A method for determining the end-capping rate of linear ester-terminated polylactic acid

Abstract

The application discloses a method for determining the end-capping rate of linear ester end-capped polylactic acid, which is detected by using a nuclear magnetic resonance spectroscopy method, specifically, the content of hydrogen of the oxygen atom adjacent carbon in the end-capped ester group of a test sample is detected first, so that the content of the end-capping group is calculated, then the end hydroxyl group of the test sample is derivatized by using trifluoroacetic anhydride, the content of fluorine is detected, so that the content of the end hydroxyl group is calculated, and finally the end-capping rate is calculated by the ratio of the content of the end-capping group and the content of the end hydroxyl group. In the application, the trifluoroacetic anhydride derivatization is combined with the nuclear magnetic method to detect the hydroxyl group content of the high molecular polylactic acid, so that the end-capping rate of the linear ester end-capped polylactic acid is calculated, and a technical blank for detecting the hydroxyl group content of the high molecular polylactic acid is filled.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of analytical detection, and particularly relates to a method for measuring the end-capping rate of linear ester end-capped polylactic acid. BACKGROUND

[0002] In recent years, non-petroleum-based degradable materials have been increasingly concerned. Among 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 the fields of textiles, food packaging, drug release, tissue engineering, etc. At present, there are two methods for preparing polylactic acid, namely, lactide ring-opening polymerization method and direct polycondensation method, among which the lactide ring-opening polymerization method is widely adopted. The reaction formulas of the lactide ring-opening polymerization method and the direct polycondensation method are as follows:

[0003]

[0004] Polylactic acid end-capping is to change the chemical structure of the end of the polylactic acid chain to improve its comprehensive performance and expand its application field. By measuring the end-capping rate, the effect of the end-capping reaction can be directly evaluated, which provides a basis for optimizing the end-capping process and helps to evaluate the stability of product batch quality. In addition, it can also help to predict the biodegradation performance.

[0005] At present, the conventional method for measuring the end-capping rate is non-water titration, which is calculated by (acid value before end-capping - acid value after end-capping) / acid value before end-capping. This method has low cost, but it requires obtaining the sample before end-capping and solving the solubility problem of high polymers. For a fully continuous production process, only the sample after end-capping can be obtained, and the sample before end-capping cannot be obtained, thus limiting the application of this method.

[0006] Patent CN111458453A discloses a method for testing the hydroxyl value of polylactic acid containing lactide. The method is to first contact the polylactic acid sample to be tested with an acid anhydride solution containing an organic base, heat and reflux, then cool to room temperature, add water for hydrolysis reaction, then titrate with a standard alkali solution to obtain the titration test value of the polylactic acid sample to be tested, 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, the polylactic acid sample to be tested is contacted with an organic base, heat and reflux, then cool the system to room temperature, add water for hydrolysis reaction, then titrate with a standard alkali solution to obtain the apparent acid value of the polylactic acid sample to be tested. The actual hydroxyl value is obtained by adding the apparent hydroxyl value and the apparent acid value. However, when the inventors used this method to detect polylactic acid end-capping, they found that high molecular weight polylactic acid (about 200,000 Da) could not be dissolved, which made it difficult to hydrolyze in water and could not obtain accurate titration test values.

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

[0008] The application aims to provide a method for determining the end-capping rate of linear ester end-capped polylactic acid, comprising the following steps:

[0009] Step 1, taking the test sample, dissolving it in chloroform, adding internal standard solution A, then using a nuclear magnetic resonance spectrometer to determine the content of hydrogen of the carbon adjacent to the oxygen atom in the end-capped ester group, and calculating the content of the end-capping group;

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

[0011] Step 2, taking the test sample and reacting it with the derivatization reagent trifluoroacetic anhydride, blowing dry the reactants with nitrogen, adding toluene and then blowing dry with nitrogen, then dissolving in deuterated chloroform and adding internal standard solution B, then using a nuclear magnetic resonance spectrometer to determine the content of fluorine, and calculating the content of the terminal hydroxyl group;

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

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

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

[0015] Further, the linear ester end-capped polylactic acid is octadecanol end-capped linear polylactic acid, the internal standard A is tetrachloronitrobenzene, and the internal standard B is trifluorotoluene.

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

[0017] Further, in step 1, a certain volume (V 2’ ) of spiked test sample solution is precisely measured into a nuclear magnetic tube, and 1 1H spectrum is collected; 1 The 1H-NMR key instrument parameters are: number of empty scans 2, number of scans 128, relaxation time 10 s, and acquisition time 3.28 s.

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

[0019] The content of the end-capping group octadecanol (mol / g) = (Ix’ ×n s’ / N , / I s’ ) / (V 2’ / V 1’ ×m ’ ),

[0020] wherein, I x’ is the integral area of the test sample; I s’ is the integral area of the internal standard 4-chloronitrobenzene; n s’ is the molar mass of 4-chloronitrobenzene in the NMR tube; m ’ is the sample weight; N , is the number of hydrogen atoms adjacent to the oxygen atom of the end capping group of the test sample; V 2’ is the volume of the test sample solution added into the NMR tube; V 1’ is the total volume of the test sample solution.

[0021] Further, 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 ratio of the amount of the test sample to deuterated chloroform is 0.1 g:800 μl.

[0022] Further, in step 2, the NMR spectrometer is used for precise measurement of a certain volume (V2, ml) of the test sample solution added into the NMR tube, and the 19 F spectrum is collected. 19 The key instrument parameters of the F-NMR are: 4 times of empty scanning, 64 times of scanning, 60 s of relaxation time, 0.52 s of acquisition time, and -68.8 of radio frequency offset point.

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

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

[0025] wherein, I x is the integral area of the test sample; I s is the integral area of the internal standard 4-chloronitrobenzene; n s is the molar mass of 4-chloronitrobenzene in the NMR tube; m is the sample weight; V2 is the volume of the test sample solution added into the NMR tube; V1 is the total volume of the 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 synthesis, processing, degradation, modification and other aspects, and the hydroxyl content is an important index for measuring the quality and performance of polylactic acid. However, the existing hydroxyl content determination method adopts titration method, which is only suitable for polylactic acid with low molecular weight. Due to the solubility problem of high molecular weight polylactic acid, the titration method is not suitable for the determination of the hydroxyl content of high molecular weight polylactic acid. The present application determines the hydroxyl content of high molecular weight polylactic acid by trifluoroacetic anhydride derivatization combined with nuclear magnetic method, which fills the technical gap of the 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 application can complete the end-capping rate test only by using the capped sample.

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

[0030] Figure 1 Typical hydrogen spectrum for determination of octadecanol content in Example 1.

[0031] Figure 2 Typical fluorine spectrum for determination of end hydroxyl content in Example 1. DETAILED DESCRIPTION

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

[0033] In the following examples, the experimental methods used are conventional methods unless otherwise specified.

[0034] In the following examples, the materials, reagents, etc. used are commercially available unless otherwise specified.

[0035] Example 1

[0036] The determination object of this embodiment is linear ester end-capped polylactic acid capped with octadecanol, and the molecular weight is 100,000 Da-150,000 Da. The detection method is shown in the following formula:

[0037]

[0038] The molar amount of octadecanol (octadecanol content) is determined by hydrogen spectrum of nuclear magnetic resonance spectroscopy, and the CH2 connected with O is quantified; the molar amount of OH (end hydroxyl content) is determined by fluorine spectrum of nuclear magnetic resonance spectroscopy, and the end hydroxyl is quantified by F after being derivatized by trifluoroacetic anhydride.

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

[0040] Step 1, octadecanol content determination, take about 0.1 g of the test sample and place it in a glass vial, accurately take 1 ml of chloroform and add it to the glass vial, after the sample is dissolved, accurately add 150 μl of 5 mg / ml of tetrachloronitrobenzene internal standard solution (take an appropriate amount of tetrachloronitrobenzene, dissolve it with deuterated chloroform and dilute to the mark, mix well, and prepare the tetrachloronitrobenzene internal standard solution, which is prepared immediately before use), mix well, prepare the spiked test sample solution, accurately take 600 μl of the spiked test sample solution and transfer it to a nuclear magnetic tube, collect 1 H spectrum. 1 The H-NMR key instrument parameters are as follows: empty scan times (DS): 2; scan times (NS): 128; relaxation time (D1): 10 s; acquisition time (AQ): 3.28 s. After baseline correction of the 1 H spectrum, the integral is calculated, and the content of the capping group octadecanol (mol / g) is calculated according to the following formula:

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

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

[0043] Step 2, determination of terminal hydroxyl content: Take approximately 0.1 g of the test sample and place it in a glass vial. Add 2 ml of chloroform. After the sample dissolves, add 200 μl of the derivatization reagent trifluoroacetic anhydride dropwise while shaking. Tighten the glass vial cap and let it stand at room temperature for 30 min. Immediately place it in an automated nitrogen evaporator to remove volatile components. Then add 1 ml of toluene and immediately place it in the automated nitrogen evaporator to continue removing volatile components until dry. Add 800 μl of deuterated chloroform and 60 μl of 5 mg / ml trifluorotoluene internal standard solution (prepare a suitable amount of trifluorotoluene by dissolving it in deuterated chloroform and diluting to the mark, mixing well, and preparing the trifluorotoluene internal standard solution immediately before use). Mix well to prepare the spiked test sample solution. Accurately measure 600 μl of the spiked test sample solution and transfer it to an NMR tube for sampling. 19 F spectrum. 19 Key F-NMR instrument parameters are: Dry scan number (DS): 4; Scan number (NS): 64; Relaxation time (D1): 60 s; Acquisition time (AQ): 0.52 s; Radio frequency offset (O1P): -68.8. 19 After phase adjustment and baseline correction of the F-spectrum, integration is performed, and the terminal hydroxyl content (mol / g) is 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 represents the integral area of ​​the test sample. s The integral area of ​​the internal standard trifluorotoluene; n s 1 is the molar amount of internal standard trifluorotoluene (mol); m is the sample weight (g); 600 is the volume of the spiked sample solution in the NMR tube (μl); 860 is the total volume of the spiked sample solution (μl).

[0046] II. Methodological Validation:

[0047] 1. Method validation for the determination of terminal hydroxyl content

[0048] 1.1 Amount of Derivatization Reagent Added: The amounts of derivatization reagent added were examined at 50 μl, 100 μl, 200 μl, and 300 μl. As shown in the table below, when the amounts of derivatization reagent added were 50 μl and 100 μl, the content of terminal hydroxyl groups was low, indicating incomplete derivatization; when the amounts of derivatization reagent added were 200 μl and 300 μl, the content of terminal hydroxyl groups tended to stabilize, indicating complete derivatization.

[0049]

[0050] 1.2 Derivation time: The derivation time was investigated for 10 min, 30 min, 1 h and 2 h, respectively. From the following table, it can be seen that the end hydroxyl group content is lower when the derivation is 10 min, and the end hydroxyl group content tends to be stable when the derivation is 30 min, 1 h and 2 h, which indicates that the derivation is complete.

[0051]

[0052] 1.3 Reproducibility: The RSD of the end hydroxyl group content of 6 parallel test samples is 0.9%, which indicates that the reproducibility of the method is good.

[0053]

[0054] 1.4 Intermediate precision (different dates), the RSD of the end hydroxyl group content is 1.5%.

[0055]

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

[0057]

[0058] 2. End-capping group octadecanol content determination method validation

[0059] 2.1 Reproducibility: The RSD of the end-capping group octadecanol content of 6 parallel test samples is 1.0%, which indicates that the reproducibility of the method is good.

[0060]

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

[0062]

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

[0064]

[0065] After the above method validation proves that the detection method established by the present application is reliable and effective, the method is used to detect two batches of octadecanol-terminated linear ester-terminated polylactic acid samples (molecular weight is 100,000 Da-150,000 Da), and the end-capping rates of the two batches of samples are 85.0% and 63.9%, respectively.

Claims

1. A method for determining the end-capping rate of linear ester-terminated polylactic acid, characterized by, The method comprises the following steps: Step 1, taking the test sample, dissolving it in chloroform, adding internal standard solution A, and then using a nuclear magnetic resonance spectrometer to measure the content of hydrogen of the carbon adjacent to the oxygen atom in the capped ester group, so as to calculate the content of the capped group; The internal standard solution A is obtained by dissolving internal standard A in deuterated chloroform, and the molar ratio of hydrogen in internal standard A to the target hydrogen in the test sample is 0.5:1-1.5:1; Step 2, taking the test sample and reacting it with the derivatization reagent trifluoroacetic anhydride, blowing dry the reactants with nitrogen, adding toluene and then blowing dry with nitrogen, then dissolving in deuterated chloroform and adding internal standard solution B, and then using a nuclear magnetic resonance spectrometer to measure the content of fluorine, so as to calculate the content of the terminal hydroxyl group; The internal standard solution B is obtained by dissolving internal standard B in deuterated chloroform, and the molar ratio of fluorine in internal standard B to fluorine in the test sample after derivatization is 0.5:1-1.5:1; Step 3, the capping rate is calculated by the formula: (content of capped group / content of terminal hydroxyl group) x 100%. The linear ester-capped polylactic acid has a molecular weight of 10,000 Da-500,000 Da.

2. The method of claim 1, wherein, The linear ester-capped polylactic acid is octadecanol-capped linear polylactic acid, the internal standard A is tetrachloronitrobenzene, and the internal standard B is trifluorotoluene.

3. The method of claim 2, wherein, In step 1, the ratio of the amount of test sample to chloroform is 1ml of chloroform for every 0.1g of test sample to prepare a spiked test sample solution.

4. The method of claim 3, wherein, The determination in Step 1 is performed by precisely measuring a certain volume of the sample solution to be tested to which a standard is added into a nuclear magnetic tube, and collecting 1 H spectrum; 1 The H -NMR key instrument parameters are: empty scanning times 2, scanning times 128, relaxation time 10 s, and acquisition time 3.28 s.

5. The method of claim 4, wherein, The formula for calculating the content of the capped group in step 1 is as follows: End-capped group octadecanol content (mol / g) = (I x’ × n s’ / N , / I s’ ) / (V 2’ / V 1’ × m ’ ), Wherein, I x’ is the integral area of the test sample; I s’ is the integral area of the internal standard tetrachloronitrobenzene; n s’ is the molar mass of tetrachloronitrobenzene in the NMR tube; m ’ is the sample weight of the test sample; N , is the number of hydrogen atoms adjacent to the oxygen atom of the end-capping group of the test sample; V 2’ is the volume of the test sample solution in the NMR tube; V 1’ is the total volume of the test sample solution.

6. The method of claim 1, wherein, In step 2, the molar ratio of the test sample to trifluoroacetic anhydride is 1:500-1:1000, the reaction time is 30min-1h, and the ratio of the amount of test sample to deuterated chloroform is 0.1g:800ul.

7. The method of claim 6, wherein, The determination in Step 2 is performed by precisely measuring a certain volume of the sample solution to be tested into a nuclear magnetic tube, and collecting 19 F spectrum. 19 The key instrument parameters of F-NMR are: 4 times of empty scanning, 64 times of scanning, 60 s of relaxation time, 0.52 s of acquisition time, and -68.8 of radio frequency offset point.

8. The method of claim 7, wherein, The formula for calculating the content of the terminal hydroxyl group in step 2 is as follows: End hydroxyl content (mol / g) = (I x × n s / (V2 / V1 x m), s ) / (V2 / V1 x m), Wherein, I x is the integral area of the test sample; I s is the integral area of the internal standard trifluorotoluene; n s is the molar mass of the internal standard trifluorotoluene; m is the sample weight of the test sample; V2 is the volume of the test sample solution in the NMR tube; and V1 is the total volume of the test sample solution.

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