GB1598093A - Sulphamoyl-benzoic acid derivatives having aromatic substituents and a process for their manufacture - Google Patents
Sulphamoyl-benzoic acid derivatives having aromatic substituents and a process for their manufacture Download PDFInfo
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- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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Abstract
The compounds of formula I are obtained by reacting 3-nitro-4-halogeno-benzoic acid derivatives of formula II with compounds of formula III and subsequent reduction of the nitro group. The reaction is carried out in the presence of copper powder. The substituents in formulae I, II and III have the meanings given in Claim 1. The radicals B and R<1> can be cleaved by acid or alkaline hydrolysis before or after the reduction of the nitro group. The compounds obtained can be used as intermediates for the preparation of diuretics and saluretics. <IMAGE>
Description
(54) SULPHAMOYLBENZOIC ACID DERIVATIVES
HAVING AROMATIC SUBSTITUENTS AND A
PROCESS FOR THEIR MANUFACTURE
(71) We, HOECHST AKTIENGE
SELLSCHAFT, a body corporate organised according to the laws of the Federal
Republic of Germany, of 6230
Frankfurt/Main 80, Postfach 80 03 20,
Federal Republic of Germany, do hereby declare the invention for which we pray that a patent may be granted to us, and the method by which it is to be performed, to be particularly described in and by the following statement:- The present invention provides a sulphamoylbenzoic acid derivative having an aromatic substituent, of the general formula
in which represents a monocyclic or bicyclic radical comprising at least one aromatic carbocyclic or aromatic heterocyclic ring, which is unsubstituted or substituted by one or more substituents, any two or more of which may be the same or different, selected from halogen atoms, alkyl and alkoxy radicals having from 1 to 3 carbon atoms, methylenedioxy, usually 3,4 methylene - dioxy, benzyloxy, -NO2, =-N, OH, formyl and acetyl groups and carboxylate radicals -COOR in which R represents an alkyl radical,
R' represents a hydrogen atom or an alkyl group having from 1 to 4 carbon atoms, and
B represents the protective group
in which
R3 represents a hydrogen atom or a lower alkyl radical, and R4 and R5 may be the same or different and each represents a lower alkyl radical or are bonded to one another to form, with the nitrogen atom, a saturated ring, or
R3 and R4 are bonded to one another to form, with the carbon atom and nitrogen atom to which they are attached, a saturated ring, and
R5 represents a lower alkyl radical.
When used herein in connection with alkyl radicals, the term "lower" denotes such radicals that have 1 to 4 carbon atoms.
The protective group represented by B is preferably
Other suitable protective groups are, for example, those in which the substituents R3,
R4 and R5 have the meanings shown in
Table A below.
TABLE A
R3 R4 R5
CH3 CH3 CH3
H C2H5 C2H5 C4H9 CH3 CH3 H I CH3 CH3 H CH3 C2H5 -CH2-CH2-CH2- CH3
CH3 -CH2-CH2CH2CH2-CH2- Attached to the benzene ring containing the SO2NB substituent, ortho thereto, is an aromatic ring which may be carbocyclic or heterocyclic and which may optionally be fused to a further carbocyclic or heterocyclic ring. The radical may be unsubstituted or substituted as specified above. Thus, for example may represent a benzene or naphthalene ring or a 5 - membered or 6 - membered heteroaryl ring, e.g. a thiophene, pyridine, pyrimidine, thiazole, pyrazole, pyrazine, pyridazine, quinoline or isoquinoline ring, each of which may be unsubstituted or substituted as specified above.
The present invention also provides a sulphamoylbenzoic acid derivative having an aromatic substituent of the general formula
in which
R' and B have the meanings given above.
The present invention also provides a salt of a compound of the general formula I and a salt of a compound of the general formula
IV.
These compounds, more particularly the carboxylic acid esters of compounds of the general formulae I and IV, may be used as intermediates in the preparation of a compound of the general formula
in which Ar and R' have the meanings given above, or a salt thereof. Some of these compounds are described and claimed in coendingalication 80.21700 (Serial No.
1598094) (HOE 76/F 2 89 B).
The present invention further provides a process for the preparation of a compound of the general formula V, which comprises
(a) hydrolysing a compound of the general formula I in which R' represents an alkyl group having from 1 to 4 carbon atoms, or
(b) hydrolysing a compound of the general formula IV in which R' represents an alkyl group having from 1 to 4 carbon atoms and reducing the compound thus formed, to obtain the free carboxylic acid of the general formula V, and, if desired, esterifying the acid or converting it to a salt.
The hydrolysis mentioned under (a) and (b) may be carried out under acid or alkaline conditions and removes the protective group B as well as forming the carboxylic acid.
An ester of the general formula I may be prepared from an ester of the general formula IV by reduction. The compound of the general formula IV may be prepared from a compound of the general formula
in which B has the meaning given above, X represents a chlorine, bromine or iodine atom and R" represents an alkyl group having from 1 to 4 carbon atoms, by reaction with a compound of the general formula v in which Y represents a halogen atom and
has the meaning given above in the presence
of copper powder.
The present invention further provides a process for the preparation of a compound of the general formula IV, which comprises reacting a compound of the general formula
II with a compound of the general formula FY ; (111) in which Ar and Y have the meanings given above, and for the preparation of a compound of the general formula I in which R1 represents an alkyl radical having from 1 to 4 carbon atoms, which comprises reducing a compound of
the general formula IV in which R' represents an alkyl radical having from 1 to 4 carbon atoms
The invention furthermore especially provides a process for the preparation of a sulphamoylbenzoic acid derivative of the general formula
in which and Rl have the meanings given above and
B' represents two hydrogen atoms or has the meaning given for B above, which comprises
(i) reacting a 3 - nitro - 4 halogenobenzoic acid derivative of the general formula
in which X represents a chlorine, bromine or iodine atom, Rl' represents an alkyl group having from 1 to 4 carbon atoms, and
R3, R4 and R5 have the meanings given above, with a compound of the general formula (Y III in which Y represents a halogen atom and
Qr has the meaning given above, in the presence of copper powder, to give a compound of the general formula
in which the radicals Rl', R3, R4 and R5 and have the meanings given above, and
(ii) (a) reducing the nitro group in a compound of the general formula IV to form a compound of the general formula I' in which B' does not represent hydrogen atoms and Rl has the meaning given for Rl', and, if desired, hydrolysing this compound under acid or alkaline conditions, or (b) hydrolysing the compound of the general formula IV under acid or alkaline conditions, and subsequently reducing the nitro group, and, if desired,
(iii) esterifying the acid formed or converting it into a salt.
The preparation of starting materials of the general formula II is described in
German Offenlegungsschrift 2,461,601.
It is known from the literature (for example Jerry March, Advanced Organic
Chemistry, McGraw-Hill Book Company, and Kogakusha Company Ltd 1968, page 508) that compounds which contain
SO2NH2 groups cannot be subjected to condensation in the presence of copper powder (Ullmann reaction) because side reactions take place which prevent the desired synthesis of biaryl compounds.
Surprisingly, a compound of the general formula II in which the sulphonamide group is blocked by the protective group B can be reacted with an aryl halide of the general formula III in the presence of fine copper powder in accordance with the method of an Ullmann reaction to give a biaryl derivative of the general formula IV in very good yields.
It is thought that formation of a biaryl compound under the relatively severe conditions of the Ullmann reaction is even promoted by the sulphamoyl group thus protected. The good yields and the very specific course of the reaction suggest autocatalysis caused by a possible internal complexing of the intermediately formed
Cu-organic compound by the basic N atom of the protective group and thus a stabilising of this intermediate stage.
In a compound of the general formula III,
Y preferably represents an iodine or bromine atom.
The reaction of the compounds of the general formulae II and III, together with the copper powder, is usually carried out at a temperature of from 50 to 2000 C, preferably from 150 to 2000C, in the melt or in an inert high-boiling solvent. When the reaction is carried out in solution, in some cases the copper powder may be added immediately and in other cases it should be added only when the reaction temperature has been reached. If the reaction is carried out in the melt, it is advantageous to use nitrogen or another inert gas as a blanketing gas. The higher-boiling organic solvents dimethylformamide, dimethylacetamide, tetramethylurea and N - methylpyrrolidone have proved to be especially suitable.
However, solvents such as diînethylsulphoxide, sulpholan, hexamethylphosphoric acid trisamide, pyridine, quinoline or various higher boiling aromatic, aliphatic and alicyclic hydrocarbons may also be used. The metallic copper is usually employed in the form of very fine commercial copper powder. However, it may also be activated beforehand by washing commercial copper powder with a 0.02 molar aqueous solution of the disodium salt of ethylenediaminetetraacetic acid or by treating it with iodine.
The copper powder is usually employed in excess. If a solvent is used, a slight excess (10-20%) is frequently sufficient. In the melt, on the other hand, a two-fold to fivefold excess is usually advantageous. The copper powder may also be employed in combination with one or more copper salts, for example a copper (I) halide or Cu2O.
The conversion of the nitro group into the amino group may be effected by a process which is customary in the literature, for example by catalytic hydrogenation with hydrogen and Raney nickel as a catalyst.
However, it is also possible to use the customary noble metal catalysts, such as, for example, palladium-on-charcoal or platinum oxide.
The catalytic hydrogenation may be carried out in a manner known per se (for example "Organikum", Berlin Deutscher
Verlag der Wissenschaften, 5. Auflage, page 271-277, page 507-510). The reaction may be carried out in a solvent in the presence of a catalyst. Preferred solvents are organic solvents, such as, for example, methanol, ethanol, ethyl acetate, dioxan or other polar solvents, especially amide, e.g.
dimethylformamide or dimethylacetamide, or, if B'=2 H and R'=H, the reaction may also be carried out in an aqueous solution of an alkali metal salt.
The hydrogenation may be carried out at room temperature and under normal pressure, or at elevated temperature and under elevated pressure, for example 50"C and 50 atmospheres, in an autoclave.
The protective group B and the ester radical R" may be split off by hydrolysis carried out in the customary manner either under alkaline conditions, for example with a dilute alkali metal hydroxide or alkaline earth metal hydroxide, or under acid conditions with a dilute inorganic acid.
Hydrolysis may be performed before or after reduction of the nitro group.
Thus, hydrogenation of a compound of the general formula IV leads to a compound of the invention of the general formula I.
This compound may then, if desired, be hydrolysed to give a 3 - amino - 5 sulphamoyl - benzoic acid substituted by an aromatic radical in the 4- position (compound V). The same compound may be obtained by hydrolysis of the compound IV and then reduction.
To prepare an ester of the general formula I' in which B' represents two hydrogen atoms (compound V), the hydrolysed compound, e.g. of the general formula I' (Rl=H) obtained by the process according to the invention, may be subsequently esterified in the customary manner with a (C1-C4) aliphatic alcohol.
A large number of substituted diaryl compounds of the general formula I' may be manufactured by the process of the invention, some of which are mentioned below.
TABLE B
(compounds of the general formula I)
3 - amino - 4 - (4' - methylphenyl) - 5
N,N - dimethylaminomethylene
aminosulphonylbenzoic acid methyl ester,
3 - amino - 4 - (5 - methyl - 2
thienyl) - 5 - N,N - dimethylamino
methyleneaminosulphonylbenzoic acid
methyl ester, 3 - amino - 4- (5 - formyl- 2thienyl) - 5 - N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester,
3 - amino - 4 - (2 - thiazolyl) - 5 - N,N dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester, 3 - amino - 4 - (6 - methyl - 2pyridyl)- 5- N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester,
3 - amino - 4 - (3 - pyridyl) - 5 - N,N dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester, and
3 - amino - 4 - (2 - pyridyl) - 5 - N,N dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
TABLE C
(compounds of the general formula V)
3 - amino - 4 - (4' - methylphenyl) - 5 sulphamoylbenzoic acid,
3 - amino - 4 - (5 - methyl - 2 thienyl) - 5 - sulphamoylbenzoic acid,
3 - amino - 4 - (5 - formyl - 2 thienyl) - 5 - sulphamoylbenzoic acid,
3 - amino - 4 - (2 - thiazolyl) - 5 sulphamoylbenzoic acid,
3 - amino - 4 - (6 - methyl - 2 pyridyl) - 5 - sulphamoylbenzoic acid,
3 - amino - 4 - (3 - pyridyl) - 5 sulphamoylbenzoic acid, and
3 - amino - 4 - (2 - pyridyl) - 5 sulphamoylbenzoic acid.
Compounds of the general formula I are useful intermediate products for the synthesis of medicaments, in particular of diuretic agents and saluretic agents. Thus, for example, compounds of the general formula I in which
OAr represents an unsubstituted or substituted phenyl radical can be used as starting materials for the synthesis of sulphamoylbenzoic acid derivatives having a diuretic and saluretic action, such as are described in German Offenlegungsschrift 2,442,696.
The following Examples illustrate the invention.
Example 1
3 - amino - 4 - phenyl - 5 - N,N
dimethylaminomethyleneamino
sulphonylbenzoic acid methyl ester (I)
a) 3 - nitro - 4 - phenyl - 5 - N,N - dimethylaminomethyleneaminosul
phonylbenzoic acid methyl ester (IV)
70 g (0.2 mole) of 3 - nitro - 4 - chloro 5 - N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester are mixed with 50 g of very fine copper powder; and 100 g of iodobenzene are added. The mixture is warmed to 170--180"C under a N2 atmosphere and whilst stirring well, and the melt is kept at this temperature for about 2.5 hours. It gradually becomes viscous and a greenishbrown sludge forms. Excess iodobenzene is then distilled off and the residue is digested with n-hexane. The rock-hard mass which remains is dissolved in acetone, the copper and copper halides are filtered off and the solution is evaporated. The oil which remains is digested twice with isopropyl ether or petroleum ether and dissolved in glacial acetic acid and the solution is added dropwise to ice-water whilst stirring vigorously. A yellow substance flocculates out. It is separated off, washed thoroughly and dried at 50 in vacuo. Crude yield (only still slightly contaminated) 70 g, recrystallisation from CH3OH.
Yield 64.4 g=82%
Light yellow needles of melting point 145-1460C.
The reaction can also be carried out in dimethylformamide or tetramethylurea as the solvent.
(b) 3 - amino - 4 - phenyl - 5 - N,N
dimethylaminomethyleneamino
sulphonylbenzoic acid methyl ester (I)
40g of the nitro compound (1 a) are dissolved in ethyl acetate and hydrogenated in a duck-shaped shaking vessel with Raney nickel as the catalyst for 2 hours at room temperature and under normal pressure.
Thereafter, the mixture is filtered, the residue is washed several times with acetone and the filtrate is concentrated.
Recrystallisation from CH3OH/a little acetone
Yield 34.6 g.
Colourless crystals of melting point 1 89-1900C.
Example 2
3 - amino - 4 - phenyl - 5
sulphamoyl - benzoic acid (V) a) 3 - nitro - 4 - phenyl - 5 - N,N- dimethylaminomethyleneamino
sulphonylbenzoic acid methyl ester (1
a) is heated under reflux with 2 N
NaOH until a clear solution has
formed. 3 - nitro - 4 - phenyl - 5
sulphamoylbenzoic acid is precipitated
in the cold with 4 N HC1 and
recrystallised from hot water.
Yellow crystals of melting point 209--211"C.
The amino compound is obtained by catalytic hydrogenation with Raney nickel in dimethylformamide.
b) 3 - amino - 4 - phenyl - 5 - N,N
dimethylaminomethyleneaminosul
phonylbenzoic acid methyl ester (1
b) is saponified and precipitated as
described under (2 a).
Recrystallisation from water
Melting point 244--2460C.
Example 3
3 - amino - 4 - (4' - methoxyphenyl)
5 - N,N - dimethylamino
methyleneaminosulphonylbenzoic acid
methyl ester (I)
a) 3 - nitro - 4 - (4' - methoxyphenyl)
5 - N,N - dimethylamino
methyleneaminosulphonylbenzoic acid
methyl ester (IV)
35 g (0.1 mole) of 3 - nitro - 4 - chloro 5 - N,N - dimethylaminomethyleneaminosulfonylbenzoic acid methyl ester are mixed with 36 g (N0.15 mole) of iodoanisole and 20 g of very fine copper powder and the mixture is heated under nitrogen. The reaction starts fairly abruptly at about 180"C and the temperature must be kept between 182000C by cooling. After the melt has solidified to form a thick sludge, it is cooled, the solid mass is boiled up with acetone, the mixture is filtered and the filtrate is evaporated and methanol is added to the residue. On standing overnight, the product crystallises out
Yield 19 g
Recrystallisation from ethanol,
Melting point 178--180"C.
b) The nitro compound (3 a) is dissolved
in ethyl acetate and hydrogenated in a
duck-shaped shaking vessel with Raney
nickel as the catalyst at room
temperature and under normal
pressure (absorption of hydrogen for 1 hour). The mixture is then filtered,
the filtrate is concentrated and the
residue is recrystallised from CH3OH/a
little acetone.
Colourless crystals of melting point 212--213"C.
Example 4
3 - amino - 4 - (2 - thienyl) - 5 - N,N
dimethylaminomethyleneaminosul
phonylbenzoic acid methyl ester (I)
a)3 -nitro - 4 - (2 - thienyl) - 5 -N,N dimethylaminomethyleneaminosul -- phonylbenzoic acid methyl ester (IV)
70 g of 3 - nitro - 4 - chloro - 5 -N,N dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester, 60 g of very fine copper powder and 100 g of 2 bromothiophen are mixed thoroughly and the mixture is heated at 1800 for 6 hours under a nitrogen atmosphere. It is then allowed to cool and is digested several times with diisopropyl ether, under the influence of heat. (Excess 2 bromothiophen can be recovered from the diisopropyl ether). The solid product is dissolved in hot dimethylformamide, the solution is filtered and the filtrate is added dropwise to ice-water. The product which has precipitated (crude yield 59 g) is recrystallised from acetone/CH3OH or acetonitrile.
Yield 46.4 g
Yellow crystals of melting point 232--233"C.
b) The nitro compound (4 a) is dissolved
in dimethylformamide and
hydrogenated with Raney nickel as the
catalyst at 50"C and under 50
atmospheres for 8 hours. The mixture is
then filtered and the
dimethylformamide solution is added
dropwise to three times the amount of
ice-water. The amine which has
precipitated is boiled up with CH3OH.
Analysis sample recrystallised from nitromethane.
Colourless crystals of melting point 220221 .
Example 5 3 - amino - 4 - (3 - thienyl) - 5 - N,N
dimethylaminomethyleneaminosul phonylbenzoic acid methyl ester (I)
a) 3 - nitro - 4 - (3 - thienyl) - 5 - N,N
dimethylaminomethyleneaminosul
phonylbenzoic acid methyl ester SIV) 70 g of 3- nitro - 4- chloro - 5
N,N - dimethylaminomethyleneaminosul phonylbenzoic acid methyl ester are mixed with 60 g of copper powder and 100 g of 3 - bromothiophen and the mixture is heated to 1800C for " - hours under nitrogen.
Working up analogous to the procedure of Example (4 a)
Recrystallisation from glacial acetic acid or acetonitrile melting point 197--198"C.
b) The nitro compound is dissolved in
dimethylformamide and hydrogenated
for 3 hours at room temperature and
under normal pressure with Raney
nickel as the catalyst. After filtering the
mixture, the filtrate is added dropwise
to ice-water and the product which has
precipitated is isolated.
Recrystallisation from CHsOH or CH3NO2.
Melting point 220221 C.
Example 6 2 - amino - 4,2' - di - methoxycarbonyl
methyleneaminosulfonyl - biphenyl (I)
a) 2 - nitro - 4,2' - di - methoxy
carbonyl - 6 - N,N - dimethylamino
methyleneaminosulphonylbiphenyl (IV) 95 g (0.27 mole) oi 2 - nitro - 4 - chloro 5 - N,N - dimethylamino- methyleneaminosulphonylbenzoic acid methyl ester together with 35 g (0.55 mole) of very fine copper powder and 83 g (0.31 mole) of 2 - iodobenzoic acid methyl ester are heated under reflux in absolute dimethylformamide for 4 hours. Thereafter, the solvent is evaporated off and the residue is digested several times with hot acetone.
The acetone fractions are concentrated together and the residue is recrystallised from CH3OH/a little acetone.
This gives 53 g of a light yellow product of melting point 168--169"C.
b) The nitro compound (6 a) is dissolved in
absolute dimethylformamide and
hydrogenated with Raney nickel as the
catalyst at room temperature and under
normal pressure for 4 hours. The
mixture is filtered and the product is
precipitated with water.
On recrystallisation or on warming in a solvent, for example glacial acetic acid, the product cyclises immediately with the formation of the 5,6 - di-hydro phenanthridine system.
The compounds of Examples 4a and 5a can be used to prepare 3 - amino - 4 - (2 thienyl) - 5 - sulphamoylbenzoic acid, and 3 - amino - 4 - (3 - thienyl) - 5 - sulphamoylbenzoic acid, respectively by the method of Example 2.
These compounds can also be prepared by hydrolysis of the compounds of
Examples 4b and 5b.
WHAT WE CLAIM IS:
1. A compound of the general formula
in which represents a monocyclic or bicyclic radical
comprising at least one aromatic
carbocyclic or aromatic heterocyclic ring,
which is unsubstituted or substituted by one or more substituents, any two or more of which may be the same or different,
selected from halogen atoms, alkyl and
alkoxy radicals having from 1 to 3 carbon
atoms, methylene-dioxy, benzyloxy, -NO2, -C-N, OH, formyl and acetyl groups and carboxylate radicals -COOR in which R represents an alkyl radical,
R' represents a hydrogen atom or an alkyl
group having from 1 to 4 carbon atoms, and
B represents the protective group
in which
R3 represents a hydrogen atom or a lower alkyl radical, and
R4 and R5 may be the same or different and each represents a lower alkyl radical or are bonded to one another to form, with the nitrogen atom, a saturated ring, or
R3 and R4 are bonded to one another to form, with the carbon atom and nitrogen atom to which they are attached, a saturated ring, and
R5 represents a lower alkyl radical, or a salt thereof.
2. A compound as claimed in claim 1, in which B represents the =CHN(CH3)2 group.
3. A compound as claimed in claim 1, in which B is any one of the groups indicated by Table A herein.
4. A compound as claimed in any one of claims 1 to 3, wherein represents an unsubstituted or substituted benzene, naphthalene thiophene, pyridine, pyrimidine, thiazole, pyrazole, pyrazine, pyridazine, quinoline or isoquinoline ring.
5.3 amino - 4 - phenyl - 5 -N,N, -di methylaminomethyleneaminosulphonylben- zoic acid methyl ester.
6: 3 - Amino - 4 - (4' - methoxyphenyfl - 5 - N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
7. 3 - Amino - 4-(2-thienyl)- 5 N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
8. 3 - Amino - 4 - (3 - thienyl) - 5
N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
9. 2 - Arnino - 4,2' - di - methoxycarbonyl - 6 - N,N - dimethylaminomethyleneaminosulphonylbiphenyl.
10. Any one of the compounds indicated in Table B herein.
11. A compound of the general formula
in which OAr Rl and B have the meanings given in claim 1, or a salt thereof.
12. A compound as claimed in claim 11, in which B has the meaning given in claim 2.
13. A compound as claimed in claim 11, in which B has the meaning given in claim 3.
14. A compound as claimed in any one of claims 11 to 13, in which has the meaning given in claim 4.
15. 3 - Nitro - 4 - phenyl - 5 - N,N - di methylaminomethyleneaminosulphonyl- benzoic acid methyl ester.
**WARNING** end of DESC field may overlap start of CLMS **.
Claims (35)
1. A compound of the general formula
in which represents a monocyclic or bicyclic radical
comprising at least one aromatic
carbocyclic or aromatic heterocyclic ring,
which is unsubstituted or substituted by one or more substituents, any two or more of which may be the same or different,
selected from halogen atoms, alkyl and
alkoxy radicals having from 1 to 3 carbon
atoms, methylene-dioxy, benzyloxy, -NO2, -C-N, OH, formyl and acetyl groups and carboxylate radicals -COOR in which R represents an alkyl radical,
R' represents a hydrogen atom or an alkyl
group having from 1 to 4 carbon atoms, and
B represents the protective group
in which
R3 represents a hydrogen atom or a lower alkyl radical, and
R4 and R5 may be the same or different and each represents a lower alkyl radical or are bonded to one another to form, with the nitrogen atom, a saturated ring, or
R3 and R4 are bonded to one another to form, with the carbon atom and nitrogen atom to which they are attached, a saturated ring, and
R5 represents a lower alkyl radical, or a salt thereof.
2. A compound as claimed in claim 1, in which B represents the =CHN(CH3)2 group.
3. A compound as claimed in claim 1, in which B is any one of the groups indicated by Table A herein.
4. A compound as claimed in any one of claims 1 to 3, wherein represents an unsubstituted or substituted benzene, naphthalene thiophene, pyridine, pyrimidine, thiazole, pyrazole, pyrazine, pyridazine, quinoline or isoquinoline ring.
5.3 amino - 4 - phenyl - 5 -N,N, -di methylaminomethyleneaminosulphonylben- zoic acid methyl ester.
6: 3 - Amino - 4 - (4' - methoxyphenyfl - 5 - N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
7. 3 - Amino - 4-(2-thienyl)- 5 N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
8. 3 - Amino - 4 - (3 - thienyl) - 5
N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
9. 2 - Arnino - 4,2' - di - methoxycarbonyl - 6 - N,N - dimethylaminomethyleneaminosulphonylbiphenyl.
10. Any one of the compounds indicated in Table B herein.
11. A compound of the general formula
in which OAr Rl and B have the meanings given in claim 1, or a salt thereof.
12. A compound as claimed in claim 11, in which B has the meaning given in claim 2.
13. A compound as claimed in claim 11, in which B has the meaning given in claim 3.
14. A compound as claimed in any one of claims 11 to 13, in which has the meaning given in claim 4.
15. 3 - Nitro - 4 - phenyl - 5 - N,N - di methylaminomethyleneaminosulphonyl- benzoic acid methyl ester.
16. 3 - Nitro - 4 - (4' - methoxy
phenyl) - 5 - N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
17. 3 - Nitro - 4 - (2 - thienyl) - 5 - N,N dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
18. 3 Nitro - 4 - (3 - thienyl) - 5
N,N - dimethylaminomethyleneaminosulphonylbenzoic acid methyl ester.
19. 2 - Nitro - 4,2' - di - methoxycarbonyl - 6 - N,N- dimethylaminomethyleneaminosulphonyl - biphenyl.
20. The 3 - nitro analogue of any one of the 3 - amino compounds indicated in
Table B herein.
21. A process for the preparation of a compound of the general formula
in which and R' have the meanings given in claim 1, or a salt thereof, which comprises
(a) hydrolysing under acid or alkaline
conditions a compound of the general
formula
in which
3 and B have the meanings given in claim 1 and R' represents an alkyl group having from 1 to 4 carbon atoms, or
(b) hydrolysing under acid or alkaline
conditions a compound of the general
formula
in which OAr and B have the meanings given in claim 1 and Rl represents an alkyl group having 1 to 4 carbon atoms, and reducing the compound thus formed, and, if desired, esterifying the acid or converting it into a salt.
22. A process as claimed in claim 21, carried out substantially as described in
Example 2 herein.
23. A compound of the general formula V shown in claim 21 or a salt thereof, whenever prepared by a process as claimed in claim 21 or claim 22.
24. A process for the preparation of a compound of the general formula
in which
R' and B have the meanings given in claim 1 or a salt thereof, which comprises reacting a compound of the general formula
in which B has the meaning given in claim 1,
X represents a chlorine, bromine or iodine atom and R" represents an alkyl group having from 1 to 4 carbon atoms, with a compound of the general formula v in which Y represents a halogen atom and has the meaning given in claim 1 in the presence of copper powder.
25. A process as claimed in claim 24,
carried out substantially as described in any one of Examples la, 3a, 4a, 5a and 6a
herein.
26. A compound of the general formula
IV shown in claim 24 or a salt thereof,
whenever prepared by a process as claimed
in claim 24 or claim 25.
27. A process for the preparation of a
compound of the general formula
in which
3 Rl and B have the meanings given in claim 1 or a salt thereof, which comprises reducing a compound of the general formula
in which and B have the meanings given in claim 1 and R" represents an alkyl radical having 1 to 4 carbon atoms.
28. A process as claimed in claim 27, carried out substantially as described in any one of Examples 1b, 3b, 4b, 5b and 6b herein.
29. A compound of the general formula I shown in claim 27, or a salt thereof, whenever prepared by a process as claimed in claim 27 or claim 28.
30. A process for the preparation of a compound of the general formula
in which Ar and R' have the meanings given in claim 1 and B' represents two hydrogen atoms or has the meaning given for B in claim 1, or for preparing a salt thereof, which comprises (i) reacting a 3 - nitro 4 - halogenobenzoic acid derivative of the general formula
in which X represents a chlorine, bromine or iodine atom, R" represents an alkyl group having from 1 to 4 carbon atoms, and
R3, R4 and RS have the meanings given in claim 1, with a compound of the general formula Fy III in which Y represents a halogen atom and
OAr has the meaning given in claim 1, in the presence of copper powder, to give a compound of the general formula
in which the radical R1' has the meaning given above and the radicals R3, R4 and R5 and
3 have the meanings given in claim 1, and
(ii) (a) reducing the nitro group in a
compound of the general formula IV to
form a compound of the general
formula I' in which B' does not
represent hydrogen atoms and R' has
the meaning given for R1 and, if
desired, hydrolysing this compound
under acid or alkaline conditions, or
(b) hydrolysing the compound of the
general formula IV under acid or
alkaline conditions, and subsequently
reducing the nitro group,
and, if desired,
(iii) esterifying the acid formed or
converting it into a salt.
31. A process as claimed in claim 30, wherein Y represents an iodine or bromine atom.
32. A process as claimed in claim 30 or claim 31, wherein the reaction between a compound of the general formula II and a compound of the general formula III is carried out at 150 to 2000C in a melt or in a high-boiling solvent.
33. A process as claimed in claim 32, wherein the solvent is dimethylformamide, dimethylacetamide, tetramethylurea, or Nmethylpyrrolidone.
34. - A process as claimed in claim 30, carried out substantially as described in any one of Examples 1 and 3 to 6 herein or as described in Examples la and 2 herein.
35. A compound of the general formula I' shown in claim 30 or a salt thereof, whenever prepared by a process as claimed in any one of claims 30 to 34.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE2654795A DE2654795C2 (en) | 1976-12-03 | 1976-12-03 | Process for the preparation of aromatically substituted sulfamoylbenzoic acid derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| GB1598093A true GB1598093A (en) | 1981-09-16 |
Family
ID=5994580
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB21700/80A Expired GB1598094A (en) | 1976-12-03 | 1977-12-02 | Sulphamoylbenzoic acid derivatives having aromatic substituents |
| GB50343/77A Expired GB1598093A (en) | 1976-12-03 | 1977-12-02 | Sulphamoyl-benzoic acid derivatives having aromatic substituents and a process for their manufacture |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| GB21700/80A Expired GB1598094A (en) | 1976-12-03 | 1977-12-02 | Sulphamoylbenzoic acid derivatives having aromatic substituents |
Country Status (5)
| Country | Link |
|---|---|
| JP (1) | JPS5371043A (en) |
| CH (1) | CH630350A5 (en) |
| DE (1) | DE2654795C2 (en) |
| FR (1) | FR2372805B1 (en) |
| GB (2) | GB1598094A (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2849646A1 (en) * | 1978-11-16 | 1980-06-04 | Hoechst Ag | THIENYLBENZOESAE DERIVATIVES AND METHOD FOR THE PRODUCTION THEREOF |
| DE3911549A1 (en) * | 1989-04-08 | 1990-10-31 | Hoechst Ag | NAPHTYLALKYLAMINO SUBSTITUTED SULFAMOYLBENZOESAE DERIVATIVES, METHOD FOR THE PRODUCTION THEREOF AND THEIR USE AS A MEDICINAL PRODUCT |
| WO2019193161A1 (en) | 2018-04-06 | 2019-10-10 | Universität Wien | Bumetanide derivatives for the therapy of stroke and other neurological diseases/disorders involving nkccs |
| EA202092326A1 (en) | 2018-04-06 | 2021-03-19 | Цилентин Аг | BUMETHANIDE DERIVATIVES FOR THE TREATMENT OF HYPERHYDROSIS |
-
1976
- 1976-12-03 DE DE2654795A patent/DE2654795C2/en not_active Expired
-
1977
- 1977-11-30 CH CH1466177A patent/CH630350A5/en not_active IP Right Cessation
- 1977-12-02 GB GB21700/80A patent/GB1598094A/en not_active Expired
- 1977-12-02 GB GB50343/77A patent/GB1598093A/en not_active Expired
- 1977-12-02 FR FR7736423A patent/FR2372805B1/fr not_active Expired
- 1977-12-03 JP JP14561877A patent/JPS5371043A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| FR2372805B1 (en) | 1981-11-27 |
| DE2654795C2 (en) | 1985-10-10 |
| JPS5371043A (en) | 1978-06-24 |
| CH630350A5 (en) | 1982-06-15 |
| DE2654795A1 (en) | 1978-06-08 |
| FR2372805A1 (en) | 1978-06-30 |
| GB1598094A (en) | 1981-09-16 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PS | Patent sealed | ||
| PCNP | Patent ceased through non-payment of renewal fee |