CN105294548A - Preparation method of 2-amino-5-bromopyridine - Google Patents
Preparation method of 2-amino-5-bromopyridine Download PDFInfo
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- CN105294548A CN105294548A CN201510825548.4A CN201510825548A CN105294548A CN 105294548 A CN105294548 A CN 105294548A CN 201510825548 A CN201510825548 A CN 201510825548A CN 105294548 A CN105294548 A CN 105294548A
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- aminopyridine
- bromopyridine
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- C—CHEMISTRY; METALLURGY
- 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
- C07D213/73—Unsubstituted amino or imino radicals
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention belongs to the technical field of organic synthesis, and concretely relates to a preparation method of 2-amino-5-bromopyridine. The method is characterized in that 2-aminopyridine as a raw material reacts with phenyltrimethylammonium tribromide in a solvent dichloromethane or trichloromethane at 20-50DEG C for 1-3h, and a molar ratio of 2-aminopyridine to phenyltrimethylammonium tribromide is 0.7-1.4. The method has the advantages of avoiding of generation of a large amount of 3-position byproducts in traditional preparation methods, reduction of raw material wastes and later stage separation load, easy obtaining of the raw material 2-aminopyridine, low cost, mild reaction conditions of the above route, high yield, no generation of 3-position byproducts in the whole process, and industrialization prospect.
Description
Technical field
The invention belongs to technical field of organic synthesis, be specifically related to a kind of preparation method of 2-amino-5-pyridine.
background technology
Pyridine and its derivatives is distributed in nature widely.Many plant constituents are as all contained pyridine ring compound in the structure of alkaloid etc., they are the bases producing many important compound, are indispensable raw materials during medicine, agricultural chemicals, dyestuff, tensio-active agent, rubber ingredients, fodder additives, foodstuff additive, tackiness agent etc. are produced.Amino-5 bromopyridines of 2-are a kind of important medicine intermediates, can be used for synthesizing PI
3kinase inhibitor, haloperidid derivative and thiazolyl thiourea compound, aminopyrazole derivatives selective dopamine D
3receptor stimulant, the medicines such as synthesis imidazo [1,2-a] pyridine compounds VEGFR-2 inhibitor, are also used for the treatment of autoimmune disorder, diseases associated with inflammation, cardiovascular disorder, nerve move back the various diseases such as shape property disease, allergy.
At present, conventional method take PA as raw material, adopt bromine as bromizating agent, use in normally that bromine is water-soluble, chloroform, tetracol phenixin equal solvent, but bromine has very large volatility and toxic, operation, storage, transport are all inconvenient, and are difficult to obtain single bromination product for active aromatics, are developing new bromizating agent for a long time to replace bromine always.Phosphorus tribromide, NBS are solid brominated dose that comparatively early uses, but also have more shortcoming, as NBS costly, preparation is also inconvenient.Phosphorus tribromide has strong sharp aroma, is corrosive, water-soluble rear soluble.
Summary of the invention
The object of the invention is to overcome bromizating agent in prior art expensive, be corrosive, the technical deficiency such as 3 by products are many, a kind of preparation method of new 2-amino-5-bromopyridine is provided.
For solving the problems of the technologies described above, the technical solution used in the present invention is as follows:
A preparation method for 2-amino-5-bromopyridine, reactions steps is as follows:
Take PA as raw material, with methylene dichloride or trichloromethane for solvent, at the temperature of 20-50 DEG C, react 1-3 hour with phenyltrimethyl-ammonium tribromide, the mol ratio of described PA and phenyltrimethyl-ammonium tribromide is 0.7-1.4.
Further, the consumption of described solvent is every gram of PA 20-35ml.
Further, the consumption of described solvent is every gram of PA 30ml.
Further, described temperature is preferably 30 DEG C.
Further, described PA and phenyltrimethyl-ammonium tribromide mol ratio are 0.9-1.3.
The beneficial effect of technical scheme of the present invention is adopted to be:
(1) generation of a large amount of 3 by products in traditional preparation methods is avoided, the load that the waste decreasing raw material was separated with the later stage;
(2) raw material PA is easy to get, and cost is low, this route reaction mild condition, and yield is high, and whole process generates without 3 by products, has industrial prospect.
Embodiment
Below by embodiment, the present invention is further described, not for limiting right of the present invention.
Embodiment 1
By 9.4g2-aminopyridine (0.1mol), 37.6g phenyltrimethyl-ammonium tribromide (0.1mol) and 300ml chloroform join in 1L there-necked flask, mechanical stirring is inserted in there-necked flask, thermometer and condensing reflux pipe, start stirring to make it to mix, stir 2 hours at 30 DEG C, the saturated nacl aqueous solution washing prepared in advance with 40ml, aqueous phase is on upper strata, organic phase is in lower floor, use separating funnel layering, organic phase uses 20ml water washing 2-3 time again, layering, with anhydrous sodium sulfate drying, filter, organic phase rotary evaporation removing solvent chloroform, obtain oily matter, frozen water cools, add water precipitation solid, obtain crude product, use benzene recrystallization, filter, dry, obtain yellow solid 10g, yield 81%.
Embodiment 2
By 9.4g2-aminopyridine (0.1mol), 37.6g phenyltrimethyl-ammonium tribromide (0.1mol) and 300ml chloroform join in 1L there-necked flask, mechanical stirring is inserted in there-necked flask, thermometer and condensing reflux pipe, start stirring to make it to mix, stir 2 hours at 25 DEG C, the saturated nacl aqueous solution washing prepared in advance with 40ml, aqueous phase is on upper strata, organic phase is in lower floor, use separating funnel layering, organic phase uses 20ml water washing 2-3 time again, layering, with anhydrous sodium sulfate drying, filter, organic phase rotary evaporation removing solvent chloroform, obtain oily matter, frozen water cools, add water precipitation solid, obtain crude product, use benzene recrystallization, filter, dry, obtain yellow solid 8.43g, yield 78%.
The present embodiment is preferred forms.
Embodiment 3
By 9.4g2-aminopyridine (0.1mol), 37.6g(phenyltrimethyl-ammonium tribromide 0.1mol) and 300ml methylene dichloride join in 1L there-necked flask, mechanical stirring is inserted in there-necked flask, thermometer and condensing reflux pipe, start stirring to make it to mix, stir 2 hours at 30 DEG C, the saturated nacl aqueous solution washing prepared in advance with 40ml, aqueous phase is on upper strata, organic phase is in lower floor, use separating funnel layering, organic phase uses 20ml water washing 2-3 time again, layering, with anhydrous sodium sulfate drying, filter, organic phase rotary evaporation removing solvent chloroform, obtain oily matter, frozen water cools, add water precipitation solid, obtain crude product, use benzene recrystallization, filter, dry, obtain yellow solid 8.1g, yield 75%.
Claims (5)
1. the preparation method of a 2-amino-5-bromopyridine, it is characterized in that reactions steps is as follows: take PA as raw material, with methylene dichloride or trichloromethane for solvent, at the temperature of 20-50 DEG C, react 1-3 hour with phenyltrimethyl-ammonium tribromide, the mol ratio of described PA and phenyltrimethyl-ammonium tribromide is 0.7-1.4.
2. the preparation method of a kind of 2-amino-5-bromopyridine according to claim 1, is characterized in that: the consumption of described solvent is every gram of PA 20-35ml.
3. the preparation method of a kind of 2-amino-5-bromopyridine according to claim 4, is characterized in that: the consumption of described solvent is every gram of PA 30ml.
4. the preparation method of a kind of 2-amino-5-bromopyridine according to claim 1, is characterized in that: described temperature is preferably 30 DEG C.
5. the preparation method of a kind of 2-amino-5-bromopyridine according to claim 1, is characterized in that: described PA and phenyltrimethyl-ammonium tribromide mol ratio are 0.9-1.3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201510825548.4A CN105294548A (en) | 2015-11-24 | 2015-11-24 | Preparation method of 2-amino-5-bromopyridine |
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| CN201510825548.4A CN105294548A (en) | 2015-11-24 | 2015-11-24 | Preparation method of 2-amino-5-bromopyridine |
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| CN105294548A true CN105294548A (en) | 2016-02-03 |
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| CN201510825548.4A Pending CN105294548A (en) | 2015-11-24 | 2015-11-24 | Preparation method of 2-amino-5-bromopyridine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108864036A (en) * | 2018-08-01 | 2018-11-23 | 江苏八巨药业有限公司 | The method for preparing D- (+)-α-(2 thiophene ethyl amine base)-α-(2- chlorphenyl) methyl acetate hydrochloride |
-
2015
- 2015-11-24 CN CN201510825548.4A patent/CN105294548A/en active Pending
Non-Patent Citations (4)
| Title |
|---|
| TLABO C. LEBOHO，ET AL.: "The acid-catalysed synthesis of 7-azaindoles from 3-alkynyl-2-aminopyridines and their antimicrobial activity", 《ORGANIC & BIOMOLECULAR CHEMISTRY》 * |
| XIN-LE LI，ET AL.: "A facile,regioselective and controllable bromination of aromatic amines using a CuBr2/Oxone system", 《RSC ADV.》 * |
| 姚昌盛等: "三溴化苯基三甲铵工业化制备、应用及回收利用", 《徐州师范大学学报 (自然科学版)》 * |
| 王道林等: "3-（2-苯并呋喃酰基）薁-1-羧酸甲酯的有效合成", 《有机化学》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108864036A (en) * | 2018-08-01 | 2018-11-23 | 江苏八巨药业有限公司 | The method for preparing D- (+)-α-(2 thiophene ethyl amine base)-α-(2- chlorphenyl) methyl acetate hydrochloride |
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Application publication date: 20160203 |