CS266174B1 - A method for the analytical determination of 1-nitro-2-methylthio-2-alkylaminoethenes - Google Patents

Abstract

The solution concerns a method for the analytical determination of l-nitro-2-methylthio-2-alkylaminoethene, which due to its weak basicity cannot be successfully titrated acidimetrically, but which can be converted by the action of alkylamines, for example methylamine or ethylamine, in an organic solvent environment, for example methanol, ethanol or benzene and the like, to l-nitro-2,2-bis (alkylamino) -ethenes, which can then be easily titrated with a volumetric solution of perchloric acid in a non-aqueous environment with potentiometric or visual indication of the equivalence point.

Description

The invention relates to in which R represents an analytical method for the determination of substances represented by the general formula I, a lower alkyl group with a C 1 to or a benzyl group:

^ ^SCH 3. i> _t N (Ή -í '(1 j

These compounds are important intermediates in the synthesis of pharmacodynamically important active substances used in the therapy of gastric and duodenal ulcers, gastric hyperacidity, pathological hypersecretory conditions and the like, such as ranitidine-type preparations.

Only methods for the determination of these compounds using liquid or thin layer chromatography with densitometric evaluation of chromatograms are described in the literature.

Attempts to determine the compounds of the formula I by titration with a standard solution of perchloric acid in a non-aqueous medium have shown that the basicity of the R-NH group is too weak here, so that only a very flat and difficult-to-assess inflex is obtained on the titration curve. If this titration is performed in the environment of acetic anhydride, the inflex is better evaluable, but the results found fluctuate considerably and are mainly lower than it actually is. Under these conditions, the R-NH group, especially at prolonged reaction times or elevated temperatures, acetylates relatively quickly, thus losing its basic character and the yields of acidimetric titration therefore decrease. .

It has now been found that compounds of formula II, *

^ NH-R O _? N-CH-C (II) ^ NH-R 'in which R ar may be the same or different and have the same meaning as R for the compounds of formula I can be titrated in a non-aqueous medium with a standard solution of perchloric acid very easily and with accurately reproducible results. .

The solution to the problem, therefore, was to find a suitable, easily and rapidly feasible process for the quantitative conversion of the methyl mercapto compounds of the formula I into 1-nitro-2,2-bis (alkylamino) ethenes of the formula II.

It is generally known to react C-methylthio groups with primary amines, in which methyl mercaptan is cleaved to give the secondary amine in the sense of the equation

-C-SCH '+ H _O NR'---> -C-NH-R '+ CH 2 SH

Z j

Various alkylamines and arylamines have now been tested for the reaction of the compounds of the formula I with positive results. Due to the analytical determination technique, when it is necessary to work with excess alkylamine and then completely remove it after conversion, lower alkylamines such as methylamine or ethylamine, whose solutions in low-boiling organic solvents such as methanol, ethanol or benzene can then be easily evaporated.

The most suitable method for solving this problem has proved to be the process according to the invention, according to which the compounds of the general formula sch ₃ o ₂ n-ch = c \ ^.

NH-R

EN 266 174 Bl is converted by an excess of methylamine or ethylamine in methanol, ethanol or benzene, to compounds of formula III-NH-R ₂ N-CH = C-NH-R '(III) wherein R has the meanings «un as in formulas 1 and Π and R 'is an alkyl radical for the conversion of the alkylamine used, for example methyl or ethyl. The reaction proceeds according to the equation _{^ ^ sch 3} ^ NH-R 'o ₂ n-ch = c ^ + r'-nh ₂ -> o ₂ n-ch = c + ch ₃ sh.

. ^ NH-R ^ NH-R

Under the above conditions, the conversion already takes place very quickly at 20 to 25 [deg.] C., so that on an analytical scale it is completely completed within 20 minutes.

The excess alkylamine R'-NH ₂ and the solvent of XII are dissolved in anhydrous acetic acid and then evaporated on a water bath, the remaining residue and then titrated easily with a standard solution of perchloric acid with potentiometric or visual indication of the equivalence point.

The following examples of embodiments of the analytical assay according to the invention merely illustrate this, but do not limit its general validity.

Example 1 mg of 1-nitro-2-methylthio-2-methylaminoethene are dissolved in 2 ml of an ethanolic solution of methylamine (c = 240 mg / ml) in a titration flask, the solution is stirred for 20 minutes and then evaporated to dryness on a water bath. The residue is dissolved in 30 ml of acetic acid and titrated potentiometrically on a tungsten and graphite electrode with a standard solution of HClO2 (c = 0.05 mol / l).

ml of a standard solution of HCl (4 = 0.05 mol / l corresponds to 7.409 5 mg of 1-nitro-2H-methylthio-2-methylaminoethene).

Example 2 mg of 1-nitro-2-methylthio-2-methylaminoethene are dissolved in 2 ml of an ethanolic solution of methylamine (c = 240 mg / ml) in a titration flask and the procedure is the same as in Example 1, except that the solution is titrated visually. for crystal violet from purple to blue-green color.

Example 3 mg of 1-nitro-2-methylthio-2-ethylaminoethene are mixed in a titration flask with 2 ml of a methanolic solution of ethylamine (c = 250 mg / ml) and the procedure is the same as in Example 1.

ml of a standard solution of HCl ₄ (c = 0,05 mol / l) corresponds to 8,111 mg of 1-nitro-2-methylthio-2-ethylaminoethene.

Example 4 mg of l-nitro-2-methylthio-2-benzylaminoethenu in the titration flask dissolved in 2 ml benzene solution of methylamine (c = 200 mg / ml), and proceeding as in Example 1. 1 ml of standard solution HC1O ₄ ( c = 0.05 mol / l) corresponds to 11.214 5 mg of 1-nitro-2-methylthio-2-benzylaminoethene.

Claims (1)

OBJECT OF THE INVENTION Method for the analytical determination of 1-nitro-2-methylthio-2-alkylaminoethenes of general formula * 1 O ₂ N-CH = C (i) NH-R in which R represents a lower alkyl group with up to or a benzyl group, characterized in that these substances are converted by treatment with lower alkylamines, such as methylamine or ethylamine, in a suitable organic solvent, for example methanol, ethanol or benzene. II ^ NH-R '(II) NH-R in which R has the same meaning as in formula I and R 'is an amine substituent used for the conversion, for example methyl or ethyl, after which these diamine derivatives of formula II are titrated in a non-aqueous medium with a standard solution of perchloric acid using a potentiometric or visual equivalence method. point.