CN111056996A - Synthetic method of 3-bromopyridine - Google Patents
Synthetic method of 3-bromopyridine Download PDFInfo
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- CN111056996A CN111056996A CN201911181900.XA CN201911181900A CN111056996A CN 111056996 A CN111056996 A CN 111056996A CN 201911181900 A CN201911181900 A CN 201911181900A CN 111056996 A CN111056996 A CN 111056996A
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- bromopyridine
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
- C07D213/61—Halogen atoms or nitro radicals
Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of 3-bromopyridine, which comprises the following steps: (1) dripping bromine into pyridine and 80-95% sulfuric acid at 0 ℃ to react for 7-8 hours at 140 ℃; (2) after the reaction is finished, cooling, pouring into ice water, and adjusting the pH value to be 8 by using 6N sodium hydroxide; (3) extracting with organic solvent, layering, drying, filtering, concentrating, and distilling. The beneficial effects of the invention are as follows: high yield, mild reaction conditions, simple reaction steps, simple and easily obtained raw materials and suitability for industrial production.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthetic method of 3-bromopyridine.
Background
3-bromopyridine is commonly used as a pharmaceutical, a pesticide, and an organic synthesis intermediate. Can be used for synthesizing a balofloxacin intermediate 3-methylamino piperidine of a sars medicine. The synthesis method of 3-bromopyridine commonly adopts the following steps: (1) reacting pyridine and aluminum trichloride with bromine; (2) after 3-aminopyridine is brominated, diazotization is carried out, and Sandmeyer reaction is carried out to obtain the product. The method (1) has the defects of low yield, high anhydrous requirement in the reaction process, difficult stirring of salification, low positioning effect of bromination of the pyridine hydrogen chloride salt, easy generation of brominated products in other positions, great troubles for post-treatment and low yield. The method (2) has expensive raw materials and is not suitable for industrialization.
Disclosure of Invention
The technical problem to be solved by the invention is as follows: overcomes the defects of low yield, high requirement on reaction conditions and expensive raw materials in the prior art, and provides a synthetic method of 3-bromopyridine, which has the advantages of high yield, mild reaction conditions, simple operation and suitability for industrialization.
In order to solve the technical problem, the synthesis method of 3-bromopyridine hydrochloride provided by the invention comprises the following steps:
the reaction equation of the method of the invention is as follows:
a method for synthesizing 3-bromopyridine comprises the following steps:
(1) dripping bromine into pyridine and 80-95% sulfuric acid at 0 ℃ to react for 7-8 hours at 140 ℃;
(2) after the reaction is finished, cooling, pouring into ice water, and adjusting the pH value to be 8 by using 6N sodium hydroxide;
(3) extracting with organic solvent, layering, drying, filtering, concentrating, and distilling.
Further, the optimum reaction temperature in the step (1) is 135 ℃, and the molar ratio of bromine to pyridine is 3.7: 1.
Further, in the step (1), the optimal reaction time is 8 hours, and the optimal sulfuric acid concentration is 95%.
Further, the organic solvent in the step (3) is petroleum ether.
Further, after the concentration in the step (3), the Vigreux column is used for distillation.
The beneficial effects of the invention are as follows: high yield, mild reaction conditions, simple reaction steps, simple and easily obtained raw materials and suitability for industrial production.
Detailed Description
In order to further illustrate the invention, some examples are given below. These examples are purely illustrative and are intended to be a detailed description of the invention and should not be taken as limiting the invention.
Example 1
Dropping 8.8g bromine (50mmol) into 15ml (185mmol) and 95% sulfuric acid at 0 deg.C, reacting at 130 deg.C for 8 hr, cooling after reaction, pouring into ice water, adjusting pH to 8 with 6N sodium hydroxide, extracting with 60ml petroleum ether for three times, drying several layers with anhydrous sodium sulfate after layering, filtering to remove desiccant, concentrating organic layer, and distilling with Vigreux column. Gas phase analysis of the components of the remaining substances, detection conditions: n is a radical of290ml/min，H2120ml/min, column temperature 165 deg.C, sample injection 4ul, yield 75%.
Example 2
8.8g of bromine (50mmol) were added dropwise to 15ml (185mmol) at 0 deg.C) Reacting with 80% sulfuric acid at 130 deg.C for 8 hr, cooling, pouring into ice water, adjusting pH to 8 with 6N sodium hydroxide, extracting with 60ml petroleum ether for three times, layering, drying with anhydrous sodium sulfate, filtering to remove desiccant, concentrating organic layer, and distilling with Vigreux column. Gas phase analysis of the components of the remaining substances, detection conditions: n is a radical of290ml/min，H2120ml/min, column temperature 165 deg.C, sample injection 4ul, yield 65%.
Example 3
Dropping 8.8g bromine (50mmol) into 15ml (185mmol) and 90% sulfuric acid at 0 deg.C, reacting at 130 deg.C for 8 hr, cooling after reaction, pouring into ice water, adjusting pH to 8 with 6N sodium hydroxide, extracting with 60ml petroleum ether for three times, drying several layers with anhydrous sodium sulfate after layering, filtering to remove desiccant, concentrating organic layer, and distilling with Vigreux column. Gas phase analysis of the components of the remaining substances, detection conditions: n is a radical of290ml/min，H2120ml/min, column temperature 165 deg.C, sample injection 4ul, yield 70%.
Example 4
Dropping 8.8g bromine (50mmol) into 15ml (185mmol) and 95% sulfuric acid at 0 deg.C, reacting at 130 deg.C for 7 hr, cooling after reaction, pouring into ice water, adjusting pH to 8 with 6N sodium hydroxide, extracting with 60ml petroleum ether for three times, drying several layers with anhydrous sodium sulfate after layering, filtering to remove desiccant, concentrating organic layer, and distilling with Vigreux column. Gas phase analysis of the components of the remaining substances, detection conditions: n is a radical of290ml/min，H2120ml/min, column temperature 165 deg.C, sample injection 4ul, yield 72%.
Claims (5)
1. A synthetic method of 3-bromopyridine is characterized by comprising the following steps:
(1) dripping bromine into pyridine and 80-95% sulfuric acid at 0 ℃ to react for 7-8 hours at 140 ℃;
(2) after the reaction is finished, cooling, pouring into ice water, and adjusting the pH value to be 8 by using 6N sodium hydroxide;
(3) extracting with organic solvent, layering, drying, filtering, concentrating, and distilling.
2. The method for synthesizing 3-bromopyridine according to claim 1, wherein the method comprises the following steps: the optimum reaction temperature in step (1) is 135 ℃ and the bromine to pyridine molar ratio is 3.7: 1.
3. The method for synthesizing 3-bromopyridine according to claim 1, wherein the method comprises the following steps: in the step (1), the optimal reaction time is 8 hours, and the optimal sulfuric acid concentration is 95%.
4. The method for synthesizing 3-bromopyridine according to claim 1, wherein the method comprises the following steps: the organic solvent in the step (3) is petroleum ether.
5. The method for synthesizing 3-bromopyridine according to claim 1, wherein the method comprises the following steps: and (4) distilling by using a Vigreux column after concentrating in the step (3).
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911181900.XA CN111056996A (en) | 2019-11-27 | 2019-11-27 | Synthetic method of 3-bromopyridine |
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| CN201911181900.XA CN111056996A (en) | 2019-11-27 | 2019-11-27 | Synthetic method of 3-bromopyridine |
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| CN201911181900.XA Pending CN111056996A (en) | 2019-11-27 | 2019-11-27 | Synthetic method of 3-bromopyridine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112125839A (en) * | 2020-10-13 | 2020-12-25 | 安徽国星生物化学有限公司 | 3-bromopyridine continuous synthesis process and device |
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- 2019-11-27 CN CN201911181900.XA patent/CN111056996A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112125839A (en) * | 2020-10-13 | 2020-12-25 | 安徽国星生物化学有限公司 | 3-bromopyridine continuous synthesis process and device |
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Application publication date: 20200424 |