CN105237468A - New method for synthesizing 2-hydroxyethylpyridine - Google Patents
New method for synthesizing 2-hydroxyethylpyridine Download PDFInfo
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- CN105237468A CN105237468A CN201510643320.3A CN201510643320A CN105237468A CN 105237468 A CN105237468 A CN 105237468A CN 201510643320 A CN201510643320 A CN 201510643320A CN 105237468 A CN105237468 A CN 105237468A
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- paraformaldehyde
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- picoline
- methylpyridine
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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
- C07D213/24—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 substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
- C07D213/30—Oxygen atoms
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- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a new method for synthesizing 2-hydroxyethylpyridin. The method comprises the following steps: 1, adding 2-methylpyridine and paraformaldehyde (calculated by unimolecular formaldehyde) into a reaction kettle according to a molar ratio of 1:2, and adding small amounts of water, a catalyst and a solvent DMF, wherein the amount of water is 0.5 times that of paraformaldehyde, the amount of the catalyst is 1-3% of that of 2-methylpyridine, and the amount of the solvent is 3-5 times that of paraformaldehyde; and 2, heating the reaction kettle to 90-100DEG C, reacting for 2-3h, heating to 110-120DEG C, carrying out a refluxing reaction for 30-40h, carrying out normal distillation to obtain unreacted 2-methylpyridine and the unreacted solvent to obtain crude 2-hydroxyethylpyridin, heating, carrying out reduced pressure distillation, and collecting a substance with the boiling range of 110-120DEG C, that is 2-hydroxyethylpyridin. The method has the advantages of simple process, easy separation and convenient and pollution-free treatment of the solvent and the above product, easily available catalyst, production cost reduction and improvement of the conversion rate of 2-methylpyridine.
Description
Technical field
The invention belongs to the synthesis of pyridine compounds and their, refer more particularly to a kind of novel method of synthesizing 2-hydroxyethyl pyridine.
Technical background
2-hydroxyethyl pyridine is a kind of important chemical industry and medicine intermediate, mainly uses 2-picoline and paraformaldehyde or formaldehyde solution to synthesize at present.
In the patent of publication number CN1580046A, with the weight ratio of 2-picoline and paraformaldehyde and catalyzer for 10:0.3 ~ 1.2:0.03 ~ 0.12, under reacting 10 ~ 30h condition at temperature 90 ~ 180 DEG C, synthesize 2-hydroxyethyl pyridine.Its Raw 2-picoline consumption is excessive and the product obtained is few, and per pass conversion is low, is 3 ~ 5%, and the amount reclaiming 2-picoline is large, and production cost is high, and loss amount is large, and industrial production is difficult to realize.
In the patent of publication number CN102731372, take THF as solvent, organic bases is catalyzer, reacts 3 ~ 5h, obtain 2-hydroxyethyl pyridine at-60 ~ 60 DEG C.This method has higher requirements to raw material and operation, under cold condition, is unfavorable for that this reaction is carried out, low conversion rate, and uses organic alkali as a catalyst, and price is more expensive and can not reuse, and cost is higher, is difficult to industrialization.
Publication number is in the patent of 104109114A, is catalyzer, reacts in autoclave with solid super-strong acid, all obtains 2-hydroxyethyl pyridine.This method has higher requirements to equipment requirements and maintenance thereof, and transformation efficiency is not high, and by product is more, and the later stage is separated more difficult.
In the patent of publication number CN102863375A, with NaOH, KOH solution for catalyzer, the mass ratio of feed intake 2-picoline and formaldehyde solution is 10:1, and pressure is 0.5Mpa, obtains 2-hydroxyethyl pyridine.This method per pass conversion is low, and by product is more, not easily separated.
The article of periodical " fine-chemical intermediate " the 4th phase the 42nd volume in the 2012nd adopts soda acid two class catalyzer, discuss the influence factors such as catalyst levels, reaction ratio, reaction times, reach a conclusion: the mol ratio of 2-picoline and paraformaldehyde is 5:1, catalyzer made by triethylamine, reaction times 40h, obtain product 2-hydroxyethyl pyridine, transformation efficiency is 6.6%.
The article of periodical phase the 4th " Sichuan chemical industry and corrosion control " calendar year 2001 the 1st volume adopts phenylformic acid to make catalyzer, obtains optimum process condition: the mol ratio of 2-picoline and formaldehyde is 2:1, and reaction 40h, obtain hydroxyethyl pyridine, per pass conversion is 14.64%.
For above method, adopt the feed ratio of 2-picoline and paraformaldehyde or formaldehyde large, obtain product 2-hydroxyethyl pyridine few, the per pass conversion of 2-picoline is low, and yield is large, and waste is many, and production cost is high, is unfavorable for industrial production.Make catalyzer with organic bases, per pass conversion is low, and considerably increases its cost.Reaction under high pressure is higher to equipment requirements, and the by product obtained is more, is unfavorable for subsequent disposal, adds production cost.
Summary of the invention
For the deficiencies in the prior art, it is solvent with DMF that the object of the invention is to provide a kind of, and with 2-picoline and paraformaldehyde for raw material, oxalic acid is the novel method of catalyst preparing 2-hydroxyethyl pyridine.The equation of this reaction is:
This reaction is nucleophilic addition, increases polar solvent, is conducive to activating pyridine ring, thus pending methyl group activity is strengthened greatly, add the probability of C atom attack formaldehyde.Solvent DMF had both activated 2-picoline, enhancing-CH
3nucleophilicity, again can the C+ ion that formed of stabilized oxymethylene, thus greatly promote 2-picoline to transform and the selectivity of 2-hydroxyethyl pyridine.Its principle is shown below:
In addition, add the polarity that a small amount of water both enhanced solution and also promote paraformaldehyde depolymerization, facilitate this reaction.This reaction is also reversible reaction, adds the consumption of cheap raw material paraformaldehyde, is more conducive to the conversion of valuable raw material 2-picoline, thus improves the transformation efficiency of 2-picoline.Solvent DMF differs comparatively large with 2-hydroxyethyl pyridine boiling point, be easily separated, and recoverable.It is high that the present invention obtains product boiling point, more easily separated with raw material, and purity is high, reduce aftertreatment cost, and technique is simply environment friendly and pollution-free.
Object of the present invention is realized by following scheme: a kind of novel method of synthesizing 2-hydroxyethyl pyridine, with 2-picoline and paraformaldehyde and water for raw material, with DMF solution for solvent, at an acidic catalyst condition 110 ~ 120 DEG C, react 30 ~ 40h, synthesis 2-hydroxyethyl pyridine.
Concrete steps are as follows: by 2-picoline and paraformaldehyde and catalyzer in molar ratio 1:2:0.1 add in reactor, add solvent DMF and water again, its quality is respectively 3 and 0.5 times of paraformaldehyde, first depolymerization reaction at 90 ~ 100 DEG C, reflux at reheating 110 DEG C after completing 30 ~ 40h, the 2-picoline solution (can be recycled) containing paraformaldehyde, catalyzer, water and DMF is distilled out under having reacted rear elder generation 150 DEG C of normal pressures, be warming up to 180 DEG C of underpressure distillation again, the cut collecting 110 ~ 120 DEG C is 2-hydroxyethyl pyridine.
Its processing parameter
1. raw material molar ratio: 2-picoline: paraformaldehyde (by unit molecule formaldehyde): catalyzer=1:2 ~ 4:0.1 ~ 0.3;
2.DMF and water consumption: DMF: paraformaldehyde=3 ~ 5:1, water: paraformaldehyde=1 ~ 0.5:1;
3. catalyzer: oxalic acid or acetic acid, Mono Chloro Acetic Acid, phenylformic acid;
4. reaction conditions: temperature 110 DEG C, normal pressure, the time is 30 ~ 40h;
5. products obtained therefrom: faint yellow viscous liquid, boiling point 240 DEG C, purity >=99%.
Beneficial effect of the present invention: a kind of method of synthesizing 2-hydroxyethyl pyridine in DMF solvent is provided.One be the per pass conversion of 2-picoline up to 45%, and raw material feed ratio is little, has both reduced the recovery of 2-picoline, decreases its waste, and solvent can recycle, reduces production cost.Two is that this product differs comparatively large, more easily separated with the boiling point of solvent and raw material, really reduces the cost of product treatment.Three is that this reaction no coupling product produces, and purity is high, and production technique is simple, low for equipment requirements, and environment friendly and pollution-free.
Embodiment
The present invention is further illustrated in conjunction with following specific embodiment.
Embodiment 1
Take 95.0g2-picoline, 61.3g paraformaldehyde in there-necked flask, then adds 1.02g acetic acid and 100.0gDMF, 31.0g water, stirs 2 ~ 3h, be heated to 110 DEG C in time not having solid at 90 DEG C, reaction 30h.Distill out 2-picoline at first normal pressure 150 DEG C, then rise to 180 DEG C, underpressure distillation is collected 110 ~ 120 DEG C of cuts and is product 2-hydroxyethyl pyridine.Through gas chromatography determination, per pass conversion is 35.15%, and purity is 99.9%.
Embodiment 2
Take 76.0g2-picoline, 49.3g paraformaldehyde in there-necked flask, then adds 0.82g oxalic acid and 150.0gDMF, 25.0g water, stirs 2 ~ 3h, be heated to 110 DEG C in time not having solid at 90 DEG C, reaction 30h.Distill out 2-picoline at first normal pressure 150 DEG C, then rise to 180 DEG C, underpressure distillation is collected 110 ~ 120 DEG C of cuts and is product 2-hydroxyethyl pyridine.Through gas chromatography determination, per pass conversion is 36.73%, and purity is 99.0%.
Embodiment 3
Take 34.28g2-picoline, 22.3g paraformaldehyde in there-necked flask, then adds 0.32g phenylformic acid and 50.0gDMF, 15.0g water, stirs 2 ~ 3h, be heated to 110 DEG C in time not having solid at 90 DEG C, reaction 30h.Distill out 2-picoline at first normal pressure 150 DEG C, then rise to 180 DEG C, underpressure distillation is collected 110 ~ 120 DEG C of cuts and is product 2-hydroxyethyl pyridine.Through gas chromatography determination, per pass conversion is 31.37%, and purity is 99.9%.
Claims (4)
1. synthesize a novel method for 2-hydroxyethyl pyridine, it is characterized in that 2-picoline and paraformaldehyde synthesize 2-hydroxyethyl pyridine under catalyzer and solvent condition.
2. by a kind of novel method of synthesizing 2-hydroxyethyl pyridine according to claim 1, solvent for use is DMF, and wherein the mass ratio of DMF and paraformaldehyde is 3 ~ 5:1.
3. by a kind of novel method of synthesizing 2-hydroxyethyl pyridine according to claim 1, raw materials used 2-picoline: paraformaldehyde: catalyst molar ratio=1:2:0.02.
4. by a kind of novel method of synthesizing 2-hydroxyethyl pyridine according to claim 1, de-polymerization temperature is 80 ~ 90 DEG C, and the depolymerization time is 2 ~ 3h, and reflux temperature is 110 ~ 120 DEG C, and return time is 30 ~ 40h.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201510643320.3A CN105237468B (en) | 2015-10-08 | 2015-10-08 | A kind of method for synthesizing 2 ethoxy pyridines |
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| CN201510643320.3A CN105237468B (en) | 2015-10-08 | 2015-10-08 | A kind of method for synthesizing 2 ethoxy pyridines |
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| CN105237468A true CN105237468A (en) | 2016-01-13 |
| CN105237468B CN105237468B (en) | 2018-03-27 |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112028817A (en) * | 2019-12-18 | 2020-12-04 | 上海中西三维药业有限公司 | Preparation method of 2-vinylpyridine |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1580046A (en) * | 2004-05-18 | 2005-02-16 | 淄博张店东方化学股份有限公司 | Process for large-scale preparation of 2-hydroxyethyl pyridine |
| CN101698658A (en) * | 2009-10-16 | 2010-04-28 | 厦门森美达生物技术有限公司 | Method for preparing wormer sec-Butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate |
| JP2010270008A (en) * | 2009-05-19 | 2010-12-02 | Sanyo Chem Ind Ltd | Method of producing pyridine ethanol derivative |
| CN102731372A (en) * | 2012-07-16 | 2012-10-17 | 山东天一化学股份有限公司 | Preparation method of 2-ethoxyl pyridina |
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- 2015-10-08 CN CN201510643320.3A patent/CN105237468B/en not_active Expired - Fee Related
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1580046A (en) * | 2004-05-18 | 2005-02-16 | 淄博张店东方化学股份有限公司 | Process for large-scale preparation of 2-hydroxyethyl pyridine |
| JP2010270008A (en) * | 2009-05-19 | 2010-12-02 | Sanyo Chem Ind Ltd | Method of producing pyridine ethanol derivative |
| CN101698658A (en) * | 2009-10-16 | 2010-04-28 | 厦门森美达生物技术有限公司 | Method for preparing wormer sec-Butyl 2-(2-hydroxyethyl)piperidine-1-carboxylate |
| CN102731372A (en) * | 2012-07-16 | 2012-10-17 | 山东天一化学股份有限公司 | Preparation method of 2-ethoxyl pyridina |
Non-Patent Citations (2)
| Title |
|---|
| 杨海燕等: "2-羟乙基吡啶的常压合成研究", 《精细化工中间体》 * |
| 蒋敏等: "正交优化盐酸倍他司汀的合成工艺", 《安徽化工》 * |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112028817A (en) * | 2019-12-18 | 2020-12-04 | 上海中西三维药业有限公司 | Preparation method of 2-vinylpyridine |
| CN112028817B (en) * | 2019-12-18 | 2023-10-03 | 上海中西三维药业有限公司 | Preparation method of 2-vinyl pyridine |
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| CN105237468B (en) | 2018-03-27 |
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Granted publication date: 20180327 Termination date: 20181008 |