Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-03-15
2001-02-27
Higel, Floyd D. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C548S263200, C504S139000
Reexamination Certificate
active
06194583
ABSTRACT:
The present invention relates to the field of organic chemical synthesis. In particular, the invention is a process for synthesizing a triazol compound, namely the herbicide ethyl &agr;-2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate (the “Herbicide”).
The Herbicide, prepared by a different process, is disclosed and claimed in U.S. Pat. No. 5,125,958, issued Jun. 30, 1992. In that process the 5-amino intermediate of the present process is diazotized with t-butyl nitrite to give an intermediate that is reacted with a large excess of ethyl acrylate to yield the Herbicide. It will be apparent that for large scale preparations the process of the present invention is not only safer, but more cost effective than the process disclosed in the patent.
SUMMARY OF THE INVENTION
The present invention relates to a new method for preparing the Herbicide using, in one embodiment thereof, a halogen placed in the 5-position of an intermediate, 1-(2,4-disubstituted-phenyl)-4-difluoromethyl4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole, in which the 5-position of the phenyl ring is either unsubstituted or carries an amino group. In this embodiment, the resulting 1-(2,4-disubstituted-5-halophenyl)-4-difluoromethyl4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole is then preferably reacted with an alkyl alkanoate in the presence of a suitable palladium catalyst, affording a second intermediate, alkyl &agr;-acetyl-2,4-disubstituted-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]benzenepropanoate. This second intermediate is preferably chlorinated with sodium hypochlorite, then reacted with a suitable base in the same reaction vessel, affording alkyl &agr;-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-(2,4-disubstituted)-benzenepropanoate. When the appropriate substituents are chosen, the product of this sequence of reactions is ethyl &agr;-2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1 -yl]-4-fluorobenzenepropanoate (the “Herbicide”).
In particular, the present invention relates to a process for preparing Compound E of the formula
in which X and Y are the same or different and are independently selected from halo, alkyl, cycloalkyl, alkoxy, nitro, and hetercyclyl, and R is alkyl or haloalkyl having 1 to 10 carbon atoms, comprising combining Intermediate D of the formula
wherein X, Y, and R are defined as for Compound E, with about 1 to about 5 molar equivalents (M eq) of an alkanoic acid, about 1 to about 9 M eq of sodium hypochlorite, and about 1 to about 5 M eq of a base, the amounts of all reagents relative to 1.0 M eq of Intermediate D, and recovering Compound E. In a preferred embodiment, X and Y are halo, and R has 1 to 4 carbon atoms. In another preferred embodiment of this process, about one molar equivalent of Intermediate D is dissolved in alcohol at ambient temperature to which the following are added, with stirring: (a) about 1.0 to about 1.2 molar equivalents of an organic acid having up to 7 carbon atoms; (b) about 1.0 to about 1.2 molar equivalents of sodium hypochlorite; (c) about 1.0 to about 1.4 molar equivalents of sodium bicarbonate or ammonium hydroxide; and the stirring is continued at a temperature in the range of about 25° C. to about 60° C., and Compound E is recovered. This preferred embodiment more particularly relates to the addition of about 1.2 molar equivalents of each of acetic acid, sodium hypochlorite, and ammonium hydroxide.
In another embodiment, Intermediate D is preferably prepared by reacting an Intermediate B of the formula
in which Z′ is halo, with an alkanoate C of the formula
in which R″ is hydrogen or —CH(CH
3
)OH, in the presence of a suitable palladium(II) catalyst and an amine R′
3
N in which R′ is alkyl of 1 to 5 carbon atoms. For this embodiment, Intermediate B can be prepared by reacting an Intermediate A of the formula
in which Z is hydrogen or amino, with a suitable halogenating agent in the presence of a suitable strong acid.
In yet another embodiment, the present invention relates to a process for preparing ethyl &agr;-2-dichloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]-4-fluorobenzenepropanoate (the “Herbicide”), comprising reacting ethyl &agr;-acetyl-2-chloro-5-[4-(difluoromethyl)-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazol-1-yl]4-fluorobenzenepropanoate (“Intermediate D”), first with sodium hypochlorite, then with a suitable base, recovering the Herbicide, said Intermediate D being prepared by reacting 1-(4-chloro-2-fluoro-5-bromo or 5-iodophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole (“Intermediate B”), with ethyl 3-hydroxy-2-methylenebutanoate or ethyl acrylate in the presence of a suitable palladium catalyst and a tertiary amine, said Intermediate B being prepared by reacting 1-(4-chloro-2-fluorophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole with a suitable brominating or iodinating agent in the presence of an acid. For this embodiment, Intermediate D is preferably recovered after heating the combination of one molar equivalent of Intermediate B, about 1.0 to about 1.3 molar equivalents of ethyl 3-hydroxy-2-methylenebutanoate or ethyl acrylate, about 0.01 to about 0.03 molar equivalent of a suitable palladium catalyst, and about 1.25 to about 3.5 molar equivalents of a tertiary amine to a suitable temperature in the range of about 120° C. to about 135° C. and for about 1 hour to about 4 hours, said suitable palladium catalyst being selected from the group consisting of palladium(II) acetate, palladium(II) on carbon, and bis(benzonitrile)dichloropalladium(II). In the context of this embodiment, about one molar equivalent of 1-(4-chloro-2-fluorophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole (“triazole”) is preferably dissolved with stirring in an amount of oleum sufficient to dissolve the triazole, thereby forming a triazole solution, the triazole solution is cooled in an ice bath, about one molar equivalent of bromine or iodine is added to the triazole solution, the triazole solution is further stirred at ambient temperature for at least 30 minutes, and Intermediate B is recovered.
In yet another preferred embodiment, the present invention relates to a compound of the formula
where X is fluoro, Y is chloro, and Z′ is —CH
2
CH[C(O)CH
3
]CO
2
C
2
H
5
, bromo, or iodo.
DEFINITIONS
The modifier “about” is used herein to indicate that certain preferred operating ranges, such as ranges for molar ratios for reactants, material amounts, and temperature, are not fixedly determined. The meaning will often be apparent to one of ordinary skill. For example, a recitation of a temperature range of about 120° C. to about 135° C. in reference to, for example, an organic chemical reaction would be interpreted to include other like temperatures that can be expected to favor a useful reaction rate for the reaction, such as 105° C. or 150° C. Where guidance from the experience of those of ordinary skill is lacking, guidance from the context is lacking, and where a more specific rule is not recited below, the “about” range shall be not more than 10% of the absolute value of an end point or 10% of the range recited, whichever is less.
As used in this specification and unless otherwise indicated the substituent terms alkyl, cycloalkyl, alkoxy, alkanoate, alkanoic, and haloalkyl, used alone or as part of a larger moiety, includes straight or branched chains of at least one or two carbon atoms, as appropriate to the substituent, and preferably up to 12 carbon atoms, more preferably up to ten carbon atoms, most preferably up to seven carbon atoms. “Halogen” or “halo” refers to fluorine, bromine, iodine, or chlorine.
DESCRIPTION OF THE INVENTION
In the first step of the process of the present invention a 1-(2,4-disubstituted-5-halophenyl)-4-difluoromethyl-4,5-dihydro-3-methyl-5-oxo-1H-1,2,4-triazole B, in which X and Y are
Crispino Gerard A.
Goudar Jaidev S.
FMC Corporation
FMC Corporation
Higel Floyd D.
Sackey Ebenezer
LandOfFree
Process for the preparation of a triazolinone herbicide does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of a triazolinone herbicide, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of a triazolinone herbicide will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-2577418