SU1122947A1 - Method of determination of heterocyclic nitrogen-containing bases - Google Patents

Abstract

SUCCUD DETERMINED HETEROCYCLIC NITROGEN-CONTAINING CAPTS CURRENT OVERVIEW CURRENT OVERVIEW CURRENT CURRENT OTHERWORDS CURRENT ANNUAL REMEDIATION CURRENT ANNUAL REMEDIATIONS AND CURRENT RELATIONS TO CURRENT ANALYSIS sequentially, and the analysis of the filtrate is carried out by photocollection in an alcohol medium. : 1 (L s

Description

4 The invention relates to analytical chemistry, in particular to methods of analysis, materials using optical methods, and can be used in the chemical and pharmaceutical industry to control the quality of intermediates, such as aminothiazole, dihydropapaverine base, etc. in the manufacture of drugs - nitazole, papaverine et al., as well as for examining mother liquors in the production of caffeine and similar compounds for their disposal. A known method for acid-base titration of heterocyclic nitrogen-containing bases or their salts in aqueous or non-aqueous media is to dissolve the sample in an aqueous or non-aqueous solvent, titrate the bases of the acids (or their salts with alkali) with the indicator — bromophenol blue, and calculate the number of hemogrames and the number of hemogrames from the samples of hemograms and hemogrames. compound ij However, this method, when used, gives an error of determination of 20–30 rel.% due to the fact that not only heterocyclic nitrogen-containing titers are titrated in an aqueous medium. basis ™ neither but. other organic nitrogen bases. The application of this method for the determination of amivothiazole, the base of dihydropapaverine or caffeine in a non-aqueous medium is impossible due to the fact that the objects of analysis themselves are in the aqueous phase. A known Kjeldahl method for determining heterocyclic nitrogen-containing bases, based on the transition of organic nitrogen to C1MMONIUM sulfate when heated. samples with concentrated sulfuric acid followed by isolation and determination of ammonia 2. This method does not provide sufficient accuracy (error is 3-5 rel.%) in determining the aminothiazole, the base of dihydropapaverine and caffeine because it is difficult to control the end of the process. base conversion to ammonium sulfate. In addition, the known method is long (3-6 hours) and dangerous due to the use of heating with concentrated sulfuric acid. A weight method for analyzing heterocyclic nitrogen-containing bases is also known, including weighing the sample, adding picrolonic acid to it, settling the precipitate formed, separating it from the liquid, washing the precipitate with water, drying it, weighing the dried precipitate, and calculating the amount of detectable compounds H. The weight analysis method does not provide sufficient accuracy for the determination of the aminothiaeol, the base of dihydropapaverine or caffeine (the error is 5-7 rel.%), As the sample is lost during long-term operations: settling, washing, drying, etc. A known method for the quantitative determination of heterocyclic nitrogen-containing bases (aminothiaol), including the selection of the analyzed sample in an amount of 25 ml, the addition of 25 ml of water, evaporation of it on the iron ring above the electric plate to a volume of 20 ml. Then, from the cooled concentrated solution of the sample, 2-aminothiazole is liberated with a 40% sodium hydroxide solution to a clearly alkaline reaction to phenolphthalein paper with vigorous cooling. The precipitate of 2-aminothiazole is filtered on a Buchner i; washed with water until completely dissolved (450 ml of water). The washings are transferred to a 500 ml flask, and 10-15 ml of strong HC1 is added thereto until acidic reaction to the end paper. The solution is made up to the mark with water and stirred. I Take 25 ml of the solution from the flask, dilute with water and titrate the excess acidity with 0.5 N, sodium hydroxide solution with an indicator of methyl orange, and then titrate 2-aminothiazole with an indicator of phenolphthalein 4. The disadvantages of this method are the analysis duration and overestimation by 2-4% of the results due to the fact that not only nitrogen in the ring but also other nitrogen-containing bases is titrated during titration (Tables 2 and 3). In addition, a method is known for quantifying heterocyclic nitrogen-containing bases (dihydropapaverine base), including weighing 0.5 g of sample, dissolving it in 20 ml of diluted HC1 when heated, and extracting the solution with chloroform three times in 20.15 and 10 ml, respectively. The extracts are then filtered through a chloroform-moistened filter into a 150 ml Erlenmeyer flask. The chloroform solution is evaporated, the chloroform is distilled off to dryness in a water bath, the residue is dissolved in 25 ml of ethyl alcohol, a few drops of phenol-phthalein are added and titrated with a 0.1N sodium hydroxide solution to a pink color of 5J. The disadvantages of this method are the laboriousness, duration and overestimation of results by 2% due to the extraction of all the presence of j

primary compounds.

The closest in technical essence and the achieved result to the invention is a method for quantitative determination of heterocyclic nitrogen-containing bases, including sample processing with a solution of a complexing agent containing bismuth and iodine ions, filter; The precipitate is formed and the filtrate is studied; a sample of the KBil4 complexing agent is prepared for sample processing by mixing solutions of potassium iodide and bismuth nitrate, and the study of the filtrate is performed by direct titration of the excess Bi with Trilon B until the titration solution 6j is decolorized,

The disadvantages of the known method are low accuracy of determination (error 10–15 rel.%, Caused by the color of the test solutions preventing the fixation of the end point of the titration; prolonged formation of a precipitate (15–20 min) due to the lack of optimal complexation conditions, i.e. insufficient concentration of the initial reagents; the need for preliminary preparation of a solution of an unstable reagent-free VHF whose optical density varies with time which entails the obligatory titration of this solution by Trilon B to establish a specific titer value at the time of determination.

The aim of the invention is to simplify the method and improve its accuracy.

The goal is achieved in that according to the method of sequential processing of the analyzed sample with solutions of potassium iodide and bismuth nitrate followed by filtration and analysis of the filtrate by photocolorimetry in an alcohol medium, processing of the analyzed sample with solutions of iodide of bismuth nitrate and bismuth nitrate is performed sequentially and the filtrate is analyzed. These are photocolorimetration in a pyrite medium.

Sequential processing of the sample with potassium iodides and bismuth nitrate helps to accelerate the formation of a precipitate when certain compounds pass into it, therefore, their absence in the filtrate is ensured and the accuracy of determination is improved.

Carrying out the study of the filtrate photocolorimetrically in an alcoholic medium makes it possible to increase the accuracy of determining the heterocyclic nitrogen-containing bases found in industrial solutions of chemical-pharmaceutical productions (nitazole, papaverine, caffeine) by reducing the concentration of the filtrate when creating an alcoholic medium and ensuring that it is possible to accurately measure its optical density ( The optical density of the filtrate is significantly higher than 1; its conversion into an alcohol medium allows accurate measurement. the optical density of which becomes a value less than 1, by lowering the concentration of the filtrate on dilution with alcohol).

To implement the method, calibration graphs are pre-constructed for solutions of 2-aminothiazole, dihydropapaverine base, and caffeine of known concentrations using ethyl alcohol as a comparison solution.

The construction of the calibration graph for the 2-aminothiazol solution is carried out as follows.

A series of standard solutions of 2-aminothiazole are prepared with a concentration of 120-200 g / l in 15% hydrochloric acid. Then, a sample of 12.5 ml is pipetted from each standard solution and transferred to a 25 ml volumetric flask. The volume is adjusted to the mark with 15% hydrochloric acid ..

Then in a conical flask is placed

7 ml of potassium iodide added

0.5 ml of a standard solution of 2-aminothiazole from a volumetric flask, and gradually pour 7 ml of a solution of bismuth nitrate with constant stirring. When the latter is added, a bright red precipitate is formed, which after 10 minutes of exposure is filtered off.

1 ml of the filtrate is diluted with ethyl alcohol in a 50 ml volumetric flask, after which 5 ml of the resulting solution is diluted once more with ethyl alcohol in a 25 ml volumetric flask. Then, the optical density of the prepared solution is measured on a FEK-56 photocolorimeter at a wavelength of 344 nm in a cuvette 10 mm long.

8 As the comparison solution, ethyl alcohol is used. Based on the obtained values of optical density, a calibration graph of the dependence of the optical density on the content of aminothiazole in the sample was constructed.

Calibration graphs for the dihydropapaverine and caffeine base solutions are constructed similarly.

Example. Determination of 2-aminothiazole.

12.5 ml of sample - a solution containing 2-aminothiazole in the amount of 13.5; 15.7; 14.0 and 17.4%, alternately placed in a volumetric flask of 25 ml

and the volume is adjusted to the mark with 15% hydrochloric acid.

Then, 0.5 ml of each of the prepared solutions is transferred into conical flasks containing 7 ml of potassium iodide, after which there (7 ml) of bismuth nitrate is gradually added with constant stirring, and 2.-aminothiazole precipitates in the form of its complexon to KVP4 i. a red precipitate is formed). After a 10-minute soak, the precipitates formed are filtered. Brooded, For the study. The filtrate is converted into an alcohol medium by diluting this with alcohol in a 50 ml volumetric flask by photocolorimetrication of the filtrate, and 5 ml of the resulting solution is diluted once more with ethyl alcohol in a 25 ml volumetric flask. Then, photocolorimetry of the proposed solution is carried out - measuring the optical density (D) on a FEC-56 photocolorimeter at 344 in a 10 ml cuvette. Ethyl alcohol is used as a comparison solution.

Using the measured optical density value, the percentage of 2-aminothiazole in the test solution is determined using the previously constructed calibration graph.

In order to accumulate statistical material and the reproducibility characteristics of the method, a six-fold analysis of artificial model mixtures containing 2-aglinotiazole was carried out. 13.0 and -17.0%.

The results of determining the percentage of 2-aminothiazole in the artificial model mixture are given in Table 1.

At the same time, the content of 2-aminothiazole is determined by a known 4J method taken as the base object.

The results of quantitative determination of 2-aminothiazole by the proposed and known methods are given in table. 2,

Example 2. Determination of the base of dihydropapaverine ..

In 25 ml volumetric flasks, 7 ml of 0.3 M solution of potassium iodide is added in 2 ml volumes of 15% hydrochloric acid and 1 ml sample of the solution containing dihydropapaverine base in the amount of 6.8; 8.3 and 2.4%. Then, with constant agitation, 7 ml of a 0.15 M solution of bismuth nitrate is gradually added thereto. After a 10 minute run, the precipitates formed are filtered out. For the study of the FILTER-TO .E by photocolorimetry, 1 ml of each filtrate is transferred to the alcohol medium when diluted with ethyl alcohol in a 50 ml volumetric flask. 3 ml of the resulting solution was diluted once more with ethyl alcohol in a 25 ml volumetric flask. Then, photocolorimetry of this solution is carried out to measure the optical density (D) on a photocolorimeter at 344 N in a 10 ml cuvette. Ethyl alcohol is used as a comparison solution.

From the measured value of optical density using the previously constructed calibration graph, the percentage is determined. content of dihydropapaverine base in the model mixture

At the same time, the content of the base of dihydropapaverine is determined by the known method taken as the base object.

The results of the quantitative determination of the base of dihydropapaverine are suggested by LM and are shown in known methods in Table. 3

Example 3 Determination of caffeine.

, In measuring flasks with 25 mi, 7 ml of 0.3 M solution of potassium iodide are placed in each, then one ml of SOLYANOKIS sample is added per ml. Of this solution containing caffeine in an amount of 1-6.0. and 12.5%. / Then, with constant agitation, 7 ml of a 0.15 M solution of bismuth nitrate are also poured in there. After a 10-minute exposure, the precipitates formed are filtered off. To investigate the filtrates by photocolorimeting, 1 ml of each filtrate is transferred into an alcohol medium when diluted with ethyl alcohol in 50 ml volumetric flasks. Then, 5 ml of the solution obtained is further diluted with ethyl alcohol in a 25 MJi volumetric flask, and the solution is photocolorimetric, i.e. The optical density was measured using a FEC-56 photocolorimeter at 344 nm in a 10 ml cuvette. Ethyl alcohol is used as a comparison solution.

From the measured absorbance value, the percentage of caffeine in the model mixture is determined using a pre-built calibration graph.

The results of the quantitative determination of caffeine are given in Table. four.

As can be seen from the sample and table data. 1-4, the proposed method, in comparison with the known, allows to increase the accuracy of the analysis for

by determining only heterocyclic nitrogen-containing bases without other nitrogen-containing groups (error 0.8–1 rel.% instead of 2.0–4.0 6 tons.%).

The use of the proposed method for the quantitative determination of heterocyclic nitrogen-containing bases provides, as compared with the known method, an increase in the accuracy of determination; simplifying the analysis by eliminating the need for labor-intensive operations; reduction of the determination time (from 2 hours to 30 minutes).

Table

6.7

0.27 8.3 0.25 2.3 0.325

Set

Optical density (D) caffeine,%

0.252 0.255 0.340 0.334

8.5

10.0

3.8

Table 4

Found, - caffeine,%

16.1. 15.9 12.3 12.6

Claims (1)

CIIUCOD AND THE DEFINITIONS OF A HETEROCYCLIC NITROGEN CONTAINING BASIS using processing an analyzed sample with solutions of potassium iodide and bismuth nitrate followed by filtration and analysis of the filtrate, which differs from the fact that, in order to simplify the method and increase the analysis accuracy potassium iodide and bismuth nitrate are carried out sequentially and the filtrate analysis is carried out by photocolometry in an alcohol medium.