DE873548C - Process for the preparation of diarylsulfone pellets - Google Patents

Description

Process for the preparation of diarylsulfone derivatives It has been found that valuable diarylsulfone derivatives are obtained if 4.-nitroaryl halides, which can be substituted in the core by alkyl sulfone radicals, with salts of aryl mercapto compounds condensed, the in the core also alkylsulfone and in the 4-position to the mercapto group may contain a nitrogen-containing radical that can be converted into an amino group, whereby the starting materials are chosen so that at least in the thioethers formed a ring-bonded alkyl sulfone group is included, and then the thioether group oxidized to the sulfon group and, if necessary, the residues which can be converted into amino groups converted into amino groups. As nitrogen-containing residues which can be converted into amino groups especially acylamino and nitro groups come in addition to other suitable radicals of these Kind in consideration.

Instead of the aforementioned salts of aryl mercapto compounds, it is also possible to use corresponding salts of arylsulfinic acids, which can contain a nitrogen-containing radical which can be converted into an amino group in the 4-position to the sulfinic acid group. This route leads directly to diarylsulfones. Instead of the alkyl sulfone groups, the starting materials can, in suitable cases, also contain corresponding alkyl sulfoxide or alkyl sulfide groups which are converted into alkyl sulfone groups by oxidation. The compounds obtainable by the process have, for. B. the general formula in which G and G 'denote amino groups or nitrogen-containing radicals which can be converted into amino groups.

These diarylsulfone derivatives are chemically potent agents for combating bacteria and other parasites, in particular for combating Strepto-, gono- and pneumococcal infections as well as those caused by anaerobes Infections in the human or animal body. The connections draw are characterized by good tolerance.

The starting materials used for the process according to the invention are, for example the following 4-nitroaryl halides into consideration: i-nitro-4-chlorobenzene, i-INTitro-4-bromobenzene, 5-nitro-2-chlorophenyl-methyl-sulfone, 5-nitro-2-bromophenyl-methyl-sulfone, 5-nitro-2-chlorophenyl-ethyl sulfone, 5-nitro-2-chlorophenyl isopropyl sulfone, 5-nitro-2-chlorophenyl oxethyl sulfone, 5-nitro-2-chlorophenyl-diethylaminoethyl-sulfone, 5-nitro-2-chlorophenyl-sulfonacetic acid ester and the like

These nitroaryl halides or nitrohalogenarylsulfones are used according to the invention brought to reaction with aryl mercaptans, the aryl mercaptans being expedient in the form of their alkali compounds or in the presence of acid-binding agents is working. Aryl mercaptans that are suitable for this purpose are, for example: Phenyhuercaptan, 4-nitrophenyl mercaptan, 4-acylaminoaryl mercaptans, such as 4-acetylaminophenyl mercaptan, 4-propionylaminophenyl mercaptan; 4-nitro-2-methylsulfon-phenyl mercaptan, 4-nitro-2-ethylsulfon-phenyl mercaptan as well as other aryl mercaptans which are in addition to the 4-position to the mercapto group nitrogen-containing residues that can be converted into amino groups, as well as others Substituents such as B. alkoxy groups, halogen and the like.

After condensation and isolation of the thioethers obtained these are subjected to the oxidation to the corresponding sulfones, whereby one uses standard procedures. One uses z. B. concentrated as an oxidizing agent Nitric acid, hydrogen peroxide in glacial acetic acid, potassium permanganate, etc. The work-up takes place in a known manner.

The nitrogen-containing groups can then be found in the sulfones obtained convert in the usual way into amino groups or optionally also acylamino groups, where, for example, nitro groups, azo or azoxy groups are subjected to the reduction, while existing acylamino groups are saponified, carbonamide or carboxylic acid hydrazide groups be rearranged to amino groups. If desired, the introduction can refer to this of acyl residues in the amino groups, also in a known manner he follows.

According to one embodiment of the process, instead of the aryl mercapto compounds also use salts of arylsulfinic acids. Benzenesulfinic acid, for example, can be used for this purpose and their core substitution products, particularly 4-nitrobenzenesulfinic acid and 4-acylaminobenzenesulfinic acids etc. into consideration. The arylsulfinic acids can also have further core substituents, such as Contain halogen, alkoxy groups and alkyl sulfone groups. The implementation takes place on the usual route, likewise the isolation of the reaction products obtained. Man in this way arrives directly at the diarylsulfone derivatives.

The compounds obtainable by the process are generally well-crystallizing bodies. Some compounds are listed below, for example: ETC. EXAMPLE i 23 parts by weight of sodium are dissolved in 2500 parts by volume of methanol and 155 parts by weight of freshly prepared dry p-nitrophenylcaptan are added, after which the mixture is refluxed until completely dissolved. 236 parts by weight of 2-chloro-5-nitrophenyhnethylsulfone are added in portions to the still warm solution, refluxed for about 1/2 hour, suction filtered and the thioether formed is washed with hot methanol, then with water and finally again with methanol and ether. The thioether has the formula and shows the melting point 223 to 227 °.

For oxidation, 28 g parts by weight of this thioether are poured over 150 parts by volume of nitric acid (i.e. - 1.39) in the presence of a small amount of vanadic acid, whereupon 150 parts by volume of fuming nitric acid (i.e. 1.51) are gradually added. The solution obtained is then heated on a water bath for 3 to 4 hours and then poured into 2 liters of water. The formed sulfone of the formula precipitates in dense white flakes. It shows the melting point 212 to 214 °.

This product, which as such already has a chemotherapeutic effect, is subjected to reduction, whereby a mixture of 65 parts by weight of tin powder, 100 parts by volume of water and = oo parts by volume of conc. Prepares hydrochloric acid, into which 32.2 parts by weight of the sulfone are gradually introduced with stirring. A certain amount of conc. Hydrochloric acid is added until all the sulfone has dissolved, avoiding a temperature increase above 40 °. After the solution has become clear, the mixture is stirred for a further 1/2 hour, the undissolved tin is filtered off and the mixture is made strongly alkaline with sodium hydroxide solution. The flaky diamino compound that arises is filtered off with suction and washed out well with dilute sodium hydroxide solution and water. The amino compound obtained has the formula and crystallizes after recrystallization from 30% acetic acid in the form of large shiny plates. Melting point 184 to z85 °.

The amino compound is recovered by heating with excess Acetic anhydride the corresponding diacetylamino compound. This compound crystallizes from dilute acetic acid in platelets which melt at 211-2i2 ° (uncorr.). Example 2 25 parts by weight of 2-chloro-5-nitrophenyl-ethyl-sulfone are dissolved in a solution of 15.5 parts by weight of 4-nitrophenyl mercaptan and 5.6 parts by weight of potassium hydroxide entered in 300 parts by weight of 80% methanol and refluxed, until the mixture is only slightly light red in color. After cooling, it will Sucked off the product, washed it well with water and methanol and, if necessary, removed it Recrystallized glacial acetic acid or acetic anhydride.

The 4,4'-dinitro-2-ethylsulfon-diphenylsulfide thus obtained is analogously as described in example i, with conc. Nitric acid to the 4,4'-dinitro-2-ethylsulphone-diphenylsulphone oxidized, which is obtained as a pale yellowish, finely crystalline powder. The reduction the above-mentioned dinitro body is carried out as indicated in Example i, the 4,4'-diamino-2-ethylsulphone-diphenylsulphone is obtained in white crystals. The diamino compound can be converted into the corresponding by treatment with acetic anhydride Acetyl bodies are transferred.

Claims (2)

PATENT CLAIMS: i. Process for the production of diarylsulfone derivatives, characterized in that 4-nitroaryl halides, the nucleus by alkyl sulfone radicals may be substituted, condensed with salts of aryl mercapto compounds, the in the core likewise alkylsulfonic acid residues and one in the 4-position to the mercapto group nitrogenous, a residue that can be converted into an amino group can, with the proviso that in the thioether formed by appropriate selection the starting materials contain at least one nucleus-bonded alkyl sulfone group, whereupon the thioether group is then oxidized to the sulfone group and optionally the residues which can be converted into amino groups are converted into amine groups. 2. Process according to Claim r, characterized in that instead of the salts of Arylnnercaptoverbindungen salts of arylsulfinic acids used, which are in the 4-position to the sulfinic acid group a nitrogen-containing group which can be converted into an amino group May contain remainder, whereupon convertible into amino groups in the sulfone formed Residues are optionally converted into amino groups.