CN103193705A - Synthesis method of 2-chloronicotinic acid and derivative thereof - Google Patents
Synthesis method of 2-chloronicotinic acid and derivative thereof Download PDFInfo
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- CN103193705A CN103193705A CN2013100946343A CN201310094634A CN103193705A CN 103193705 A CN103193705 A CN 103193705A CN 2013100946343 A CN2013100946343 A CN 2013100946343A CN 201310094634 A CN201310094634 A CN 201310094634A CN 103193705 A CN103193705 A CN 103193705A
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Abstract
The invention discloses a synthesis method of 2-chloronicotinic acid and a derivative of 2-chloronicotinic acid. The synthesis method comprises the following steps of: adding a compound shown in formula (II) and an organic solvent into a high-pressure reaction kettle, stirring, dissolving and introducing hydrogen chloride gas to be 0.2-1.0MPa, sealing and carrying out heat preservation reaction at 20-100 DEG C, tracking and monitoring till the reaction is accomplished, releasing the pressure, completely discharging the hydrogen chloride gas, and carrying out later treatment on a reaction liquid so as to prepare the 2-chloronicotinic acid derivative shown in formula (I). The synthesis method adopts hydrogen chloride which is higher than ordinary pressure for reaction, so that the use amount of hydrogen chloride is reduced, the product yield is increased, a byproduct can be recycled and reused, and the three-waste emission and environmental pollution are reduced.
Description
(1) technical field
The present invention relates to the method for a kind of synthetic pesticide and medicine intermediate 2-chlorine apellagrin and derivative thereof.
(2) background technology
2-chlorine apellagrin and derivative thereof are the important intermediate of producing agricultural chemicals and medicine, as herbicide nicosulfuron, diflufenican, sterilant boscalid amine, anti-AIDS drug nevirapine, anti-depression medicine Midanping, non-steroidal anti-inflammatory analgesics niflumic acid and VP-74 etc.What the production of 2-chlorine apellagrin was generally adopted at present is the technology of 3-picoline (or derivatives thereof) chlorination, and there are two very distinct issues in this technology.The one, have bigger potential safety hazard: because this technology uses a large amount of phosphorus oxychloride as solvent and chlorination reagent, and phosphorus oxychloride belongs to hypertoxic chemical, and reaction is violent, causes security incident to happen occasionally; The 2nd, environmental pollution is serious: a large amount of phosphorus-containing wastewaters is difficult to handle, and poisonous strong acid waste gas harm is very big.
US4987232 and CN101367760 have reported and have used N, N-dimethyl-5-amido-2-cyano group-2,4-pentadienoic acid ethyl ester (formula II, R=CO
2C
2H
5, R
4=R
5=CH
3) under normal pressure, react synthetic 2-chlorine apellagrin ethyl ester with hydrogenchloride, in the method for the synthetic 2-chlorine apellagrin of further hydrolysis.This method need consume a large amount of hydrogenchloride, and yield is on the low side, and the dimethylamine by product that produces is difficult to reclaim, and wastewater flow rate is bigger.Therefore, be necessary aforesaid method is improved, the process for cleanly preparing that is fit to industrial applications is provided.
(3) summary of the invention
The object of the invention provides a kind of with N-substituting group-5-amido-2-cyano group-2, and the method for the synthetic 2-chlorine apellagrin of 4-pentadienoic acid derivates and derivative thereof, the key of this method are that this side should carry out under hydrogenchloride pressure is higher than the condition of normal pressure.
The technical solution used in the present invention is:
A kind of synthetic method suc as formula the 2-chlorine apellagrin derivative shown in (I), described method is:
Compound and organic solvent shown in the adding formula (II) in the autoclave, after the stirring and dissolving, feed hydrogen chloride gas to 0.2～1.0MPa, under 20～100 ℃ of temperature, airtight insulation reaction, gas-chromatography follow the tracks of to detect after react completely, pressure release, emptying hydrogen chloride gas, reaction solution aftertreatment prepare suc as formula the 2-chlorine apellagrin derivative shown in (I).
In formula (I) or the formula (II), R is-shown in the CN, formula (a)-CO
2R
1Or shown in the formula (b)-CONR
2R
3
In the formula (a), R
1The alkyl of expression H or C1～C6 is preferably methyl or ethyl; In the formula (b), R
2Or R
3Independent separately is the alkyl of H or C1～C6, preferred R
2Or R
3Be methyl.
Be R be preferably-CN ,-CON (CH
3)
2,-CO
2CH
3Or-CO
2C
2H
5As R=CON (CH
3)
2The time, formula I represents N, N-dimethyl-2-chloro-nicotinamide is the intermediate of ultra-high efficiency weedicide nicoculsfuron.
In the formula (II), R
4Or R
5Independent separately is the alkyl or phenyl of H, C1～C6, and being preferably independent separately is methyl, ethyl, propyl group, butyl or phenyl.
Reaction formula involved in the present invention is as follows:
Organic solvent of the present invention is benzene, toluene, chlorobenzene, methylene dichloride, ethylene dichloride, chloroform, tetracol phenixin, methyl alcohol, ethanol, Virahol, methyl acetate, ethyl acetate, methyl-phenoxide, ether, diisopropyl ether or methyl tertiary butyl ether, be preferably toluene, ethylene dichloride, ethyl acetate or methyl tertiary butyl ether, most preferably be ethyl acetate or methyl tertiary butyl ether.
Described volume of organic solvent consumption is counted 2～5L/mol usually with the amount of substance of the compound shown in the formula (II).
The temperature of reaction of the present invention is preferably 30～50 ℃.
The present invention adopts gas-chromatography to follow the tracks of and detects to reacting completely, and the common reaction times is 4～20 hours, preferred 8～10 hours.
The pressure of hydrogen chloride gas is 0.2～1.0MPa in the present invention's reaction, can not influence reaction result greater than 1.0MPa, but can increase the requirement to equipment.
Further, preferably feed hydrogen chloride gas to 0.5～0.7MPa.
Described autoclave is generally the autoclave of the stainless steel of inner liner polytetrafluoroethylene.
Normally bubbling air or nitrogen are with the emptying hydrogen chloride gas for described emptying hydrogen chloride gas, and this is this area method in common.
Reaction solution post-treating method of the present invention is: add sodium hydroxide solution adjust pH to 0.5～6 in the reaction solution, standing demix gets water layer and organic layer, water layer use with react in identical organic solvent extraction, merge all organic layers then, decompression removes solvent, obtain 2-chlorine apellagrin derivative crude product, described 2-chlorine apellagrin derivative crude product makes suc as formula the 2-chlorine apellagrin derivative product shown in (I) again through rectifying or recrystallization.
Described 2-chlorine apellagrin derivative crude product is that product is further made with extra care again through rectifying or recrystallization, and according to the difference of product, concrete purification condition is also different, and those skilled in the art can select different purification conditions voluntarily according to the characteristic of product.Concrete, at the target product in the embodiment of the invention, adopted following process for purification:
When (1) target product is 2-chlorine apellagrin methyl esters, will remove the 2-chlorine apellagrin methyl esters crude product rectification under vacuum that solvent obtains, collect 100～110 ℃/1mmHg cut, make 2-chlorine apellagrin methyl esters product;
When (2) target product is 2-chlorine apellagrin ethyl ester, remove the 2-chlorine apellagrin ethyl ester crude product rectification under vacuum that solvent obtains, collect 110～115 ℃/1mmHg cut, make 2-chlorine apellagrin ethyl ester product;
When (3) target product is 2-chlorine cigarette nitrile, remove the 2-chlorine cigarette nitrile crude product hexanaphthene recrystallization that solvent obtains, make 2-chlorine cigarette nitrile product;
(4) target product is N, during N-dimethyl-2-chloro-nicotinamide, removes the N that solvent obtains, and N-dimethyl-2-chloro-nicotinamide crude product sherwood oil recrystallization makes N, N-dimethyl-2-chloro-nicotinamide product;
Add sodium hydroxide solution adjust pH to 0.5～6 in the described reaction solution, make the product shown in the formula (I) and by product R
4R
5NH enters organic phase respectively to be separated with water, regulates the size of pH value and product and the R shown in the formula (I)
4R
5The alkalescence of NH is relevant, works as R
4R
5When NH was methylphenylamine or N-ethylaniline, preferred adjust pH was 0.5～2.5, works as R
4R
5When NH was dipropyl amine, preferred adjust pH was 5～6; Work as R
4R
5When NH was dibutylamine, preferred adjust pH was 4～5.Those skilled in the art can set up the scope of transferring pH on their own according to the alkalescence of product and by product, make product obtain separating.
Further, by product R
4R
5NH can recycle, recovery method be with water layer use with react in the water that obtains behind the identical organic solvent extraction to regulate the pH value with sodium hydroxide solution be 10～12, then standing demix, get organic phase rectifying and obtain highly purified R
4R
5NH.
Comparatively concrete, recommend the method for the invention to carry out according to the following steps: compound and the organic solvent shown in the adding formula (II) in the autoclave, after the stirring and dissolving, feed hydrogen chloride gas to 0.2～1.0MPa, under 30～50 ℃ of temperature, airtight insulation reaction, gas-chromatography follow the tracks of to detect after react completely, pressure release, the emptying hydrogen chloride gas, reaction solution adds sodium hydroxide solution adjust pH to 0.5～6, and standing demix gets water layer and organic layer, water layer use with react in identical organic solvent extraction, merge all organic layers then, decompression removes solvent, obtains 2-chlorine apellagrin derivative crude product, described 2-chlorine apellagrin derivative crude product makes suc as formula the 2-chlorine apellagrin derivative product shown in (I) again through rectifying or recrystallization; Described organic solvent is toluene, ethylene dichloride, ethyl acetate or methyl tertiary butyl ether.
The present invention make suc as formula the 2-chlorine apellagrin derivative shown in (I) further under alkaline condition hydrolysis can obtain the 2-chlorine apellagrin, this is the step that well known to a person skilled in the art preparation 2-chlorine apellagrin.
The beneficial effect of the synthetic method of 2-chlorine apellagrin of the present invention and derivative thereof is mainly reflected in: (1) reduces raw material hydrogenchloride consumption, reduces more than 50% than existing method, saves cost, and reduces the pollution of exhaust emissions; (2) fast reaction speed has reduced the reaction times; (3) improve reaction yield, yield can reach more than 95%; (4) by product can be recycled, and reduces environmental pollution, improves resource utilization.
(4) embodiment
The present invention is described further below in conjunction with specific embodiment, but protection scope of the present invention is not limited in this:
Synthesizing of embodiment 1:2-chlorine apellagrin methyl esters
In 500mL lining tetrafluoro autoclave, add N-methyl-N-phenyl-5-amino-2-cyano group-2,4-pentadienoic acid methyl esters (24.2g, 0.1mol) and methyl tertiary butyl ether 250mL, the stirring at room dissolving feeds dry hydrogen chloride gas to 1.0MPa, is warming up to 50 ℃ of stirring reactions, gas-chromatography is followed the tracks of and is detected to reacting completely, reaction 4h, pressure release, blowing air is discharged unnecessary HCl.Be neutralized to pH=0.5～1.5 with 10%NaOH solution, standing demix, water layer extracts with 20mL * 2 methyl tertiary butyl ethers.Merge all organic layers, the decompression precipitation, 100～110 ℃/1mmHg cut is collected in the resistates rectification under vacuum, gets colourless liquid 16.5g, yield 95.3%.
The water that obtains after the methyl tertiary butyl ether extraction adds 40%NaOH solution and is adjusted to pH=10～12, standing demix, and methylphenylamine is reclaimed in organic layer rectifying, gets colourless liquid 8.6g.
Synthesizing of embodiment 2:2-chlorine apellagrin ethyl ester
In 500mL lining tetrafluoro autoclave, add N, N-dipropyl-5-amino-2-cyano group-2,4-pentadienoic acid ethyl ester (25.0g, 0.1mol) with ethyl acetate 250mL, the stirring at room dissolving, feed dry hydrogen chloride gas to 0.6MPa, be warming up to 40 ℃ of stirring reactions, gas-chromatography is followed the tracks of and is detected to reacting completely reaction 10h, pressure release, blowing air is discharged unnecessary HCl.Be neutralized to pH=5～6 with 10%NaOH solution, standing demix, water layer 20mL * 2 ethyl acetate extractions.Merge all organic layers, the decompression precipitation, 110～115 ℃/1mmHg cut is collected in the resistates rectification under vacuum, gets colourless liquid 17.7g, yield 95.1%.
The water that obtains after the extraction of ethyl acetate ether adds 40%NaOH solution and is adjusted to pH=10～12, standing demix, and dipropyl amine is reclaimed in organic layer rectifying, gets colourless liquid 8.5g.
Synthesizing of embodiment 3:2-chlorine cigarette nitrile
In 500mL lining tetrafluoro autoclave, add N, N-dibutyl-5-amino-2-cyano group-2,4-pentadiene acyl cyanide (23.1g, 0.1mol) with toluene 250mL, the stirring at room dissolving, feed dry hydrogen chloride gas to 0.2MPa, be warming up to 30 ℃ of stirring reactions, gas-chromatography is followed the tracks of and is detected to reacting completely reaction 15h, pressure release, blowing air is discharged unnecessary HCl.Be neutralized to pH=4～5 with 10%NaOH solution, standing demix, water layer extracts with 20mL * 2 toluene.Merge all organic layers, the decompression precipitation, resistates hexanaphthene recrystallization gets colorless solid 13.4g, yield 96.4%.
The water that water layer obtains after the toluene extraction adds 40%NaOH solution and is adjusted to pH=10～12, standing demix, and dibutylamine is reclaimed in organic layer rectifying, gets colourless liquid 11.4g.
Embodiment 4:N, N-dimethyl-2-chloro-nicotinamide synthetic
N-ethyl-N-phenyl-the N ' shown in the adding formula (II-a) in 500mL lining tetrafluoro autoclave, N '-dimethyl-5-amino-2-cyano group-2, the 4-Pentadienamide (26.9g, 0.1mol) with ethylene dichloride 250mL, the stirring at room dissolving, feed dry hydrogen chloride gas to 0.7MPa, be warming up to 50 ℃ of stirring reactions, gas-chromatography is followed the tracks of and is detected to reacting completely reaction 4h, pressure release, blowing air is discharged unnecessary HCl.Be neutralized to pH=1～2 with 10%NaOH solution, standing demix, water layer extracts with 20mL * 2 ethylene dichloride.Merge all organic layers, the decompression precipitation, resistates sherwood oil recrystallization gets light yellow crystal N, N-dimethyl-2-chloro-nicotinamide 17.7g, yield 95.8%.
The water that obtains after the ethylene dichloride extraction adds 40%NaOH solution and is adjusted to pH=10～12, standing demix, and N-ethylaniline is reclaimed in organic layer rectifying, gets colourless liquid 8.8g.Comparative Examples 1: synthetic 2-chlorine apellagrin methyl esters under the normal pressure
In the 500mL there-necked flask, add N-methyl-N-phenyl-5-amino-2-cyano group-2,4-pentadienoic acid methyl esters (24.2g, 0.1mol) and methyl tertiary butyl ether 250mL, the stirring at room dissolving, normal pressure feeds dry hydrogen chloride gas to saturated, not open closely go into hydrogen chloride gas, stirring reaction 24h, blowing air is discharged unnecessary HCl.Post-treating method gets colourless liquid 14.4g with embodiment 1, yield 84.1%.
Embodiment 5: by the synthetic 2-chlorine apellagrin of 2-chlorine apellagrin methyl esters hydrolysis
In the 250mL there-necked flask, add sodium hydroxide 5.6g(0.14mol) and water 100mL, stirring and dissolving adds the 2-chlorine apellagrin methyl esters 1.7g (0.1mol) that embodiment 1 makes, and is heated to 80～85 ℃, and stirring reaction 2h, HPLC detect to reacting and finish.Be cooled to room temperature, regulate pH=1～2, stirred crystallization 2h with 30% hydrochloric acid.Suction filtration, washing, drying get white powder 15.5g, yield 98.4%.
Claims (8)
1. synthetic method suc as formula the 2-chlorine apellagrin derivative shown in (I) is characterized in that described method is:
Compound and organic solvent shown in the adding formula (II) in the autoclave, after the stirring and dissolving, feed hydrogen chloride gas to 0.2～1.0MPa, under 20～100 ℃ of temperature, airtight insulation reaction, gas-chromatography follow the tracks of to detect after react completely, pressure release, emptying hydrogen chloride gas, reaction solution aftertreatment prepare suc as formula the 2-chlorine apellagrin derivative shown in (I);
In formula (I) or the formula (II), R is-shown in the CN, formula (a)-CO
2R
1Or shown in the formula (b)-CONR
2R
3
In the formula (a), R
1The alkyl of expression H or C1～C6; In the formula (b), R
2Or R
3Independent separately is the alkyl of H or C1～C6;
In the formula (II), R
4Or R
5Independent separately is the alkyl or phenyl of H, C1～C6.
2. the method for claim 1 is characterized in that in the described formula (a) R
1Be methyl or ethyl.
3. the method for claim 1 is characterized in that in the described formula (b) R
2Or R
3Be methyl.
4. the method for claim 1 is characterized in that in the described formula (II) R
4Or R
5Independent separately is methyl, ethyl, propyl group, butyl or phenyl.
5. the method for claim 1 is characterized in that described organic solvent is benzene, toluene, chlorobenzene, methylene dichloride, ethylene dichloride, chloroform, tetracol phenixin, methyl alcohol, ethanol, Virahol, methyl acetate, ethyl acetate, methyl-phenoxide, ether, diisopropyl ether or methyl tertiary butyl ether.
6. the method for claim 1, the temperature that it is characterized in that described reaction is 30～50 ℃.
7. the method for claim 1, it is characterized in that described reaction solution post-treating method is: add sodium hydroxide solution adjust pH to 0.5～6 in the reaction solution, standing demix gets water layer and organic layer, water layer use with react in identical organic solvent extraction, merge all organic layers then, decompression removes solvent, obtains 2-chlorine apellagrin derivative crude product, described 2-chlorine apellagrin derivative crude product makes suc as formula the 2-chlorine apellagrin derivative product shown in (I) again through rectifying or recrystallization.
8. the method for claim 1, it is characterized in that described method carries out according to the following steps: compound and the organic solvent shown in the adding formula (II) in the autoclave, after the stirring and dissolving, feed hydrogen chloride gas to 0.2～1.0MPa, under 30～50 ℃ of temperature, airtight insulation reaction, gas-chromatography follow the tracks of to detect after react completely, pressure release, the emptying hydrogen chloride gas, reaction solution adds sodium hydroxide solution adjust pH to 0.5～6, and standing demix gets water layer and organic layer, water layer use with react in identical organic solvent extraction, merge all organic layers then, decompression removes solvent, obtains 2-chlorine apellagrin derivative crude product, described 2-chlorine apellagrin derivative crude product makes suc as formula the 2-chlorine apellagrin derivative product shown in (I) again through rectifying or recrystallization; Described organic solvent is toluene, ethylene dichloride, ethyl acetate or methyl tertiary butyl ether.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945316A (en) * | 2015-06-04 | 2015-09-30 | 山东师范大学 | Method for synthesizing 2-halogenated nicotinic acid ester and intermediates thereof through microwave method |
| CN105001154A (en) * | 2015-06-04 | 2015-10-28 | 山东师范大学 | Method for synthesizing 2-halogenated nicotinate and intermediate thereof through ionic liquid method |
| CN104945317B (en) * | 2015-06-04 | 2018-03-30 | 山东师范大学 | A kind of method of supercritical ultrasonics technology synthesis 2- halos nicotinate and its intermediate |
| CN108017578A (en) * | 2016-10-31 | 2018-05-11 | 江苏丰山集团股份有限公司 | A kind of chloro- N of 2-, the preparation method of N- dimethyl nicotinamides |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0397281A2 (en) * | 1989-05-12 | 1990-11-14 | DowElanco | An improved process for the preparation of 3,5,6-trichloropyridin-2-ol |
| CN101367760A (en) * | 2008-10-08 | 2009-02-18 | 南开大学 | Synthesis of 2-chlorine apellagrin |
-
2013
- 2013-03-22 CN CN2013100946343A patent/CN103193705A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0397281A2 (en) * | 1989-05-12 | 1990-11-14 | DowElanco | An improved process for the preparation of 3,5,6-trichloropyridin-2-ol |
| CN101367760A (en) * | 2008-10-08 | 2009-02-18 | 南开大学 | Synthesis of 2-chlorine apellagrin |
Non-Patent Citations (3)
| Title |
|---|
| ROBERT CHURCH等: "New synthetic routes to 3-,5- and 6-aryl-2-chloropyridines", 《JOURNAL OF ORGANIC CHEMISTRY》, vol. 60, no. 12, 30 June 1995 (1995-06-30), pages 3750 - 3758 * |
| ZHANGQI WEI等: "The cyclization of 2-chloro nicotinic acid", 《ADVANCED MATERIALS RESEARCH》, vol. 233235, 31 May 2011 (2011-05-31) * |
| 王红伟等: "2－氯烟酸的合成进展", 《杭州化工》, vol. 40, no. 3, 15 September 2010 (2010-09-15), pages 9 - 10 * |
Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104945316A (en) * | 2015-06-04 | 2015-09-30 | 山东师范大学 | Method for synthesizing 2-halogenated nicotinic acid ester and intermediates thereof through microwave method |
| CN105001154A (en) * | 2015-06-04 | 2015-10-28 | 山东师范大学 | Method for synthesizing 2-halogenated nicotinate and intermediate thereof through ionic liquid method |
| CN105001154B (en) * | 2015-06-04 | 2017-10-03 | 山东师范大学 | A kind of method of ionic liquid method synthesis 2- halos nicotinate and its intermediate |
| CN104945317B (en) * | 2015-06-04 | 2018-03-30 | 山东师范大学 | A kind of method of supercritical ultrasonics technology synthesis 2- halos nicotinate and its intermediate |
| CN104945316B (en) * | 2015-06-04 | 2018-05-04 | 山东师范大学 | A kind of method of microwave method synthesis 2- halos nicotinate and its intermediate |
| CN108017578A (en) * | 2016-10-31 | 2018-05-11 | 江苏丰山集团股份有限公司 | A kind of chloro- N of 2-, the preparation method of N- dimethyl nicotinamides |
| CN108017578B (en) * | 2016-10-31 | 2021-06-08 | 江苏丰山集团股份有限公司 | Preparation method of 2-chloro-N, N-dimethylnicotinamide |
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Application publication date: 20130710 |