HK1061687B - 2-phenylbenzimidazole-5-sulphonic acid from isolated 3, 4-diaminobenzenesulphonic acid and use thereof in cosmetic preparations - Google Patents

Description

2-phenylbenzimidazole-5-sulfonic acid from isolated 3, 4-diaminobenzenesulfonic acid and use thereof for producing cosmetics

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Technical Field

2-Phenylbenzimidazole-5-sulfonic acid or its sodium salt is an important skin protectant and can be added to sunscreen agents to absorb ultraviolet light at 280-320nm ("UV-B ray"). This is known from DE-A676103.

Such products have been commercially available, for example from Haarmann & Reimer GmbH under the name NeoHeliopan, which is well known to those skilled in the art. The relevant prior art relating to such products can be found, for example, in EP-A669323.

For the synthesis, it has been proposed to heat 1, 2-diaminobenzene, benzoic acid or benzoic acid derivatives (such as benzoates or benzonitriles) and sulfonic acids together. However, the yield of pure product is only 49-60% (see DE 4203072).

This process is difficult to implement on an industrial scale because, under the required reaction conditions, benzoic acid sublimes from the mixture and blocks the exhaust gas lines.

If 1, 2-diaminobenzene is reacted with alkyl benzoates under acid catalysis, N-alkylated compounds are formed.

One known process involves the condensation of 1, 2-diaminobenzene with benzoic acid in the presence of polyphosphoric acid to give a benzimidazole, which is then sulfonated, for example with chlorosulfonic acid (am. chem. Soc.79, 427 (1957)).

This process is difficult to industrialize because it is uneconomical to handle the very viscous and expensive polyphosphoric acid, in which a large amount of phosphoric acid phase enters the receiving water channel and is eutrophicated.

Another method comprises condensing 1, 2-diaminobenzene with benzaldehyde in the presence of sulfurous acid to obtain 2-phenylbenzimidazole, followed by sulfonation; however, it is known that under such conditions, 1-benzyl-2-phenylbenzimidazole is formed as an undesired secondary product and that it is difficult to isolate them.

The sulfonation step is likewise problematic, since, among other minor constituents, isomeric sulfonic acids are also formed, which are difficult to separate. Moreover, the products obtained by this synthesis are often in discoloured form, meaning that the products are not suitable for the applications required in the cosmetic field.

Thus, there remains a need for a process that can produce 2-phenylbenzimidazole-sulfonic acid in high purity and high yield, while at the same time being easy to implement. It is therefore an object of the present invention to provide a novel process for preparing 2-phenylbenzimidazole sulfonic acid.

Surprisingly, it has now been found that isolated 3, 4-diaminobenzenesulphonic acid can be reacted with benzaldehyde and sulphonic acid to give 2-phenylbenzimidazole-5-sulphonic acid and that this product can be obtained in high yield and purity. It is also possible that after a single redissolution from an aqueous medium, the product is of high purity, in particular bright white, and can be used for cosmetic purposes.

This method is not predictable from the description of the prior art.

Accordingly, the present invention provides a process for the preparation of 2-phenylbenzimidazole-5-sulphonic acid, characterised in that it comprises reacting in aqueous solution at a pH of from 4 to 7 with from 0.9 to 1.5 mol of benzaldehyde and from 1.0 to 3.0 mol of SO per mole of 3, 4-diaminobenzenesulphonic acid₂Or containing 1.0 to 3.0 mol of SO₂The resulting product can also be purified by addition of an oxidizing agent.

The 3, 4-diaminobenzenesulphonic acid required here has hitherto not been available industrially; however, a new method for preparing the compound by sulfonating 1, 2-diaminobenzene can prepare the compound in large quantities, and thus has technical advantages as described herein.

In a preferred embodiment of the process according to the invention, initially, sufficient base is added to the aqueous suspension of 3, 4-diaminobenzenesulphonic acid so that any adhering sulphuric acid is neutralized as is the sulphonic acid. Suitable bases are LiOH, NaOH, KOH, lithium, sodium or potassium carbonate or bicarbonate, MgO, MgCO₃However, it is also possible to use organic bases, such as trialkylamines or pyridines, in stoichiometric amounts or as additives in a few percent and in mixtures with other bases.

NaOH and KOH are preferred bases.

In general, the amount of base is adjusted by the amount of acid adhered and contained, and the pH should be between 7 and 4, preferably in the range of 6 to 5.

The amount of water used is likewise not critical and is selected on the one hand according to the stirrability and on the other hand according to the highest concentration to achieve the highest space-time yield.

The specific amount of water is 0.5-3 liters, preferably 1-1.5 liters, per mole of the starting material.

Then, sulfurous acid is used as SO₂Preferably in the form of its alkali metal salt, e.g. NaHSO₃、Na₂S₂O₅Or Na₂SO₃Although it is also possible to add to SO₂Metered in gaseous form and reacted in situ with the base.

The effect of sulfite is two:

on the one hand, the intermediate of benzaldehyde used as a reaction component to form a sulfite adduct is converted into a water-soluble form, so that the reaction can be carried out in a homogeneous medium; on the other hand, sulfites act as oxidizing agents for the initially formed 2-phenylbenzimidazoline sulfonic acid; the 2-phenylbenzimidazoline sulfonic acid is then converted to the desired phenylbenzimidazole sulfonic acid.

The salt used is preferably NaHSO₃、Na₂S₂O₅Or Na₂SO₃. With any SO₂As such, these salts are present in an amount corresponding to 1-3 moles SO per mole diaminobenzenesulphonic acid₂The amount of (B) is preferably 1.1 to 2.5 mol, more preferably 1.2 to 2.2 mol/mol.

Finally, about a stoichiometric amount of benzaldehyde was added.

If the molar ratio is too low, the yield decreases, and an excess of benzaldehyde causes the wastewater to be contaminated with the excess of benzaldehyde. In general, a molar ratio of 0.85 to 1.5, preferably 0.9 to 1.1, more preferably 1.05 to 1.1, mol/mol is employed.

The process is carried out at a temperature of 25-130 ℃, preferably in the range of 50-90 ℃, most preferably 60-80 ℃. The process is insensitive to temperature changes, but the temperature should not be too low, otherwise the reaction proceeds too slowly; at treatment temperatures significantly above 100 c, the use of pressure equipment is required.

The desired reaction time within the selected range can be readily determined by one skilled in the art, for example, using IR spectroscopy, HPLC, thin layer chromatography, or similar analytical methods. The reaction is carried out at a temperature in the range of 60 to 80 ℃ for a time in the range of 0.5 to 2 hours.

Small amounts of solids and/or turbidity can be removed by methods known to those skilled in the art, for example by treatment with activated carbon, silica gel, cellulose powder, kaolin or similar aids which can be separated off after treatment by methods such as filtration, centrifugation, membrane dialysis and the like.

Preferably, an adsorbent is used which also removes the discolored minor components from the solution; most suitable are various standard commercial types of activated carbon such as Norite.

The clear solution after filtration is acidified with an acid. Suitable acids for acidification are sulfuric acid, and also hydrochloric acid or acetic acid. The use of acetic acid has proven particularly successful.

By controlling the appropriate temperature and/or adding seed crystals, the desired product precipitates out and is converted into a particularly readily filterable form. Methods of this type are known to those skilled in the art.

Finally, the product is isolated by filtration, centrifugation or similar methods, washed (to remove salts), and dried or further processed in the wet state.

If the purity, in particular the optical aspect, obtained is still unsatisfactory, the product can be redissolved in a base or treated with a small amount of an oxidizing agent. Examples of suitable oxidizing agents that can be used are: KMnO₄、FeCl₃Chlorine lye, hydrogen peroxide, addition products which may also be used with urea or sodium borate, K₂S₂O₈And active oxygen.

Potassium permanganate is preferred. The amount is preferably from 0.5 to 3 g, preferably from 1 to 2 g/mol, per mole.

After the reaction, the product is preferably isolated and dissolved; then an oxidizing agent is added, the mixture is clarified with one of the above-mentioned adsorbents, separated and the purified product is precipitated by acidification.

However, if sufficiently pure 3, 4-diaminobenzenesulphonic acid is used, in most cases, the addition of an oxidizing agent may not be necessary.

If the abovementioned 1, 2-diaminobenzenesulphonic acid is used, this process is sufficient to obtain a product which meets most of the requirements.

In contrast, the 1, 2-diaminobenzenesulphonic acid solution is obtained by hydrogenating 2-nitroaniline-4-sulphonic acid in Raney nickel catalyst or Pd/C in aqueous solution and the sulphonic acid is not separated from the solution, so that the crude 2-phenylbenzimidazole-5-sulphonic acid obtained from the 1, 2-diaminobenzenesulphonic acid solution must be reprecipitated at least 3 times, in most cases 4 to 5 times, in order to meet the purity requirements of the cosmetics industry, in particular in terms of pure white color.

The invention therefore also provides the use of the 2-phenylbenzimidazole-5-sulphonic acid according to the invention for the preparation of cosmetics.

Example 1

1250 ml of water are initially introduced and 1.0 mol of 3, 4-diaminobenzenesulphonic acid (approx. 50% strength, sulphuric acid-wet; prepared from 1, 2-diaminobenzene and sulphuric acid) are added.

Sufficient NaOH (45-50% strength) was added dropwise to form a clear solution, and the pH was adjusted to 5.5. Adding 200 g of Na₂S₂O₅The mixture was heated to 60 ℃ and 116 g (1.08 mol) of benzaldehyde were gradually added dropwise. The mixture is heated to 80 ℃, stirred for 1 hour, clarified with 8 g of activated carbon, filtered off after which the activated carbon is filtered off and acidified with an acid (for example with acetic acid) at 80 ℃.

The mixture was stirred until cooled, filtered with suction and washed with water.

320 g of wet product were obtained, from which 245 g of dry product were obtained (yield: 89.3%).

For most applications, the purity of this product is sufficient.

If a particularly pure and particularly white product is desired, the above product can be dissolved in dilute NaOH (or without intermediate drying), potassium permanganate is added in a few grams, heated with activated carbon, clarified and precipitated again by acidification.

Then, 240 g of a dry product was obtained (yield: 98.0%).

Claims (17)

1. A process for the preparation of 2-phenylbenzimidazole-5-sulphonic acid, characterised in that it comprises reacting in aqueous solution at a pH of 4 to 7, per mole of 3, 4-diaminobenzenesulphonic acid, 0.9 to 1.5 moles of benzaldehyde and 1.0 to 3.0 moles of SO₂Or containing 1.0 to 3.0 mol of SO₂The reagent (c) is reacted.

2. The method of claim 1, wherein the 3, 4-diaminobenzene sulfonic acid is obtained by sulfonating 1, 2-diaminobenzene.

3. The process according to claim 1 or 2, characterized in that the reaction is carried out at a pH in the range of 5 to 7.

4. The process according to any one of claims 1-2, characterized in that the amount of benzaldehyde used is 1.05-1.1 mol/mol of 3, 4-diaminobenzenesulphonic acid.

5. The method of claim 3, wherein the benzaldehyde is used in an amount of 1.05 to 1.1 moles per mole of 3, 4-diaminobenzenesulfonic acid.

6. The process according to any one of claims 1 to 2, wherein the reaction is carried out at a temperature in the range of from 25 to 130 ℃.

7. The method of claim 3, wherein the reaction is carried out at a temperature in the range of 25 to 130 ℃.

8. The method of claim 4, wherein the reaction is carried out at a temperature in the range of 25 to 130 ℃.

9. The method of claim 5, wherein the reaction is carried out at a temperature in the range of 25 ℃ to 130 ℃.

10. The process according to any one of claims 1 to 2, further comprising whitening the obtained 2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.

11. The method of claim 3, further comprising whitening the obtained 2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.

12. The method of claim 4, further comprising whitening the obtained-2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.

13. The method of claim 5, further comprising whitening the obtained 2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.

14. The method of claim 6, further comprising whitening the obtained 2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.

15. The method of claim 7, further comprising whitening the obtained 2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.

16. The method of claim 8, further comprising whitening the obtained 2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.

17. The method of claim 9, further comprising whitening the obtained 2-phenylbenzimidazole-5-sulfonic acid by treatment with an oxidizing agent.