BACKGROUND OF THE INVENTION It is well known that incorporating fluorine into organic compounds can beneficially alter their characteristics. For example, fluorine is known to improve a material's surface properties, such as gas/moisture permeability and surface tension.

Such characteristics are important for polymers used in finishes, coatings, films, and the like. Additionally, fluorine is known to improve chemical properties, such as hydrolytic stability and potency. Improving chemical properties is especially important in bioactive organic compounds where minimizing dosage is a primary concern. Consequently, the incorporation of fluorinated groups, particularly trifluoromethyl groups, is common in the preparation of biomedical materials.

(See, for example, A Becker, Inventory of Industrial Fluorobiochemicals (Editions Eyrolles (1996)). Therefore, fluorinated organic compounds are desirable for many applications.

The effectiveness of fluorination, however, depends significantly upon the placement of the fluorine in the compound. For example, in bioactive compounds, relatively few fluorine atoms per molecule, typically from about 1 to about 3, are required to impart the desired effect, provided that the fluorine atoms are located at key positions in the molecule. Since the effectiveness of fluorination is often critically dependent on placement, the industry continually seeks new and effective means for selectively fluorinating organic compounds.

Therefore, the selective incorporation of fluorine at specific sites in organic molecules, particularly complex organic molecules, has created a need for new fluorochemical reagents and synthesis methodologies. The present invention fulfills this need among others.

DESCRIPTION OF THE INVENTION AND PREFERRED EMBODIMENTS The present invention provides a family of fluorinated vinyl oxirane compounds which are useful as intermediates for making other compounds, including polymeric compounds, that include fluorine atoms. The vinyl oxirane compounds of the present invention combine the beneficial properties of fluorine with the reactive properties of vinyl oxirane compounds. The reactivity of vinyl oxirane compounds arises from their dual functionality-a terminal vinyl group and an epoxide ring. Either independently or in concert, these functional groups enable vinyl oxirane compounds to react readily with a diverse array of organic compounds. The incorporation of one or more fluorine atoms into a vinyl oxirane compound therefore results in a fluorinated compound which in turn can be used for introducing fluorine atoms into other materials including, for example, commercially-significant materials such as bioactives which are used for biomedical or agricultural applications and polymers which are used for finishes and coatings.

One aspect of the present invention comprises a fluorinated compound of the following general formula:

wherein: R is a fluorine, hydrogen, an unsubstituted or substituted aliphatic or unsubstituted or substituted aromatic radical; Rl is an unsubstituted or substituted aliphatic radical, or unsubstituted or substituted aromatic radical; and R2 is a hydrogen, an unsubstituted or substituted aliphatic radical, or unsubstituted or substituted aromatic radical.

Another aspect of the invention is the provision of a process for preparing a fluorinated vinyl oxirane compound, preferably of Formula (1). In a preferred embodiment, the process comprises: (a) converting an allylic halide having at least one fluorinated group to a fluorinated homoallylic alcohol using a metallic reagent; and (b) converting the fluorinated homoallylic alcohol to the fluorinated vinyl oxirane using a base.

Yet another aspect of the present invention relates to uses for a fluorinated vinyl oxirane compound, preferably of Formula (1). The use may comprise any conventional use for a vinyl oxirane compound. In preferred embodiments, a fluorinated vinyl oxirane compound is reacted with a carbon nucleophile to produce a fluorinated allylic alcohol, or with one or more unsaturated monomers to produce a fluorinated polymer having epoxide functionality which is available for other reactions, for example, cross linking, if desired.

Still another aspect of the present invention are the fluorinated organic compounds produced by reacting the fluorinated vinyl oxirane compound as mentioned above.

Various aspects of the invention are related to the fluorinated vinyl oxirane compound of Formula (1). In that formula, R can be fluorine, hydrogen, an unsubstituted or substituted aliphatic radical, or an unsubstituted or substituted aromatic radical. Preferably, R is fluorine, hydrogen, an unsubstituted or substituted Cl-calo aliphatic radical, an unsubstituted or substituted C3-C, o alicyclic

radical, or an unsubstituted or substituted C6-C, 5 aromatic radical. More preferably, R is fluorine, hydrogen, an unsubstituted or substituted Cl-Clo alkyl, an unsubstituted or substituted C3-C8 cycloalkyl, an unsubstituted or substituted 3-6 ring member heterocyclic radical, an unsubstituted or substituted C6-CIs aryl or an unsubstituted or substituted aralkyl. Examples of substitution groups include fluorine, Cl-C6alkyls, C,-C6halogenated alkyls, C6-CIs aryls, Cl-C6 alkoxys, and cyanos.

R as a Cl-Clo alkyl may be straight chain or branched, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, pentyl, isopentyl, hexyl, heptyl, octyl, and ethylhexyl. In a more preferred class of alkyls, R is a perfluorinated Cl-C6 alkyl, in the most preferred class, R is trifluoromethyl.

R as a C3-C8 cycloalkyl may be, for example, cyclopropyl, cyclobutyl, cyclopentyl, methylcyclopentyl, cyclohexyl, methylcyclohexyl, dimethylcyclohexyl, cycloheptyl or cyclooctyl, and, preferably, cyclohexyl.

R as a 3-6 ring member heterocyclic radical may have any known heterocylic atom such as N, O, and S. Suitable fluorinated heterocycles include, for example, pyridine, pyran, thiophan, pyrrole, furan, and thiophen.

R as a C6-CIs aryl may be, for example, phenyl,-o-tolyl,-m-tolyl,-p-tolyl, -o-xylyl,-m-xylyl,-p-xylyl,-alpha-naphthyl or-beta-naphthyl. In a preferred class of aryl compounds, R is a C6-C8 aryl or a C12-C14 aryl, especially perfluoroaryl, such as pentafluorophenyl and nonofluoronaphthyl.

R as a fluorinated C7-C, 3 aralkyl may be, for example, benzyl, methylbenzyl, methoxybenzyl, diphenylmethyl, phenylethyl, or phenylpropyl. In a preferred class of aralkyl compounds, R is a C7-Cg aralkyl, especially pentafluorobenzyl.

In a still more preferred embodiment, R is fluorine or a polyhalogenated Cl-C3 alkyl such as CF3 CF2CI, CF2H, C1CF2, and CICF2CF2.

In Formula (1), R, can be an unsubstituted or substituted aliphatic radical, or an unsubstituted or substituted aromatic radical. Preferably, R, is an unsubstituted or substituted Cl-C1O aliphatic radical, an unsubstituted or substituted C3-CI0 alicyclic radical, or an unsubstituted or substituted C6 C, 5 aromatic radical. More preferably, R, is an unsubstituted or substituted Cl-Clo alkyl, an unsubstituted or substituted C3-C8 cycloalkyl, an unsubstituted or substituted 3-6 ring member heterocyclic radical, an unsubstituted or substituted C6 C, 5 aryl, or an unsubstituted or substituted aralkyl. Examples of substitution groups include fluorine, Cl-C6alkyls, C,-C6halogenated alkyls, C6-C, ^ aryls, C,-C6 alkoxys, nitros, aminos (primary and secondary), amidos, and cyanos.

R, as a Cl-Cl0 alkyl may be a straight chain or branched molecule, for example, methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, n-heptyl, n-octyl, or 2-ethylhexyl. Additionally, any of these groups may substituted with methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, methanesulphonyl, cyano, bromine, chlorine or fluorine, among others, to form such substituted alkyl groups as methoxymethyl, 2-methoxyethyl, 2-ethoxymethyl, 2-n-butoxyethyl, 3-methoxypropyl, 1-methoxybutyl, 2-methoxybutyl, methanesulphonylmethyl, 2-methanesulphonylethyl, 2-cyanoethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, trichloromethyl, 2-chloroethyl, 2- (chloromethyl) ethyl, 2,2,2-trichloroethyl, 2-chloro-n-propyl or 3-chloro-n-butyl. In a preferred class of <BR> <BR> <BR> <BR> alkyls, R, is an C,-C6 alkyl, which may be substituted by cyano, halogen or C,-C4 alkoxy, especially methyl, ethyl, n-butyl, 2-cyanoethyl, 1- (chloromethyl) ethyl or 2-methoxyethyl. In another preferred class of alkyls, R, is a branched alkyl, preferably a C2-C6 branched alkyl, especially isobutyl.

R, as a C3-Cg cycloalkyl may be, for example, cyclopropyl, cyclobutyl, cyclopentyl, methylcyclopentyl, cyclohexyl, methylcyclohexyl, dimethylcyclohexyl, cycloheptyl or cyclooctyl, preferably cyclohexyl. Any of these groups may be substituted with, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy,

cyano, chlorine or fluorine. In a preferred class of cycloalkyl, R, is a Cs-C7 cycloalkyl, and, more preferably, cyclohexyl.

R, as a 3-6 ring member heterocyclic radical may include any known heterocylic atom such as N, O, and S. Suitable heterocycles include, for example, pyridine, pyran, thiophan, pyrrole, furan, and thiophen.

R, as aC6-C, 5aryl may be, for example, phenyl, o-tolyl, m-tolyl, p-tolyl, o-xylyl, m-xylyl, p-xylyl, alpha-naphthyl or beta-naphthyl. Any of these groups may be substituted with, for example, halogen, C,-C4 alkoxy or nitro. In a preferred class of aryls, R, is C6-C8 aryl or C, 2-C, 4 aryl, and, more preferably, phenyl or naphthyl.

R, asC7-C, 3aralkyl may be, for example, benzyl, 4-methylbenzyl, o-methoxybenzyl, p-methoxybenzyl, diphenylmethyl, 2-phenylethyl, 2-phenylpropyl or 3-phenylpropyl, preferably C7-C9 aralkyl, especially benzyl.

In a still more preferred embodiment, R, is an aryl group, especially a substituted or unsubstituted phenyl group.

R2 is similar to R, with regard to the preferred and more preferred groups described above, however, R2 may also be a hydrogen radical and the still more preferred embodiment of R2 is hydrogen.

In Table 1 below, a preferred selection of group combinations for Formula (1) is presented. It should be noted that the combinations listed are for illustrative purposes and other combinations of R, R,, and R2 are well within the scope of the invention.

TABLE 1-Preferred Combinations of R, R1, and R2

Combination R R R 1 F phenyl H 2 F isopropyl H 3 F n-butyl H 4 F phenyl phenyl 2-fluoro-4-H5F chlorophenyl phenylH6CF3 7 CF, t-butyl H 2-thienylH8CF3 2-furanylH9CF3 10C1CF, phenylH t-butylH11ClCF2 12 C1CF7 methyl methyl phenylH13ClCF2CF2CF2 isopropylH14ClCF2CF2CF2 4-CH3-phenylH15ClCF2CF2CF2 16 HCF7 phenyl H ethylH17HCF2 18 HCF7 sec-butyl H 3-fluorophenylH19HCF2 20 H 2-naphthyl H The synthesis of fluorinated vinyl oxirane compounds of Forumla (1) is novel. In a preferred embodiment, the synthesis begins with a starting material comprising an allylic halide substituted with at least one fluorinated group. A preferred family of such starting materials has the following formula:

RCF2CX2_ZCHCHZXZ (2) wherein X is a halogen other than fluorine and z is 0 or 1. In a more preferred embodiment, the interior halogen in Formula (2) is chlorine resulting in the followingformula: RCF2CCl2_ZCHCH2X,. (3) One approach to synthesizing this compound when X=Cl and z=0 or 1 to form RCF2CCI=CHCH2CI or RCF2CC12CH=CH2, respectively, is taught, for example, in U. S. Patent No. 5,481,050 and M. Van Der Puy, 81 J. FLUORINE CHEM. 187 (1997). Another method of synthesizing the compound of Formula (3) when z= 1 and X=Br or I to from RCF2CCl=CHCH2Br or RCF2CC1=CHCH2I, respectively, is provided in U. S. Patent No. 5,654,473. An even more preferred embodiment of the invention starts with an allylic halide of Formula (3) wherein z=1 and X is either Br or I.

The fluorinated vinyl oxiranes are made in two steps from the starting material. First, the starting material is converted to a fluorinated homoallylic alcohol having a terminal vinyl group. Second, the fluorinated homoallylic alcohol is converted to a fluorinated vinyl oxirane.

In the first step, the conversion is performed preferably by producing an organometallic reagent of the starting material and then reacting it with a carbonyl compound to form a fluorinated homoallylic alcohol. The organometallic reagent can be produced from the starting using conventional techniques.

In a preferred embodiment, the starting material of Formula (2) is reacted with a transitional metal in a non-reactive solvent to form a fluorinated organometallic compound having the following formula: RCF2CX (MX) CH=CH2 (4)

wherein M is a transition metal. In a more preferred embodiment, wherein the allylic halide of Formula (3) is used, the resulting fluorinated organometallic compound has the following formula: RCF2CCI (MX) CH=CH2 (5) A metal should be used such that the resulting organometallic compound is not so reactive that it is unstable and consequently reacts too readily with the other reaction materials before reacting with the carbonyl compound. For example, a Grignard reagent tends to be too reactive. The transition metal is preferably selected from zinc, cadmium, or copper, and, most preferably, the metal is zinc. The solvent may be water or an organic solvent. Preferably, the solvent is an organic solvent, and, more preferably, it is an amide solvent, such as dimethylformamide or dimethylacetamide, or an ether solvent, such as dioxane, dimethoxyethane, or tetrahydrofuran (THF). In cases where the starting material is CF3CC12CH=CH2 or CF3CCl=CHCH2CI, which tends to be less reactive than compounds having terminal bromine or iodine, it is preferable to use amide solvents, most preferably, dimethylformamide.

In light of this disclosure, someone skilled in the art can readily determine and optimize the reaction conditions for preparing the organometallic reactant without undue experimentation. Typically, the reaction occurs at temperatures of about 0 to about 100°C, and preferably at about 20 to about 50°C. For example, the reaction of the starting material of Formula (3) with a zinc and THF occurs at room temperature. After an induction period, the reaction becomes moderately exothermic, making temperature control with a cooling bath desirable, especially for larger scale preparations.

Next, the fluorinated organometallic reagent of formula (4) is reacted with a carbonyl compound to form a fluorinated homoallylic alcohol having the following formula: R, R2C (OH) C (RCF2) XCH=CH2. (6)

The R, and R2 groups of this formula are the same as those in Formula (1) and are introduced to this compound via the carbonyl compound. In a more preferred embodiment, a fluorinated organometallic reagent of Formula (5) is reacted with an aldehyde or a ketone to form a fluorinated homoallylic alcohol having the following formula:

With an aldehyde (R, R2CO,), R2 is a hydrogen radical, and with a ketone (R, COR2) neither R, or R2 is a hydrogen radical. The most preferred carbonyl compound is an aldehyde.

Since the fluorinated organometallic reagent tends to be highly reactive, it is preferred to introduce the carbonyl compound as soon as possible to limit unwanted reactions. Therefore, in the preferred embodiment, the carbonyl compound is present in the metallic solution described above so that it reacts immediately with the reagent before the latter has an opportunity to react with the other reaction materials such as the starting material. In light of this disclosure, someone skilled

in the art can readily determine and optimize the reaction conditions for preparing a fluorinated homoallylic alcohol without undue experimentation.

The alcohol product of the first step is generally a high-boiling liquid which is readily recovered by distillation. Nevertheless, the crude product may be sufficiently pure to use in the second step without further purification.

In the second step, the alcohol prepared in the first step is treated with a base to form the oxirane. For example, when the alcohol of Formula (7) is used, introducing at least a molar equivalent of base removes HC1 from the compound causing an oxirane to form. The base may be organic or inorganic. Preferred inorganic bases include, for example, aqueous NaOH, KOH, or NaCO3 solutions, and preferred organic bases include, for example, amines and alkoxides.

When an aqueous base is used, the reaction mixture of the fluorinated allylic alcohol and base tends be two phases since the alcohol is immiscible in water.

Consequently, it is preferable to undertake steps to facilitate mixing. One common approach is to heat the reaction mixture. Although effective in increasing miscibility, heating tends to increase the formation of unwanted by-products.

Therefore, other techniques for promoting mixing are preferred. Examples of such techniques include, for example, the use of phase-transfer catalysts, such as tetraalkylammonium salts ("quats") to allow the reaction to be conducted at the lower end of the temperature range. Alternatively, a co-solvent may be used, such as methanol, acetonitrile, dimethylsulfoxide, dimethylformamide, and the like.

In light of this disclosure, someone skilled in the art can readily determine and optimize the reaction conditions for preparing the fluorinated vinyl oxirane compound without undue experimentation. Generally, reaction temperatures generally range from about 25 to about 150°C, and reaction times range from a few minutes to several hours.

According to the present invention, a family of fluorinated vinyl oxirane compounds is provided which can be used to introduce fluorinated groups into organic molecules. The fluorinated vinyl oxirane compounds of the present

invention can be used in a similar fashion as any conventional vinyl oxirane compound is used. Vinyl oxiranes compounds are particularly useful in the preparation of bioactive allylic alcohols of diverse structure (see J. A. Marshall, Chemical Reviews, 89 (1989) 1503). Other uses of vinyl oxiranes, include, for example, wash resistant finishes for fabrics (CA 115: P10793t), water proofing (CA 113: P99720w and 101: P56025h), and in various polymers (CA 108: P151166h, 96: P53289q, 99: P89595n), since they can be copolymerized with e. g. ethylene.

Still other applications of the compound of the present invention will be apparent to someone skilled in the art in light of this disclosure.

EXAMPLES The following examples are illustrative of the practice of the present invention.

Example 1.

This example illustrates the preparation of 2-tifluoromethyl-2-vinyl-3-phenyl oxirane from CF3CCl=CHCH2I.

Zinc powder (10.2 g) was activated by treatment with 20 ml 1 N HC1, followed by washing with 25 ml ethanol and 2x25 ml ether. Residual ether was flushed out with a stream of nitrogen. Dry THF (70 ml) was then added, followed by 11.0 g (0.104 mol) of benzaldehyde. The mixture was stirred mechanically while adding 27.0 g (0.0998 mol) of CF3CC1=CHCH2I over 35 minutes with water bath cooling to keep the temperature at 25-30 °C. Stirring was continued for 1 hour. The slurry was filtered and the filtrate treated with 100 ml 2 N HC1. The organic layer was separated and the aqueous phase extracted with 100 ml ether. The combined organic layers were washed with water and dried (Na2SO4). Removal of volatiles at the pump gave 21.6 g of 95 % pure product by GC analysis. Distillation provided 18.9 g (76 % yield) of the alcohol PhCH (OH) CCl (CF3) CH=CH2, bp 77 °C at 0.8 mm Hg.'H NMR (for major diastereomer) 8: 7.3 (Ar); 6.2 (dd, 1 H, J = 16.7 and 10.8 Hz, CH=CH2); 5.6 (2 H, CH=CH 2); 5. 1 (s, 1 H, CHOH); 2.9 (bs, 1 H, OH).'"FNMR8:-71.7ppm. IR (cm-'): 3451 (OH); 1645 (weak); 1495;

1410; 1456; 1249; 1188; 1171; 730; 701. Analysis: Calc. for jH. oClFO (250.65): C, 52.71; H, 4.02 %. Found: C, 53.09; H, 3.92 %.

The alcohol prepared as described above (8.0 g, 31.9 mmol) was stirred with 18 ml 2 N NaOH at 85 °C for 0.5 hour. The cooled reaction mixture was neutralized and the organic product taken up in 25 ml CH2C12, washed with 15 ml water, 15 ml aq. NaCl, dried (Na2SO4), and distilled at 5 mm Hg to give 4.7 g (22 mmol, 69 % yield) of the oxirane, bp 59-63 °C (isomer ratio 10: 1).'H NMR 8: 7.3 (5 H); 5.5 (m, 3 H); 4.5 (s, 1 H).).'9F NMR 6:-75.5 (s, major isomer);-69.2 (s, minor isomer) ppm. Analysis: Calc. for CllHgF3O (214.19): C, 61.68; H, 4. 24%. Found: C, 61.63; H, 4. 31%.

Example 2.

This example illustrates the preparation of 2-trifluoromethyl-2-vinyl-3- isopropyloxirane from CF3CC1=CHCH2I.

In a manner similar to that used in Example 1, zinc powder was reacted with CF3CC1=CHCH2I in the presence of isobutyraldehyde to give (CH3) 2CHCH (OH) CC1 (CF3) CH=CH2, bp 91 °C at 48 mm Hg.'9F NMR:-72.8 ppm (major isomer).

The alcohol so obtained was stirred vigorously with 1.1 equivalents of 1 N NaOH at 65-70 °C for 2 hours. The corresponding oxirane, bp 44-48 °C at 55 mm Hg, was obtained in good yield.'H NMR: 1.0 (dd, 6 H), 1.4 (m, 1 H), 3.0 (d, 1 H), 5.4-6.2 (3 H) ppm.'9F NMR:-76.3 ppm.

Example 3.

This example illustrates the preparation of 2-trifluoromethyl-2-vinyl-3-phenyl oxirane from CF3CCl=CHCH2Cl.

To a stirred mixture of activated Zn powder (40 g, 0.60 mol), 500 ml anhydrous dimethyl formamide, and 54 ml (0.56 mol) of benzaldehyde, under N2,

were added 90 g (0.51 mol) of CF3CCl=CH-CH2Cl drop-wise over a period of 60 minutes. The reaction flask was placed in a water bath to moderate the exothermic reaction during the addition of CF3CC1=CHCH2Cl. After complete addition of CF3CCl=CHCH2Cl, the reaction mixture was stirred for an additional hour at room temperature and filtered. To the filtrate, 1 liter of 2N HC1 and water (500 ml) were sequentially added with stirring. The lower layer was separated, washed with 2% aqueous NaHSO3 (2x100 ml), water (100 ml), dried (MgSO4), and concentrated under reduced pressure to afford 80 g of crude alcohol, which was used in the next step without further purification.

To the crude alcohol obtained above, 125 ml 2N NaOH was added, and the mixture stirred at 85 °C for 45 minutes. The reaction mixture was cooled to room temperature, neutralized with 2N HC1, and the organic material extracted with 300 ml CH2C12. The organic solution was washed with water (2x100 ml), brine (50 ml), dried (MgS04), and concentrated on a rotary evaporator. Distillation of the resultant material afforded 36.0 g of 2-trifluoromethyl-2-vinyl-3-phenyloxirane.

Example 4.

This example illustrates the preparation of 2-trifluoromethyl-2-vinyl-3-phenyl oxirane from CF3CC12CH=CH2.

To a stirred mixture of activated Zn powder (1.3 g, 20 mmol), anhydrous DMF (20 ml), and C6H^CHO (2.12 g, 20 mmol) were added CF3CC12CH=CH2 (3.0 g, 17 mmol) drop-wise and the resultant reaction mixture was stirred under a nitrogen atmosphere for 1 hour. Work-up of the reaction mixture, as described in Example 3, afforded 1-phenyl-2-chloro-2-trifluoromethylbut-3-en-1-ol (2.5 g). The crude alcohol was treated with 2N NaOH and worked-up, as described in Example 3, to afford 2.0 g of the corresponding oxirane.