-trifluoromethylcyclohexene, 1-fluoro-3-methoxycyclohexene, 2,6-dimethyl-1-fluorocyclohexene and 1-fluoro-4-nitrocyclohexene.
Fluorocycloalkenes synthesized by any method can be used. For example, it can be used a fluorocycloalkene in a
Fukumura Kouki
Hayashi Hidetoshi
Kusumoto Masahiko
Sonoda Hiroshi
Burns Doane , Swecker, Mathis LLP
Mitsui Chemicals Inc.
Price Elvis O.
Richter Johann
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