Method for preparation of 2-methyl-1,2-benzisothiazolin-3-one

This invention relates to a method for preparation of 2-methyl-1,2-benzisothiazolin-3-one from 1,2-benzisothiazolin-3-one.

Methylation of 1,2-benzisothiazolin-3-one with agents such as methyl iodide and dimethyl sulfate is known. For example, A. Reissert & E. Manus, Chem. Ber ., (1928), vol. 61, pp. 1308-1316, disclose methylation of 1,2-benzisothiazolin-3-one with methyl iodide. However, this reaction produces mostly the O-alkylation product rather than 2-methyl-1,2-benzisothiazolin-3-one. There is a need for a more effective preparation of 2-methyl-1,2-benzisothiazolin-3-one from 1,2-benzisothiazolin-3-one.

The problem addressed by this invention is to provide an improved preparation of 2-methyl-1,2-benzisothiazolin-3-one from 1,2-benzisothiazolin-3-one.

The present invention is directed to a method for preparation of 2-methyl-1,2-benzisothiazolin-3-one from 1,2-benzisothiazolin-3-one; said method comprising contacting 1,2-benzisothiazolin-3-one with an alkali metal hydroxide and dimethyl sulfate.

“BIT” is 1,2-benzisothiazolin-3-one. “MBIT” is 2-methyl-1,2-benzisothiazolin-3-one. Unless otherwise specified, temperatures are in degrees centigrade (° C.), references to percentages are percentages by weight (wt %) and amounts and ratios are on a weight basis. Unless otherwise specified, all operations were performed at room temperature (20-25° C.) and at atmospheric pressure (101 kPa).

Preferably, the peak temperature of the reaction mixture during dimethyl sulfate addition is no greater than 40° C., preferably no greater than 35° C., preferably no greater than 30° C., preferably no greater than 25° C., preferably no greater than 20° C., preferably no greater than 15° C., preferably no greater than 10° C.; preferably the peak temperature of the reaction mixture is at least −5° C., preferably at least 0° C., preferably at least 2° C., preferably at least 4° C.

Preferably, the alkali metal hydroxide is sodium, lithium or potassium hydroxide; preferably sodium or potassium hydroxide. Mixtures of alkali metal hydroxides may be used. Preferably, the ratio of moles of hydroxide to moles of BIT is at least 0.7/1, preferably at least 0.8/1, preferably at least 0.9/1, preferably at least 0.95/1, preferably at least 1/1; preferably no greater than 2/1, preferably no greater than 1.5/1, preferably no greater than 1.2/1, preferably no greater than 1.1/1, preferably no greater than 1.05/1.

Preferably, the reaction is carried out in a solvent or mixture of solvents. Preferred solvents include, e.g., water, acetonitrile and other polar aprotic solvents (e.g., N,N-dimethylformamide), and ethers (e.g., polyethylene glycol ethers, glymes, dibutyl ether, crown ethers). Water is especially preferred.

Preferably, BIT and the alkali metal hydroxide are combined (preferably in solvent(s)) and the resulting mixture is contacted with dimethyl sulfate. Preferably, BIT, solvent and the alkali metal hydroxide are combined to form a mixture comprising the alkali metal salt of BIT, and then dimethyl sulfate is added to the mixture comprising the alkali metal salt of BIT. Preferably, the dimethyl sulfate is added at a rate which allows the reaction temperature to remain within the preferred limits. This rate can be determined easily based on various factors including, e.g., cooling capacity of the equipment, size of the reactor, the temperature at the beginning of the addition, heat capacity of the reaction mixture and other factors known in the art.

The reaction time may be determined by the usual known methods, e.g., taking samples for analysis to determine completeness of alkylation, and will of course depend on the temperature and the exact nature of the reactants. In general, it is preferred that the reaction time is at least 10 minutes, preferably at least 15 minutes, preferably at least 30 minutes. The upper bound on the reaction time is not critical because the product is stable in the reaction mixture, but for practical reasons it is preferred that it not exceed 24 hours, preferably 12 hours, preferably 6 hours. The reaction time is measured starting at completion of dimethyl sulfate addition. Preferably, the reaction occurs at approximately normal atmospheric pressure (101 kPa±10%).

MBIT is the desired product resulting from methylation on the nitrogen atom of BIT (“N-alkylation”) by dimethyl sulfate. 2-methoxy-1,2-benzisothiazole (MOBIT) is the undesired byproduct resulting from methylation on the carbonyl oxygen atom of BIT (“O-alkylation”). Separation of the N-methyl product from the O-methyl product may be achieved using standard techniques for separation of organic compounds, e.g., crystallization, distillation and extraction.