DE1244771B - Process for the preparation of Aminotroponsulfonsäureestern - Google Patents

Description

PUNDESRKPUBLIK DEUTSCHLAND DEUTSCHES '/ MW ^ PATENTAMT

EDITORIAL

Int α .:

C07c

«Η

German class. 12 o / 25

Number 1 244 771

File number. S 96070IV b / 12 ο

Filing date March 20, 1965

Open date: 20 July 1967

The invention relates to a method for Production of new aminotroponsulfonic acid esters of the general formula

Process for the production of
Aminotroponic sulfonic acid esters

A / ⁰

(D

wherein X is hydrogen, a straight or branched Ci-Cs-alkyl radical, the phenyl radical or bromine, R "is a straight or branched Q-C6-alkyl radical, an optionally substituted by Q-C5-alkyl phenyl radical or the benzyl group and R 'represents a Ci-Cs-alkyl radical and η can assume the value 1 or 2

The Ammotroponsulfonsaureester of the formula (I) are previously unknown substances that surprisingly analgesic and anti-inflammatory activities own

According to the invention, the Ammotroponsulfonsaureester of the above formula (I) can be prepared by a compound of the general formula

Applicant

Sankyo Company, Limited, Tokyo

representative

Dipl -Ing K Kiekeben, patent attorney,

Berlin 19, Kaiserdamm 28

Named as the inventor
Genshun Sunagawa,
Nobuo Soma,
Yoshio Sato, Tokyo

Claimed priority

Japan March 24, 1964 (39-16064)

(H)

NHR

worm X has the meaning described above and R represents hydrogen or the above-defined R ″, with a low molecular weight dialkyl sulfate

For the reaction according to the invention, low molecular weight Dialkyl sulfates, such as dimethyl or dietary sulfate, used

The inventive reaction is carried out in the presence or absence of an inert organic solvent, for example benzene, toluene or dioxane In general, it enpfiehlt to apply as the reaction temperature, the reflux temperature of the solvent used or a temperature in the range of about 100 to 15O ⁰ C

After completion of the reaction, the reaction product becomes as usual, for example by adding of some water, worked up A crystalline substance separates out, which through Filtration won and then by knocking out or purified by chromatography. The ammotropone derivative used as the starting material of the above formula (II), which is used in the present process, can easily are produced by reaction of the corresponding tropondate with hydrazine or by alkylation The invention is illustrated by the following examples explained in more detail

example 1

A mixture of 6.0 g of 2-Ammotropon and 12 g of dimethyl sulfate in 60 ml of toluene is taken for 3 hours Stirring heated to reflux. After the reaction has ended, the reaction mixture is allowed to cool left to stand, shaken with water and then the Toluene phase washed with water and over anhydrous Sodium sulfate dried. The toluene solution is concentrated under reduced pressure, and the residue obtained is chromium-coated on aluminum oxide

709 617/576

matographiert Elution with benzene and then with chloroform, and the subsequent removal of the chloroform from the eluate gives a crystalline substance that is umkristalhsiert from ethanol and 0.5 g of 2 - Methylaminotropon - 5 - sulfonsauremethylester obtained which melts at 131 ⁰ C

Example 2

A mixture of 1.5 g of 2-amino-7-methyltropone and 3 g of dimethyl sulfate in 15 ml of toluene is heated under reflux for 2 hours with stirring toluene phase washed with water and dried over anhydrous sodium sulfate the toluene is then distilled off to obtain a crystalline substance remains which is umkristalhsiert of benzene and 0.5 g of 2-methylamino-7-methyltropon-5-sulfonsauremethylester obtained which melts at 148 ⁰ C

Example 3

A mixture of 3 g of 2-amino-7-phenyltropone and 6 g of dimethyl sulfate in 30 ml of toluene is heated under reflux for 3 hours with stirring dried over anhydrous sodium sulfate. The toluene is distilled off to give a crystalline substance which is dissolved in benzene, the resulting solution is subjected to aluminum oxide chromatography to give the crude product which is further recrystallized from benzene and 0.6 g of the pure 2-Methylammo-7-phenyltropon-5-sulfonsauremethylesters obtained which melts at 185 to 187 ⁰ C.

Example 4

A mixture of 2 g of 2-amino-7-bromotropone and 4 g of dimethyl sulfate in 20 ml of toluene is 2 hours refluxed with stirring. After the reaction has ended, the reaction mixture is cooled down left to stand, shaken with water and washed the toluene phase with water and over anhydrous sodium sulfate dried The toluene distilled off wildly, leaving a residue obtained a crystalline substance which is recrystallized from benzene and 0.5 g of 2-methylammo-7-bromotropone-5-sulfonic acid methyl ester which melts at 184 to 185 ° C

Example 5

A mixture of 4.0 g of 2-methylaminotropone and 8.0 g of dimethyl sulfate in 40 ml of toluene is refluxed for 5 hours with stirring. After the reaction has ended, the reaction mixture is left to cool, shaken with water and the toluene phase washed with water and over dried anhydrous sodium sulfate. The toluene solution is concentrated under reduced pressure and the residue is subjected to aluminum oxide chromatography. Elution with benzene and then with chloroform, followed by removal of the chloroform, gives a crystalline substance which is recrystallized from ethanol, resulting in 0.5 g of 2- Methylamlnotroρon-5-sulfonic acid ester, which melts at 131 ⁰ C

Example 6

A mixture of 2 g of 2-Methylammo-7-bromotropone and 12 ml of dimethyl sulfate for 1 hour at 13O ⁰ C with stirring heated After completion of the reaction the non-reacted dimethyl sulfate is removed by distillation, to the residue water is added, then the mixture is neutralized by adding sodium bicarbonate to separate out a crystalline substance.The substance is recovered by filtration and kneaded from ethanol to give 1.5 g of methyl 2-methylamino-7-bromotropon-5-sulfonate, which melts at 184 to 185 ° C

Example 7

A mixture of 5.0 g of 2-benzylaminotropon and 10 g of dimethyl sulfate in 10 ml of toluene are refluxed for 7 hours with stirring. After completion the reaction, the reaction mixture is allowed to stand to cool, stirred with water and Left to stand for a while to a crystalline substance to be deposited, which is recovered by filtration and recrystallized from dioxane, 1.0 g 2-Benzylaminotropon-5,7-disulfonic acid dimethyl ester incurred, which melts at 208 ° C

Example 8

A mixture of 9.0 g of 2- (p-Toluidmo) -7-bromotropone and 30 ml of dimethyl sulfate for 5 hours with stirring to a temperature of 120-130 ⁰ C heated After completion of the reaction, the reaction mixture is cooled, a crystalline substance which is recovered by filtration. The mother liquor is concentrated under reduced pressure, and methanol is added to the residue to separate a crystalline substance, which is recovered by filtration. The crystalline substance is kneaded from ethanol to give 9.1 g of 2- (p-Toluidmo) -7-bromotropone-5-sulfonic acid methyl ester, which melts ^{at 171 G C.}

Example 9

A mixture of 2.0 g of methyl 2-benzylammotropon-5-sulfonate and 4.0 g of dimethyl sulfate in 20 ml of toluene is heated under reflux for 5 hours with stirring deposit a crystalline substance, which is then recovered by filtration and then is umkristallisieit from dioxane to give 1.0 g of 2-Benzylammotropon-5,7-disulfonsauredimethylester anfallt melting at 208 ⁰ C

Example 10

Em mixture of 3.0 g of methyl 2-methylaminotropon-5-sulfonate and 10 g of dimethyl sulfate in 20 ml of toluene is heated under reflux for 10 hours with stirring depositing crystalline substance is recovered by filtration and then umkristalhsiert from ethanol to give 1.0 g l-Methylarmnotropon-S ^ -disulfonsauredimethylester anfallt melting at 195 ⁰ C

Claims (1)

Claim Process for the preparation of aminotroponic sulfonic acid esters the general formula (RO ₃ S) _n NHR " wherein X is hydrogen, a Ci-Cs-alkyl radical, the Phenyl radical or bromine, R "a Q-Cs-alkyl radical, one optionally by Q-Cs-alkyl groups substituted phenyl radical or the benzyl group and R 'represents a Q-Cs-alkyl radical and η can assume the value 1 or 2, characterized in that a compound of the general formula NHR wherein X has the meaning described above and R is hydrogen or that defined above R ″ is reacted with a low molecular weight dialkyl sulfate