CN103787963A - Efficient preparation of 4-dimethylaminopyridine - Google Patents
Efficient preparation of 4-dimethylaminopyridine Download PDFInfo
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- CN103787963A CN103787963A CN201310706964.3A CN201310706964A CN103787963A CN 103787963 A CN103787963 A CN 103787963A CN 201310706964 A CN201310706964 A CN 201310706964A CN 103787963 A CN103787963 A CN 103787963A
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- 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
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Abstract
The invention discloses a new method for preparing 4-dimethylaminopyridine (DMAP) with a one-kettle process by taking 4-cyanopyridine and acrylic acid as main raw materials. The method mainly comprises the following steps: performing quaternization of 4-cyanopyridine with acrylic acid to obtain an intermediate; reacting with an amination reagent; neutralizing acid in the system in the presence of a pH regulator to enable the product to be free, wherein the reaction period is greatly shortened; and performing simple separation and purification to obtain a target product DMAP. In the method disclosed by the invention, the reaction conditions are mild, the synthesis method is simple, the DMAP synthesis can be efficiently performed through simple technological operation, and the obtained product has high purity and high yield; and the method is suitable for large-scale industrial production.
Description
Technical field
The present invention relates to a kind of one still process that adopts take 4-cyanopyridine and vinylformic acid as main raw material and prepare the novel method of DMAP.
Background technology
DMAP, is a kind of new and effective acylation catalyst, in the organic reactions such as the acylations of alcohol, enol, amine, phenol, enol ester, isocyanide ester class and transesterify, alcohols etherificate, is widely used.In addition, DMAP can also be served as anti-phase phase-transfer catalyst, for surface reaction.Because it has that speed of response is fast, mild condition, solvent applicatory be extensive; and product yield is compared with advantages of higher; and be applicable to sterically hindered large alcohols and some acylation reactions to the unsettled oxy-compound of acid; DMAP is widely used in the fine chemistry industry production fields such as medicine, agricultural chemicals, spices, petrochemical complex, has broad application prospects.
The method of synthetic DMAP is more.Conventionally laboratory can be prepared by 4-substituted pyridines: as 4-aminopyridine method, 4-tri-silyloxy pyridine methods, 4-pyridone method, 4-chloropyridine method etc., the common shortcoming of these class methods is that raw material sources difficulty, productive rate are generally on the low side.Industrial production technique mainly contains double amidopyridine salt method and 4-cyanopyridine method.Wherein two pyridine methods, take pyridine and sulfur oxychloride as raw material, first make intermediate 4-(4-pyridyl) pyridinium chloride hydrochloride, then react generation DMAP with dimethylamine or dimethyl formamide.4-cyanopyridine method is take 4-cyanopyridine and 2-vinyl pyridine, dimethylamine as starting raw material, and take water and acetone as mixed solvent, the 2 h cracking intermediates that reflux in dilute alkaline soln, make DMAP.The DMAP product yield that above technique obtains is low, only 60 ~ 75%, is difficult to obtain highly purified product in production operation, general all lower than 98.5%.And above two kinds of techniques all need polystep reaction, and intermediate also needs just can carry out the next step through separating-purifying, technique starting raw material price loaded down with trivial details, that use is high, pollutes greatly, and " three wastes " are difficult for processing.
During the DMAP that patent 4158093 is reported synthesizes, 4-cyanopyridine and 2-vinyl pyridine, under a kind of existence of strong acid, obtain 4-cyanopyridine vinyl adducts hydrochloride, and this hydrochloride carries out nucleophilic substitution reaction, and then under NaOH exists, cracking obtains DMAP.Synthesis step is loaded down with trivial details, intermediate also needs just can carry out the next step through separating-purifying, and gained DMAP yield is lower, cost is high, pollution is large.
The people such as Sun Shunneng are at " chemical reagent " (Vol.12,1989,357) report in the synthetic and application of DMAP: in ethyl acetate medium, take pyridine and thionyl chloride after raw material carries out back flow reaction, first steam except ethyl acetate and unreacted pyridine and thionyl chloride, obtain intermediate with dehydrated alcohol processing again, finally carry out nucleophilic substitution reaction with DMF again and obtain finished product.Operate intermediate relatively loaded down with trivial details and that obtain unstable, can decompose as stirring waits under External Force Acting; And high temperature can cause side reaction to increase for a long time, affects the yield of product.
Summary of the invention
In order to make up shortcomings and deficiencies of the prior art, the object of the present invention is to provide the novel method of the synthetic DMAP of a kind of one still process.Be quaternary ammonium intermediate without separation and purification, directly add aminated reagent to replace cyano group, then decompose and obtain target product through pH adjusting agent, raw material propylene acid recycle, the rate of recovery reaches more than 95%.The method reaction conditions gentleness, technique is simple, purity and yield is high, it is little to lose.
The synthetic method of a kind of high-content, low cost DMAP, it is characterized in that, concentrated hydrochloric acid is splashed in the mixing solutions of 4-cyanopyridine, vinylformic acid and water, stir, and be warming up to 50 ~ 60 ° of C, insulation 4 ~ 8 h, after insulation finishes, naturally cool to room temperature, disposable aminated reagent, 30 ~ 50 ° of C stirring 1 ~ 3 h of adding, then add appropriate pH adjusting agent, under reflux conditions, continue reaction 0.5-3 h, stop stirring and be down to room temperature after stratification and carry out solid-liquid separation, washing and drying obtains DMAP finished product.
Described a kind of high-content, the synthetic method of low cost DMAP, is characterized in that, 4-cyanopyridine and vinylformic acid mol ratio are 1.0 ~ 2.5:1.
Described a kind of high-content, the synthetic method of low cost DMAP, the mass ratio that it is characterized in that added 4-cyanopyridine and concentrated hydrochloric acid, water, aminated reagent is 1:1 ~ 1.5:0.7 ~ 1.0:05 ~ 0.9.
Described a kind of high-content, the synthetic method of low cost DMAP, is characterized in that adopted aminated reagent is one or more the compound in following material: dimethylamine hydrochloride, DMF, dimethylamine.
Described a kind of high-content, the synthetic method of low cost DMAP, is characterized in that adding pH adjusting agent to make the pH of reaction system be stabilized in 10.5 ~ 13.
Described a kind of high-content, the synthetic method of low cost DMAP, it is characterized in that pH adjusting agent adopts the mixing solutions of one or several compositions in volatile salt, sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, bicarbonate of ammonia, sodium bicarbonate, saleratus, SODIUM PHOSPHATE, MONOBASIC, potassium primary phosphate, pH adjusting agent concentration of polymer solution is 20 ~ 40%.
A synthetic method for high-content, low cost DMAP, is characterized in that comprising the following steps:
In DMAP aftertreatment, stop stirring and be down to room temperature after stratification and carry out solid-liquid separation, organic phase only needs washing and drying, has save re-crystallization step in operation.
The advantage of a kind of method of effectively preparing DMAP provided by the invention:
(1), on the Research foundation of 4-cyanopyridine method, having overcome tradition needs the deficiencies such as three-step reaction, intermediate need just can carry out next step reaction through separating-purifying, technique is loaded down with trivial details, starting material are expensive;
(2) quaternary ammonium intermediate, without separation and purification, directly adds aminated reagent, has effectively shortened reaction time, has also avoided the lower long time of the condition of high temperature simultaneously, has reduced the generation of side reaction, has effectively improved product content and yield;
(3) obtain highly purified finished product by aftertreatments such as simple solid-liquid separation, washing and dryings, reduced the loss of product, thereby obtain higher reaction yield;
(4) reduced production cost, therefore method of the present invention is suitable for suitability for industrialized production.
Embodiment
What below enumerate is only several specific embodiments of the present invention.Obviously, the invention is not restricted to above embodiment, all distortion of directly being derived or associated by content disclosed by the invention, all should think protection scope of the present invention.
Embodiment 1
In the enamel glass reactor of 3000 L, add successively 4-cyanopyridine 200 Kg, vinylformic acid 107 Kg, water 170 Kg, stir, then drip 50 ℃ of insulation 5 h after 260 Kg concentrated hydrochloric acids.Be cooled to after room temperature the disposable 150 Kg dimethyl formamides that add, 35 ℃ of insulation 2 h.Insulation finishes rear dropping 30%K
2cO
3solution, after 10.5 ~ 13, is incubated 1 h to pH value under reflux conditions.After system is cooling, suction filtration is removed water layer, and solid phase is washed, is drying to obtain DMAP finished product, and HPLC analyzes content 99.24%, yield 92.3%.Mp110 ~ 111.6 ℃ (WRS-1A numeral melting point instrument).
Embodiment 2
In the enamel glass reactor of 3000 L, add successively 4-cyanopyridine 200 Kg, vinylformic acid 107 Kg, water 170 Kg, stir, then drip 55 ℃ of insulation 4 h after 260 Kg concentrated hydrochloric acids.Be cooled to after room temperature the disposable 420 Kg dimethylamine (33%) that add, 40 ℃ of insulation 1.5 h.Insulation finishes rear dropping 30%NaOH solution, after 11.5 ~ 12, is incubated 1.5 h to pH value under reflux conditions.After system is cooling, suction filtration is removed water layer, and solid phase is washed, is drying to obtain DMAP finished product, and HPLC analyzes content 98.6%, yield 90.4%.Mp111 ~ 111.9 ℃ (WRS-1A numeral melting point instrument).
Embodiment 3
In the enamel glass reactor of 3000 L, add successively 4-cyanopyridine 200 Kg, vinylformic acid 107 Kg, water 170 Kg, stir, then drip 55 ℃ of insulation 6 h after 260 Kg concentrated hydrochloric acids.Be cooled to after room temperature the disposable 155 Kg dimethyl hydrochlorides that add, 35 ℃ of insulation 2 h.Insulation finishes rear dropping 30%Na
2cO
3solution, after 11 ~ 12, is incubated 2 h to pH value under reflux conditions.After system is cooling, suction filtration is removed water layer, and solid phase is washed, is drying to obtain DMAP finished product, and HPLC analyzes content 96.2%, yield 87.3%.Mp110.3 ~ 112.1 ℃ (WRS-1A numeral melting point instrument).
Embodiment 4
In the enamel glass reactor of 3000 L, add successively 4-cyanopyridine 200 Kg, vinylformic acid 107 Kg, water 170 Kg, concentrated hydrochloric acid 260 Kg, stir, 60 ℃ of insulation 5 h.Be cooled to after room temperature the disposable 420 Kg dimethylamine (33%) that add, 40 ℃ of insulation 2 h.Insulation finishes rear dropping 30%NaOH solution, after 11.5 ~ 13, is incubated 2 h to pH value under reflux conditions.After system is cooling, suction filtration is removed water layer, and solid phase is washed, is drying to obtain DMAP finished product, and HPLC analyzes content 95.9%, yield 88.2%.Mp111.5 ~ 112.3 ℃ (WRS-1A numeral melting point instrument).
Embodiment 5
In the enamel glass reactor of 3000 L, add successively 4-cyanopyridine 200 Kg, vinylformic acid 107 Kg, water 170 Kg, concentrated hydrochloric acid 260 Kg, stir, 60 ℃ of insulation 5 h.Be cooled to after room temperature the disposable 155 Kg dimethyl hydrochlorides that add, 50 ℃ of insulation 2 h.Insulation finishes rear dropping 30%KOH solution, after 11.5 ~ 13, is incubated 2 h to pH value under reflux conditions.After system is cooling, suction filtration is removed water layer, and solid phase is washed, is drying to obtain DMAP finished product, and HPLC analyzes content 94.3%, yield 89.2%.Mp110.2 ~ 111.6 ℃ (WRS-1A numeral melting point instrument).
Claims (6)
1. the synthetic method of a high-content, low cost DMAP, it is characterized in that, concentrated hydrochloric acid is splashed in the mixing solutions of 4-cyanopyridine, vinylformic acid and water, stir, and be warming up to 50 ~ 60 ° of C, insulation 4 ~ 8 h, after insulation finishes, naturally cool to room temperature, disposable aminated reagent, 30 ~ 50 ° of C stirring 1 ~ 3 h of adding, then add appropriate pH adjusting agent, under reflux conditions, continue reaction 0.5-3 h, stop stirring and be down to room temperature after stratification and carry out solid-liquid separation, washing and drying obtains DMAP finished product.
2. the synthetic method of a kind of high-content according to claim 1, low cost DMAP, is characterized in that, 4-cyanopyridine and vinylformic acid mol ratio are 1.0 ~ 2.5:1.
3. the synthetic method of a kind of high-content according to claim 1 and 2, low cost DMAP, the mass ratio that it is characterized in that added 4-cyanopyridine and concentrated hydrochloric acid, water, aminated reagent is 1:1 ~ 1.5:0.7 ~ 1.0:05 ~ 0.9.
4. the synthetic method of a kind of high-content according to claim 1, low cost DMAP, it is characterized in that adopted aminated reagent is one or more the compound in following material: dimethylamine hydrochloride, DMF, dimethylamine.
5. the synthetic method of a kind of high-content according to claim 1, low cost DMAP, is characterized in that adding pH adjusting agent to make the pH of reaction system be stabilized in 10.5 ~ 13.
6. the synthetic method of a kind of high-content, low cost DMAP according to claim 1 or 5, it is characterized in that pH adjusting agent adopts the mixing solutions of one or several compositions in volatile salt, sodium hydroxide, potassium hydroxide, sodium carbonate, salt of wormwood, bicarbonate of ammonia, sodium bicarbonate, saleratus, SODIUM PHOSPHATE, MONOBASIC, potassium primary phosphate, pH adjusting agent concentration of polymer solution is 20 ~ 40%.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111320572A (en) * | 2020-04-15 | 2020-06-23 | 杭州瑞思新材料有限公司 | Preparation method of substituted pyridine |
| CN111320571A (en) * | 2020-04-15 | 2020-06-23 | 杭州瑞思新材料有限公司 | Novel method for preparing 4-dimethylaminopyridine |
| CN111454201A (en) * | 2020-04-15 | 2020-07-28 | 杭州瑞思新材料有限公司 | Novel method for preparing efficient acylation catalyst material |
| CN111592488A (en) * | 2019-11-18 | 2020-08-28 | 河南郑大嘉源环保技术有限公司 | Method for efficiently preparing 4-dimethylaminopyridine |
| CN114478369A (en) * | 2022-01-11 | 2022-05-13 | 浙江工业大学 | Method for continuously preparing 4-dimethylaminopyridine by using microchannel reactor |
Citations (2)
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| US4772713A (en) * | 1985-01-16 | 1988-09-20 | Nepera, Inc. | Quaternary pyridine salts useful for preparation of 4-substituted pyridines |
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| US4772713A (en) * | 1985-01-16 | 1988-09-20 | Nepera, Inc. | Quaternary pyridine salts useful for preparation of 4-substituted pyridines |
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Non-Patent Citations (2)
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111592488A (en) * | 2019-11-18 | 2020-08-28 | 河南郑大嘉源环保技术有限公司 | Method for efficiently preparing 4-dimethylaminopyridine |
| CN111320572A (en) * | 2020-04-15 | 2020-06-23 | 杭州瑞思新材料有限公司 | Preparation method of substituted pyridine |
| CN111320571A (en) * | 2020-04-15 | 2020-06-23 | 杭州瑞思新材料有限公司 | Novel method for preparing 4-dimethylaminopyridine |
| CN111454201A (en) * | 2020-04-15 | 2020-07-28 | 杭州瑞思新材料有限公司 | Novel method for preparing efficient acylation catalyst material |
| CN111320571B (en) * | 2020-04-15 | 2021-07-23 | 杭州瑞思新材料有限公司 | Method for preparing 4-dimethylaminopyridine |
| CN111320572B (en) * | 2020-04-15 | 2021-07-23 | 杭州瑞思新材料有限公司 | Preparation method of substituted pyridine |
| CN111454201B (en) * | 2020-04-15 | 2022-01-04 | 杭州瑞思新材料有限公司 | Novel method for preparing efficient acylation catalyst material |
| CN114478369A (en) * | 2022-01-11 | 2022-05-13 | 浙江工业大学 | Method for continuously preparing 4-dimethylaminopyridine by using microchannel reactor |
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Application publication date: 20140514 |