Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2001-02-20
2002-10-22
Tsang, Cecilia (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06469175
ABSTRACT:
FIELD OF THE INVENTION
This invention relates to methods of purifying thiadiazoles. More particularly, this invention pertains to methods of purifying 2-(methylthio)-5-trifluoromethyl)-1,3,4-thiadiazole using multiple acid extractions.
BACKGROUND OF THE INVENTION
The reaction of methyldithiocarbazinate (MDTC) with trifluoroacetic acid (TFA) forms a mixture of 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole (TDA) and 2,5-bis-(methylthio)-1,3,4-thiadiazole (bis by-product). Unfortunately, it is often difficult to remove the bis by-product from the resulting mixture without undesirable losses of TDA.
Prasad et al., U.S. Pat. No. 5,898,074, disclose a process of making 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole comprising the steps of reacting methyldithiocarbazinate with a molar excess of trifluoroacetic acid in the absence of phosphoryl chloride, wherein the molar ratio of trifluoroacetic acid to methyldithiocarbazinate is from about 1.1:1 to about 5:1 and water is a by-product of reaction; and recovering the excess trifluoroacetic acid. Prasad et al. teach that the organic phase of the reaction mixture is mixed with 70 wt % sulfuric acid to protonize the major impurity and extract it into the aqueous phase.
Prasad et al., U.S. Pat. No. 6,005,114, disclose a process of making 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole comprising the steps of reacting methyldithiocarbazinate and trifluoroacetic acid in a molar ratio of methyldithiocarbazinate to trifluoroacetic acid of from about 4:1 to about 1:5 and in the absence of phosphorus trichloride to form a mixture of 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole and 2,5-bis-(methylthio)-1,3,4-thiadiazole; and selectively removing the 2,5-bis-(methylthio)-1,3,4-thiadiazole by acidification of the reaction mixture followed by phase separation.
Prasad et al., U.S. Pat. No. 6,034,245 disclose a process of making 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole comprising the steps of reacting methyldithiocarbazinate with trifluoroacetic acid in the absence of phosphorus trichloride to form a mixture of 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole and 2,5-bis-(methylthio)-1,3,4-thiadiazole, wherein the molar ratio of methyldithiocarbazinate to trifluoroacetic acid is from about 4:1 to about 1:5 and the mixture contains a first organic phase and a first aqueous phase. Prasad et al. teach separating the first organic phase and the first aqueous phase; acidifying the first organic phase with a concentrated inorganic acid, resulting in the formation of a second organic phase and a second aqueous phase, wherein the 2,5-bis-(methylthio)-1,3,4-thiadiazole is soluble in the second aqueous phase; and separating the second organic phase and the second aqueous phase, wherein the 2,5-bis-(methylthio)-1,3,4-thiadiazole remains in the second aqueous phase.
Unfortunately, it has been found that a single acid extraction of the organic phase of a 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole reaction mixture often results in poor yields and/or purity when utilized commercially. Thus, there is a need for processes for preparation or purification of 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole which result in good yields and/or purity when utilized commercially.
SUMMARY OF THE INVENTION
Accordingly, it is an object of the present invention to obviate problems of the prior art. It is a further object of the present invention to. provide methods of purifying 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole good yields and/or purity.
These and additional objects are provided by the methods of the invention.
In accordance with one aspect of the invention there are provided methods of purifying 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole comprising the steps of providing a first 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole composition comprising 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole and organic solvent; performing a first extraction of the 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole composition with a first inorganic acid solution; and performing a second extraction of the 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole composition with a second inorganic acid solution.
In accordance with another aspect of the invention there are provided methods of purifying 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole comprising the steps of providing a first composition comprising 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole and organic solvent and a second composition comprising 2-methylthio-5-trifluoromethyl-1,3,4-thiadiazole and organic solvent; performing a first extraction of the first composition with a first inorganic acid solution; performing a second extraction of the first composition with a second inorganic acid solution; performing a first extraction of the second composition with the second inorganic acid solution; and performing a second extraction of the second composition with a third inorganic acid solution.
In accordance with yet another aspect of the invention there are provided processes of making 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole. The processes comprise the steps of reacting methyldithiocarbazinate with trifluoroacetic acid thereby forming a reaction mixture; isolating a first organic phase from the reaction mixture; acidifying the first organic phase with a first inorganic acid solution, thereby forming a second organic phase and a second aqueous phase; separating the second organic phase and the second aqueous phase; acidifying the second organic phase with a second inorganic acid solution, thereby forming a third organic phase and a third aqueous phase; and separating the third organic phase and the third aqueous. The 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole is present in the third organic phase.
The methods of the invention of the invention are advantageous in that the TDA obtained is of high purity, and the amount of TDA loss during purification is decreased as compared to methods using a single acid extraction.
These and additional aspects, objects and advantages of the invention are more fully described in the following detailed description.
DETAILED DESCRIPTION
The reaction of methyldithiocarbazinate (MDTC) with trifluoroacetic acid (TFA) forms a mixture of 2-(methylthio)-5-(trifluoromethyl)-1,3,4-thiadiazole (TDA) and 2,5-bis-(methylthio)-1,3,4-thiadiazole (bis by-product). The reaction of MDTC with TFA forms a reaction mixture comprising an aqueous phase, which is removed from the reaction mixture by azeotropic distillation, and an organic phase. The TDA and bis by-product are contained in the organic phase.
While not being bound by theory, it is believed that both the bis by-product and the TDA form complexes with acid, and that the bis by-product can displace TDA from TDA-acid complexes. The displacement can be diagrammed in the reaction shown below:
A+TDA→(A•TDA)
A+Bis→(A•Bis)
(A•TDA)+Bis→(A•Bis)+TDA
wherein “A” represents an acid, preferably an inorganic acid such as sulfuric acid, “(A•TDA)” represents a TDA-acid complex, and “(Bis•TDA)” represents a bis by-product-acid complex. The TDA-acid complex and bis by-product-acid complex are acid soluble, and thus may be removed from an organic phase with an acid solution, preferably an inorganic acid solution.
A single acid extraction often results is loss of TDA into the acid solution, or undesirable levels of bis by-product in the organic phase. It has unexpectedly been found that multiple acid extractions, particularly acid extractions wherein a first extraction is performed using an acid solution which was previously used in a prior extraction, results in improved yield and purity of TDA. As used herein, “acid extraction” refers to a process in which an organic phase is acidified with an acid solution, and as a result of acidification, a second organic phase and aqueous phase are formed. Thus “multiple acid extractions” refers to a process in which a second organic phase is obtained from the first acid ex
Hanson Joe J.
Jackman Dennis E.
Bayer Corporation
Gil Joseph C.
Harmuth Raymond J.
Sackey Ebenezer
Tsang Cecilia
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