AU2018100844A4

AU2018100844A4 - Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method

Info

Publication number: AU2018100844A4
Application number: AU2018100844A
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: 2018-08-09
Anticipated expiration: 2026-06-20
Also published as: GB201713868D0; IES20180203A2; CN108238886A

Abstract

Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method Abstract The present invention discloses chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method, comprises the following steps:2,3 -dihydroxy-4,5,6-trichloro-aniline, cyclohexane solution is added to the reaction vessel, slowly raising the temperature, raising the temperature, then adds 10 potassium sulfate solution, reacts; continues to add the 2,3-dichloropropene solution, reduces the temperature, adds tricarbonyl menthyl manganese in batches, controls the stirring speed, continues to react, then the solution layers, the temperature is decreased, washed several times with sodium chloride solution, several times with ethylene oxide solution, several times with 1,4-dichlorobutane solution, recrystallized in 15 dichloropentane solution, dehydrated with dehydrating agent, got the finished product o-tetrachlorobenzoquinone. Figure 1 80 - 4000 3500 3000 2500 2000 1500 1000 500 Figure 1

Description

The present invention discloses chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method, comprises the following steps:2,3-dihydroxy-4,5,6-trichloro-aniline, cyclohexane solution is added to the reaction vessel, slowly raising the temperature, raising the temperature, then adds potassium sulfate solution, reacts; continues to add the 2,3-dichloropropene solution, reduces the temperature, adds tricarbonyl menthyl manganese in batches, controls the stirring speed, continues to react, then the solution layers, the temperature is decreased, washed several times with sodium chloride solution, several times with ethylene oxide solution, several times with 1,4-dichlorobutane solution, recrystallized in dichloropentane solution, dehydrated with dehydrating agent, got the finished product o -tetrachlorobenzo quinone.

Figure 1

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Figure 1

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Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method

FIELD OF THE INVENTION

The present invention relates to a method for preparing a pharmaceutical intermediate which belongs to the field of organic synthesis, more particularly, relates to chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method.

GENERAL BACKGROUND

O-tetrachlorobenzoquinone is mainly used as chlormadinone synthesis 10 intermediates and organic synthesis dehydrogenation reagents. Most of the existing synthesis methods are using the process that pentachlorophenol reacts with nitric acid in chloroform. However, this method requires the use of nitric acid as one of the reactants, due to strong corrosion and oxidation capacity of nitric acid, the equipment corrosion resistance requirements are higher, equipment manufacturing and maintenance costs are high, is not conducive to reducing production costs, and the synthesis method is complicated and the final yield is not very high. Therefore, it is necessary to propose a new synthesis method.

SUMMARY

Based on the technical problems of the background technology, the purpose of the present invention is to provide chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method, comprises the following steps:

A: 2,3-dihydroxy-4,5,6-trichloro-aniline, cyclohexane solution is added to the reaction vessel, slowly raising the temperature, raising the temperature to 25-31 °C in 90-130 min, then adds potassium sulfate solution, reacts for 1-2 h;

B: continues to add the 2,3-dichloropropene solution, reduces the temperature to

15-22 °C, adds tricarbonyl menthyl manganese in batches, controls the stirring speed at 150-180 rpm, continues to react for 90-130 min, then the solution layers, the temperature is decreased to 5-9 ° C, washed several times with sodium chloride solution, several times with ethylene oxide solution, several times with

1,4-dichlorobutane solution, recrystallized in dichloropentane solution, dehydrated

2018100844 20 Jun2018 with dehydrating agent, got the finished product o-tetrachlorobenzoquinone.

Preferably, the cyclohexane solution has a mass fraction of 20-26%.

Preferably, the potassium sulfate solution has a mass fraction of 10-15%.

Preferably, the mass fraction of the 2,3-dichloropropene solution is 35-42%.

Preferably, the sodium chloride solution has a mass fraction of 10-16%.

Preferably, the ethylene oxide solution has a mass fraction of 40-46%. Preferably, the mass fraction of 1,4-dichlorobutane solution is50-55%. Preferably, the dichloropentane has a mass fraction of 75-83%.

Throughout the reaction process can be the following reaction formula:

Compared with the synthesis method disclosed in the background art, the invention provides chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method, it is unnecessary to use nitric acid as reactants, avoiding the equipment effected by the corrosion and oxidation of nitric acid and reducing equipment manufacturing and maintenance costs, which is conducive to reducing production costs, 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 o -letrac h lorobenzo q uino ne.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

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

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Embodiment 1

Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method, comprises the following steps:

A: 3 mol 2,3-dihydroxy-4,5,6-trichloro-aniline, 1.3L cyclohexane solution with a 5 mass fraction of 20% is added to the reaction vessel, slowly raising the temperature, raising the temperature to 25°C in 90 min, then adds 800 ml potassium sulfate solution with a mass fraction of 10%, reacts for 1 h;

B: continues to add the 6 mol 2,3-dichloropropene solution with a mass fraction of 35%, reduces the temperature to 15 °C, adds 3mol tricarbonyl menthyl manganese in batches, controls the stirring speed at 150 rpm, continues to react for 90 min, then the solution layers, the temperature is decreased to 5 ° C, washed 3 times with sodium chloride solution with a mass fraction of 10%, 5 times with ethylene oxide solution with a mass fraction of 40%, 2 times with 1,4-dichlorobutane solution with a mass fraction of 50%, recrystallized in dichloropentane solution with a mass fraction of

75%, dehydrated with anhydrous magnesium sulfate dehydrating agent, got the finished product o-tetrachlorobenzoquinone 641.77 g, yield of 87%.

Embodiment 2

A: 3 mol 2,3-dihydroxy-4,5,6-trichloro-aniline, 1.3L cyclohexane solution with a mass fraction of 23.5% is added to the reaction vessel, slowly raising the temperature, raising the temperature to 28°C in 110 min, then adds 800 ml potassium sulfate solution with a mass fraction of 12.5%, reacts for 1.5 h;

B: continues to add the 6.5 mol 2,3-dichloropropene solution with a mass fraction of 37%, reduces the temperature to 17 °C, adds 3.5mol tricarbonyl menthyl manganese in batches, controls the stirring speed at 165 rpm, continues to react for 110 min, then the solution layers, the temperature is decreased to 7°C, washed 3 times with sodium chloride solution with a mass fraction of 13%, 6 times with ethylene oxide solution with a mass fraction of 43%, 3 times with 1,4-dichlorobutane solution with a mass fraction of 52.5%, recrystallized in dichloropentane solution with a mass fraction of

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79%, dehydrated with anhydrous calcium chloride dehydrating agent, got the finished product o-tetrachlorobenzoquinone 671.28 g, yield of 91%.

Embodiment 3

Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method, 5 comprises the following steps:

A: 3 mol 2,3-dihydroxy-4,5,6-trichloro-aniline, 1.3L cyclohexane solution with a mass fraction of 26% is added to the reaction vessel, slowly raising the temperature, raising the temperature to 31 °C in 130 min, then adds 800 ml potassium sulfate solution with a mass fraction of 15%, reacts for 2 h;

B: continues to add the 7 mol 2,3-dichloropropene solution with a mass fraction of 42%, reduces the temperature to 22 °C, adds 4mol tricarbonyl menthyl manganese in batches, controls the stirring speed at 180 rpm, continues to react for 130 min, then the solution layers, the temperature is decreased to 9 °C, washed 3 times with sodium chloride solution with a mass fraction of 16%, 7 times with ethylene oxide solution with a mass fraction of 46%, 4 times with 1,4-dichlorobutane solution with a mass fraction of 55%, recrystallized in dichloropentane solution with a mass fraction of 83%, dehydrated with anhydrous magnesium sulfate dehydrating agent, got the finished product o-tetrachlorobenzoquinone 693.41 g, yield of 94%.

Infrared analysis of finished product o-tetrachlorobenzoquinone, 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)	(%)	(cm'¹)	(%)
1	780	14	17	77
2	814	48	10	47
3	1153	27	13	59
4	1186	58	23	21
5	1230	34	19	17
6	1252	9	31	49
7	1293	61	26	21

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8	1513	24	13	61
9	1558	36	17	49
10	1682	10	35	39
11	1704	38	11	11
12	3348	59	1001	10

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. Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method, comprises the following steps:

5 A:
2,3-dihydroxy-4,5,6-trichloro-aniline, cyclohexane solution is added to the reaction vessel, slowly raising the temperature, raising the temperature to 25-31 °C in 90-130 min, then adds potassium sulfate solution, reacts for 1-2 h;

B: continues to add the 2,3-dichloropropene solution, reduces the temperature to 15-22 °C, adds tricarbonyl menthyl manganese in batches, controls the stirring speed

10 at 150-180 rpm, continues to react for 90-130 min, then the solution layers, the temperature is decreased to 5-9 °C, washed several times with sodium chloride solution, several times with ethylene oxide solution, several times with 1,4-dichlorobutane solution, recrystallized in dichloropentane solution, dehydrated with dehydrating agent, got the finished product o-tetrachlorobenzoquinone.

15 2. Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method according to claim 1 wherein the cyclohexane solution has a mass fraction of

20-26%.
3. Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method according to claim 1 wherein the potassium sulfate solution has a mass

20 fraction of 10-15%.
4. Chlormadinone drug intermediates o-tetrachlorobenzoquinone synthesis method according to claim 1 wherein the mass fraction of the 2,3-dichloropropene solution is 35-42%.

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Figure 1