DE3607317A1 - Method of preparing 4-hydroxy-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide - Google Patents

Abstract

A method is described of preparing, a sweetener from 1,2-benzoisothiazol-3(2H)-one 1,1-dioxide by anodic oxidation in the presence of trifluoroacetic acid or trifluoromethanesulphonic acid and, optionally, of salts which increase the conductivity. The oxidation takes place in an anhydrous medium and the 4-trifluoroacetyl-1,2-benzoisothiazol-3(2H)-one 1,1-dioxide, which forms as an intermediate if, for example, trifluoroacetic acid is used, is decomposed with water to form the desired product.

Description

Process for the preparation of 4-hydroxy

1,2-Benzisothiazol-3 (2H) -one-l, l-dioxide The invention relates to a new process for the preparation of 4-hydroxy-1,2-benzisothiazol-3 (2H) -one-l, l-dioxide. This compound has the formula and has been described as a sweetener with superior sensory qualities by European Patent No. 0 038 458 (corresponding to US Patent No. 4,404,230). In the same publication, 4 processes for their production were described, but each of them run over 4 to 7 stages, starting with inexpensive starting materials. However, since a sweetener can be produced in large quantities and at the lowest possible prices, there was a need to find a synthetic route that was as simple as possible and that could be carried out on an industrial scale, starting from a cheap educt that was available in large quantities.

This problem could be solved by the fact that the 1,2-benzisothiazol-3 (2H) -one-l, l-dioxide (Saccharin (R) cf.

Formula II below) is anodically oxidized in a one-step process to give 4-hydroxy-1,2-benzisothiazol-3 (2H) -one-1,1-dioxide in the presence of trifluoroacetic acid or trifluoromethanesulfonic acid. The starting compound is produced on an industrial scale and is therefore available as a cheap starting compound. The following reaction scheme illustrates this oxidation: In the compound of the formula Ia, R is the CF3CO or CF3SO2 group.

The reaction, which proceeds in the absence of water, takes place in the presence of trifluoroacetic acid, in the presence of a conductive salt and optionally an organic one Solvent at temperatures between 0OC and 500C, but preferably at room temperature. The anodic oxidation can take the form of a discontinuous as well as in Be carried out in the form of a continuous process.

In the discontinuous process, the formed Product, preferably after passing a certain amount of electricity through suitable Methods removed and the unreacted compound of formula 1-1 by adding additional starting compound and then re-oxidized electrochemically. If the process is carried out continuously, the product formed is of the formula I continuously isolated from the reaction mixture; the latter is supplemented by something new Educt of the formula II, fed back into the anodic oxidation circuit. the intermediate formed compound of formula Ia is independent on the way the process is carried out, decomposed by means of water. For anodic oxidation A number of organic solvents and electrolytes are suitable, all What they have in common, however, is the highest possible anodic decomposition potential. Suitable Solvents are, for example, dichloromethane, sulfolane, acetonitrile, dimethylformamide, Dimethyl sulfoxide, dimethylacetamide, tetrahydrofuran, pyridine, acetic acid or nitromethane. However, mixtures of these solvents can also be used. Particularly suitable Conductive salts are tetraalkylammonium fluoroborates, such as tetraethylammonium fluoroborate, Tetra-n-butylammonium fluoroborate, but also alkali trifluoroacetates, such as sodium or potassium trifluoroacetate, or alkali perchlorates, such as sodium or lithium perchlorate. Additions of aluminum oxide or trifluoroacetic anhydride work in some Cases very favorably on the yield by using these substances for anhydrous conditions care for.

The voltage required depends very much on the experimental setup, for example the type and configuration of the electrodes, the distance between the electrodes, on the type of electrolytes and solvents used. The potential can get through the attachment of a reference electrode can be checked. It is chosen so that the formation of decomposition products, such as hexafluoroethane, when using Trifluoroacetic acid, or further oxidation of the intermediate of the formula Ia does not takes place.

In general, an amount of current of 2 to 4 F applied per mole of reacted starting material.

A large number of possible electrodes are suitable for the production of electrodes Materials, the only requirement is a certain oxidation stability. It is suitable So there are quite a few of oxide electrodes, such as lead dioxide, but also platinum or other precious metal electrodes, under technical conditions also lead, lead dioxide, glassy carbon, graphite or carbon electrodes. The electrodes can be in plate or network form, for example in the form that the The cathode is a spiral that is in the center of a network cylinder that serves as an anode, lies.

When performing electrolytic oxidation, it is also possible to separate the cathode compartment from the anode compartment by a semi-permeable diaphragm, in order to prevent a reduction of the compound of formula I formed in the cathode compartment. It is recommended to use materials that are solvent-resistant and have a low resistance.

The reaction can be carried out in the usually available Perform electrolysis apparatus, such as those used e.g.

by L. Eberson and H. Schäfer in “Advances in Chemical Research / Topics in Current Chemistry ", 21, pages 1 to 39 (Springer-Verlag, Berlin-Heidelberg-New York 1971), the use of capillary gap cells being particular Offers advantages.

It is known that in the presence of trifluoroacetic acid and sodium trifluoroacetate and of organic solvents such as acetone, the anodic oxidation of alkyl aromatics or acyl aromatics to be ring-trifluoroacetoxylated and, optionally, side-chain trifluoroacetoxylated Products. It is believed that the nuclear substitution via aromatic radical cations leads, which are particularly stable in the strong trifluoroacetic acid.

Different isomers are formed in the process; the isomer distribution found corresponds to that calculated according to the INDO method for the aromatic radical cation positive charge density distribution (cf. Z. Blum, L. Cedheim and K. Nyberg, Acta Chem. Scand. B 29, 715 [1975]).

In the present case the anodic oxidation by means of an intermediate Trifluoroacetoxylation would have (also after knowledge of the review by Kunihisa Yoshida, Electrooxidation in Organic Chemistry, The Role of Cation Radicals as Synthetic Intermediates, A Wiley-Interscience Publication, John Wiley and Sons, New York, in particular page 209) it must be expected that in addition to 4-hydroxy-1,2-benzisothiazol-2 (3H) -one-l, l-dioxide the isomers with hydroxyl groups also occur in the other positions on the aromatic, resulting in a reduction in the yield of the compound of formula I and too considerable Difficulties in isolating the pure compound would have led. Instead of this but arises in the anodic oxidation of the compound of formula II only Compound of the formula I, which can be converted by suitable measures can be carried out practically quantitatively. Surprising if you know the state of the art this selectivity of oxidation.

It should not go unmentioned that the compound of formula II for decades in electroplating, especially as an additive to nickel baths, is used. But it has never been observed and described that this compound can be oxidatively hydroxylated in the process (1. Dubsky and P. Kozak, Metalloberfläche Angewandte Elektrochemie 27, page 217 to 227, 1973, especially page 223, column 1).

In summary it can be said that the oxidation of the compound II only for connection I was not foreseeable.

The following examples are intended to explain the essence of the invention in more detail: Example 1 4.6 g (25 mmol) of 1,2-benzisothiazol-3 (2H) -one-l, l-dioxide (saccharin (R)) were in a mixture consisting of 65 ml of methylene chloride, 35 ml of trifluoroacetic acid and 2 , 1 g of tetraethylammonium tetrafluoroborate, dissolved. The solution was in an electrolysis trough without separation of the cathode and anode compartment (undivided cell) using a platinum spiral (wire diameter 1 mm, spiral diameter 0.5 cm, spiral length 7.5 cm) as the cathode and a cylindrical platinum mesh (cylinder diameter 3.5 cm , Cylinder height 5 cm, cylinder area 5 cm 2) electrolyzed as an anode at room temperature. A dry rectifier with a potentiometer was used as the power source. An ammeter connected in series was used to determine the ampere hours and a voltmeter was used to determine the potential between cathode and anode (approx. 5-7 volts). After an amount of current of approx. 0.5 Ah had been consumed, the electrolysis was stopped. The solution was poured into ice water. The organic phase was separated off and combined with the chloroform extracts of the aqueous phase. After evaporation of the solvent, the residue was partitioned between an aqueous iron (III) chloride solution and methylene chloride. 2.7 g of starting material were recovered from the methylene chloride phase. The iron (III) chloride solution was made alkaline and filtered. The filtrate was now acidified and extracted with methylene chloride. After evaporation and recrystallization from water, 1.2 g of 4-hydroxy-1,2-benzisothiazol-3 (2H) -one-1,1-dioxide were obtained. This corresponds to a yield of 58% calculated on the converted starting material and a current efficiency of 67%.

Melting point: 2280C.

MS: 199 (M +), 136, 119 and 108 m / e.

C7H5NO4S (199.19) Calcd .: C 42.20 H 2.53 N 7.03 S 16.10 Found: 42.25 2.62 7.02 16.00 The presence of an isomeric 5- or 6- or 7-hydroxy compound could not be proven.

Example 2 The reaction was carried out according to that described in Example 1 Method. The unreacted starting material was separated off by column chromatography on silica gel (MN silica gel 60; 0.063-0.2 mm; Macherey + Nagel, 5160 Düren, item no. 81533) using ethylene chloride / ethyl acetate / glacial acetic acid (100: 30: 5) as the eluent.

First, 2.65 g of the unreacted starting product were eluted, thereafter, after subsequent recrystallization, the end product could be obtained in 61% yield (based on converted material) are obtained; Melting point: 2280C C7H5NO4S (199.19) Be. : C 42.20 H 2.53 N 7.03 S 16.10 Found: 42.30 2.64 7.05 16.10 Example 3 4.6 g (25 mmol) of 1,2-benzisothiazol-3 (2H) -one-l, l-dioxide (saccharin (R)) were in a mixture consisting of 65 ml of methylene chloride, 35 ml of trifluoroacetic acid and 2.1 g of tetraethylammonium tetrafluoroborate, dissolved. This solution was in an electrolysis vessel with a diaphragm (glass frit) using a round platinum mesh each (Diameter of cathode 5 cm, diameter of anode 6 cm, distance between the electrode surfaces 2 cm) in the cathode and anode compartment at room temperature. The work-up took place analogously to Example 1. The yield of 4-hydroxy-1,2-benzisothiazol-3 (2H) -one-1,1-dioxide was 56% (based on converted material); Melting point: 2280C.

C7H5NO4S (199.19) Calcd .: C 42.20 H 2.53 N 7.02 S 16.10 Found: 42.14 2.70 6.95 16.00 Example 4 The reaction was carried out analogously to that in the example 1 method described, but with the addition of 0.2 mol of trifluoroacetic anhydride per mole of starting compound.

Yield of 4-hydroxy-1,2-benzisothiazol-3 (2H) -one-l, l-dioxide 62% (calculated on the converted starting material).

Example 5 The procedure was analogous to that in the example 1 method described, but using 50 ml of trifluoroacetic acid and 50 ml of methylene chloride as solvent and 6.8 g (0.5 molar) of sodium trifluoroacetate as conductive salt.

Yield: 56% (calculated on the converted starting material).

Example 6 The procedure was analogous to that in the example 5, but with the additional use of 0.5 g of trifluoroacetic anhydride.

Yield: 58% (calculated on the converted starting material).

Example 7 The procedure was carried out in analogy to Example 3, however using sodium trifluoroacetate (0.5 molar) as the conductive salt and trifluoroacetic acid and methylene chloride in a volume ratio of 1: 1.

Yield 52% (calculated on converted starting material).

Example 8 The procedure was carried out in analogy to Example 7, however with the additional use of 1 g of trifluoroacetic anhydride.

Yield: 56% (calculated on the converted starting material).

Example 9 The procedure was analogous to that in the example 1, but using 0.5 mol of sodium trifluoroacetate per mole of starting compound.

Yield: 59% (calculated on the converted starting material).

Example 10 The procedure was as described in Example 1 but without methylene chloride as a solvent. Instead, 50 ml of trifluoroacetic acid were used used.

Yield: 52% (calculated on the converted starting material).

Example 11 The procedure was carried out as described in Example 10; in addition, 20 ml of trifluoroacetic anhydride and 5 g of sodium trifluoroacetate were added added.

Yield 65% (calculated on converted starting material).

Example 12 The procedure was carried out as described in Example 1, instead of tetraethylammonium tetrafluoroborate, however, 2.5 g of tetrabutylammonium tetrafluoroborate were used used.

Yield: 56% (of theory).

Instead, the equivalent amount of tetrabutylammonium perchlorate was used a, a yield of 52% was obtained (calculated on the converted starting material).

Example 13 The procedure was carried out as described in Example 1; instead of 65 ml of methylene chloride, a mixture of 35 ml of methylene chloride and 35 ml of trifluoromethanesulfonic acid used (v: v = l: l).

Example 14 4.6 g (25 mmol) 1,2-Benzisothiazol-3 (2H) -one-1,2-dioxide (Saccarin (R)) were dissolved in 30 ml of trifluoroacetic acid and mixed with 4 g of sodium trifluoroacetate offset. The solution was electrolyzed as in Example 1. After a lot of electricity of 0.4 Ah was consumed, the solution was added to water. It was with Extracted chloroform and worked up analogously to Example 1. In addition to 3.3 g of starting material after recrystallization from water, 0.92 g of 4-hydroxy-1,2-benzisothiazol-3 (2H) -one-1,1-dioxide obtain. This corresponds to a yield of 61% calculated on the converted starting material; Melting point: 2280C MS: 199 (M +), 136, 119 and 108 m / e C7H5NO4S (199.19) Calc .: C 42.20 H 2.53 N 7.03 S 16.10 Found: 41.98 2.48 7.06 16.20 Here, too, a search for isomers remained unsuccessful in the finished reaction mixture.

Claims (7)

Claims 1.) Process for the preparation of 4-hydroxy-1,2-benzisothiazol-3 (2H) -one-l, l-dioxide of the formula by anodic oxidation of 1,2-benzisothiazol-3 (2H) -one-l, l-dioxide in the presence of trifluoroacetic acid or trifluoromethanesulfonic acid with exclusion of water and in the presence of a conductive salt. 2.) The method according to claim 1, characterized by the additional Use of an organic solvent. 3.) Method according to claim 1 or 2, characterized in that as solvents dichloromethane, sulfolane, acetonitrile, dimethylformamide, dimethyl sulfoxide, Dimethylacetamide, tetrahydrofuran, pyridine, acetic acid, nitromethane, or mixtures of these substances, as conductive salts, tetraalkylammonium tetrafluoroborates, alkali trifluoroacetates or alkali perchlorates can be used. 4.) Method according to claim 1, 2 and 3, characterized in that aluminum oxide or trifluoroacetic anhydride are also added to the reaction mixture will. 5.) Method according to one of the preceding claims, characterized in that that an amount of current of 2 to 4 F per mole of converted starting material is used. 6.) Method according to one of the preceding claims, characterized in that that oxide electrodes or electrodes made of noble metals or lead electrodes, glassy carbon electrodes or carbon electrodes can be used. 7.) Method according to one of the preceding claims, characterized in that that the anode compartment is protected from the cathode compartment by a diaphragm.