CN102993090A - Method for synthesizing 2,6-diamino pyridine - Google Patents
Method for synthesizing 2,6-diamino pyridine Download PDFInfo
- Publication number
- CN102993090A CN102993090A CN2012103837273A CN201210383727A CN102993090A CN 102993090 A CN102993090 A CN 102993090A CN 2012103837273 A CN2012103837273 A CN 2012103837273A CN 201210383727 A CN201210383727 A CN 201210383727A CN 102993090 A CN102993090 A CN 102993090A
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- CN
- China
- Prior art keywords
- pyridine
- synthetic method
- dihalo
- product
- liquefied ammonia
- 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
- 238000000034 method Methods 0.000 title abstract description 7
- VHNQIURBCCNWDN-UHFFFAOYSA-N pyridine-2,6-diamine Chemical compound NC1=CC=CC(N)=N1 VHNQIURBCCNWDN-UHFFFAOYSA-N 0.000 title abstract description 5
- 230000002194 synthesizing effect Effects 0.000 title abstract 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims abstract description 25
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000000047 product Substances 0.000 claims abstract description 16
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 7
- 239000012043 crude product Substances 0.000 claims abstract description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 24
- 229910021529 ammonia Inorganic materials 0.000 claims description 12
- 238000006243 chemical reaction Methods 0.000 claims description 12
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-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 10
- 238000010189 synthetic method Methods 0.000 claims description 10
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 claims description 5
- 229910052707 ruthenium Inorganic materials 0.000 claims description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052794 bromium Inorganic materials 0.000 claims description 4
- 229910052751 metal Inorganic materials 0.000 claims description 2
- 239000002184 metal 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
- 238000007670 refining Methods 0.000 abstract description 4
- 150000003222 pyridines Chemical class 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 6
- 238000012545 processing Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 238000013022 venting Methods 0.000 description 3
- 239000003643 water by type Substances 0.000 description 3
- 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 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- UJABSZITRMATFL-UHFFFAOYSA-N 2-methyl-5-phenylfuran-3-carbonyl chloride Chemical compound ClC(=O)C1=C(C)OC(C=2C=CC=CC=2)=C1 UJABSZITRMATFL-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 150000003927 aminopyridines Chemical class 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000004043 dyeing Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 229960003799 phenazopyridine hydrochloride Drugs 0.000 description 1
- 230000000176 photostabilization Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
Abstract
The invention discloses a method for synthesizing 2,6-diamino pyridine, which is characterized by comprising the following steps of: in a high-pressure reactor, adding 2,6-dihalogenated pyridine, solvent and catalyst; closing the high-pressure reactor; filling 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 2,6-diamino pyridine has the advantages that the method is simple in process, easy in operation and excellent in product selectivity; and the product purity is greater than 99%, and total yield is 75-85%.
Description
Technical field
The present invention relates to a kind of synthetic method of DAP.
Background technology
DAP is a kind of traditional organic chemistry product, is mainly used in the high-end Field of Fine Chemicals such as medicine, agricultural chemicals, is the important intermediate of our the treatment medicine for urological system phenazopyridine hydrochloride produced.In addition, this product also is applied to have hair dyed in the series product, because this product is relatively good as the synthetic hair dyeing product photostabilization of intermediate.At present, the synthesis technique yield of DAP is lower, and by product is more, therefore, improves product yield and purity and has very much a Research Significance.
Summary of the invention
The synthetic method that the purpose of this invention is to provide a kind of DAP.
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 autoclave, add 2,6-dihalo pyridine, solvent and catalyzer, close high-pressure reactor, pass into liquefied ammonia, reaction obtains crude product under 200-1000 ℃ of temperature, makes with extra care to get target product by toluene again, and reaction equation is:
Wherein, described X is respectively Cl, F or Br.
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, described 2, the mol ratio of 6-dihalo pyridine and liquefied ammonia is 1:4-150, and catalyst levels is the 0.01-10% of 2,6-dihalo pyridine weight, and solvent load is the 1-50 of 2,6-dihalo pyridine weight.
Further, described 2, the mol ratio of 6-dihalo pyridine and liquefied ammonia is 1:10-30, and catalyst levels is the 0.2-2% of 2,6-dihalo pyridine weight.
Further, described temperature of reaction is 250-450 ℃.
The invention has the advantages that: technique of the present invention is simple, and is easy to operate, and product selectivity is good, and product purity is greater than 99%, and total recovery reaches 75-85%.
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
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 2
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 ℃ of stirring reactions 12 hours behind the off-response device, after reaction finished, the liquefied ammonia that venting is unnecessary added 300 ml waters, stirring is cooled to 0-5 ℃, filtration obtains solid 95 grams, with refining 99.3% DAP product 83.5 grams that obtain of toluene, fusing point 121.3-122.5 ℃, yield 76.6%.
Embodiment 3
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 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 102 grams, with toluene refining obtain 99.3% 2,6-diamino-pyridine product 92.8 grams, fusing point 122.3-122.7 ℃, yield 85.1%.
Claims (6)
1. one kind 2, the synthetic method of 6-diamino-pyridine, it is characterized in that: in autoclave, add 2,6-dihalo pyridine, solvent and catalyzer, close high-pressure reactor, pass into liquefied ammonia, reaction obtains crude product under 200-1000 ℃ of temperature, makes with extra care to get target product by toluene again, and reaction equation is:
;
Wherein, described X is respectively Cl, F or Br.
2. the synthetic method of a kind of DAP 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 DAP 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. according to claim 1 a kind of 2, the synthetic method of 6-diamino-pyridine, it is characterized in that: described 2, the mol ratio of 6-dihalo pyridine and liquefied ammonia is 1:4-150, catalyst levels is 2, the 0.01-10% of 6-dihalo pyridine weight, solvent load are the 1-50 of 2,6-dihalo pyridine weight.
5. the synthetic method of a kind of DAP according to claim 4 is characterized in that: described 2, the mol ratio of 6-dihalo pyridine and liquefied ammonia is 1:10-30, and catalyst levels is the 0.2-2% of 2,6-dihalo pyridine weight.
6. the synthetic method of a kind of DAP according to claim 1, it is characterized in that: described temperature of reaction is 250-450 ℃.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210383727.3A CN102993090B (en) | 2012-10-11 | 2012-10-11 | Method for synthesizing 2,6-diamino pyridine |
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| Application Number | Priority Date | Filing Date | Title |
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| CN201210383727.3A CN102993090B (en) | 2012-10-11 | 2012-10-11 | Method for synthesizing 2,6-diamino pyridine |
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| CN102993090A true CN102993090A (en) | 2013-03-27 |
| CN102993090B CN102993090B (en) | 2014-09-03 |
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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 |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003006420A1 (en) * | 2001-07-12 | 2003-01-23 | Yale University | Catalytic method to convert aryl compounds to aryl amines |
| WO2006124283A1 (en) * | 2005-05-12 | 2006-11-23 | Boehringer Ingelheim International, Gmbh | Bis-amination of aryl halides |
| WO2009018504A1 (en) * | 2007-08-01 | 2009-02-05 | E. I. Du Pont De Nemours And Company | 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 |
| WO2010080488A1 (en) * | 2008-12-18 | 2010-07-15 | E. I. Du Pont De Nemours And Company | Continuous liquid-phase process for the synthesis of diaminopyridines from glutaronitriles |
-
2012
- 2012-10-11 CN CN201210383727.3A patent/CN102993090B/en not_active Expired - Fee Related
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2003006420A1 (en) * | 2001-07-12 | 2003-01-23 | Yale University | Catalytic method to convert aryl compounds to aryl amines |
| WO2006124283A1 (en) * | 2005-05-12 | 2006-11-23 | Boehringer Ingelheim International, Gmbh | Bis-amination of aryl halides |
| WO2009018504A1 (en) * | 2007-08-01 | 2009-02-05 | E. I. Du Pont De Nemours And Company | 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 |
| WO2010080488A1 (en) * | 2008-12-18 | 2010-07-15 | E. I. Du Pont De Nemours And Company | Continuous liquid-phase process for the synthesis of diaminopyridines from glutaronitriles |
| 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 |
Non-Patent Citations (3)
| 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.》 * |
| 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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| CN102993090B (en) | 2014-09-03 |
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Inventor after: Wang Defeng Inventor after: Zhang Yaobing Inventor after: Wang Bingcai Inventor after: Zhang Yancheng Inventor after: Shi Fei 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 YAOBING WANG BINGCAI ZHANG YANCHENG SHI FEI |
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Effective date of registration: 20161009 Address after: 226500 Zhang Yang village, Shi Zhuang Town, Jiangsu, Rugao Patentee after: Donggang Nantong Chemical Co., Ltd. Address before: 226500 Shi Zhuang Town, Nantong City, Jiangsu, Rugao Patentee before: Huafeng Chemical Co., Ltd., Nantong City |
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Effective date of registration: 20161229 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: Donggang Nantong Chemical Co., Ltd. |
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Effective date of registration: 20171215 Address after: 065402 Langfang city of Hebei province Xianghe County ZTE Backstreet No. 11 Tin Yuet District Building 3 room 2201 unit 2 Patentee after: Jiang Shulin Address before: 226500 Zhang Yang village, Shi Zhuang Town, Jiangsu, Rugao Patentee before: Huafeng Chemical Co., Ltd., Nantong City |
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Granted publication date: 20140903 Termination date: 20191011 |