Method for judging phenoxy cyclophosphazene synthesis reaction end point
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.
2. The method for determining the endpoint of a phenoxycyclophosphazene synthesis reaction according to claim 1, 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 1:1, gradient elution procedure as follows:
；
The mobile phase for constant volume is as follows: acetonitrile according to volume ratio: methanol-water ═ 4: 1; wherein the volume ratio of methanol to water is 1: 1.
3. the method for determining an end point of a phenoxycyclophosphazene synthesis reaction according to claim 2,
the liquid chromatography conditions were as follows:
detection wavelength: 200 nm-220 nm;
column temperature: 25-30 ℃;
sample introduction volume: 10-20 mul;
initial flow rate: 0.75 mL/min;
sample introduction concentration is calculated by phenoxy cyclophosphazene synthesis reaction solution: 0.69 mg/mL-5.00 mg/mL.
4. The method for determining the endpoint of a synthesis reaction of phenoxycyclophosphazene according to claim 3, wherein the detection wavelength is 210nm, the column temperature is 27 ℃, and the injection volume is 20 μ L.
5. The method for determining the endpoint of a phenoxycyclophosphazene synthesis reaction of claim 3, wherein the injection concentration is 1 mg/mL.
6. The method for determining the end point of a phenoxy cyclophosphazene synthesis reaction according to claim 2, wherein the gradient elution is:
。
7. The method for determining the endpoint of a phenoxycyclophosphazene synthesis reaction according to any one of claims 1 to 6, wherein the solution to be tested is filtered through a 0.45 μm organic filter membrane.
8. The method for determining the end point of the synthesis reaction of phenoxyl cyclophosphazene as claimed in any one of claims 1 to 6, wherein the mobile phase of the liquid chromatograph is filtered by an organic filter membrane of 0.45 μm and then is subjected to ultrasonic treatment for 30-40 min.
Background
The phenoxy cyclophosphazene is a halogen-free flame retardant, has a unique P, 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 laminate, LED (light emitting diode) light emitting diode, powder coating, encapsulating material and high polymer material, and is an excellent fireproof flame retardant material and self-extinguishing material.
At present, phenoxycyclophosphazenes are generally prepared by a substitution reaction of potassium or sodium phenolate (prepared by reacting phenol with sodium or potassium hydroxide) and chlorocyclophosphazene, 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 firstly substituted, 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 the 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 many times to detect in synthetic reaction process, and the detection of earlier stage mainly detects through the residual amount of raw materials potassium phenolate (sodium phenolate) and chloro cyclic phosphazene, and when being close to the reaction terminal point, the raw materials consume almost totally, and main impurity in its reaction liquid is: 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 thereof. 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 the above, 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 a phenoxy cyclophosphazene synthesis reaction solution into a mobile phase (acetonitrile: methanol-water (1:1) ═ 4:1) 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: 1);
initial flow rate: 0.75 mL/min;
detection wavelength: 200 nm-220 nm;
gradient elution is adopted, and the initial proportion of the phase B is 15-25%; the gradient elution procedure is shown in table 1;
column temperature: 25-30 ℃;
sample introduction 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 using 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 muL.
Preferably, the injection concentration is 1 mg/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 invention can directly use the reaction solution for detection, and under the detection condition provided by the invention, the phenoxy cyclophosphazene, the intermediate and each impurity are well separated, and the peak emergence time is proper (as shown in figure 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 Shandong New materials Ltd.
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: 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 using a 0.45-micrometer organic filter membrane, and then carrying out ultrasonic treatment for 30-40 min;
a detector: an ultraviolet detector;
detection wavelength: 210 nm;
column temperature: 27 ℃;
sample introduction volume: 20 mu L of the solution;
sample introduction concentration: 1 mg/mL.
TABLE 2 gradient elution time program
Serial number
Time(min)
Module
Command
Value (B phase)
1
0.01
Pump and method of operating the same
B.Conc
20
2
10.00
Pump and method of operating the same
B.Conc
20
3
10.01
Pump and method of operating the same
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 and method of operating the same
B.Conc
20
7
35.01
Controller
Stop
2.2 sample solution preparation
The phenoxycyclophosphazene reaction solutions (incomplete reaction and reaction end point) are accurately weighed, 10mg of each phenoxycyclophosphazene reaction solution is placed in a 10mL volumetric flask, an appropriate amount of mobile phase (acetonitrile: methanol-water (1:1) ═ 4:1) is added to dissolve and dilute to the mark, and the solution is filtered through a 0.45 mu m organic filter membrane. 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 FIGS. 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 10.067 min. 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, produced by Shandong Taxing New Material Co., Ltd;
preparing a sample solution: accurately weighing 10.2mg of phenoxy cyclophosphazene reaction solution in 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, which was regarded 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
Numbering
Concentration (peak area) of intermediate
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 which is repeatedly added into the same sample for 6 times 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, manufactured by Shandong Taxing New Material Co., Ltd.
Preparing a sample solution: 6 parts (10.5mg, 10.6mg, 10.0mg, 10.3mg, 10.5mg, 10.2mg) of the same phenoxyl cyclophosphazene reaction solution sample are accurately weighed respectively and placed in a 10mL volumetric flask, an appropriate amount of mobile phase is added for dissolution and dilution to the scale, and a 0.45 mu m organic filter membrane 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 ratio of the average concentration of the intermediate to the target product in the synthesis reaction solution is 0.888: 99.112, RSD calculated as 0.63% and 0.01%, respectively, is very reproducible.
3.3 detection and quantitation limits
Phenoxy cyclophosphazene reaction solution samples: 210315, produced by Shandong Taxing New Material Co., Ltd;
preparing a sample solution: accurately weighing 10.5mg of phenoxyl cyclophosphazene reaction solution into a 10mL volumetric flask, adding a proper amount of mobile phase for dissolving, 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 2.1, and the S/N of the target product tested was 15.25. The detection limit concentration of the sample solution is approximately equal to 0.21mg/mL according to the detection limit S/N which is 3; the limit concentration of the sample solution was determined to be about 0.69mg/mL, based on the limit S/N of 10.
