IL154798A - Intermediate compounds for the preparation of pesticidal fluoroolefin compounds and process for their preparation - Google Patents

Abstract

A compound of the formula wherein R is hydrogen or C1-C4 alkyl, or R and R1 are taken together with the carbon atom to which they are attached to form a cyclopropyl group; R1 is C1-C4 alkyl or cyclopropyl, or R and R1 are taken together with the carbon atom to which they are attached to form a cyclopropyl group; Ar is phenyl optionally substituted with any combination of from one to three halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy gorups, or 1 - or 2-naphthyl optionally substituted with any combination of from one to three halogen, C1-C4 alkyl, C1-C4 haloalkyl, C1-C4 alkoxy or C1-C4 haloalkoxy groups; and the configuration of the groups ArCRR1- and -CH2Br about the double bond being predominately mutually trans. 2384 י" ד באלול התשס" ד - August 31, 2004

Description

pwM w O>p m ip o iN iNi o jmtoiJi INTERMEDIATE COMPOUNDS FOR THE PREPARATION OF PESTICIDAL FLUOROOLEFIN COMPOUNDS AND PROCESS FOR THEIR PREPARATION PAT/5314 HE FIELD OF INVENTION The present invention was divided out of Israel Patent Application IL 120965 ("the parent application") and relates to intermediate compounds which are useful for the preparation of pesticidal fluoroolefin compounds and to a process for their preparation.

BACKGROUND OF THE INVENTION Fluoroolefin compounds which are useful as pesticidal agents are described in WO 94/06741 and GB 2,288,803-A. Those references also describe processes for the preparation of fluoroolefin compounds. However, those processes are not entirely satisfactory because the fluoroolefin compounds are produced in relatively low yields. Those references also fail to teach how to make the intermediate compounds of the present invention.

SUMMARY OF THE INVENTION The present invention provides a compound having the structural formula III (III) wherein R is hydrogen or Ci-C4alkyl, or R and Ri are taken together with the carbon atom to which they are attached to form a cyclopropyl group ; Ri is or cyclopropyl, or R and Ri are taken together with the carbon atom to which they are attached to form a cyclopropyl group; Ar is phenyl optionally substituted with any combination of from one to three halogen, Cx-C^alkyl, Cx-C^haloalkyl , Ci-C4alkoxy or Ci-Chaloalkoxy groups, or 1- or 2-naphthyl optionally substituted with any combination of from one to three halogen, Ci-C4alkyl, C1-C4haloalkyl , C!-C4alkoxy or Ci~C4haloalkoxy groups; and the configuration of the groups ArCR x- and -CH2Br about the double bond being predominately mutually trans .

The present invention also provides a process for making a compound of formula III (III) wherein Ar, R and Ri are as described above, which process comprises reacting a 4-aryl-2-fluoro-2-butene-l-ol compound having the structural formula II (ID wherein R, Rl and Ar are as described above with a brominating agent selected from the group consisting of a bromine-triphenyl phosphine complex, phosphorous tribromine, thionyl bromide, HBr, and mixtures thereof, in a solvent at a temperature of about 50 °C to 130°C.

Other objects and advantages of the present invention and of the invention of the parent application will be apparent to those skilled in the art from the description below and the appended claims .

The description below includes matter which relates to the invention of the parent application and is not claimed herein, but is retained for the sake of completeness .

DETAILED DESCRIPTION OF THE INVENTION A preferred embodiment of the invention of the parent application comprises reacting a 4-aryl-2-fluoro-2-butene-l-ol of formula II with at least about one molar equivalent of a brominating agent, preferably in a temperature range of about 50 °C to 130°C, in the presence of a first solvent to form a 4-aryl-l-bromo-2-fluoro-2-butene of formula III, and reacting the formula III compound with about 0.001 to 0.1, preferably about 0.005 to 0.1, molar equivalent of palladium catalyst, at least about 2 molar equivalents, preferably about 2-6 molar equivalents of a base, and a boronic acid of formula IV, preferably 1 molar equivalent of a boronic acid in a temperature range of about 50°C to 130 °C, in the presence of a second solvent.

The present invention relates to the 4-aryl-l-bromo-2-fluoro-2-butene compounds which are utilized in the process of the parent invention and to a process for their preparation. The 4-aryl-l-bromo-2-fluoro-2-butene compounds have the structural formula III (Ill) wherein R is hydrogen or and R-L is Cn-Cjalkyl or cyclopropyl, or R and Rx are taken together with the carbon atom to which they are attached to form a cyclopropyl group; Ar is phenyl optionally substituted with any combination of from one to three halogen, C1-C^ lkyl, C^-C^haloalkyl, C^-C^alkoxy or C1-^haloalkoxy groups , or 1- or 2-naphthyl optionally substituted with any combination of from one to three halogen, C^-C^alkyl, C1-C^haloalkyl , C1-^alkoxy or C^-dhaloalkoxy groups; and the configuration of the groups ArCRRx- and -CH2Br about the double bond is predominately mutually trans.

Exemplary of halogen hereinabove are fluorine, chlorine, bromine and iodine. The terms "C-, -C4haloalkyl" and "C1-C^haloalkoxy" are defined as a C^-C^alkyl group and a C^-C^alkoxy group substituted with one or more halogen atoms, respectively.

The product formula I compounds may be isolated by diluting the reaction mixture with water and extracting the product with a suitable extraction solvent. In the isolation procedure, conventional extraction solvents such as ether, ethyl acetate, toluene, methylene chloride and the like may be utilized.

Brominating agents suitable for use in the process of this invention include, but are not limited to, bromine/triphenyl phosphine complexes, phosphorus tribromide, thionyl bromide, concentrated hydrobromic acid, and the like, and mixtures thereof. Bromine/tri-phenyl phosphine complexes are preferred brominating agents .

First solvents suitable for use in the present invention include, but are not limited to, aromatic hydrocarbons such as toluene, benzene, xylenes, mesitylene and the like, halogenated aromatic hydrocarbons such as chlorobenzene , fluorobenzene and the like, carboxylic acid amides such as N,N-dimethyl-formamide and the like, ethers such as tetrahydrofuran, dioxane and the like, and halogenated hydrocarbons such as chloroform, carbon tetrachloride and the like, and mixtures thereof. Preferred first solvents include halogenated hydrocarbons with carbon tetrachloride being more preferred.

Second solvents useful in the process of this invention include, but are not limited to, aromatic hydrocarbons such as toluene, benzene, xylenes, mesitylene and the like, halogenated aromatic hydro-carbons such as chlorobenzene, fluorobenzene and the like, carboxylic acid amides such as N, N-dimethylform-amide and the like, glycols such as dimethoxyethane and the like, such as methanol, ethanol and the like, ketones such as acetone and the like, and ethers such as tetrahydrofuran, dioxane and the like, and mixtures thereof, and mixtures with water. Preferred second solvents include aromatic hydrocarbons and aromatic hydrocarbon/C1-C4alcohol mixtures with a toluene/ethanol mixture being more preferred.

Palladium catalysts suitable for use in the present invention include, but are not limited to, palladium (0) catalysts such as bis (dibenzylideneacetone) alladium ( 0 ) , tetrakis (triphenylphosphine) alladium (0) and the like, palladium (II) catalysts such as bis (acetonitrile ) -palladium (II) chloride, bis (triphenylphosphine ) - palladium(II) chloride, [1 , 4 -bis (diphenylphosphine) -butane] palladium (II) dichloride, [1, 1' -bis (diphenyl-phosphino) ferrocene] palladium (II) diacetate, palladium (II) acetate, palladium ( II) chloride and the like, and palladium on activated carbon, and mixtures thereof. Preferred catalysts include palladium (0) catalysts with bis (dibenzylideneacetone) alladium (0) being more preferred.

Bases suitable for use in this invention include, but are not limited to, alkali metal carbonates such as sodium carbonate and potassium carbonate, alkaline earth metal carbonates such as calcium carbonate and the like, alkali metal hydrogen carbonates such as sodium hydrogen carbonate and the like, alkali metal hydroxides such as sodium hydroxide and potassium hydroxide, alkaline earth metal hydroxides such as calcium hydroxide and the like, alkali metal such as potassium tert-butoxide and the like, thallium (I) carbonate, thallium (I) , thallium (I) hydroxide, and tri (C - ^alky! ) amines such as trimethylamine , and mixtures thereof. Preferred bases include alkali metal carbonates with potassium carbonate being more preferred.

In another preferred embodiment of the parent invention, a 4-aryl-l-bromo-2-fluoro- 2 -butene of formula III is reacted with a palladium catalyst, a base and a boronic acid of formula IV.

Boronic acids of formula IV, boronic anhydrides of formula V, and borate esters of formula VI may be prepared, as illustrated in Flow Diagram I, by reacting an aryl compound of formula VII with a tri ( -C-aikyl ) borate of formula VIII to form the formula VI borate ester, and hydrolyzing the formula VI borate ester with aqueous acid to form the boronic acid of formula IV which may spontaneously combine with other formula IV compounds to form the boronic anhydride of formula V.

I FLOW DIAGRAM I (VII) (M = Li or MgBr) B(OR2)3 (VIII) (R20)2B-Ari (VI) (HO) 2B-Ari (IV) -H20 V 2 Ar ^B 0 0 Ar 0 Ar (V) Starting 4-aryl-2-fluoro-2-butene-l-ol compounds of formula II may be prepared according to the procedures described in WO 94/06741 and GB 2,288, 803 -A.

In another preferred embodiment of the parent invention, a 4-aryl-2-fluoro-2-butene-l-ol of formula II is reacted with a brominating agent in a temperature range of about 50 °C to 130 °C, and a 4 -aryl - 1 -bromo- 2 -fluoro-2-butene of formula III is reacted with a palladium catalyst, a base and a formula IV, V or VI compound in a temperature range of about 50 °C to 130 °C .

Preferred formula I fluoroolefin compounds which may be prepared by the process of this invention are those wherein R is hydrogen and Rx is isopropyl or cyclopropyl, or R and Rx are methyl, or R and Rx are taken together with the carbon atom to which they are attached to form a cyclopropyl group; Ar is phenyl optionally substituted with any combination groups; and Ar1 is 3 -phenoxyphenyl optionally substituted with any combination of from one to five halogen, C^- alkyl, Ci-Cjhaloalkyl , C^-C^alkoxy or C^-C^haloalkoxy groups, 3-biphenyl optionally substituted with any combination of from one to five halogen, C^-C^haloalkoxy groups, 3-benzylphenyl optionally substituted with any combination of from one to five halogen, C^-C^alkyl, C^-C^haloalkyl , C^-C^alkoxy or C^-^haloalkoxy groups, or 3-benzoylphenyl optionally substituted with any combination of from one to five halogen, C^-C^haloalkoxy groups.

The process of the present invention is also preferably used for the preparation of pesticidal fluoroolefins of formula I wherein R and Rx are methyl, or R and Rx are taken together with the carbon atom to which they are attached to form a cyclopropyl group; Ar is phenyl optionally substituted with any combination of from one to three halogen, C1-C^alkyl, C1- ^haloalkyl, C^-C^alkoxy or ^-^haloalkoxy groups and Ara is 3-phenoxyphenyl optionally substituted with any combination of from one to five halogen, groups In order to facilitate a further understanding of the invention, the following examples are presented primarily for the purpose of illustrating more specific details thereof. The scope of the invention should not be deemed limited by the examples, but encompasses all the subject matter defined in the claims.

EXAM LE 1 Preparation of 1- (p-Chlorophenvl) -1- (3-bromo-2-flnproprppeayl) cyclopropane, (Z) - Under a nitrogen atmosphere, a solution of bromine (0.767 g, 4.8 mmol) in carbon tetrachloride at ice-water bath temperature is treated sequentially with a solution of triphenylphosphine (1.26 g, 4.8 mmol) in carbon tetrachloride and a solution of 3- [1- (p-chlorophenyl) -cyclopropyl] -2-fluoro-2-propen-l-ol , (Z)- (0.907 g, 4 mmol) in carbon tetrachloride, heated to and stirred at reflux for 70 minutes, cooled to room temperature, and poured into petroleum ether. The resultant mixture is filtered, and the filtrate is concentrated in vacuo to obtain a residue. The residue is dissolved in petroleum ether and passed through a plug of silica gel (eluted with hexanes) to obtain an oil. Flash column chromatography of the oil using silica gel and a 3:20 methylene chloride/hexanes solution gives the title product as a colorless oil (0.73 g, 63% yield) which is identified by MR spectral analyses.

EXAMPLE 2 Preparation of 1- (p-Chlorophenvl) -1- r2-fluoro-3- (4-fluoro-3 -phenoxyphenyl) propenvlT cyclopropane .—(Z) - Under a nitrogen atmosphere, a mixture of l-(p-chlorophenyl ) -1- (3-bromo-2-fluoropropenyl ) cyclopropane, (Z) - (0.434 g, 1.5 mmol) , 4 -fluoro-3 -phenoxybenzene-boronic acid (0.452 g, 1.95 mmol), potassium carbonate (1.86 g, 13.5 mmol) and bis (dibenzylideneacetone) -palladium (0) (Pd(dba)2, 4.3 mg, 0.075 mmol) in toluene is heated at 80 °C for one hour, cooled to room temperature, diluted with water, and filtered through diatomaceous earth. The phases are separated and the aqueous phase is extracted with ethyl acetate. The organic phase and ethyl acetate extract are combined, washed with water, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain a residue . Flash column chromatography of the residue using silica gel and a 3:20 methylene chloride/hexanes solution gives the title product as an oil (0.274 g, 63% yield) which is identified by NMR spectral analyses.

As can be seen from the data in Examples 1 and 2 , 1- (p-chlorophenyl) -1- [2-fluoro-3- (4-fluoro-3 -phenoxy- phenyl) propenyl] cyclopropane, (Z)- is obtained in 40% yield from 3- [1- (p-chlorophenyl) cyclopropyl] -2-fluoro-2- propen-l-ol, (Z)-. In contrast, WO 94/06741 discloses that 1- (p-chlorophenyl) -1- [2-fluoro-3- (4-fluoro-3- phenoxyphenyl) propenyl] cyclopropane, (Z) - is obtained in 20% yield from 3- [1- (p-chlorophenyl) cyclopropyl] -2- fluoro-2-propen-l-ol , (Z) - .

Preparafcion of l-Bromo-4- (p-chloroohenvl) -2-flvorP- thyl-2-pentene, (2) - Under a nitrogen atmosphere, a solution of triphenyl phosphine (0.96 g, 4.25 mmol) in carbon tetrachloride at -5 °C is treated dropwise with a solution of bromine (0.679 g, 4.25 mmol) in carbon tetrachloride, warmed to and stirred at room temperature for 45 minutes, treated with a solution of 4- (p-chlorophenyl) -2-fluoro-4 -methyl -2-penten-l-ol, (Z) - (0.81 g, 3.54 mmol) in carbon tetrachloride, refluxed for 2 hours, cooled to room temperature, and poured into petroleum ether. The resultant mixture is filtered through diatomaceous earth. The filtrate is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine, dried over anhydrous sodium sulfate and concentrated in vacuo to obtain an oil . Flash column chromatography of the oil using silica gel and a 1:9 ethyl acetate/hexanes solution gives the title product as a colorless oil (0.736 g, 71% yield) which is identified by MR spectral analyses.

Preparation of 4- (p-Chlorophenyl) -2-flUQgp-1- (4-fluoro-3 -phenoxyphenvl) -4 -methvl-2 -pentene .—£Zl___ Under a nitrogen atmosphere, a mixture of l-bromo-4-(p-chlorophenyl) -2-fluoro-4 -methyl -2 -pentene, (Z) - (320.8 mg, 1.1 mmol) , bis (dibenzylideneacetone) palladium ( 0 ) (Pd(dba)2, 31.6 mg, 0.055 mmol) in toluene (8 mL) is treated with potassium carbonate (608 mg, 4.4 mmol), degassed, treated with a solution of 4-fluoro-3-phenoxybenzeneboronic acid (331.8 mg, 1.43 mmol) in ethanol (2 mL) , refluxed for 45 minutes, cooled to room temperature, and filtered through diatomaceous earth. The filtrate is diluted with ethyl acetate, and the resultant solution is washed sequentially with water and brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a residue. Flash column chromatography of the residue using silica gel and a 1:9 ethyl acetate/hexanes solution gives the title product as a colorless liquid (401 mg, 91% yield) which is identified by MR spectral analyses.

As can be seen from the data in Examples 3 and 4, 4- (p-chlorophenyl) -2-fluoro-l- (4-fluoro-3-phenoxyphenyl) -4-methyl-2-pentene, (2)- is obtained in 65% yield from 4-(p-chlorophenyl) -2-fluoro- -methyl-2 -penten-l-ol, (2) - . In contrast, GB 2,288,803-A discloses that 4- (p-chlorophenyl) -2-fluoro-l- (4-fluoro-3-phenoxyphenyl) -4-methyl-2-pentene, (2)- is obtained in 37% yield from 4-{p-chloro-phenyl) -2-fluoro-4-methyl-2-penten-l-ol, (2)-.

EXAMPLE 5 Preparation of 4-Fluoro-3-phenoxybenzeneboronic acid A solution of 5-bromo-2-fluorophenyl phenyl ether (8.01 g, 3 mmol) in tetrahydrofuran is added dropwise to a mixture of magnesium turnings (0.0802 g, 3.3 mmol), a crystal of iodine and a few drops of 1, 2-dibromoethane in tetrahydrof ran at 50-55 °C under nitrogen. After the addition is complete, the reaction mixture is stirred at 50-55 °C for 70 minutes and cooled to room temperature. The cooled mixture is added over 25 minutes to a solution of trimethyl borate (4.09 mL, 3.6 mmol) in diethyl ether at dry-ice/acetone bath temperature. After the addition is complete, the mixture is stirred at dry-ice/acetone bath temperature for 20 minutes, allowed to warm to -10 °C over 25 minutes, diluted sequentially with acetic acid and water, stirred at room temperature for 30 minutes, and extracted with ether. The organic extract is washed with water, dried over anhydrous sodium sulfate, and concentrated in vacuo to obtain a residue . A mixture of the residue in water is heated over a steam bath for 30 minutes, cooled to room temperature and filtered to obtain a solid which is washed with hexanes and dried to give the title product as a colorless solid (5.7 g, mp 177-180 °C, 82% yield) .

Claims (7)

154798/2 -16- CLAIMS :

1. A compound having the structural formula III (III) wherein R is hydrogen or Ci-C4alkyl , or R and Ri are taken together the carbon atom to which they are attached to form a cyclopropy1 group; Ri is Ci-C4alkyl or cyclopropyl, or R and Ri are taken together with the carbon atom to which they attached to form a cyclopropyl group; Ar is phenyl optionally substituted with any combination of from one to three halogen, Ci-C4alkyl , Ci-C4haloalkyl , Ci-C4alkoxy or Ci-C4haloalkoxy groups, or 1- or 2-naphthyl optionally substituted with any combination of from one to three halogen, Ci-C4alkyl , Ci-C4haloalkyl , Ci-C4alko y or Ci~C4haloalkoxy groups; and the configuration of the groups ArCRRi- and -CH2-3r about the double bond being predominately mutually trans.

2. The compound according to claim 1 selected from the group consisting of > 1- (p-chlorophenyl) -1- (3-bromo-2-fluoropropenyl) cyclopropane, (Z)-; and l-bromo-4- (p-chlorophenyl) -2-fluoro-4-methyl-2-pentene, (Z)-.

3. A process for making a compound according to claim which process comprises reacting a 4-aryl-2-fluoro-2-butene-l compound having the structural formula II (ID 154798/2 -17- wherein R, Ri and Ar are as defined in claim 1, with a brominating agent selected from the group consisting of a bromine-triphenyl phosphine complex, phosphorous tribromine, thionyl bromide, HBr, and mixtures thereof, in a solvent at a temperature of about 50°C-130°C.

4. Use of a compound having the structural formula III in the preparation of a fluoroolefin compound having the structural formula I 1 (I) wherein R is hydrogen or C^- ^alkyl, and Rx is or cyclopropyl, or R and Rx are taken together with the carbon atom to which they are attached to form a cyclopropyl group; Ar is phenyl optionally substituted with any combination of from one to three halogen, C1-C4alkyl, groups , or 1- or 2-naphthyl optionally substituted with any combination of from one to three halogen, Cj- ^alkyl, Ci-C4haloalkyl, ^-^alko y or C^-C^haloalkoxy groups; Ara is phenoxyphenyl optionally substituted with any combination of from one to five halogen, or groups, biphenyl optionally substituted with any combination of from one to five halogen, C1-C4alkyl, groups , benzylphenyl optionally substituted with any combination of from one to five halogen, Cj.-^haloalkoxy groups, or benzoylphenyl optionally substituted with any combination of from one to five halo en 154798 -18- C1-Cjalkyl, or C^-C^haloalkoxy groups; and the configuration of the groups about the double bond is predominately mutually trans, comprising reacting a 4-aryl-l-bromo-2-fluoro-2-butene compound having the structural formula III (III) wherein Ar, R and Rx are as described above with about 0.001 to 0.1 molar equivalent of a palladium catalyst, at least about 2 molar equivalents of a base, and a boronic acid having the structural formula IV, a boronic anhydride having the structural formula V or a borate ester having the structural formula VI (HO) 2B-Ari (IV) (V) (R.O^B-A^ (VI) 154798 -19- wherein R2 is Ci-C alkyl and Ari is as described above, at a temperature of about 50°C-130°C in the presence of a solvent, substantially as described in the specification.

5. The use of a compound of formula III according to claim 4 wherein the palladium catalyst is selected from the group consisting of bis (dibenzylideneacetone) palladium(O) , tetrakis (triphenylphosphine) palladium(O) , bis (acetonitrile)palladium(II) chloride, bis (triphenylphosphine) palladium (II) chloride, [1, -bis (diphenylphosphine) butane] palladium (II) dichloride , [1,1' -bis (diphenylphosphino) ferrocene]palladium(II) diacetate, palladium(II) acetate, palladium(II) chloride and palladium on activated carbon and mixtures thereof; and the base is selected from the group consisting of an alkali metal carbonate, an alkaline earth metal carbonate, an alkali metal hydrogen carbonate, an alkali metal hydroxide, an alkaline earth metal hydroxide, an alkali metal Ci-C6alkoxide, thallium (I) carbonate, a thallium(I) Ci-C6alkoxide, thallium (I) hydroxide and a tri (Ci-C4alkyl) amine and mixtures thereof.

6. Use of a compound of formula III according to claim 5 wherein the palladium catalyst is bis (dibenzylideneacetone) palladium (0) and the base is alkali metal carbonate.

7. Use of a compound of formula III according to claim 6 wherein the solvent is selected from a group consisting of an aromatic hydrocarbon, a halogenated aromatic hydrocarbon, a carboxylic acid amide, a glycol, a Ci-C4alcohol , a ketone and an ether and mixtures thereof and mixtures with water.