CH384567A - Process for the preparation of new benzophenone sulfonamides - Google Patents

Description

  

  



  Process for the preparation of new benzophenone sulfonamides
The present invention relates to a process for the preparation of new benzophenone sulfonamides with valuable pharmacological properties.



   It has surprisingly been found that benzophenone sulfonamides of the formula
EMI1.1
 where R, a halogen atom, an amino group or a low molecular weight alkyl or alkoxy group, Rz hydrogen, a halogen atom, a low molecular weight alkoxy group, a carboxyl or carbalkoxy group, an unsubstituted or low molecular weight alkyl, alkenyl, hydroxyalkyl or polymethylene radical or the 3 -Oxapentylene (1,5) radical substituted sulfamyl, carbamyl or carbamylalkoxy group, or a carboxyalkoxy group, R3 the same as R2 or an alkanoylamino or nitro group, with unsubstituted and monosubstituted carbamyl groups, if present,

   are in the m or p position to the -CO group, R4 is hydrogen, a halogen atom or a low molecular weight alkoxy group, have excellent diuretic activity. Here, the mutual ratio of the ions excreted is very favorable for some therapeutic purposes, in that, for example, the potassium excretion is relatively low compared to the sodium excretion and, on the other hand, the strong sodium excretion is offset by a considerable increase in the chlorine and water excretion. Some of the compounds defined above are also suitable as intermediates for the preparation of further diuretically active substances.
The compounds defined above are prepared by adding compounds of the formula
EMI1.2
 with oxidizing agents, e.g.

   B. with potassium permanganate solution treated. Starting material of formula II is z. B. 3-sulfamyl-4-chloro-diphenylmethane.



  These and other compounds of the formula II can be prepared, for example, from the corresponding 4-substituted 3-halosulfonyldiphenylmethanes by reaction with ammonia.



   In compounds obtained according to the invention, further substituents can be introduced or existing ones can be converted into others. In particular, compounds of the formula I in which R3 is represented by a nitro group, or Rs and / or Ri by amino groups, can be converted into other compounds falling under the formula I. For example, compounds of the formula I in which R3 is represented by a nitro group, while Ri, R2 and R4 have the meaning given above, can be reduced to compounds with an amino group R3.

   Such compounds and compounds with an amino group Rl can be converted into diazonium salts which can be further reacted by various methods known per se.



   Examples include the conversion of the diazonium halides into corresponding halogen compounds (R3 undloder Rt = halogen, especially chlorine) or in cyano compounds by treating their solutions with cuprous halide, copper powder or potassium cuprocyanide, the decomposition of diazonium salts, e.g. B. sulfates, with low molecular weight alkanols to alkoxy compounds (R3 and / or Ri = alkoxy groups) and the replacement of the diazonium group by hydrogen by treating the diazonium salts with aqueous sodium hypophosphite solution, with formic acid, formamide, dimethylformamide or an alcohol.



   All of the aforementioned conversion products, with the exception of the cyano compounds, again fall under the formula I; by partial or complete hydrolysis of the cyano compounds, however, compounds falling under the formula I with a carbamyl or. Carboxyl group R3 or R2. In addition, suitable diazonium chlorides of compounds of the formula I can be converted into sulfochlorides by treatment with sulfur dioxide, and the latter with ammonia or suitable aliphatic amines, that is to say low molecular weight mono- and dialkylamines, monoalkanolamines, dialkanolamines, N-alkylalkanolamines or with pyrrolidine , Piperidine or morpholine to form compounds with an optionally substituted sulfamyl group R2.



   In the following example, parts are parts by weight; these are related to parts of volume as g to cm3. The temperatures are given in degrees Celsius.



   example
32.6 parts of 4-chloro-2'-carboxy-diphenylmethane-3-sulfonamide (melting point 194, 5), which is obtained by reducing 4-chloro-3-aminobenzophenone-2'-carboxylic acid with zinc dust and ammonia but lead the amino group into the sulfamyl group by diazotizing and decomposing the diazonium halide with sulfur dioxide in the presence of copper salts, such as copper chloride, can be easily prepared, are dissolved in 400 parts of solid sodium hydroxide solution and at 90 to 95 by the gradual addition of 520 parts of a 5 loigen aqueous solution Solution of potassium permanganate oxidized. After adding a little sodium bisulfite, the precipitated manganese dioxide is filtered off.



  The 4-chloro-2'-carboxy-benzophenone-3-sulfonamide is precipitated from the filtrate by acidification with hydrochloric acid. The melting point is 2230 after repeated recrystallization from water.



   In an analogous way the following are obtained:
4-chloro-benzophenone-3, 4'-disulfonamide,
M.p. 201-202.



   4-chloro-benzophenone-3, 3'-disulfonamide,
M.p. 236.



      4-bromo-benzophenone-3, 4'-disulfonamide,
M.p. 229, 5.



   4, 4'-dichloro-benzophenone-3, 3'-disulfonamide,
M.p. 237.



   4,4'-dibromobenzophenone-3, 3'-disulfonamide,
4, 4'-difluoro-benzophenone-3, 3'-disulfonamide, 4-chloro-4'-methoxy-benzophenone-3-sulfonamide,
M.p. 161.



   4,4'-dimethoxy-benzophenone-3,3'-disulfonamide,
M.p. 292.



      4-chloro-ethoxy-benzophenone-3'-sulfonamide,
M.p. 161.



      4-chloro-2'-carboxymethoxy-benzophenone-
3-sulfonamide, m.p. 178, 5-182j.



      4-chloro-2'-carbethoxy-benzophenone-
3-sulfonamide, m.p. 150, 5-153.



      4-chloro-2'-carbamylmethoxy-benzophenone-
3-sulfonamide, 4-chloro-2'-diethylcarbamylmethoxy-benzophenone-3-sulfonamide, 4-chloro-2'-diallylcarbamylmethoxy-benzophenone-3-sulfonamide, 4-chloro-4! -Carbamyl-benzophenone-3 -sulfonamide,
M.p. 244-247.



   4-chloro-4'-carboxy-methoxy-benzophenone
3-sulfonamide, m.p. 191-193, 5w.



   4-chloro-4'-carbamylmethoxy-benzophenone
3-sulfonamide, m.p. 233-237¯.



      4-chloro-4'-dimethylcarbamylmethoxy-benzophenone-3-sulfonamide, m.p. 144, 5-147.



      4-chloro-4 '- (ss-carbamyl-ethoxy) -benzophenone-
3-sulfonamide,
4-chloro-4 '- (ss-diethylcarbamyl-ethoxy) -benzo- phenone-3-sulfonamide,
4-chloro-3'-ethylsulfamyl-benzophenone-3-sulfonamide, m.p. 231-232.



      4-chloro-3'-ethylsulfamyl-benzophenone-3-sulfonamide, m.p. 213.



      4-chloro-3'-diethylsulfamyl-benzophenone-
3-sulfonamide, m.p. 163.



      4-chloro-3'-sulfonic acid piperidide benzophenone
3-sulfonamide, 4-chloro-3'-sulfonic acid morpholide-benzophenone-
3-sulfonamide,
4-chloro-3'-i-hydroxy-ethylsulfamyl-benzophenone-
3-sulfonamide, m.p. 149.



      4-chloro-3'-carboxyl-4'-n-propoxy-benzophenone-
3-sulfonamide, m.p. 188.



   4-chloro-4'-carboxy-benzophenone-3-sulfonamide,
M.p. 272-278, 50.



   4-chloro-3'-nitro-4'-carboxy-benzophenone
3-sulfonamide, m.p. 213-215.



   4-chloro-2'-dimethylcarbamyl-benzophenone
3-sulfonamide, m.p. 173-175¯.



      4-chloro-2'-diethylcarbamyl-benzophenone-
3-sulfonamide, m.p. 202-204.

 

Claims (1)

PATENT CLAIM Process for the preparation of new Benzophenonsulfonamiden of the formula EMI3.1 where Rt is a halogen atom, an amino group or a low molecular weight alkyl or alkoxy group, R2 is hydrogen, a halogen atom, a low molecular weight alkoxy group, a carboxyl or carbalkoxy group, an unsubstituted or low molecular weight alkyl, alkenyl, hydroxyalkyl or polymethylene radical or the 3- Oxapentylene (1,5) radical substituted sulfamyl, carbamyl or carbamylalkoxy group, or a carboxyalkoxy group, R3 the same as R2 or an alkanoylamino or nitro group, unsubstituted and monosubstituted carbamyl groups, if present, being in m- or p -Position to the -CO group, R4 is hydrogen, a halogen atom or a low molecular weight alkoxy group, characterized in that a compound of the formula EMI3.2 treated with oxidizing agents. SUBClaims 1. The method according to claim, characterized in that one starts from compounds of the formula II, in which R, halogen and R2 are an unsubstituted or substituted by low molecular weight alkyl groups carbamyl group which is in the p- or m-position to the -CH2 group, mean. 2. The method according to claim, characterized in that one starts from compounds of the formula II in which Ri is a chlorine atom and R2 is a disubstituted carbamyl group which is in the ortho position to the -CH2 group.