PROCESS FOR PRODUCING FLUORINATED DICARBONYL COMPOUND

Abstract: An industrial process for producing a fluorinated dicarbonyl compound in a high yield, wherein a dicarbonyl compound represented by the general formula R¹COCHR²COR³ (wherein R¹ represents hydrogen, halogen, or (un)substituted alkyl or aryl; R² represents hydrogen, halogen, or (un)substituted alkyl or aryl; and R³ represents hydrogen, or (un)substituted alkyl, aryl, alkoxy or aryloxy, provided at least two groups selected from among R¹, R² and R³ may be combined together to form a part of a cyclic structure which may contain a heteroatom) is reacted with fluorine (F₂) either in at least one solvent selected from the group consisting of C₁-C₅ halogenated hydrocarbons and nitrile compounds or in a solvent in the presence of a salt or an acid with a pKa value of 6 or less to give a fluorinated derivative represented by the general formula R¹COCFR²COR³ (wherein R¹, R² and R³ are each as defined above).

Description: The present invention relates to a process for preparing a fluorine-containing dicarbonyl compound. In particular, the present invention relates to a process for preparing a fluorine-containing dicarbonyl compound from a readily available dicarbonyl compound as a raw material using a cheap fluorine gas in a single step. A fluorine-containing dicarbonyl compound of the formula: R 1 COCFR 2 COR 3 wherein R 1 is a hydrogen atom, or a substituted or unsubstituted alkyl or aryl group; R 2 is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl or aryl group; and R 3 is a hydrogen atom, or a substituted or unsubstituted alkyl, aryl, alkoxy or aryloxy group, provided that at least two of R 1 , R 2 and R 3 may together form a part of a cyclic structure with or without a hetero atom is a useful intermediate in the synthesis of agrochemicals, etc. (see EP-A-0 468 766, J. Org. Chem., 48 , 724-727 (1983), J. Fluorine Chem., 56 , 141 (1992), and Bull. Chem. Soc. Jpn., 54, 3221 (1981)). As preparation processes of the fluorine-containing dicarbonyl compound of the formula (II), that is, a fluorine-containing β-diketone or β-ketoester, the following processes (1) through (5) are known: (1) The β-diketone or β-ketoester is converted to its metal salt and then reacted with FClO 3 (Justus Liebigs Ann. Chim., 677, 9 (1964) and J. Org. Chem., 57, 2196 (1992)); with CH 3 COOF (J. Org. Chem., 48, 724 (1983)); with N-fluoroperfluoropiperidine (J. Fluorine Chem., 52 , 389 (1991)); with a N-fluoropyridinium salt (J. Am. Chem. Soc., 112, 8563 (1990) and JP-A-62-207228); with N-fluorosultam (Tetrahedron Lett., 29, 6087 (1988) and Helv. Chim. Acta., 72, 1248 (1989)). (2) The β-diketone or β-ketoester is reacted with a xenon compound (C 19 XeF 6 ) (Tetrahedron Lett., 21 , 277 (1980)); with CH 3 COOF (J. Org. Chem., 48, 724 (1983)); with xenon difluoride in the presence of an acid catalyst (J. Chem. Soc., Chem. Commun., 1980, 759); with a N-fluoropyridinium salt in the presence or absence of an acid catalyst (J. Am. Chem. Soc., 112 , 8563 (1990) and JP-A-62-207228); with N-fluorobis(trifluoromethanesulfonyl)amide (J. Chem. Soc., Chem. Commun., 1991 , 179). (3) The β-diketone or β-ketoester is converted to a corresponding trimethylsilylenol ether and then reacted with fluorine at -78°C (J. Org. Chem., 52, 4309 (1987). (4) The β-ketoester is chlorinated and then reacted with potassium fluoride in a crown ether for a long time (J. Am. Chem. Soc., 58, 1803 (1936) and Synthesis, 1977, 189). (5) From a perfluoroolefin, for example, hexafluoropropene as a starting material, the fluorine containing β-diketone or β-ketoester is prepared through many steps (Chem. Lett., 1107 (1980) or Izv. Akad. Nauk, SSSR, Ser. Khim., 1980, 2827 (CA95-6431z). In addition, J. Org. Chem., 57, 2196 (1992) describes that the fluorine-containing β-ketoester is prepared by the fluorination (10 % F 2 /N 2 ) of the β-ketoester (Process (6)). But, the processes (1) and (2) have drawbacks that an expensive fluorination reagent should be used, the synthesis of the fluorination reagent is complicated, some reagents should be prepared under a very low reaction temperature condition, and they should be used immediately after their synthesis at the low temperature, since they are decomposed at room temperature. The processes (3), (4) and (5) require multi-step reactions. Further, the process (3) has drawbacks that the fluorination should be carried out at a very low temperature, and a yield is low, the process (4) has drawbacks that an expensive crown ether should be used, a reaction time is long, and a yield is low, and the process (5) has drawbacks that the starting materials are expensive, and it is not a general process because of the small number of the available starting materials. The above described fluorination process (6) of the β-ketoester wastes a large amount of the starting material because of an insufficient yield, and produces a variety of by-products. Since a fluorine atom has a small atomic weight (F = 19) and a small polarity, in general, it is difficult to separate fluorine-containing compounds. Therefore, a preparation process which produces a variety of by-products is not an industrially advantageous process, since a complicated separation process is required after the reaction. Accordingly, none of the above processes (1) through (6) is satisfactory, when they are carried out industrially. An object of the present invention is to provide an industrially advantage process for preparing a fluorine-containing dicarbonyl compound of the formula (II), which can solve the above described drawbacks and can give the desired product in a good yield. The present invention provides a process for preparing a fluorine-containing dicarbonyl compound of the formula: R 1 COCFR 2 COR 3 wherein R 1 is a hydrogen atom, or a substituted or unsubstituted alkyl or aryl group; R 2 is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl or aryl group; and R 3 is a hydrogen atom, or a substituted or unsubstituted alkyl, aryl, alkoxy or aryloxy group, provided that at least two of R 1 , R 2 and R 3 may together form a part of a cyclic structure with or without a hetero atom, comprising reacting a dicarbonyl compound of the formula: R 1 COCHR 2 COR 3 wherein R 1 , R 2 and R 3 are the same as defined above with fluorine (F 2 ) in at least one solvent selected from the group consisting of halogenated hydrocarbons having 1 to 5 carbon atoms and nitrile compounds. In the present invention, the alkyl group means an alkyl group having 1 to 20 carbon atom, preferably 1 to 10 carbon atoms. Optionally, the alkyl group may be substituted with a substituent such as a halogen atom, a hydroxyl group, a cyano group, an aryl group, an acyl group, an alkoxy group, an aryloxy group, an acyloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, an alkanesulfonyl group, an arylsulfonyl group or an acylamino group. The aryl group means an aromatic group having 6 to 14 carbon atoms, preferably 6 to 10 carbon atoms. The aryl group may be substituted with a substituent such as an alkyl group, a halogen atom, a cyano group, a nitro group, an acyl group, an acyloxy group, an alkoxycarbonyl group, an aryloxycarbonyl group, an alkanesulfonyl group or an arylsulfonyl group. The alkoxy group means an alkoxy group having 1 to 20 carbon atoms, preferably 1 to 10 carbon atoms. The alkoxy group may be substituted by the same substituent as those exemplified in connection with the alkyl group. The aryloxy group means an aryloxy group having 6 to 14 carbon atoms, preferably 6 to 10 carbon atoms. The aryloxy group may be substituted by the same substituent as those exemplified in connection with the aryl group. Examples of the cyclic structure formed by the combination of R 1 , R 2 and R 3 are a monocyclic group, a dicyclic group or a polycyclic group, having 3 to 20 members. The halogen atom may be a fluorine atom, a chlorine atom, a bromine atom or an iodine atom. The dicarbonyl compound of the formula (I) which is used as the raw material in the process of the present invention may be commercially available or synthesized easily by a conventional synthesis method. Examples of the dicarbonyl compound of the formula (I) are as follows: HCOCH 2 COH, CH 3 COCH 2 COH, CH 3 COCH 2 COCH 3 , CH 3 COCH 2 CO-C 2 H 5 , CH 3 COCH 2 COC 5 H 11 , CH 3 COCH 2 COC 8 H 17 , CH 3 COCH 2 COC 10 H 21 , CH 3 COCH(CH 3 )COCH 3 , CH 3 COCH(C 8 H 17 )COCH 3 , CH 3 COCHFCOCH 3 , CH 3 CO-CHClCOCH 3 , CH 3 COCHBrCOCH 3 , CH 3 COCHICOCH 3 , PhCOCH 2 COCH 3 , CH 3 COCHPhCOCH 3 , PhCOCH 2 COPh, PhCOCHFCOPh, CH 3 COCH 2 COCH 2 Ph, CH 3 COCH(CH 2 Ph)COCH 3 , ClCH 2 COCH 2 COCH 3 , BrCH 2 COCH 2 COCH 3 , CF 3 CO-CH 2 COCH 3 , CF 3 COCH 2 COCF 3 , CF 3 COCHFCOCF 3 , C 6 H 5 COCH 2 COC 6 H 5 ), C 6 F 5 COCH 2 COC 6 F 5 , C 6 F 5 COCHFCOC 6 F 5 , HCOCH 2 COOCH 3 , HCOCH 2 COOC 2 H 5 , CH 3 COCH 2 COOC 2 H 5 , CH 3 COCH 2 COO-C 3 H 7 , CH 3 COCH 2 COOC 4 H 9 , CH 3 COCH 2 COOC 8 H 17 , CH 3 COCH(CH 3 )COOCH 3 , PhCH 2 COCH 2 COOCH 3 , CH 3 COCH 2 COOPh, CH 3 COCH 2 COOCH 2 Ph, CH 3 CO-CHPhCOOC 3 H 7 , CH 3 COCH(CH 2 Ph)COOC 2 H 5 , CH 3 COCHFCOOC 2 H 5 , CH 3 CO-CHClCOOC 2 H 5 , CH 3 COCHBrCOOC 2 H 5 , CH 3 COCHlCOOC 2 H 5 , FCH 2 COCH 2 -COOC 2 H 5 , ClCH 2 COCH 2 COOCH 3 , The process is effective, in particular, when the starting compound is a six-member compound of the formula: wherein R' is a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, or a substituted or unsubstituted alkyl, aryl, alkoxyl or aryloxy group, and R 3 is the same as defined above, or a dicarbonyl compound of the formula wherein R 1 and R 3 are the same as defined above, and R" is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group. A solvent which can be used in the process is a halogenated hydrocarbon having 1 to 5 carbon atoms or a nitrile compound. Examples of the halogenated hydrocarbon are chloroform, dichloromethane, chloromethane, carbon tetrachloride, chloroethane, dichloroethane, trichloroethane, tetrachloroethane, trichlorotrifluoroethane, tetrafluoroethane, chlorotrifluoroethane, or perfluoropentane. Among them, chloroform is preferred. Examples of the nitrile compound are acetonitrile or propionitrile. Among them, acetonitrile is preferred. The above solvent may be used in combination with other solvent so long as the characteristics of the present invention are not impaired. Fluorine (F 2 ) to be used in the present invention is preferably used in a diluted form with an inert gas so that a volume percentage of the inert gas is from 99.9 % to 50 %, to suppress the violent reactivity of the fluorine. Examples of the diluent inert gas are nitrogen, helium argon or carbon dioxide. An amount of the fluorine may not be uniformly determined, since it varies with an introduction manner, a reaction temperature, a kind of the reaction solvent or a reaction apparatus. A person skilled in the art can easily determine the amount of the fluorine to be used by carrying out some simple preliminary experiments with aiming an amount necessary for substantially disappearing the dicarbonyl compound of the formula (I) which is the starting material. A reaction temperature is selected from a range between -120°C and +80°C. To carry out the reaction effectively in a high yield, the reaction temperature is preferably from -100°C to +50°C, in particular, from -80°C to +30°C. In the case of the dicarbonyl compound of the formula (I) in which R 2 is a hydrogen, a product which is produced after twice repeating the reaction of the present invention according to the following reaction formula, that is, a fluorine-containing carbonyl compound of the formula (II) in which R 2 is a fluorine atom is obtained: Alternatively, when R 2 in the formula (I) is a fluorine atom, the difluorinated dicarbonyl compound can be obtained by a single step. According to the present invention, the fluorine-containing carbonyl compound of the formula (II) is prepared in a good yield in a single step from the dicarbonyl compound of the formula (I), which is commercially available or easily synthesized, as the starting material using cheap fluorine gas. This fluorine-containing dicarbonyl compound can be used as a highly active intermediate of agrochemicals, and the like. The present invention will be illustrated by Examples, Example 1 (not included by the invention) A mixed gas of 5 % F 2 /95 % N 2 was flowed at a rate of 15 ml/min. in a mixture of ethyl cyclohexanone-2-carboxylate (340 mg, 2 mmol), sodium acetate (165 mg, 2 mmol) and acetic acid (2 ml), while stirring and cooling on a water bath at 12°C. An amount of supplied F 2 was 86 ml (3.8 mmol). After the reaction, the reaction mixture was quantitatively analyzed by 19 F-NMR to find that ethyl 2-fluorocyclohexnanone-2-carboxylate was formed in a yield of 88 %. The structure of the product was confirmed by comparing the product, which was isolated by post treatment, with the structure of the standard sample according to the conventional method. Examples 2-14 Under the conditions shown in Table 1, ethyl cyclohexanone-2-carboxylate was fluorinated in the same manner as in Example 1. The results are shown in Table 1 together with those of Example 1. Examples 15 to 20 Under the conditions shown in Table 2, various dicarbonyl compounds were fluorinated in the same manner as in Example 1. The results are shown in Table 2. The structures of the products were identified by comparing the spectra of the products with those of the standard samples. Comparative Examples 1 to 6 Under the conditions shown in Table 3, various dicarbonyl compounds were fluorinated in the same manner as in Example 1. The results are shown in Table 3. The structures of the products were identified by comparing the spectra of the products with those of the standard samples.

Claims: A process for preparing a fluorine-containing dicarbonyl compound of the formula: R 1 COCFR 2 COR 3 wherein R 1 is a hydrogen atom, or a substituted or unsubstituted alkyl or aryl group; R 2 is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl or aryl group; and R 3 is a hydrogen atom, or a substituted or unsubstituted alkyl, aryl, alkoxy or aryloxy group, provided that at least two of R 1 , R 2 and R 3 may together form a part of a cyclic structure with or without a hetero atom, comprising reacting a dicarbonyl compound of the formula: R 1 COCHR 2 COR 3 wherein R 1 , R 2 and R 3 are the same as defined above with fluorine (F 2 ) in at least one solvent selected from the group consisting of halogenated hydrocarbons having 1 to 5 carbon atoms and nitrile compounds. The process according to claim 1, wherein said dicarbonyl compound (I) is a six-membered compound of the formula: wherein R' is a hydrogen atom, a halogen atom, a hydroxyl group, a cyano group, or a substituted or unsubstituted alkyl, aryl, alkoxyl or aryloxy group, and R 3 is the same as defined above, or a dicarbonyl compound of the formula wherein R 1 and R 3 are the same as defined above, and R" is a hydrogen atom, a halogen atom, or a substituted or unsubstituted alkyl group. The process according to claim 1, wherein said solvent is chloroform or acetonitrile.

Inventors: TOMIZAWA GINJIRO, UMEMOTO TERUO, TOMIZAWA, GINJIRO, UMEMOTO, TERUO, TOMIZAWA, GINJIRO, MEC KENKYUSHO OF DAIKIN, UMEMOTO, TERUO, MEC KENKYUSHO OF DAIKIN
Applicants: DAIKIN IND LTD, DAIKIN INDUSTRIES, LIMITED
Application year: 1993
Main classification: C07C45
IPC codes: C07C67, C07C45, C07C205, C07B39, C07C49