Патент USA US2108712код для вставки
2,108,712 Patented Feb. 15, 1938 UNITED STATES PATENT OFFICE 2,108,712 HETEROOYGLIC‘ HYDROXY COMPOUNDS Ernst Herdieckerhoff, Opladen, near Cologne, and Eduard Tschunkur, (lologne-Mulheim, Ger many, assignors to I. G. Farbenindustrie Ak tiengesellschaft, Frankfort-on-the-Main, Ger many No Drawing. Application October 5, 1934, Se rial No. 747,090. In Germany October 12, 1933 4 Claims. (Cl. 260-44) The present invention relates to a process for the manufacture of heterocyclic hydroxy com pounds, more particularly it relates to com pounds which may' be represented by the proba ble general formula: wherein 0: stands for sulfur or oxygen. In accordance with the present . invention heterocyclic hydroxy compounds of the above identi?ed formula are prepared by starting with a sulfonic acid of the general formula: saponifying agents, such as dilute phosphoric acid or dilute aqueous alkalies, such as dilute aqueous caustic soda lye or dilute aqueous caus tic potassium lye, say from 1-10% strength, gen erally require higher temperatures, say from *1 about 50° to about 100° C. It is to be understood that the statements hereinbefore made with re gard to the concentration and temperature are in no Way limitative and that the conditions of working may be varied in any suitable‘ manner 10 without departing from the spirit of our inven tion. The sulfonic; acids used as starting compon ents in our invention are obtainable, for example, according to the process described in the appli cation for Letters Patent Serial No. ‘723,611, filed May 2, 1934 and having the title “Heterocyclic sulfonic acids and process of making same”, by reacting upon the corresponding Z-mercapto de wherein a: means the same as stated above, or a salt thereof, especially a water soluble salt, such as an alkali metal salt, and treating the same rivatives, favorably in an alkaline medium, with " an oxidizing agent in a quantity corresponding to at least 3 atoms of active oxygen for each atom with a saponifying agent. The reaction proceeds of the 2-mercapto derivative. Further these sul in such a manner that the sulfonic acid group is fonic acids are obtainable by reacting upon com saponi?ed with a splitting off of sulfurous acid. pounds of the formula: As saponifying agents suitable for carrying out the process there come into consideration all the agents known in the art for performing saponifi cation; for example, there can be used acid saponifying agents, such as diluted aqueous min 3 o, eral acids, for example, hydrochloric acid, sul furic acid, phosphoric acid and the like, further acid salts, such as bisulfate and the like. Like— wise the process can be performed with the aid \ C-Cl / arylen wherein as means the same as stated above, with a sul?te. to . It is self-understood that in performing our new process it is not necessary to start with the isolated sulfonic acids, but the same can be di of an alkaline saponifying agent, dilute aqueous caustic soda lye or aqueous caustic potassium lye being enumerated by way of example. The conditions of working, i. e. temperature and concentration of the saponifying agent, de pend to a high degree on the speci?c heterocyclic sulfonic acid which is subjected to the reaction and to the speci?c saponifying agent used. Thus, for example, when subjecting an oxazole-Z-sul rectly saponi?ed in the reaction mixtures result "35 ing from their process of manufacture. The invention is illustrated by the following fonic acid to our new process, there can be gen mula : applied moderate conditions, while in case 4 erally of thiazole sulfonic acids generally stronger con examples, without being limited thereto: Example 1.—50 kgs. of the sodium salt of benzoxazole-Z-sulfonic acid are dissolved in 300-400 litres of warm water, and the solution is Weakly acidi?ed with hydrochloric acid. The Z-hydroxybenzoxazole having the following for /N .\ ditions, such as the application of an aqueous mineral acid, say of about 1 to 5% strength, and higher temperatures, say‘ between about 50 and aboutv 100° C., are preferable. Quite generally, when using strong saponifying agents, such as. dilute aqueous mineral acids, say of from about . l to about 5% strength, the saponi?cation can be performed at lower temperatures, in some cases even at normal temperature, while weaker of the melting point 140° C. separates in a good yield with splitting off of sulfurous acid. Example 2.—-50 kgs. of the sodium salt of s~ naphthoxazole-Z-sulfonic acid are dissolved in about 300 litres of warm water; on acidifying the solution with sulfuric acid, sulfurous acid is 55 2 2,108,712 split off with formation of Z-hydroxy-c-naph thoxazole of the formula: 5-chloro-2-hydroxybenzothiazole of the formula: 01 OH \s of the melting point 218° C. ‘6-methoxy-2-hydroxybenzothiazole of the for mula : 10 of the melting point 206° C. in a good yield. benzothiazole are dissolved with about 240 kgs. of aqueous caustic soda lye of 50% strength in 15 about 1000 litres of water at 20-30° C., and to the solution there are slowly added, while stirring, 340 kgs. of aqueous hydrogen peroxide solution of 30% strength. Thereby is formed in a rather quantitative yield the sodium salt of the 2-hy 20 droxy-6-nitrobenzothiazole having in the free state the following formula: 25 O2N— 10 /N\o-on Example 3.-—212 kgs. of 2-mercapto-6-nitro— H300~ \s / of the melting point 163-164° C. 15 2-hydroxy-a-naphthothiazole of the formula: 20 \s by splitting oif sulfurous acid from the corre of the melting point 287-288" C. 2-hydroxy-p-naphthothiazole of the formula: 25 sponding 2-sulfonic acid which intermediarily has formed. After redissolving from aqueous 30 caustic soda lye and salting out with common 30 salt, the sodium salt of 2-hydroxy-6-nitrobenzo thiazole is obtained in form of yellowish crys tals; the free compound shows the melting point 35 V40 252° C. In an analogous manner there is prepared the 2-hydroXy-5—nitrobenzothiazole of the melt 35 ing point 282° 0. Example 4.—40 kgs. of 2-mercapto-benzothia of the melting point 235° C. zole are dissolved with 25 kgs. of aqueous caustic in accordance with the new process can be used soda lye of 50% strength in 100 litres of water, as intermediate products for the manufacture of and at 20-30° C. there is slowly added a solution of 80 kgs. of potassium permanganate in about 800 litres of water. After this the reaction mix ture is heated to 80-90° (3., and the manganese 45 sludge formed is ?ltered off. The ?ltrate con taining the benzothiazole-Z-sulfonic- acid is ren dered acid to congo with hydrochloric acid, while hot, whereupon the bulk of the 2-hydroxybenzo thiazole separates directly with a strong de A further quantity of the 2 hydroxybenzothiazole crystallizes on cooling. The output is about 90% of theory. The product The Z-hydroxyarylene compounds obtainable synthetic drugs and other technically valuable 40 substances. We claim: 1. The process of preparing a compound of the group consisting of 2~hydroxyoxazoles and 2 hydroxythiazoles which comprises splitting o?f 45 sulfurous acid from a compound of the general formula: 50 velopment of S02. having the following formula: 55 is very pure and shows the melting point of 60 138° C. The process can also be performed at other temperatures between about 50 and about 100° C. In an analogous manner there are prepared from the corresponding benzothiazole-2-sulfonic 65 acids or naphthothiazole-Z-sulfonic acids re spectively: 4-chloro-2-hydroxybenzothiazole of the formula: . ar C-eS 03y \ / 50 X wherein ar stands for an arylene radical of the benzene or naphthalene series, :0 stands for a member of the group consisting of sulfur and oxygen, and 1! stands for a member of the group 55 consisting of hydrogen and a monovalent metallic radical, by treating with an acid saponifying agent. 2. A process as claimed in claim 1, in which a dilute aqueous mineral acid is used as saponify 60 ing agent. 3. The process of preparing 2-hydroxyoxazole which comprises treating oxazole-Z-sulfonic acid with dilute aqueous hydrochloric acid at normal temperature. 65 4. The process of preparing 2-hyclroxybenzo thiazole which comprises treating benzothiazole 2-sulfonic acid with dilute aqueous hydrochloric acid at a temperature between about 50 and about 100° C. 70 70 ERNST HERDIECKERHOFF. of the melting point 204-205" C. EDUARD TSCHUNKUR.