CN113406229B

CN113406229B - Method for judging phenoxy cyclophosphazene synthesis reaction end point

Info

Publication number: CN113406229B
Application number: CN202110671668.9A
Authority: CN
Inventors: 宋传君; 索伟; 冯菲菲; 孟令健; 王艳辉; 徐有敏; 段金凤; 刘婷
Original assignee: Shandong Taixing New Materials Co ltd
Current assignee: Shandong Taixing New Materials Co ltd
Priority date: 2021-06-17
Filing date: 2021-06-17
Publication date: 2022-11-29
Anticipated expiration: 2041-06-17
Also published as: CN113406229A

Abstract

The invention discloses a method for judging the end point of a phenoxyl cyclophosphazene synthesis reaction. The synthetic phenoxy cyclophosphazene reaction solution is added into a mobile phase (acetonitrile: methanol-water (1) = 4): 1) to be constant in volume and then directly introduced into a chromatographic column, and the mixture is subjected to gradient elution and ultraviolet detector detection, and then the ratio of a reaction intermediate to a target product is analyzed by adopting a liquid chromatography area normalization method, so that the reaction endpoint can be effectively judged. The method can directly use the reaction solution for detection, and under the detection conditions provided by the invention, the phenoxy cyclophosphazene, the intermediate and impurities are well separated, and the peak emergence time is proper. Proved by methodology, the method has the advantages of strong specificity, high accuracy, high sensitivity and good stability.

Description

Method for judging phenoxy cyclophosphazene synthesis reaction end point

Technical Field

The invention belongs to the field of analytical chemistry, and particularly relates to a method for judging an end point of a phenoxy cyclophosphazene synthesis reaction.

Background

The phenoxy cyclophosphazene is a halogen-free flame retardant, has a unique P and N hybrid structure, shows the characteristics of high thermal stability, flame retardance, high Limiting Oxygen Index (LOI), low smoke release performance and the like, belongs to an additive type halogen-free flame retardant, is widely used for epoxy resin, copper-clad plates, LED (light-emitting diode) light-emitting diodes, powder coatings, encapsulating materials and high polymer materials, and is an excellent fireproof flame retardant material and a self-extinguishing material.

At present, phenoxycyclophosphazenes are generally prepared by substitution reaction of potassium or sodium phenolate (prepared by phenol with sodium or potassium hydroxide) and chlorocyclophosphazenes, and according to the substitution reaction analysis: each phosphorus on the phosphorus-nitrogen ring is connected with two chloride ions, in the process of substituting chlorine by phenoxy, stepwise substitution is carried out due to steric hindrance, one chlorine is substituted first, then the second chlorine is substituted, the reaction end point takes the end point that all the chlorine on the chlorocyclophosphazene is substituted by phenoxy completely, the target product phenoxy cyclophosphazene is a mixture containing tetramer, trimer, dimer and linearity, and the trimer (hexaphenoxy cyclotriphosphazene) is taken as the main component. The reaction solvent at the end of the synthesis reaction is chlorobenzene, and the concentration of phenoxy cyclophosphazene in the reaction solution is about 25%. In the actual production, the end point of the synthetic reaction of the phenoxy cyclophosphazene needs to be judged, so that the low purity (high chlorine content) caused by incomplete reaction is avoided, and the increase of byproducts and the reduction of the production efficiency caused by excessive reaction are also avoided. Phenoxy cyclic phosphazene needs to detect many times in the synthetic reaction process, and the detection of early stage mainly detects through the residual quantity of raw materials potassium phenolate (sodium phenolate) and chlorocyclophosphazene, and when the reaction endpoint is approached, the raw materials are basically consumed up, and the main impurities in its reaction liquid are: the intermediate which is not completely reacted, namely the cyclic phosphazene containing phenoxy and chlorine and not completely substituted by phenoxy in the reaction process (because of more substituent groups, a certain time is needed for sufficient reaction), is mainly chloropentaphenoxy cyclotriphosphazene as the intermediate when the reaction end point is approached by research and analysis.

In the prior art, the detection of phenoxy cyclophosphazene is carried out on finished products of the phenoxy cyclophosphazene. If the end point of the reaction is judged by adopting a finished product, the finished product is obtained by carrying out post-treatment, concentration and drying on a phenoxy cyclophosphazene sample, and then the finished product is detected by adopting methods such as Fourier transform infrared spectroscopy, nuclear magnetic resonance, X-ray diffraction analysis, mass spectrum, thermogravimetric analysis, differential scanning calorimetry analysis, high-efficiency liquid phase and the like.

Compared with the detection of a phenoxy cyclophosphazene finished product, the detection of the phenoxy cyclophosphazene reaction liquid has the following difficulties: the reaction solution contains more compounds (the product is a more complex mixture), and the traditional method can not effectively identify the change process of the chlorine in the phenoxy substituted chloro-cyclophosphazene in the production process, whether the reaction is sufficient and the proportion of the intermediate and the target product at the reaction end point. In view of this, the invention provides a method for determining an end point of a phenoxy cyclophosphazene synthesis reaction, which directly adopts a reaction solution for detection, and solves the problem of determining the end point of the phenoxy cyclophosphazene synthesis reaction.

Disclosure of Invention

Aiming at the problems, the invention provides a method for judging the end point of the synthesis reaction of phenoxy cyclophosphazene.

The technical scheme of the invention is as follows: a method for judging the end point of phenoxyl cyclophosphazene synthesis reaction is characterized in that,

(1) Adding phenoxy cyclophosphazene synthesis reaction solution into a mobile phase (acetonitrile: methanol-water (1) = 4) for constant volume, filtering to obtain a solution to be detected, taking acetonitrile as an A phase of the mobile phase and a mixed system of methanol and water as a B phase of the mobile phase, performing gradient elution, and detecting by using a liquid chromatograph to obtain a chromatographic peak area;

(2) Obtaining the concentration (peak area) ratio of an intermediate and a target product (hexaphenoxycyclotriphosphazene) in the liquid to be tested by adopting a liquid chromatography area normalization method; if the concentration of the intermediate is less than or equal to 1 percent, the reaction is complete.

The liquid chromatography conditions were as follows:

a chromatographic column: C18-WR (5. Mu.L, 4.6X 150 mm);

mobile phase: phase a-acetonitrile; phase B-methanol + water (1;

initial flow rate: 0.75mL/min;

detection wavelength: 200 nm-220 nm;

gradient elution is adopted, and the initial proportion of phase B is 15-25%; the gradient elution procedure is shown in table 1;

column temperature: 25-30 ℃;

sample injection volume: 10-20 mul;

sample introduction concentration (calculated by phenoxy cyclophosphazene synthesis reaction solution): 0.69 mg/mL-5.00 mg/mL.

TABLE 1 gradient elution time program

Serial number	Time(min)	Value (B phase)
			1	0.01	15～25
2	10.00	15～25
			3	10.01	5～10
4	30.00	5～10
			5	30.01	15～25
6	35.00	15～25
			7	35.01

Further, the sample solution is filtered by a 0.45 μm organic filter membrane; and filtering the mobile phase of the liquid chromatograph by a 0.45-micrometer organic filter membrane, and then carrying out ultrasonic treatment for 30-40 min.

Preferably, the detection wavelength is 210nm, the column temperature is 27 ℃, and the injection volume is 20 μ L.

Preferably, the injection concentration is 1mg/mL.

The invention has the beneficial effects that:

1. because the components in the reaction solution are relatively complex, the invention selects a chromatographic column and designs a mobile phase according to the characteristics of the reaction solvent, the target product (mixture) and the intermediate, and as can be seen from FIGS. 1-2: by adopting the chromatographic column and the flow combined gradient elution, the intermediate peak and the target product peak can be well distinguished. On the other hand, the reaction solution has byproduct salts, and the addition of water in the mobile phase is beneficial to enabling the salts to flow out of the chromatographic column and protecting the chromatographic column.

2. The method can directly use the reaction solution for detection, and under the detection conditions provided by the invention, the phenoxy cyclophosphazene, the intermediate and the impurities are well separated, and the peak emergence time is appropriate (as shown in figures 1-2).

3. Proved by methodology, the method has the advantages of strong specificity, high accuracy, high sensitivity and good stability.

Therefore, the method provided by the invention can better realize the monitoring of the end point of the synthetic reaction of phenoxy cyclophosphazene, and is beneficial to guiding the synthesis of materials in the production process to obtain the high-quality phenoxy cyclophosphazene.

Drawings

FIG. 1 is an HPLC chromatogram of incomplete reaction in the synthesis process of a phenoxy cyclophosphazene reaction solution provided by the invention;

FIG. 2 is an HPLC chromatogram of the reaction end point of the phenoxyl cyclophosphazene synthesis reaction solution provided by the invention.

Detailed Description

The effect is illustrated below with reference to the examples, wherein phenoxycyclophosphazene is produced by santalin new materials limited.

Example 1: phenoxy cyclophosphazene synthesis reaction end point determination test

1 instruments and materials

1.1 Instrument: a high performance liquid chromatograph (gradient elution setting can be performed);

1.2 reagent: acetonitrile and methanol are both in chromatographic grade, and water is ultrapure water.

2 methods and results

2.1 high performance liquid chromatography conditions:

a chromatographic column: C18-WR (5. Mu.L, 4.6X 150 mm);

mobile phase: phase a-acetonitrile; phase B-methanol + water (1; gradient elution is adopted, and the initial proportion of B phase is 20%; the gradient elution time program is shown in table 2; filtering a mobile phase of a chromatograph by a 0.45-micron organic filter membrane, and then carrying out ultrasonic treatment for 30-40 min;

a detector: an ultraviolet detector;

detection wavelength: 210nm;

column temperature: 27 ℃;

sample introduction volume: 20 mu L of the solution;

sample introduction concentration: 1mg/mL.

TABLE 2 gradient elution time program

Serial number	Time(min)	Module	Command	Value (B phase)
					1	0.01	Pump	B.Conc		20
2	10.00	Pump and method of operating the same	B.Conc								20
					3	10.01	Pump	B.Conc	8
4	30.00	Pump and method of operating the same	B.Conc	8
					5	30.01	Pump and method of operating the same	B.Conc		20
6	35.00	Pump	B.Conc	20
					7	35.01	Controller	Stop

2.2 sample solution preparation

The phenoxycyclophosphazene reaction solution (incomplete reaction and reaction end point) is accurately weighed, 10mg of the phenoxycyclophosphazene reaction solution is placed in a 10mL volumetric flask, and an appropriate amount of mobile phase (acetonitrile: methanol-water (1) = 4). Shaking up. This solution was used as a sample solution.

2.3 detection

Precisely measuring 2.2 sample solution, performing HPLC detection according to 2.1 chromatographic conditions, and recording chromatogram. The results are shown in FIGS. 1-2. As can be seen from fig. 1-2, the phenoxy cyclotriphosphazene reaction solution has good peak shape, good separation degree between the components (chlorobenzene, intermediate, hexaphenoxy cyclotriphosphazene (trimer), tetramer, dimer and line), and good separation between the target product (hexaphenoxy cyclotriphosphazene) and the intermediate (the intermediate is mainly chloropentaphenoxy cyclotriphosphazene at the end of the reaction), as shown in fig. 1, the retention time RT of the intermediate is 9.312min, and the RT of the target product is 10.067min. Therefore, the method is highly specific.

Meanwhile, as can be seen from fig. 1-2: the concentration of the intermediate of fig. 2 (reaction complete) is significantly reduced compared to fig. 1 (reaction incomplete), demonstrating the reliability of the process.

3 validation of analytical methods

3.1 precision

Phenoxy cyclophosphazene reaction solution samples: 210316, available from Shandong Taixing New Material Co., ltd;

preparing a sample solution: accurately weighing 10.2mg of phenoxy cyclophosphazene reaction solution into a 10mL volumetric flask, adding a proper amount of mobile phase for dissolving and diluting to a scale, filtering with a 0.45 mu m organic filter membrane, and shaking up. The concentration of this sample solution was 1.02mg/mL, and this was used as a sample solution. The same sample was repeated 6 times, HPLC detection was performed under 2.1 chromatographic conditions, the chromatographic peak area was recorded, and the ratio of the reaction intermediate to the target product was analyzed by liquid chromatographic area normalization, with the results shown in Table 3.

TABLE 3 results of precision test

Number of	Concentration of intermediate (peak area)%	Target product concentration (peak area)%
			1	3.671	96.329
2	3.668	96.332
			3	3.681	96.319
4	3.665	96.335
			5	3.672	96.328
6	3.659	96.341
			Average concentration (peak area)%	3.669	96.331
RSD(％)	0.18	0.01

As can be seen from Table 3, the RSD% of each component concentration of 6 times of repeated entering of the same sample is 0.18% and 0.01%, the requirement that the RSD% is less than 2% is met, the explanation precision is good, and the test feasibility is high.

3.2 repeatability test

Phenoxy cyclophosphazene reaction solution samples: 210419, produced by Shandong Taxing New materials, inc.

Preparing a sample solution: 6 parts (10.5mg, 10.6mg,10.0mg,10.3mg,10.5mg and 10.2mg) of the same phenoxyl cyclophosphazene reaction solution sample are accurately weighed into a 10mL volumetric flask, an appropriate amount of mobile phase is added for dissolution and dilution to the scale, and an organic filter membrane with the diameter of 0.45 mu m is shaken up. Phenoxy cyclophosphazene reaction solutions with different concentrations are obtained to be used as test solutions. HPLC detection was performed under the chromatographic conditions of 2.1, the chromatographic peak area was recorded, and the ratio of the reaction intermediate to the target product was analyzed by liquid chromatographic area normalization, with the results shown in Table 4.

TABLE 4 results of the repeatability tests

Numbering	Concentration (peak area) of intermediate	Target product concentration (peak area)%
			1	0.891	99.109
2	0.882	99.118
			3	0.884	99.116
4	0.892	99.108
			5	0.896	99.104
6	0.881	99.119
			Average concentration (peak area)%	0.888	99.112
RSD(％)	0.63	0.01

As can be seen from table 4, the average concentration ratio of intermediates to target product in the synthesis reaction solution was 0.888:99.112, calculated RSD of 0.63% and 0.01%, respectively, the reproducibility was good.

3.3 detection and quantitation limits

Phenoxy cyclophosphazene reaction solution samples: 210315, a new material from Shandong Taxing, inc.;

preparing a sample solution: accurately weighing 10.5mg of phenoxy cyclophosphazene reaction solution into a 10mL volumetric flask, adding a proper amount of mobile phase for dissolving and diluting to a scale, and shaking up. The sample solution had a concentration of 1.05mg/mL and was used as a test solution. HPLC detection was performed according to chromatographic conditions of 2.1, S/N =15.25 for the target product tested. The detection limit concentration of the sample solution is approximately equal to 0.21mg/mL according to the detection limit S/N = 3; the quantitative limit concentration of the sample solution ≈ 0.69mg/mL can be obtained with respect to the quantitative limit S/N = 10.

Claims

1. A method for judging the end point of phenoxyl cyclophosphazene synthesis reaction is characterized in that,

(1) Adding phenoxy cyclophosphazene synthesis reaction solution into a mobile phase for constant volume, filtering to obtain a solution to be detected, taking acetonitrile as an A phase of the mobile phase and a mixed system of methanol and water as a B phase of the mobile phase, performing gradient elution, and detecting by using a liquid chromatograph to obtain a chromatographic peak area;

(2) Obtaining the concentration ratio of the intermediate to the target product in the solution to be detected by adopting a liquid chromatography area normalization method; if the concentration of the intermediate is less than or equal to 1 percent, the reaction is complete;

the phenoxy cyclotriphosphazene synthesis reaction solution contains chlorobenzene, an intermediate, a trimer, a tetramer, a dimer and a linear body, wherein the trimer is hexaphenoxy cyclotriphosphazene; at the end of the reaction, the intermediate takes chloropentaphenoxy cyclotriphosphazene as the main component;

wherein the chromatographic column is a C18-WR chromatographic column, and the mobile phase: phase a-acetonitrile; phase B-methanol + water, methanol and water volume ratio 1, gradient elution procedure as follows:

serial number Time/min B phase/%) 1 0.01 15～25 2 10.00 15～25 3 10.01 5～10 4 30.00 5～10 5 30.01 15～25 6 35.00 15～25

；

The mobile phase for constant volume is as follows: acetonitrile according to volume ratio: methanol-water = 4; wherein the volume ratio of methanol to water is 1:1;

wherein, the liquid phase chromatographic conditions are as follows:

detection wavelength: 200 nm-220 nm;

column temperature: 25-30 ℃;

sample introduction volume: 10-20 mul;

initial flow rate: 0.75mL/min;

sample introduction concentration is calculated by phenoxy cyclophosphazene synthesis reaction solution: 0.69 mg/mL-5.00 mg/mL.

2. The method for determining the endpoint of a phenoxy cyclophosphazene synthesis reaction according to claim 1, wherein the detection wavelength is 210nm, the column temperature is 27 ℃, and the injection volume is 20 μ L.

3. The method for determining the endpoint of a phenoxycyclophosphazene synthesis reaction according to claim 1, wherein the sample injection concentration is 1mg/mL.

4. The method for determining the end point of a phenoxy cyclophosphazene synthesis reaction according to claim 1, wherein the gradient elution is:

serial number Time(min) B phase/%) 1 0.01 20 2 10.00 20 3 10.01 8 4 30.00 8 5 30.01 20 6 35.00 20

。

5. The method for determining the endpoint of a phenoxycyclophosphazene synthesis reaction according to any one of claims 1 to 4, wherein the solution to be tested is filtered through a 0.45 μm organic filter membrane.

6. The method for determining the end point of a phenoxy cyclophosphazene synthesis reaction according to any one of claims 1 to 4, wherein the mobile phase of the liquid chromatograph is subjected to ultrasonic treatment for 30 to 40min after being filtered by a 0.45 μm organic filter membrane.