Method for determining blocking rate of linear ester-terminated polylactic acid

Abstract

The invention discloses a method for measuring the end-capping rate of linear ester end-capped polylactic acid, which adopts a nuclear magnetic resonance spectroscopy method for detection and specifically comprises the following steps: firstly, detecting the content of hydrogen of ortho-carbon of an oxygen atom in an end-capped ester group of a test sample so as to calculate the content of an end-capped group; then derivatization is conducted on terminal hydroxyl groups of the test sample through trifluoroacetic anhydride, the content of the terminal hydroxyl groups is calculated by measuring the content of fluorine, and finally the end capping rate is calculated through the ratio of the content of the end capping groups to the content of the terminal hydroxyl groups. According to the method, the hydroxyl content of the high-molecular polylactic acid is measured by combining trifluoroacetic anhydride derivatization with a nuclear magnetic method, so that the blocking rate of the linear ester-terminated polylactic acid is calculated, and the technical blank of measuring the hydroxyl content of the high-molecular polylactic acid at present is filled up.

Description

Technical Field

[0001] The invention belongs to the technical field of analysis and detection, and particularly relates to a method for determining the end-capping rate of linear ester-capped polylactic acid. Background Art

[0002] In recent years, non-petroleum-based biodegradable materials have received more and more attention. Among the many biodegradable materials, polylactic acid (PLA), as a new type of environmentally friendly polymer material, has gradually received more attention and is widely used in textiles, food packaging, drug sustained release, tissue engineering and other fields. At present, there are two methods for preparing polylactic acid, namely, lactide ring-opening polymerization and direct polycondensation, among which lactide ring-opening polymerization is widely used. The reaction formulas of lactide ring-opening polymerization and direct polycondensation are as follows:

[0003]

[0004] Polylactic acid end-capping is to improve its comprehensive performance and expand its application areas by changing the chemical structure of the end of the polylactic acid chain. By measuring the end-capping rate, the effect of the end-capping reaction can be intuitively evaluated, providing a basis for optimizing the end-capping process, and can also help evaluate the stability of product batch quality. In addition, it can also help predict biodegradability.

[0005] At present, the conventional method for determining the end-capping rate is the non-aqueous titration method, which is calculated using (acid value before end-capping - acid value after end-capping) / acid value before end-capping. This method is low-cost, but the premise is that it is necessary to obtain a sample before end-capping, and at the same time, it is necessary to solve the solubility problem of the polymer; for a fully continuous production process, only a sample after end-capping can be obtained, and a sample before end-capping cannot be obtained, which limits the application of this method.

[0006] Patent CN111458453A discloses a method for testing the hydroxyl value in polylactic acid containing lactide, which method is to first contact the polylactic acid sample to be tested with an anhydride solution containing an organic base, heat and reflux treatment, then cool to room temperature, add water for hydrolysis reaction, and then titrate with an alkali standard solution to obtain the titration test value of the polylactic acid sample to be tested, and then deduct the titration test value of the blank sample to obtain the apparent hydroxyl value of the polylactic acid sample to be tested; then contact the polylactic acid sample to be tested with an organic base, heat and reflux treatment, then cool the system to room temperature, add water for hydrolysis reaction, and then titrate with an alkali standard solution to obtain the apparent acid value of the polylactic acid sample to be tested; and add the apparent hydroxyl value and the apparent acid value to obtain the actual hydroxyl value. However, when the inventor used this method to perform polylactic acid end-capping detection, he found that high molecular weight polylactic acid (about 200,000Da) could not be dissolved, resulting in difficulty in hydrolysis in water, and it was impossible to obtain an accurate titration test value.

[0007] Therefore, the present application designs to use nuclear magnetic resonance spectroscopy to determine the end-capping rate of high molecular weight linear ester-terminated polylactic acid. Summary of the invention

[0008] The object of the present invention is to provide a method for measuring the end-capping rate of linear ester-terminated polylactic acid, comprising the following steps:

[0009] Step 1, take the test sample, dissolve it in chloroform, add internal standard solution A, and then use nuclear magnetic resonance spectrometer to determine the hydrogen content of the carbon adjacent to the oxygen atom in the blocked ester group, and calculate the content of the blocked group;

[0010] The internal standard solution A is obtained by dissolving the internal standard A in deuterated chloroform, and the molar ratio of hydrogen in the internal standard A to the target hydrogen in the test sample is 0.5:1 to 1.5:1;

[0011] Step 2, taking the test sample and the derivatization reagent trifluoroacetic anhydride to react, the reactant is blown dry with nitrogen, toluene is added and then blown dry with nitrogen, then dissolved with deuterated chloroform and internal standard solution B is added, and then the fluorine content is determined by nuclear magnetic resonance spectrometer, and the content of terminal hydroxyl groups is calculated;

[0012] The internal standard solution B is obtained by dissolving the internal standard B in deuterated chloroform, and the molar ratio of the fluorine in the internal standard B to the fluorine in the test sample after derivatization is 0.5:1 to 1.5:1;

[0013] Step 3, calculating the end-capping rate by the formula: (content of end-capping groups / content of terminal hydroxyl groups)×100%;

[0014] The molecular weight of the linear ester-terminated polylactic acid is 10,000Da to 500,000Da.

[0015] Furthermore, the linear ester-terminated polylactic acid is octadecyl alcohol-terminated linear polylactic acid, the internal standard A is tetrachloronitrobenzene, and the internal standard B is trifluorotoluene.

[0016] Furthermore, in step 1, the ratio of the sample to chloroform is: 0.1 g of the sample is dissolved in 1 ml of chloroform to prepare a spiked sample solution (volume V 1’ ).

[0017] Furthermore, in step 1, the determination by nuclear magnetic resonance spectrometer is to precisely measure a certain volume (V 2’ ) Add the sample solution to the NMR tube and collect 1 H spectrum; 1 The key instrument parameters of H-NMR were: 2 empty scans, 128 scans, 10 s relaxation time, and 3.28 s acquisition time.

[0018] Furthermore, the formula for calculating the content of the end-capping group in step 1 is as follows:

[0019] Capping group octadecyl alcohol content (mol / g) = (Ix’ ×n s’ / N , / I s’ ) / (V 2’ / V 1’ ×m ’ ),

[0020] Among them, I x’ I is the integral area of ​​the test sample; s’ is the integrated area of ​​internal standard tetrachloronitrobenzene; n s’ is the molar amount of tetrachloronitrobenzene in the NMR tube; m ’ is the sample weight of the test product; N , V is the number of hydrogen atoms adjacent to the carbon atoms of the oxygen atom in the end-capping group of the test sample; 2’ V is the volume of the spiked sample solution in the NMR tube; 1’ is the total volume of the spiked test solution.

[0021] Furthermore, in step 2, the molar ratio of the test sample to trifluoroacetic anhydride is 1:500 to 1:1000, the reaction time is 30 min to 1 h, and the usage ratio of the test sample to deuterated chloroform is 0.1 g:800 μl.

[0022] Furthermore, in step 2, the determination by nuclear magnetic resonance spectrometer is to precisely measure a certain volume (V2, ml) of the spiked test solution into a nuclear magnetic tube, and collect 19 F spectrum; 19 The key instrument parameters of F-NMR are: 4 empty scans, 64 scans, 60s relaxation time, 0.52s acquisition time, and -68.8 RF offset site.

[0023] Furthermore, the formula for calculating the terminal hydroxyl content in step 2 is as follows:

[0024] Terminal hydroxyl content (mol / g) = (I x ×n s / I s ) / (V2 / V1×m),

[0025] Among them, I x I is the integral area of ​​the test sample; s is the integrated area of ​​internal standard trifluorotoluene; n s is the molar amount of internal standard trifluorotoluene; m is the sample weight of the test sample; V2 is the volume of the spiked test sample solution in the NMR tube; V1 is the total volume of the spiked test sample solution.

[0026] The hydroxyl content of polylactic acid not only plays an important role in evaluating and controlling its molecular weight, but also directly affects its performance in many aspects such as synthesis, processing, degradation, and modification. The hydroxyl content is an important indicator for measuring the quality and performance of polylactic acid. However, the existing method for determining the hydroxyl content adopts a titration method, which is only applicable to polylactic acid with a lower molecular weight. Due to the solubility problem of high molecular weight polylactic acid, it is not suitable for the determination of the hydroxyl content of high molecular weight polylactic acid. The present invention determines the hydroxyl content of high molecular weight polylactic acid by derivatization with trifluoroacetic anhydride combined with nuclear magnetic resonance, filling the technical gap in the current determination of the hydroxyl content of high molecular weight polylactic acid.

[0027] Beneficial effects:

[0028] 1. Compared with the non-aqueous titration method, the detection method of the present invention can complete the capping rate test by using only the capped samples.

[0029] 2. Compared with the method disclosed in patent CN111458453A, the detection method of the present invention uses chloroform as a solvent, high molecular weight polylactic acid is easily soluble in chloroform, and the method is simple to operate. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 This is a typical hydrogen spectrum for the determination of the octadecyl alcohol content in Example 1.

[0031] Figure 2 This is a typical fluorine spectrum for the determination of the terminal hydroxyl content in Example 1. DETAILED DESCRIPTION

[0032] The preferred embodiments of the present invention will be described in detail below in conjunction with examples. It should be understood that the following examples are provided only for the purpose of illustration and are not intended to limit the scope of the present invention. Those skilled in the art may make various modifications and substitutions to the present invention without departing from the purpose and spirit of the present invention.

[0033] Unless otherwise specified, the experimental methods used in the following examples are conventional methods.

[0034] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources.

[0035] Example 1

[0036] The object of determination in this embodiment is linear ester-terminated polylactic acid terminated with octadecyl alcohol, and the molecular weight is between 100,000Da and 150,000Da. The detection method is as follows:

[0037]

[0038] Among them, the molar amount of octadecyl alcohol (octadecyl alcohol content) is determined by hydrogen spectrum of nuclear magnetic resonance spectroscopy and quantified by CH2 connected to O; the molar amount of OH (terminal hydroxyl content) is determined by fluorine spectrum of nuclear magnetic resonance spectroscopy and quantified by F after derivatization of terminal hydroxyl groups with trifluoroacetic anhydride.

[0039] 1. The specific steps are as follows:

[0040] Step 1, octadecyl alcohol content determination, take about 0.1g of the test sample, put it in a glass vial, accurately measure 1ml of chloroform and add it to the glass vial, after the sample is dissolved, accurately add 150μl of 5mg / ml tetrachloronitrobenzene internal standard solution (take an appropriate amount of tetrachloronitrobenzene, dissolve it in deuterated chloroform and make up to the scale, mix well, prepare tetrachloronitrobenzene internal standard solution, prepare it before use), mix well, prepare the spiked test solution, accurately measure 600μl of the spiked test solution and transfer it to the NMR tube, collect 1 H spectrum. 1 The key instrument parameters of H-NMR are: number of scans (DS): 2; number of scans (NS): 128; relaxation time (D1): 10s; acquisition time (AQ): 3.28s. 1 The H spectrum was integrated after baseline correction, and the content of the capping group octadecyl alcohol (mol / g) was calculated according to the following formula:

[0041] Capping group octadecyl alcohol content (mol / g) = (I x’ ×n s’ / 2I s’ ) / (600 / 1150×m ’ ),

[0042] Among them, I x’ I is the integral area of ​​the test sample; s’ is the integrated area of ​​internal standard tetrachloronitrobenzene; n s’ is the molar amount of tetrachloronitrobenzene in the NMR tube (mol); m ’ is the sample weight of the test sample (g); 2 is the end-capping group of the test sample (—O—CH2—(CH2) 16 —CH3) oxygen atom adjacent to the C number; 600 is the volume of the spiked test solution in the NMR tube (μl); 1150 is the total volume of the spiked test solution (μl).

[0043] Step 2, determination of terminal hydroxyl content, take about 0.1g of the test sample, place it in a glass vial, add 2ml of chloroform, and after the sample is dissolved, add 200μl of the derivatization reagent trifluoroacetic anhydride dropwise while shaking, tighten the lid of the glass vial, place it at room temperature for 30 minutes, and immediately place it in an automatic nitrogen blowdown instrument to remove the volatile components. Then add 1ml of toluene, immediately place it in an automatic nitrogen blowdown instrument, and continue to remove the volatile components until it is blown dry. Add 800μl of deuterated chloroform and 60μl of 5mg / ml trifluorotoluene internal standard solution (take an appropriate amount of trifluorotoluene, dissolve it in deuterated chloroform and make up to the scale, mix well, and the prepared trifluorotoluene internal standard solution should be prepared before use), mix well to prepare the spiked test sample solution, accurately measure 600μl of the spiked test sample solution and transfer it to the nuclear magnetic tube, and collect 19 F spectrum. 19 The key instrument parameters of F-NMR are: number of empty scans (DS): 4; number of scans (NS): 64; relaxation time (D1): 60s; acquisition time (AQ): 0.52s; radio frequency offset position (O1P): -68.8. 19 After phase adjustment and baseline correction, the F spectrum was integrated and the terminal hydroxyl content (mol / g) was calculated according to the following formula:

[0044] Terminal hydroxyl content (mol / g) = (I x ×n s / I s ) / (600 / 860×m),

[0045] Among them, I x I is the integral area of ​​the test sample; s is the integrated area of ​​internal standard trifluorotoluene; n s is the molar amount of internal standard trifluorotoluene (mol); m is the sample weight of the test sample (g); 600 is the volume of the spiked test sample solution in the NMR tube (μl); 860 is the total volume of the spiked test sample solution (μl).

[0046] 2. Methodological Validation:

[0047] 1. Validation of the method for determining the terminal hydroxyl content

[0048] 1.1 Derivatization reagent addition amount: The derivatization reagent addition amount was investigated at 50μl, 100μl, 200μl and 300μl. As shown in the table below, when the derivatization reagent addition amount was 50μl and 100μl, the terminal hydroxyl content was low, indicating that the derivatization was not complete; when the derivatization reagent addition amount was 200μl and 300μl, the terminal hydroxyl content tended to be stable, indicating that the derivatization was complete.

[0049]

[0050] 1.2 Derivatization time: The derivatization time was 10 min, 30 min, 1 h and 2 h. As shown in the table below, when the derivatization was 10 min, the terminal hydroxyl content was low, and when the derivatization was 30 min, 1 h and 2 h, the terminal hydroxyl content tended to be stable, indicating that the derivatization was complete.

[0051]

[0052] 1.3 Repeatability: The RSD of the terminal hydroxyl content of 6 parallel samples was 0.9%, indicating that the method had good repeatability.

[0053]

[0054] 1.4 Intermediate precision (different dates), the RSD of terminal hydroxyl content was 1.5%.

[0055]

[0056] 1.5 Intermediate precision (different personnel), RSD of terminal hydroxyl content is 1.4%.

[0057]

[0058] 2. Verification of the methodological determination of the content of the capping group octadecyl alcohol

[0059] 2.1 Repeatability: The RSD of the capping group octadecyl alcohol content of 6 parallel samples was 1.0%, indicating that the method had good repeatability.

[0060]

[0061] 2.2 Intermediate precision (different dates), the RSD of the content of the end-capping group octadecyl alcohol was 1.1%.

[0062]

[0063] 2.3 Intermediate precision (different personnel), the RSD of the content of the end-capping group octadecyl alcohol is 1.1%.

[0064]

[0065] After the above methodological verification proved that the detection method established by the present invention is reliable and effective, the method was used to detect two batches of linear ester-terminated polylactic acid samples (molecular weight between 100,000Da and 150,000Da) capped with octadecyl alcohol, and the capping rates of the two batches of samples were 85.0% and 63.9%, respectively.

Claims

1. A method for determining the end-capping rate of linear ester-terminated polylactic acid, characterized in that: The following steps are involved: Step 1, take a test sample, dissolve it in chloroform, add internal standard solution A, and then use nuclear magnetic resonance spectrometer to determine the hydrogen content of the carbon adjacent to the oxygen atom in the blocked ester group, and calculate the content of the blocked group; The internal standard solution A is obtained by dissolving the internal standard A in deuterated chloroform, and the molar ratio of hydrogen in the internal standard A to the target hydrogen in the test sample is 0.5:1 to 1.5:1; Step 2, reacting the test sample with a derivatization reagent, trifluoroacetic anhydride, blowing the reactant with nitrogen, adding toluene and then blowing it with nitrogen, then dissolving it with deuterated chloroform and adding internal standard solution B, then using a nuclear magnetic resonance spectrometer to determine the fluorine content, and calculating the content of the terminal hydroxyl group; The internal standard solution B is obtained by dissolving the internal standard B in deuterated chloroform, and the molar ratio of the fluorine in the internal standard B to the fluorine in the test sample after derivatization is 0.5:1 to 1.5:1; Step 3, the end-capping rate is calculated by the formula: (content of end-capping groups / content of terminal hydroxyl groups) × 100%; The molecular weight of the linear ester-terminated polylactic acid is 10,000Da to 500,000Da.

2. The method according to claim 1, characterized in that The linear ester-terminated polylactic acid is octadecyl alcohol-terminated linear polylactic acid, the internal standard A is tetrachloronitrobenzene, and the internal standard B is trifluorotoluene.

3. The method according to claim 2, characterized in that In step 1, the ratio of the sample to chloroform is: 1 ml of chloroform is used to dissolve every 0.1 g of the sample to prepare a spiked sample solution.

4. The method according to claim 3, characterized in that In step 1, the nuclear magnetic resonance spectrometer is used to measure a certain volume of the spiked sample solution into the nuclear magnetic resonance tube and collect 1 H spectrum; 1 The key instrument parameters of H-NMR were: 2 empty scans, 128 scans, 10 s relaxation time, and 3.28 s acquisition time.

5. The method according to claim 4, characterized in that The formula for calculating the end-capping group content in step 1 is as follows: Capping group octadecyl alcohol content (mol / g) = (I x’ ×n s’ / N , / I s’ ) / (V 2’ / V 1’ ×m ’ ), Among them, I x’ I is the integral area of ​​the test sample; s’ is the integrated area of ​​internal standard tetrachloronitrobenzene; n s’ is the molar amount of tetrachloronitrobenzene in the NMR tube; m ’ is the sample weight of the test product; N , V is the number of hydrogen atoms adjacent to the carbon atoms of the oxygen atom in the end-capping group of the test sample; 2’ V is the volume of the spiked sample solution in the NMR tube; 1’ is the total volume of the spiked test solution.

6. The method according to claim 1, characterized in that In step 2, the molar ratio of the test sample to trifluoroacetic anhydride is 1:500-1:1000, the reaction time is 30 min-1 h, and the dosage ratio of the test sample to deuterated chloroform is 0.1 g:800 μl.

7. The method according to claim 6, characterized in that In step 2, the nuclear magnetic resonance spectrometer is used to measure a certain volume of the spiked test solution into the nuclear magnetic resonance tube and collect 19 F spectrum; 19 The key instrument parameters of F-NMR are: 4 empty scans, 64 scans, 60s relaxation time, 0.52s acquisition time, and -68.8 RF offset site.

8. The method according to claim 7, characterized in that The formula for calculating the terminal hydroxyl content in step 2 is as follows: End hydroxyl content (mol / g) = (I x ×n s / I s ) / (V2 / V1×m), Among them, I x I is the integral area of ​​the test sample; s is the integrated area of ​​internal standard trifluorotoluene; n s is the molar amount of internal standard trifluorotoluene; m is the sample weight of the test sample; V2 is the volume of the spiked test sample solution in the NMR tube; V1 is the total volume of the spiked test sample solution.

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