CN102993089B - Method for synthesizing aminopyridine - Google Patents
Method for synthesizing aminopyridine Download PDFInfo
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- CN102993089B CN102993089B CN201210383381.7A CN201210383381A CN102993089B CN 102993089 B CN102993089 B CN 102993089B CN 201210383381 A CN201210383381 A CN 201210383381A CN 102993089 B CN102993089 B CN 102993089B
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- CN
- China
- Prior art keywords
- aminopyridine
- haloperidid
- liquefied ammonia
- synthetic method
- synthesizing
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- 150000003927 aminopyridines Chemical class 0.000 title claims abstract description 13
- 238000000034 method Methods 0.000 title abstract description 5
- 230000002194 synthesizing effect Effects 0.000 title abstract 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 33
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 20
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 239000000047 product Substances 0.000 claims abstract description 10
- 238000007670 refining Methods 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 239000012043 crude product Substances 0.000 claims abstract description 4
- 229910021529 ammonia Inorganic materials 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 15
- KCDNYRPDKSGQCM-UHFFFAOYSA-N 4-[4-(3-chlorophenyl)-4-(pyrrolidine-1-carbonyl)piperidin-1-yl]-1-(4-fluorophenyl)butan-1-one Chemical compound C1=CC(F)=CC=C1C(=O)CCCN1CCC(C=2C=C(Cl)C=CC=2)(C(=O)N2CCCC2)CC1 KCDNYRPDKSGQCM-UHFFFAOYSA-N 0.000 claims description 12
- SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 10
- 238000010189 synthetic method Methods 0.000 claims description 9
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 6
- 229910052707 ruthenium Inorganic materials 0.000 claims description 6
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 239000011259 mixed solution Substances 0.000 claims description 2
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 2
- 239000007788 liquid Substances 0.000 abstract 1
- 150000003222 pyridines Chemical class 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 8
- 238000012545 processing Methods 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- 238000013022 venting Methods 0.000 description 4
- 239000003643 water by type Substances 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- OKDGRDCXVWSXDC-UHFFFAOYSA-N 2-chloropyridine Chemical compound ClC1=CC=CC=N1 OKDGRDCXVWSXDC-UHFFFAOYSA-N 0.000 description 1
- FNRMMDCDHWCQTH-UHFFFAOYSA-N 2-chloropyridine;3-chloropyridine;4-chloropyridine Chemical compound ClC1=CC=NC=C1.ClC1=CC=CN=C1.ClC1=CC=CC=N1 FNRMMDCDHWCQTH-UHFFFAOYSA-N 0.000 description 1
- NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- -1 aminopyridine compounds Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000000975 dye Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229910052763 palladium Inorganic materials 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 229910052703 rhodium Inorganic materials 0.000 description 1
- 239000010948 rhodium Substances 0.000 description 1
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Abstract
The invention discloses a method for synthesizing aminopyridine, which is characterized by comprising the following steps of: adding a solvent and a catalyst in mixing liquid of halogenated pyridine and liquid ammonia; reacting at temperature of 200-1000 DEG C to obtain a crude product; and refining by methyl benzene to obtain the target product. The method for synthesizing aminopyridine has the advantages that the synthesizing method disclosed by the invention is simple, low in cost, easy in operation, good in product selectivity, and high in total yield to be 65-85%.
Description
Technical field
The present invention relates to a kind of synthetic method of aminopyridine.
Background technology
Aminopyridine be contain ammonia the material with heterocycle structure, in vitochemical many fields, be widely used in, be the important intermediate of manufacturing the gas chromatography matter such as medicine, synthetic dyestuff, be mainly used in the high-end Field of Fine Chemicals such as medicine, agricultural chemicals and novel material.Along with scientific and technical development, the demand of high purity aminopyridine compounds also increases gradually, and the synthetic route of studying a kind of high-content, low cost and easy-operating aminopyridine becomes very meaningful.
Summary of the invention
The synthetic method that the object of this invention is to provide the aminopyridine that a kind of technique is simple, side reaction is little, yield is high.
In order to solve the problems of the technologies described above, the technical solution used in the present invention is: a kind of synthetic method of aminopyridine, it is characterized in that: in the mixed solution of haloperidid and liquefied ammonia, add solvent and catalyzer, at 200-1000 ℃ of temperature, reaction obtains crude product, by toluene is refining, obtain target product again, reaction equation is:
。
Wherein, described R
1for H, Cl, F, Br, R
2for H, Cl, F, Br, corresponding R
3and R
4be respectively H and NH
2.
Further, described solvent is quinoline or derivatives thereof.
Further, described catalyzer is palladium, ruthenium, rhodium or by three kinds of content of metal, is surpassed 10% carried catalyst.
Further, the mol ratio of described haloperidid and liquefied ammonia is 1:4-150, and catalyst levels is the 0.01-10% of haloperidid weight, and solvent load is the 1-50 of haloperidid weight.
Further, the mol ratio of described haloperidid and liquefied ammonia is 1:10-30, and catalyst levels is the 0.2-2% of haloperidid weight.
Further, described temperature of reaction is 250-450 ℃.
The invention has the advantages that: by halogenated pyrimidine and liquefied ammonia under catalysts and solvents effect, high-temperature high-voltage reaction obtains crude product, after refining, obtain target product, synthetic method of the present invention is simple, cost is low, easy to operate, product selectivity good, and total recovery reaches 65-85%.
Embodiment
In order to make the public can fully understand technical spirit of the present invention and beneficial effect; applicant will describe in detail the specific embodiment of the present invention below; but applicant is not the restriction to technical scheme to the description of embodiment, anyly according to the present invention design, changes in the form rather than substance all and should be considered as protection scope of the present invention.
Embodiment 1
The 3-bromopyridine that adds 1mol in autoclave, the nanometer ruthenium C catalyst that the charge capacity of activated processing is 10% and the quinoline of 800 milliliters, close high-pressure reactor, pass into the liquefied ammonia of 20mol, after off-response device, be warmed up to 350 ℃, stirring reaction 12 hours, after reaction finishes, the liquefied ammonia that venting is unnecessary, adds 300 ml waters, stirs and is cooled to 0-5 ℃, filtration obtains 91 grams of solids, with refining 58.3 grams of 99.2% products, 65 ℃ of fusing points, yield 62% of obtaining of toluene.
Embodiment 2
The 2-chloropyridine that adds 1mol in autoclave, the nanometer ruthenium C catalyst that the charge capacity of activated processing is 10% and the quinoline of 800 milliliters, close high-pressure reactor, pass into the liquefied ammonia of 20mol, after off-response device, be warmed up to 350 ℃, stirring reaction 12 hours, after reaction finishes, the liquefied ammonia that venting is unnecessary, adds 300 ml waters, stirs and is cooled to 0-5 ℃, filtration obtains 102 grams of solids, with refining 68.6 grams of 99.1% products, fusing point 122.3-122.7 ℃, the yield 73% of obtaining of toluene.
Embodiment 3
In autoclave, add 2 of 1mol, 6-dichloropyridine, the charge capacity of activated processing is 10% nanometer ruthenium C catalyst and the quinoline of 800 milliliters, close high-pressure reactor, pass into the liquefied ammonia of 20mol, after off-response device, be warmed up to 350 ℃, stirring reaction 12 hours, after reaction finishes, the liquefied ammonia that venting is unnecessary, add 300 ml waters, stir and be cooled to 0-5 ℃, filter and obtain 89 grams of solids, with toluene refining obtain 99.1% 2,81.8 grams of 6-diamino-pyridine products, fusing point 121.1-122.3 ℃, yield 75%.
Embodiment 4
In autoclave, add 2 of 1mol, 6-bromine chloropyridine, the nanometer ruthenium C catalyst that the charge capacity of activated processing is 10% and the quinoline of 800 milliliters, close high-pressure reactor, pass into the liquefied ammonia of 20mol, after off-response device, be warmed up to 350 ℃, stirring reaction 12 hours, after reaction finishes, the liquefied ammonia that venting is unnecessary, add 300 ml waters, stirring is cooled to 0-5 ℃, filters and obtains 102 grams of solids, with refining 92.8 grams of 99.3% products that obtain of toluene, fusing point 122.3-122.7 ℃, yield 85.1%.
Claims (4)
1. a synthetic method for aminopyridine, is characterized in that: in the mixed solution of haloperidid and liquefied ammonia, add solvent and catalyzer, reaction obtains crude product at 200-1000 ℃ of temperature, then obtains target product by toluene is refining, and reaction equation is:
；
Wherein, described R
1for H, Cl, F, Br, R
2for H, Cl, F, Br, corresponding R
3and R
4be respectively H and NH
2; Described catalyzer is that charge capacity is 10% ruthenium C catalyst, and described solvent is quinoline.
2. the synthetic method of a kind of aminopyridine according to claim 1, is characterized in that: the mol ratio of described haloperidid and liquefied ammonia is 1:4-150, and catalyst levels is the 0.01-10% of haloperidid weight, and solvent load is the 1-50 of haloperidid weight.
3. the synthetic method of a kind of aminopyridine according to claim 2, is characterized in that: the mol ratio of described haloperidid and liquefied ammonia is 1:10-30, and catalyst levels is the 0.2-2% of haloperidid weight.
4. the synthetic method of a kind of aminopyridine according to claim 1, is characterized in that: described temperature of reaction is 250-450 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
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| CN201210383381.7A CN102993089B (en) | 2012-10-11 | 2012-10-11 | Method for synthesizing aminopyridine |
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|---|---|---|---|
| CN201210383381.7A CN102993089B (en) | 2012-10-11 | 2012-10-11 | Method for synthesizing aminopyridine |
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| CN102993089A CN102993089A (en) | 2013-03-27 |
| CN102993089B true CN102993089B (en) | 2014-07-16 |
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| CN103288720B (en) * | 2013-06-09 | 2015-05-27 | 南通市华峰化工有限责任公司 | High-pressure synthetic method of 2,6-diaminopyridine |
Citations (4)
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|---|---|---|---|---|
| CN101723885A (en) * | 2008-10-24 | 2010-06-09 | 朱比兰特奥甘诺斯有限公司 | Improved method for preparing diaminopyridine |
| US20100160678A1 (en) * | 2008-12-18 | 2010-06-24 | E. I. Du Pont De Nemours And Company | Process for the synthesis of 2,6-diamino-3,5-dinitrotoluene |
| WO2011084773A2 (en) * | 2009-12-21 | 2011-07-14 | E. I. Du Pont De Nemours And Company | Process for the synthesis of 1-amino-3-halo-4,6-dinitrobenzene |
| CN102256946A (en) * | 2008-12-18 | 2011-11-23 | 纳幕尔杜邦公司 | Continuous liquid-phase process for the synthesis of diaminopyridines from glutaronitriles |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006124283A1 (en) * | 2005-05-12 | 2006-11-23 | Boehringer Ingelheim International, Gmbh | Bis-amination of aryl halides |
| KR20100050524A (en) * | 2007-08-01 | 2010-05-13 | 이 아이 듀폰 디 네모아 앤드 캄파니 | Process for the synthesis of diaminopyridine and related compounds |
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101723885A (en) * | 2008-10-24 | 2010-06-09 | 朱比兰特奥甘诺斯有限公司 | Improved method for preparing diaminopyridine |
| US20100160678A1 (en) * | 2008-12-18 | 2010-06-24 | E. I. Du Pont De Nemours And Company | Process for the synthesis of 2,6-diamino-3,5-dinitrotoluene |
| CN102256946A (en) * | 2008-12-18 | 2011-11-23 | 纳幕尔杜邦公司 | Continuous liquid-phase process for the synthesis of diaminopyridines from glutaronitriles |
| WO2011084773A2 (en) * | 2009-12-21 | 2011-07-14 | E. I. Du Pont De Nemours And Company | Process for the synthesis of 1-amino-3-halo-4,6-dinitrobenzene |
Non-Patent Citations (5)
| Title |
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| Bei-Sih Liao，等.Diamination of Phenylene Dihalides Catalyzed by a Dicopper Complex.《J. Org. Chem.》.2012,第77卷第6653-6656页. * |
| Efficient synthesis of aminopyridine derivatives by copper catalyzed amination reactions;Mohammed K. Elmkaddem等;《Chem. Commun.》;20091007;第46卷;第926页表格5中第3式化合物 * |
| Mohammed K. Elmkaddem等.Efficient synthesis of aminopyridine derivatives by copper catalyzed amination reactions.《Chem. Commun.》.2009,第46卷第926页表格5中第3式化合物. |
| 汪蓓蕾，等.2 6一二氨基毗咤的合成研究.《安徽科技》.2000 |
| 汪蓓蕾,等.2, 6一二氨基毗咤的合成研究.《安徽科技》.2000,(第8期),第37页. * |
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Inventor after: Wang Defeng Inventor after: Zhang Yancheng Inventor after: Zhang Yaobing Inventor before: Wang Defeng Inventor before: Zhu Xiaofei Inventor before: Wang Bingcai Inventor before: Zhang Yaobin Inventor before: Shi Fei Inventor before: Yu Jianjun |
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Free format text: CORRECT: INVENTOR; FROM: WANG DEFENG ZHU XIAOFEI WANG BINGCAI ZHANG YAOBIN SHI FEI YU JIANJUN TO: WANG DEFENG ZHANG YANCHENG ZHANG YAOBING |
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Effective date of registration: 20170104 Address after: 226500 Zhang Yang village, Shi Zhuang Town, Jiangsu, Rugao Patentee after: Huafeng Chemical Co., Ltd., Nantong Address before: 226500 Zhang Yang village, Shi Zhuang Town, Jiangsu, Rugao Patentee before: Nantong Zhongyi Chemical Co., Ltd. |
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