Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2002-08-15
2003-09-16
Ramsuer, Robert W. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C546S276100
Reexamination Certificate
active
06620943
ABSTRACT:
This invention relates to improved processes for preparing 1-arylpyrazole pesticides such as 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphinylpyrazole known as Fipronil (Pesticide Manual 11
th
Edition), and for the intermediates used in its preparation 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole and 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyanopyrazol-4-yl disulphide.
European Patent Publication No.295117 describes the preparation of 5-amino-1-(2,6-dichloro4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphinylpyrazole by the oxidation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole with 3-chloroperbenzoic acid. The use of trifluoroacetic acid and hydrogen peroxide (forming trifluoroperacetic acid in situ) for the oxidation of sulphides to sulphoxides and/or sulphones is known and is generally useful for the oxidation of electron deficient sulphides such as trifluoromethylsulphides which are less readily oxidised than other sulphides. Such procedures have been reported in the literature, for example in the preparation of certain 1-arylpyrazole pesticides.
A problem encountered in the preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphinylpyrazole by the oxidation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole is the co-formation of the corresponding sulphone compound 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphonylpyrazole, which is difficult to remove from the sulphoxide. A number of oxidants (including amongst others sodium vanadate, sodium tungstate, peracetic acid, performic acid and pertrichloroacetic acid) have been employed in an attempt to obtain an efficient and regioselective oxidation which will provide 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylsulphinylpyrazole in pure form and which may also be utilised for large scale preparations. All of the above methods were found to be unsatisfactory in one respect or another.
It has now been found that a mixture of trifluoroacetic acid and hydrogen peroxide (trifluoroperacetic acid) gives excellent results in terms of both selectivity and yield.
However a problem of using the trifluoroacetic acid and hydrogen peroxide mixture on large scales is that it leads to corrosion of the glass linings of industrial reaction vessels, which is rapid (typically 300 &mgr;m/year) even at ambient temperatures, whilst at 80° C. the speed of corrosion increases to about 1430 &mgr;m/year. This corrosion occurs as a result of the formation of hydrogen fluoride, and therefore prohibits the use of this reagent mixture in such vessels.
It has now been found that the addition of a corrosion inhibiting compound such as boric acid to the reaction mixture inhibits the corrosion process and reduces the speed of corrosion to a level that is typically less than 5 &mgr;m/year.
European Patent Publication No. 0374061 and J-L. Clavel et.al. in J. Chem. Soc. Perkin I, (1992), 3371-3375 describe the preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyanopyrazol-4-yl disulphide, and the further conversion of this disulphide to the pesticidally active 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole by reaction with trifluoromethyl bromide in the presence of sodium formate and sulphur dioxide in N,N-dimethylformamide in an autoclave at low pressure (typically 13 bars) at 60° C.
However on larger scales the reaction is very exothermic which results in a substantial pressure increase in the vessel and associated operator hazard.
Moreover it is necessary to add the trifluoromethyl bromide quickly (generally within 0.5 hour), because the mixture of disulphide, sodium formate, sulphur dioxide and N,N-dimethylformamide has been found to be unstable (typically leading to 55% degradation into unwanted by-products within 2 hours at 50° C.). This requirement for rapid addition of trifluoromethyl bromide is not compatible with the exothermic nature of the reaction.
In order to overcome these problems and develop a process which can be used on a large scale other conditions have been sought.
In the above described procedures the reaction was performed by addition of the trifluoromethyl bromide to a mixture of the other components. A new process has now been developed in which the order of addition is different.
European Patent Publication No. 0374061 describes the preparation of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyanopyrazol-4-yl disulphide by the reaction of 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-thiocyanatopyrazole with base, and the further conversion of this disulphide to the pesticidally active 5-amino-1-(2,6-dichloro-4-trifluoromethylphenyl)-3-cyano-4-trifluoromethylthiopyrazole.
European Patent Publication No. 295117 discloses a process for the preparation of 1-aryl-3,5-disubstituted-pyrazol-4-yl disulphides by the hydrolysis of the corresponding 4-thiocyanatopyrazole derivatives using hydrochloric acid in ethanol, or by reduction using sodium borohydride in ethanol, or by treatment with aqueous sodium hydroxide under phase transfer conditions in the presence of chloroform and benzyltriethylamrnonium chloride.
The preparation of the above 5-amino-1-aryl-3-cyano-4-thiocyanatopyrazole intermediates is also described in European Patent Publication Numbers 0374061 and 295117, and these are obtained by the thiocyanation of the corresponding 5-amino-1-aryl-3-cyanopyrazole derivatives using an alkali metal or ammonium thiocyanate in the presence of bromine and methanol at low temperature.
The above 2-step process for the preparation of 5-amino-1-aryl-3-cyanopyrazol-4-yl disulphide intermediates from 5-amino-1-aryl-3-cyanopyrazoles presents several problems which limit its usefulness for application on large scales:
i) the thiocyanation step is generally performed at very low temperatures,
ii) the mixture of bromine and methanol used in the thiocyanation reaction may form explosive mixtures,
iii) the above reactions involve heterogeneous mixtures, and
iv) it is difficult to obtain complete transformations to product in either reaction stage.
In order to overcome these problems other conditions have been sought. Thus the explosive hazard may be avoided in the thiocyanation reaction by replacing the methanol with a mixture of dichloromethane and water, however this procedure is not efficient on large scales.
The thiocyanation reaction may alternatively be successfully carried out using an alkali metal or ammonium thiocyanate in the presence of hydrogen peroxide and a mineral acid such as hydrochloric acid in a solvent such as an alcohol for example methanol. An improved procedure for the subsequent hydrolysis step has been found which involves the use of a base such as an alkali metal hydroxide, for example sodium hydroxide, in the presence of formaldehyde and a solvent such as aqueous methanol, however the disulphide thus obtained is very powdery and difficult to filter. Furthermore in order to obtain the above disulphide in satisfactory quality it is necessary to subject the starting material 5-amino-1-aryl-3-cyanopyrazole to additional purification before it is used in the thiocyanation and hydrolysis reactions.
Hence it may be appreciated that the above 2-step procedure is inefficient for an industrial process, and a single step method lacking these disadvantages would clearly be preferred.
The present invention seeks to provide improved or more economical methods for the preparation of pesticides.
It is a first object of the present invention to provide a convenient process for preparing 5-amino-1-aryl-3-cyano-4-trifluoromethylsulphinylpyrazole pesticides, which are obtained in high yield and high purity.
It is a further object of the present invention to provide a process for preparing 5-amino-1-aryl-3-cyano-4-trifluoromethylsulphinylpyrazole pesticides which is simple and safe to perform, and whi
Charreau Philippe
Clavel Jean-Louis
Le Bars Sylvie
Pelta Isabelle
Bayer Cropscience SA
Burns Doane Swecker & Mathis L.L.P.
Ramsuer Robert W.
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