CS263624B1 - Method for purifying 3 (2H) -benzo [d] isothiazolone-1,1-dioxide - Google Patents

Abstract

The solution relates to a method for purifying 3(2H)-benzo/d/isothiazolone-1,1-dioxide of formula I a) or its salts of general formula II, where the compound of formula I is precipitated from aqueous solutions of its salts of general formula II with thorough mixing by slow addition of mineral acid, at temperatures of 50 to 80 °C by adjusting the pH to a value of 1 and lower. The obtained product is separated from the mother liquors, for example, by filtration or centrifugation.

Description

The present invention relates to a process for purifying 3 (2H) -benzo [d] isothiazolone-1,1-dioxide (saccharin) of the formula I

IH (I) and / or its salts of formula II

Sat ₂

NM (II) wherein M = Na, K, NH ^, Ca ^^ '^ ^M L / 2 "and / or mixtures thereof.

Saccharin and its sodium salt are among the most widespread artificial sweeteners. They are prepared by a variety of procedures, the largest of which in the world has been achieved by the classical Fahlberg-Remsen procedure. According to this procedure, the 2-toluenesulfonyl chloride prepared by the chlorosulfonation of toluene is converted by reaction with ammonia to 2-toluenesulfonamide. This, after oxidation with potassium permanganate, yields saccharin. The saccharin thus prepared contains various impurities, predominantly 2-toluenesulfonamide (J. Assoc. Offic. Anal. Chem. 59, 1051 (1976), J. Chromatogr. 268 (1983)).

In the 1970s, the United States and Canada objected to the use of saccharin I and its sodium salt as an artificial sweetener. The reason was a suspicion of carcinogenicity (eg Med. Nutr. 13, 23 (1977), Exp. Onkol. 5, 21 (1983)), but this suspicion has so far neither been confirmed nor refuted. show that carcinogenicity of sweeteners containing saccharin or its sodium salt can be caused by impurities present in saccharin, especially sulfonamides.

By FAO Food and Nutrition Paper 17, pp. 111-114 (1980), is the limit of safe saccharin consumption in an adult of 2.5 mg / kg body weight per day, provided that the toluenesulonamides of formula III

CH ₃ (III) in saccharin is less than 25 ppm. The content of toluenesulfonamides of the formula III in the saccharin produced by the Fahlberg-Remsen process varies between 1000 and 10,000 ppm. Numerous approaches have been proposed to reduce their saccharin content. In the above overview of the refining process, the term saccharin encompasses both its acid form of formula I and its salts of formula II, since both known forms can easily be converted into one another as desired (see, eg, Beilstein's Handbuch der organischem Chemie, 4 ed. , Volume XXVII, p. 170, Springer Verlag Berlin (1937).

The first group comprises processes utilizing the extraction of aqueous solutions of salts of Formula II with organic solvents such as dichloromethane (U.S. Pat. No. 4,158,006, Ger. 2,730,861,

GB 1,580,715, DD Pat. 130,579), ethyl acetate, butyl acetate, butyl acetate or mixtures thereof (JP.

U.S. Pat. No. 8,035,092, U.S. Pat. 3,988,344). Another group consists of processes to remove residual toluenesulfonamides of formula III by chemical reaction, such as oxidation with potassium permanganate DD pat. 140 881), reaction with nitration mixture (MS AO 92 910), or reaction with nitrites in the environment of strong mineral acids (DD pat. 143 610). The adsorption of toluenesulfonamides of the formula III from an aqueous solution of the sodium potassium saccharin (of the formula II, M = Na, K) on activated carbon and other adsorbents is described in AO 135 157. Mineral acid precipitation of saccharin of the formula I from aqueous solutions of the salts of formula II ° C according to AO 238 944 also leads to a reduced toluenesulfonamide product of the formula III.

All of the saccharin refining processes mentioned have a number of disadvantages, including handling of flammable or toxic solvents and the need for their regeneration in the case of extraction purification, reducing the saccharin yield of the DD pat. 140,881, the possibility of contaminating the product with nitrites and nitrates and reducing saccharin yield in DD pat. 143 610 and MS. AO 92 910 and difficult adsorbent regeneration in the process along AO 135 157. By the procedure according to MS. AO 238 944 also results in considerable saccharin losses, since, due to the high precipitation temperature, a considerable portion of the saccharin of formula I remains dissolved in the mother liquors and a portion of the saccharin of formula I undergoes hydrolysis to the acid ammonium salt of 2-sulfobenzoic acid. A more significant disadvantage of the process of AO 238 944 is that the toluenesulfonamides of formula (III) in the product obtained exceed the permitted limit of 25 ppm, even at precipitation temperatures above 90 ° C, where the amount of isolated saccharin of formula I is only 30-40% theoretical yield.

The above disadvantages are eliminated by the process of purification of 3 (2H) -benzo [d] -isothiazolone-1,1-dioxide of formula II and / or its salts of formula II from the toluenesulfonamides of formula III according to the invention, which consists in their salts of formula II, prepared by neutralizing the saccharin of formula I with an aqueous solution or aqueous suspension of the corresponding base (see, e.g., Bielstein's Handbuch der Organischen Chemie, Vol. XXVII, p. 170, Springer-Verlag Berlin 1937), respectively. by dissolving the salt of formula (II) in water, the saccharin of formula (I) precipitates with complete mixing by gradually adding a strong mineral acid such as hydrochloric acid or sulfuric acid at temperatures of 50-80 ° C, adjusting the pH of the mixture to 1 or lower. The separated purified saccharin of formula I is separated from the mother liquors by conventional methods such as filtration, centrifugation, and the like. The saccharin of formula I obtained above with a toluene sulfonamide content in the range of 30 to 200 ppm is readily converted to any salt of formula I less than 20 ppm of the toluenesulfonamides of formula III. An aqueous solution of saccharin sodium potassium (formula II, M = Na), K), excellent in the oxidation of 2-toluenesulfonamide, may also be used to prepare saccharin of formula III by the process of the invention, but manganese dioxide and unreacted 2-toluenesulfoamide .

The process of the invention has a number of advantages. This is achieved at a minimum loss (not exceeding 20%) of high product quality since the toluenesulfonamides of formula III can be reduced from thousands of ppm to ppm. At the same time, this method is simple and requires no special equipment and chemicals.

The invention and its effects are illustrated in more detail in the following examples, which are illustrative only and in no way limit the scope of the invention.

Example 1

125 g of saccharin of the formula I containing 3,410 ppm of toluenesulfonamides of the general formula III were dissolved in 210 ml of a 20% aqueous potassium carbonate solution. The resulting saccharin potassium salt solution was diluted to 1000 mL with water. The saccharin of formula I was precipitated from this pH 10 solution with vigorous stirring at 75 ° C by uniformly adding 10% hydrochloric acid at an average rate of 4 ml / min for about 70 minutes, until a pH of 0 to 1 was achieved (universal indicator paper check) . The product was collected by filtration (frit S-2) and washed with cold water on the filter. 108.3 grams of saccharin (I) containing 65 ppm of toluenesulfonamides (III) were obtained.

Example 2

125 g of saccharin of the formula I containing 3,410 ppm of the toluenesulfonamides of the formula III were dissolved in 325 ml of a 5% ammonia solution. The resulting saccharin ammonium salt solution was diluted to 1000 mL with water. From this solution of pH 9, 105.6 g of saccharin (I) containing 47 ppm of toluenesulfonamides (XII) were obtained as described in Example 1.

Example 3

140 g of the saccharin anhydrous salt of formula II (M = Na) containing 1,620 ppm of the toluenesulfonamides of the formula III were dissolved in 500 ml of water, and the volume of the solution was then made up to 1000 ml with water. The saccharin of formula I was obtained from this pH 7 solution as described in Example 1. From this saccharin of formula I a sodium salt of formula II (M = Na) pH pH = 7 was gradually added by adding 10% aqueous sodium carbonate solution. Evaporation of water and drying of the precipitated salt of formula II (M = Na) containing 51 ppm of the toluenesulfonamides of formula III.

He attaches

The manganese dioxide was filtered from the reaction mixture after the oxidation of 2-toluenesulfonamide with potassium permanganate. After separation, the pH of the solution was adjusted with hydrochloric acid from the original 13 to 115 g / l of saccharin in the filtrate (calculated on saccharin of formula I) was 115 g / l and the toluenesulfonamides of formula III was 2900 ppm.

a) From 5,000 filtrate, saccharin of formula I was precipitated at 25 ° C by adding 900 ml of 20% hydrochloric acid. The average feed rate of hydrochloric acid was 50 ml / min. The resulting precipitate was filtered off and washed twice with 500 ml of water on the filter. It was obtained

560 g of saccharin of formula I containing 3,150 ppm of toluenesulfonamides of formula III.

b) Of 700 ml of the filtrate, with intensive precipitation with 10% hydrochloric acid at 65 ° C, the saccharin of formula I. The average acid dosing rate was 6 ml / min, the resulting pH of the mixture was 0 to 1. After filtration of the mother liquors, 10% sodium hydroxide solution was added with stirring until all the solid phase dissolved and the pH of the solution reached approximately 6. Then the sodium salt solution of formula 1K (M = Na) was diluted with water to a volume of 630 ml. The saccharin of formula I was precipitated from this solution as described above with hydrochloric acid at 50 ° C. The product was isolated by filtration and washed with cold water on the filter. 71.0 g of saccharin (I) containing 11.3 ppm of toluenesulfonamides (III) were obtained.

Example 5

From the reaction mixture after oxidation of the 2-toluenesulfonamides with potassium permanganate, a solution of 119 g / l of sodium saccharin (M = Na) K) (recalculated to saccharin of formula I) was obtained as described in Example 4. The toluenesulfonamides of formula III in this solution were 2,740 ppm.

a) From 1000 ml of the solution, saccharin of the formula I was precipitated at 25 ° C by adding 140 ml of 20% hydrochloric acid. The average rate of hydrochloric acid was 10 ml / min. The resulting pH was 0 to 1. The resulting precipitate was filtered off and washed twice with 100 ml of water. 114 g of saccharin were obtained with a content of toluenesulfonamides of 2,390 ppm.

b) The saccharin of formula I was obtained from 1,850 l of the solution as described in Example 4 and b). The first precipitation temperature was maintained at 72-76 ° C, the average rate of 10% hydrochloric acid was 3.7 l / min after for 2 hours. The second precipitation temperature ranged from 64 to 67 ° C, with an average feed rate of 10% hydrochloric acid of 3.2 l / min for 2 hours. The sodium saccharin solution prepared for the second precipitation was diluted with water on a centrifuge. 188 kg of saccharin (I) containing 4.9 ppm of toluenesulfonamides (III) were obtained.

Claims (1)

A method of purification of 3 (2H) -benzophenylisotheazolone-1,1-dioxide of formula I (I) wherein M is Na, KnNH 2. (a) or mixtures thereof from toluenesulfonamides M of formula III (II), _CH3 (III) _{'SO2 NH2} precipitation saccharin of formula I from aqueous solutions of its salts of formula II, prepared by dissolving the salt of formula II in water, neutralization saccharin of formula I with aqueous solutions or suspensions of the appropriate base, by oxidation of 2-toluenesulfonamide potassium permanganate or by another oxidizing agent carried out with efficient mixing by successive addition of a mineral acid, an acid such as hydrochloric acid or sulfuric acid, characterized in that the gradual precipitation is carried out at temperatures of 50 to 80 ° C by adjusting the pH to 1 or lower, it is separated from the mother liquors by conventional means, such as filtration, centrifugation and the like, and optionally converted to the desired salt of formula (II) by known methods.