AU2018101108A4 - Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method - Google Patents
Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method Download PDFInfo
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- C07—ORGANIC CHEMISTRY
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- C07C46/00—Preparation of quinones
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Abstract
Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method Abstract The present invention discloses aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method, comprises the following steps: 2,3,5,6-tetrachloro-1,4-dimethoxybenzene solution and potassium chloride were added to the reaction vessel, controlled the temperature of the solution, added 10 aluminum acetylacetonate powder in batches, controlled the stirring speed rpm, reacted;: added the tributyl borate solution, raised the temperature, and then added the sodium nitrate solution, reacted, after the solution layered, reduced the temperature, washed with hexyl ether solution for several times, washed with 3-methyl pyridine solution for several times, recrystallized from the chloroacetyl chloride solution, 15 dehydrated with dehydration, got the finished product tetrachlorobenzoquinone. Figure 1 Oo0 3500 3000 2500 2000 1500 1000 500 Figure I
Description
The present invention discloses aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method, comprises the following steps:
2,3,5,6-tetrachloro-l,4-dimethoxybenzene solution and potassium chloride were added to the reaction vessel, controlled the temperature of the solution, added 10 aluminum acetylacetonate powder in batches, controlled the stirring speed rpm, reacted;: added the tributyl borate solution, raised the temperature, and then added the sodium nitrate solution, reacted, after the solution layered, reduced the temperature, washed with hexyl ether solution for several times, washed with 3-methyl pyridine solution for several times, recrystallized from the chloroacetyl chloride solution, 15 dehydrated with dehydration, got the finished product tetrachlorobenzoquinone.
Figure 1
2018101108 11 Aug 2018
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Figure 1 ι
2018101108 11 Aug 2018
Aminoquinone drug intermediates 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 aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method.
GENERAL BACKGROUND
Tetrachlorobenzoquinone in the pharmaceutical industry is mainly used for the 10 production of anti-malignant tumor drug imine quinone, anti-aldosterone drug spironolactone. Tetrachlorobenzoquinone is reducted with sulfur dioxide at room temperature, obtained tetrachloroquinone, which is pesticides and macromolecules intermediates. Most of the existing synthesis methods using the process that obtains by the oxidation of pentachlorophenol, 20% sodium pentachlorophenol solution is 15 added to the reactor, acidificated with equimolar hydrochloric acidwith a mass fraction of 35%, stirred into a paste. And then 6% weight of sodium pentachlorophenol’ anhydrous ferric chloride is put into, heated to 70 °C or more, begins to pass into chlorine, maintained the reaction temperature above 95 °C, to the reaction of the oil completely clear without particles as the end. Removing the water 20 layer, adds 98% concentrated sulfuric acid, obtained tetrachloroquinone. This synthesis method requires the use of hydrochloric acid, chlorine and concentrated sulfuric acid as reactants, hydrochloric acid and concentrated sulfuric acid are all corrosive liquids, the requirements of the equipment’s corrosion resistance are higher, and chlorine is a toxic gas, the health of synthesis operators get greater harm, the 25 synthesis process is of high risk, and the reaction temperature should be above 95 °C, the reaction energy consumption is high, resulting in increased cost of the reaction, 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 aminoquinone drug intermediates tetrachlorobenzoquinonc synthesis method, comprises the following steps:
A: 2,3,5,6-tctrachloro-l,4-dimethoxybcnzene solution and potassium chloride were added to the reaction vessel, controlled the temperature of the solution at 40-46 QC, added aluminum aeetylacctonatc powder in batches, controlled the stirring speed at 230-260 rpm, reacted for 90-130 min;
B: added the tributyl borate solution, raised the temperature to 50-58°C, and then added the sodium nitrate solution, reacted for 1-2 h, after the solution layered, reduced the temperature to 15-22 °C, washed with hexyl ether solution for several times, washed with 3-mcthyl pyridine solution for several times, recrystallized from the chloroacctyl chloride solution, dehydrated with dehydration, got the finished product 1 et rach Iorobenzo q uinonc.
Preferably, the potassium chloride solution has a mass fraction of 10-16%.
Preferably, the mass fraction of the tributyl borate solution is 30-37%.
Preferably, the sodium nitrate solution has a mass fraction of 20-25%.
Preferably, the hexyl ether solution has a mass fraction of 50-57%.
Preferably, the mass fraction Df 3-methyl pyridine solution is 60-66%.
Preferably, the chloroacetyl chloride solution has a mass fraction of 80-87%.
Throughout the reaction process can be the following reaction formula:
+ C.
C15H2] AlOg
the synthesis method disclosed in the background art, the invention provides aminoquinonc drug intermediates tctraehlorobenzoquinone synthesis method, it is unnecessary to use hydrochloric acid, chlorine and concentrated sulfuric acid as the reactants, avoiding the corrosive liquids hydrochloric acid and concentrated sulfuric acid’s bad effects, reducing the synthesis cost, avoiding the toxic gas chlorine’ bad effect on the synthesis operator health, reducing the risk factor of the synthesis process, and the reaction process temperature is also reduced, the reaction process energy consumption is reduced, the reaction cost is reduced, 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 tetrachlorobenzoquinone.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method, comprises the following steps:
A: 2 mol 2,3,5,6-tetrachloro-l,4-dimethoxybenzene solution and 1.9L potassium chloride solution with a mass fraction of 10% were added to the reaction vessel, controlled the temperature of the solution at 40 °C, 3 mol added aluminum acetylacetonate powder in 2 times, controlled the stirring speed at 230 rpm, reacted for 90 min;
B: added 4 mol tributyl borate solution with a mass fraction of 30%, raised the temperature to 50°C, and then added 2.2L sodium nitrate solution with a mass fraction of 20%, reacted for 1 h, after the solution layered, reduced the temperature to 15 °C, washed with hexyl ether solution with a mass fraction of 50% for 2 times, washed with
3-methyl pyridine solution with a mass fraction of 60% for 4 times, recrystallized from the chloroacetyl chloride solution with a mass fraction of 80%, dehydrated with anhydrous calcium chloride dehydration, got the finished product tetrachlorobenzoquinone 471.38g, yield of 96.2%.
Embodiment 2
Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method, comprises the following steps:
A: 2 mol 2,3,5,6-tetrachloro-l,4-dimethoxybenzene solution and 1.9L potassium chloride solution with a mass fraction of 13% were added to the reaction vessel, controlled the temperature of the solution at 43 °C, 3.5 mol added aluminum acetylacetonate powder in 3 times, controlled the stirring speed at 245 rpm, reacted for 110 min;
B: added 5 mol tributyl borate solution with a mass fraction of 33.5%, raised the temperature to 54°C, and then added 2.2L sodium nitrate solution with a mass fraction of 22.5%, reacted for 1.5 h, after the solution layered, reduced the temperature to 18 °C, washed with hexyl ether solution with a mass fraction of 53.5% for 3 times, washed with 3-methyl pyridine solution with a mass fraction of 63% for 5 times, recrystallized from the chloroacetyl chloride solution with a mass fraction of 83.5%, dehydrated with anhydrous sodium sulfate dehydration, got the finished product tetrachlorobenzoquinone 475.79g, yield of 97.1%.
Embodiment 3
Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method, comprises the following steps:
A: 2 mol 2,3,5,6-tetrachloro-l,4-dimethoxybenzene solution and 1.9L potassium chloride solution with a mass fraction of 16% were added to the reaction vessel, controlled the temperature of the solution at 46 °C, 4 mol added aluminum acetylacetonate powder in 4 times, controlled the stirring speed at 260 rpm, reacted for 130 min;
B: added 6 mol tributyl borate solution with a mass fraction of 37%, raised the temperature to 58°C, and then added 2.2L sodium nitrate solution with a mass fraction of 25%, reacted for 2 h, after the solution layered, reduced the temperature to 22 °C, washed with hexyl ether solution with a mass fraction of 57% for 4 times, washed with
3-methyl pyridine solution with a mass fraction of 66% for 6 times, recrystallized from the chloroacetyl chloride solution with a mass fraction of 87%, dehydrated with anhydrous calcium chloride dehydration, got the finished product tetrachlorobenzoquinone 479.7lg, yield of 97.9%.
Infrared analysis of finished product tetrachlorobenzoquinone, infrared spectrum is shown in figure 1, the analysis of data is shown in table 1.
2018101108 11 Aug 2018
Table 1 Peak data
| Serial | Peak position | Transmittance | Half width | Peak difference |
| number | (cm'1) | (%) | (cnf1) | (%) |
| 1 | 883 | 40 | 34 | 56 |
| 2 | 1059 | 61 | 15 | 9 |
| 3 | 1071 | 63 | 17 | 9 |
| 4 | 1306 | 50 | 40 | 39 |
| 5 | 1680 | 9 | 44 | 81 |
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.
Claims (5)
- Claims1. Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method, comprises the following steps:A: 2,3,5,6-tetrachloro-l,4-dimethoxybenzene solution and potassium chloride were added to the reaction vessel, controlled the temperature of the solution at 40-46 °C, added aluminum acetylacetonate powder in batches, controlled the stirring speed at 230-260 rpm, reacted for 90-130 min;B: added the tributyl borate solution, raised the temperature to 50-58°C, and then added the sodium nitrate solution, reacted for 1-2 h, after the solution layered, reduced the temperature to 15-22 °C, washed with hexyl ether solution for several times, washed with 3-methyl pyridine solution for several times, recrystallized from the chloroacetyl chloride solution, dehydrated with dehydration, got the finished product tetrachlorobenzoquinone.
- 2. Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method according to claim 1 wherein the potassium chloride solution has a mass fraction of 10-16%.
- 3. Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method according to claim 1 wherein the mass fraction of the tributyl borate solution is 30-37%.
- 4. Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method according to claim 1 wherein the sodium nitrate solution has a mass fraction of 20-25%.
- 5. Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method according to claim 1 wherein the hexyl ether solution has a mass fraction of 50-57%.2018101108 11 Aug 20181/1Figure 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201710718276.7A CN108238876A (en) | 2017-08-21 | 2017-08-21 | The synthetic method of quinone imine pharmaceutical intermediate tetrachloroquinone |
| CN2017107182767 | 2017-08-21 |
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| Publication Number | Publication Date |
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| AU2018101108A4 true AU2018101108A4 (en) | 2018-09-06 |
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| AU2018101108A Ceased AU2018101108A4 (en) | 2017-08-21 | 2018-08-11 | Aminoquinone drug intermediates tetrachlorobenzoquinone synthesis method |
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|---|---|
| CN (1) | CN108238876A (en) |
| AU (1) | AU2018101108A4 (en) |
| GB (1) | GB201714073D0 (en) |
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2017
- 2017-08-21 CN CN201710718276.7A patent/CN108238876A/en active Pending
- 2017-09-04 GB GBGB1714073.2A patent/GB201714073D0/en not_active Ceased
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| CN108238876A (en) | 2018-07-03 |
| GB201714073D0 (en) | 2017-10-18 |
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