Claims
- 1. A gem-dihalocyclohexane compound of the formula ##STR28## wherein X is chlorine or fluorine and R.sub.1 and R.sub.2 are independently selected from the group consisting of --H, --CH.sub.2 OH, --COF, --COCl, --CF.sub.3, --CN, ##STR29## and --CH.sub.2 CH.sub.2R, wherein R is --H or alkyl of 1-4 carbon atoms; with the proviso that at least one of R.sub.1 and R.sub.2 is other than --H.
- 2. A compound according to claim 1 wherein X is chlorine.
- 3. A compound according to claim 1 wherein X is fluorine.
- 4. A compound according to claim 1 wherein R.sub.1 and R.sub.2 are the same.
- 5. A compound of the formula ##STR30##
- 6. A compound of the formula ##STR31##
- 7. A compound of the formula ##STR32##
- 8. A compound of the formula ##STR33##
- 9. A compound of the formula ##STR34##
- 10. A gem-dihalocyclohexane compound of the formula ##STR35## wherein X is chlorine or fluorine and R.sub.1 is --H and R.sub.2 is selected from the group consisting of --CH.sub.2 OH, --COF, --CF.sub.3, CN, ##STR36## and --CH.sub.2 CH.sub.2R, wherein R is --H or alkyl or 1-4 carbon atoms.
- 11. A gem-dihalocyclohexane compound of the formula ##STR37## wherein X is chlorine or fluorine and R.sub.1 is selected from the group consisting of --CH.sub.2 OH, --COF, --COCl, --CF.sub.3, --CN, ##STR38## and --CH.sub.2 CH.sub.2R, wherein R is --H or alkyl or 1-4 carbon atoms and R.sub.2 is H.
CROSS-REFERENCE TO RELATED APPLICATIONS
This is a continuation-in-part of copending application Ser. No. 604,272, now U.S. Pat. No. 4,517,372.
This invention relates to fluorinated carbocyclic compounds and to a method for the preparation thereof. The fluorinated carbocyclic compounds prepared in accordance with the invention include optionally substituted gem-dihalocyclohexane compounds, fluorocyclohexenyl compounds and fluoro aromatic compounds, useful as chemical intermediates for the synthesis of a wide variety of end products, especially for the synthesis of pesticides, pharmaceuticals and polymers. Thus, for example, the fluoroaromatic compounds are particularly useful in the synthesis of a wide variety of diphenyl ether herbicides and the like by reaction, in a known manner with an alkali metal phenoxide.
There are, at present, only a limited number of synthetic methods for producing fluorine substituted aromatic substrates, and these methods are generally not commercially attractive. See Max M. Boudakian, Encyclopedia of Chemical Technology, Kirk-Othmer 3rd Ed., Vol. 10, pp. 901-936. One method is the Schiemann reaction, in which a diazonium fluoroborate salt is decomposed, converting an aniline to a fluorobenzene derivative. On an industrial scale, substituted anilines are diazotized with sodium nitrite in anhydrous hydrogen fluoride, followed by in situ decomposition of the aryldiazonium fluoride. However, the reaction conditions, variable yields, and environmentally troublesome by-products present difficulties when this reaction is employed in a large scale commercial process.
Aromatic substrates with electron withdrawing groups can be reacted with fluoride ions to replace chlorine substituents and yield fluoroaromatic derivatives. These reactions are usually conducted under vigorous conditions and proceed by nucleophilic substitution with fluoride ions. The positional requirement for electron withdrawing substituents as well as special solvents and waste KF/KCl salts limits the synthetic utility of this type of reaction.
The common method of halogenating an aromatic substrate is by a Lewis acid catalyzed electrophilic substitution type reaction. There are numerous reagents suitable for bromination and chlorination but few available for fluorination. Molecular fluorine is much too reactive and results in poor selectivity in most reactions. The synthetic approach has been to design less reactive fluorinating agents, but each reagent has its drawbacks for commercial application.
The preparation of 1-fluorocycloalkene from the corresponding 1,1-difluorocycloalkane by reaction with anhydrous neutral alumina is disclosed in Strobach et al., J. Org. Chem., Vol. 36, pages 818-820 (1971). The 1,1-difluorocycloalkane is prepared by reaction of the corresponding cyclic ketone and sulfur tetrafluordde.
Hasek et al, J. Amer. Chem. Soc., 82, 543 (1960) disclose the preparation of gem-difluorocycloalkanes by reaction of the corresponding cyclic ketone with sulfur tetrafluoride and hydrogen fluoride. Among the specific reactions disclosed in the reference is the reaction of cyclohexanone with sulfur tetrafluoride at temperatures below 50.degree. Celsius to form 1,1-difluorocyclohexane.
The process of the present invention utilizes chlorocyclohexenyl compounds as starting reactants. The chlorocyclohexenyl compounds employed are, for the most part, known compounds, some of which are commercially available. These compounds may be conveniently prepared by a Dills-Alder reaction of a suitable diene, such as chloroprene, with various dienophiles. See, for example, I. Inukai and M, Kasai, J. Org. Chem. 30, 3567 (1965). The preparation of chlorocyclohexenyl compounds in this manner may be represented schematically by the following equation: ##STR6##
In the process of the present invention, the chlorocyclohexene starting reactant is converted to a gem-dihalo intermediate and then to a corresponding fluorocyclohexene intermediate. Some of the fluorocyclohexene intermediates are known compounds and have been shown in the literature to be prepared by means of a Diels-Alder reaction utilizing fluoroprene in the following manner. (A. A. Petrov and A. V. Tumanova CA 51 g) ##STR7##
However, the making and handling of fluoroprene on a commercial scale presents serious difficulties, including explosion hazards, due to the unstable nature of fluoroprene. By the process of the present invention the difficulties and hazards associated with the making and handling of fluoroprene are avoided.
It is therefore an object of the present invention to provide a novel synthetic route for the preparation of mono- and di-substituted fluoro aromatic compounds. It is a further object of the invention to provide novel substituted fluorocarbocyclic intermediate compounds which can be used in the synthesis of substituted fluoro-aromatic compounds.
In accordance with this invention, fluoro-substituted carbocyclic compounds are prepared by
(A) reacting hydrogen fluoride with a chloro-cyclohexenyl compound of the formula ##STR8## where R.sub.1 and R.sub.2 are independently selected from the group consisting of --H, --CH.sub.2 OH, --COF, --COCl, --CF.sub.3, --CN, ##STR9## and --CH.sub.2 R, where R is --H or alkyl of 1-4 carbon atoms, to form a gem-dihalocyclohexane compound of the formula ##STR10## where X is chlorine or fluorine and R.sub.1 and R.sub.2 are as defined above,
(B) dehydrohalogenating the gem-dihalocyclohexane compound in the vapor phase to form fluoro-cyclohexenyl compound of the formula ##STR11##
(C) and contacting the fluoro-cyclohexenyl compound, in the vapor phase, with a dehydrogenation catalyst to form a fluoro-substituted aromatic compound of the formula ##STR12##
The preferred compounds employed in the process of this invention are those shown above, wherein R.sub.1 and R.sub.2 are the same or wherein either R.sub.1 or R.sub.2, preferably R.sub.2 are hydrogen.
Novel fluorinated carbocylic compounds that may be prepared in accordance with the present invention include substituted gem-dihalocyclohexane compounds exemplified by the formula ##STR13## wherein X is chlorine or fluorine and R.sub.1 and R.sub.2 are independently selected from the group consisting of --H, --CH.sub.2 OH, --COF, --COCl, --CF.sub.3, --CN, ##STR14## and --CH.sub.2 CH.sub.2 R, where R is --H or alkyl of 1-4 carbon atoms, with the proviso that at least one of R.sub.1 and R.sub.2 is other than --H.
The synthesis of the gem-dihalocyclohexane intermediates is accomplished by reaction of hydrogen fluoride with a chlorocyclohexenyl compound in a manner exemplified by the following equation. ##STR15##
The reaction proceeds stepwise, and if pushed to completion will result in high yields of the gem-difluorocyclohexane compound. However, by appropriate limitation of time, temperature or hydrogen fluoride reactant, high yields of the chlorofluorocyclohexane compound may be recovered. Typical reaction products are a mixture of the two which may be conveniently separated, for example, by conventional physical separation techniques, such as fractional distillation, fractional crystallization, or the like. When the product is to be employed in the further preparation of fluorocyclohexenyl compounds, or fluoroaromatic compounds, such separation is not necessary, since either of these gem-dihalocyclohexane compounds may be employed for this purpose. The reaction of the chlorocylohexenyl compound with hydrogen fluoride is preferably carried out in the liquid phase, most preferably under reflux conditions. It is preferred to carry out the reaction neat, however, a solvent, for example diethyl ether, may be employed if desired.
The dehydrohalogenation reaction of the gem-dihalo intermediate(s) to form a fluorocyclohexenyl compound is exemplified by the following equation: ##STR16## where X is Cl or F and R.sub.1 and R.sub.2 are as previously defined. It has been found preferable to remove excess hydrogen fluoride from the fluorination step, for example by vaporization, at the start or prior to the dehydrohalogenation step. The dehydrohalogenation step is preferably carried out in the vapor phase at atmospheric pressure, although sub-atmospheric or super-atmospheric conditions may be employed. The reaction may be carried out neat, however, it has been found that yields may be increased when a solvent such as a chlorinated aromatic solvent is employed. Suitable solvents include for example, monochlorobenzene, dichlorobenzene, trichlorobenzene, chloroxylenes, and the like. The temperature employed will depend on the boiling point of the solvent, but will typically be in the range of about 160.degree. to about 460.degree. Celsius and preferably in the range of about 240.degree. to about 340.degree. Celsius. The dehydrohalogenation reaction may be carried out at a lower temperature, such us about 200.degree. Celsius when carried out in the presence of an alumina catalyst. However, the alumina catalyst serves preferentially as dehydrofluorination catalyst and thus is only recommended when the gem-dihalocyclohexane reactant is predominantly the gem-difluorocycloalkane. When an alumina catalyst is used in the presence of a chloro-fluorocyclohexane reactant, the formation of chloro-cyclohexenyl products is favored. When it is desired to drive the reaction in the direction of formation of the fluoroaromatic product directly, it is preferred to employ a dehydrogenation catalyst, such as a noble metal catalyst and the like.
The aromatization of the fluorocyclohexenyl intermediate is exemplified by the following equation: ##STR17## where R.sub.1 and R.sub.2 are as defined above. The reaction is carried out in the vapor phase in the presence of a dehydrogenation catalyst. Suitable dehydrogenation catalysts include, for example, platinum, palladium, rhodium, iridium, ruthenium, rhenium, or nickel metals, either in elemental form or as an M.degree. compound or complex thereof, either unsupported or on a suitable support. Other suitable catalysts include copper chromite, which is believed to have the formula CuO.sup..multidot. Cr.sub.2 O.sub.3, chromium oxide, molybdenum oxide, tungsten oxide, and vanadium oxide. Typical catalyst supports include for example activated carbon, charcoal, silicon carbide, silica gel, alumina, acidic silica-alumina, silica, titania, zirconia, kieselguhr, mixed rare earth oxides, carbonates, barium carbonate, barium sulfate, calcium carbonate, pumice, silica alumina mixtures, zeolites, and the like. Suitable catalytic complexes include the M.degree. compounds where M is Pd, Pt, Ni, rhodium or ruthenium, and is bound in the structure by phosphine, phosphite or carbamyl ligands. Complexes of this type are generally soluble in the reaction mixtures employed in the process of this invention. Typical complexes include tetrakis(triphenylphosphine)platium (O); Bis[bis(1,2-diphenylphosphino)ethane]palladium (O); Bis[bis(1,2-diphenylphosphino)benzene]palladium (O); Bis(1,5-cyclooctadiene)nickel (O); Tetrakis(triethylphosphite)nickel (O); Tetrakis(triphenylphosphine)nickel (O) and tetrakis(triphenylphosphite)nickel (O); chlorotris(triphenylphosphine)rhodium (I); and dichlorotris(triphenylphosphine)ruthenium (II). A preferred catalyst system is palladium on a carbon support. The reaction is generally carried out at a temperature of about 200.degree. to about 400.degree. and preferably about 250.degree. to about 350.degree. Celsius.
The aromatization reaction may be carried out neat. However, it has been found preferable to carry out the reaction in the presence of a solvent, preferably a halocarbon solvent which may serve as a hydrogen acceptor.
The hydrogen acceptors which may be employed in the aromatization step of this invention include those materials known in the art as hydrogen acceptors in like reactions. For example, the hydrogen acceptors include olefins containing 2 to 20 carbon atoms, aromatic nitro-compounds such as nitrobenzene, certain carbonyl compounds such as aldehydes and ketones, and certain halocarbon compounds capable of exchanging at least one chlorine, bromine, or iodine atom per molecule for a hydrogen atom. Preferred hydrogen acceptors for this purpose are halocarbons of the formula: ##STR18## where Y is Cl, Br or I; Z is Cl, Br or I; m is 0 to 4; n is 0 to 3, p is 0 to 3, and m+n is at least 1; with the proviso that when m is 0, p is at least 1. Suitable halocarbon hydrogen acceptors are chloro-, bromo-, and iodoaromatic wherein the chloro-, bromo-, or iodo-, substituent is present either on the aromatic ring or on a side-chain such as an alkyl or alkoxy side-chain, including, for example, halobenzenes such as chlorobenzene, dichlorobenzene, trichlorobenzene, tetrachlorobenzene, bromobenzene, dibromobenzene, tribromobenzene, tetrabromobenzene; chlorotoluenes such as orthochlorotoluenes, orthobromotoluenes, dibromotoluene, tribromotoluene, tetrabromotoluene orthoiodotoluene, metaiodotoluene, paraiodotoluene, diiodotoluenes, triiodotoluenes, tetraiodotoluenes; benzylchlorides, such as 2-chlorobenzene chloride, 2,6-dichlorobenzylchloride, 2,3,6-trichlorobenzychloride, benzalchlorides, benzotrichloride, benzylbromide, benzalbromide, benzotribromide, benzyliodide, orthochlorobenzotrichloride, parachlorobenzotrichloride, parachlorobenzotrifluoride, various halogenated fused ring aromatics, such as the haloaphthalenes and haloanthracenes, wherein the halo is chloro, bromo or iodo.
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Continuation in Parts (1)
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Number |
Date |
Country |
| Parent |
604272 |
May 1984 |
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Patent Grant
4792618
