Organic compounds -- part of the class 532-570 series – Organic compounds – Pteroyl per se or having -c- – wherein x is chalcogen – bonded...
Reexamination Certificate
2001-09-24
2002-08-13
Berch, Mark L. (Department: 1624)
Organic compounds -- part of the class 532-570 series
Organic compounds
Pteroyl per se or having -c-, wherein x is chalcogen, bonded...
Reexamination Certificate
active
06433169
ABSTRACT:
BACKGROUND OF THE INVENTION
The present invention concerns a process for the preparation of 2-alkoxy-6-trifluoromethyl-N-([1,2,4]triazolo[1,5-c]pyrimidin-2-yl) benzenesulfonamides. More particularly, the present invention concerns the preparation of these compounds in which the 2-alkoxy substituent of the benzenesulfonamide ring is introduced in the last step by contacting the corresponding 2-fluoro substituted material with the appropriate alkoxide.
U.S. Pat. No. 5,858,924 describes certain substituted benzenesulfonamide compounds and their use as herbicides. Among the disclosed herbicides, the 2-alkoxy-6-trifluoromethyl-N-([1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamides are particularly useful. Normally these materials are prepared by condensing the appropriately substituted 2-amino[1,2,4]triazolo-[1,5-c]pyrimidine with the appropriately substituted benzenesulfonyl chloride.
It would be advantageous to have an alternative process to produce these materials. It would be particularly advantageous to have a process in which the 2-alkoxy substituent of the benzenesulfonamide ring is added late in the process, especially when the alkoxy substituent is substituted with fluorine atoms and its introduction requires one of the more expensive starting materials employed in the overall manufacturing scheme.
SUMMARY OF THE INVENTION
The present invention concerns a process for the preparation of a 2-alkoxy-6-trifluoromethyl-N-([1,2,4]triazolo[1,5-c]pyrimidin-2-yl) benzenesulfonamide of Formula I
wherein
W represents H or O(C
1
-C
3
alkyl);
Z represents H or O(C
1
-C
3
alkyl), with the proviso that at least one of W or Z represents O(C
1
-C
3
alkyl); and
R represents C
1
-C
4
alkyl optionally substituted with at least 2 and up to the maximum possible number of fluorine atoms
which comprises contacting a 2-fluoro-6-trifluoromethyl-N-([1,2,4]triazolo-[1,5-c]pyrimidin-2-yl)benzenesulfonamide of Formula II
wherein
W and Z are as previously defined
with an alcohol ROH wherein R is as previously defmed and at least 2 molar equivalents of base in a polar aprotic organic solvent.
DETAILED DESCRIPTION OF THE INVENTION
The term alkyl and derivative terms such as alkoxy and alcohol, as used herein, include straight chain, branched chain and cyclic groups. Thus, typical alkyl groups are methyl, ethyl, 1-methylethyl, propyl, cyclopropyl, butyl, 1,1-dimethylethyl, cyclobutyl and 1-methylpropyl. Methyl and ethyl are often preferred. Alkyl groups are sometimes referred to as normal (n), iso (i), secondary (s) or tertiary (t). Typical alkyls optionally substituted with at least 2 and up to the maximum possible number of fluorine atoms include trifluoromethyl, 2,2,2-tri-fluoroethyl, 2,2-difluoroethyl and 2,2,3,3,3-pentafluoropropyl.
The 2-fluoro-6-trifluoromethyl-N-([1,2,4]triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide starting materials are described in U.S. Pat. No. 5,858,924 and can be prepared by condensing the appropriately substituted 2-amino[1,2,4]triazolo[1,5-c]pyrimidine with 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride. The 2-fluoro-6-trifluoromethylbenzenesulfonyl chloride can be prepared, for example, from 2-fluoro-6-trifluoromethylaniline by diazotization followed by treatment with sulfur dioxide and cupric chloride.
The conversion of the 2-fluorobenzenesulfonamide to the corresponding 2-alkoxybenzenesulfonamide is accomplished by contacting the 2-fluorobenzenesulfonamide with the appropriate alcohol and at least 2 equivalents of base in a polar aprotic solvent.
Although higher alcohols can be used in the present process, since the more herbicidally effective 2-alkoxy-6-trifluoromethyl-N-([1,2,4]triazolo-[1,5-c]pyrimidin-2-yl)benzenesulfonamides contain C
1
-C
4
alkoxy groups, the preferred alcohols are the corresponding C
1
-C
4
alcohols. The most preferred alcohols are those substituted with at least 2 and up to the maximum possible number of fluorine atoms. While only a stoichiometric amount of alcohol is required to achieve complete conversion, oftentimes it is beneficial to employ an excess of the alcohol. Because of the relative convenience with which the alcohol can be recovered and recycled, for example, by distillation, two- to three-fold or more molar excesses of the alcohol can be employed. A further benefit to having excess alcohol is increased yield, purity, and reduced cycle time.
Since it is necessary to convert at least one equivalent of the alcohol to the corresponding alkoxide and since another equivalent of base is consumed in neutralizing the relatively acidic sulfonamide proton, at least two equivalents of base based on the amount of sulfonamide are required. An additional excess of base is often preferred. Any base or mixture of bases which is sufficiently strong to convert the alcohol to the alkoxide is suitable, as long as it does not cause degradation to the starting materials or product. Sodium hydroxide, potassium hydroxide, sodium hydride, potassium hydride and potassium t-butoxide are examples of acceptable bases with potassium t-butoxide and sodium hydride being preferred.
Polar aprotic organic solvents are employed as the reaction medium in the present process. Suitable polar aprotic organic solvents include alkyl nitrites such as acetonitrile, ethers such as tetrahydrofuran, 1,4-dioxane and 1,2-dimethoxyethane, carboxylic esters such as ethyl acetate, carboxylic amides such as dimethyl formamide, dimethyl acetamide and N-methyl pyrrolidinone, ureas such as 1,3-dimethyl-2-imidazolidinone or mixtures thereof.
The reaction is conducted at a temperature from about −10° C. to about 40° C. The optimal temperature can be readily determined by routine optimization. The preferred temperature is from about 10° C. to about 30° C.
The pressure under which the process is performed is not critical and the process is usually carried out at or slightly above atmospheric pressure. The process is preferably conducted under a dry inert atmosphere such as that provided by a nitrogen blanket.
The final product can be isolated and recovered by conventional procedures well known to those skilled in the art. Typically, the reaction mixture is diluted with water and the precipitated product is collected by filtration and dried.
In a typical reaction, the 2-fluoro-6-trifluoromethyl-N-([1,2,4]-triazolo[1,5-c]pyrimidin-2-yl)benzenesulfonamide starting material is at least partially dissolved in the polar aprotic organic solvent and treated with about 2-3 equivalents of base and 2-3 equivalents of alcohol at 10-30° C. for about 15-30 hours. After the reaction is complete, the reaction mixture is diluted with water and the precipitated product is collected by filtration and dried.
REFERENCES:
patent: 5858924 (1999-01-01), Johnson et al.
Gonzalez Michael Allen
Otterbacher Eric Wayne
Berch Mark L.
Dow AgroSciences LLC
Mixan Craig E.
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