| PATENT NUMBER | This data is not available for free |
| PATENT GRANT DATE | December 5, 1995 |
| PATENT TITLE |
Process for preparing 2-arylbenzimidazole-5-sulfonic acids |
| PATENT ABSTRACT |
The invention relates to an improved process for preparing 2-arylbenzimidazole-5-sulfonic acids of the formula I, ##STR1## in which Ar is unsubstituted phenyl or phenyl substituted by one or more C.sub.1 -C.sub.6 alkyl or alkoxy groups and m is 1, 2 or 3, wherein o-phenylenediamine is reacted in the presence of sulfuric acid at between room temperature and 250.degree. C. with a benzoic acid derivative of the formula II Ar(--X).sub.m II in which Ar and m are as above, and X is COO-alkyl, where alkyl is n-alkyl having from 1 to 6 C atoms, COOH, COCl, COBr or CN, and new arylbenzimidazole acids of the formula Ia ##STR2## |
| PATENT INVENTORS | This data is not available for free |
| PATENT ASSIGNEE | This data is not available for free |
| PATENT FILE DATE | October 1, 1993 |
| PATENT CT FILE DATE | January 27, 1993 |
| PATENT CT NUMBER | This data is not available for free |
| PATENT CT PUB NUMBER | This data is not available for free |
| PATENT CT PUB DATE | August 5, 1993 |
| PATENT FOREIGN APPLICATION PRIORITY DATA | This data is not available for free |
| PATENT REFERENCES CITED |
K. K. Preobrazhenskii, et al., "2-Alkylbenzimidazoles and their sulfo derivatives", Chemical Abstracts, vol. 84, No. 7, Abstract No. 30963t (Aug. 14, 1976), p. 454. L. S. Efros, "Imidazole derivatives. VII. Preparation of sulfonic acids of benzimidazole by baking method", Chemical Abstracts, vol. 48, see Column 4524, (1953). |
| PATENT PARENT CASE TEXT | This data is not available for free |
| PATENT CLAIMS |
We claim: 1. A single-step process for preparing a 2-arylbenzimidazole-5-sulfonic acid of formula I ##STR7## wherein Ar is phenyl or phenyl substituted by one or more C.sub.1-6 -alkyl or -alkoxy groups, and m is 1, 2 or 3, comprising reacting o-phenylenediamine in a solvent in the presence of sulfuric acid at between room temperature and 250.degree. C. with a benzoic acid derivative of formula II Ar--(X).sub.m II wherein Ar is as defined above, and X is COO-alkyl, wherein alkyl is C.sub.1-6 -n-alkyl, COOH, COCl, COBr or CN. 2. A process of claim 1, wherein the o-phenylenediame and the benzoic acid derivative of formula II are introduced together into the sulfuric acid. 3. A process of claim 1, wherein the sulfuric acid is the solvent for the reaction. 4. A process of claim 1, wherein the solvent comprises 1-50% water. 5. A process of claim 1, wherein the reaction is conducted for 1-5 hours at 80.degree.-140.degree. C., and then for an additional 0.5-5 hours at 170.degree.-250.degree. C. 6. A process of claim 1, wherein m is 1. 7. A process of claim 1, wherein m is 2 and Ar is 1,3- or 1,4-phenylene or 1,3- or 1,4-phenylene substituted by 1-4 C.sub.1-6 -alkyl or -alkoxy groups. 8. A process of claim 1, wherein m is 3 and Ar is ##STR8## -------------------------------------------------------------------------------- |
| PATENT DESCRIPTION |
The invention relates to an improved process for preparing 2-arylbenzimidazole-5-sulfonic acids of the formula I, ##STR3## in which Ar is unsubstituted phenyl or phenyl substituted by one or more C.sub.1 -C.sub.6 alkyl or alkoxy groups and m is 1, 2 or 3, wherein o-phenylenediamine is reacted in the presence of sulfuric acid at between room temperature and 250.degree. C. with a benzoic acid derivative of the formula II Ar(--X).sub.m II in which Ar and m are as above, and X is COO-alkyl, where alkyl is n-alkyl having from 1 to 6 C atoms, COOH, COCl, COBr or CN. 2-Phenylbenzimidazole-5-sulfonic acid (Eusolex 232) is an important water-soluble UV-B radiation filter with wide application in cosmetics. Its use as a UV radiation filter is described, for example, in German Reich Patent No. 676 103. Its preparation proceeds, according to, for example, V. G. Sayapin et al., KhGC [Chemistry of Heterocyclic Compounds] 6, 1970, 630-632, in a two-stage reaction in which 2-phenylbenzimidazole is first prepared from 1,2-phenylenediamine and the bisulfite adduct of benzaldehyde or from phenylenediamine and benzoic acid in the presence of polyphosphoric acid, and is then reacted with chlorosulfonic acid. A survey of the preparation of 2-substituted benzimidazoles can be found, for example, in Chemical Reviews Vol. 74, No. 3, 1974 p 279 ff. ##STR4## This process nevertheless has great disadvantages: a) It is a two-stage process and therefore more complicated and more expensive. b) Industrial handling of chlorosulfonic acid causes problems since 2-phenylbenzimidazole disulfonic acids can be formed which can be separated out only with difficulty. c) In the first preparation processes for phenylbenzimidazole, sodium hydrogen sulfite must be used in large excess, so that large amounts of sulfur dioxide are given off during working up; 1-benzyl-2-phenylbenzimidazole can be formed as a byproduct, which can be separated out only with difficulty. In the second process for preparing phenylbenzimidazole from benzoic acid phosphoric acid passes into the waste water, which is undesirable because Of eutrophication of water courses and lakes. The disadvantages of the abovementioned process can be conveniently circumvented: it has surprisingly been found that in the condensation reaction of 1,2-diphenylenediamine with benzoic acid in sulfuric acid at high temperatures intermediate products are directly sulfonated, so that 2-phenylbenzimidazole-5-sulfonic acid is formed directly without isolation of an intermediate. DE 12 82 855 describes the use of 1,3-bis-(5-sulfobenzimidazol-2-yl)benzene as a water-soluble UV-B radiation filter. Its preparation proceeds analogously to that of 2-phenylbenzimidazole in a two-stage process. The invention thus relates to an improved process for preparing 2-arylbenzimidazole-5-sulfonic acids of the formula I, ##STR5## in which Ar is unsubstituted phenyl or phenyl substituted by one or more C.sub.1 -C.sub.6 alkyl or alkoxy groups and m is 1, 2 or 3, wherein o-phenylenediamine is reacted in the presence of sulfuric acid at between room temperature and 250.degree. C. with a benzoic acid derivative of the formula II Ar(--X).sub.m II in which Ar and m are as above, and X is COO-alkyl, where alkyl is n-alkyl having from 1 to 6 C atoms, COOH, COCl, COBr or CN, in particular where from 1 to 10 mol, preferably from 3 to 8 mol, particularly from 4 to 7 mol of sulfuric acid are used per 1 mol of o-phenylenediamine. The invention further relates to such a process in which the benzoic acid derivative is introduced into the sulfuric acid, o-phenylenediamine of the formula II is subsequently added, and the mixture is heated to from 150.degree. C. to 220.degree. C., or in which o-phenylenediamine and the benzoic acid derivative are introduced together into the sulfuric acid. A further preferred embodiment is a process in which the sulfuric acid is used as solvent, particularly in which 50-100% sulfuric acid is used and/or in which the solvent contains from 1 to 50% of water. In a particularly preferred embodiment of the process of the invention, the mixture of the reactants is stirred for about from 1 to 5 hours at temperatures between 80.degree. and 140.degree. C., subsequently heated to temperatures between 170.degree. and 250.degree. C. and stirred for another 0.5 to 5 hours. Carrying out the process of the invention per se is simple. The sulfuric acid, preferably in the form of a 50-100% solution, in particular as a concentrated about 96% solution, forms the initial charge. In general from 1 to 10 mol, preferably from 3 to 8 mol, in particular from 4 to 7 mol of sulfuric acid are used per 1 mol of phenylenediamine. The method of adding the reactants benzoic acid and phenylenediamine is not critical. In general one of the two reactants is added at room temperature, which generally causes the mixture to warm to temperatures between 80.degree. and 140.degree. C. The second reactant is slowly added at this temperature, during which the temperature of the reaction mixture may rise further. The reaction mixture is subsequently heated slowly to temperatures between 165.degree. and 250.degree. C., preferably between 175.degree. and 200.degree.C., in particular to the boiling point of the mixture, and maintained at this temperature for from 1 to 5 hours, optionally with stirring. The reaction mixture is subsequently allowed to cool, preferably to temperatures between 100.degree. and 150.degree. C., and water is added. After stirring for a short time, preferably from 20 minutes to 2 hours, at from 50.degree. to 80.degree. C., the solid components are separated off, preferably washed with warm water and dried. Some of the compounds of the formula I are known and some are new. The invention relates also to the new compounds of the formula I, in particular the compounds of the formula Ia, in which m is 2 and Ar is a group of the formula ##STR6## in which R is C.sub.1-6 -alkyl or alkoxy and n is 0, 1, 2, 3 or 4. Surprisingly, it has been found that the compounds of the formula Ia are suitable as water-soluble UV-A filters, whereas similar known compounds are UV-B filters. To purify the dried crude product, the latter is preferably suspended in water and neutralized with diluted base. After purification of the solution so obtained, preferably with activated carbon, it is preferably heated to temperatures between 50.degree. and 100.degree. C. and acidified with a mineral acid, preferably concentrated hydrochloric acid. The precipitated sulfonic acid is separated off, washed with preferably warm water and dried. In the formula I Ar is unsubstituted phenyl or phenyl substituted by one or more C.sub.1 -C .sub.6 alkyl or alkoxy groups, preferably unsubstituted phenyl or phenyl substituted, particularly in the 4-, 3-, 3,4- or 3,5-position, by 1 or 2 C.sub.1 -C .sub.3 alkyl or alkoxy groups, in particular unsubstituted phenyl. In the case where m=2 Ar is preferably 1-, 3- or 1,4-phenylene, in particular 1,4-phenylene. In the case where m=3 Ar is preferably benzene-1,3,5-triyl. In the formula II X is COO-alkyl, in which alkyl is n-alkyl having from 1 to 6 C atoms, preferably 1 or 2 C atoms, COOH, COCl or CN, preferably COOH, COOCH.sub.3, COCl or CN, in particular COOH or CN. The advantages of the process over the previously mentioned processes are: a) Simple single-stage process, no difficulties with pH control. b) The product is not contaminated by 1-benzyl-2-phenylbenzimidazole-6-sulfonic acid and 2-phenylbenzimidazoledisulfonic acids. c) No elemental sulfur is formed, so that the waste water has a substantially lower chemical oxygen demand. d) The intermediate products can be very simply and quickly centrifuged off and washed. e) The yield is comparable to or greater than that in the processes known from the prior art. f) Addition of sodium hydrogen sulfite is not needed, so that handling of sulfur dioxide is no longer necessary either. The invention further relates to cosmetic preparations which contain an effective amount of at least one compound of the formula Ia in a carrier suitable for cosmetics. Preference is given to such cosmetic preparations which contain from 0.1 to 10% by weight, preferably from 0.4 to 1.0% by weight, in particular about 0.5% by weight, of at least one compound of the formula Ia, in particular preparations which additionally contain a UV-B filter. The invention further relates to the use of the compounds of the formula Ia as a cosmetic product or as a medicament. The invention furthermore relates to the compound of the formula Ia for use in the preventive treatment of inflammations and allergies of the skin, and for use in the prevention of certain types of cancer. The invention likewise relates to pharmaceutical preparations which contain an effective amount of at least one compound of the formula Ia in a physiologically tolerated carrier or excipient, in particular for topical application. The invention furthermore relates to the use of the compounds of the formula Ia as medicaments. Even without further explanations it is assumed that a person skilled in the art can use the above description in the widest scope. The preferred embodiments are hence to be taken as only descriptive, not as an in any way limiting disclosure. The complete disclosure of all applications, patents and publications cited above or below, and the corresponding application P 42 03 072, filed on 04.02.92, granted on 03.07.92 as German Patent DE-42 03 072 C, is incorporated into this application by reference. |
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