CN105237468B - A kind of method for synthesizing 2 ethoxy pyridines - Google Patents
A kind of method for synthesizing 2 ethoxy pyridines Download PDFInfo
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- CN105237468B CN105237468B CN201510643320.3A CN201510643320A CN105237468B CN 105237468 B CN105237468 B CN 105237468B CN 201510643320 A CN201510643320 A CN 201510643320A CN 105237468 B CN105237468 B CN 105237468B
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- picolines
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- solvent
- paraformaldehyde
- ethoxy
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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 kind of method for synthesizing 2 ethoxy pyridines, comprise the following steps：（1）By 2 picolines and paraformaldehyde（Press the calculating of unimolecule formaldehyde）It is 1 in molar ratio:2 ratio is added in reactor, adds a small amount of water, catalyst and solvent DMF, and the amount of its reclaimed water is 0.5 times of paraformaldehyde, and the amount of catalyst is the 1 ~ 3% of 2 picolines, and the amount of solvent is 3 ~ 5 times of paraformaldehyde.（2）Temperature of reaction kettle is first raised to 90 ~ 100 DEG C of 2 ~ 3 h of reaction, after be heated to 110 120 DEG C of h of back flow reaction 30 ~ 40, first air-distillation goes out complete 2 picolines and solvent of unreacted, obtain the ethoxy pyridine of crude product 2, temperature is raised again, it is evaporated under reduced pressure, it is 2 ethoxy pyridines to collect the material that boiling range is 110 ~ 120 DEG C.Present invention process is simple, and solvent is easily separated with product and convenient post-treatment is pollution-free, and catalyst is easy to get, and improves the conversion ratio of 2 picolines while reducing production cost again.
Description
Technical field
The invention belongs to the synthesis of pyridine compounds and their, more particularly to a kind of new method of synthesis 2- ethoxy pyridines.
Background technology
2- ethoxy pyridines are a kind of important chemical industry and medicine intermediate, presently mainly with 2- picolines and poly
Formaldehyde or formalin synthesis.
In publication number CN1580046A patent, using the weight ratio of 2- picolines and paraformaldehyde and catalyst as 10:
0.3~1.2 :0.03 ~ 0. 12, react at 90 ~ 180 DEG C of temperature and synthesize 2- ethoxy pyridines under the conditions of 10 ~ 30h.Wherein raw material
2- picoline dosages are excessive and obtained product is few, and conversion per pass is low, are 3 ~ 5%, and it is big to reclaim the amount of 2- picolines, raw
It is high to produce cost, loss amount is big, and industrial production is difficult to.
In publication number CN102731372 patent, using THF as solvent, organic base is catalyst, reaction 3 at -60 ~ 60 DEG C ~
5h, obtain 2- ethoxy pyridines.The method has higher requirements to raw material and operation, under cryogenic conditions, be unfavorable for this react into
OK, conversion ratio is low, and with organic alkali as a catalyst, expensive and can not reuse, and cost is higher, it is difficult to industrializes.
In Publication No. 104109114A patent, using solid super-strong acid as catalyst, react in autoclave, all obtain
2- ethoxy pyridines.The method has higher requirements to equipment requirement and its maintenance, and conversion ratio is not high, and accessory substance is more, the later stage point
From more difficult.
In publication number CN102863375A patent, using NaOH, KOH solution as catalyst, feed intake 2- picolines and first
The mass ratio of aldehyde solution is 10:1, pressure 0.5Mpa, obtain 2- ethoxy pyridines.The method conversion per pass is low, and accessory substance
It is more, it is not readily separated.
Periodical《Fine-chemical intermediate》The 4th phase article of volume 42 in 2012nd uses the class catalyst of soda acid two, discusses
The influence factors such as catalyst amount, reaction ratio, reaction time, it was therefore concluded that：Mole of 2- picolines and paraformaldehyde
Than for 5:1, triethylamine makees catalyst, reaction time 40h, obtains product 2- ethoxy pyridines, conversion ratio 6.6%.
Periodical《Sichuan chemical industry and corrosion control》The 1st phase article of volume 4 makees catalyst using benzoic acid within 2001, obtains
Optimum process condition：The mol ratio of 2- picolines and formaldehyde is 2:1,40h is reacted, obtains ethoxy pyridine, conversion per pass
For 14.64%.
For above method, the rate of charge using 2- picolines and paraformaldehyde or formaldehyde is big, obtains product 2- hydroxyl second
Yl pyridines are few, and the conversion per pass of 2- picolines is low, and yield is big, and waste is more, and production cost is high, is unfavorable for industrial production.
Catalyst is made with organic base, conversion per pass is low, and considerably increases its cost.Reaction under high pressure is higher to equipment requirement, and
The accessory substance arrived is more, is unfavorable for subsequent treatment, adds production cost.
The content of the invention
In view of the shortcomings of the prior art, it is an object of the present invention to provide one kind using DMF as solvent, with 2- picolines and poly
Formaldehyde is raw material, and ethanedioic acid is the new method of catalyst preparation 2- ethoxy pyridines.The equation of this reaction is：
This reaction is nucleophilic addition, increases polar solvent, is advantageous to activate pyridine ring, so that pending methyl group activity is big
Big enhancing, add the probability of C atom attack formaldehyde.Solvent DMF had both activated 2- picolines, enhancing-CH3Nucleophilicity,
The C+ ions that and can stabilized oxymethylene is formed, so as to greatly promote the selectivity of the conversion of 2- picolines and 2- ethoxy pyridines.Its
Principle is shown below：
Both enhance the polarity of solution in addition, adding a small amount of water or promoted paraformaldehyde depolymerization, and promote the reaction.This is anti-
It should also be reversible reaction, add the dosage of cheap raw material paraformaldehyde, be more beneficial for the conversion of valuable raw material 2- picolines,
So as to improve the conversion ratio of 2- picolines.Solvent DMF differs larger with 2- ethoxy pyridine boiling points, can be easily separated, and can
Recycle.The present invention obtains product boiling point height, more easily separated with raw material, and purity is high, reduces post processing cost, Er Qiegong
Skill is simple and environmentally-friendly pollution-free.
The purpose of the present invention is realized by following scheme：A kind of new method of synthesis 2- ethoxy pyridines, with 2- methyl pyrroles
Pyridine and paraformaldehyde and water be raw material, using DMF solution as solvent, the reaction 30 ~ 40 at 110 ~ 120 DEG C of acidic catalyst condition
H, synthesize 2- ethoxy pyridines.
Comprise the following steps that：By 2- picolines and paraformaldehyde and catalyst in molar ratio 1: 2 :0.1 adds instead
Answer in kettle, add solvent DMF and water, its quality is respectively 3 and 0.5 times of paraformaldehyde, and first depolymerization is anti-at 90 ~ 100 DEG C
Should, after the completion of be heated at 110 DEG C 30 ~ 40 h of backflow, first distilled out after the completion of reaction under 150 DEG C of normal pressures containing paraformaldehyde,
The 2- picoline solutions of catalyst, water and DMF（It can be recycled）, then 180 DEG C of vacuum distillations are warming up to, collect 110 ~ 120
DEG C cut be 2- ethoxy pyridines.
Its technological parameter
1. raw material molar ratio：2- picolines:Paraformaldehyde（Based on unimolecule formaldehyde）:Catalyst=1: 2~
4 : 0.1~0.3；
2. DMF and water consumption：DMF:Paraformaldehyde=3 ~ 5:1, water：Paraformaldehyde=1 ~ 0.5: 1；
3. catalyst：Ethanedioic acid or acetic acid, monoxone, benzoic acid；
4. reaction condition：110 DEG C of temperature, normal pressure, time are 30 ~ 40 h；
5. products obtained therefrom：Faint yellow viscous liquid, 240 DEG C of boiling point, purity >=99%.
Beneficial effect of the present invention：A kind of method that 2- ethoxy pyridines are synthesized in DMF solvent is provided.First, 2- methyl pyrroles
The conversion per pass of pyridine is up to 45%, and raw material rate of charge is small, has both reduced the recovery of 2- picolines, decreases its waste, and
Solvent can recycle, and reduce production cost.Second, this product differs larger with the boiling point of solvent and raw material, it is easier to point
From really reducing the cost of product treatment.Third, this reaction no coupling product produces, purity is high, simple production process, to equipment
It is it is required that low and environment friendly and pollution-free.
Embodiment
The present invention is further illustrated with reference to specific examples below.
Embodiment 1
Weigh 95.0 g 2- picolines, 61.3 g paraformaldehydes in there-necked flask, add 1.02 g acetic acid and
100.0 g DMF, 31.0 g water, 2 ~ 3 h are stirred at 90 DEG C, 110 DEG C are heated to when no solid, react 30 h.First normal pressure
2- picolines are distilled out at 150 DEG C, then rise to 180 DEG C, it is product 2- ethoxys to be evaporated under reduced pressure and collect 110 ~ 120 DEG C of cuts
Pyridine.Determined through gas chromatography, conversion per pass 35.15%, purity 99.9%.
Embodiment 2
Weigh 76.0 g 2- picolines, 49.3 g paraformaldehydes in there-necked flask, add 0.82 g ethanedioic acids and
150.0 g DMF, 25.0 g water, 2 ~ 3 h are stirred at 90 DEG C, 110 DEG C are heated to when no solid, react 30 h.First normal pressure
2- picolines are distilled out at 150 DEG C, then rise to 180 DEG C, it is product 2- ethoxys to be evaporated under reduced pressure and collect 110 ~ 120 DEG C of cuts
Pyridine.Determined through gas chromatography, conversion per pass 36.73%, purity 99.0%.
Embodiment 3
Weigh 34.28 g 2- picolines, 22.3 g paraformaldehydes in there-necked flask, add 0.32 g benzoic acid and
50.0 g DMF, 15.0 g water, 2 ~ 3 h are stirred at 90 DEG C, 110 DEG C are heated to when no solid, react 30 h.First normal pressure
2- picolines are distilled out at 150 DEG C, then rise to 180 DEG C, it is product 2- ethoxys to be evaporated under reduced pressure and collect 110 ~ 120 DEG C of cuts
Pyridine.Determined through gas chromatography, conversion per pass 31.37%, purity 99.9%.
Claims (1)
- A kind of 1. method of synthesis 2- ethoxy pyridines, it is characterised in that comprise the steps：Weigh 76.0 g 2- methyl pyrroles Pyridine, 49.3 g paraformaldehydes add 0.82 g ethanedioic acids and 150.0g DMF in there-necked flask, 25.0 g water, are stirred at 90 DEG C 2 ~ 3 h are mixed, 110 DEG C are heated to when no solid, react 30 h；2- picolines are distilled out at first 150 DEG C of normal pressure, then are risen to 180 DEG C, it is product 2- ethoxy pyridines to be evaporated under reduced pressure and collect 110 ~ 120 DEG C of cuts.
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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 CN105237468A (en) | 2016-01-13 |
| CN105237468B true CN105237468B (en) | 2018-03-27 |
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| 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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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN1253438C (en) * | 2004-05-18 | 2006-04-26 | 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 |
| CN101698658B (en) * | 2009-10-16 | 2012-06-13 | 长汀劲美生物科技有限公司 | 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 |
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