CN101768036A - Method for preparing heterocyclic aromatic compound replaced by aryl in alcohol solvent - Google Patents
Method for preparing heterocyclic aromatic compound replaced by aryl in alcohol solvent Download PDFInfo
- Publication number
- CN101768036A CN101768036A CN201010300623A CN201010300623A CN101768036A CN 101768036 A CN101768036 A CN 101768036A CN 201010300623 A CN201010300623 A CN 201010300623A CN 201010300623 A CN201010300623 A CN 201010300623A CN 101768036 A CN101768036 A CN 101768036A
- Authority
- CN
- China
- Prior art keywords
- reaction
- aromatic compound
- ethyl acetate
- product
- bromo
- 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
Abstract
The invention provides a method for preparing a heterocyclic aromatic compound replaced by aryl in an alcohol solvent, belonging to the technical field of catalytic chemistry. The method utilizes Suzuki crossed coupling reaction between a halogenated heterocyclic aromatic compound and aryl boric acid to prepare the heterocyclic aromatic compound replaced by the aryl. The halogenated heterocyclic aromatic compound, the aryl boric acid, alkali and a catalyst are added into glycol or polyethylene glycol (2 to 4mL) according to the molar ratio of 0.5:0.75:1.0:0.00025 to 0.0025; reaction is carried out for 5 to 300 minutes in air under the temperature of 80 DEG C; saturated salt solution is added after the reaction is finished, reaction products are extracted by ethyl acetate, organic phases are merged, drying and filtering are carried out by anhydrous Na2SO4, and then filtering solution is concentrated and separated by column chromatography, so as to obtain the pure heterocyclic aromatic compound replaced by the aryl. The method has the following characteristics: a ligand, a phase transferring agent or an accelerating agent does not need to be added; the protection of inert gases is not needed; the method is friendly to the environment; the using quantity of the palladium catalyst is small, the reaction is quick, the yield is high, and the product separation is simple.
Description
Technical field
The present invention relates to a kind of method of the azepine aromatic compound that the preparation aryl replaces in alcoholic solvent, it belongs to the organic compound technical field of catalytic chemistry.
Background technology
The nitrogen heterocyclic that aryl replaces extensively is present in (Chem.Commun.2009,3699 in natural product, medicine and the multiple organic functional material; Chem.Mater., 2008,20,6254; J.Am.Chem.Soc., 2006,128,16641).The catalytic Suzuki linked reaction of palladium is to form one of the effective means of aryl azepine aromatic ring structure (Chem.Rev.1995,95,2457).So far, the method for the azepine aromatic compound that the preparation aryl of bibliographical information replaces generally need be used air and water sensitive, synthetic difficulty, expensive phosphine part are promoted, and the reaction times is grown (Angew.Chem.Int.Ed., 2008,47,4695; Angew.Chem.Int.Ed., 2008,47,928; J.Am.Chem.Soc., 2007,129,3358; Angew.Chem.Int.Ed.2002,41,23,4500-4503; Org.Lett., 2009,11,345; Org.Lett., 2009,11,381).Thereby development is simple, cheap, the preparation method that efficiently reaches general aryl substituted nitrogen heterocyclic aromatic compound has the important application prospect.
In recent years, bibliographical information aqueous phase do not need the promoted Suzuki reaction system of part to prepare azepine aromatic compound (Chem.Commun., 2009,6267 that aryl replaces; Eur.J.Org.Chem., 2009,110; Green Chem., 2008,10,868; Chem.Commun., 2007,5069).Yet deficiencies such as the method for bibliographical information exists still that catalyst levels is big, reactive behavior is low, long reaction time or versatility difference.Do not appear in the newspapers so far and need not part and promote efficiently to activate the universal method that halo azepine aromatic compound is used for Suzuki prepared in reaction aryl substituted nitrogen heterocyclic aromatic derivatives.
Summary of the invention
The Suzuki cross-coupling reaction that the purpose of this invention is to provide a kind of simple to operate, cheap, high reactivity and the general palladium catalysis halo azepine aromatic compound that carries out and aryl boric acid in ethylene glycol or two polyoxyethylene glycol prepares the catalysis novel process of the azepine aromatic compound that aryl replaces.
Technical scheme of the present invention is: a kind of method of the azepine aromatic compound that the preparation aryl replaces in alcoholic solvent: in air, at first add 2.0～4.0mL ethylene glycol or two polyoxyethylene glycol in the round-bottomed flask, add 0.00025～0.0025mmol palladium catalyst, 1.0mmol alkali, 0.5mmol halo azepine aromatic compound, 0.75mmol aryl boric acid then successively, carried out the Suzuki cross-coupling reaction 5～300 minutes in 80 Fei stirring, after reaction finishes, with 15ml * 3 ethyl acetate extraction reaction product, merge organic phase, use anhydrous Na
2SO
4Drying is filtered, and filtrate concentrates, and uses column chromatography, and makes the azepine aromatic compound that analytically pure aryl replaces.
Among the above-mentioned preparation method, described palladium catalyst is selected from palladium or Palladous chloride.
Among the above-mentioned preparation method, described alkali is selected from potassiumphosphate, sodium hydroxide or potassium hydroxide.
Among the above-mentioned preparation method, described halo nitrogen heterocyclic is selected from 2-bromopyridine, 2-bromo-5-fluorine pyridine, 2-bromo-5-picoline, 2-bromo-6-picoline, 2-bromo-6-nitropyridine, 3-bromopyridine, 2-amino-3-bromo-5-picoline, 2-amino-5-bromopyridine, 3-bromo-6-methoxypyridine, 2-chlorine piperazine, 3-bromo-quinoline, 2-amino-5-bromo pyrimi piperidine or 5-bromo pyrimi piperidine.
Among the above-mentioned preparation method, described aryl boric acid is selected from phenylo boric acid, 2-methylphenylboronic acid, 3-methylphenylboronic acid, 4-methylphenylboronic acid, 2-methoxyphenylboronic acid, 3-methoxyphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorobenzoic boric acid or 4-chlorobenzene boric acid.
The invention has the beneficial effects as follows: the preparation method of the azepine aromatic compound that this aryl replaces does not use part or promotor, does not need protection of inert gas, reaction medium environmental friendliness, reaction under mild conditions, palladium catalyst consumption are few; substrate is widely applicable; reaction fast, yield is high, product separation is simple, has a wide range of applications at aspects such as synthesizing of natural product, medicine, agricultural chemicals, weedicide and polymer conductive material, liquid crystal material.
Embodiment
The preparation of embodiment 12-phenylpyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 22-phenylpyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), sodium hydroxide (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 32-phenylpyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassium hydroxide (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 96%.
The preparation of embodiment 42-phenylpyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), Palladous chloride (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 95%.
The preparation of embodiment 52-phenylpyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL two polyoxyethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 15min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 62-(4-aminomethyl phenyl) pyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, 4-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 4mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 72-(2-aminomethyl phenyl) pyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, 2-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 60min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 94%.
The preparation of embodiment 82-(4-p-methoxy-phenyl) pyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, 4-methoxyphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 40min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 92-(4-fluorophenyl) pyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, 4-fluorobenzoic boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 20min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 102-(4-chloro-phenyl-) pyridine
In air, take by weighing 2-bromopyridine (0.5mmol) successively, 4-chlorobenzene boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 96%.
The preparation of embodiment 112-(4-aminomethyl phenyl)-5-fluorine pyridine
In air, take by weighing 2-bromo-5-fluorine pyridine (0.5mmol) successively, 4-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 10min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 96%.
The preparation of embodiment 122-methyl-6-phenylpyridine
In air, take by weighing 2-bromo-6-picoline (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 20min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 92%.
The preparation of embodiment 132-methyl-6-(4-methyl) phenylpyridine
In air, take by weighing 2-bromo-6-picoline (0.5mmol) successively, 4-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 15min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 91%.
The preparation of embodiment 142-phenyl-5-picoline
In air, take by weighing 2-bromo-5-picoline (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 35min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 152-(4-methyl) phenyl-5-picoline
In air, take by weighing 2-bromo-5-picoline (0.5mmol) successively, 4-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 60min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 94%.
The preparation of embodiment 162-phenyl-5-nitropyridine
In air, take by weighing 2-bromo-5-nitropyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 20min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/49), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 173-phenylpyridine
In air, take by weighing 3-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 15min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 183-(4-methyl) phenylpyridine
In air, take by weighing 3-bromopyridine (0.5mmol) successively, 4-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 15min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 193-(3-methyl) phenylpyridine
In air, take by weighing 3-bromopyridine (0.5mmol) successively, 3-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 10min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 203-(2-methyl) phenylpyridine
In air, take by weighing 3-bromopyridine (0.5mmol) successively, 2-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 180min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 96%.
The preparation of embodiment 213-(4-fluorine) phenylpyridine
In air, take by weighing 3-bromopyridine (0.5mmol) successively, 4-fluorobenzoic boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 96%.
The preparation of embodiment 222-amino-3-phenyl-5-picoline
In air, take by weighing 2-amino-3-bromo-5-picoline (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 240min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 93%.
The preparation of embodiment 232-amino-5-phenyl pyridine
In air, take by weighing 2-amino-5-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL two polyoxyethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 180min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 96%.
The preparation of embodiment 242-methoxyl group-5-phenylpyridine
In air, take by weighing 2-methoxyl group-5-bromopyridine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.00025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 5min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 252-methoxyl group-5-(4-fluorophenyl) pyridine
In air, take by weighing 2-methoxyl group-5-bromopyridine (0.5mmol) successively, 4-fluorobenzoic boric acid (0.75mmol), palladium (0.00025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 12min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 262-methoxyl group-5-(2-methyl) phenylpyridine
In air, take by weighing 2-methoxyl group-5-bromopyridine (0.5mmol) successively, 2-methylphenylboronic acid (0.75mmol), palladium (0.00025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 25min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 96%.
The preparation of embodiment 272-methoxyl group-5-(4-methoxyl group) phenylpyridine
In air, take by weighing 2-methoxyl group-5-bromopyridine (0.5mmol) successively, 4-methoxyphenylboronic acid (0.75mmol), palladium (0.00025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 40min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 282-methoxyl group-5-(3-methyl) phenylpyridine
In air, take by weighing 2-methoxyl group-5-bromopyridine (0.5mmol) successively, 3-methylphenylboronic acid (0.75mmol), palladium (0.00025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 25min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/5), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 95%.
The preparation of embodiment 295-phenyl pyrimidine
In air, take by weighing 5-bromo pyrimi piperidine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0005mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 20min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 305-(4-methyl) phenyl pyrimidine
In air, take by weighing 5-bromo pyrimi piperidine (0.5mmol) successively, 4-methylphenylboronic acid (0.75mmol), palladium (0.0005mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 7min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 315-(4-fluorine) phenyl pyrimidine
In air, take by weighing 5-bromo pyrimi piperidine (0.5mmol) successively, 4-fluorobenzoic boric acid (0.75mmol), palladium (0.0005mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 30min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 98%.
The preparation of embodiment 322-amino-5-phenyl pyrimidine
In air, take by weighing 2-amino-5-bromo pyrimi piperidine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 7min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1.5/1), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 99%.
The preparation of embodiment 333-phenylquinoline
In air, take by weighing 3-bromoquinoline (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 25min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 93%.
The preparation of embodiment 343-(2-methyl) phenylquinoline
In air, take by weighing 3-bromoquinoline (0.5mmol) successively, 2-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 85min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 80%.
The preparation of embodiment 352-phenyl pyrazines
In air, take by weighing 2-chloropyrazine (0.5mmol) successively, phenylo boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 45min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 94%.
The preparation of embodiment 362-(4-methyl) phenyl pyrazines
In air, take by weighing 2-chloropyrazine (0.5mmol) successively, 4-methylphenylboronic acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 20min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 94%.
The preparation of embodiment 372-(4-fluorine) phenyl pyrazines
In air, take by weighing 2-chloropyrazine (0.5mmol) successively, 4-fluorobenzoic boric acid (0.75mmol), palladium (0.0025mmol), potassiumphosphate (1.0mmol) also is transferred in the 25mL round-bottomed flask, adds 2mL ethylene glycol subsequently in the 25mL round-bottomed flask.At 80 Fei lower magnetic force stirring reaction 95min, thin-layer chromatography is followed the tracks of reaction.Reaction finishes the back and adds the 15mL saturated aqueous common salt and with ethyl acetate (15mL * 3) extractive reaction product, merge organic phase, anhydrous Na
2SO
4Drying is filtered, use Rotary Evaporators concentrate thick product, column chromatography obtains target product, the elutriant that column chromatography is used is ethyl acetate/petroleum ether (V/V=1/20), product structure passes through
1H NMR and mass spectrum are identified.Separation yield reaches 88%.
Claims (5)
1. the method for the azepine aromatic compound that the preparation aryl replaces in alcoholic solvent, it is characterized in that: in air, at first 2.0～4.0mL ethylene glycol or two polyoxyethylene glycol are added in the round-bottomed flask, add 0.00025～0.0025mmol palladium catalyst then successively, 1.0mmol alkali, 0.5mmol halo azepine aromatic compound, 0.75mmol aryl boric acid, carried out the Suzuki cross-coupling reaction 5～300 minutes in 80 Fei stirring, after reaction finishes, with 15ml * 3 ethyl acetate extraction reaction product, merge organic phase, with anhydrous Na 2SO4 drying, filter, filtrate concentrates, and uses column chromatography, and makes the azepine aromatic compound that analytically pure aryl replaces.
2. according to the method for the described a kind of azepine aromatic compound that the preparation aryl replaces in alcoholic solvent of claim 1, it is characterized in that: described palladium catalyst is selected from palladium or Palladous chloride.
3. according to the method for the described a kind of azepine aromatic compound that the preparation aryl replaces in alcoholic solvent of claim 1, it is characterized in that: described alkali is selected from potassiumphosphate, sodium hydroxide or potassium hydroxide.
4. according to the method for the described a kind of azepine aromatic compound that the preparation aryl replaces in alcoholic solvent of claim 1, it is characterized in that: described halo azepine aromatic compound is selected from 2-bromopyridine, 2-bromo-5-fluorine pyridine, 2-bromo-5-picoline, 2-bromo-6-picoline, 2-bromo-6-nitropyridine, 3-bromopyridine, 2-amino-3-bromo-5-picoline, 2-amino-5-bromopyridine, 3-bromo-6-methoxypyridine, 2-chlorine piperazine, 3-bromo-quinoline, 2-amino-5-bromo pyrimi piperidine or 5-bromo pyrimi piperidine.
5. according to the method for the described a kind of azepine aromatic compound that the preparation aryl replaces in alcoholic solvent of claim 1, it is characterized in that: described aryl boric acid is selected from phenylo boric acid, 2-methylphenylboronic acid, 3-methylphenylboronic acid, 4-methylphenylboronic acid, 2-methoxyphenylboronic acid, 3-methoxyphenylboronic acid, 4-methoxyphenylboronic acid, 4-fluorobenzoic boric acid or 4-chlorobenzene boric acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010300623 CN101768036B (en) | 2010-01-23 | 2010-01-23 | Method for preparing heterocyclic aromatic compound replaced by aryl in alcohol solvent |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201010300623 CN101768036B (en) | 2010-01-23 | 2010-01-23 | Method for preparing heterocyclic aromatic compound replaced by aryl in alcohol solvent |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101768036A true CN101768036A (en) | 2010-07-07 |
| CN101768036B CN101768036B (en) | 2013-05-08 |
Family
ID=42501161
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201010300623 Expired - Fee Related CN101768036B (en) | 2010-01-23 | 2010-01-23 | Method for preparing heterocyclic aromatic compound replaced by aryl in alcohol solvent |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101768036B (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112010906A (en) * | 2020-08-31 | 2020-12-01 | 中国海洋石油集团有限公司 | Bisphosphite and preparation method and application thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101675040A (en) * | 2007-05-03 | 2010-03-17 | 辉瑞有限公司 | Pyridine derivatives |
| CN100569713C (en) * | 2007-05-15 | 2009-12-16 | 大连理工大学 | A kind of preparation method of biphenyl compound |
-
2010
- 2010-01-23 CN CN 201010300623 patent/CN101768036B/en not_active Expired - Fee Related
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112010906A (en) * | 2020-08-31 | 2020-12-01 | 中国海洋石油集团有限公司 | Bisphosphite and preparation method and application thereof |
| CN112010906B (en) * | 2020-08-31 | 2021-09-28 | 中国海洋石油集团有限公司 | Bisphosphite and preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN101768036B (en) | 2013-05-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN100569713C (en) | A kind of preparation method of biphenyl compound | |
| Hajiashrafi et al. | Erbium-organic framework as heterogeneous Lewis acid catalysis for Hantzsch coupling and tetrahydro-4H-chromene synthesis | |
| Mohan et al. | Superparamagnetic copper ferrite nanoparticles catalyzed aerobic, ligand-free, regioselective hydroboration of alkynes: influence of synergistic effect | |
| CN105037062A (en) | Alcohol-based ternary deep-eutectic solvent and preparation method thereof | |
| CN101638352B (en) | Aryl-replaced nitrogen heterocyclic compound preparation method | |
| CN101774871A (en) | Method for preparing biaryl compound in pure water | |
| CN101768036A (en) | Method for preparing heterocyclic aromatic compound replaced by aryl in alcohol solvent | |
| CN105732619A (en) | Synthesizing method of 5,6,7,8-tetrahydropyridino-[2,3-d]pyrimidine compound | |
| CN101948366A (en) | Method for preparing 4-(diphenylamino)biaryl compound in water phase | |
| CN102491968A (en) | Method for preparing carbazolyl biaryl compound in aqueous phase | |
| CN101857517B (en) | Method for preparing fluorobiaryl compound in pure water solution | |
| CN103232324B (en) | The preparation method of a kind of (R)-3,5-pairs of (trifluoromethyl) phenylethyl alcohols | |
| CN104961734A (en) | Method for synthetizing medical intermediate heterocyclic group pyridine N-oxide | |
| CN108722480A (en) | A kind of double heterocyclic aldehydes contracting -2,8- diamino-Tr*ger ' s Base schiff base catalysts and preparation method | |
| CN104725409A (en) | Borane-pyridine pre-ligand, preparation method and application of borane-pyridine pre-ligand, and preparation method of aryl boric acid ester | |
| CN103242378B (en) | Ferrocenyl pyrimidine pincer ligand and preparation method thereof | |
| CN104876929A (en) | Synthesis method and application of 1,2,3,4-tetrahydronaphthyridine compound | |
| CN105001156B (en) | A kind of three component reaction system synthetic methods of quinoline | |
| CN106478627A (en) | A kind of 6,12,18 triaryl, 5,11,17 benzo three quinoline and its synthetic method | |
| CN113024611A (en) | Novel N-heterocyclic carbene cyclic palladium compound and preparation method and application thereof | |
| CN106349249A (en) | Method for green synthesis of norcantharidin derivative | |
| Zong et al. | An imidazolium ionic compound-supported palladium complex as an efficient catalyst for Suzuki–Miyaura reactions in aqueous media | |
| CN105294776A (en) | Method for preparing symmetric dimer of nitrogen heterocyclic ring aromatic compound | |
| CN102942429A (en) | Method for preparing aza or thia aryl biaryl compound by aid of palladium and carbon catalysts | |
| CN114163385B (en) | Method for promoting oxidation of tetrahydroisoquinoline compounds to lactam compounds by using surfactant |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20130508 Termination date: 20160123 |
|
| EXPY | Termination of patent right or utility model |