CN105315197A - 2-chloro-5-pyridylaldehyde production method - Google Patents
2-chloro-5-pyridylaldehyde production method Download PDFInfo
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- CN105315197A CN105315197A CN201410363354.2A CN201410363354A CN105315197A CN 105315197 A CN105315197 A CN 105315197A CN 201410363354 A CN201410363354 A CN 201410363354A CN 105315197 A CN105315197 A CN 105315197A
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Abstract
The present invention discloses a 2-chloro-5-pyridylaldehyde production method. The method is characterized in that 2-chloro-5-chloromethyl pyridine, chlorine gas and inorganic acid are used as raw materials, and the method comprises the following process steps: step one, carrying out a chlorination reaction of 2-chloro-5-chloromethyl pyridine and chlorine gas, using gas chromatography to control the chlorination level, and carrying out rectification to obtain 2-chloro-5-dichloromethyl pyridine; step two, enabling 2-chloro-5-dichloromethyl pyridine obtained in the step one and inorganic acid to react, wherein the reaction temperature is 50-140 DEG C and the reaction time is 1-4 hours; and step three, enabling reaction liquor obtained in the step two and water to react to obtain a product, namely 2-chloro-5-pyridylaldehyde, wherein the reaction temperature is 0-80 DEG C. The 2-chloro-5-pyridylaldehyde production method disclosed by the present invention does not have side reactions, and the product purity is high and is 99.5% or above.
Description
Technical field
The present invention relates to the manufacture method of the chloro-5-pyridylaldehyde of a kind of 2-.
Background technology
The production of the chloro-5-pyridylaldehyde of existing 2-take CMP as raw material, obtains the chloro-5-pyridylaldehyde of 2-by oxidizing reaction, or obtain with 6-chloro-3-pyridinecarboxylic acid hydrogenating reduction.Can be there is a lot of side reactions in oxidizing reaction, product is complicated, separation difficulty.The subject matter of reduction reaction is that the degree of depth of reducing is difficult to control, and need special hydrogenation catalyst, expensive being difficult to obtains simultaneously.
Summary of the invention
The manufacture method of the chloro-5-pyridylaldehyde of 2-of the present invention, adopts CCMP, chlorine and mineral acid to be raw material, and reaction generates the chloro-5-pyridylaldehyde of 2-, and there is not side reaction, product purity is high, reaches more than 99.5%.
Technical scheme of the present invention is as follows: the manufacture method of the chloro-5-pyridylaldehyde of 2-, and it, obtains through following processing step for raw material with CCMP, chlorine and mineral acid:
Step one: CCMP and chlorine are carried out chlorination reaction, then obtain 2-chloro-5-dichloromethyl pyridine through rectifying;
Step 2: chloro-for the 2-of step one gained 5-dichloromethyl pyridine and mineral acid are reacted, temperature of reaction is between 50 ~ 140 DEG C, and the reaction times is 1 ~ 4 hour;
Step 3: the reaction solution of step 2 gained and water are reacted, temperature of reaction, between 0 ~ 80 DEG C, obtains the chloro-5-pyridylaldehyde of resultant 2-;
Described mineral acid can be the vitriol oil, phosphoric acid or nitric acid in the present invention, and its preferred version is the vitriol oil, and its reaction equation is:
The temperature of 2-chloro-5-dichloromethyl pyridine and inorganic acid reaction is between 110 ~ 120 DEG C, and the reaction times is 1.5 ~ 2.5 hours.Use the vitriol oil and 2-chloro-5-dichloromethyl pyridine to react in step 2, their weight proportion is 2 ︰ 1 ~ 8 ︰ 1.In step 2, its preferred version of weight proportion of the vitriol oil and 2-chloro-5-dichloromethyl pyridine is 3 ︰ 1 ~ 6 ︰ 1.
The temperature that the reaction solution of step 2 gained and water react is between 0 ~ 10 DEG C; When the reaction solution of step 2 gained and water react, its charged material weight proportioning is: 2-chloro-5-dichloromethane yl pyridines ︰ frozen water=1 ︰ 10 ~ 1 ︰ 100.
The reaction solution of step 2 gained and water react, and gained white depositions is the chloro-5-pyridylaldehyde of 2-, after filtration, dry and obtain the chloro-5-pyridylaldehyde of 2-; Or the filter cake after filtering is added to the water, uses liquid caustic soda adjust pH, make the pH value of solution reach 8 ~ 11, filter and obtain the chloro-5-pyridylaldehyde of 2-.During with liquid caustic soda adjust pH, preferred pH value is 8.5 ~ 9.5.
Adopt as above after technical scheme, the present invention take CCMP as raw material, 2-chloro-5-dichloromethyl pyridine is obtained through chlorination, rectifying, 2-chloro-5-dichloromethyl pyridine is first with mineral acid, be obtained by reacting the chloro-5-pyridylaldehyde of 2-again with water, there is not side reaction, product purity is high, reach more than 99.5, this product is mainly used as medicine intermediate, is one of raw material of production for treating acquired immune deficiency syndrome (AIDS), is also used as organic synthesis intermediate simultaneously.
Embodiment
Embodiment one: be 2004100655033 according to application number, denomination of invention is the patent application of the method for synthesis 2-5-5-flumethiazine, carry out chlorination reaction, after chlorination starts, use gas chromatographic analysis reaction mass, when the content of 2-chloro-5-trichloromethylpyridine reaches 0.3%, stop chlorination reaction, the mixture distillation of the CCMP obtained and 2-chloro-5-dichloromethyl pyridine is removed desolventizing tetracol phenixin, then underpressure distillation, removing CCMP, obtain 2-chloro-5-dichloromethyl pyridine, fusing point 60 DEG C, purity 98.5%.The cut of removing is recovered and carries out lower batch chlorination.
Embodiment two: be 2004100655033 according to application number, denomination of invention is the patent application of the method for synthesis 2-5-5-flumethiazine, carry out chlorination reaction, after chlorination starts, use gas chromatographic analysis reaction mass, when the content of CCMP is less than 0.5%, stop chlorination reaction, the mixture distillation of the 2-chloro-5-dichloromethyl pyridine obtained and 2-chloro-5-trichloromethylpyridine is removed desolventizing tetracol phenixin, then underpressure distillation, removing CCMP, collect the mixture of 2-5-dichloromethyl pyridine and 2-chloro-5-trichloromethylpyridine, gas chromatographic analysis, 2-chloro-5-dichloromethyl pyridine 76%, 2-chloro-5-trichloromethylpyridine 23%, yield 98%.
Embodiment three: go out in the 1000ml four-hole boiling flask of pipe to drop into the vitriol oil 600 grams taking into account tail gas guide with stirrer and temperature, opens and stirs, slowly flowed in flask by 100 grams of 2-chloro-5-dichloromethyl pyridines.Then, be slowly warmed up to 120 DEG C, when temperature reaches 80 DEG C, start have hydrogen chloride gas to release, import alkali liquor absorption by tail gas delivery line.Start insulation when temperature reaches 110 DEG C, between 110-120 DEG C, be incubated 2 hours terminate reaction, reduce the temperature to 30 DEG C.Then reaction solution is slowly joined in the frozen water of 1000 grams of ice and 2000 grams of water compositions, stir while add reaction solution limit, adularescent Precipitation.After adding, continue to stir, then filter, 50 DEG C of oven dry obtain 64.3 grams of chloro-5-pyridylaldehydes of 2-, liquid spectrum analysis purity: 99.45%, yield 90.1%.
Its reaction equation is:
The manufacture method of the chloro-5-pyridylaldehyde of embodiment four, five, six: 2-is identical with embodiment three, and reaction process condition is in table one:
Table one
Embodiment seven: go out in the 1000ml four-hole boiling flask of pipe to drop into the vitriol oil 600 grams taking into account tail gas guide with stirrer and temperature, open and stir, the mixture of 100 grams of 2-chloro-5-dichloromethyls pyridine (76%) and 2-chloro-5-trichloromethylpyridine (23%) is slowly flowed in flask.Then, be slowly warmed up to 120 DEG C, when temperature reaches 80 DEG C, start have hydrogen chloride gas to release, import alkali liquor absorption by tail gas delivery line.Start insulation when temperature reaches 110 DEG C, between 110-120 DEG C, be incubated 2 hours terminate reaction, reduce the temperature to 30 DEG C.Then reaction solution is slowly joined in the frozen water of 1000 grams of ice and 2000 grams of water compositions, stir while add reaction solution limit, adularescent Precipitation.After adding, continue to stir, then filter.Filter cake (wetting) is added in the water of its weight 2 times, with 10% liquid caustic soda adjust pH, make the pH value of solution reach 9, stir 30 minutes, filter and obtain the chloro-5-pyridylaldehyde of 2-.Filtrate, with 10% hydrochloric acid adjust pH, makes the pH value of solution reach 3, adularescent Precipitation, stirs 30 minutes, filters and obtains 6-chlorine apellagrin.The 50 DEG C of oven dry of the chloro-5-pyridylaldehyde of 2-, obtain 52.4 grams, liquid spectrum analysis purity: 99.36%, yield 95.7%.6-chlorine apellagrin 105 DEG C oven dry, obtains 18.4 grams, liquid spectrum analysis purity: 99.1%, yield 91.6%.
In the present invention 2-chloro-5-dichloromethyl pyridine except with strong sulfuric acid response, also can with the inorganic acid reaction such as phosphoric acid or nitric acid; The temperature of 2-chloro-5-dichloromethyl pyridine and inorganic acid reaction is best between 110 ~ 120 DEG C, and reaction times the best is 1.5 ~ 2.5 hours.The weight proportion that the vitriol oil and 2-chloro-5-dichloromethyl pyridine react is 2 ︰ 1 ~ 8 ︰ 1, and its preferred version is 3 ︰ 1 ~ 6 ︰ 1.After 2-chloro-5-dichloromethyl pyridine and inorganic acid reaction, the temperature that the reaction solution of gained and water react is best between 0 ~ 10 DEG C; The weight proportion of 2-chloro-5-dichloromethane yl pyridines ︰ frozen water is 1 ︰ 10 ~ 1 ︰ 100, and the best is 1 ︰ 30 ~ 1 ︰ 60.
Claims (10)
1. a manufacture method for the chloro-5-pyridylaldehyde of 2-, is characterized in that it with CCMP, chlorine and mineral acid for raw material, obtains through following processing step:
Step one: CCMP and chlorine are carried out chlorination reaction, then obtain 2-chloro-5-dichloromethyl pyridine through rectifying;
Step 2: 2-step one generated chloro-5-dichloromethyl pyridine and mineral acid react, temperature of reaction is between 50 ~ 140 DEG C, and the reaction times is 1 ~ 4 hour;
Step 3: the reaction solution of step 2 gained and water are reacted, temperature of reaction, between 0 ~ 80 DEG C, obtains the chloro-5-pyridylaldehyde of resultant 2-.
2. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 1, is characterized in that described mineral acid is the vitriol oil, phosphoric acid or nitric acid.
3. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 2, when it is characterized in that using the vitriol oil in step 2, the weight proportion of the vitriol oil and 2-chloro-5-dichloromethyl pyridine is 2 ︰ 1 ~ 8 ︰ 1.
4. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 1, it is characterized in that the temperature of 2-chloro-5-dichloromethyl pyridine and inorganic acid reaction is between 110 ~ 120 DEG C, the reaction times is 1.5 ~ 2.5 hours.
5. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 1, is characterized in that temperature that the reaction solution of step 2 gained and water reacts is between 0 ~ 10 DEG C.
6. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 3, is characterized in that weight proportion 3 ︰ 1 ~ 6 ︰ 1 of the vitriol oil and 2-chloro-5-dichloromethyl pyridine in step 2.
7. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 1, is characterized in that the reaction solution of step 2 gained and water react, and gained white depositions is the chloro-5-pyridylaldehyde of 2-, filters, and dries and obtains the chloro-5-pyridylaldehyde of 2-.
8. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 1, it is characterized in that reaction solution and the water of step 2 gained react, gained white depositions is the chloro-5-pyridylaldehyde of 2-, after filtration, filter cake is added to the water, use liquid caustic soda adjust pH, make the pH value of solution reach 8 ~ 11, filter and obtain the chloro-5-pyridylaldehyde of 2-.
9. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 8, when it is characterized in that with liquid caustic soda adjust pH, makes the pH value of solution reach 8.5 ~ 9.5.
10. the manufacture method of the chloro-5-pyridylaldehyde of 2-according to claim 1, when it is characterized in that the reaction solution of step 2 gained and water react, its charged material weight proportioning is: 2-chloro-5-dichloromethane yl pyridines ︰ frozen water=1 ︰ 10 ~ 1 ︰ 100.
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106243028A (en) * | 2016-07-28 | 2016-12-21 | 南京红太阳生物化学有限责任公司 | A kind of oxidation step synthesizes the method for 2 chlorine apellagrins |
| CN106243019A (en) * | 2016-07-28 | 2016-12-21 | 南京红太阳生物化学有限责任公司 | A kind of method preparing 2 chlorine 5 chloromethylpyridine |
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2014
- 2014-07-29 CN CN201410363354.2A patent/CN105315197A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN106243028A (en) * | 2016-07-28 | 2016-12-21 | 南京红太阳生物化学有限责任公司 | A kind of oxidation step synthesizes the method for 2 chlorine apellagrins |
| CN106243019A (en) * | 2016-07-28 | 2016-12-21 | 南京红太阳生物化学有限责任公司 | A kind of method preparing 2 chlorine 5 chloromethylpyridine |
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