CN111320571A - Novel method for preparing 4-dimethylaminopyridine - Google Patents
Novel method for preparing 4-dimethylaminopyridine Download PDFInfo
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- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 title claims abstract description 83
- 238000000034 method Methods 0.000 title claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 96
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 56
- 239000002994 raw material Substances 0.000 claims abstract description 43
- GPHQHTOMRSGBNZ-UHFFFAOYSA-N pyridine-4-carbonitrile Chemical compound N#CC1=CC=NC=C1 GPHQHTOMRSGBNZ-UHFFFAOYSA-N 0.000 claims abstract description 29
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims abstract description 27
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims abstract description 27
- QIGBRXMKCJKVMJ-UHFFFAOYSA-N Hydroquinone Chemical compound OC1=CC=C(O)C=C1 QIGBRXMKCJKVMJ-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000003756 stirring Methods 0.000 claims abstract description 8
- 238000004821 distillation Methods 0.000 claims abstract description 7
- 238000010438 heat treatment Methods 0.000 claims abstract description 6
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 46
- 238000000605 extraction Methods 0.000 claims description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 30
- 239000000243 solution Substances 0.000 claims description 19
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
- 238000011084 recovery Methods 0.000 claims description 14
- 230000008569 process Effects 0.000 claims description 12
- 239000007788 liquid Substances 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 10
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 8
- 239000007864 aqueous solution Substances 0.000 claims description 8
- 238000001816 cooling Methods 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 7
- 239000013078 crystal Substances 0.000 claims description 7
- 239000012071 phase Substances 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 5
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 4
- 238000004042 decolorization Methods 0.000 claims description 4
- 230000001502 supplementing effect Effects 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000003518 caustics Substances 0.000 claims 1
- 238000002360 preparation method Methods 0.000 claims 1
- 239000007858 starting material Substances 0.000 claims 1
- 239000000203 mixture Substances 0.000 abstract description 8
- 239000003112 inhibitor Substances 0.000 abstract description 5
- 238000006116 polymerization reaction Methods 0.000 abstract description 5
- 238000007086 side reaction Methods 0.000 abstract description 3
- 239000000047 product Substances 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical group C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
- 235000011121 sodium hydroxide Nutrition 0.000 description 8
- 239000003054 catalyst Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 5
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 5
- KGIGUEBEKRSTEW-UHFFFAOYSA-N 2-vinylpyridine Chemical compound C=CC1=CC=CC=N1 KGIGUEBEKRSTEW-UHFFFAOYSA-N 0.000 description 4
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 230000010933 acylation Effects 0.000 description 3
- 238000005917 acylation reaction Methods 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 230000006872 improvement Effects 0.000 description 3
- 239000012265 solid product Substances 0.000 description 3
- 238000006467 substitution reaction Methods 0.000 description 3
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Substances ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 3
- 239000002699 waste material Substances 0.000 description 3
- TWUUWLUYSIVBMY-UHFFFAOYSA-N 4-(2h-pyridin-1-yl)pyridin-1-ium;chloride;hydrochloride Chemical compound Cl.[Cl-].C1C=CC=CN1C1=CC=[NH+]C=C1 TWUUWLUYSIVBMY-UHFFFAOYSA-N 0.000 description 2
- GCNTZFIIOFTKIY-UHFFFAOYSA-N 4-hydroxypyridine Chemical compound OC1=CC=NC=C1 GCNTZFIIOFTKIY-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000003197 catalytic effect Effects 0.000 description 2
- 239000013067 intermediate product Substances 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 239000002351 wastewater Substances 0.000 description 2
- PVMNPAUTCMBOMO-UHFFFAOYSA-N 4-chloropyridine Chemical compound ClC1=CC=NC=C1 PVMNPAUTCMBOMO-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 229910006124 SOCl2 Inorganic materials 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- -1 bipyridyl salt Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000012295 chemical reaction liquid Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical group 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 150000007529 inorganic bases Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000002304 perfume Substances 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 230000026731 phosphorylation Effects 0.000 description 1
- 238000006366 phosphorylation reaction Methods 0.000 description 1
- 239000003495 polar organic solvent Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- PTWLOSARXIJRRJ-UHFFFAOYSA-N pyridin-1-ium-4-sulfonate Chemical compound OS(=O)(=O)C1=CC=NC=C1 PTWLOSARXIJRRJ-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000007790 solid phase Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- PYUVWRKNVLSJJE-UHFFFAOYSA-N trimethyl(pyridin-4-yl)silane Chemical compound C[Si](C)(C)C1=CC=NC=C1 PYUVWRKNVLSJJE-UHFFFAOYSA-N 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- 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
- C07D213/72—Nitrogen atoms
- C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention discloses a new method for preparing 4-dimethylaminopyridine, which comprises the steps of putting an acrylic acid raw material into a reaction kettle, putting a concentrated hydrochloric acid raw material into the reaction kettle, putting hydroquinone into the reaction kettle, heating and stirring the mixture, and stirring the mixture at the temperature of between 80 and 100 ℃ for reaction for 2 to 4 hours; slowly adding 4-cyanopyridine raw material at the temperature of 80-100 ℃, wherein the feeding time is 1-2 hours, continuously reacting for 1-2 hours after the feeding is finished, and carrying out reduced pressure distillation to recover excessive hydrochloric acid. In the present invention, acrylic acid is sufficiently activated to undergo a sufficient radical protecting reaction with 4-cyanopyridine. Meanwhile, hydroquinone is added as a polymerization inhibitor of acrylic acid, so that other side reactions are not generated at high temperature.
Description
Technical Field
The invention relates to the technical field of chemical industry, in particular to a novel method for preparing 4-dimethylaminopyridine.
Background
4-dimethylamino pyridine is a white crystal powder with molecular formula C, which is a novel high-efficiency catalyst widely used in chemical synthesis7H10N2. The molecular structure is as follows:
4-Dimethylaminopyridine (DMAP) with CAS registry number 1122-58-3.
4-dimethylamino pyridine is a novel high-efficiency catalyst widely used for chemical synthesis in recent years, the resonance of dimethylamino group for supplying electrons on the structure and a mother ring (pyridine ring) can strongly activate nitrogen atoms on the ring for nucleophilic substitution, and the acylation (phosphorylation, sulfonylation and carbon acylation) reaction of alcohol and amine with high steric hindrance and low reactivity is remarkably catalyzed, and the activity of the catalyst is about 10 of pyridine4-6And (4) doubling. The catalyst has high catalytic capability in various reactions such as acylation, alkylation, etherification, esterification and ester exchange in organic synthesis, pharmaceutical synthesis, pesticides, medicines, dyes, perfumes, polymer chemistry and analytical chemistry, has extremely obvious effect on improving yield, and can also be used as a phase transfer catalyst for interface reaction. Its advantages are: the catalyst is small in dosage, and generally only needs 0.01-5% of the mole number of a reaction substrate, and acid generated by the reaction can be neutralized by organic base or inorganic base; the reaction condition is mild, the reaction can be carried out at room temperature, and the energy is saved; the solvent has wide selection range and can be carried out in polar and non-polar organic solvents; the reaction time is short, pyridine is used for reacting for a long time, and DMAP is used for completing the reaction within minutes, so that the labor productivity is greatly improved; the yield is high, for example, when pyridine is used for hardly reacting hydroxyl compounds with large steric hindrance, the yield of DMAP can reach 80-90%, so that the reaction yield and the product quality can be improved, and the process can be simplified; less side reaction, less smell and less three wastes; DMAP has become one of the most commonly used catalysts for organic synthesizers due to its superior catalytic properties, known as a "super catalyst".
Many methods for synthesizing DMAP have been reported, including the 4-pyridone method, the 4-chloropyridine method, the 4-hydroxypyridine method, the 4-pyridinesulfonic acid method, and the 4-trimethylsilylpyridine method. However, the DMAP synthesis method in industry mainly uses pyridine and SOCl2The intermediate product N- (4-pyridyl) pyridine chloride hydrochloride (namely bipyridyl salt) is prepared by reaction as a raw material, and then the intermediate product N- (4-pyridyl) pyridine chloride hydrochloride and DMF are refluxed to prepare DMAP. The method has the advantages of cheap and easily obtained raw materials, simple and convenient operation and short process flow, but the conversion rate of the raw material pyridine is low, and is generally below 40%. Meanwhile, the dosage of thionyl chloride is large, the discharge amount of three wastes is large, the treatment is difficult, and the pollution to the environment is very serious. Is provided withThe reports that DMAP is prepared by taking 4-cyanopyridine as a raw material and dimethylamine aqueous solution as an amination reagent under the activation of 2-vinylpyridine have relatively mild reaction conditions and greatly improved reaction yield. However, the 2-vinylpyridine used in the method is high in price, and the recycling effect is not ideal, so that the industrial application is hindered.
Disclosure of Invention
The invention mainly solves the defects in the prior art and provides a novel method for preparing 4-dimethylaminopyridine.
The invention is realized by the following technical scheme for achieving the aim:
the invention discloses a novel method for preparing 4-dimethylaminopyridine, which comprises the following steps:
(1) adding an acrylic acid raw material, a concentrated hydrochloric acid raw material and hydroquinone into a reaction kettle, heating and stirring, and stirring and reacting at the temperature of 80-100 ℃ for 2-4 hours;
(2) slowly adding 4-cyanopyridine raw material at the temperature of 80-100 ℃, wherein the feeding time is 1-2 hours, continuously reacting for 1-2 hours after the feeding is finished, and recovering excessive hydrochloric acid by reduced pressure distillation;
(3) slowly dripping the obtained reaction solution into 40 percent dimethylamine aqueous solution under the condition of keeping the temperature at 80-100 ℃, controlling the reaction temperature to reflux at 50 ℃, controlling the dripping time to be 1-2 hours, and then keeping the temperature for 1-2 hours for reaction;
(4) slowly dripping liquid alkali raw materials at the temperature of 50-70 ℃, simultaneously carrying out reduced pressure distillation to recover excessive dimethylamine, wherein the dripping time is 1-2 hours, after the dripping is finished, heating, and controlling a reaction system to continuously react for 1-2 hours at the temperature of 80-100 ℃ to finish the reaction;
(5) after the reaction is finished, transferring the reaction solution into an extraction kettle while the reaction solution is hot, and adding toluene or xylene for extraction, wherein the extraction temperature is 80-100 ℃;
(6) adding the organic phase obtained by extraction into active carbon for decoloring and filtering, and cooling to separate out white crystals, namely the product 4-dimethylaminopyridine;
(7) adding hydrochloric acid into the raffinate phase obtained by extraction to adjust the pH value to 5-7, adding the next batch of raw material 4-cyanopyridine at the temperature of 90-100 ℃ for extraction and recovery, directly putting the organic phase after extraction into the next batch of reaction kettle, and beginning the next batch of reaction after supplementing part of raw materials.
As a further improvement, the liquid caustic soda raw material is sodium hydroxide.
As a further improvement, the molar ratio of the raw materials in the method is 4-cyanopyridine: acrylic acid: hydrogen chloride (hydrochloric acid): hydroquinone: dimethylamine: sodium hydroxide ═ 1.0: 1.1-1.3: 2.2-3.3: 0.0055-0.0065: 2.0-4.0: 4.0-6.0.
As a further improvement, the recovery rate of acrylic acid in the method of the invention is more than 93%, the yield of 4-dimethylaminopyridine calculated by 4-cyanopyridine is more than 97%, and the content of 4-dimethylaminopyridine is more than 99.0%.
The invention has the following beneficial effects:
1. according to the reaction mechanism and the reaction kinetics principle, the acrylic acid raw material and the cheap hydrochloric acid raw material are firstly reacted, so that the reaction probability of the acrylic acid is reduced after the hydrochloric acid is directly salified with the 4-cyanopyridine. In the present invention, acrylic acid is sufficiently activated to undergo a sufficient radical protecting reaction with 4-cyanopyridine. Meanwhile, hydroquinone is added as a polymerization inhibitor of acrylic acid, so that other side reactions are not generated at high temperature.
2. After acrylic acid is fully activated, the 4-cyanopyridine raw material is slowly added into the reaction system, so that the 4-cyanopyridine raw material can be further ensured to be fully reacted with the acrylic acid, and the product selectivity and the product yield are improved. The excessive hydrochloric acid is beneficial to the combination of the hydrochloric acid and the waste water, and after the reaction is finished, the excessive hydrochloric acid is recovered, so that the water content in the system can be reduced, and the total amount of salts in the three wastes can be reduced.
3. The present invention further comprises slowly dropping the reaction solution into the dimethylamine aqueous solution to carry out the substitution reaction while keeping the temperature of the reaction solution at a high temperature. The high temperature state ensures the fluidity and low viscosity of the reaction liquid, thereby being beneficial to mass transfer and reaction, and the high excess proportion of dimethylamine further ensures the complete proceeding of the substitution reaction.
4. After the substitution reaction is finished, adding liquid alkali and recovering dimethylamine, so that the consumption of the raw material dimethylamine can be reduced, the cost is reduced, and the system can be rapidly heated, thereby completing the hydrolysis reaction.
5. The invention adopts a hot extraction mode to directly extract and take out a high-purity product, decolors and crystallizes the product while the product is hot to obtain a high-purity product DMAP, thereby greatly saving energy. In the raffinate phase obtained after the thermal extraction, the method directly adds acid for neutralization, and adopts the next batch of raw material 4-cyanopyridine for thermal extraction, thereby not only recovering the acrylic acid in the raffinate phase, but also recovering part of unreacted raw materials, greatly reducing COD in the wastewater, reducing the treatment difficulty, greatly improving the recovery rate of the acrylic acid in the process, improving the yield of the product and reducing the comprehensive cost.
6. In the reaction, due to the comprehensive utilization of the process, the recovery rate of acrylic acid in the process is more than 93%, the yield of 4-dimethylaminopyridine calculated by 4-cyanopyridine is more than 97%, and the content of 4-dimethylaminopyridine is more than 99.0%.
Detailed Description
The technical solution of the present invention will be further described in detail with reference to specific examples, but the scope of the present invention is not limited to the examples.
Example 1
(1) 1.1mol of acrylic acid raw material, 2.2mol of concentrated hydrochloric acid raw material (hydrogen chloride mol number is 2.2mol), 0.0055mol of polymerization inhibitor hydroquinone are added into the reaction kettle, and the mixture is heated and stirred. The reaction was stirred at a temperature of 80 ℃ for 4 hours.
(2) Slowly adding 1.0mol of 4-cyanopyridine raw material at the temperature of 80 ℃, wherein the adding time is 2 hours, and continuing the reaction for 2 hours after the adding is finished. And (5) distilling under reduced pressure to recover excessive hydrochloric acid.
(3) The obtained reaction solution was slowly dropped into a 40% dimethylamine aqueous solution (molar number of dimethylamine: 2.0mol) while keeping the temperature at 80 ℃, the reaction temperature was controlled to 50 ℃ for reflux, the dropping time was controlled to 1 hour, and then the reaction was carried out by keeping the temperature for 1 hour.
(4) At a temperature of 50 ℃, slowly dripping liquid alkali raw materials (the mass concentration is 30 percent, the mole number of sodium hydroxide is 4.0mol), simultaneously decompressing, distilling and recovering excessive dimethylamine, and the dripping time is 2 hours. After the dropwise addition, the temperature is raised, and the reaction system is controlled to continue to react at 80 ℃ for 2 hours, so that the reaction is finished.
(5) After the reaction is finished, the reaction solution is transferred into an extraction kettle while the reaction solution is hot. Toluene was added for extraction. The extraction temperature was 80 ℃.
(6) Adding the organic phase obtained by extraction into active carbon for decolorization and filtration, and cooling to separate out white crystals, namely the product 4-dimethylaminopyridine.
(7) Adding hydrochloric acid into the raffinate phase obtained by extraction to adjust the pH value to 5, adding 1.0mol of the next batch of raw material 4-cyanopyridine at the temperature of 90 ℃ for extraction and recovery, directly putting the organic phase after extraction into the next batch of reaction kettle, and starting the next batch of reaction.
The white solid product 4-dimethylamino pyridine can be obtained through the reaction. The recovery rate of acrylic acid in the process is calculated to be 93%, the yield of 4-dimethylamino pyridine calculated by 4-cyanopyridine is 97%, and the content of 4-dimethylamino pyridine is 99.2%.
Example 2
(1) 1.3mol of acrylic acid raw material, 3.3mol of concentrated hydrochloric acid raw material (the mole number of hydrogen chloride is 3.3mol), 0.0065mol of polymerization inhibitor hydroquinone are added into a reaction kettle, and the mixture is heated and stirred. The reaction was stirred at a temperature of 100 ℃ for 2 hours.
(2) Slowly adding 1.0mol of 4-cyanopyridine raw material at the temperature of 100 ℃, wherein the adding time is 1 hour, and continuing the reaction for 1 hour after the adding is finished. And (5) distilling under reduced pressure to recover excessive hydrochloric acid.
(3) The obtained reaction solution was slowly dropped into a 40% dimethylamine aqueous solution (mole number of dimethylamine: 4.0mol) while keeping the temperature at 100 ℃, the reaction temperature was controlled at 50 ℃ for reflux, the dropping time was controlled at 2 hours, and then the reaction was carried out by keeping the temperature for 2 hours.
(4) At a temperature of 70 ℃, slowly dropping liquid alkali raw materials (mass concentration is 50 percent, and the mole number of sodium hydroxide is 6.0mol), simultaneously decompressing, distilling and recovering excessive dimethylamine, wherein the dropping time is 1 hour. After the dropwise addition, the temperature is raised, and the reaction system is controlled to continue to react at 100 ℃ for 1 hour, so that the reaction is finished.
(5) After the reaction is finished, the reaction solution is transferred into an extraction kettle while the reaction solution is hot. Adding dimethylbenzene for extraction. The extraction temperature was 100 ℃.
(6) Adding the organic phase obtained by extraction into active carbon for decolorization and filtration, and cooling to separate out white crystals, namely the product 4-dimethylaminopyridine.
(7) Adding hydrochloric acid into the raffinate phase obtained by extraction to adjust the pH value to 7, adding 1.0mol of the next batch of raw material 4-cyanopyridine at the temperature of 100 ℃ for extraction and recovery, directly putting the organic phase after extraction into the next batch of reaction kettle, and starting the next batch of reaction.
The white solid product 4-dimethylamino pyridine can be obtained through the reaction. The recovery rate of acrylic acid in the process is calculated to be 94%, the yield of 4-dimethylamino pyridine calculated by 4-cyanopyridine is 98%, and the content of 4-dimethylamino pyridine is 99.5%.
Example 3
(1) 1.2mol of acrylic acid raw material, 2.5mol of concentrated hydrochloric acid raw material (hydrogen chloride mol number is 2.5mol), 0.006mol of polymerization inhibitor hydroquinone are added into a reaction kettle, and the mixture is heated and stirred. The reaction was stirred at a temperature of 90 ℃ for 3 hours.
(2) At the temperature of 90 ℃, 1.0mol of 4-cyanopyridine raw material is slowly added for 1.5 hours, and after the addition is finished, the reaction is continued for 1.5 hours. And (5) distilling under reduced pressure to recover excessive hydrochloric acid.
(3) The obtained reaction solution was slowly dropped into a 40% dimethylamine aqueous solution (molar amount of dimethylamine: 3.0mol) while keeping the temperature at 90 ℃ and the reaction temperature was controlled to 50 ℃ for reflux, and the dropping time was controlled to 1.5 hours, after which the reaction was carried out with keeping the temperature for 1.5 hours.
(4) At a temperature of 60 ℃, slowly dropwise adding a liquid alkali raw material (the mass concentration is 40 percent, and the mole number of sodium hydroxide is 5.0mol), simultaneously carrying out reduced pressure distillation to recover excessive dimethylamine, wherein the dropwise adding time is 1.5 hours. After the dropwise addition, the temperature was raised, and the reaction was terminated after the reaction system was controlled to continue the reaction at 90 ℃ for 1.5 hours.
(5) After the reaction is finished, the reaction solution is transferred into an extraction kettle while the reaction solution is hot. Toluene was added for extraction. The extraction temperature was 90 ℃.
(6) Adding the organic phase obtained by extraction into active carbon for decolorization and filtration, and cooling to separate out white crystals, namely the product 4-dimethylaminopyridine.
(7) Adding hydrochloric acid into the raffinate phase obtained by extraction to adjust the pH value to 6, adding 1.0mol of the next batch of raw material 4-cyanopyridine at the temperature of 95 ℃ for extraction and recovery, directly putting the organic phase after extraction into the next batch of reaction kettle, and starting the next batch of reaction.
The white solid product 4-dimethylamino pyridine can be obtained through the reaction. The recovery rate of acrylic acid in the process is calculated to be 95%, the yield of 4-dimethylamino pyridine calculated by 4-cyanopyridine is 98.6%, and the content of 4-dimethylamino pyridine is 99.6%.
Comparative example 4
31.5g (0.303mol) of 4-cyanopyridine, 25mL of water, 44g (37mL) of concentrated hydrochloric acid, and 21g (0.200mol) of 2-vinylpyridine were successively charged into a stirred tank reactor, and mixed at 60 ℃ for 6 hours. After cooling to 30 ℃, 36.5mLw (dimethylamine) ═ 32% dimethylamine aqueous solution was added dropwise, and the mixture was stirred vigorously at 30 ℃ for 2 hours. Adding 200ml (NaOH) 40% liquid alkali, heating and boiling under reflux for 2 h. After the solution was cooled, an oil layer was separated, dried over anhydrous sodium sulfate, and distilled under reduced pressure, and the first collected fraction was 15.0g of 2-vinylpyridine (recovery rate: 71.4%). And (3) continuing reduced pressure distillation, cooling the collected fraction to obtain a light yellow solid, recrystallizing with ethyl acetate, and decoloring with activated carbon to obtain a white crystal DMAP27.3g, wherein the yield is 74.0%, and the test content is 99.0%.
Comparative example 5
200g of 4-cyanopyridine, 107g of acrylic acid and 170g of water are sequentially added into a stirred tank reactor and stirred uniformly. 260g of concentrated hydrochloric acid was further added dropwise thereto, and the mixture was kept at 55 ℃ for 4 hours. After cooling to room temperature, 420g of dimethylamine in water (33% by weight) were added in one portion and the mixture was incubated at 40 ℃ for 1.5 hours. After the heat preservation is finished, liquid caustic soda with the weight concentration of 30% is dripped until the pH value is 12, and the heat preservation is carried out for 1.5 hours under the reflux condition. And after the system is cooled, removing the water layer by suction filtration, washing with solid phase water, and drying to obtain a finished product of the 4-dimethylaminopyridine. The content of the product is 96.5 percent by detection, and the yield is 70 percent. Adjusting the pH value of the water layer after suction filtration to 5 by adopting hydrochloric acid, adding toluene for extraction, and testing the recovery rate of acrylic acid to be 31 percent after desolventizing.
Comparative example 6
200g of 4-cyanopyridine and 107g of acrylic acid are sequentially added into a stirring tank type reactor, hydrogen chloride gas is introduced into the reaction tank through a vent pipe under the stirring of 55 ℃, the vent pipe is blocked within half an hour, the reaction cannot be continued, and the reaction is stopped.
Finally, it should also be noted that the above list is only a specific implementation example of the present invention. It is obvious that the invention is not limited to the above embodiment examples, but that many variations are possible. All modifications which can be derived or suggested by a person skilled in the art from the disclosure of the present invention are to be considered within the scope of the invention.
Claims (4)
1. A novel method for preparing 4-dimethylaminopyridine is characterized by comprising the following steps:
1) adding acrylic acid raw material, concentrated hydrochloric acid raw material and hydroquinone into a reaction kettle, heating and stirring, and stirring and reacting at the temperature of 80-100 ℃ for 2-4 hours;
2) slowly adding a 4-cyanopyridine raw material at the temperature of 80-100 ℃, wherein the feeding time is 1-2 hours, continuously reacting for 1-2 hours after the feeding is finished, and recovering excessive hydrochloric acid by reduced pressure distillation;
3) slowly dripping the obtained reaction solution into 40 percent dimethylamine aqueous solution under the condition of keeping the temperature at 80-100 ℃, controlling the reaction temperature to reflux at 50 ℃, controlling the dripping time to be 1-2 hours, and then keeping the temperature for 1-2 hours for reaction;
4) slowly dripping liquid alkali raw materials at the temperature of 50-70 ℃, simultaneously carrying out reduced pressure distillation to recover excessive dimethylamine, wherein the dripping time is 1-2 hours, after the dripping is finished, heating, and controlling a reaction system to continuously react for 1-2 hours at the temperature of 80-100 ℃ to finish the reaction;
5) after the reaction is finished, transferring the reaction solution into an extraction kettle while the reaction solution is hot, and adding toluene or xylene for extraction, wherein the extraction temperature is 80-100 ℃;
6) adding the organic phase obtained by extraction into active carbon for decolorization and filtration, and cooling to separate out white crystals, namely the product 4-dimethylaminopyridine;
7) adding hydrochloric acid into the raffinate phase obtained by extraction to adjust the pH value to 5-7, adding the next batch of raw material 4-cyanopyridine at the temperature of 90-100 ℃ for extraction and recovery, directly putting the extracted organic phase into the next batch of reaction kettle, and beginning the next batch of reaction after supplementing part of raw materials.
2. The process of claim 1, wherein the liquid caustic is sodium hydroxide.
3. The novel process for the preparation of 4-dimethylaminopyridine according to claim 2, wherein the molar ratio of the starting materials is 4-cyanopyridine: acrylic acid: hydrochloric acid: hydroquinone: dimethylamine: sodium hydroxide ═ 1.0: 1.1-1.3: 2.2-3.3: 0.0055-0.0065: 2.0-4.0: 4.0-6.0.
4. The process of claim 1, 2 or 3 wherein the recovery of acrylic acid in the process is greater than 93%, the yield of 4-dimethylaminopyridine based on 4-cyanopyridine is greater than 97%, and the content of 4-dimethylaminopyridine is greater than 99.0%.
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| CN109608332A (en) * | 2019-01-18 | 2019-04-12 | 西安优耐特容器制造有限公司 | The method for being catalyzed continuous 14 ester of acrylic acid synthesizing using microwave-microreactor |
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| CN109608332A (en) * | 2019-01-18 | 2019-04-12 | 西安优耐特容器制造有限公司 | The method for being catalyzed continuous 14 ester of acrylic acid synthesizing using microwave-microreactor |
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