An analysis method and application of monobenzyl dodecanedioate

Abstract

The invention discloses an analysis method for monobenzyl dodecanedioate and an application thereof. The method of the invention comprises using liquid chromatography to detect a sample to be tested containing monobenzyl dodecanedioate. The method of the invention has high accuracy and precision, good linearity, and extremely low detection limit and quantitative limit, and can be used to monitor the reaction of monobenzyl dodecanedioate and evaluate product quality.

Description

Technical Field

[0001] The invention belongs to the technical field of analytical chemistry, and particularly relates to a liquid phase analysis method for monobenzyl dodecanedioate. Background Art

[0002] Benzyl dodecanedioate is an important intermediate in organic synthesis, but there is no established method for monitoring the reaction process and finished product quality of this product. In order to better monitor the reaction, effectively separate impurities, raw materials, and solvents, and conduct qualitative and quantitative analysis of benzyl dodecanedioate and its reaction solution, it is urgent to provide an effective analysis method to provide strong support for the production control and product quality control of benzyl dodecanedioate. Summary of the invention

[0003] In view of the deficiencies in the prior art, the present invention provides an analytical method for dodecanedioic acid monobenzyl ester, and has passed the methodological verification. This method can simultaneously monitor dodecanedioic acid, benzyl alcohol, dodecanedioic acid monobenzyl ester and dodecanedioic acid dibenzyl ester, and can detect the residual amount of dodecanoic acid in dodecanedioic acid monobenzyl ester by the external standard curve method. The analytical method adopts liquid chromatography to effectively separate and analyze dodecanedioic acid monobenzyl ester and its related impurities, raw materials and solvents. The analytical method is simple to operate, has a short analysis time and high detection efficiency. It can simultaneously meet the monitoring of the reaction process, impurity control, and the detection of dodecanedioic acid residues and finished product quality.

[0004] The structure of benzyl dodecanedioate is shown below:

[0005] .

[0006] According to one aspect of the present invention, a method for analyzing monobenzyl dodecanedioate is provided, the method comprising using liquid chromatography to detect a sample containing monobenzyl dodecanedioate, the liquid chromatography conditions comprising: using 0.05-0.2% phosphoric acid aqueous solution as mobile phase A, using acetonitrile as mobile phase B, and using gradient elution for elution, the procedure of the gradient elution comprising:

[0007] .

[0008] In the method of the present invention, using aqueous phosphoric acid solution as the mobile phase A eluent can better provide a certain pH buffering capacity, help stabilize the pH value of the mobile phase, ensure the stability and repeatability of the chromatographic analysis of this method, and ensure the normal distribution of the peak shapes of various substances.

[0009] In some embodiments, the concentration of the phosphoric acid aqueous solution is 0.08-0.12%, more preferably 0.1%.

[0010] In some embodiments, the volume proportion of mobile phase A is 0-65%, and the volume proportion of mobile phase B is 35-100%.

[0011] In some embodiments, the gradient elution procedure comprises:

[0012] .

[0013] In some embodiments, the liquid chromatography conditions include: a detection wavelength of 210 nm. At this detection wavelength, not only can dodecanedioic acid be detected, but also the quality requirements for dodecanedioic acid monobenzyl ester can be met.

[0014] In some embodiments, the liquid chromatography conditions include: a flow rate of 0.8-1.2 mL / min, preferably 1.0 mL / min.

[0015] In some embodiments, the liquid chromatography conditions include: a column temperature of 30-35°C, preferably 35°C.

[0016] In some embodiments, the liquid chromatography conditions include: an injection volume of 8-12 μL, preferably 10 μL.

[0017] In some embodiments, the liquid chromatography conditions include: the chromatographic column is a C18 chromatographic column, preferably a XDB-C18 chromatographic column. In some specific embodiments, the liquid chromatography uses an Agilent HPLC1260, using an AgilentXDB-C18 250×4.60mm×5µm chromatographic column.

[0018] In some embodiments, the conditions of the liquid chromatography include: the sample to be tested includes monobenzyl dodecanedioate or a monobenzyl dodecanedioate reaction solution obtained by reacting dodecanoic acid and benzyl alcohol.

[0019] In some embodiments, the liquid chromatography conditions include: the sample to be tested includes one or more of benzyl alcohol, dodecanedioic acid, toluene, monobenzyl dodecanedioate and dibenzyl dodecanedioate.

[0020] In some embodiments, the liquid chromatography conditions include: the solvent in the sample to be tested includes acetonitrile.

[0021] In some embodiments, the conditions of the liquid chromatography include: the method further includes: separating or performing qualitative and / or quantitative analysis on the sample to be tested according to the chromatogram obtained by detection.

[0022] In some embodiments, methanol, dodecanedioic acid, toluene, monobenzyl dodecanedioate and dibenzyl dodecanedioate are separated and qualitatively analyzed according to the retention time of the liquid chromatography.

[0023] In some embodiments, the external standard curve method is used to quantitatively analyze dodecanedioic acid and / or dodecanedioic acid monobenzyl ester.

[0024] In some embodiments, the sample to be tested is subjected to liquid chromatography detection, and the accurate content of dodecanedioic acid and dodecanedioic acid monobenzyl ester is calculated using the established external standard curve. At the same time, the method can also monitor the impurity dodecanedioic acid dibenzyl ester and the raw material benzyl alcohol, provide powerful guidance for the synthesis of dodecanedioic acid monobenzyl ester, and accurately evaluate the product.

[0025] In some embodiments, the method comprises the steps of:

[0026] (1) taking a standard solution of dodecanedioic acid and / or dodecanedioic acid monobenzyl ester, and preparing standard solutions with different concentration gradients;

[0027] (2) subjecting the standard solution of the concentration gradient to liquid chromatography to obtain a chromatogram corresponding to each standard solution, and plotting a standard curve with the concentration of each standard solution as the abscissa and the average peak area as the ordinate;

[0028] (3) The sample to be tested is subjected to the same liquid chromatography to obtain a chromatogram of the sample to be tested, and the corresponding content is obtained through the peak area of ​​the sample to be tested and the standard curve.

[0029] According to another aspect of the present invention, there is provided an application of the method of the present invention in production control and product quality control of monobenzyl dodecanedioate.

[0030] In some embodiments, the method is used to separate a mixture comprising one or more of benzyl alcohol, dodecanedioic acid, toluene, monobenzyl dodecanedioate, and dibenzyl dodecanedioate.

[0031] In some embodiments, the method is used for qualitative and / or quantitative detection of monobenzyl dodecanedioate.

[0032] In some embodiments, the method is used to qualitatively and / or quantitatively detect dodecanedioic acid.

[0033] In some embodiments, the method is used to qualitatively and / or quantitatively detect benzyl alcohol.

[0034] In some embodiments, the method is used for qualitative and / or quantitative detection of toluene.

[0035] In some embodiments, the method is used for qualitative and / or quantitative detection of dibenzyl dodecanedioate.

[0036] The method of the invention has high accuracy and precision, good linearity, and extremely low detection limit and quantitative limit, and can be used to monitor the reaction of monobenzyl dodecanedioate and evaluate product quality. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 A liquid chromatogram obtained according to Example 1 is shown.

[0038] Figure 2 The mixed standard curve of dodecanedioic acid and dodecanedioic acid monobenzyl ester obtained according to Example 2 is shown.

[0039] Figure 3 A standard curve for dodecanedioic acid obtained according to Example 2 is shown.

[0040] Figure 4 The standard curve of dodecanedioic acid monobenzyl ester obtained according to Example 2 is shown.

[0041] Figure 5 A liquid chromatogram obtained according to Example 3 is shown.

[0042] Figure 6 A liquid chromatogram obtained according to Example 4 is shown.

[0043] Figure 7 A liquid chromatogram obtained according to Example 5 is shown.

[0044] Figure 8 A liquid chromatogram obtained according to Example 6 is shown.

[0045] Fig. 9 A liquid chromatogram obtained according to Example 7 is shown.

[0046] Fig.10 A liquid chromatogram obtained according to Example 8 is shown.

[0047] Fig.11 A liquid chromatogram obtained according to Example 9 is shown. DETAILED DESCRIPTION

[0048] In order to make the purpose, technical scheme and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. The specific embodiments described herein are only used to explain the present invention and are not intended to constitute any limitation to the present invention. In addition, in the following description, the description of known structures and technologies is omitted to avoid unnecessary confusion of the concepts of the present disclosure. Such structures and technologies are also described in many publications.

[0049] Example 1

[0050] The reaction liquid of monobenzyl dodecanedioate is prepared by reacting dodecanoic acid and benzyl alcohol, and the reaction solvent is toluene.

[0051] The reaction solution of benzyl dodecanedioate was tested under the conditions shown in Table 1. Figure 1 Liquid chromatogram shown.

[0052]

[0053] Depend on Figure 1 As can be seen from the liquid chromatogram, the components shown in Table 2 below were separated by this method.

[0054]

[0055] Example 2 Methodology Verification

[0056] The accuracy, precision, stability, linearity, detection limit and quantification limit of the analytical method established in Example 1 were verified by method validation experiments. The content of the standard product of monobenzyl dodecanedioate was 99.70%, and dodecanedioic acid was purchased from Maclean (analytical grade sample).

[0057] (1) Accuracy experiment

[0058] According to the method in Table 1 of Example 1, the standard sample of monobenzyl dodecanedioate was measured five times in parallel. The results of the parallel measurements are shown in Table 3 below.

[0059]

[0060] According to the results in Table 3, it can be seen that the average relative error of this method is 0.18, which has high accuracy.

[0061] (2) Precision experiment

[0062] The precision of the method was calculated based on the results of five measurements in the accuracy experiment (1). The results are shown in Table 4.

[0063]

[0064] According to the results in Table 4, it can be seen that the standard deviation of this method is 0.14 and the RSD is 0.14%, which has high precision and good stability.

[0065] (3) Linear detection

[0066] Prepare 100~1000ppm of monobenzyl dodecanedioate standard product, using acetonitrile as solvent.

[0067] Prepare 200~2000ppm of dodecanedioic acid and use acetonitrile as solvent.

[0068] Establishment of standard curve: Prepare 5 test solutions of different concentration levels, wherein the 5 concentration levels of dodecanedioic acid are 200ppm, 400ppm, 1000ppm, 1600ppm, and 2000ppm, and the 5 concentration levels of dodecanedioic acid monobenzyl ester are 100ppm, 200ppm, 500ppm, 800ppm, and 1000ppm, respectively. Detect according to the method of Table 1 in Example 1 to obtain a mixed standard curve of dodecanedioic acid and dodecanedioic acid monobenzyl ester ( Figure 2 ).

[0069] The standard curves were drawn with the mass concentration of dodecanedioic acid as the horizontal axis and the average peak area as the vertical axis, and with the mass concentration of dodecanedioic acid monobenzyl ester as the horizontal axis and the average peak area as the vertical axis, as shown in the figure: Figure 3 and Figure 4 shown.

[0070] The linear equation of dodecanedioic acid is y=0.2465x-0.4609, and the linear correlation coefficient R 2 =0.99998.

[0071] The linear equation of monobenzyl dodecanedioate is y=13.0419x+27.8089, and the linear correlation coefficient is R 2 =0.99991.

[0072] (4) Detection limit and quantification limit

[0073] For dodecanedioic acid, the detection limit concentration corresponding to a 3-fold signal-to-noise ratio (S / N=3) was 17.14 μg / mL, and the quantification limit corresponding to a 10-fold signal-to-noise ratio (S / N=3) was 56.57 μg / mL.

[0074] For monobenzyl dodecanedioate, the detection limit concentration corresponding to a 3-fold signal-to-noise ratio (S / N=3) was 0.73 μg / mL, and the quantification limit corresponding to a 10-fold signal-to-noise ratio (S / N=3) was 2.40 μg / mL.

[0075] Example 3

[0076] Benzyl alcohol, dodecanedioic acid, and dodecanedioic acid monobenzyl ester were mixed and diluted with acetonitrile to prepare the test solution. The test was performed according to the method in Table 1 of Example 1, except that the elution conditions were adjusted to isocratic elution with a ratio of mobile phase B to mobile phase A of 80:20.

[0077] Liquid chromatography Figure 5 The results show that the dodecanedioic acid and benzyl alcohol in the raw material are completely coated together.

[0078] Example 4

[0079] The test solution is the same as in Example 3, and is tested according to the method in Table 1 in Example 1, except that the elution conditions are adjusted to the gradient elution shown in Table 5 below:

[0080]

[0081] Liquid chromatography Figure 6 The results show that the dodecanedioic acid and benzyl alcohol in the raw material are completely coated together, and the peak of benzyl alcohol is tailing.

[0082] Example 5

[0083] The test solution is the same as in Example 3, and is tested according to the method in Table 1 in Example 1, except that the elution conditions are adjusted to the gradient elution shown in Table 6 below:

[0084]

[0085] Liquid chromatography Figure 7 The results show that dodecanedioic acid and benzyl alcohol in the raw material are effectively separated, and the peak shape is normally distributed.

[0086] Example 6

[0087] The test solution is the same as that in Example 3 and is tested according to the method in Example 1, except that pure water is used as mobile phase A.

[0088] Liquid chromatography Figure 8 The results show that the peak of monobenzyl dodecanedioate is split.

[0089] Example 7

[0090] The test solution is the same as that in Example 3 and is detected according to the method in Example 1, except that 0.1% trifluoroacetic acid is used as mobile phase A.

[0091] Liquid chromatography Fig. 9 The results show that the peak shape and peak width of monobenzyl dodecanedioate meet the requirements, but the acidity of trifluoroacetic acid is too strong.

[0092] Example 8

[0093] The test solution is the same as that in Example 3 and is detected according to the method in Example 1, except that 0.1% formic acid is used as mobile phase A.

[0094] Liquid chromatography Fig.10 The results show that benzyl dodecanedioate has severe tailing.

[0095] Example 9

[0096] The test solution is the same as that in Example 3, and the test is performed according to the method in Example 1.

[0097] Liquid chromatography Fig.11 The results show that choosing 0.1% phosphoric acid as mobile phase A can avoid the shortcomings of trifluoroacetic acid and formic acid.

[0098] The technical solution of the present invention is not limited to the above-mentioned specific embodiments. All technical variations made according to the technical solution of the present invention fall within the protection scope of the present invention.

Claims

1. A method for analyzing monobenzyl dodecanedioate, characterized in that: The analytical method comprises using liquid chromatography to detect a sample containing monobenzyl dodecanedioate, wherein the conditions of the liquid chromatography comprise: using 0.05-0.2% phosphoric acid aqueous solution as mobile phase A, using acetonitrile as mobile phase B, and using gradient elution for elution. The procedure of the gradient elution includes: 。 2. The analysis method of dodecanedioic acid monobenzyl ester according to claim 1, characterized in that: The concentration of the phosphoric acid aqueous solution is 0.08-0.12%; and / or The volume proportion of mobile phase A is 0-65%, and the volume proportion of mobile phase B is 35-100%.

3. The analysis method of dodecanedioic acid monobenzyl ester according to claim 1, characterized in that: The procedure of the gradient elution includes: 。 4. The analysis method of dodecanedioic acid monobenzyl ester according to claim 1, characterized in that: The conditions of the liquid chromatography include: The detection wavelength is 210 nm; and / or Flow rate of 0.8-1.2 mL / min; and / or Column temperature is 30-35°C; and / or Injection volume is 8-12 μL; and / or The chromatographic column is a C18 chromatographic column.

5. The analysis method of dodecanedioic acid monobenzyl ester according to claim 4, characterized in that: The conditions of the liquid chromatography include: The flow rate is 1.0 mL / min; and / or The column temperature is 35°C; and / or The injection volume was 10 μL.

6. The analysis method of dodecanedioic acid monobenzyl ester according to claim 1, characterized in that: The concentration of the phosphoric acid aqueous solution is 0.1%.

7. The analysis method of dodecanedioic acid monobenzyl ester according to claim 1, characterized in that: The sample to be tested includes one or more of benzyl alcohol, dodecanedioic acid, toluene, monobenzyl dodecanedioate and dibenzyl dodecanedioate; and / or The solvent in the sample to be tested includes acetonitrile.

8. The method for analyzing monobenzyl dodecanedioate according to claim 1, characterized in that: The method further comprises: separating the sample to be tested or performing qualitative and / or quantitative analysis according to the chromatogram obtained by the detection.

9. Use of the analytical method for monobenzyl dodecanedioate according to any one of claims 1 to 8 in production control and product quality control of monobenzyl dodecanedioate.

10. The use according to claim 9, characterized in that: The method is used for separating a mixture containing one or more of benzyl alcohol, dodecanedioic acid, toluene, monobenzyl dodecanedioate, and dibenzyl dodecanedioate, or for qualitatively and quantitatively detecting monobenzyl dodecanedioate, dodecanedioic acid, benzyl alcohol, toluene, and / or dibenzyl dodecanedioate.

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