CN108503566B

CN108503566B - Preparation method of fine chemical intermediate

Info

Publication number: CN108503566B
Application number: CN201810453832.7A
Authority: CN
Inventors: 刘可
Original assignee: Anhui Jixi County Huihuang Chemical Co ltd
Current assignee: ANHUI JIXI COUNTY HUIHUANG CHEMICAL Co.,Ltd.
Priority date: 2018-05-14
Filing date: 2018-05-14
Publication date: 2020-04-28
Anticipated expiration: 2038-05-14
Also published as: CN108503566A

Abstract

The invention relates to a preparation method of a fine chemical intermediate, which comprises the following steps: (a) adding p-methylsulfonyl toluene and concentrated H into a reaction vessel₂SO₄Stirring and dissolving, dripping fuming nitric acid under the condition of ice bath, removing the ice bath after dripping, and heating to 80-120 ℃ for reaction; pouring into a large amount of ice water to separate out white solid, performing suction filtration, and drying a filter cake to obtain a compound ii; (b) adding said compound ii and concentrated H to another reaction vessel₂SO₄Stirring for dissolving, and adding Dasimetin oxidant and K in portions under ice bath condition₂Cr₂O₇Removing the ice bath and reacting at room temperature; extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography. Thus greatly reducing K₂Cr₂O₇The usage amount of (A) is beneficial to improving the purity and the yield of the final product.

Description

Preparation method of fine chemical intermediate

Technical Field

The invention belongs to the field of fine chemical intermediates, and particularly relates to a preparation method of 4-methylsulfonyl-2, 6-dinitrobenzoic acid.

Background

4-methylsulfonyl-2, 6-dinitrobenzoic acid is an important organic synthesis intermediate, is applied to the production of dyes, medicines and pesticides, and is prepared by using 2-nitro-4-methylsulfonyl toluene as a raw material. Because the benzene ring of the 2-nitro-4-methylsulfonyl toluene is provided with two electron-withdrawing groups, the oxidation difficulty is higher, and the control of the oxidation degree is difficult. For example, the oxidation by the existing sodium dichromate oxidation method needs to use excessive sodium dichromate, which generates high-concentration chromium-containing waste liquid, and the final yield is only 88% and the product purity is 99%, which obviously cannot meet the synthesis requirement of the medical intermediate.

Disclosure of Invention

The invention aims to overcome the defects of the prior art and provide a preparation method of a fine chemical intermediate.

In order to achieve the purpose, the invention adopts the technical scheme that: a preparation method of a fine chemical intermediate comprises the following steps:

(a) adding p-methylsulfonyl toluene and concentrated H into a reaction vessel₂SO₄Stirring and dissolving, dripping fuming nitric acid under the condition of ice bath, removing the ice bath after dripping, and heating to 80-120 ℃ for reaction; falling downSeparating out white solid in a large amount of ice water, carrying out suction filtration, and drying a filter cake to obtain a compound ii;

(b) adding said compound ii and concentrated H to another reaction vessel₂SO₄Stirring for dissolving, and adding Dismetin oxidant (i.e. DMP) and K in portions under ice bath condition₂Cr₂O₇Removing the ice bath and reacting at room temperature; extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography.

Optimally, in step (b), the desselatin oxidant and K₂Cr₂O₇The mass ratio of (A) to (B) is 8-10: 1.

Further, in step (b), the desselatin oxidant and K₂Cr₂O₇The mass ratio of (A) to (B) is 10: 1.

Due to the application of the technical scheme, compared with the prior art, the invention has the following advantages: the preparation method of the fine chemical intermediate of the invention is that the dessimidine oxidant and the K are added in batches₂Cr₂O₇Thereby achieving sufficient oxidation of compound ii, which substantially reduces K₂Cr₂O₇The usage amount of (A) is beneficial to improving the purity and the yield of the final product.

Drawings

FIG. 1 is a flow chart of a preparation method of a fine chemical intermediate of the invention;

FIG. 2 is a nuclear magnetic spectrum of a compound ii in the preparation method of the fine chemical intermediate;

FIG. 3 is a nuclear magnetic spectrum of a compound i in the preparation method of the fine chemical intermediate.

Detailed Description

The preparation method of the fine chemical intermediate comprises the following steps: (a) adding p-methylsulfonyl toluene and concentrated H into a reaction vessel₂SO₄Stirring and dissolving, dripping fuming nitric acid under the condition of ice bath, removing the ice bath after dripping, and heating to 80-120 ℃ for reaction; pouring into ice water to separate out white solid, filtering, and dryingFiltering the filter cake to obtain a compound ii; (b) adding said compound ii and concentrated H to another reaction vessel₂SO₄Stirring for dissolving, and adding Dasimetin oxidant and K in portions under ice bath condition₂Cr₂O₇Removing the ice bath and reacting at room temperature; extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography. By batchwise addition of dessimidine oxidant and K₂Cr₂O₇Thereby achieving sufficient oxidation of compound ii, which substantially reduces K₂Cr₂O₇The usage amount of (A) is beneficial to improving the purity and the yield of the final product. In step (b), the dessimidine oxidant and K₂Cr₂O₇The mass ratio of (A) to (B) is preferably 8-10: 1; most preferably 10: 1.

The following detailed description of preferred embodiments of the invention is provided:

example 1

This example provides a preparation method of fine chemical intermediates, as shown in fig. 1, which comprises the following steps:

(a) to a 250 mL three-necked flask was added p-methylsulfonyltoluene (20 g, 117.6 mmol, 1 eq) and concentrated H₂SO₄(40 mL, commercially available), stirring to dissolve, dropping fuming nitric acid (60 mL, dropping speed 20mL/10 min) under ice bath condition, removing ice bath, heating to 100 deg.C, and reacting for 2.5 h (TLC shows that the raw materials are completely reacted); slowly pouring the reaction liquid into a large amount of ice water, separating out a large amount of white solids, performing suction filtration, and drying a filter cake to obtain 28g of a compound ii as a white solid; the nuclear magnetic spectrum is shown in figure 2, and specifically comprises the following steps:¹H NMR(400 MHz, DMSO-d ₆) δ (ppm): 8.53 (s, 1、2H), 3.18 (s,3H), 2.69 (s, 3H)。ESI-MS m/z calcd: : C₈H₈N₂O₆S([M-H]^-); 259.01, found: 259.0；

(b) to a 250 mL single-neck flask was added compound ii (10 g, 38.4 mmol, 1 eq) and concentrated H₂SO₄(70 mL, commercially available), dissolved with stirring, and K was added in three portions under ice-bath₂Cr₂O₇(1.14 g, 3.84 mmol, 0.1 eq) and DMP (38.4 mmol, 1 eq) (the mass of each batch added is one third of the total mass of the mixture), and after the addition, the ice bath is removed and the reaction is carried out overnight at room temperature (about 8-12 h, at which time TLC shows the reaction of the raw materials is complete); the reaction was slowly poured into ice water (about 50 mL), extracted with ethyl acetate (60 mL each time for 5 times), dried over anhydrous sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to give 10.5g of compound i (yield 95%, purity 99.5%) as a yellow solid, whose nuclear magnetic spectrum is shown in fig. 3, specifically:¹H NMR (400 MHz, DMSO-d ₆) δ (ppm): 8.90 (s, 2H), 3.45(s, 3H)。ESI-MS m/z calcd: C₈H₆N₂O₈S([M-H]^-);288.98, found: 289.1。

example 2

This example provides a process for the preparation of a fine chemical intermediate, which is essentially the same as that of example 1, except that: bringing the DMP to 30.7 mmol in step (b); finally, 10.0g of Compound i (yield 90%, purity 99.2%) was obtained as a yellow solid.

Example 3

This example provides a process for the preparation of a fine chemical intermediate, which is essentially the same as that of example 1, except that: bringing the DMP to 32.6mmol in step (b); finally, 10.2g of Compound i (92% yield, 99.3% purity) was obtained as a yellow solid.

Comparative example 1

This example provides a process for the preparation of a fine chemical intermediate, which is essentially the same as that of example 1, except that: k in step (b)₂Cr₂O₇And the mixture of DMP is added in one portion; 9.2g of Compound i (85% yield, 89.3% purity) are obtained as a yellow solid.

Comparative example 2

This example provides a process for the preparation of a fine chemical intermediate, which is essentially the same as that of example 1, except that: adding only 3.84 mmoleK in step (b)₂Cr₂O₇(ii) a Finally 4.5g of Compound i are obtained as a yellow solid (yield 47%, purity)89.5%).

Comparative example 3

This example provides a process for the preparation of a fine chemical intermediate, which is essentially the same as that of example 1, except that: only 69.2 mmoleK was added in step (b)₂Cr₂O₇(ii) a The final product was 10g of Compound i as a yellow solid (yield 90%, purity 99.0%).

The above embodiments are merely illustrative of the technical concept and features of the present invention, and the purpose thereof is to enable those skilled in the art to understand the content of the present invention and implement the invention, and not to limit the scope of the invention, and all equivalent changes or modifications made according to the spirit of the present invention should be covered by the scope of the present invention.

Claims

1. The preparation method of the fine chemical intermediate is characterized in that the reaction route is as follows:

the method comprises the following steps:

(a) adding p-methylsulfonyl toluene and concentrated H into a reaction vessel₂SO₄Stirring and dissolving, dripping fuming nitric acid under the condition of ice bath, removing the ice bath after dripping, and heating to 80-120 ℃ for reaction; pouring into a large amount of ice water to separate out white solid, performing suction filtration, and drying a filter cake to obtain a compound ii;

(b) adding said compound ii and concentrated H to another reaction vessel₂SO₄Stirring for dissolving, and adding Dasimetin oxidant and K in portions under ice bath condition₂Cr₂O₇Removing the ice bath and reacting at room temperature; extracting with ethyl acetate, drying with anhydrous sodium sulfate, concentrating under reduced pressure, and purifying by column chromatography; the dessimidine oxidant and K₂Cr₂O₇The mass ratio of (A) to (B) is 8-10: 1.

2. the fine chemical engineering intermediate of claim 1A method of making a body, comprising: in step (b), the dessimidine oxidant and K₂Cr₂O₇The mass ratio of (A) to (B) is 10: 1.