阅读说明：本技术 一种快速检测2-氯-1-（4-异丁基苯）丙酮含量的方法 (Method for rapidly detecting content of 2-chloro-1- (4-isobutylbenzene) acetone ) 是由 杜德平 徐文辉 寇祖星 张哲� 孙科 贾健波 徐冬冬 张田 于 2021-09-14 设计创作，主要内容包括：本发明提供了一种快速检测2-氯-1-(4-异丁基苯)丙酮含量的方法,先通过测定不同含量的2-氯-1-(4-异丁基苯)丙酮溶液的近红外吸收光谱；在相同的光谱测量条件下测定已知含量2-氯-1-(4-异丁基苯)丙酮溶液的验证样品得到2-氯-1-(4-异丁基苯)丙酮含量预测值,分析预测值与已知含量参考值得到二者的相关性图,然后通过相关性图快速检测2-氯-1-(4-异丁基苯)丙酮的含量；本发明解决了布洛芬生产过程中对中间体2-氯-1-(4-异丁基苯)丙酮传统检测方法烦琐、耗时等问题。(The invention provides a method for rapidly detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone, which comprises the steps of firstly determining the near-infrared absorption spectra of 2-chloro-1- (4-isobutylbenzene) acetone solutions with different contents; determining a verification sample of a known content of 2-chloro-1- (4-isobutylbenzene) acetone solution under the same spectral measurement condition to obtain a predicted value of the content of 2-chloro-1- (4-isobutylbenzene) acetone, analyzing the predicted value and a reference value of the known content to obtain a correlation diagram of the predicted value and the reference value of the known content, and then rapidly detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone through the correlation diagram; the invention solves the problems of complex and time-consuming traditional detection method for the intermediate 2-chloro-1- (4-isobutylbenzene) acetone in the production process of ibuprofen.)

1. A method for rapidly detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone is characterized by utilizing a near infrared spectrum technology for rapid detection, and comprises the following steps:

(1) preparing a series of 2-chloro-1- (4-isobutylbenzene) acetone solutions with known content;

(2) near-infrared absorption spectrum scanning is carried out on the 2-chloro-1- (4-isobutylbenzene) acetone solution with known content;

(3) performing Baseline Correction and optical path Correction on the obtained near infrared spectrum optical data;

(4) performing partial least squares regression analysis (PLS) by using chemometrics analysis software Unscamblebler to obtain a near infrared quantitative analysis model;

(5) determining a verification sample of the solution with the known content of 2-chloro-1- (4-isobutylbenzene) acetone under the same spectral measurement condition, and calculating by a quantitative analysis model to obtain a predicted value of the content of 2-chloro-1- (4-isobutylbenzene) acetone; and analyzing the correlation between the predicted value and the reference value with known content.

2. The method for rapidly detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone as claimed in claim 1, wherein 36 parts of 2-chloro-1- (4-isobutylbenzene) acetone solution with known content is prepared in step (1) with content ranging from 91.81 to 96.55% (g/ml).

3. The method as claimed in claim 1, wherein the step (2) is performed by scanning a solution of known 2-chloro-1- (4-isobutylbenzene) acetone with a wavelength of 9300-4700cm by using a near infrared spectrometer^-1Resolution of 16cm^-1The measurement temperature was 18-25 ℃.

Technical Field

The invention belongs to the technical field of chemical analysis, and relates to a method for rapidly detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone.

Technical Field

2-chloro-1- (4-isobutylbenzene) propanone, formula C₁₃H₁₇ClO is easy to dissolve in methylene dichloride, petroleum ether and other organic solvents, and the product is a main intermediate for producing the non-steroidal anti-inflammatory drug ibuprofen. The mainstream synthetic route of 2-chloro-1- (4-isobutylbenzene) acetone is that isobutylbenzene and chloropropionyl chloride are used as raw materials, and the product is prepared through Friedel-crafts acylation reaction, and the intermediate is subjected to condensation, transposition rearrangement, hydrolysis, acidification and other reactions to produce ibuprofen.

The existing method for detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone in production mainly comprises a gas phase area normalization method and a liquid phase internal standard method, but the two methods have relatively complicated sample preparation steps, long retention time of a main component peak, and about 40-60 minutes is needed for each detection, so that the improvement of the yield of ibuprofen is severely restricted. Therefore, it is imperative to search a method for simply and rapidly detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone.

As a modern analysis technology, the near infrared spectrum analysis technology has the characteristics of simplicity, convenience, rapidness, no damage to a sample structure, capability of realizing on-line analysis and the like, and is applied to content detection of pharmaceutical and chemical intermediates. Therefore, the invention adopts the near infrared spectrum analysis technology to establish a method for rapidly detecting the content of the 2-chloro-1- (4-isobutylbenzene) acetone.

Disclosure of Invention

The invention provides a method for rapidly detecting the content of 2-chloro-1- (4-isobutylbenzene) acetone, which comprises the following steps:

(1) preparing a series of 2-chloro-1- (4-isobutylbenzene) acetone solutions with known content;

(2) near-infrared absorption spectrum scanning is carried out on the 2-chloro-1- (4-isobutylbenzene) acetone solution with known content;

(3) performing Baseline Correction and optical path Correction on the obtained near infrared spectrum optical data;

(4) performing partial least squares regression analysis (PLS) by using chemometrics analysis software Unscamblebler to obtain a near infrared quantitative analysis model;

(5) and (3) determining a verification sample of the solution with the known content of 2-chloro-1- (4-isobutylbenzene) acetone under the same spectral measurement condition, and calculating by using a quantitative analysis model to obtain a predicted value of the content of the 2-chloro-1- (4-isobutylbenzene) acetone.

And analyzing the correlation between the predicted value and the reference value with known content.

The preparation of a series of known amounts of 2-chloro-1- (4-isobutylbenzene) acetone solution was 36 parts, ranging in amount from 91.81 to 96.55% (g/ml).

The near infrared absorption spectrum scanning is carried out on the 2-chloro-1- (4-isobutylbenzene) acetone solution with the known content, and the wavelength range is 9300-4700cm^-1Resolution of 16cm^-1The number of scanning times: the average spectrum was stored 64 times with a measurement temperature of 18-25 ℃ and 3 scans of each sample.

The invention solves the problems of complex and time-consuming traditional detection method for the intermediate 2-chloro-1- (4-isobutylbenzene) acetone in the production process of ibuprofen.

Drawings

FIG. 1 shows the near-infrared absorption spectra of 2-chloro-1- (4-isobutylbenzene) acetone solutions with different contents;

FIG. 2 is a graph showing the correlation between the reference value and the predicted value of the content of the 2-chloro-1- (4-isobutylbenzene) acetone solution.

Detailed Description

In order to make the objects, technical solutions and effects of the present invention clearer and clearer, the present invention will be further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

Example 1

1. 36 parts of 2-chloro-1- (4-isobutylbenzene) acetone solution with different contents are prepared, the content range is 91.81-96.55% (g/ml), and the content range can cover the content range (92-96%, g/ml) of the 2-chloro-1- (4-isobutylbenzene) acetone solution in the production, and specific data are shown in a table 1:

TABLE 1 content data of 36 parts of 2-chloro-1- (4-isobutylbenzene) acetone solution.

2. Using an MB3600 near infrared spectrometer of ABB company, respectively carrying out near infrared spectrum measurement on 36 parts of 2-chloro-1- (4-isobutylbenzene) acetone solution with known content, taking air as reference, and setting scanning wavelength ranges as follows: 9300-4700 cm-^-1Resolution ratio: 16cm^-1The number of scanning times: the measurement was repeated 3 times for each sample 64 times, and the spectrum was averaged. The near infrared absorption spectra of the obtained acetone solutions with different contents of 2-chloro-1- (4-isobutylbenzene) are shown in FIG. 1.

3. And carrying out Baseline Correction and optical path Correction on the obtained near infrared spectrum optical data.

4. Partial least squares regression analysis (PLS) was performed using the chemometrics analysis software Unscamblebler to obtain the coefficients of certainty (R) for the near infrared quantitative analysis model²) At 0.9217, the cross-validation Root Mean Square Error (RMSEC) was 0.5093 and the prediction Root Mean Square Error (RMSEP) was 0.5909.

5. 16 parts of validation samples of the acetone solution with the known content of 2-chloro-1- (4-isobutylbenzene) are determined under the same spectral measurement condition, and the predicted value of the content of the 2-chloro-1- (4-isobutylbenzene) acetone is obtained by calculation through a quantitative analysis model. The specific values are shown in table 2, and the correlation diagram shown in fig. 2 is obtained by analyzing the predicted values and the reference values with known contents. As can be seen from FIG. 2, the method of the present invention has a good correlation between the predicted value of the 2-chloro-1- (4-isobutylbenzene) acetone content of the sample and the reference value, R is 0.998, therefore, the near infrared detection data can be determined to be accurate and reliable, and the method can realize the rapid detection of the 2-chloro-1- (4-isobutylbenzene) acetone content.

Table 2. 18 validation sample predictor and reference data.

Serial number	Reference value	Prediction value	Absolute deviation
				1	91.84	91.79	0.05
2	92.57	92.60	-0.03
				3	93.37	93.27	0.10
4	94.34	94.40	-0.06
				5	94.45	94.50	-0.05
6	94.94	95.05	-0.11
				7	94.90	95.10	-0.20
8	95.42	95.46	-0.03
				9	95.53	95.58	-0.04
10	96.05	95.90	0.15
				11	95.70	95.83	-0.13
12	95.84	95.86	-0.02
				13	95.84	95.90	-0.06
14	95.94	96.03	-0.08
				15	96.20	96.15	0.06
16	96.29	96.31	-0.02