CN110156577A - A kind of synthetic method of Beta-bromo ether compound - Google Patents
A kind of synthetic method of Beta-bromo ether compound Download PDFInfo
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- CN110156577A CN110156577A CN201910427916.8A CN201910427916A CN110156577A CN 110156577 A CN110156577 A CN 110156577A CN 201910427916 A CN201910427916 A CN 201910427916A CN 110156577 A CN110156577 A CN 110156577A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/05—Preparation of ethers by addition of compounds to unsaturated compounds
- C07C41/06—Preparation of ethers by addition of compounds to unsaturated compounds by addition of organic compounds only
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/18—Preparation of ethers by reactions not forming ether-oxygen bonds
- C07C41/22—Preparation of ethers by reactions not forming ether-oxygen bonds by introduction of halogens; by substitution of halogen atoms by other halogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
- C07C41/34—Separation; Purification; Stabilisation; Use of additives
- C07C41/36—Separation; Purification; Stabilisation; Use of additives by solid-liquid treatment; by chemisorption
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- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
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Abstract
The invention discloses a kind of synthetic methods of Beta-bromo ether compound, the method are as follows: respectively using indenes and trans stilbene as raw material, the zinc-aluminum hydrotalcite of methanol, alkali halide and bromate intercalation is added and is uniformly mixed, under the action of inorganic acid, it is stirred to react at 25-50 DEG C 1-6 hours under normal pressure, TLC tracking fully reacting obtains that reaction mixture is post-treated to respectively obtain bromo- 1 methoxyindan of 2- and 1, the bromo- 2- Ethyl Methyl Ether of 2- diphenyl -1-.The present invention uses the zinc-aluminum hydrotalcite and alkali metal bromide of bromate intercalation, more safety and environmental protection；Reaction condition is more mild, and the reaction time is shorter, and yield is preferable；It is easy to operate, the formation speed of halogen source can be controlled by changing reaction condition, controllability is strong.
Description
(1) technical field
The present invention relates to a kind of synthetic method of bromo ether compound, in particular to bromo- 1 methoxyindan of 2- and
The synthetic method of the bromo- 2- Ethyl Methyl Ether of 1,2- diphenyl -1-.
(2) background technique
Bromo- 1 methoxyindan of 2- and 1, the bromo- 2- Ethyl Methyl Ether of 2- diphenyl -1- are widely used in organic synthesis, can
To be further converted to other functional groups, practical value with higher.Such as ninhydrin can be used for amino acid detection and
The fingerprint identification of public security department, the bromo- 1- indone of 2- is then a kind of medicine intermediate, can be synthesized for treating HIV-1 infection
Indinavir；The bromo- 2- Ethyl Methyl Ether of 1,2- diphenyl -1- be also as synthesis fluorescent whitening agent, dyestuff, scintillation reagent,
The common intermediate of drug.
The method of synthesis bromo- 1 methoxyindan of 2- mainly has at present: 1. use NBS as halide reagent, in methanol solution
It is middle to be reacted (Bar, Sukanta, Canadian Journal of Chemistry-Revue at 0 DEG C with indenes
Canadienne Chimie, 88 (7), 605-612), this method uses NBS, can generate a large amount of debirs, reaction condition
Compare harsh；2. using Br2And CH3OH is as reactant (Tutar A, Cakmak O, Balci M, Journal of
It Chemical Research 2010,37 (52): 507-511) is, that solvent synthesizes bromo- 1 methoxyindan of 2- in carbon tetrachloride,
It is larger to the health effect of people the method use toxic reagent bromine simple substance.
The method of the synthesis bromo- 2- Ethyl Methyl Ether of 1,2- diphenyl -1- has: 1. use aqueous sulfuric acid, potassium bromide, bromic acid
Potassium, trans stilbene and methanol are reactant, synthesized the compound (Agrawal M K, Adimurthy S,
Ganguly B, Tetrahedron, 2009,65 (14): 2791-2797), this method reaction time is longer, and has used dense
Sulfuric acid.2. using PhN+Me3·Br3 -The substance (Nandkishor has been synthesized using methanol as solvent and reactant for bromine source
N,Karade,Sumit V,Gampawar,Girdharilal B,Tiwari, Letters in Organic Chemistry,
4 (6), 419-422), this method generates a large amount of debirs, does not meet the requirement of Green Chemistry.
The above method has pollution, severe reaction conditions, using toxic reagent to environment, therefore there are many insufficient and defect
Find a kind of mild condition, the new method of synthesis two substance easy to operate it is still necessary to.
(3) summary of the invention
To solve present in bromo- 1 methoxyindan of current 2- and the bromo- 2- Ethyl Methyl Ether synthesis of 1,2- diphenyl -1-
The problems such as polluting high larger, toxicity and severe reaction conditions, the present invention provide a kind of safety and environmental protection, reaction condition mild β-
The synthetic method of bromo ether compound.
The present invention adopts the following technical scheme that:
A kind of synthetic method of Beta-bromo ether compound, it is characterised in that: the method carries out in accordance with the following steps:
Respectively using indenes and trans stilbene as raw material, the zinc of methanol, alkali halide and bromate intercalation is added
Aluminum hydrotalcite (ZnAl-BrO3 -- LDHs) and be uniformly mixed, under the action of inorganic acid, it is stirred to react at 25-50 DEG C under normal pressure
1-6 hours, TLC tracking fully reacting obtained that reaction mixture is post-treated to respectively obtain bromo- 1 methoxyindan of 2- and 1,2- bis-
The bromo- 2- Ethyl Methyl Ether of phenyl -1-；Halogen ion in the alkali halide and in the zinc-aluminum hydrotalcite of bromate intercalation
The amount of the substance of bromate the ratio between be 0.5~5:1；Halogen in the indenes or trans stilbene and alkali halide from
The ratio between amount of substance of son is 1:0.5~3.
Further, bromate in the hydrotalcite of the halogen ion in the preferably described alkali halide and bromate intercalation
The amount of substance the ratio between be 1~2:1.
Further, the amount of the preferably described indenes or the substance of the halogen ion in trans stilbene and alkali halide it
Than for 1:1~2.
Further, the volumetric usage of the methanol be calculated as 5 with the amount of the substance of the indenes or trans stilbene~
15mL/mmol, preferably 6~8mL/mmol.
Further, the alkali metal bromide is potassium bromide, sodium bromide or lithium bromide, preferably lithium bromide.
Further, the inorganic acid is hydrochloric acid, nitric acid or sulfuric acid, preferably hydrochloric acid.
Further, the concentration of hydrochloric acid is 0.5-6mol/L, preferably 2mol/L.
Further, the additional amount of the inorganic acid on the basis of dissolving the reactant just.
Further, the post-processing approach of reaction solution of the present invention are as follows: after reaction, gained reaction solution is through being centrifuged off
Hydrotalcite solid, obtained liquid are placed in separatory funnel, and organic solvent and ultrapure water is added, and merge organic phase, acquired solution
Column chromatography silica gel is added, vacuum distillation removes solvent, and it is the petroleum ether of 5:1 with volume ratio that remaining solid is separated through column chromatography
It is eluant, eluent with ethyl acetate, collects the eluent containing target product, the eluent vacuum distillation removes solvent and obtains mesh
Mark product.
Further, the method for the invention is recommended to carry out as follows:
Respectively using indenes and trans stilbene as raw material, the zinc-aluminium neatly of methanol, potassium bromide and bromate intercalation is added
Stone (ZnAl-BrO3 -- LDHs) and it is uniformly mixed, hydrotalcite is dissolved by the way that the hydrochloric acid of 2mol/L is added dropwise, in 25-50 under normal pressure
It being stirred to react at DEG C 1-6 hours, reaction mixture is centrifuged off hydrotalcite solid, and obtained liquid is placed in separatory funnel,
Organic solvent and ultrapure water is added, merges organic phase, column chromatography silica gel is added in acquired solution, and vacuum distillation removes solvent, remaining
Solid is separated through column chromatography, collects the eluent of target product, and eluent is evaporated under reduced pressure away solvent and respectively obtains 2- bromo- 1
Methoxyindan and the bromo- 2- Ethyl Methyl Ether of 1,2- diphenyl -1-；Halogen ion and bromic acid in the alkali halide
In the hydrotalcite of root cutting layer the amount of the substance of bromate the ratio between be 1~2:1；The indenes and trans stilbene and alkali metal
The ratio between amount of substance of halogen ion in halide is 1:1~2；The volume of the methanol is with the indenes or trans- hexichol second
The amount of the substance of alkene is calculated as 6~8mL/mmol.
The zinc-aluminum hydrotalcite ZnAl-BrO for the bromate intercalation that the present invention uses3 --- LDHs, those skilled in the art can be with
It is open according to existing literature (Wang Ligeng, Zheng Feixiang, Jiang Chenxing, Ni Zheming, silicate journal, 2015,43 (5): 672-677.)
Method is voluntarily prepared.(the scope of protection of the present invention is not limited to this)
Compared with prior art, the present invention has the advantage that
The present invention uses the zinc-aluminum hydrotalcite and alkali metal bromide of bromate intercalation, more safety and environmental protection；Reaction condition
More mild, the reaction time is shorter, and yield is preferable；It is easy to operate, the generation of halogen source can be controlled by changing reaction condition
Speed, controllability are strong.
(4) specific embodiment
The present invention is by some embodiment to further illustrate the technical scheme of the present inventions, but protection scope of the present invention is not
It is limited to this.
Accurately weigh 7.55g NaBrO3(AR, 0.05mol) is formulated as 100mL solution and is put into four-hole boiling flask the bottom of as
Liquid；Weigh 29.75g Zn (NO3)2·6H2O (AR, 0.10mol) and 18.75g Al (NO3)3·9H2O (AR, 0.05mol) matches
It is made as 200mL mixing salt solution；Separately weighing 12.00g NaOH (AR, 0.30mol) is configured to 200mL lye；It will using double drop methods
Saline solution and lye are slowly dropped in four-hole boiling flask simultaneously, are stirred strongly under room temperature, and adjusting drop speed and keeping pH value is 7 (± 0.2),
Continue to stir half an hour after dripping.For 24 hours in 70 DEG C of crystallization by gained slurries, filtering and washing is ground after 60 DEG C of dry 18h, is obtained
Product.
Embodiment 1
2mmol (0.232g) indenes, 2mmol (0.174g) lithium bromide are added in 50mL three-neck flask, 12mL is added
Methanol is added dropwise 2mol/L hydrochloric acid stirring and dissolving, is subsequently added into the zinc-aluminum hydrotalcite ZnAl-BrO of 1.2g bromate intercalation3 -- LDHs,
Magnetic agitation 5 hours at 25 DEG C, track fully reacting by TLC.After reaction, it is centrifuged using centrifuge 6000r/min
Zinc-aluminum hydrotalcite solid is removed, gained liquid is placed in separatory funnel, and methylene chloride and deionized water is added, will react resulting
Organic matter is extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes solvent, remaining mixture
Separated by column chromatography, using volume ratio for 5:1 petroleum ether and ethyl acetate as eluant, eluent, collect the elution containing product
Liquid, eluent are evaporated off solvent and obtain pure products, yield 83%.
Characterize data:1H NMR(500MHz,CDCl3)δ7.38-7.25(m,4H),5.05(s, 1H),4.49(s,1H),
3.70-3.25(m,5H)；13C NMR(126MHz,CDCl3)δ 143.20,140.15,129.27,127.37,125.86,
125.32,93.37,58.21,51.43, 42.28；HRMS(ESI,m/s):Calculated for C10H11BrO(M+H)+
227.0072, found 227.0070.
Embodiment 2
2mmol (0.232g) indenes, 2mmol (0.174g) lithium bromide are added in 50mL three-neck flask, 16mL is added
Methanol is added dropwise 2mol/L hydrochloric acid stirring and dissolving, is subsequently added into the zinc-aluminum hydrotalcite ZnAl-BrO of 1.2g bromate intercalation3 -- LDHs,
Magnetic agitation 5 hours at 25 DEG C, track fully reacting by TLC.After reaction, it is centrifuged using centrifuge 6000r/min
Zinc-aluminum hydrotalcite solid is removed, gained liquid is placed in separatory funnel, and methylene chloride and deionized water is added, will react resulting
Organic matter is extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes solvent, remaining mixture
It is separated by column chromatography, collects the eluent containing product, eluent is evaporated off solvent and obtains pure products, yield 83%.
Characterize data:1H NMR(500MHz,CDCl3)δ7.38-7.25(m,4H),5.05(s, 1H),4.49(s,1H),
3.70-3.25(m,5H)；13C NMR(126MHz,CDCl3)δ 143.20,140.15,129.27,127.37,125.86,
125.32,93.37,58.21,51.43, 42.28；HRMS(ESI,m/s):Calculated for C10H11BrO(M+H)+
227.0072, found 227.0070.
Embodiment 3
2mmol (0.232g) indenes, 2mmol (0.174g) lithium bromide are added in 50mL three-neck flask, 12mL is added
Methanol is added dropwise 2mol/L hydrochloric acid stirring and dissolving, is subsequently added into the zinc-aluminum hydrotalcite ZnAl-BrO of 2g bromate intercalation3 -- LDHs, in
Magnetic agitation 5 hours at 25 DEG C, track fully reacting by TLC.After reaction, it is removed using centrifuge 6000r/min centrifugation
Zinc-aluminum hydrotalcite solid is removed, gained liquid is placed in separatory funnel, methylene chloride and deionized water is added, will react resulting has
Machine object is extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes solvent, remaining mixture warp
Column chromatography separation is crossed, the eluent containing product is collected, eluent is evaporated off solvent and obtains pure products, yield 80%.
Characterize data:1H NMR(500MHz,CDCl3)δ7.38-7.25(m,4H),5.05(s, 1H),4.49(s,1H),
3.70-3.25(m,5H)；13C NMR(126MHz,CDCl3)δ 143.20,140.15,129.27,127.37,125.86,
125.32,93.37,58.21,51.43, 42.28；HRMS(ESI,m/s):Calculated for C10H11BrO(M+H)+
227.0072, found 227.0070.
Embodiment 4
2mmol (0.232g) indenes, 2mmol (0.174g) lithium bromide are added in 50mL three-neck flask, 16mL is added
Methanol is added dropwise 2mol/L hydrochloric acid stirring and dissolving, is subsequently added into the zinc-aluminum hydrotalcite ZnAl-BrO of 2g bromate intercalation3 -- LDHs, in
Magnetic agitation 5 hours at 25 DEG C, track fully reacting by TLC.After reaction, it is removed using centrifuge 6000r/min centrifugation
Zinc-aluminum hydrotalcite solid is removed, gained liquid is placed in separatory funnel, methylene chloride and deionized water is added, will react resulting has
Machine object is extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes solvent, remaining mixture warp
Column chromatography separation is crossed, the eluent containing product is collected, eluent is evaporated off solvent and obtains pure products, yield 85%.
Characterize data:1H NMR(500MHz,CDCl3)δ7.38-7.25(m,4H),5.05(s, 1H),4.49(s,1H),
3.70-3.25(m,5H)；13C NMR(126MHz,CDCl3)δ 143.20,140.15,129.27,127.37,125.86,
125.32,93.37,58.21,51.43, 42.28；HRMS(ESI,m/s):Calculated for C10H11BrO(M+H)+
227.0072, found 227.0070.
Embodiment 5
2mmol (0.232g) indenes, 4mmol (0.348g) lithium bromide are added in 50mL three-neck flask, 12mL is added
Methanol is added dropwise 2mol/L hydrochloric acid stirring and dissolving, is subsequently added into the zinc-aluminum hydrotalcite ZnAl-BrO of 1.2g bromate intercalation3 -- LDHs,
Magnetic agitation 5 hours at 25 DEG C, track fully reacting by TLC.After reaction, it is centrifuged using centrifuge 6000r/min
Zinc-aluminum hydrotalcite solid is removed, gained liquid is placed in separatory funnel, and methylene chloride and deionized water is added, will react resulting
Organic matter is extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes solvent, remaining mixture
It is separated by column chromatography, collects the eluent containing product, eluent is evaporated off solvent and obtains pure products, yield 85%.
Characterize data:1H NMR(500MHz,CDCl3)δ7.38-7.25(m,4H),5.05(s, 1H),4.49(s,1H),
3.70-3.25(m,5H)；13C NMR(126MHz,CDCl3)δ 143.20,140.15,129.27,127.37,125.86,
125.32,93.37,58.21,51.43, 42.28；HRMS(ESI,m/s):Calculated for C10H11BrO(M+H)+
227.0072, found 227.0070.
Embodiment 6
2mmol (0.232g) indenes, 4mmol (0.348g) lithium bromide are added in 50mL three-neck flask, 16mL is added
Methanol is added dropwise 2mol/L hydrochloric acid stirring and dissolving, is subsequently added into the zinc-aluminum hydrotalcite ZnAl-BrO of 1.2g bromate intercalation3 -- LDHs,
Magnetic agitation 5 hours at 25 DEG C, track fully reacting by TLC.After reaction, it is centrifuged using centrifuge 6000r/min
Zinc-aluminum hydrotalcite solid is removed, gained liquid is placed in separatory funnel, and methylene chloride and deionized water is added, will react resulting
Organic matter is extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes solvent, remaining mixture
It is separated by column chromatography, collects the eluent containing product, eluent is evaporated off solvent and obtains pure products, yield 80%.
Characterize data:1H NMR(500MHz,CDCl3)δ7.38-7.25(m,4H),5.05(s, 1H),4.49(s,1H),
3.70-3.25(m,5H)；13C NMR(126MHz,CDCl3)δ 143.20,140.15,129.27,127.37,125.86,
125.32,93.37,58.21,51.43, 42.28；HRMS(ESI,m/s):Calculated for C10H11BrO(M+H)+
227.0072, found 227.0070.
Characterize data:1H NMR(500MHz,CDCl3)δ7.38-7.25(m,4H),5.05(s, 1H),4.49(s,1H),
3.70-3.25(m,5H)；13C NMR(126MHz,CDCl3)δ 143.20,140.15,129.27,127.37,125.86,
125.32,93.37,58.21,51.43, 42.28；HRMS(ESI,m/s):Calculated for C10H11BrO(M+H)+
227.0072, found 227.0070.
Embodiment 7
2mmol (0.360g) trans stilbene, 2mmol (0.174g) lithium bromide are added in 50mL three-neck flask,
12mL methanol is added, 2mol/L hydrochloric acid stirring and dissolving is added dropwise, is subsequently added into the zinc-aluminum hydrotalcite ZnAl- of 1.2g bromate intercalation
BrO3 -- LDHs, magnetic agitation 5 hours at 25 DEG C, tracks fully reacting by TLC.After reaction, using centrifuge
6000r/min is centrifuged off zinc-aluminum hydrotalcite solid, and gained liquid is placed in separatory funnel, and methylene chloride and deionization is added
Water will react resulting organic matter and be extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes
Solvent, remaining mixture are separated by column chromatography, collect the eluent containing product, and eluent is evaporated off solvent and obtains pure production
Object, yield 82%.
Characterize data:1H NMR(500MHz,CDCl3) δ 7.33-7.24 (m, 10H), 5.63 (d, J=6.8Hz, 1H),
4.93 (d, J=6.8Hz, 1H), 3.27 (s, 3H)；13C NMR(126 MHz,CDCl3)δ138.23,138.07,129.41,
129.42,128.65,128.72,128.35, 97.17,55.72,50.16；HRMS(ESI,m/s):Calculated for
C15H15BrO (M+H)+291.0385,found 291.0387.
Embodiment 8
2mmol (0.360g) trans stilbene, 2mmol (0.232g) indenes, 2mmol (0.174g) lithium bromide are added
Into 50mL three-neck flask, 16mL methanol is added, 2mol/L hydrochloric acid stirring and dissolving is added dropwise, is subsequently added into 1.2g bromate intercalation
Zinc-aluminum hydrotalcite ZnAl-BrO3 -- LDHs, magnetic agitation 5 hours at 25 DEG C, tracks fully reacting by TLC.Reaction knot
Shu Hou is centrifuged off zinc-aluminum hydrotalcite solid using centrifuge 6000r/min, and gained liquid is placed in separatory funnel, is added two
Chloromethanes and deionized water will be reacted resulting organic matter and be extracted in methylene chloride phase, and column is added in acquired solution and chromatographs silicon
Glue, vacuum distillation remove solvent, and remaining mixture is separated by column chromatography, collect the eluent containing product, and eluent steams
Except solvent obtains pure products, yield 82%.
Characterize data:1H NMR(500MHz,CDCl3) δ 7.33-7.24 (m, 10H), 5.63 (d, J=6.8Hz, 1H),
4.93 (d, J=6.8Hz, 1H), 3.27 (s, 3H)；13C NMR(126 MHz,CDCl3)δ138.23,138.07,129.41,
129.42,128.65,128.72,128.35, 97.17,55.72,50.16；HRMS(ESI,m/s):Calculated for
C15H15BrO (M+H)+291.0385,found 291.0387.
Embodiment 9
2mmol (0.360g) trans stilbene, 2mmol (0.174g) lithium bromide are added in 50mL three-neck flask,
12mL methanol is added, 2mol/L hydrochloric acid stirring and dissolving is added dropwise, is subsequently added into the zinc-aluminum hydrotalcite ZnAl- of 2g bromate intercalation
BrO3 -- LDHs, magnetic agitation 5 hours at 25 DEG C, tracks fully reacting by TLC.After reaction, using centrifuge
6000r/min is centrifuged off zinc-aluminum hydrotalcite solid, and gained liquid is placed in separatory funnel, and methylene chloride and deionization is added
Water will react resulting organic matter and be extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes
Solvent, remaining mixture are separated by column chromatography, collect the eluent containing product, and eluent is evaporated off solvent and obtains pure production
Object, yield 85%.
Characterize data:1H NMR(500MHz,CDCl3) δ 7.33-7.24 (m, 10H), 5.63 (d, J=6.8Hz, 1H),
4.93 (d, J=6.8Hz, 1H), 3.27 (s, 3H)；13C NMR(126 MHz,CDCl3)δ138.23,138.07,129.41,
129.42,128.65,128.72,128.35, 97.17,55.72,50.16；HRMS(ESI,m/s):Calculated for
C15H15BrO (M+H)+291.0385,found 291.0387.
Embodiment 10
2mmol (0.360g) trans stilbene, 2mmol (0.174g) lithium bromide are added in 50mL three-neck flask,
16mL methanol is added, 2mol/L hydrochloric acid stirring and dissolving is added dropwise, is subsequently added into the zinc-aluminum hydrotalcite ZnAl- of 2g bromate intercalation
BrO3 -- LDHs, magnetic agitation 5 hours at 25 DEG C, tracks fully reacting by TLC.After reaction, using centrifuge
6000r/min is centrifuged off zinc-aluminum hydrotalcite solid, and gained liquid is placed in separatory funnel, and methylene chloride and deionization is added
Water will react resulting organic matter and be extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes
Solvent, remaining mixture are separated by column chromatography, collect the eluent containing product, and eluent is evaporated off solvent and obtains pure production
Object, yield 86%.
Characterize data:1H NMR(500MHz,CDCl3) δ 7.33-7.24 (m, 10H), 5.63 (d, J=6.8Hz, 1H),
4.93 (d, J=6.8Hz, 1H), 3.27 (s, 3H)；13C NMR(126 MHz,CDCl3)δ138.23,138.07,129.41,
129.42,128.65,128.72,128.35, 97.17,55.72,50.16；HRMS(ESI,m/s):Calculated for
C15H15BrO (M+H)+291.0385,found 291.0387.
Embodiment 11
2mmol (0.360g) trans stilbene, 4mmol (0.348g) lithium bromide are added in 50mL three-neck flask,
12mL methanol is added, 2mol/L hydrochloric acid stirring and dissolving is added dropwise, is subsequently added into the zinc-aluminum hydrotalcite ZnAl- of 1.2g bromate intercalation
BrO3 -- LDHs, magnetic agitation 5 hours at 25 DEG C, tracks fully reacting by TLC.After reaction, using centrifuge
6000r/min is centrifuged off zinc-aluminum hydrotalcite solid, and gained liquid is placed in separatory funnel, and methylene chloride and deionization is added
Water will react resulting organic matter and be extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes
Solvent, remaining mixture are separated by column chromatography, collect the eluent containing product, and eluent is evaporated off solvent and obtains pure production
Object, yield 82%.
Characterize data:1H NMR(500MHz,CDCl3) δ 7.33-7.24 (m, 10H), 5.63 (d, J=6.8Hz, 1H),
4.93 (d, J=6.8Hz, 1H), 3.27 (s, 3H)；13C NMR(126 MHz,CDCl3)δ138.23,138.07,129.41,
129.42,128.65,128.72,128.35, 97.17,55.72,50.16；HRMS(ESI,m/s):Calculated for
C15H15BrO (M+H)+291.0385,found 291.0387.
Embodiment 12
2mmol (0.360g) trans stilbene, 4mmol (0.348g) lithium bromide are added in 50mL three-neck flask,
16mL methanol is added, 2mol/L hydrochloric acid stirring and dissolving is added dropwise, is subsequently added into the zinc-aluminum hydrotalcite ZnAl- of 1.2g bromate intercalation
BrO3 -- LDHs, magnetic agitation 5 hours at 25 DEG C, tracks fully reacting by TLC.After reaction, using centrifuge
6000r/min is centrifuged off zinc-aluminum hydrotalcite solid, and gained liquid is placed in separatory funnel, and methylene chloride and deionization is added
Water will react resulting organic matter and be extracted in methylene chloride phase, and column chromatography silica gel is added in acquired solution, and vacuum distillation removes
Solvent, remaining mixture are separated by column chromatography, collect the eluent containing product, and eluent is evaporated off solvent and obtains pure production
Object, yield 85%.
Characterize data:1H NMR(500MHz,CDCl3) δ 7.33-7.24 (m, 10H), 5.63 (d, J=6.8Hz, 1H),
4.93 (d, J=6.8Hz, 1H), 3.27 (s, 3H)；13C NMR(126 MHz,CDCl3)δ138.23,138.07,129.41,
129.42,128.65,128.72,128.35, 97.17,55.72,50.16；HRMS(ESI,m/s):Calculated for
C15H15BrO (M+H)+291.0385,found 291.0387。
Claims (9)
1. a kind of synthetic method of Beta-bromo ether compound, it is characterised in that: the method carries out in accordance with the following steps:
Respectively using indenes and trans stilbene as raw material, the zinc-aluminium water of methanol, alkali halide and bromate intercalation is added
Talcum is simultaneously uniformly mixed, and under the action of inorganic acid, is stirred to react at 25-50 DEG C 1-6 hours under normal pressure, and reaction mixing is obtained
Liquid is post-treated to respectively obtain bromo- 1 methoxyindan of 2- and the bromo- 2- Ethyl Methyl Ether of 1,2- diphenyl -1-；The alkali metal
Halogen ion in halide and in the zinc-aluminum hydrotalcite of bromate intercalation the amount of the substance of bromate the ratio between be 0.5~5:1；Institute
The ratio between amount of substance of halogen ion in indenes or trans stilbene and alkali halide stated is 1:0.5~3.
2. the method as described in claim 1, it is characterised in that: halogen ion and bromic acid root cutting in the alkali halide
Layer hydrotalcite in bromate substance amount the ratio between be 1~2:1.
3. the method as described in claim 1, it is characterised in that: in the indenes or trans stilbene and alkali halide
The ratio between the amount of substance of halogen ion be 1:1~2.
4. the method as described in claim 1, it is characterised in that: the volumetric usage of the methanol is with the indenes or trans- two
The amount of the substance of styrene is calculated as 5~15mL/mmol.
5. the method as described in claim 1, it is characterised in that: the alkali metal bromide is potassium bromide, sodium bromide or bromine
Change lithium.
6. the method as described in claim 1, it is characterised in that: the inorganic acid is hydrochloric acid, nitric acid or sulfuric acid.
7. method as claimed in claim 6, it is characterised in that: the concentration of hydrochloric acid is 0.5-6mol/L.
8. method as described in claim 1 or 6, it is characterised in that: the additional amount of the inorganic acid is described to dissolve just
Reactant on the basis of.
9. the method as described in claim 1, it is characterised in that: the post-processing approach of the reaction solution are as follows: after reaction, institute
It obtains reaction solution and is centrifuged off hydrotalcite solid, obtained liquid is placed in separatory funnel, and organic solvent and ultrapure water is added, and is closed
And column chromatography silica gel is added in organic phase, acquired solution, vacuum distillation removes solvent, and remaining solid is separated through column chromatography, with body
Product is eluant, eluent than the petroleum ether and ethyl acetate for being 5:1, collects the eluent containing target product, and the eluent, which depressurizes, to be steamed
Distillation goes solvent to obtain target product.
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