AU2018100842A4

AU2018100842A4 - Pharmaceutical intermediates adipic acid synthesis method

Info

Publication number: AU2018100842A4
Application number: AU2018100842A
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: 2017-08-19
Filing date: 2018-06-20
Publication date: 2018-08-02
Anticipated expiration: 2026-06-20
Also published as: CN108238927A; GB201713865D0

Abstract

Pharmaceutical intermediates adipic acid synthesis method Abstract 5 The present invention discloses pharmaceutical intermediates adipic acid synthesis method, comprises the following steps: 2-bromo-cyclohexylamine and potassium sulfate solution is added to the reaction vessel, the stirring speed is controlled, slowly raised the temperature, raised the temperature, continue to react; hexachlorocyclochrome is added in batches, raised the temperature, then the 10 heptanoate solution is added, continued the reaction, sodium nitrate solution is added, reduced the temperature, the solution layer is separated, washed with cyclopentane solution, washed with 3-hexanol solution, recrystallizated in the 3-methyl pyridine solution, dehydrated with dehydration, got the finished adipic acid. 15 Figure 1

Description

The present invention discloses pharmaceutical intermediates adipic acid synthesis method, comprises the following steps: 2-bromo-cyclohexylamine and potassium sulfate solution is added to the reaction vessel, the stirring speed is controlled, slowly raised the temperature, raised the temperature, continue to react; hexachlorocyclochrome is added in batches, raised the temperature, then the heptanoate solution is added, continued the reaction, sodium nitrate solution is added, reduced the temperature, the solution layer is separated, washed with cyclopentane solution, washed with 3-hexanol solution, recrystallizated in the 3-methyl pyridine solution, dehydrated with dehydration, got the finished adipic acid.

Figure 1

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Pharmaceutical intermediates adipic 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 pharmaceutical intermediates adipic acid synthesis method.

GENERAL BACKGROLND

Adipic acid is a raw material for pharmaceuticals, yeast purification, insecticides, 10 adhesives, synthesis leathers, synthesis dyes and fragrances. It is also used in the manufacture of plasticizers and lubricants, organic synthesis, fluxes, resins, plastics. It can be used for the production of various ester products, but also for the polyurethane elastomer raw materials. Most of the existing synthesis methods using cyclohexane as raw material, acetic acid as solvent, cobalt and bromide as catalyst, react for 10-13h at the situation of 2MP and 90°C, the final yield of 75%.

This kind of synthesis method requires the use of cobalt and bromide. This compound has high environmental pollution, higher cost of later pollution treatment, higher reaction cost and higher reaction temperature which is above 90 °C, higher energy consumption; longer reaction time, which reached 10-13h, is not conducive to reducing the cost of response, the synthesis method is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthesis method.

SLMMARY

Based on the technical problems of the background technology, the purpose of the present invention is to provide pharmaceutical intermediates adipic acid synthesis method, comprises the following steps:

A: 2-bromo-cyclohexylamine and potassium sulfate solution is added to the reaction vessel, the stirring speed is controlled at 170-210 rpm, slowly raised the temperature, raised the temperature to 30-40 °C within 80-110 min, continue to react for 50-80 min;

B: hexachlorocyclochrome is added in batches in 1-2 h, raised the temperature to

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45-52 °C, then the heptanoate solution is added, continued the reaction for 90-130 min, sodium nitrate solution is added, reduced the temperature to 5-9 °C, the solution layer is separated, washed with cyclopentane solution, washed with 3-hexanol solution, recrystallizated in the 3-methyl pyridine solution, dehydrated with dehydration, got the finished adipic acid.

Preferably, the potassium sulfate solution has a mass fraction of 10-16%. Preferably, the mass fraction of the heptanoate solution is 30-37%.

Preferably, the sodium nitrate solution has a mass fraction of 10-15%.

Preferably, the cyclopentane solution has a mass fraction of 40-47%.

Preferably, the mass fraction of 3-hexanol solution is 55-62%.

Preferably, the mass fraction of 3-methyl pyridine solution is 80-86%.

Throughout the reaction process can be the following reaction formula:

NH₂

C₈H_I6O₂ + Cr(CO)₆ _J

COOH

OH₂)₄

COOH

Compared with the synthesis method disclosed in the background art, the invention provides pharmaceutical intermediates adipic acid synthesis method, it is unnecessary to use cobalt and bromide, avoiding the pollution of this compound on the environment, reducing the cost of post-pollution treatment, and the cost of the reaction, and the reaction temperature is low, it is unnecessary to reach more than 90 °C, which leads to lower energy consumption; reaction time is shortened, and no longer need 10-13h, it is conducive to reducing the cost of response, thus reducing intermediate links reaction, decreasing the reaction time and improving the reaction yield, at the same time, 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 DRAWINGS

Figure 1 is the infrared analysis spectrum of finished product adipic acid.

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DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

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

Embodiment 1

Pharmaceutical intermediates adipic acid synthesis method, comprises the following steps:

A: 3mol 2-bromo-cyclohexylamine and 1.3L potassium sulfate solution with a mass fraction of 10% is added to the reaction vessel, the stirring speed is controlled at 170 rpm, slowly raised the temperature, raised the temperature to 30 °C within 80 min, continue to react for 50 min;

B: 3 mol hexachlorocyclochrome is added for 2 times in 1 h, raised the temperature to 45 °C, then 6mol heptanoate solution with a mass fraction of 30% is added, continued the reaction for 90 min, 900ml sodium nitrate solution with a mass fraction of 10% is added, reduced the temperature to 5 °C, the solution layer is separated, washed with cyclopentane solution with a mass fraction of 40%, washed with

3-hexanol solution with a mass fraction of 55%, recrystallizated in the 3-methyl pyridine solution with a mass fraction of 80%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished adipic acid 385.44g, yield of 88%.

Embodiment 2

A: 3mol 2-bromo-cyclohexylamine and 1.3L potassium sulfate solution with a mass fraction of 13% is added to the reaction vessel, the stirring speed is controlled at 190 rpm, slowly raised the temperature, raised the temperature to 35 °C within 95 min, continue to react for 65 min;

B: 3.5 mol hexachlorocyclochrome is added for 3 times in 1.5 h, raised the temperature to 48.5 °C, then 7mol heptanoate solution with a mass fraction of 34% is added, continued the reaction for 110 min, 900ml sodium nitrate solution with a mass fraction of 13% is added, reduced the temperature to 7°C, the solution layer is separated, washed with cyclopentane solution with a mass fraction of 44%, washed with

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3-hexanol solution with a mass fraction of 58%, recrystallizated in the 3-methyl pyridine solution with a mass fraction of 83.5%, dehydrated with anhydrous potassium carbonate dehydration, got the finished adipic acid 402.96g, yield of 92%.

Embodiment 3

A: 3mol 2-bromo-cyclohexylamine and 1.3L potassium sulfate solution with a mass fraction of 16% is added to the reaction vessel, the stirring speed is controlled at 210 rpm, slowly raised the temperature, raised the temperature to 40 °C within 110 min, continue to react for 80 min;

B: 4 mol hexachlorocyclochrome is added for 4 times in 2 h, raised the temperature to 52 °C, then 8mol heptanoate solution with a mass fraction of 37% is added, continued the reaction for 130 min, 900ml sodium nitrate solution with a mass fraction of 15% is added, reduced the temperature to 9°C, the solution layer is separated, washed with cyclopentane solution with a mass fraction of 47%, washed with 3-hexanol solution with a mass fraction of 62%, recrystallizated in the 3-methyl pyridine solution with a mass fraction of 86%, dehydrated with anhydrous magnesium sulfate dehydration, got the finished adipic acid 416. lg, yield of 95%.

Infrared analysis of finished product adipic acid, infrared spectrum is shown in figure 1, the analysis of data is shown in table 1.

Table 1 peak data

Serial	Peak position	Transmittance	Half width	Peak difference
number	(cm'¹)	(%)	(cnf¹)	(%)
1	678	67	34	24
2	931	48	89	35
3	1188	34	39	43
4	1279	21	57	53
5	1355	61	43	11

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.

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Claims

Claims

1. Pharmaceutical intermediates adipic acid synthesis method, comprises the following steps:

5 A:
2-bromo-cyclohexylamine and potassium sulfate solution is added to the reaction vessel, the stirring speed is controlled at 170-210 rpm, slowly raised the temperature, raised the temperature to 30-40 °C within 80-110 min, continue to react for 50-80 min;

B: hexachlorocyclochrome is added in batches in 1-2 h, raised the temperature to 10 45-52 °C, then the heptanoate solution is added, continued the reaction for 90-130 min, sodium nitrate solution is added, reduced the temperature to 5-9 °C, the solution layer is separated, washed with cyclopentane solution, washed with 3-hexanol solution, recrystallizated in the 3-methyl pyridine solution, dehydrated with dehydration, got the finished adipic acid.

15 2. Pharmaceutical intermediates adipic acid synthesis method according to claim

1 wherein the potassium sulfate solution has a mass fraction of 10-16%.
3. Pharmaceutical intermediates adipic acid synthesis method according to claim 1 wherein the mass fraction of the heptanoate solution is 30-37%.
4. Pharmaceutical intermediates adipic acid synthesis method according to claim

20 1 wherein the sodium nitrate solution has a mass fraction of 10-15%.

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Figure 1