Process for the preparation of...

Details Process for the preparation of... Process for the preparation of...

2001-05-04

2002-09-03

Ramsuer, Robert W. (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Nitriles

C558S410000

Reexamination Certificate

active

06444838

ABSTRACT:

BACKGROUND OF THE INVENTION
Certain fluoroolefin compounds are known to possess insecticidal and acaricidal activity (see, e.g., U.S. Pat. No. 5,248,834; GB 2,288,803-A; WO 94/06741; WO 97/16067; and U.S. Pat. No. 5,998,673. However, the fluoroolefin compounds disclosed in those patents and patent applications are outside the scope of the present invention. U.S. Pat. No. 5,248,834 generically discloses certain 1-aryl-1-(3-aryl-1,2-difluoroprop-1-enyl)cyclopropane compounds. However, that patent does not provide a method to prepare those compounds. In fact, U.S. Pat. No. 5,248,834 does not provide a method to prepare any fluoroolefin compounds.
1,4-diaryl-2-fluoro-4-cyano-2-butenes and a method for their preparation are described in U.S. Pat. No. 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 1,4-diaryl-2-fluoro-4-cyano-2-butenes.
It is also an object of the present invention to provide intermediates useful in said process.
These and other objects of the present invention will become more apparent from the detailed description thereof set forth below.
SUMMARY OF THE INVENTION
The present invention provides a process for the preparation of insecticidal and acaricidal 1,4-diaryl-2-fluoro-4-cyano-2-butene compounds of structural formula I
wherein
Ar is phenyl optionally substituted with any combination of from one to three halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
1- or 2-naphthyl optionally substituted with any combination of from one to three halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups, or
a 5- or 6-membered heteroaromatic ring optionally substituted with any combination of from one to three halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups;
R is hydrogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
3
-C
6
cycloalkyl or C
3
-C
6
halocycloalkyl; and
Ar
1
is phenoxyphenyl optionally substituted with any combination of from one to six halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
phenyl optionally substituted with any combination of from one to five halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
biphenyl optionally substituted with any combination of from one to five halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
phenoxypyridyl optionally substituted with any combination of from one to five halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
benzylpyridyl optionally substituted with any combination of from one to five halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
benzylphenyl optionally substituted with any combination of from one to five halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
benzoylphenyl optionally substituted with any combination of from one to five halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups,
1- or 2-naphthyl optionally substituted with any combination of from one to three halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups, or
a 5- or 6-membered heteroaromatic ring optionally substituted with any combination of from one to three halogen, C
1
-C
4
alkyl, C
1
-C
4
haloalkyl, C
1
-C
4
alkoxy or C
1
-C
4
haloalkoxy groups; 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 a nucleophilic replaceabale leaving group, such as halogen, alkylsulphonyloxy or arylsulphonyloxy, especially chloro, bromo, iodo, tosyloxy, mesyloxy or the like, with a cyanide delivering reagent in a first solvent to afford a cyano intermediate of formula III;
(b) reacting said cyano intermediate III with an aldehyde of formula IV
in the presence of a base in a second solvent to yield an anion which is acidified to afford a diene of formula V
and
(c) reacting said diene V with magnesium in the presence of a third solvent.
This invention also provides intermediate dienes of structural formula V.
DETAILED DESCRIPTION OF THE INVENTION
Although a method for the preparation of insecticidal and acaricidal 1,4-diaryl-2-fluoro-4-cyano-2-butenes is described in U.S. Pat. No. 5,998,673, alternative more effective methods contribute to the enhanced availability of these useful insecticidal and acaricidal agents.
Advantageously, the present invention provides an effective and practical method for the preparation of 1,4-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 optionally in the presence of 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 1,4-diaryl-2-fluoro-4-cyano-2-butene I. The process is depicted in Flow Diagram I.
Intermediate aldehydes IV may be prepared as described in U.S. Pat. No. 5,998,673.
First solvents suitable for use in the inventive process include polar aprotic solvents such as dimethylformamide, dimethylsulfoxide, N-methylpyrrolidone or the like, preferably dimethylsulfoxide.
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, magnesiochlorodiethylamide (Et
2
NMgCl), 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 strong mineral acids such as HCl, HBr or H
2
SO
4
, preferably HCl or H
2
SO
4
.
In actual practice, intermediate II, preferably wherein X is Br, 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; said cyano intermediate III is treated with aldehyde IV in the presence of a base, preferable an alkali metal amide, preferably 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 1,4-diaryl-2-fluoro-4-cyano-2-butene I.
The process depicted in Flow Diagram I provides 1,4-diaryl-2-fluoro-4-cyano-2-butene I having predominantly the (Z)-configuration. Formula I compounds wherein the double bond is in the (E)—configuration may be prepared by isomerizing 1,4-diaryl-2-fluoro-4-cyano-2-butene I which are predominantly in the (Z)—configuration u

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