AU2018100833A4

AU2018100833A4 - The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method

Info

Publication number: AU2018100833A4
Application number: AU2018100833A
Authority: AU
Inventors: genan guan
Original assignee: Chengdu Qianye Longhua Petroleum Engineering Technology Consulting Co Ltd
Current assignee: Chengdu Qianye Longhua Petroleum Engineering Technology Consulting Co Ltd
Priority date: 2017-07-03
Filing date: 2018-06-19
Publication date: 2018-08-02
Anticipated expiration: 2026-06-19
Also published as: CN108238904A; GB201713549D0

Abstract

The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method Abstract 5 The present invention discloses the bleeding aromatic acid drugs intermediates p-toluic acid synthesis method, comprises the following steps: 4-methyl-toluene ether, and potassium chloride solution were added to the reaction vessel, controlled the stirring speed, raised the temperature of the solution, continued to react, added lanthanum oxide powder, raised the temperature of the solution, reacted; then added 10 methyl butylenate solution, raised the temperature of the solution, controlled the stirring speed, reacted, reduced the temperature of the solution, added potassium sulfate solution, layered solution, washed with the nitrile solution, washed with the p-chlorine nitrate solution, recrystallized in dihexylamine solution, dehydrated with dehydration, got the finished product p-toluic acid. Figure 1

Description

The present invention discloses the bleeding aromatic acid drugs intermediates p-toluic acid synthesis method, comprises the following steps: 4-methyl-toluene ether, and potassium chloride solution were added to the reaction vessel, controlled the stirring speed, raised the temperature of the solution, continued to react, added lanthanum oxide powder, raised the temperature of the solution, reacted; then added methyl butylenate solution, raised the temperature of the solution, controlled the stirring speed, reacted, reduced the temperature of the solution, added potassium sulfate solution, layered solution, washed with the nitrile solution, washed with the p-chlorine nitrate solution, recrystallized in dihexylamine solution, dehydrated with dehydration, got the finished product p-toluic acid.

Figure 1

2018100833 19 Jun2018

The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method

FIELD OF THE INVENTION

The present invention relates to a method for preparing a pharmaceutical 5 intermediate which belongs to the field of organic synthesis, more particularly, relates to the bleeding aromatic acid drugs intermediates p-toluic acid synthesis method.

GENERAL BACKGROUND

P-toluic acid is mainly used in the manufacture of bleeding aromatic acid, toluene, p-toluenyl chloride, photosensitive material etc, it is used in organic synthesis intermediates and pesticide industry to produce fungicides. Most of the existing synthetic methods are concentrated nitric acid oxidation xylene, react for 30h, which can be produced for p-toluic acid, and the yield is 58%. This method of production requires concentrated nitric acid as reactant, attributes to higher risk, requires high corrosion resistance for equipment in the process and high cost of equipment maintenance, it is not conducive to reducing the overall production cost, and synthetic process needs more than 30 hours, production time is too long, the final yield is not high, only about 58%, so it is necessary to put forward a new method synthesis.

SUMMARY

Based on the technical problems of the background technology, the purpose of the present invention is to provide the bleeding aromatic acid drugs intermediates p-toluic acid synthesis method, comprises the following steps:

A: 4-methyl-toluene ether, and 1.5L potassium chloride solution were added to the reaction vessel, controlled the stirring speed at 230-260rpm,raised the temperature of the solution to 30-38 °C continued to react for 60-90min,added lanthanum oxide powder, raised the temperature of the solution to 40-46 °C,reacted for 2-3h;

B: then added methyl butylenate solution, raised the temperature of the solution to 50-55 °C, controlled the stirring speed at 310-350 rpm, reacted for 90-130 min, reduced the temperature of the solution to 10-15 °C, added 1.6 L potassium sulfate solution, layered solution, washed with the nitrile solution, washed with the p-chlorine nitrate solution, recrystallized in dihexylamine solution, dehydrated with dehydration,

2018100833 19 Jun 2018 got the finished product p-toluic acid.

Preferably, the potassium chloride solution has a mass fraction of 10-17%. Preferably, the mass fraction of the methyl butylenate solution is 40-45%. Preferably, the potassium sulfate solution has a mass fraction of 15-21%. Preferably, the nitrile solution has a mass fraction of 45-52%.

Preferably, the mass fraction of p-chlorine nitrate solution is 60-65%, Preferably, the dihexylamine solution has a mass fraction of 80-87%. Throughout the reaction process can be the following reaction formula:

COOH

Γί

CHj

Compared with the synthetic method disclosed in the background art, the invention provides the bleeding aromatic acid drugs intermediates p-toluic acid synthesis method, it is unnecessary to use concentrated nitric acid as reaction and raw materials, reduce the risk in the process of synthesis coefficient, the corrosion of equipment requirements, the cost of equipment maintenance, and the overall production cost, synthetic process need only a few hours, speed up the production time, reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same lime, the present invention provides a new synthetic route which has laid a good foundation for further enhancing the yield of the reaction.

DESCRIPTION OF THE DRAWING

Figure 1 is the ^l3CNMR infrared analysis spectrum of finished product p-toluic acid.

Figure 2 is carbon atomic marker of a molecule p-toluic acid.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The following examples with reference to specific embodiments of the present invention are further illustrated:

2018100833 19 Jun 2018

Embodiment 1

The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method, comprises the following steps:

A: 2mol 4-methyl-toluene ether, and 1.5L potassium chloride solution with a mass 5 fraction of 10% were added to the reaction vessel, controlled the stirring speed at 230rpm,raised the temperature of the solution to 30°C,continued to react for 60min,added 2mol lanthanum oxide powder, raised the temperature of the solution to

40°C,reacted for 2h;

B: then added 4mol methyl butylenate solution with a mass fraction of 10 40%,raised the temperature of the solution to 50 °C,controlled the stirring speed at 310 rpm, reacted for 90min, reduced the temperature of the solution to 10 °C, added 1.6 L potassium sulfate solution with a mass fraction of 15%,layered solution, washed with the nitrile solution with a mass fraction of 45%, washed with the p-chlorine nitrate solution with a mass fraction of 60%, recrystallized in dihexylamine solution with a mass fraction of 80%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished product p-toluic acid 239.36g, yield of 88%.

Embodiment 2

A: 2mol 4-methyl-toluene ether, and 1.5L potassium chloride solution with a mass fraction of 16% were added to the reaction vessel, controlled the stirring speed at 250rpm,raised the temperature of the solution to 37°C,continued to react for 82min, added 2.8mol lanthanum oxide powder, raised the temperature of the solution to 41 °C,reacted for 2.2h;

B: then added 5mol methyl butylenate solution with a mass fraction of

43%,raised the temperature of the solution to 52 °C,controlled the stirring speed at 330 rpm, reacted for 120min, reduced the temperature of the solution to 12°C,added 1.6 L potassium sulfate solution with a mass fraction of 17%,layered solution, washed with the nitrile solution with a mass fraction of 48%,washed with the p-chlorine nitrate solution with a mass fraction of 62%,recrystallized in dihexylamine solution with a

2018100833 19 Jun 2018 mass fraction of 83%, dehydrated with anhydrous potassium carbonate dehydration, got the finished product p-toluic acid 247.52g, yield of 91%.

Embodiment 3

The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method, 5 comprises the following steps:

A: 2mol 4-methyl-toluene ether, and 1.5L potassium chloride solution with a mass fraction of 17% were added to the reaction vessel, controlled the stirring speed at 260rpm,raised the temperature of the solution to 38°C,continued to react for 90min,added 3mol lanthanum oxide powder, raised the temperature of the solution to

46 °C,reacted for 3h;

B: then added 6mol methyl butylenate solution with a mass fraction of 45%,raised the temperature of the solution to 55 °C,controlled the stirring speed at 350 rpm, reacted for 130min, reduced the temperature of the solution to 15 °C,added 1.6 L potassium sulfate solution with a mass fraction of 21%,layered solution, washed with the nitrile solution with a mass fraction of 52%,washed with the p-chlorine nitrate solution with a mass fraction of 65%,recrystallized in dihexylamine solution with a mass fraction of 87%,dehydrated with anhydrous magnesium sulfate dehydration, got the finished product p-toluic acid 258.4g, yield of 95%.

Infrared analysis of finished product p-toluic acid, ¹³CNMR infrared spectrum is shown in figure 1, the analysis data is shown in table 1.

The carbon atomic number markers in the molecules of p-toluic acid are shown in figure 2.

The detailed operation analysis process is as follows:

Frequency: 15.09 MHz

Sample and solvent ratio:0.130 g:0.9 ml DMSO-d6

Table 1 13C NMR analysis data

Chemical displacement Spectrum peak area Integral atomic number

167.34 239 1

142.98

317

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129.37	1000	3 *
129.09	922	4 *
128.13	256	5
21.10	361	6

The embodiments of the present invention are merely preferred embodiments of the present invention, but the range of the present invention is not limited this, and any person who is familiar with those skilled in the arts, within the technical range of the present invention. It is intended that the technical solution and its inventive concept be replaced or modified equivalently with reference to the range of the invention.

2018100833 19 Jun 2018

Claims

Claims

1. The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method, comprises the following steps:

5 A: 4-methyl-toluene ether, and 1.5L potassium chloride solution were added to the reaction vessel, controlled the stirring speed at 230-260rpm,raised the temperature of the solution to 30-38 °C continued to react for 60-90min,added lanthanum oxide powder, raised the temperature of the solution to 40-46 °C, reacted for
2-3h;

B: then added methyl butylenate solution, raised the temperature of the solution 10 to 50-55 °C controlled the stirring speed at 310-350 rpm, reacted for 90-130 min, reduced the temperature of the solution to 10-15 °C, added 1.6 L potassium sulfate solution, layered solution, washed with the nitrile solution, washed with the p-chlorine nitrate solution, recrystallized in dihexylamine solution, dehydrated with dehydration, got the finished product p-toluic acid.

15 2. The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method according to claim 1 wherein the potassium chloride solution has a mass fraction of

10-17%.
3. The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method according to claim 1 wherein the mass fraction of the methyl butylenate solution is

20 40-45%.
4. The bleeding aromatic acid drugs intermediates p-toluic acid synthesis method according to claim 1 wherein the potassium sulfate solution has a mass fraction of

15-21%

1/1

2018100833 09 Jul 2018 ppm

Figure 1 , ' ^lH

Figure 2