AU2018100845A4 - Trienegolinone intermediates dichlorobenzoquinone synthesis method - Google Patents
Trienegolinone intermediates dichlorobenzoquinone synthesis method Download PDFInfo
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- AU2018100845A4 AU2018100845A4 AU2018100845A AU2018100845A AU2018100845A4 AU 2018100845 A4 AU2018100845 A4 AU 2018100845A4 AU 2018100845 A AU2018100845 A AU 2018100845A AU 2018100845 A AU2018100845 A AU 2018100845A AU 2018100845 A4 AU2018100845 A4 AU 2018100845A4
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- dichlorobenzoquinone
- trienegolinone
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
Abstract
Trienegolinone intermediates dichlorobenzoquinone synthesis method Abstract 5 The present invention discloses trienegolinone intermediates dichlorobenzoquinone synthesis method, comprises the following steps: dicyanodiamine p-dibenzyl ether and sodium chloride solution are added to the reaction vessel, raises the temperature of the solution, controlls the stirring speed, react;:3- chloropropionate is added in batches, raising the temperature, nickel carbon 10 tetrachloride is added, washed with sodium nitrate solution for several times, extracted with several times with xylene solution, combined extract, washed with propylamine solution, recrystallized in the 2-methyl-1-butanol solution, dehydrated with dehydration, got the product dichloro dicyanoquinone. 15 Figure 1
Description
The present invention discloses trienegolinone intermediates dichlorobenzoquinone synthesis method, comprises the following steps: dicyanodiamine p-dibenzyl ether and sodium chloride solution are added to the reaction vessel, raises the temperature of the solution, contrails the stirring speed, react;:3- chloropropionate is added in batches, raising the temperature, nickel carbon tetrachloride is added, washed with sodium nitrate solution for several times, extracted with several times with xylene solution, combined extract, washed with propylamine solution, recrystallized in the 2-methyl-l-butanol solution, dehydrated with dehydration, got the product dichloro dicyanoquinone.
Figure 1
2018100845 21 Jun 2018
Trienegolinone intermediates dichlorobenzoquinone 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 trienegolinone intermediates dichlorobenzoquinone synthesis method.
GENERAL BACKGROUND
Dichlorobenzoquinone is an excellent dehydrogenation reagent, mainly used for steroid hormone synthesis and dehydrogenation in some advanced perfume synthesis, which can be used to efficiently synthesize 1,2-benzisoxazole compounds with Ph3P; General deprotecting agents for a variety of compounds such as thioacetals, acetals and ketals; and electron transfer agents for the synthesis of quinolines through imines and alkynes or olefins. The existing synthesis methods are mostly using the process that 2,3-dicyanohydroquinone and hydrochloric acid are stirred into the slurry, added 70% nitric acid slowly at about 35 °C, continued to stirr for lh, filtered, washed with carbon tetrachloride, dried , got the dichloro dicyanoquinone. However, this synthesis method requires the use of 2,3-dicyanohydroquinone and hydrochloric acid, nitric acid as reactants, due to 2,3-dicyanohydroquinone is a high toxicity compounds, the production is of a greater harm to the operator; hydrochloric acid, nitric acid solution are corrosive, the equipment is of high resistance to corrosion, resulting in increased 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 trienegolinone intermediates dichlorobenzoquinone synthesis method, comprises the following steps:
A: dicyanodiamine p-dibenzyl ether and sodium chloride solution are added to the reaction vessel, raises the temperature of the solution to 30-38 °C, contrails the stirring speed at 130-160 rpm, react for 90-120 min;
2018100845 21 Jun 2018
B; 3- chloropropionate is added in batches within 50-80 min, raising the temperature to 40-45 ’C, nickel carbon tetrachloride is added for 2-3 hours, washed with sodium nitrate solution for several times, extracted with several times with xylene solution, combined extract, washed with propylamine solution, re crystallized in the
2-methyl-1-butanol solution, dehydrated with dehydration, got the product dichloro dicyanoquinone.
Preferably, the sodium chloride solution has a mass fraction of 15-21%,
Preferably, the mass fraction of the 3- chloropropionate solution is 30-36%.
Preferably, the sodium nitrate solution has a mass fraction of 10-15%.
Preferably, the xylene solution has a mass fraction of 40-47%.
Preferably, the mass fraction of propylamine solution is 65-72%.
Preferably, the 2-inethyl-l-butanol has a mass fraction of 80-86%.
Throughout the reaction process can be the following reaction formula:
Compared with the synthesis method disclosed in the background art, the invention provides trienegolinone intermediates dichloro benzoquinone synthesis method, it is unnecessary to use 2,3-dicyanohydroquinone and hydrochloric acid, nitric acid as reactants, avoiding the health hazards caused by toxic compounds
2,3-dicyanohydroquinone to the operator, avoiding the use of strong corrosive solution of hydrochloric acid, nitric acid as reactants, reducing the corrosion of equipment, 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.
2018100845 21 Jun 2018
DESCRIPTION OF THE DRAWINGS
Figure 1 is the infrared analysis spectrum of finished product dichlorobenzoquinone.
DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS
The following examples with reference to specific embodiments of the present invention are further illustrated:
Embodiment 1
Trienegolinone intermediates dichlorobenzoquinone synthesis method, comprises the following steps:
A: 2 mol dicyanodiamine p-dibenzyl ether and 1.6L sodium chloride solution with a mass fraction of 15% are added to the reaction vessel, raises the temperature of the solution to 30 °C, contrails the stirring speed at 130rpm, react for 90 min;
B: 6 mol 3-chloropropionate with a mass fraction of 30% is added in 2 times within 50 min, raising the temperature to 40 °C, 3 mol nickel carbon tetrachloride is added for 2 hours, washed with sodium nitrate solution with a mass fraction of 10% for 3 times, extracted with 5 times with xylene solution with a mass fraction of 40%, combined extract, washed with propylamine solution with a mass fraction of 65%, recrystallized in the 2-methyl-l-butanol solution with a mass fraction of 80%, dehydrated with anhydrous sodium sulfate dehydration, got the product dichloro dicyanoquinone 404.66g,yield of 89%.
Embodiment 2
Trienegolinone intermediates dichlorobenzoquinone synthesis method, comprises the following steps:
A: 2 mol dicyanodiamine p-dibenzyl ether and 1.6L sodium chloride solution with a mass fraction of 17% are added to the reaction vessel, raises the temperature of the solution to 35 °C, contrails the stirring speed at 145rpm, react for 105 min;
B: 7 mol 3-chloropropionate with a mass fraction of 33% is added in 3 times within 65 min, raising the temperature to 43 °C, 3.5 mol nickel carbon tetrachloride is added for 2.5 hours, washed with sodium nitrate solution with a mass fraction of 12.5% for 4 times, extracted with 6 times with xylene solution with a mass fraction of 43.5%,
2018100845 21 Jun 2018 combined extract, washed with propylamine solution with a mass fraction of 68%, recrystallized in the 2-methyl-l-butanol solution with a mass fraction of 83%, dehydrated with anhydrous potassium carbonate dehydration, got the product dichloro dicyanoquinone 417.68g,yield of 92%.
Embodiment 3
Trienegolinone intermediates dichlorobenzoquinone synthesis method, comprises the following steps:
A: 2 mol dicyanodiamine p-dibenzyl ether and 1.6L sodium chloride solution with a mass fraction of 21% are added to the reaction vessel, raises the temperature of the solution to 38 °C, contrails the stirring speed at 160rpm, react for 120 min;
B: 8 mol 3-chloropropionate with a mass fraction of 36% is added in 4 times within 80 min, raising the temperature to 45 °C, 4 mol nickel carbon tetrachloride is added for 3 hours, washed with sodium nitrate solution with a mass fraction of 15% for 5 times, extracted with 7 times with xylene solution with a mass fraction of 47%, combined extract, washed with propylamine solution with a mass fraction of 72%, recrystallized in the 2-methyl-l-butanol solution with a mass fraction of 86%, dehydrated with phosphorus pentoxide dehydration, got the product dichloro dicyanoquinone 435.84g,yield of 96%.
Infrared analysis of finished product dichloro dicyanoquinone, 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 | (cm1) | (%) | (cm1) | (%) |
| 1 | 725 | 39 | 9 | 56 |
| 2 | 805 | 32 | 15 | 65 |
| 3 | 900 | 53 | 10 | 43 |
| 4 | 1178 | 9 | 30 | 86 |
| 5 | 1271 | 57 | 33 | 40 |
| 6 | 1383 | 58 | 25 | 36 |
| 7 | 1469 | 37 | 44 | 47 |
2018100845 21 Jun 2018
| 8 | 1560 | 51 | 37 | 24 |
| 9 | 1680 | 11 | 51 | 76 |
| 10 | 2938 | 11 | 150 | 87 |
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.
2018100845 21 Jun 2018
Claims (3)
- Claims1. Trienegolinone intermediates dichlorobenzoquinone synthesis method, comprises the following steps:5 A: dicyanodiamine p-dibenzyl ether and sodium chloride solution are added to the reaction vessel, raises the temperature of the solution to 30-38 °C, contrails the stirring speed at 130-160 rpm, react for 90-120 min;B: 3- chloropropionate is added in batches within 50-80 min, raising the temperature to 40-45 °C, nickel carbon tetrachloride is added for 2-3 hours, washed10 with sodium nitrate solution for several times, extracted with several times with xylene solution, combined extract, washed with propylamine solution, recrystallized in the 2-methyl-l-butanol solution, dehydrated with dehydration, got the product dichloro dicyanoquinone.
- 2. Trienegolinone intermediates dichlorobenzoquinone synthesis method15 according to claim 1 wherein the sodium chloride solution has a mass fraction of15-21%.
- 3. Trienegolinone intermediates dichlorobenzoquinone synthesis method according to claim 1 wherein the mass fraction of the 3- chloropropionate solution is30-36%.20 4. Trienegolinone intermediates dichlorobenzoquinone synthesis method according to claim 1 wherein the sodium nitrate solution has a mass fraction of10-15%2018100845 21 Jun 20181/1Figure 1
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN2017107000453 | 2017-08-19 | ||
| CN201710700045.3A CN108238978A (en) | 2017-08-19 | 2017-08-19 | The synthetic method of dl-18-methyl-norgestrienone pharmaceutical intermediate dichlorodicyanobenzoquinone |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2018100845A4 true AU2018100845A4 (en) | 2018-08-02 |
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| AU2018100845A Ceased AU2018100845A4 (en) | 2017-08-19 | 2018-06-21 | Trienegolinone intermediates dichlorobenzoquinone synthesis method |
Country Status (4)
| Country | Link |
|---|---|
| CN (1) | CN108238978A (en) |
| AU (1) | AU2018100845A4 (en) |
| GB (1) | GB201713869D0 (en) |
| IE (1) | IES20180202A2 (en) |
-
2017
- 2017-08-19 CN CN201710700045.3A patent/CN108238978A/en active Pending
- 2017-08-30 GB GBGB1713869.4A patent/GB201713869D0/en not_active Ceased
-
2018
- 2018-06-21 AU AU2018100845A patent/AU2018100845A4/en not_active Ceased
- 2018-06-26 IE IES20180202 patent/IES20180202A2/en not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| IES20180202A2 (en) | 2019-11-13 |
| CN108238978A (en) | 2018-07-03 |
| GB201713869D0 (en) | 2017-10-11 |
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