CN108640870A - A method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines - Google Patents
A method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines Download PDFInfo
- Publication number
- CN108640870A CN108640870A CN201810323879.1A CN201810323879A CN108640870A CN 108640870 A CN108640870 A CN 108640870A CN 201810323879 A CN201810323879 A CN 201810323879A CN 108640870 A CN108640870 A CN 108640870A
- Authority
- CN
- China
- Prior art keywords
- added
- nitropyridines
- methoxyl group
- ethyl acetate
- methyl
- 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
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
- C07D213/62—Oxygen or sulfur atoms
- C07D213/63—One oxygen atom
- C07D213/65—One oxygen atom attached in position 3 or 5
Abstract
The invention discloses a kind of method of 6 bromomethyl of synthesis, 3 methoxyl group, 2 nitropyridine, synthesis step is:First 6 methyl, 3 hydroxyl, 2 nitropyridine, magnesium iodide and water are mixed, are added dropwise to dimethyl suflfate heating reaction 24 hours, ethyl acetate extraction boils off ethyl acetate and obtains 6 methyl, 3 methoxyl group, 2 nitropyridine；Carbon tetrachloride, sodium bromide stirring and dissolving is added, it is added dropwise to hydrogen peroxide heating reaction, boil off carbon tetrachloride, add water 200ml, ethyl acetate extracts, and boils off ethyl acetate and obtains 6 bromomethyl, 3 methoxyl group, 2 nitropyridine crude product, by column chromatography for separation, acetonitrile water is recrystallized to give 6 bromomethyl, 3 methoxyl group, 2 nitropyridine, yield 75%.
Description
Technical field
The present invention relates to a kind of synthetic method, a method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines.
Background technology
Physical efficiency is widely used in pesticide, medicine, dyestuff, fragrance etc. among pyridines organic chemical industry, is a kind of heavy
The organic chemical industry's intermediate wanted, purposes are very extensive.Noval chemical compound obtained from phenyl ring is substituted often with higher by pyridine
Bioactivity or lower toxicity, therefore people substitute the phenyl ring having in kind molecular structure with pyridine groups in recent years, or
Introducing other groups, which perform the derivatization, in molecule of some containing pyridine groups is desirably to obtain new reactive compound.So far
Introduced until the present how to synthesize 6- bromomethyl -3- methoxyl group -2- nitropyridines method it is seldom, it is general to synthesize 6- bromomethyls -3-
Methoxyl group -2- nitropyridines will use all very high iodomethane of toxicity price, and reaction temperature is difficult to control, it is difficult to be used for work
Industry metaplasia is produced.
Invention content
A kind of reaction condition of present invention offer is mild, raw material is easy to get, prepares convenient 6- bromomethyls -3- methoxyl group -2- nitre
The synthetic method of yl pyridines.
In order to achieve the above objectives, the synthetic route of 6- bromomethyls -3- methoxyl group -2- nitropyridines of the present invention is：
The building-up process of 6- bromomethyls -3- methoxyl group -2- nitropyridines of the present invention includes the following steps：
The synthesis of 6- methyl -3- methoxyl group -2- nitropyridines
(1) in 250mL four-hole bottles be added 15.4g 6- methyl -3- hydroxyl -2- nitropyridines, 16.5g magnesium iodides and
100g water, heating water bath are added dropwise to dimethyl suflfate 14.5g and react 18-24 hours to 75 DEG C；
(2) extraction of 200mL ethyl acetate is added, branch vibration layer steams ethyl acetate, and ethyl alcohol recrystallization obtains 6- methyl -3-
Methoxyl group -2- nitropyridines 16.1g.
The synthesis of 6- bromomethyl -3- methoxyl group -2- nitropyridines
(1) in 500mL four-hole bottles be added 10.1g 6- methyl -3- methoxyl group -2- nitropyridines, sodium bromide 10.3g and
Carbon tetrachloride 100mL, is heated to reflux, and is added dropwise to 11g hydrogen peroxide, and the reaction was continued 36-48 hours after dripping；
(2) sodium hydroxide solution of 100mL1M is added after having reacted, it is cooling, the extraction of 200mL ethyl acetate is added, steams
Ethyl acetate obtains yellow oil；
(3) yellow oil is detached with alumina column chromatography, is then recrystallized, is obtained yellowish with 75% acetonitrile solution
Color 6- bromomethyl -3- methoxyl group -2- nitropyridines, crystallization.
Specific embodiment
The building-up process of 6- bromomethyls -3- methoxyl group -2- nitropyridines of the present invention includes the following steps：
6- methyl -3- hydroxyl -2- the nitropyridines of 15.4g, 16.5g magnesium iodides and 100g are added in 250mL four-hole bottles
Water, heating water bath are added dropwise to dimethyl suflfate 14.5g and react 18-24 hours to 75 DEG C；The extraction of 200mL ethyl acetate is added, point
Water layer is removed, ethyl acetate is steamed, ethyl alcohol recrystallization obtains 6- methyl -3- methoxyl group -2- nitropyridines 16.1g.In 500mL four-hole bottles
The middle 6- methyl -3- methoxyl group -2- nitropyridines that 10.1g is added, sodium bromide 10.3g and carbon tetrachloride 100mL, are heated to reflux,
It is added dropwise to 11g hydrogen peroxide, the reaction was continued 36-48 hours after dripping；The sodium hydroxide solution of 100mL1M is added after having reacted,
It is cooling, the extraction of 200mL ethyl acetate is added, steams ethyl acetate and obtains yellow oil；Yellow oil alumina column chromatography
Then separation is recrystallized with 75% acetonitrile solution, obtains faint yellow 6- bromomethyls -3- methoxyl group -2- nitropyridines, tied
Crystalline substance, simultaneously calculated yield of weighing.
Example 1
6- methyl -3- hydroxyl -2- the nitropyridines of 15.4g, 16.5g magnesium iodides and 100g are added in 250mL four-hole bottles
Water, heating water bath are added dropwise to dimethyl suflfate 14.5g and react 18 hours to 75 DEG C；The extraction of 200mL ethyl acetate is added, divides and goes
Water layer, steams ethyl acetate, and ethyl alcohol recrystallization obtains 6- methyl -3- methoxyl group -2- nitropyridines 16.1g.In 500mL four-hole bottles
6- methyl -3- methoxyl group -2- the nitropyridines of 10.1g, sodium bromide 10.3g and carbon tetrachloride 100mL is added, is heated to reflux, drips
11g hydrogen peroxide is added, the reaction was continued 36 hours after dripping；The sodium hydroxide solution of 100mL1M is added after having reacted, it is cooling,
The extraction of 200mL ethyl acetate is added, steams ethyl acetate and obtains yellow oil；Yellow oil is detached with alumina column chromatography,
Then it is recrystallized with 75% acetonitrile solution, obtains faint yellow 6- bromomethyls -3- methoxyl group -2- nitropyridines crystallization 11.1g,
Yield is 75%.
Example 2
6- methyl -3- hydroxyl -2- the nitropyridines of 15.4g, 16.5g magnesium iodides and 100g are added in 250mL four-hole bottles
Water, heating water bath are added dropwise to dimethyl suflfate 14.5g and react 20 hours to 75 DEG C；The extraction of 200mL ethyl acetate is added, divides and goes
Water layer, steams ethyl acetate, and ethyl alcohol recrystallization obtains 6- methyl -3- methoxyl group -2- nitropyridines 16.1g.In 500mL four-hole bottles
6- methyl -3- methoxyl group -2- the nitropyridines of 10.1g, sodium bromide 10.3g and carbon tetrachloride 100mL is added, is heated to reflux, drips
11g hydrogen peroxide is added, the reaction was continued 40 hours after dripping；The sodium hydroxide solution of 100mL1M is added after having reacted, it is cooling,
The extraction of 200mL ethyl acetate is added, steams ethyl acetate and obtains yellow oil；Yellow oil is detached with alumina column chromatography,
Then it is recrystallized with 75% acetonitrile solution, obtains faint yellow 6- bromomethyls -3- methoxyl group -2- nitropyridines crystallization 11.1g,
Yield is 75%.
Example 3
6- methyl -3- hydroxyl -2- the nitropyridines of 15.4g, 16.5g magnesium iodides and 100g are added in 250mL four-hole bottles
Water, heating water bath are added dropwise to dimethyl suflfate 14.5g and react 24 hours to 75 DEG C；The extraction of 200mL ethyl acetate is added, divides and goes
Water layer, steams ethyl acetate, and ethyl alcohol recrystallization obtains 6- methyl -3- methoxyl group -2- nitropyridines 16.1g.In 500mL four-hole bottles
6- methyl -3- methoxyl group -2- the nitropyridines of 10.1g, sodium bromide 10.3g and carbon tetrachloride 100mL is added, is heated to reflux, drips
11g hydrogen peroxide is added, the reaction was continued 48 hours after dripping；The sodium hydroxide solution of 100mL1M is added after having reacted, it is cooling,
The extraction of 200mL ethyl acetate is added, steams ethyl acetate and obtains yellow oil；Yellow oil is detached with alumina column chromatography,
Then it is recrystallized with 75% acetonitrile solution, obtains faint yellow 6- bromomethyls -3- methoxyl group -2- nitropyridines crystallization 11.1g,
Yield is 75%.
Claims (1)
1. a kind of method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines, it is characterised in that specifically synthesis step is：
(1) the 6- methyl -3- hydroxyl -2- nitropyridines of 15.4g, 16.5g magnesium iodides and 100g are added in 250mL four-hole bottles
Water, heating water bath are added dropwise to dimethyl suflfate 14.5g to 75 DEG C, react 18-24 hours；
(2) extraction of 200mL ethyl acetate is added, branch vibration layer steams ethyl acetate, and ethyl alcohol recrystallization obtains 6- methyl -3- methoxies
Base -2- nitropyridines 16.1g；
(3) the 6- methyl -3- methoxyl group -2- nitropyridines of 10.1g, sodium bromide 10.3g and tetrachloro are added in 500mL four-hole bottles
Change carbon 100mL, be heated to reflux, be added dropwise to 11g hydrogen peroxide, the reaction was continued 36-48 hours after dripping；
(4) sodium hydroxide solution of 100mL1M is added after having reacted, it is cooling, the extraction of 200mL ethyl acetate is added, steams acetic acid
Ethyl ester obtains yellow oil；
(5) yellow oil is detached with alumina column chromatography, is then recrystallized with 75% acetonitrile solution, is obtained faint yellow 6-
Bromomethyl -3- methoxyl group -2- nitropyridines, crystallization.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810323879.1A CN108640870A (en) | 2018-04-12 | 2018-04-12 | A method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201810323879.1A CN108640870A (en) | 2018-04-12 | 2018-04-12 | A method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108640870A true CN108640870A (en) | 2018-10-12 |
Family
ID=63746229
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201810323879.1A Pending CN108640870A (en) | 2018-04-12 | 2018-04-12 | A method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN108640870A (en) |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103068802A (en) * | 2010-06-21 | 2013-04-24 | 爱泰益科私人有限公司 | Compounds for treating proliferative disorders |
| CN105294573A (en) * | 2015-06-16 | 2016-02-03 | 厦门医学高等专科学校 | Method for synthesizing 4,6-dichloro-2-(propylthio)-5-aminopyrimidine |
| WO2016189552A2 (en) * | 2015-05-26 | 2016-12-01 | Ipca Laboratories Limited | Novel recovery and recycling process of unwanted enantiomers of 2-aminopropyl indoline derivatives |
| CN107417603A (en) * | 2017-05-17 | 2017-12-01 | 江苏斯威森生物医药工程研究中心有限公司 | A kind of Crizotinib intermediate preparation method |
-
2018
- 2018-04-12 CN CN201810323879.1A patent/CN108640870A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103068802A (en) * | 2010-06-21 | 2013-04-24 | 爱泰益科私人有限公司 | Compounds for treating proliferative disorders |
| WO2016189552A2 (en) * | 2015-05-26 | 2016-12-01 | Ipca Laboratories Limited | Novel recovery and recycling process of unwanted enantiomers of 2-aminopropyl indoline derivatives |
| CN105294573A (en) * | 2015-06-16 | 2016-02-03 | 厦门医学高等专科学校 | Method for synthesizing 4,6-dichloro-2-(propylthio)-5-aminopyrimidine |
| CN107417603A (en) * | 2017-05-17 | 2017-12-01 | 江苏斯威森生物医药工程研究中心有限公司 | A kind of Crizotinib intermediate preparation method |
Non-Patent Citations (1)
| Title |
|---|
| TIANGONG LU ET AL: "discovery of (E)-3-((styrylasulfonyl)methyl)pyridine and (E)-2-((styrylsulfonyl)methyl)pyridine Derivatives as Anticancer Agents:synthesis, Structure-Activity Relationships, and Biological Activities", 《JOURNAL OF MEDICINAL CHEMISTRY》 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN105859721B (en) | A kind of Yi Bulu replaces the preparation method of Buddhist nun | |
| CN104803964B (en) | Multi-substituent isocoumarin derivative and preparation method thereof | |
| CN104892614B (en) | A kind of synthetic method of 6H iso-indoles simultaneously ketone derivatives of [2,1 α] indoles 6 | |
| CN105949118B (en) | A kind of preparation method of 2- aryl quinoline derivatives | |
| CN108822035B (en) | Preparation method of 4-substituted thiophenyl isoquinoline-1 (2H) -ketone compound | |
| CN107513050A (en) | The preparation method that a kind of olefin(e) acid bromine lactonizes | |
| CN106543156A (en) | It is a kind of to reduce epoxychloropropane residue in triglycidyl isocyanurate (TGIC) | |
| CN107892654B (en) | Isolongifolane-based fluorescent acid-base indicator and synthetic method and application thereof | |
| CN105153013B (en) | The synthetic method of the ketone of 6 bromine isoindoline 1 | |
| CN108640870A (en) | A method of synthesis 6- bromomethyl -3- methoxyl group -2- nitropyridines | |
| CN106008316A (en) | New method for synthesizing Ledipasvir chiral intermediate | |
| CN105646327A (en) | 2-perfluoroalkyl indole derivative and synthesis method thereof | |
| CN113717132B (en) | Key intermediate of antiepileptic drug and preparation method thereof | |
| CN106397377B (en) | The method of fluorine on a kind of electron rich five-ring heterocycles acid and its derivative decarboxylation | |
| CN106866511B (en) | A kind of preparation method of polysubstituted pyridine derivative | |
| CN106543081B (en) | Preparation method of 1-difluoroalkylisoquinoline | |
| CN105111161B (en) | A kind of method of efficient coupling series connection 2 phenyl benzoxazoles of synthesis and its derivative | |
| CN114702425A (en) | Preparation method of (S) -2-amino- (S) -3- [ pyrrolidone-2' ] alanine derivative and intermediate | |
| CN106866608B (en) | A kind of preparation method of fluoro -3,4- dihydrocoumarin derivative | |
| CN102344419A (en) | Preparation method of broad-spectrum antifungal drug fluconazole | |
| CN112430205B (en) | Preparation method of arylpyrrole compound | |
| CN105085431B (en) | 4 (4 first ammonia thiazolinyl phenyl) 3 morpholones and preparation method thereof | |
| CN104447528B (en) | The preparation method of pyridine-2,3-diethyl dicarboxylate | |
| CN108689914A (en) | A method of chipal compounds are prepared using intermediate | |
| CN104447178B (en) | A kind of 3, the synthetic method of 4-dibenzanthracene |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| WD01 | Invention patent application deemed withdrawn after publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20181012 |