FI58917B - PROCEDURE FOR FRAMSTAELLNING AV BIS- (2-PYRIDYL-1-OXID) DISULFID - Google Patents

Description

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Pttairt · och reglst «r * tyr« lMfl '' AntekM uttagd oeh utUkrtfUn publlcerid 30.01.81 (32) (33) (31) Pyydttty «uoikw · —Btglrd prlorittt 02.05 * 7 ^ USA (US) U66328 True-Styrkt (71 ) Olin Corporation, 275 Winchester Avenue, New Haven, Connecticut 0650U, USA (72) Haywood Hooks, Jr., West Haven, Connecticut, James Jerome Pitts,

Hamden, Connecticut, USA (US) (7 ^) Oy Kolster Ab (5 * 0 Process for the preparation of bis- (2-pyridyl-1-oxide) disulfide -Förfarande för framställning av bis- (2-pyridyl-1-oxide) disulfide This invention relates to an improved overall synthesis of bis- (2-pyridyl-1-oxide) disulfide to give the product in high purity and high yield, and more particularly to an overall synthesis of said disulfide compound by in-situ oxidation of an alkali metal salt of 2-mercaptopyridine which is obtained by oxidizing 2-chloropyridine with permaleic acid, followed by mercaptation with the selected sulfide and hydrogen peroxide using the selected pH conditions.

The preparation of bis- (2-pyridyl-1-oxide) disulfide (also referred to as 2,2'-di-thiodipyridine-1,1'-dioxide), hereinafter referred to as disulfide, has been extensively described previously in U.S. Patent 27I + 2H76. , wherein the mercaptopyridine-1-oxide is reacted with an oxidizing agent. U.S. Patent No. 375,9932 also generally discloses the preparation of a disulfide compound using an in-situ preparation technique in which mercaptopyridine is not isolated. Although these literature references broadly disclose the method of preparation of disulfide, problems have been encountered with the use of the alkali metal salt of 2-mercaptopyridine-1-oxide in an in-situ technique to obtain an alkali metal salt by oxidizing 2-chloropyridine with permaleic acid to form the N-oxide. to form a salt. When using this system, oxidation by known techniques, e.g., as disclosed in U.S. Patent No. 27 ^ 2 ^ 76, resulted in the formation of undesired by-products such as early metal maleate and alkali metal fumarate. This contaminated the desired disulfide product and reduced the yield.

It has now been found that by using permaleic acid in the total synthesis of disulfide in the preparation of 2-chloropyridine-1-oxide, the formation of the above by-products can be avoided and surprisingly high yields obtained by carrying out the final oxidation in the presence of hydrogen peroxide at selected pH conditions. More specifically, the oxidation of the alkali metal salt of 2-mercaptopyridine-1-oxide is performed at a pH of about 1 + -5 and preferably between about 1.5-5 *. The overall reaction scheme of the present invention is represented by the following equation:

pemaleiinihappox ^ v. NaSH

o o H 2 O 2, 1 pH U-5 Π n i * o 0

In the reaction of the present invention described above, 2-chloropyridine is oxidized to the N-oxide using permaleic acid according to known methods, such as that disclosed in U.S. Patent 29518U1 +. Mercaptation of 2-chloro-pyridine N-oxide is performed using alkali metal sulfide or alkali metal hydrosulfide according to known methods, such as disclosed in U.S. Patent 2686786. A key step in this invention is the oxidation of the alkali metal salt of 2-mercaptopyridine-1-oxide prepared from 58917 using hydrogen peroxide. .U-5. By maintaining the reaction under these conditions, contamination of undesired impurities, mainly due to salts of fumaric acid, is avoided and surprisingly high yields are obtained.

In carrying out the reaction of this invention, the temperature may generally be maintained between about 15 ° C and 35 ° C, with a range of about 20 ° C to 30 ° C being preferred. The hydrogen peroxide content can be varied and generally an aqueous solution of about 5 ~ 30% is used. Generally, a stoichiometric ratio of alkali metal salt of 2-mercaptopyridine to hydrogen peroxide of about 2 moles of mercaptopyridine salt n, per mole of peroxide or a small excess, up to about 15% peroxide, is used.

It is also generally desirable to stir the reaction mixture during the peroxide oxidation step to maintain an effective dilute hydrogen peroxide solution.

The pH of the reaction mixture is generally adjusted prior to the peroxide oxidation step using a suitable acidifying agent such as non-oxidizing raineric acids such as HCl and non-oxidizing organic acids.

Although 2-chloropyridine has been shown to be the desired starting material in the process of this invention, other 2-halopyridines and substituted halopyridines containing groups such as lower alkyl and lower alkoxy groups that do not adversely affect the reaction may be used.

Isolation of the final product after oxidation is accomplished by a standard filtration procedure.

The disulfide compounds prepared according to the process of this invention have various known uses, especially as bactericidal and fungicidal agents in various applications, such as the fight against crop diseases and in plastics and fabrics to resist mold or other fungi, as disclosed in U.S. Patent 2jU2hj6. The following examples further illustrate this invention.

Example 1

A 2-liter three-necked flask equipped with a stirrer, thermometer, and addition funnel was charged with 1,866 g of a reaction mixture containing the sodium salt of 2-mercaptopyridine-1-oxide. The composition of this reaction mixture was 7.2% (135 g) of the sodium salt of 2-mercaptopyridine-1-oxide, 7% of sodium chloride and 13-1% of total sodium maleate and sodium fumarate. This mixture was obtained by oxidizing 2-chloropyridine with permaleic acid and mercaptizing with NaSH. The pH was then adjusted to 1.5 with concentrated hydrochloric acid and the resulting warm solution was cooled to 25 ° C and 52 mL of 30% hydrogen peroxide (12% excess over stoichiometry) in ΐ6θ mL of water was added dropwise over 30 minutes with stirring. The reaction was slightly exothermic with a temperature rise of about 30 ° C at the end of the peroxide addition. Stirring of the now precipitated bis- (2-pyridyl-1-oxide) disulfide product was continued for another 2 hours to ensure completion of the reaction. The disulfide product formed was collected by filtration and the filter cake was washed with 50 ml of water and then with 50 ml of methanol. After air drying, a total of 112 g (98% yield based on the starting sodium salt of 2-mercaptopyridine-1-oxide) of bis- (2-pyridyl-1-oxide) disulfide with a melting point of 200-201 ° C and a concentration of 98% was obtained. .

Example 2 Using the same procedure as in Example I and a reaction mixture containing 25.6 g of the sodium salt of 2-mercaptopyridine-1-oxide, 1 g of 10% hydrogen peroxide, pH U, 0 and a reaction time of 18 hours, 17.0 g were obtained. disulfide product (79 * 8% yield calculated as sodium salt) with a content of 97 * 8% ·

Example 3 Using the same procedure as in Example I and a reaction mixture containing 25.6 g of the sodium salt of 2-mercaptopyridine-1-oxide, 1U of 10 # of hydrogen peroxide, pH 5.0 at a reaction temperature of 20-23 ° C and 18 reaction time, 19.0 g of disulfide product (yield $ 89.3 calculated as the sodium salt) was obtained with a concentration of 97.7% ·

Example ί

For comparison, the same procedure was followed as in Example II at a pH of 3.0. 23.5 g of product were obtained, but was contaminated with large amounts of fumaric acid impurities.

Example 5

For comparison, the same procedure was followed as in Example III with a pH of 5.5 and a reaction time of 72 hours. 10.5 g (^ 9.3% yield) of product were obtained.

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