1,4-DIARYL-2-FLUORO-4-CYANO-2-BUTENES, PROCESS FOR THEIR PREPARATION AND INTERMEDIATES USEFUL THEREFOR

Abstract: The present invention provides 1,4-diaryl-2-fluoro-4-cyano-2-butene compounds having the sturctural formula (I), a process for their preparation, and intermediates useful therefor.

Description: l,4-DIARYL-2-FLUORO-4-CYANO-2-BUTENES, PROCESS FOR THEIR PREPARATION AND INTERMEDIATES USEFUL THEREFORE Certain fluoroolefin compounds are known to possess insecticidal and acaricidal activity (see, e.g., U.S. 5,248,834; GB-A 2,288,803; WO-A 94/06741; WO-A 97/16067; and U.S. 5,998,673). However, the fluoroolefin compounds disclosed in those documents are outside the scope of the present invention. U.S. 5,248,834 generically discloses certain 1-aryl-l- ( 3-aryl-l , 2-difluoroprop-1-enyl) cyclopropane compounds . However, that patent does not provide a method to prepare any fluoroolefin compounds. l,4-diaryl-2-fluoro-4-cyano-2-butenes and a method for their preparation are described in U.S. 5,998,673. Said compounds are useful as insecticidal and acaricidal agents and for protecting plants from damage caused by insect and acarid attack and infestation. Although a method for the preparation of said agents is known, alternative more effective methods contribute to the enhanced availability of these useful insecticidal and acaricidal agents . It is, therefore, an object of the present invention to provide a process for the preparation of l,4-diaryl-2-fluoro-4-cyano-2-bu- tenes. It is also an object of the present invention to provide intermediates useful in said process. The present invention provides a process for the preparation of insecticidal and acaricidal l,4-diaryl-2-fluoro-4-cyano-2-butene compounds of structural formula I R H Ar- -CF= CH- C— r 1 H CN wherein Ar is phenyl unsubstituted or substituted with any combination of from one to three halogen, Cι-C 4 alkyl, Cι-Chaloalkyl, Cχ-Calkoxy or Cχ-C 4 haloalkoxy, 1- or 2-naphthyl unsubstituted or substituted with any combination of from one to three halogen, Cι-C 4 alkyl, Cχ-C 4 haloal- kyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, or a 5- or 6-membered heteroaromatic ring unsubstituted or substituted with any combination of from one to three halogen, Cι-C 4 alkyl, Cι-C 4 haloalkyl, C ! -C 4 al o y or Cι-Chaloalkoxy; R is hydrogen, Cι-C alkyl, C 1 -C 4 haloalkyl, C 3 -C 6 cycloalkyl or C 3 -C 6 halocycloalkyl; and Ari is phenoxyphenyl unsubstituted or substituted with any combination of from one to six halogen, Cι-C 4 alkyl, Cι-Chaloalkyl, C ! -C 4 alkoxy or Cι-C 4 haloalkoxy, phenyl unsubstituted or substituted with any combination of from one to five halogen, Cχ-C alkyl, Cι-C 4 haloalkyl, Cι-C 4 al- koxy or C 1 -C 4 haloalkoxy, biphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, Cι-Chaloalkyl, Cι-C 4 al- koxy or Cι-C 4 haloalkoxy, phenoxypyridyl unsubstituted or substituted with any combina- tion of from one to five halogen, Cχ-C 4 alkyl, C 1 -C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, benzylpyridyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 al yl, Cι-C 4 haloalkyl, Cι-C 4 alkoxy or Cχ-C 4 haloalkoxy, benzylphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, C 1 -C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, benzoylphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, Cι-C 4 haloalkyl, Cι-C alkoxy or Cι-C 4 haloalkoxy, 1- or 2-naphthyl unsubstituted or substituted with any combination of from one to three halogen, C 1 -C 4 alkyl, Cι-C 4 haloal- kyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, or a 5- or 6-membered heteroaromatic ring unsubstituted or sub- stituted with any combination of from one to three halogen, Cι-C 4 alkyl, Cι-Chaloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy; or the optical isomers thereof; or the cis and trans isomers thereof which process comprises the following steps: (a) reacting an intermediate of formula II ^ Ar 1 II X wherein Ar 1 is defined as above and X is a nucleophilic replaceable leaving group, such as halogen, alkylsulphonyloxy or arylsulphonyloxy, especially Cl, Br, I, mesyloxy or tosy- loxy, with a cyanide delivering reagent in a first solvent to afford a cyano intermediate of formula III; . Ar 1 III CN (b) reacting said cyano intermediate III with an aldehyde of formula IV IV Ar- CF- CHO in the presence of a base in a second solvent to yield an anion which is acidified to afford a diene of formula V Ar—C— CF— CH— C Ar 1 V CN and (c) reacting said diene V with magnesium in the presence of a third solvent. This invention also provides novel products of formula I and intermediates of formula V. Although a method for the preparation of insecticidal and acaricidal l,4-diaryl-2-fluoro-4-cyano-2-butenes is described in U.S. 5,998,673, alternative more effective methods contribute to the enhanced availability of these useful insecticidal and acaricidal agents. The present invention provides an effective and practical method for the preparation of l,4-diaryl-2-fluoro-4-cyano-2-butenes of formula I, wherein Ar, Ar 1 and R are defined as above. In accordance with the process of the invention intermediate II is treated with a cyanide delivering reagent in a polar aprotic solvent (first solvent) to afford the cyano intermediate III. Cyano intermediate III is reacted with an aldehyde of formula IV in the presence of a base in a second solvent to yield an intermediate which is acidified to afford a diene of formula V; and said diene V is reacted with magnesium in the presence of a protic solvent (third solvent) to provide l,4-diaryl-2-fluoro-4-cyano-2-butene I. The process is depicted in Flow Diagram I. Flow Diagram I Ar 1 x = Cl, Br, I, tosyloxy, X mesyloxy II CN- Polar aprotic solvent CN III Flow Diagram I (continued] III ] Ar- :CF- CH : Ar 1 V CN tic solvent H Ar- -CF= CH- Ar 1 H CN Intermediate aldehydes IV may be prepared as described in U.S. 5,998,673. First solvents suitable for use in the inventive process include polar aprotic solvents such as dimethylfor amide, di ethylsulfo- xide, N-methylpyrrolidone or the like, preferably dimethylsulfo- xide. Second solvents suitable for use in the inventive process include aprotic solvents such as tetrahydrofuran, diethyl ether and the like, preferably tetrahydrofuran. Third solvents suitable for use in the inventive process include protic solvents such as alkanols, preferably methanol or ethanol. Cyanide ion delivering reagents include alkali metal cyanides and quarternary ammonium cyanides, preferably sodium cyanide or potassium cyanide. Bases suitable for use in the inventive process are alkali metal amides, such as lithium amide, lithium dimethylamide, lithium diisopropylamide, sodium bis (trimethylsilyl) amide, magnesiochlo- rodiethylamide (Et 2 N gCl), or the like, preferably lithium diisopropylamide . Bases may be present in amounts ranging from catalytic to excess amounts such as 10 mole % to 4.0 molar excess. Acids suitable for use in the process of the invention include mineral acids such as HCl, HBr or H 2 S0 4 , preferably HC1. Preferred intermediates II are those wherein X is Br. In a preferred process of the invention, intermediate II is treated with at least one molar equivalent of a cyanide delivering reagent, preferably sodium cyanide, in a polar aprotic solvent, preferably dimethyl sulfoxide, to yield the cyano intermediate III. Cyano intermediate III is treated with aldehyde IV in the presence of a base, preferably an alkali metal amide, prefe- rably lithium diisopropylamide in an aprotic solvent, preferably tetrahydrofuran, to yield an intermediate which on acidification, preferably with hydrochloric acid, affords diene (V); said diene (V) is reacted with magnesium in the presence of a protic solvent, preferably an alkanol, preferably methanol, or ethanol, to provide the desired l,4-diaryl-2-fluoro-4-cyano-2- butene I . The process depicted in Flow Diagram I provides l,4-diaryl-2- fluoro-4-cyano-2-butene I having predominantly the (Z)-configura- tion. Formula I compounds wherein the double bond is in the (E)- configuration may be prepared by isomerizing l,4-diaryl-2-fluoro- 4-cyano~2-butene I which are predominantly in the (Z)-configuration using conventional procedures such as exposure to light. In formula I above, 5- and 6-membered heteroaromatic rings include, but are not limited to, pyridyl, pyrazolyl, imidazolyl, triazolyl, isoxazolyl, tetrazolyl, pyrazinyl, pyridazinyl, tri- azinyl, furanyl, thienyl and thiazolyl rings each unsubstituted or substituted as described in formula I above. Exemplary of halogen hereinabove are fluorine, chlorine, bromine and iodine. The terms "Cι-C 4 haloalkyl", "C -C 6 halocycloalkyl" and "Cι-C 4 haloalkoxy" are defined as a Cι-C 4 alkyl group, a C 3 -C 6 cyclo- alkyl group and a Cχ-C 4 alkoxy group substituted with one or more halogen atoms, respectively. The present invention also provides compounds of formula V wherein the variables have the meanings as defined in formula I. R Ar C=CF CH= C Ar 1 CN In compounds of formulae I and V, resp. following meanings for groups R are preferred: R is C I -C 4 alkyl or C 3 -C 6 cycloalkyl especially isopropyl or cyclopropyl. Compounds of formulae I and V, resp. are preferred, wherein Ar denotes phenyl which is substituted by halogen or Cι-Calkoxy. Preference also is given to compounds of formulae I and V, resp. wherein Ar 1 is 3-phenoxyphenyl unsubstituted or substituted with any combination of from one to six halogen, C 1 -C 4 alkyl, Cι-Chalo- alkyl, Cι-C 4 alkoxy or Cx-Cjhaloalkoxy, 3-biphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C alkyl, Cι-Chaloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, or 3-benzylphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, Cι-Chaloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy. Moreover, particular preference is given to compounds wherein Ar 1 is 3-phenoxyphenyl unsubstituted or substituted with any combina- tion of from one to six halogen, Cι-C 4 alkyl, C 1 -C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, particularly 3-phenoxy-4-halogen- phenyl, 3-(4 '-halogen-phenoxy) -phenyl or 3-(4 '-halogen-phen- oxy)-4-halogen-phenyl. Compounds of formulae I and V, resp. are especially preferred wherein Ar is phenyl unsubstituted or substituted with any combination of from one to three halogen, Cι-Calkyl, Cι-C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 Ϊιaloalkoxy; R is hydrogen, Cι-C 4 alkyl, Cχ-C 4 haloalkyl, C 3 -C 6 cycloalkyl or C 3 -C 6 halocycloalkyl; Ar 1 is 3-phenoxyphenyl unsubstituted or substituted with any com- bination of from one to six halogen, Cι-C 4 alkyl, Cι-C 4 haloal- kyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, 3-biphenyl unsubstituted or substituted with any combination of from one to five halogen, C 1 -C 4 alkyl, Cι-C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, or 3-benzylphenyl unsubstituted or substituted with any combination of from one to five halogen, Cχ-C 4 alkyl, Cι-C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy. Compounds of formulae I and V, resp. are particularly preferred wherein Ar is phenyl unsubstituted or substituted with any combination of from one to three halogen, Cι-C alkyl, Cι-C 4 haloalkyl, Cι-C alkoxy or Cι-C 4 haloalkoxy; R is isopropyl or cyclopropyl; and Ar 1 is 3-phenoxyphenyl unsubstituted or substituted with any combination of from one to six halogen, Cι-C 4 alkyl, Cι-C 4 haloal- kyl / Cι-C 4 alkoxy or Cι-C 4 haloalkoxy. Particular preference is given to compounds of formulae I and V, resp. wherein Ar is phenyl unsubstituted or substituted with any combination of from one to three halogen, Cι-Calkyl, Cι-C 4 haloalkyl, Cι-C 4 al oxy or Cι-C 4 haloalkoxy; R is cyclopropyl; and Ar 1 is 3-phenoxyphenyl unsubstituted or substituted with any combination of from one to six halogen, Cι-C 4 alkyl, C 1 -C 4 haloal- kyl, Cι-C 4 alkoxy or Cι-Chaloalkoxy. Moreover, particular preference is given to compounds of formula I' and V, resp. wherein the variables have the meanings given in table A: Table A Synthesis Examples With due modification of the starting compounds, the protocols shown in the synthesis examples below were used for obtaining further compounds I and V. EXAMPLE 1 Preparation of (4-Fluoro-3-phenoxyphenyl)acetonitrile A mixture of -bromo-4-fluoro-3-phenoxytoluene (2.65 g, 0.0094 mol) and sodium cyanide (0.735 g, 0.0141 mol) in dimethyl sulfo- xide (15 ml) was heated at 50°C for 35 min and 90°C for 35 min. The cooled reaction mixture was diluted with water and extracted with ethyl acetate. The combined organic extracts were washed with water, saturated brine, dried over anhydrous sodium sulfate, and concentrated in vacuo to an off-white oil (1.8 g, 85.7 %) which is characterized by IR, 1 HNMR, 13 CNMR and 19 FNMR analyses. Example 2 Preparation of l-(p-Chlorophenyl)-l-cyclopropyl-2-fluoro-4- ( 4-fluoro-3-phenoxyphenyl ) -4-cyano-l, 3-butadiene To a stirred solution of ( 4-fluoro-3-phenoxyphenyl)-acetonitrile (447.2 mg, 2.1 mmol) in anhydrous tetrahydrofuran (5 ml) under nitrogen at -78°C was added via syringe a solution of lithium diisopropylamide in tetrahydrofuran (1.16 ml of 0.20M, 2.31 mmol). The reaction mixture was allowed to warm to room temperature and then stirred for 2 hr. The stirred reaction mixture was then cooled to -78°C and a solution of p-chloro-β-cyclopropyl-α-fluorocin- namaldehyde (449.3 mg, 2 mmol) in tetrahydrofuran (2 ml) was added via syringe. The reaction mixture was allowed to warm to room temperature and stirred for 48 hr. The reaction mixture was diluted with ethyl acetate and 2N hydrochloric acid, and the layers separated. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with 2N hydrochloric acid, water, dried over anhydrous sodium sulfate and concentrated in vacuo to a brown residue. Flash chromatography of this residue on silica gel eluting with ethyl acetate/hexane (1/9) afforded the title compound as a syrup (500 mg, 55.3 %), which solidified on trituration with ether to yield a pale yellow-solid (mp. 110-112°C) which was characterized by i H MR, 13 CNMR, 19 FNMR, IR and mass spectral analyses. Example 3 Preparation of l-[l-(p~Chlorophenyl)-2-fluoro-4-(4-fluoro-3-phen- oxyphenyl)-4-cyano-2-butenyl]cyclopropane, (R, S)-(Z)- A mixture of l-(p-chlorophenyl)-l-cyclopropyl-2-fluoro-4- (4-fluoro-3-phenoxyphenyl)-4-cyano-l,3-butadiene (335 mg, 0.77 mmol) and magnesium (93.8 mg, 3.86 mmol) in methanol (3 ml) and anhydrous THF (2 ml) was refluxed under nitrogen for 3 hr. The cooled reaction mixture was acidified with 2N hydrochloric acid and extracted with ethyl acetate. The combined extracts were washed with 2N hydrochloric acid, water, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was chroma- tographed on silica gel eluting with ethyl acetate/hexane (5/95) to afford the title compound as a colorless oil (46 mg, 14 %) which was characterized by i HNMR, 13 CNMR, 19 FNMR, IR and mass spectral analyses .

Claims: CLAIMS : 1. A process for the preparation of a compound of formula I wherein Ar is phenyl unsubstituted or substituted with any combination of from one to three halogen, Cι-Calkyl, Cι-C 4 halo- alkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy or 1- or 2-naphthyl unsubstituted or substituted with any combination of from one to three halogen, Cχ-C 4 alkyl, Cι-C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy; R is hydrogen, Cι-C 4 alkyl, Cι-Chaloalkyl, C 3 -C 6 cycloalkyl or C 3 -C 5 halocycloalkyl; and Ar 1 is phenoxyphenyl unsubstituted or substituted with any combination of from one to six halogen, Cι-C 4 alkyl, Cι-Chaloalkyl, Cχ-C 4 alkoxy or Cι-C 4 haloalkoxy, phenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, Cχ-C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, biphenyl unsubstituted or substituted with any combina- tion of from one to five halogen, Cι-C al yl, Cι-C 4 haloal- kyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, phenoxypyridyl unsubstituted or substituted with any combination of from one to five halogen, "Cι-C 4 alkyl, Cι-C 4 ha- loalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy, benzylpyridyl unsubstituted or substituted with any combination of from one to five halogen, C ! -C 4 alkyl, Cι-C 4 ha- loalkyl, Cι-C 4 lkoxy or Cι-C 4 haloalkoxy, benzylphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, Cχ-Chalo- alkyl, Cι-C 4 alkoxy or C 1 -C 4 haloalkoxy, benzoylphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, Cχ-C 4 ha- loalkyl, Cι-C 4 alkoxy or Cι-Chaloalkoxy, 1- or 2-naphthyl unsubstituted or substituted with any combination of from one to three halogen, Cι-C 4 alkyl, Cι-C 4 haloalkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy; or the optical isomers thereof; or the cis and trans isomers thereof, which process comprises the following steps: a) reacting an intermediate of formula II wherein Ar 1 is defined as above and X is chloro, bromo, iodo, tosyloxy or mesyloxy with a cyanide delivering reagent in a first solvent to afford a cyano intermediate of formula III ^ Ar 1 III CN b) reacting Cyano intermediate III with an aldehyde of formula IV Ar C=CF CHO IV wherein Ar and R are defined as above in the presence of a base in a second solvent to yield an anion which is acidified to afford a diene of formula V R Ar- -C= CF CH = C Ar 1 V CN and c) reacting said diene of formula V with magnesium in the presence of a third solvent to give the desired formula I product. 2. The process according to claim 1 wherein said cyanide delivering reagent is an alkali metal cyanide. 3. The process according to claim 1 wherein said first solvent is a polar aprotic solvent selected from the group consisting of dimethylsulfoxide, dimethylformamide and N-methylpyrroli- done. 4. The process according to claim 1 wherein the said base is an alkali metal amide. 5. The process according to claim 1 wherein said acid is a strong mineral acid. 6. The process according to claim 1 wherein said third solvent is an alkanol. 7. Compounds of formulae I and V according to claim 1 wherein the substitutents have the meanings as defined in formula I. 8. The compound of formula V according to claim 7 wherein Ar is phenyl unsubstituted or substituted with any combina- tion of from one to three halogen, Cι-C 4 alkyl, Cι-C 4 halo- alkyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy; R is hydrogen, Cι-C 4 alkyl, Cι-C 4 haloalkyl, C 3 -C 6 cycloalkyl or C 3 -C 6 halocycloalkyl; and Ar 1 is 3-phenoxyphenyl unsubstituted or substituted with any combination of from one to six halogen, Cι-C 4 alkyl, C;ι.-C 4 haloalkyl, Cι-C 4 alkoxy or C 1 -C 4 haloalkoxy, 3-biphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, Cι-C 4 haloal- kyl, Cι-C 4 alkoxy or Cι-C 4 haloalkoxy or 3-benzylphenyl unsubstituted or substituted with any combination of from one to five halogen, Cι-C 4 alkyl, C]_-C 4 ha- loalkyl, C ! -C 4 al oxy or Cι-C 4 haloalkoxy. 5 9. The compound of formula V according to claims 7 or 8 wherein Ar is phenyl unsubstituted or substituted with any combina- 10 tion of from one to three halogen, Cι-C 4 al yl, Cι-C 4 halo- alkyl, Cι-C 4 alkoxy or Cχ-C 4 haloalkoxy; R is isopropyl or cyclopropyl; and 15 Ar 1 is -phenoxyphenyl unsubstituted or substituted with any combination of from one to six halogen, Cι-C 4 alkyl, Cι-C 4 haloalkyl, Cι-C 4 alkoxy or Cχ-C 4 haloalkoxy. 20 10. The compound of formula v according to any one of claims 7 to 9 wherein Ar is phenyl unsubstituted or substituted with any combination of from one to three halogen, Cι-Calkyl, Cι-Chalo- 25 alkyl, Cχ-C 4 alkoxy or Cχ-C 4 haloalkoxy; R is cyclopropyl; and Ar 1 is 3-phenoxyphenyl unsubstituted or substituted with any 30 combination of from one to six halogen, Cι-C al yl, Cχ-C 4 haloalkyl, Cι-C 4 alkoxy or C 1 -C 4 haloalkoxy. 35 40 45

Inventors: HU YULIN, HUNT DAVID ALLEN, HU, YULIN, HUNT, DAVID, ALLEN
Applicants: BASF AG, BASF AKTIENGESELLSCHAFT
Application year: 2001
Main classification: C07C255
IPC codes: A01N37, C07C253, C07C255