CN102993089A - Method for synthesizing aminopyridine - Google Patents
Method for synthesizing aminopyridine Download PDFInfo
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- CN102993089A CN102993089A CN2012103833817A CN201210383381A CN102993089A CN 102993089 A CN102993089 A CN 102993089A CN 2012103833817 A CN2012103833817 A CN 2012103833817A CN 201210383381 A CN201210383381 A CN 201210383381A CN 102993089 A CN102993089 A CN 102993089A
- Authority
- CN
- China
- Prior art keywords
- aminopyridine
- haloperidid
- synthetic method
- liquefied ammonia
- reaction
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 150000003927 aminopyridines Chemical class 0.000 title claims abstract description 15
- 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 Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 12
- 238000010189 synthetic method Methods 0.000 claims description 11
- 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
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal Substances 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- 229910052703 rhodium Inorganic materials 0.000 claims description 2
- 239000010948 rhodium Substances 0.000 claims description 2
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 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
- 238000005516 engineering process Methods 0.000 description 3
- 239000003814 drug Substances 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
- VHNQIURBCCNWDN-UHFFFAOYSA-N pyridine-2,6-diamine Chemical compound NC1=CC=CC(N)=N1 VHNQIURBCCNWDN-UHFFFAOYSA-N 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
Landscapes
- Pyridine Compounds (AREA)
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, be widely used in vitochemical many fields, be the important intermediate of making 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 the development of science and technology, 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 purpose 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, reaction obtains crude product under 200-1000 ℃ of temperature, obtain target product by toluene is refining again, reaction equation is:
。
Wherein, described R
1Be H, Cl, F, Br, R
2Be H, Cl, F, Br, corresponding R
3And R
4Be respectively H and NH
2
Further, described solvent is the quinoline or derivatives thereof.
Further, described catalyzer is palladium, ruthenium, rhodium or is surpassed 10% carried catalyst by three kinds of content of metal.
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: with halogenated pyrimidine and liquefied ammonia under the catalysts and solvents effect, high-temperature high-voltage reaction obtains crude product, obtain target product after refining, synthetic method of the present invention is simple, cost is low, easy to operate, product selectivity good, total recovery reaches 65-85%.
Embodiment
In order to make the public can fully understand technical spirit of the present invention and beneficial effect; the applicant will describe in detail the specific embodiment of the present invention below; but the applicant is not restriction to technical scheme to the description of embodiment, anyly makes form and immaterial variation all should be considered as protection scope of the present invention according to the present invention's design.
Embodiment 1
The 3-bromopyridine that adds 1mol in autoclave, the charge capacity of activated processing are 10% nanometer ruthenium C catalyst and 800 milliliters quinoline, close high-pressure reactor, pass into the liquefied ammonia of 20mol, be warmed up to 350 ℃ behind the off-response device, 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 solid 91 grams, with refining 99.2% product, 58.3 grams, 65 ℃ of fusing points, the yield 62% of obtaining of toluene.
Embodiment 2
The 2-chloropyridine that adds 1mol in autoclave, the charge capacity of activated processing are 10% nanometer ruthenium C catalyst and 800 milliliters quinoline, close high-pressure reactor, pass into the liquefied ammonia of 20mol, be warmed up to 350 ℃ behind the off-response device, 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 solid 102 grams, with refining 99.1% product, 68.6 grams, fusing point 122.3-122.7 ℃, the yield 73% of obtaining of toluene.
Embodiment 3
In autoclave, add 2 of 1mol, the 6-dichloropyridine, the charge capacity of activated processing is 10% nanometer ruthenium C catalyst and 800 milliliters quinoline, close high-pressure reactor, pass into the liquefied ammonia of 20mol, be warmed up to 350 ℃ behind the off-response device, stirring reaction 12 hours is after reaction finishes, the liquefied ammonia that venting is unnecessary, add 300 ml waters, stir and be cooled to 0-5 ℃, filter and obtain solid 89 grams, with toluene refining obtain 99.1% 2,6-diamino-pyridine product 81.8 grams, fusing point 121.1-122.3 ℃, yield 75%.
Embodiment 4
In autoclave, add 2 of 1mol, 6-bromine chloropyridine, the charge capacity of activated processing is 10% nanometer ruthenium C catalyst and 800 milliliters quinoline, close high-pressure reactor, pass into the liquefied ammonia of 20mol, be warmed up to 350 ℃ behind the off-response device, 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 to obtain solid 102 grams, with refining 99.3% product, 92.8 grams that obtain of toluene, fusing point 122.3-122.7 ℃, yield 85.1%.
Claims (6)
1. the synthetic method of an aminopyridine is characterized in that: add solvent and catalyzer in the mixed solution of haloperidid and liquefied ammonia, reaction obtains crude product under 200-1000 ℃ of temperature, obtains target product by toluene is refining again, and reaction equation is:
Wherein, described R
1Be H, Cl, F, Br, R
2Be H, Cl, F, Br, corresponding R
3And R
4Be respectively H and NH
2
2. the synthetic method of a kind of aminopyridine according to claim 1, it is characterized in that: described solvent is the quinoline or derivatives thereof.
3. the synthetic method of a kind of aminopyridine according to claim 1 is characterized in that: described catalyzer is palladium, ruthenium, rhodium or is surpassed 10% carried catalyst by three kinds of content of metal.
4. the synthetic method of a kind of aminopyridine according to claim 1, it 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.
5. the synthetic method of a kind of aminopyridine according to claim 4, it is characterized in that: the mol ratio of described haloperidid and liquefied ammonia is 1:10-30, catalyst levels is the 0.2-2% of haloperidid weight.
6. the synthetic method of a kind of aminopyridine according to claim 1, it is characterized in that: described temperature of reaction is 250-450 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210383381.7A CN102993089B (en) | 2012-10-11 | 2012-10-11 | Method for synthesizing aminopyridine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201210383381.7A CN102993089B (en) | 2012-10-11 | 2012-10-11 | Method for synthesizing aminopyridine |
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| Publication Number | Publication Date |
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| CN102993089A true CN102993089A (en) | 2013-03-27 |
| CN102993089B CN102993089B (en) | 2014-07-16 |
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|---|---|---|---|
| CN201210383381.7A Expired - Fee Related CN102993089B (en) | 2012-10-11 | 2012-10-11 | Method for synthesizing aminopyridine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103288720A (en) * | 2013-06-09 | 2013-09-11 | 南通市华峰化工有限责任公司 | High-pressure synthetic method of 2,6-diaminopyridine |
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|---|---|---|---|---|
| WO2006124283A1 (en) * | 2005-05-12 | 2006-11-23 | Boehringer Ingelheim International, Gmbh | Bis-amination of aryl halides |
| 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 |
| CN101765588A (en) * | 2007-08-01 | 2010-06-30 | 纳幕尔杜邦公司 | Process for the synthesis of diaminopyridine and related compounds |
| 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 |
-
2012
- 2012-10-11 CN CN201210383381.7A patent/CN102993089B/en not_active Expired - Fee Related
Patent Citations (6)
| 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 |
| CN101765588A (en) * | 2007-08-01 | 2010-06-30 | 纳幕尔杜邦公司 | Process for the synthesis of diaminopyridine and related compounds |
| 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 (4)
| Title |
|---|
| BEI-SIH LIAO，等: "Diamination of Phenylene Dihalides Catalyzed by a Dicopper Complex", 《J. ORG. CHEM.》 * |
| MOHAMMED K. ELMKADDEM等: "Efficient synthesis of aminopyridine derivatives by copper catalyzed amination reactions", 《CHEM. COMMUN.》 * |
| 吴新民: "新法合成2，6-二氨基吐咤的研究", 《适用技术市场》 * |
| 汪蓓蕾，等: "2 , 6一二氨基毗咤的合成研究", 《安徽科技》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103288720A (en) * | 2013-06-09 | 2013-09-11 | 南通市华峰化工有限责任公司 | High-pressure synthetic method of 2,6-diaminopyridine |
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| CN102993089B (en) | 2014-07-16 |
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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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