Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
2000-09-20
2004-05-25
Stockton, Laura L. (Department: 1626)
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
Reexamination Certificate
active
06740759
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the invention
The present invention concerns a method of producing 2-alkyl-4-isothiazoline-3-one which is useful as an industrial disinfectant
2. Description of the Prior Art
The isothiazoline-3-one which has been used as industrial disinfectants has been a mixture of 2-alkyl-4-isothiazoline-3-one and 5-chloro-2-alkyl-4-isothiazoline-3-one. However, with the recent emergence of problems of mutagenicity associated with 5-chloro-2-alkyl-4-isothiazoline-3-one, the demand has risen for 2-alkyl-4-isothiazoline-3-one with a low or no content of 5-chloro-2-alkyl-4-isothiazoline-3-one.
Numerous methods of producing 2-alkyl-4-isothiazoline-3-ones have been disclosed. For example, as presented in U.S. Pat. No. 3,849,430 and European Patent 95907, N-alkyl-3-mercaptopropionamide is chlorinated in ethyl acetate solvent to obtain a mixture of 2-alkyl-4-isothiazoline-3-one and 5-chloro-2-alkyl-4-isothiazoline-3-one. However, the methods of production stated here provide no means of reducing the content of 5-chloro-2-alkyl-4-isothiazoline-3-one.
The method presented in European Patent 0437354 states a method of separating 2-alkyl-4-isothiazoline-3-one at comparatively high purity by neutralizing only the 5-chloro-2-alkyl-4-isothiazoline-3-one in a mixture of 2-alkyl-4-isothiazoline-3-one hydrochloride and 5-chloro-2-alkyl-4-isothiazoline-3-one hydrochloride using anhydrous ammonia. However, the procedures in this production method are complex and the level of 5-chloro-2-alkyl-4-isothiazoline-3-one which brings about mutagenicity is present as before. Furthermore, a significant amount of 2-alkyl-4-isothiazoline-3-one is lost when attempting to remove 5-chloro-2-alkyl-4-isothiazoline-3-one.
Furthermore, European patent 0678510 presents a method in which a mixture of 2-alkyl-4-isothiazoline-3-one hydrochloride and 5-chloro-2-alkyl-4-isothiazoline-3-one hydrochloride is heated in organic solvent. 2-alkyl-4-isothiazoline-3-one hydrochloride is refined utilizing the difference in solubility between 2-alkyl-4-isothiazoline-3-one hydrochloride and 5-chloro-2-alkyl-4-isothiazoline-3-one hydrochloride in organic solvent, but a level of 5-chloro-2-alkyl-4-isothiazoline-3-one sufficient to bring about mutagenicity remains as before, and the loss of 2-alkyl-4-isothiazoline-3-one remains unavoidable.
As indicated above, all prior art is to obtain 2-alkyl-4-isothiazoline-3-one through purification of a mixture contaminated with 5-chloro-2-alkyl-4-isothiazoline-3-one rather than preferentially producing the desired 2-alkyl-4-isothiazoline-3-one.
However, the complete removal of 5-chloro-2-alkyl-4-isothiazoline-3-one through refining procedures remains difficult, and some of the 2-alkyl-4-isothiazoline-3-one is inevitably lost. Furthermore, the production procedures become more complex as the refining process is incorporated. Accordingly, in order to obtain 2-alkyl-4-isothiazoline-3-one of high purity in an industrially profitable manner, it is advantageous to suppress the formation of 5-chloro-2-alkyl-4-isothiazoline-3-one in the production stage as much as possible, and to minimize the loss of 2-alkyl-4-isothiazoline-3-one associated with purification.
SUMMARY OF THE INVENTION
In light of aforementioned circumstances, the purpose of the present invention is to provide a method of obtaining high-purity 2-alkyl-4-isothiazoline-3-one in a profitable yield through an industrially simple method, which does not contain 5-chloro-2-alkyl-4-isothiazoline-3-one or contains it at a level low enough so as not to bring about mutagenicity.
The inventors conducted thorough examinations into methods of producing 2-alkyl-4-isothiazoline-3-one in which the generation of 5-chloro-2-alkyl-4-isothiazoline-3-one is greatly reduced, the results of which revealed the unanticipated fact that the selectivity of 2-alkyl-4-isothiazoline-3-one and 5-chloro-2-alkyl-4-isothiazoline-3-one produced varies greatly with the type of solvent used in the reaction. Specifically, a correlation between the solubility of the hydrogen chloride in the solvent used in the reaction and the ratio of production of 2-alkyl-4-isothiazoline-3-one to 5-chloro-2-alkyl-4-isothiazoline-3-one was discovered that led to the completion of the present invention.
According to the present invention, the method of producing 2-alkyl-4-isothiazoline-3-one represented by general formula (III)
(wherein R represents C1 to C8 alkyl groups or aralkyl groups) is characterized by the fact that the compound represented by formula (I) a
(wherein R has the same significance as in aforementioned formula (III)) or the compound represented by formula (II)
(wherein R has the same significance as in aforementioned formula (III)) are reacted in a solvent in which hydrogen chloride is insoluble or has low solubility with a chlorinating agent with a ratio of two equivalents of chlorinating agent per mol of formula (I) or three mole equivalents of chlorinating agent per mol of formula (II).
R in formula (I), (II) and (III) represents C1 to C8 alkyl groups or aralkyl groups. Methyl groups or normal octyl groups are preferred industrially.
Aforementioned solvent preferably should be inert to the compounds of formula (I), formula (II), formula (III) and the chlorinating agent. Inertness means that the solvent does not react with formula (I), formula (II), formula (III) or with chlorinating agent.
Furthermore, aforementioned solvent would be preferably those in which hydrogen chloride is insoluble or has low solubility. More specifically the solubility of hydrogen chloride in the preferred solvent at normal temperature/pressure would preferably be a molar fraction of 0.04 or less, more preferably 0.03 or less, still more preferably 0.02 or less.
Aforementioned solvents would preferably be selected from the organic solvents, especially from halogenated aliphatic hydrocarbons, halogenated aromatic hydrocarbons and aliphatic hydrocarbons. The solvent is preferably dichloromethane, dichloroethane, trichloroethane, tetrachloroethane, chloroform, carbon tetrachloride, monochlorobenzene, dichlorobenzene, pentane, hexane, cyclohexane, heptane, and octane.
In performing the present invention it is more preferable to isolate the hydrochloride of formula (II) which results from the reaction of the compounds of formula (I) or formula (II) with the chlorinating agent, and wash the salt with a solvent with which the salt does not react and in which the solubility of the salt is low.
Since the present invention of producing 2-alkyl-4-isothiazoline-3-one of the formula (III)
(wherein R represents C1 to C8 alkyl groups or aralkyl groups) is characterized by the fact that compound of the formula(I)
(wherein R has the same significance as in aforementioned formula (III)) or the compound represented by formula (II)
(wherein R has the same significance as in aforementioned formula (III)) is reacted in a solvent in which hydrogen chloride is insoluble or has low solubility with a chlorinating agent with a ratio of two mole equivalent per mole of compound of formula (I) or three mole equivalent per mole of compound of formula (II), virtually no 5-chloro-2-alkyl-4-isothiazoline-3-one, a mutagenic substance, is present and 2-alkyl-4-isothiazoline-3-one can be obtained at high selectivity.
Furthermore, since 2-alkyl-4-isothiazoline-3-one can be obtained selectively, purification need not be repeated as in the conventional method cited above, and leads to a quite economical process with minimal loss in yield from the refining step.
Aforementioned effects can be attained by using a solvent in which the solubility of hydrogen chloride is under 0.04 in molar fraction at normal temperature/pressure.
The production of by-products can be efficiently reduced by using a solvent in which formula (I), formula (II), formula (III) and chlorinating agent are inert.
Furthermore, higher-purity 2-alkyl-4-isothiazoline-3-one can be produced by removing the hydrochloride of formula (III) which is produced through reaction of the compound of formula (I) or formula (II) with chlorinating agen
Liu Guo-bin
Morita Masayuki
Yoneta Noriko
Chemicrea, Inc.
Nixon & Peabody LLP
Studebaker Donald R.
LandOfFree
Method for producing 2-alkyl-4-isothiazoline-3-one does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Method for producing 2-alkyl-4-isothiazoline-3-one, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Method for producing 2-alkyl-4-isothiazoline-3-one will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-3235500