CN113929634A - Synthesis method of 2, 3-dibromoquinoxaline - Google Patents
Synthesis method of 2, 3-dibromoquinoxaline Download PDFInfo
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- CN113929634A CN113929634A CN202111387867.3A CN202111387867A CN113929634A CN 113929634 A CN113929634 A CN 113929634A CN 202111387867 A CN202111387867 A CN 202111387867A CN 113929634 A CN113929634 A CN 113929634A
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- dibromoquinoxaline
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
- C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
- C07D241/40—Benzopyrazines
- C07D241/44—Benzopyrazines with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the hetero ring
Abstract
The invention relates to a synthetic method of 2, 3-dibromoquinoxaline, which belongs to the technical field of chemical synthesis; the technical problem to be solved is as follows: the synthesis method of the 2, 3-dibromoquinoxaline is provided, the safety of the synthesis reaction is improved, and the difficulty of product purification is reduced; the technical scheme is as follows: the synthesis method comprises the following steps: (1) adding a raw material, a catalyst and a solvent into a reaction vessel for reaction, wherein the raw material is 2, 3-dihydroxyquinoxaline and tribromooxyphosphorus, the catalyst is one of N, N-diethylaniline, N-dimethylformamide and triethylamine, and the solvent is one of acetonitrile and tetrahydrofuran, (2) after the reaction is finished, dropwise adding a reaction solution into ice water for cooling, and generating a solid precipitate, (3) filtering the solid precipitate, washing the solid precipitate to be neutral, and drying to obtain a crude product of the 2, 3-dibromoquinoxaline, (4) recrystallizing the crude product with the solvent, filtering, and drying to obtain a finished product of the 2, 3-dibromoquinoxaline.
Description
Technical Field
The invention relates to a synthetic method of 2, 3-dibromoquinoxaline, belongs to the technical field of chemical synthesis, and particularly relates to a synthetic method of 2, 3-dibromoquinoxaline.
Background
The structural formula of the 2, 3-dibromo quinoxaline:
the molecular formula is as follows: c8H4Br2N2
Molecular weight: 287.94
CAS NO.:23719-78-0
The application is as follows: a pharmaceutical intermediate; a material intermediate;
phosphorus pentabromide is generally used as a reactant in the synthesis of 2, 3-dibromoquinoxaline, and is high in danger, difficult to store and very severe in hydrolysis after the reaction is finished. And the polybrominated impurities generated by the phosphorus pentabromide reaction are large, which causes certain difficulty in the purification of the final product.
Disclosure of Invention
The invention overcomes the defects of the prior art, and solves the technical problems that: provides a method for synthesizing 2, 3-dibromo quinoxaline, improves the safety of the synthesis reaction and reduces the difficulty of product purification.
In order to solve the technical problems, the invention adopts the technical scheme that: a method for synthesizing 2, 3-dibromoquinoxaline comprises the following steps:
(1) adding a raw material, a catalyst and a solvent into a reaction vessel for reaction, wherein the reaction temperature is 0-110 ℃, the reaction time is 1-10 hours, the raw material is 2, 3-dihydroxyquinoxaline and tribromooxyphosphorus, the catalyst is one of N, N-diethylaniline, N-dimethylformamide and triethylamine, and the solvent is one of acetonitrile and tetrahydrofuran;
(2) after the reaction is finished, dropwise adding the reaction solution into ice water for cooling, and generating solid precipitate;
(3) filtering the solid precipitate, washing the solid precipitate to be neutral, and drying the solid precipitate to obtain a crude product of the 2, 3-dibromoquinoxaline;
(4) and recrystallizing the crude product by using a solvent, filtering and drying to obtain a finished product of the 2, 3-dibromoquinoxaline, wherein the solvent is one of methanol, ethanol and acetonitrile.
In the step (2), the amount of the ice water is 1-20 times of the solvent amount, and the cooling temperature is-15-50 ℃.
And (4) drying at the temperature of 30-120 ℃ in the step (3).
The weight of the solvent in the step (4) is 3-20 times of that of the crude product; the drying temperature is 30-100 ℃.
The solvent dosage in the step (1) is 1-30 times of the weight of the 2, 3-dihydroxy quinoxaline.
The molar ratio of the tribromooxyphosphorus oxide to the 2, 3-dihydroxyquinoxaline in the step (1) is 1: 1-10: 1.
The molar ratio of the catalyst to the 2, 3-dihydroxyquinoxaline in the step (1) is 0.01: 1-10: 1.
Compared with the prior art, the invention has the beneficial effects that: compared with the traditional phosphorus pentabromide, the phosphorus pentabromide is greatly reduced in danger, easy to store and relatively mild in hydrolysis after the reaction is finished; the impurities generated after the reaction are less and can be removed easily, and the purification difficulty of the product is reduced.
Detailed Description
The invention relates to a method for synthesizing 2, 3-dibromoquinoxaline, which comprises the following steps:
(1) adding a raw material, a catalyst and a solvent into a reaction vessel for reaction, wherein the reaction temperature is 0-110 ℃, the reaction time is 1-10 hours, the raw material is 2, 3-dihydroxyquinoxaline and tribromooxyphosphorus, the catalyst is one of N, N-diethylaniline, N-dimethylformamide and triethylamine, and the solvent is one of acetonitrile and tetrahydrofuran;
(2) after the reaction is finished, dropwise adding the reaction solution into ice water for cooling, and generating solid precipitate;
(3) filtering the solid precipitate, washing the solid precipitate to be neutral, and drying the solid precipitate to obtain a crude product of the 2, 3-dibromoquinoxaline;
(4) and recrystallizing the crude product by using a solvent, filtering and drying to obtain a finished product of the 2, 3-dibromoquinoxaline, wherein the solvent is one of methanol, ethanol and acetonitrile.
In the step (2), the amount of the ice water is 1-20 times of the solvent amount, and the cooling temperature is-15-50 ℃.
And (4) drying at the temperature of 30-120 ℃ in the step (3).
The weight of the solvent in the step (4) is 3-20 times of that of the crude product; the drying temperature is 30-100 ℃.
The solvent dosage in the step (1) is 1-30 times of the weight of the 2, 3-dihydroxy quinoxaline.
The molar ratio of the tribromooxyphosphorus oxide to the 2, 3-dihydroxyquinoxaline in the step (1) is 1: 1-10: 1.
The molar ratio of the catalyst to the 2, 3-dihydroxyquinoxaline in the step (1) is 0.01: 1-10: 1.
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions of the present invention will be clearly and completely described below with reference to the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention; all other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
Example 1
Adding 80g of acetonitrile, 16g of 2, 3-dihydroxy quinoxaline and 86.1g of tribromooxyphosphorus into a glass reaction bottle provided with a thermometer, a stirrer, a reflux condenser and a constant-pressure dropping funnel, starting stirring, dropwise adding 30.3g of triethylamine, and heating to 80 ℃ for reaction for 6 hours after dropwise adding. After the reaction, the reaction solution was dropped into 160g of ice water, and the temperature was reduced to 10 ℃ to precipitate solids. The solid was filtered, the filter cake washed with water to neutrality and the crude product dried at 100 ℃. And adding the dried crude product into methanol with the weight of 8 times to perform recrystallization, filtering, and drying at 71 ℃ to obtain the finished product of 2, 3-dibromoquinoxaline.
Example 2
80g of tetrahydrofuran, 16g of 2, 3-dihydroxy quinoxaline and 86.1g of tribromooxyphosphorus are added into a glass reaction bottle provided with a thermometer, a stirrer, a reflux condenser and a constant-pressure dropping funnel, the stirring is started, 21.9g of N, N-dimethylformamide is added dropwise, and the temperature is raised to 65 ℃ after the dropwise addition for reaction for 10 hours. After the reaction, the reaction solution was dropped into 160g of ice water, and the temperature was reduced to 10 ℃ to precipitate solids. The solid was filtered, the filter cake washed with water to neutrality and the crude product dried at 100 ℃. And adding the dried crude product into ethanol with the weight of 8 times to perform recrystallization, filtering, and drying at 83 ℃ to obtain the finished product of 2, 3-dibromoquinoxaline.
Example 3
Adding 80g of acetonitrile, 16g of 2, 3-dihydroxy quinoxaline and 86.1g of tribromooxyphosphorus into a glass reaction bottle provided with a thermometer, a stirrer, a reflux condenser and a constant-pressure dropping funnel, starting stirring, dropwise adding 44.7g of N, N-diethylaniline, and heating to 80 ℃ for reaction for 6 hours after dropwise adding. After the reaction, the reaction solution was dropped into 160g of ice water, and the temperature was reduced to 10 ℃ to precipitate solids. The solid was filtered, the filter cake washed with water to neutrality and the crude product dried at 100 ℃. And adding the dried crude product into acetonitrile with the weight of 10 times of that of the crude product for recrystallization, filtering, and drying at 87 ℃ to obtain the finished product of 2, 3-dibromoquinoxaline.
The invention adopts the tribromooxyphosphorus as a reactant, has relatively low danger, is easy to store, and has gentle hydrolysis after the reaction is finished; the impurities generated after the reaction are less and can be removed easily, and the purification difficulty of the product is reduced.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (7)
1. A method for synthesizing 2, 3-dibromo quinoxaline is characterized by comprising the following steps:
(1) adding a raw material, a catalyst and a solvent into a reaction vessel for reaction, wherein the reaction temperature is 0-110 ℃, the reaction time is 1-10 hours, the raw material is 2, 3-dihydroxyquinoxaline and tribromooxyphosphorus, the catalyst is one of N, N-diethylaniline, N-dimethylformamide and triethylamine, and the solvent is one of acetonitrile and tetrahydrofuran;
(2) after the reaction is finished, dropwise adding the reaction solution into ice water for cooling, and generating solid precipitate;
(3) filtering the solid precipitate, washing the solid precipitate to be neutral, and drying the solid precipitate to obtain a crude product of the 2, 3-dibromoquinoxaline;
(4) and recrystallizing the crude product by using a solvent, filtering and drying to obtain a finished product of the 2, 3-dibromoquinoxaline, wherein the solvent is one of methanol, ethanol and acetonitrile.
2. The method for synthesizing 2, 3-dibromoquinoxaline according to claim 1, which comprises the following steps: in the step (2), the amount of the ice water is 1-20 times of the solvent amount, and the cooling temperature is-15-50 ℃.
3. The method for synthesizing 2, 3-dibromoquinoxaline according to claim 1, which comprises the following steps: and (4) drying at the temperature of 30-120 ℃ in the step (3).
4. The method for synthesizing 2, 3-dibromoquinoxaline according to claim 1, which comprises the following steps: the weight of the solvent in the step (4) is 3-20 times of that of the crude product; the drying temperature is 30-100 ℃.
5. The method for synthesizing 2, 3-dibromoquinoxaline according to claim 1, which comprises the following steps: the solvent dosage in the step (1) is 1-30 times of the weight of the 2, 3-dihydroxy quinoxaline.
6. The method for synthesizing 2, 3-dibromoquinoxaline according to claim 1, which comprises the following steps: the molar ratio of the tribromooxyphosphorus oxide to the 2, 3-dihydroxyquinoxaline in the step (1) is 1: 1-10: 1.
7. The method for synthesizing 2, 3-dibromoquinoxaline according to claim 1, which comprises the following steps: the molar ratio of the catalyst to the 2, 3-dihydroxyquinoxaline in the step (1) is 0.01: 1-10: 1.
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011093365A1 (en) * | 2010-01-27 | 2011-08-04 | 協和発酵キリン株式会社 | Nitrogenated heterocyclic compound |
| CN104364249A (en) * | 2012-05-30 | 2015-02-18 | 霍夫曼-拉罗奇有限公司 | Triazolo compounds as pde10 inhibitors |
| CN105585577A (en) * | 2014-11-12 | 2016-05-18 | 乐金显示有限公司 | Delayed fluorescence compound, and organic light emitting diode and display device using the same |
| CN106632093A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 2-bromine-5,6-diphenyl pyrazine |
| CN112204032A (en) * | 2018-05-31 | 2021-01-08 | C&C新药研究所 | Heterocyclic derivatives and use thereof |
| CN112939877A (en) * | 2019-12-11 | 2021-06-11 | 南京理工大学 | Synthesis method of diphenylpyrazine derivative |
-
2021
- 2021-11-22 CN CN202111387867.3A patent/CN113929634A/en active Pending
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2011093365A1 (en) * | 2010-01-27 | 2011-08-04 | 協和発酵キリン株式会社 | Nitrogenated heterocyclic compound |
| CN104364249A (en) * | 2012-05-30 | 2015-02-18 | 霍夫曼-拉罗奇有限公司 | Triazolo compounds as pde10 inhibitors |
| CN105585577A (en) * | 2014-11-12 | 2016-05-18 | 乐金显示有限公司 | Delayed fluorescence compound, and organic light emitting diode and display device using the same |
| CN106632093A (en) * | 2016-11-23 | 2017-05-10 | 山东友帮生化科技有限公司 | Preparation method of 2-bromine-5,6-diphenyl pyrazine |
| CN112204032A (en) * | 2018-05-31 | 2021-01-08 | C&C新药研究所 | Heterocyclic derivatives and use thereof |
| CN112939877A (en) * | 2019-12-11 | 2021-06-11 | 南京理工大学 | Synthesis method of diphenylpyrazine derivative |
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