CN103018368B - Method for determining N-methylamino ammate in production of acesulfame - Google Patents

Abstract

The invention discloses a method for measuring ammonium acetoacetylsulfamate in the production of acesulfame-K. The steps mainly include: (1) selecting and analyzing chromatographic conditions: ODS column (4.6mm×25cm) or other equivalent chromatographic columns, wavelength 250nm, The flow rate is 1ml/min, the column temperature is 25°C, and the injection volume is 20ul; (2) Prepare tetrabutylammonium hydrogensulfate solution with deionized water to a molar concentration of 1.0-2.0mmol/L, and prepare tetrabutylammonium hydrogensulfate Ammonium solution and chromatographic grade methanol are made into a mobile phase at a volume ratio of 60:40; (3) the sample to be tested is diluted to a concentration of 0.5% to 2.0% by volume with an organic solvent to prepare a test solution; (4) use Micro-syringe draws test solution, injects high-performance liquid chromatograph, analyzes with area external standard method; (5) record the content of ammonium acetoacetamide sulfame in the tested sample. The method of the invention can accurately and quickly measure the content of ammonium acetoacetylsulfamate.

Description

Determination method of acetoacetylsulfame ammonium in the production of acesulfame potassium

technical field

The invention relates to a method for determining the intermediate ammonium acetoacetylsulfamate in the production of acesulfame potassium.

Background technique

At present, the production process of the sweetener acesulfame potassium (trade name: acesulfame potassium) is as follows: the first step reaction uses dichloromethane as a solvent to synthesize ammonium acetoacetylsulfame potassium from sulfamic acid, triethylamine and diketene ; The second step of the reaction is to synthesize acesulfame potassium with acetoacetylsulfame ammonium and sulfur trioxide sulfonated ring; finally neutralize acesulfame acid and potassium hydroxide to obtain acesulfame potassium, that is, acesulfame potassium.

U.S. Patent Application Nos. 5011982 and 5103046 mentioned in the patent documents that in the production process of the sweetener acesulfame-K, acetoacetamide ammonium sulfamate is an important intermediate, but only acetoacetamide sulfamate ammonium The structure was characterized by nuclear magnetic resonance, but no method for determining the content of ammonium acetoacetylsulfamate in the reaction solution was established. In the continuous production of acesulfame potassium, the accurate determination of the component content of ammonium acetoacetamide sulfamate can monitor the production reaction ratio, which is of great significance for improving product quality and reducing production costs. Chinese patent application number is 200610085797.5 in the patent literature discloses a kind of method that uses the area normalization method to measure the content of acetoacetylsulfame ammonium, but in practice it is found that the detection chromatographic conditions are not complete, and the area normalization method used cannot accurately measure The specific content, measurement data accuracy is not high.

Contents of the invention

The purpose of the present invention is to provide a method for the determination of ammonium acetoacetylsulfamate in the production of acesulfame-K, which has quick determination process and high accuracy of measurement data.

In order to achieve the above object, the present invention adopts the following technical solutions.

The assay method of acetoacetylsulfame ammonium in the production of acesulfame K comprises the following steps:

(1) Select analytical chromatographic conditions: ODS column (4.6mm×25cm) or other equivalent chromatographic column, wavelength 250nm, flow rate 1ml/min, column temperature 25°C, injection volume 20ul;

(2) Preparation of mobile phase: prepare tetrabutylammonium hydrogensulfate solution with deionized water to a molar concentration of 1.0～2.0mmol/L, prepare tetrabutylammonium hydrogensulfate solution and chromatographic grade methanol by volume ratio of 60:40 to make mobile phase;

(3) Preparation of test solution: take an appropriate amount of the sample to be tested, dilute the sample to be tested by volume ratio to a concentration of 0.5% to 2.0% with an organic solvent, and prepare a test solution;

(4) liquid chromatography analysis: draw test solution with micro syringe, inject high performance liquid chromatography, analyze with area external standard method;

(5) Record the content of ammonium acetoacetylsulfamate in the sample to be tested.

Further, the assay method of ammonium acetoacetamide sulfamate in the aforementioned acesulfame-K production, wherein: before the liquid chromatography analysis, the correction factor of the area external standard method is first established, and a complete analysis method of its area external standard is established; method as follows:

(1) Preparation of standard solution: with anhydrous methanol, ammonium acetoacetamide sulfame is formulated into three kinds of standard solutions of 2mg/ml, 5mg/ml and 10mg/ml by mass/volume concentration;

(2) Establishment of the correction factor: draw the standard product solution with a micro-syringe respectively, inject it into a high-performance liquid chromatograph for analysis respectively, and compare the chromatographic peak area of the standard product solution obtained with the standard product weight contained in the standard product solution After corresponding, three-point calibration is carried out to obtain the correction factor of the area external standard method, thereby establishing a complete area external standard analysis method.

Further, the aforementioned method for assaying ammonium acetoacetamide sulfamate in the production of acesulfame K, wherein: the organic solvent in step (3) is anhydrous methanol.

Further, the aforementioned method for determining ammonium acetoacetamide sulfamate in the production of acesulfame K, wherein: the volume ratio concentration of the test solution in step (3) is 1%.

Further, the aforementioned assay method for ammonium acetoacetamide sulfamate in the production of acesulfame K, wherein: the molar concentration of the tetrabutylammonium bisulfate solution is 1.7mmol/L.

Beneficial effects of the present invention: using the method described in the present invention, the content of ammonium acetoacetamide sulfamate can be accurately and quickly determined in the production process of acesulfame potassium, so that the reaction ratio in the production process can be monitored , to provide a strong basis for improving product quality and reducing production costs.

Detailed ways

The assay method of ammonium acetoacetamide sulfamate in the production of acesulfame potassium of the present invention will be further described below in conjunction with specific examples.

The present invention selects a high-performance liquid chromatograph, adopts suitable liquid chromatographic conditions, and uses a certain mobile phase to analyze the component content of ammonium acetoacetamide sulfamate in the material system. The chromatographic analysis method used in the present invention is the area external standard method, because the liquid chromatograph has different response values to different substances, so in order to accurately reflect the content of the component to be measured for the peak area, it must be based on the known amount The peak area of the component to be measured under the chromatographic conditions is used to calculate the quantitative correction factor. The correction factor in this liquid chromatography area external standard method can be calculated by analyzing the selected standard samples under the same chromatographic conditions.

In the present invention, the assay method of ammonium acetoacetamide sulfamate in the production of described acesulfame K comprises the following steps:

(1) Select analytical chromatographic conditions: ODS column (4.6mm×25cm) or other equivalent chromatographic column, wavelength 250nm, flow rate 1ml/min, column temperature 25°C, injection volume 20ul;

(2) Preparation of mobile phase: prepare tetrabutylammonium hydrogensulfate solution with deionized water to a molar concentration of 1.0～2.0mmol/L, prepare tetrabutylammonium hydrogensulfate solution and chromatographic grade methanol by volume ratio of 60:40 to make mobile phase;

(3) Preparation of the test solution: take an appropriate amount of the sample to be tested, dilute the sample to be tested by volume ratio to a concentration of 0.5% to 2.0% with anhydrous methanol, and prepare a test solution;

(4) liquid chromatography analysis: draw test solution with micro syringe, inject high performance liquid chromatography, analyze with area external standard method;

(5) Record the content of ammonium acetoacetylsulfamate in the sample to be tested.

In actual operation, before the liquid chromatography analysis, the correction factor of the area external standard method is established first, and a complete analysis method of the area external standard method is established. The method is as follows:

(1) Preparation of ammonium acetoacetamide sulfamate standard sample: the preparation method of ammonium acetoacetamide sulfamate disclosed in the patent documents of U.S. Patent Application No. 5011982 and 5103046 prepares the ammonium acetoacetamide sulfamate sample, and the The prepared samples were recrystallized three times to obtain standard samples.

(2) Preparation of standard solution: After accurately weighing the above-mentioned standard sample (accurate to 0.0002g), use anhydrous methanol to prepare the standard sample into three solutions of 2mg/ml, 5mg/ml and 10mg/ml according to the mass/volume concentration. Kind of standard solution;

(3) The establishment of the correction factor: draw the standard product solution respectively with a micro-syringe, inject the high-performance liquid chromatograph with the mobile phase as the liquid phase respectively for analysis, and compare the chromatographic peak area of the standard product solution obtained with the standard product solution After corresponding to the weight of the standard contained in the three-point correction, the correction factor of the area external standard method is obtained, so as to establish a complete area external standard analysis method.

Since the method steps of each embodiment are the same, the relevant process conditions and measurement results thereof in each embodiment are listed below in tabular form, see Table 1.

Table 1

As can be seen from the above table, under the selected chromatographic analysis conditions, samples of different concentrations are analyzed, and relevant data can be obtained, and when the concentration of the test solution is 1%, and the concentration of tetrabutylammonium bisulfate solution is at 1.7mmol/L for the best. Because the concentration of the test solution is too high or too low, it is easy to exceed the standard range of the calibration curve, resulting in a large error, and from the results of the analysis, when the concentration of tetrabutylammonium bisulfate solution is 1.0mmol/L and 2.0mmol/L None of the mobile phases prepared at 1.7mmol/L had the best separation effect.

Claims (4)

1. the assay method of acetyl acetamide ammonium sulfamate in acesulfame potassium production, comprises the following steps:

(1) the ODS post of Analysis on Selecting chromatographic condition: 4.6mm × 25cm, wavelength 250nm, flow velocity 1ml/min, 25 DEG C of column temperatures, sample size 20 μ l;

(2) preparation of mobile phase: with deionized water preparation 4-butyl ammonium hydrogen sulfate solution to volumetric molar concentration be 1.0～2.0mmol/L, by the 4-butyl ammonium hydrogen sulfate solution preparing and hplc grade methanol by volume for 60:40 makes mobile phase;

(3) preparation of test solution: get testing sample appropriate, with organic solvent, testing sample being diluted to concentration is by volume 0.5%～2.0%, is made into test solution;

(4) liquid-phase chromatographic analysis: draw test solution with micro syringe, inject high performance liquid chromatograph, analyze by area external standard method;

(5) content of the record acetyl acetamide ammonium sulfamate in testing sample of surveying;

Wherein, before liquid-phase chromatographic analysis, first set up the correction factor of area external standard method, establish its complete area external standard analytical approach; Method is as follows:

(1) preparation of standard solution: three kinds of mark product solution that with absolute methanol, acetyl acetamide ammonium sulfamate are mixed with to 2mg/ml, 5 mg/ml and 10 mg/ ml by mass/volume concentration;

(2) foundation of correction factor: draw respectively mark product solution with micro syringe, inject respectively high performance liquid chromatograph analysis, after the chromatographic peak area of obtained mark product solution is corresponding with mark product weight contained in this mark product solution, carry out three point calibrations, obtain the correction factor of this area external standard method, thereby establish a complete area external standard analytical approach.

2. the assay method of acetyl acetamide ammonium sulfamate in acesulfame potassium production according to claim 1, is characterized in that: the organic solvent in step (three) is absolute methanol.

3. the assay method of acetyl acetamide ammonium sulfamate in acesulfame potassium production according to claim 1 and 2, is characterized in that: the test solution volume by volume concentration in step (three) is 1%.

4. the assay method of acetyl acetamide ammonium sulfamate in acesulfame potassium production according to claim 1 and 2, is characterized in that: the volumetric molar concentration of 4-butyl ammonium hydrogen sulfate solution is 1.7mmol/L.