A method for detecting di(2-chloroethyl)amine hydrochloride
By using sodium hydroxide to ionize di(2-chloroethyl)amine hydrochloride and combining it with gas chromatography and a flame ionization detector, the problems of cumbersome and poor repeatability in the detection of amine hydrochlorides in the prior art are solved, and rapid, simple and efficient purity detection of di(2-chloroethyl)amine hydrochloride is achieved.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- JINAN GUODING PHARM TECH CO LTD
- Filing Date
- 2026-03-04
- Publication Date
- 2026-05-29
Smart Images
Figure CN122109370A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of detection methods, specifically to a detection method for di(2-chloroethyl)amine hydrochloride. Background Technology
[0002] Di(2-chloroethyl)amine hydrochloride is an important organic amine hydrochloride compound, frequently used as a coupling reagent or functional intermediate in organic synthesis reactions during laboratory research and the synthesis of pharmaceutical intermediates. Due to the presence of reactive groups such as chloroalkyl and amine groups in its molecular structure, it exhibits high reactivity in subsequent reactions. Its purity directly affects product quality and the stability of downstream processes; therefore, accurate and reliable purity detection is crucial. However, di(2-chloroethyl)amine hydrochloride is a high-boiling-point amine hydrochloride compound with no UV absorption, making high-performance liquid chromatography (HPLC) and gas chromatography methods based on UV detectors difficult to apply directly. Existing HPLC methods for amine hydrochloride detection mostly employ evaporative light detectors, but these methods suffer from cumbersome procedures, poor repeatability, and insufficient versatility, failing to meet the requirements for rapid, accurate, and reproducible quality control of di(2-chloroethyl)amine hydrochloride in industrial production processes.
[0003] Therefore, developing an efficient and simple method for detecting the purity of di(2-chloroethyl)amine hydrochloride is of great application value for practical production. Summary of the Invention
[0004] In view of the shortcomings of the existing technology, the purpose of this invention is to provide a method for detecting di(2-chloroethyl)amine hydrochloride.
[0005] A method for detecting di(2-chloroethyl)amine hydrochloride, comprising the following steps: (1) Di(2-chloroethyl)amine hydrochloride was freed in deionized water using an alkali to form di(2-chloroethyl)amine, and then extracted with an organic solvent to obtain the test sample; (2) The purity of the sample to be tested was determined by gas chromatography. The chromatographic conditions were as follows: the injection port temperature was 200-250℃, the initial temperature of the chromatographic column was 40-50℃, and it was maintained for 1-3 min; then the temperature was increased to 200-250℃ at a rate of 30-40℃ / min and maintained for 3-5 min; the detector temperature was 240-300℃.
[0006] In step (1), the alkali is sodium hydroxide.
[0007] In step (1), the organic solvent is ethyl acetate.
[0008] In step (1), the concentration of the sample to be tested is 115-160 mg / mL.
[0009] In step (2), the chromatographic column is a medium polarity chromatographic column.
[0010] In step (2), the carrier gas used is nitrogen.
[0011] The flow rate of the carrier gas is 0.7-1.2 mL / min.
[0012] In step (2), the air flow rate is 380-420 mL / min.
[0013] In step (2), the flow rate of hydrogen gas used is 38-42 mL / min.
[0014] In step (2), the detector used is a hydrogen flame ionization detector.
[0015] Due to the adoption of the above technical solutions, the beneficial effects of the present invention include: (1) The present invention converts di(2-chloroethyl)amine hydrochloride, which has a high boiling point and is difficult to be directly analyzed by gas chromatography, into di(2-chloroethyl)amine with a relatively low boiling point by using sodium hydroxide and extracting with organic solvents to avoid introducing additional impurities, thereby achieving indirect and accurate detection of the purity of di(2-chloroethyl)amine hydrochloride.
[0016] (2) The detection method of the present invention has simple steps, short analysis time, and is suitable for medium polarity chromatographic columns. It does not require derivatization or special detectors and is suitable for laboratory analysis and quality control in industrial production processes. It has the effects of being fast, simple, efficient and practical. Attached Figure Description
[0017] Figure 1 The image shows a gas chromatogram of the purity of di(2-chloroethyl)amine hydrochloride as determined in Example 1.
[0018] Figure 2 The image shows a gas chromatogram of the purity of di(2-chloroethyl)amine hydrochloride as determined in Example 2.
[0019] Figure 3 The image shows a gas chromatogram of the purity of di(2-chloroethyl)amine hydrochloride as detected in Example 3.
[0020] Figure 4 The image shows a gas chromatogram of the purity of di(2-chloroethyl)amine hydrochloride as determined in Comparative Example 1. Detailed Implementation
[0021] Example 1: Detection method for di(2-chloroethyl)amine hydrochloride (1) Add 25ml of deionized water and 1g of di(2-chloroethyl)amine hydrochloride to a beaker, sonicate (50Hz) for 5min, add 0.5g of sodium hydroxide and continue sonicating for 5min, add 6ml of ethyl acetate, shake for 2min, separate the contents, and obtain the test sample with a concentration of 132mg / mL. The preparation method of the blank solution is basically the same as that of the test sample, except that di(2-chloroethyl)amine hydrochloride is not added to the components. (2) Chromatographic conditions were set as follows: the gas chromatographic column was an HT-1301 capillary column (medium polarity column, 30m×0.32mm×0.25μm); the injection volume was 1μL; the detector was a flame ionization (FID) detector; nitrogen was used as the carrier gas at a flow rate of 1.0mL / min; the air flow rate was 420mL / min; the hydrogen flow rate was 40mL / min; the injection port temperature was 200℃; the detector temperature was 240℃; the injection port split ratio was 50:1; the column temperature program was as follows: the initial temperature was 40℃, maintained for 3min; then the temperature was increased to 200℃ at a rate of 30℃ / min, maintained for 5min; the detector temperature was 240℃. (3) Inject the blank solution and the test sample according to the above chromatographic conditions and record the chromatogram.
[0022] Depend on Figure 1 It can be seen that the retention time of di(2-chloroethyl)amine hydrochloride is 6.191 min (half-width at half maximum, 4.096 s), and the resolution with the adjacent impurity peak (6.702 min, half-width at half maximum, 2.026 s) is 5.9, which fully meets the baseline separation requirements (baseline separation requires a resolution ≥ 1.5). The total spectral running time is short, the main peak elution time is moderate, and the peak shape is good, making it suitable for the detection of the purity of di(2-chloroethyl)amine hydrochloride. The resolution is calculated using the following formula:
[0023] Where t1 and t2 are the retention times of di(2-chloroethyl)amine hydrochloride and the adjacent impurity peak, respectively; W1 and W2 are the baseline peak widths of di(2-chloroethyl)amine hydrochloride and the adjacent impurity peak, respectively.
[0024] Example 2: Detection method for di(2-chloroethyl)amine hydrochloride (1) Add 25ml of deionized water and 1g of di(2-chloroethyl)amine hydrochloride to a beaker, sonicate (50Hz) for 5min, add 0.5g of sodium hydroxide and continue sonicating for 5min, add 5ml of ethyl acetate, shake for 2min, separate the liquids, and obtain the test sample with a concentration of 159mg / mL. The preparation method of the blank solution is basically the same as that of the test sample, except that di(2-chloroethyl)amine hydrochloride is not added to the components. (2) Chromatographic conditions were set as follows: the gas chromatographic column was an HT-1301 capillary column (medium polarity column, 30m×0.32mm×0.25μm); the injection volume was 1μL; the detector was a flame ionization detector; nitrogen was used as the carrier gas at a flow rate of 0.7mL / min; the air flow rate was 400mL / min; the hydrogen flow rate was 38mL / min; the injection port temperature was 230℃; the detector temperature was 260℃; the injection port split ratio was 50:1; the column temperature program was as follows: the initial temperature was 45℃, maintained for 2min; then the temperature was increased to 230℃ at a rate of 35℃ / min, maintained for 4min; the detector temperature was 260℃. (3) Inject the blank solution and the test sample according to the above chromatographic conditions.
[0025] Example 3: Detection method for di(2-chloroethyl)amine hydrochloride (1) Add 25ml of deionized water and 1g of di(2-chloroethyl)amine hydrochloride to a beaker, sonicate (50Hz) for 5min, add 0.5g of sodium hydroxide and continue sonicating for 5min, add 7ml of ethyl acetate, shake for 2min, separate the contents, and obtain the test sample with a concentration of 115mg / mL. The preparation method of the blank solution is basically the same as that of the test sample, except that di(2-chloroethyl)amine hydrochloride is not added to the components. (2) Chromatographic conditions were set as follows: the gas chromatographic column was an HT-1301 capillary column (medium polarity column, 30m×0.32mm×0.25μm); the injection volume was 1μL; the detector was a flame ionization detector; nitrogen was used as the carrier gas at a flow rate of 1.2mL / min; the air flow rate was 380mL / min; the hydrogen flow rate was 42mL / min; the injection port temperature was 250℃; the detector temperature was 300℃; the injection port split ratio was 50:1; the column temperature program was as follows: the initial temperature was 50℃, maintained for 1min; then the temperature was increased to 250℃ at a rate of 40℃ / min, maintained for 3min; the detector temperature was 300℃. (3) Inject the blank solution and the test sample according to the above chromatographic conditions.
[0026] Depend on Figures 1-3 It can be seen that the retention time and peak area of the target peak in the test of di(2-chloroethyl)amine hydrochloride are highly consistent, indicating that the detection method has good repeatability and high analytical stability and reliability.
[0027] Comparative Example 1 The detection method for di(2-chloroethyl)amine hydrochloride is basically the same as that in Example 1, except that sodium hydroxide in step (1) is replaced with 1.26 g of triethylamine. Figure 4 It can be seen that an additional impurity peak appeared at the retention time of 3.013 min. The reason is that when triethylamine was used to ionize di(2-chloroethyl)amine hydrochloride, the excess triethylamine partially dissolved into the organic phase during the extraction and separation process, thus forming an additional peak in the gas chromatography analysis, which interfered with the qualitative and quantitative analysis of impurities.
[0028] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. However, any modifications, alterations, and variations made by those skilled in the art without departing from the scope of the present invention based on the disclosed technical content are equivalent embodiments of the present invention. Furthermore, any modifications, alterations, and variations made to the above embodiments based on the essential technology of the present invention are still within the protection scope of the present invention.
Claims
1. A method for detecting di(2-chloroethyl)amine hydrochloride, characterized in that, Includes the following steps: (1) Di(2-chloroethyl)amine hydrochloride was freed in deionized water using an alkali to form di(2-chloroethyl)amine, and then extracted with an organic solvent to obtain the test sample; (2) The purity of the sample to be tested was determined by gas chromatography. The chromatographic conditions were as follows: the injection port temperature was 200-250℃, the initial temperature of the chromatographic column was 40-50℃, and it was maintained for 1-3 min; then the temperature was increased to 200-250℃ at a rate of 30-40℃ / min and maintained for 3-5 min; the detector temperature was 240-300℃.
2. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (1), the alkali is sodium hydroxide.
3. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (1), the organic solvent is ethyl acetate.
4. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (1), the concentration of the sample to be tested is 115-160 mg / mL.
5. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (2), the chromatographic column is a medium polarity chromatographic column.
6. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (2), the carrier gas used is nitrogen.
7. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 6, characterized in that, The flow rate of the carrier gas is 0.7-1.2 mL / min.
8. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (2), the air flow rate is 380-420 mL / min.
9. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (2), the flow rate of hydrogen gas used is 38-42 mL / min.
10. The method for detecting di(2-chloroethyl)amine hydrochloride according to claim 1, characterized in that, In step (2), the detector used is a hydrogen flame ionization detector.