CN101012194A - Method for preparing 2,3,5-trimethylpyridine - Google Patents
Method for preparing 2,3,5-trimethylpyridine Download PDFInfo
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- CN101012194A CN101012194A CN 200610155513 CN200610155513A CN101012194A CN 101012194 A CN101012194 A CN 101012194A CN 200610155513 CN200610155513 CN 200610155513 CN 200610155513 A CN200610155513 A CN 200610155513A CN 101012194 A CN101012194 A CN 101012194A
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- ethyl
- lutidine
- trimethylpyridine
- ammonia
- bed reactor
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Abstract
The invention discloses a making method of 2, 3, 5-trimethyl pyridine, which comprises the following steps: 1) making composite catalyst of cobalt aluminium phosphate with acid degree adjuster; 2) placing the composite catalyst into fixed bed reactor; aerating propanal and ammonia gas; looping to generate 2-ethyl-3, 5-dimethyl pyridine; 3) demethylating 2-ethyl-3, 5-dimethyl pyridine and sulfur flour; obtaining the product.
Description
Technical field
The present invention relates to 2,3, the preparation method of 5-trimethylpyridine.
Background technology
2,3, the 5-trimethylpyridine is the H+/K+-ATP enzyme inhibitors omeprazole of preparation treatment digestive tract ulcer and the intermediate of tenatoprazole.Existing 2,3, the main preparation methods of 5-trimethylpyridine has following several: method one (Uzb.Khim.Zh.1990, (1), 29～31),, in the presence of the Zn-Cr-Al catalyzer, under 380 ℃, condition of normal pressure, react with propionic aldehyde and ammonia, contain 2 in the products therefrom, 3,5-trimethylpyridine 27.6%, 2-ethyl-3,5-lutidine 31.1%; Method two (day disclosure special permission 87-72666), this method be by 2-methyl-acetoacetic ester and liquefied ammonia in autoclave, react 3-amino-2-methyl-2-butylene acetoacetic ester, 2-methyl-malonic ester then, in the presence of sodium ethylate with 3-amino-2-methyl-2-butylene acetoacetic ester react 4-hydroxyl-3,5,6-trimethylammonium-2 (1H)-pyridone, again in autoclave and phosphoryl chloride react 2,4-two chloro-3,5, the 6-trimethylpyridine is catalyzer at last with 10%Pd/C, 2,4-two chloro-3,5,6-trimethylpyridine and strong aqua reaction and rectifying get 2,3, the 5-trimethylpyridine; Method three (US4658032), by 3,5-lutidine and lithium methide prepared in reaction, yield is 67%; Method four (US5061805), with 2-ethyl-3, the 5-lutidine is that raw material and sulphur react, total reflux preparation 2,3 between 150～200 ℃, 5-trimethylpyridine, theoretical yield are between 60～70%.
Wherein, method one by product is many, and 2,3, the yield of 5-trimethylpyridine is very low, separates relatively difficulty, makes cost higher; The used basic raw material of method two cyclization is 2-methyl-acetoacetic ester and 2-methyl-malonic ester, and raw material is difficult for obtaining, and operational path is longer simultaneously, uses precious metal palladium again and makes catalyzer, and total recovery is 59.4%, the cost height; The shortcoming of method three is that lithium methide is very expensive, and runs into water or just decomposition of oxygen, severe reaction conditions, and the while 3, the 5-lutidine is difficult to obtain, and therefore can not be used for industrial production; The raw material 2-ethyl-3 that method four is used, the 5-lutidine, the price comparison costliness, synthesis yield is lower, is up to 30%.
Summary of the invention
The purpose of this invention is to provide that a kind of yield is higher, cost is lower, have the preparation 2,3 of industrialization meaning, the method for 5-trimethylpyridine.
Of the present invention 2,3, the preparation method of 5-trimethylpyridine comprises the steps:
The first step dissolved in distilled water (NH
4)
3PO
43H
2O, add acid regulator, evenly stir, Xiao Suangu and aluminum nitrate are dissolved in the distilled water, slowly splash into then in the above-mentioned solution, the precipitation suction filtration that generates, washing leaching cake and drying forming again 400～600 ℃ of roastings 8～12 hours, obtain cobaltous phosphate aluminium composite catalyst, wherein, acid regulator and (NH
4)
3PO
43H
2The weight ratio of O is 0.25～0.5: 1; Xiao Suangu and (NH
4)
3PO
43H
2The mol ratio of O is 3: 4; Aluminum nitrate and (NH
4)
3PO
43H
2The mol ratio of O is 1: 2;
Second step was put into fixed-bed reactor with composite catalyst, feed propionic aldehyde and ammonia to fixed-bed reactor, under 300～450 ℃, carry out the continuous catalysis annulation, generate 2-ethyl-3, the 5-lutidine, the input speed of propionic aldehyde is 1.82～2.9mL/min, and the input speed of ammonia is for being 200mL/min.
5-lutidine and SULPHUR POWDER stirred, mixed, are warming up to 150～200 ℃ with 2-ethyl-3 the 3rd step, and carry out demethylation reaction and make 2,3, the 5-trimethylpyridine, 2-ethyl-3, the weight ratio of 5-lutidine and SULPHUR POWDER is 1～2: 1.
In order further to reduce cost, improve catalyzer work-ing life, the present invention has also further proposed the activating and regenerating method of catalyzer, process is for to rise to 500 ℃ with the fixed-bed reactor bed temperature, simultaneously bubbling air and volumetric concentration are 5～10% methyl alcohol or alcoholic acid aqueous solution 3.5hr at least, the intake velocity of air or oxygen is 100～200mL/min, the feeding speed of methyl alcohol or aqueous ethanolic solution is 0.1～0.5mL/min, stop bubbling air or oxygen and methyl alcohol or the alcoholic acid aqueous solution then, change logical nitrogen at least 3 hours, nitrogen feeding speed is 100mL～200mL/min, feeds ammonia activation at last, and ammonia speed is 100mL～200mL/min.
Among the present invention, the used acid regulator of the first step can be alkali alumina or alkaline oxygenated silicon.
Beneficial effect of the present invention is: preparation technology is simple, and raw materials cost is low, and yield height, yield can reach more than 50%, and simultaneously catalyzer can regeneration, makes to have the industrialization meaning by the production efficiency height.
Embodiment
Further specify the present invention below in conjunction with embodiment.
Embodiment 1
The first step preparation contains the cobaltous phosphate Al catalysts of acid regulator
With 250mL dissolved in distilled water 81.2g (NH
4)
3PO
43H
2The O crystal takes by weighing the 20.3g alkali alumina and pours in the 1000mL flask, adds 250mL left and right sides deionized water and stirring, with 54.9g Xiao Suangu and 42.6g aluminum nitrate 250mL dissolved in distilled water, stirs down and slowly it is splashed into (the NH that contains for preparing
4)
3PO
4In the flask of solution, stir 30min, the precipitation suction filtration of generation, and remove the distilled water wash filter cake with 4 * 200mL, filter cake is suitably dried aftershaping, can use in 12 hours 400 ℃ of roastings again.
Second step was a raw material with propionic aldehyde and ammonia, carried out annulation
A certain amount of catalyzer is added in the fixed-bed reactor, temperature rises to 450 ℃, ammonia sample introduction speed control feeds about 200mL/min, open sampling pump, the sample introduction speed of propionic aldehyde is transferred to 1.82mL/min, the gas phase analysis distillate, to 2-ethyl-3,5-lutidine content obviously reduces, and turns off sampling pump and ammonia valve, and catalyzer is waited until activation.
To containing 2-ethyl-3, the distillate of 5-lutidine crude product carries out rectifying, and acquisition content is the product more than 98%, in propionic aldehyde, and molar yield 60%.
5-lutidine and 800g SULPHUR POWDER stirred, mixed, are warming up to 150 ℃, reacted 28 hours with 400g 2-ethyl-3 the 3rd step, to raw material 2-ethyl-3, till the content of 5-lutidine is constant substantially, underpressure distillation, rectifying gets content 2 more than 99.5% then, 3,5-trimethylpyridine 230g, and reclaim 95.5g 2-ethyl-3, the 5-lutidine, with the 2-ethyl-3 that consumes, 5-lutidine meter, molar yield 84.3%.
The catalyst activation regeneration of the 4th step
The fixed-bed reactor bed temperature is risen to 500 ℃, simultaneously aerating oxygen and volumetric concentration are 5% methanol aqueous solution 3.5hr at least, the intake velocity of oxygen is 100mL/min, the feeding speed of methanol aqueous solution is 0.1mL/min, stop aerating oxygen and methanol aqueous solution then, change logical nitrogen at least 3 hours, nitrogen feeding speed is 100mL/min, feed ammonia activation at last, ammonia speed is 100mL/min.Activation finishes, and can continue reaction, and is suitable substantially with the raw catalyst activity, can the repetition of activation several.
Embodiment 2
The first step preparation contains the cobaltous phosphate Al catalysts of acid regulator
With 250mL dissolved in distilled water 81.2g (NH
4)
3PO
43H
2The O crystal takes by weighing the 32.5g alkali alumina and pours in the 1000mL flask, adds 250mL left and right sides deionized water and stirring, with 54.9g Xiao Suangu and 42.6g aluminum nitrate 250mL dissolved in distilled water, stirs down and slowly it is splashed into (the NH that contains for preparing
4)
3PO
4In the flask of solution, stir 30min, the precipitation suction filtration of generation, and remove the distilled water wash filter cake with 4 * 200mL, filter cake is suitably dried aftershaping, can use in 12 hours 400 ℃ of roastings again.
Second step was a raw material with propionic aldehyde and ammonia, carried out annulation
A certain amount of catalyzer is added in the fixed-bed reactor, temperature rises to 380 ℃, ammonia sample introduction speed control feeds about 200mL/min, open sampling pump, the sample introduction speed of propionic aldehyde is transferred to 2.32mL/min, the gas phase analysis distillate, to 2-ethyl-3,5-lutidine content obviously reduces, and turns off sampling pump and ammonia valve, and catalyzer is waited until activation.
To containing 2-ethyl-3, the distillate of 5-lutidine crude product carries out rectifying, and acquisition content is the product more than 98%, in propionic aldehyde, and molar yield 61.2%.
5-lutidine and 600g SULPHUR POWDER stirred, mixed, are warming up to 175 ℃, reacted 24 hours with 400g 2-ethyl-3 the 3rd step, to raw material 2-ethyl-3, till the content of 5-lutidine is constant substantially, underpressure distillation, rectifying gets content 2 more than 99.5% then, 3,5-trimethylpyridine 226g, and reclaim 100g 2-ethyl-3, the 5-lutidine, with the 2-ethyl-3 that consumes, 5-lutidine meter, molar yield 84.1%.
The catalyst activation regeneration of the 4th step
The fixed-bed reactor bed temperature is risen to 300 ℃, simultaneously aerating oxygen and volumetric concentration are 10% methanol aqueous solution 3.5hr at least, the intake velocity of oxygen is 150mL/min, the feeding speed of methanol aqueous solution is 0.25mL/min, stop aerating oxygen and methanol aqueous solution then, change logical nitrogen at least 3 hours, nitrogen feeding speed is 150mL/min, feed ammonia activation at last, ammonia speed is 150mL/min.Activation finishes, and can continue reaction, and is suitable substantially with the raw catalyst activity, can the repetition of activation several.
Embodiment 3
The first step preparation contains the cobaltous phosphate Al catalysts of acid regulator
With 250mL dissolved in distilled water 81.2g (NH
4)
3PO
43H
2The O crystal takes by weighing the alkaline oxygenated silicon of 40.6g and pours in the 1000mL flask, adds 250mL left and right sides deionized water and stirring, with 54.9g Xiao Suangu and 42.6g aluminum nitrate 250mL dissolved in distilled water, stirs down and slowly it is splashed into (the NH that contains for preparing
4)
3PO
4In the flask of solution, stir 30min, the precipitation suction filtration of generation, and remove the distilled water wash filter cake with 4 * 200mL, filter cake is suitably dried aftershaping, can use in 12 hours 400 ℃ of roastings again.
Second step was a raw material with propionic aldehyde and ammonia, carried out annulation
A certain amount of catalyzer is added in the fixed-bed reactor, temperature rises to 300 ℃, ammonia sample introduction speed control feeds about 200mL/min, open sampling pump, the sample introduction speed of propionic aldehyde is transferred to 2.9mL/min, the gas phase analysis distillate, to 2-ethyl-3,5-lutidine content obviously reduces, and turns off sampling pump and ammonia valve, and catalyzer is waited until activation.
To containing 2-ethyl-3, the distillate of 5-lutidine crude product carries out rectifying, and acquisition content is the product more than 98%, in propionic aldehyde, and molar yield 60.5%.
5-lutidine and 400g SULPHUR POWDER stirred, mixed, are warming up to 200 ℃, reacted 21 hours with 400g 2-ethyl-3 the 3rd step, to raw material 2-ethyl-3, till the content of 5-lutidine is constant substantially, underpressure distillation, rectifying gets content 2 more than 99.5% then, 3,5-trimethylpyridine 220g, and reclaim 106.5g 2-ethyl-3, the 5-lutidine, with the 2-ethyl-3 that consumes, 5-lutidine meter, molar yield 83.6%.
The catalyst activation regeneration of the 4th step
The fixed-bed reactor bed temperature is risen to 500 ℃, simultaneously bubbling air and volumetric concentration are 5% aqueous ethanolic solution 3.5hr at least, the intake velocity of air is 200mL/min, the feeding speed of methanol aqueous solution is 0.5mL/min, stop bubbling air and methanol aqueous solution then, change logical nitrogen at least 3 hours, nitrogen feeding speed is 200mL/min, feed ammonia activation at last, ammonia speed is 200mL/min.Activation finishes, and can continue reaction, and is suitable substantially with the raw catalyst activity, can the repetition of activation several.
Embodiment 4
Carry out the catalysis annulation with regenerated catalyst
To put into fixed-bed reactor after a certain amount of cobaltous phosphate Al catalysts regeneration that contains acid regulator, temperature rises to 400 ℃, ammonia sample introduction speed control feeds about 180mL/min, open sampling pump, the sample introduction speed of propionic aldehyde is transferred to 2.22mL/min, and the gas phase analysis distillate is to 2-ethyl-3,5-lutidine content obviously reduces, and turns off sampling pump and ammonia valve.
To containing 2-ethyl-3, the distillate of 5-lutidine crude product carries out rectifying, and acquisition content is the product more than 98%, in propionic aldehyde, and molar yield 60.5%.
5-lutidine and 600g SULPHUR POWDER stirred, mixed, are warming up to 180 ℃, reacted 22 hours with 400g 2-ethyl-3 the 3rd step, to raw material 2-ethyl-3, till the content of 5-lutidine is constant substantially, underpressure distillation, rectifying gets content 2 more than 99.5% then, 3,5-trimethylpyridine 232.5g, and reclaim 90g 2-ethyl-3, the 5-lutidine, with the 2-ethyl-3 that consumes, 5-lutidine meter, molar yield 83.7%.
Claims (3)
1.2,3, the preparation method of 5-trimethylpyridine in turn includes the following steps:
The first step dissolved in distilled water (NH
4)
3PO
43H
2O, add acid regulator, evenly stir, Xiao Suangu and aluminum nitrate are dissolved in the distilled water, slowly splash into then in the above-mentioned solution, the precipitation suction filtration that generates, washing leaching cake and drying forming again 400～600 ℃ of roastings 8～12 hours, obtain cobaltous phosphate aluminium composite catalyst, wherein, acid regulator and (NH
4)
3PO
43H
2The weight ratio of O is 0.25～0.5: 1; Xiao Suangu and (NH
4)
3PO
43H
2The mol ratio of O is 3: 4; Aluminum nitrate and (NH
4)
3PO
43H
2The mol ratio of O is 1: 2;
Second step was put into fixed-bed reactor with composite catalyst, feed propionic aldehyde and ammonia to fixed-bed reactor, under 300～450 ℃, carry out the continuous catalysis annulation, generate 2-ethyl-3, the 5-lutidine, the input speed of propionic aldehyde is 1.82～2.9mL/min, and the input speed of ammonia is for being 200mL/min;
5-lutidine and SULPHUR POWDER stirred, mixed, are warming up to 150～200 ℃ with 2-ethyl-3 the 3rd step, and carry out demethylation reaction and make 2,3, the 5-trimethylpyridine, 2-ethyl-3, the weight ratio of 5-lutidine and SULPHUR POWDER is 1～2: 1.
2. by claim 1 described 2,3, the preparation method of 5-trimethylpyridine, it is characterized in that also comprising catalyst activation regeneration, process is for to rise to 500 ℃ with the fixed-bed reactor bed temperature, simultaneously bubbling air and volumetric concentration are 5～10% methyl alcohol or alcoholic acid aqueous solution 3.5hr at least, the intake velocity of air or oxygen is 100～200mL/min, the feeding speed of methyl alcohol or aqueous ethanolic solution is 0.1～0.5mL/min, stop bubbling air or oxygen and methyl alcohol or the alcoholic acid aqueous solution then, change logical nitrogen at least 3 hours, nitrogen feeding speed is 100mL～200mL/min, feed ammonia activation at last, ammonia speed is 100mL～200mL/min.
3. by claim 1 or 2 described 2,3, the preparation method of 5-trimethylpyridine is characterized in that the used acid regulator of the first step is alkali alumina or alkaline oxygenated silicon.
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|---|---|---|---|
| CN 200610155513 CN101012194A (en) | 2006-12-27 | 2006-12-27 | Method for preparing 2,3,5-trimethylpyridine |
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|---|---|---|---|
| CN 200610155513 CN101012194A (en) | 2006-12-27 | 2006-12-27 | Method for preparing 2,3,5-trimethylpyridine |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103030591A (en) * | 2012-12-11 | 2013-04-10 | 安徽国星生物化学有限公司 | Adsorption purification method of 2, 3, 5-trimethyl pyridine |
| CN106977449A (en) * | 2017-03-21 | 2017-07-25 | 东南大学 | A kind of process for catalytic synthesis of the ethylpyridine of 3,5 dimethyl 2 |
| CN107649131A (en) * | 2017-10-18 | 2018-02-02 | 安徽工业大学 | A kind of picoline aoxidizes demethylation catalyst |
| CN112961168A (en) * | 2019-12-11 | 2021-06-15 | 台州职业技术学院 | Macrolide new compound and preparation method and application thereof |
-
2006
- 2006-12-27 CN CN 200610155513 patent/CN101012194A/en active Pending
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103030591A (en) * | 2012-12-11 | 2013-04-10 | 安徽国星生物化学有限公司 | Adsorption purification method of 2, 3, 5-trimethyl pyridine |
| CN103030591B (en) * | 2012-12-11 | 2014-08-06 | 安徽国星生物化学有限公司 | Adsorption purification method of 2, 3, 5-trimethyl pyridine |
| CN106977449A (en) * | 2017-03-21 | 2017-07-25 | 东南大学 | A kind of process for catalytic synthesis of the ethylpyridine of 3,5 dimethyl 2 |
| CN106977449B (en) * | 2017-03-21 | 2019-11-12 | 东南大学 | A kind of process for catalytic synthesis of 3,5- dimethyl -2- ethylpyridine |
| CN107649131A (en) * | 2017-10-18 | 2018-02-02 | 安徽工业大学 | A kind of picoline aoxidizes demethylation catalyst |
| CN112961168A (en) * | 2019-12-11 | 2021-06-15 | 台州职业技术学院 | Macrolide new compound and preparation method and application thereof |
| CN112961168B (en) * | 2019-12-11 | 2022-07-26 | 台州职业技术学院 | Macrolide new compound and preparation method and application thereof |
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