CN104016911A - Synthetic method of 2-amino-3,5-dibromopyridine - Google Patents
Synthetic method of 2-amino-3,5-dibromopyridine Download PDFInfo
- Publication number
- CN104016911A CN104016911A CN201410131644.4A CN201410131644A CN104016911A CN 104016911 A CN104016911 A CN 104016911A CN 201410131644 A CN201410131644 A CN 201410131644A CN 104016911 A CN104016911 A CN 104016911A
- Authority
- CN
- China
- Prior art keywords
- amino
- synthetic method
- dibromopyridine
- dibromo pyridine
- solvent
- 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.)
- Pending
Links
- 238000010189 synthetic method Methods 0.000 title claims abstract description 17
- WJMJWMSWJSACSN-UHFFFAOYSA-N 3,5-dibromopyridin-2-amine Chemical compound NC1=NC=C(Br)C=C1Br WJMJWMSWJSACSN-UHFFFAOYSA-N 0.000 title abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 26
- WGOLHUGPTDEKCF-UHFFFAOYSA-N 5-bromopyridin-2-amine Chemical compound NC1=CC=C(Br)C=N1 WGOLHUGPTDEKCF-UHFFFAOYSA-N 0.000 claims abstract description 10
- 239000002904 solvent Substances 0.000 claims abstract description 9
- 239000002994 raw material Substances 0.000 claims abstract description 6
- 239000012043 crude product Substances 0.000 claims abstract description 3
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 9
- 238000010898 silica gel chromatography Methods 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 4
- 238000001953 recrystallisation Methods 0.000 claims description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 238000000746 purification Methods 0.000 claims description 3
- GSNUFIFRDBKVIE-UHFFFAOYSA-N DMF Natural products CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 claims description 2
- 238000001704 evaporation Methods 0.000 claims description 2
- 230000008020 evaporation Effects 0.000 claims description 2
- 239000000376 reactant Substances 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 239000000126 substance Substances 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 18
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000009286 beneficial effect Effects 0.000 abstract description 2
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 abstract 2
- 239000000203 mixture Substances 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 238000002360 preparation method Methods 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000007797 corrosion Effects 0.000 description 1
- 238000005260 corrosion Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 239000002932 luster Substances 0.000 description 1
- 238000000034 method Methods 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 238000007670 refining Methods 0.000 description 1
- 235000013599 spices Nutrition 0.000 description 1
Classifications
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyridine Compounds (AREA)
Abstract
The invention belongs to the field of organic synthesis and in particular relates to a synthetic method of 2-amino-3,5-dibromopyridine. The synthetic method of 2-amino-3,5-dibromopyridine comprises the following steps: reacting raw materials including 2-amino-5-bromopyridine and N-chlorosuccinimide for 1-28 hours in a molar weight of 1:(0.5-5) in a proper solvent at 0-100 DEG C to generate a 2-amino-3,5-dibromopyridine crude product and purifying to obtain the pure product 2-amino-3,5-dibromopyridine. The synthetic method has the beneficial effects that the reaction raw materials are available and are reasonable in prices; the reaction conditions are mild; the synthetic method is easy to operate and control and is simple in aftertreatment; the product has stable quality and high purity.
Description
(1) technical field
The invention belongs to organic synthesis field, be specifically related to a kind of 2-amino-3, the synthetic method of 5-dibromo pyridine.
(2) background technology
2-amino-3,5-dibromo pyridine is the important intermediate of organic synthesis, is mainly used in medicine intermediate, organic synthesis, organic solvent, also can be applicable to the aspects such as DYE PRODUCTION, pesticide producing and spices.
Existing 2-amino-3, there is following shortcoming in the preparation of 5-dibromo pyridine:
(1) by product is more, causes the color and luster of product darker, is difficult to refining purification.Although can be with repeatedly recrystallization of organic solvent, quality still cannot meet high request, and periodic crystallisation causes product yield low, and cost increases, complex operation;
(2) pollution of the corrosion of the chemical reduction method using to equipment and environment is all very serious, at present Limit exploitation;
(3) raw material sources are limited, expensive, and comparatively trouble of operation;
(4) need to use noble metal catalyst, increase preparation cost.
The problems referred to above all need to improve.
(3) summary of the invention
The present invention, in order to make up the deficiencies in the prior art, provides 2-amino-3, the synthetic method of 5-dibromo pyridine, and this synthetic method is simple to operate, productive rate is high, is applicable to laboratory and suitability for industrialized production.
The present invention is achieved through the following technical solutions:
A kind of 2-amino-3, the synthetic method of 5-dibromo pyridine, its special character is: comprise the following steps:
Taking 2-amino-5-bromopyridine and N-bromo-succinimide as raw material, the ratio of the two amount of substance is 1:0.5-5, in suitable solvent, within 1-28 hour, generate 2-amino-3 0-100 DEG C of reaction, 5-dibromo pyridine crude product, sterling 2-amino-3 after purifying, 5-dibromo pyridine.
2-of the present invention amino-3, the synthetic method of 5-dibromo pyridine, the charging capacity of reactant and solvent is: m
2-amino-5-bromopyridine: m
solvent=1:1-10 is the ratio of weight.
2-of the present invention amino-3, the synthetic method of 5-dibromo pyridine, solvent is one or both in chloroform, ethanol, ethyl acetate, DMF, methyl alcohol and Virahol.
2-of the present invention amino-3, the synthetic method of 5-dibromo pyridine, purification step is evaporation concentration, recrystallization, silica gel column chromatography separation.
Beneficial effect of the present invention: reaction raw materials is relatively easy to get, reasonable price, reaction conditions gentleness, easy handling, is easy to control, and aftertreatment is simple, and constant product quality, and purity is high.
(4) embodiment
Embodiment 1:
In 50mL single necked round bottom flask, add 2-amino-5-bromopyridine (3.46g, 20mmol), N-bromo-succinimide (7.12g, 40mmol), methyl alcohol 15ml.Mixture in reaction flask stirring reaction 4 hours at 20 DEG C.TLC and GC are definite to have reacted.After reaction finishes, revolve and steam except desolventizing, obtain thick product, separate and obtain straight product 2-amino-3 with silica gel column chromatography, 5-dichloropyridine, after being dried, calculated yield 67.06%, purity 97.28% (GC), 102 DEG C-105.2 DEG C of fusing points (98 DEG C-106 DEG C, document).
Embodiment 2:
In 50mL single necked round bottom flask, add 2-amino-5-bromopyridine (3.46g, 20mmol), N-bromo-succinimide (7.12g, 40mmol), ethanol 18ml.Mixture in reaction flask stirring reaction 4 hours at 20 DEG C.TLC and GC are definite to have reacted.After reaction finishes, revolve and steam except desolventizing, obtain thick product, separate and obtain straight product 2-amino-3 with silica gel column chromatography, 5-dichloropyridine, after being dried, calculated yield, 60.82%, purity 98.05% (GC), 102 DEG C-105.2 DEG C of fusing points (98 DEG C-106 DEG C, document).
Embodiment 3:
In 500mL single necked round bottom flask, add 2-amino-5-bromopyridine (17.30g, 100mmol), N-bromo-succinimide (40.94g, 230mmol), ethyl acetate 120ml.Mixture in reaction flask stirring reaction 6 hours at 20 DEG C.TLC and GC are definite to have reacted.After reaction finishes, revolve and steam except desolventizing, obtain thick product, separate and obtain straight product 2-amino-3 with silica gel column chromatography, 5-dichloropyridine, after being dried, calculated yield 72.36%, purity 97.28% (GC), 102 DEG C-105.2 DEG C of fusing points (98 DEG C-106 DEG C, document).
Embodiment 4:
In 500mL single necked round bottom flask, add 2-amino-5-bromopyridine (17.30g, 100mmol), N-bromo-succinimide (40.94g, 230mmol), Virahol 120ml.Mixture in reaction flask stirring reaction 8 hours at 20 DEG C.TLC and GC are definite to have reacted.After reaction finishes, revolve and steam except desolventizing, obtain thick product, separate and obtain straight product 2-amino-3 with silica gel column chromatography, 5-dichloropyridine, after being dried, calculated yield 57.43%, purity 97.28% (GC), 102 DEG C-105.2 DEG C of fusing points (98 DEG C-106 DEG C, document).
Embodiment 5:
In 50mL single necked round bottom flask, add 2-amino-5-bromopyridine (3.46g, 20mmol), N-bromo-succinimide (1.78g, 10mmol), chloroform 2.3ml.Mixture in reaction flask stirring reaction 1 hour at 100 DEG C.TLC and GC are definite to have reacted.After reaction finishes, revolve and steam except desolventizing, obtain thick product, separate and obtain straight product 2-amino-3 with silica gel column chromatography, 5-dichloropyridine, after being dried, calculated yield 67.06%, purity 97.28% (GC), 102 DEG C-105.2 DEG C of fusing points (98 DEG C-106 DEG C, document).
Embodiment 6:
In 50mL single necked round bottom flask, add 2-amino-5-bromopyridine (3.46g, 20mmol), N-bromo-succinimide (17.8g, 100mmol), DMF36.6ml.Mixture in reaction flask stirring reaction 28 hours at 0 DEG C.TLC and GC are definite to have reacted.After reaction finishes, revolve and steam except desolventizing, recrystallization, obtains thick product, separate and obtain straight product 2-amino-3 with silica gel column chromatography, 5-dichloropyridine, after being dried, calculated yield 67.06%, purity 97.28% (GC), 102 DEG C-105.2 DEG C of fusing points (98 DEG C-106 DEG C, document).
Embodiment 7:
Chloroform 5ml, ethyl acetate 10ml form mixed solvent, mixture in reaction flask stirring reaction 10 hours at 50 DEG C. separate and obtain straight product 2-amino-3 with silica gel column chromatography, 5-dichloropyridine, after dry, calculated yield 58.01%, purity 97.28% (GC), 102 DEG C-105.2 DEG C of fusing points (98 DEG C-106 DEG C, document), other are identical with embodiment 1.
Claims (4)
1. 2-amino-3, the synthetic method of 5-dibromo pyridine, is characterized in that: comprise the following steps:
Taking 2-amino-5-bromopyridine and N-bromo-succinimide as raw material, the ratio of the two amount of substance is 1:0.5-5, in suitable solvent, within 1-28 hour, generate 2-amino-3 0-100 DEG C of reaction, 5-dibromo pyridine crude product, sterling 2-amino-3 after purifying, 5-dibromo pyridine.
2. 2-according to claim 1 amino-3, the synthetic method of 5-dibromo pyridine, is characterized in that: the charging capacity of reactant and solvent is: m2-amino-5-bromopyridine: m solvent=1:1-10 is the ratio of weight.
3. 2-according to claim 1 and 2 amino-3, the synthetic method of 5-dibromo pyridine, is characterized in that: solvent is one or both in chloroform, ethanol, ethyl acetate, DMF, methyl alcohol and Virahol.
4. 2-according to claim 1 and 2 amino-3, the synthetic method of 5-dibromo pyridine, is characterized in that: purification step is evaporation concentration, recrystallization, silica gel column chromatography separation.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410131644.4A CN104016911A (en) | 2014-04-03 | 2014-04-03 | Synthetic method of 2-amino-3,5-dibromopyridine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201410131644.4A CN104016911A (en) | 2014-04-03 | 2014-04-03 | Synthetic method of 2-amino-3,5-dibromopyridine |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN104016911A true CN104016911A (en) | 2014-09-03 |
Family
ID=51433963
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201410131644.4A Pending CN104016911A (en) | 2014-04-03 | 2014-04-03 | Synthetic method of 2-amino-3,5-dibromopyridine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN104016911A (en) |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2012163724A1 (en) * | 2011-05-31 | 2012-12-06 | F. Hoffmann-La Roche Ag | Triazolopyridine compounds |
| WO2013048214A2 (en) * | 2011-09-30 | 2013-04-04 | C&C Research Laboratories | Novel heterocyclic derivatives and their uses |
| CN103221404A (en) * | 2010-05-13 | 2013-07-24 | 安姆根有限公司 | Nitrogen heterocyclic compounds useful as PDE10 inhibitors |
-
2014
- 2014-04-03 CN CN201410131644.4A patent/CN104016911A/en active Pending
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103221404A (en) * | 2010-05-13 | 2013-07-24 | 安姆根有限公司 | Nitrogen heterocyclic compounds useful as PDE10 inhibitors |
| WO2012163724A1 (en) * | 2011-05-31 | 2012-12-06 | F. Hoffmann-La Roche Ag | Triazolopyridine compounds |
| WO2013048214A2 (en) * | 2011-09-30 | 2013-04-04 | C&C Research Laboratories | Novel heterocyclic derivatives and their uses |
Non-Patent Citations (1)
| Title |
|---|
| CAROLINE CASTERA-DUCROS等: "Targeting the human parasite Leishmania donovani: Discovery of a new promising anti-infections pharmacophore in 3-nitroimidazo[1,2-a]pyridine series", 《BIOORGANIC & MEDICINAL CHEMISTRY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Augustine et al. | Propylphosphonic anhydride (T3P®): A remarkably efficient reagent for the one-pot transformation of aromatic, heteroaromatic, and aliphatic aldehydes to nitriles | |
| CN102079725A (en) | Method for preparing 2-chloropyrimidine | |
| CN103113308B (en) | Method for preparing dihydropyrimidinone derivative | |
| CN104072347B (en) | 4-alkoxyl-1, the preparation method of 1,1-tri-fluoro-3-butene-2-one | |
| Yeom et al. | Au (I)-catalyzed tandem [3, 3]-sigmatropic rearrangement–cycloisomerization cascade as a route to spirocyclic furans | |
| Crossley et al. | Cycloaddition of benzynes and nitrile oxides: synthesis of benzisoxazoles | |
| Fang et al. | gem-Dialkylthio vinylallenes: Alkylthio-regulated reactivity and application in the divergent synthesis of pyrroles and thiophenes | |
| CN104016911A (en) | Synthetic method of 2-amino-3,5-dibromopyridine | |
| CN104725409B (en) | Part and its preparation method and application and the method for preparing aryl-boric acid ester before boranepyridine | |
| CN104016909B (en) | The synthetic method of the bromo-5-chloropyridine of a kind of 2-amino-3- | |
| CN104016910A (en) | Synthetic method of 2-amino-3-chloro-5-bromopyridine | |
| CN104610267B (en) | Method for efficiently synthesizing 6-alkyl pyrazolo [1,5-c ] quinazoline framework compound under non-catalytic condition | |
| CN112375032A (en) | Synthetic method of 3-aminopyridine formaldehyde | |
| CN102276526B (en) | Synthesis method of 2-amino pyridine compounds | |
| CN104016908B (en) | The synthetic method of amino-3, the 5-dichloropyridines of a kind of 2- | |
| Chen et al. | Transition-metal-free highly efficient synthesis of 2-pyridones from β-keto amides and ynals | |
| CN108383754B (en) | Preparation method and application of aryl oxime ester compound | |
| CN104592223A (en) | Synthetic method of 8-carboxyl imidazo (1, 2-a) pyridine | |
| CN108191736B (en) | 2, 3-disubstituted indole derivatives and preparation method thereof | |
| Tohti et al. | Brønsted Acid Catalyzed Stereospecific Dearomative Spirocyclization of Benzothiophenyl Analogues of Tertiary cis-β-Benzylstyrenes | |
| CN104725376A (en) | Synthetic method of 6-chlorine-8-carboxyl imidazo [1,2-a] pyridine | |
| CN100999509A (en) | Preparation process of 2-cyanide furan | |
| Pan et al. | One-Pot Synthesis of Substituted Indole N-Oxides: TiCl4-Mediated Baylis-Hillman Reaction of α-Oxo Cyclic Ketene-S, S-acetal with o-Nitrobenzaldehydes and Subsequent Intramolecular Cyclization | |
| CN104387363B (en) | A kind of preparation method of full substituted thiophene | |
| CN103342694A (en) | Synthesis method of 1-oxa-3-thiacyclopentane-2-thioketone compound |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| RJ01 | Rejection of invention patent application after publication |
Application publication date: 20140903 |
|
| RJ01 | Rejection of invention patent application after publication |