CN109232175A - A kind of preparation method of chloroethyl substituted aromatic compound - Google Patents

A kind of preparation method of chloroethyl substituted aromatic compound Download PDF

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CN109232175A
CN109232175A CN201811131657.6A CN201811131657A CN109232175A CN 109232175 A CN109232175 A CN 109232175A CN 201811131657 A CN201811131657 A CN 201811131657A CN 109232175 A CN109232175 A CN 109232175A
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chloroethyl
aromatic compound
bromo
substituted aromatic
chloroethanes
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杨义
蔡俊杰
罗根
蒋燕
刘应乐
刘晓强
郑玉彬
曾继蛟
高第丰
陆文杰
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Sichuan University of Science and Engineering
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Sichuan University of Science and Engineering
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    • C07C22/02—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings
    • C07C22/04—Cyclic compounds containing halogen atoms bound to an acyclic carbon atom having unsaturation in the rings containing six-membered aromatic rings
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
    • C07C255/50—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton to carbon atoms of non-condensed six-membered aromatic rings
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    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C43/00—Ethers; Compounds having groups, groups or groups
    • C07C43/02—Ethers
    • C07C43/20—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring
    • C07C43/225—Ethers having an ether-oxygen atom bound to a carbon atom of a six-membered aromatic ring containing halogen
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C47/00—Compounds having —CHO groups
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    • C07C47/55—Compounds having —CHO groups bound to carbon atoms of six—membered aromatic rings containing halogen
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    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/02—Esters of acyclic saturated monocarboxylic acids having the carboxyl group bound to an acyclic carbon atom or to hydrogen
    • C07C69/12—Acetic acid esters
    • C07C69/14—Acetic acid esters of monohydroxylic compounds
    • C07C69/145—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols
    • C07C69/157—Acetic acid esters of monohydroxylic compounds of unsaturated alcohols containing six-membered aromatic rings
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    • C07C69/76—Esters of carboxylic acids having a carboxyl group bound to a carbon atom of a six-membered aromatic ring
    • C07C69/78—Benzoic acid esters
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    • 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
    • C07D213/64—One oxygen atom attached in position 2 or 6
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    • C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
    • C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
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    • C07D333/76—Dibenzothiophenes

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Abstract

The invention belongs to organic chlorides preparation technical field, the preparation method of specially a kind of β-chloroethyl substituted aromatic compound.Steps of the method are: under reaction solution and nitrogen atmosphere, using the bromo- 2- chloroethanes of 1- and aryl boric acid as raw material, in the case where the catalyst system and weak base of Raney nickel and bipyridyliums ligand, pyridined additives act on, after heating reaches reaction end, β-chloroethyl substituted aromatic compound is obtained through separating-purifying.Preparation method of the present invention uses commercially available Raney nickel and bipyridyliums ligand cheap and easy to get for catalyst system, realizes that β-chloroethene basal orientation aromatic group orientation introduces, to efficiently prepare β-chloroethyl substituted aromatic compound.This method reaction condition is mild, and cost of material is low, and reaction step is succinctly easy to operate, and reaction scale is easy to amplify, and product separation is easy, is suitable for industrialized production.

Description

A kind of preparation method of chloroethyl substituted aromatic compound
Technical field
The invention belongs to organic chlorides preparation technical field, specially a kind of preparation of chloroethyl substituted aromatic compound Method.
Technical background
For chlorine as one of halogen, chemical property is very active, has significant impact to the production and living of the mankind.Having In machine compound probability, small organic molecule containing chlorine is seen everywhere, and can be used for producing plastics, synthetic rubber, dyestuff etc., is especially being floated Plain boiled water, disinfectant, pharmaceutical synthesis field have very important status.
For example, the antipsychotics chlorpromazine hydrochloride listed, will lose anti-after the molecule loses chlorine atom Mental disease effect；1- (2- chloroethyl) -3- (4- methylcyclohexyl) -1- nitroso ureas (Semustine), to malignant mela noma, Malignant lymphoma, brain tumor, lung cancer etc. have a better effect；1,3- bis- (2- chloroethyl) -1- nitroso ureas (are usually used in brain tumor and cranium Interior metastatic tumor), after this kind of drug containing β-chloroethyl enters human body, pass through OH by lower in physiological conditions-The effect of ion, Forming carbonium ion makes large biological molecule alkanisation, inhibits DNA of tumor cell polymerase, and DNA is inhibited to repair and RNA synthesis.Meanwhile Since the introducing of chlorine atom is so that the fat-soluble of drug increases, bioavilability increases.It is introduced when being aligned in drug molecule aromatic ring Metabolic rate can be slowed down after chlorine or β-chloroethyl to avoid the hydroxylating of aromatic ring, to extend the action time of drug.Therefore it prepares Organic products containing chlorine has significant application value.
In the modification synthesis of these organic molecules containing chlorine, chlorine atom is introduced directly into parent molecule and is introduced β- Chloroethyl segment is relatively common.
Currently, synthesis β-chloroethyl substituted aromatic compound method is concentrated mainly on before beta-hydroxyethyl aromatic compound is Body reacts preparation with thionyl chloride, and specific preparation principle is as follows:
Existing preparation method has the disadvantage that: (1) needing previously-introduced beta-hydroxyethyl segment；(2) make when chlorination reaction Thionyl chloride has toxicity, strong corrosive and tearing property；(3) it is acid to generate hydrogen chloride, sulfur dioxide for this preparation method Exhaust gas is unfavorable for environmental protection, influences green, succinct, safety industrialized production.
In addition, the problems such as energy and material consumption, successive generations of products and environmental protection is always the main problem for perplexing She Lv enterprise.It is special It is not organic chlorides manufacturing enterprise, the problems such as there are raw material route and production technologies to fall behind, technological obsolescence, product cost is high. The core solved these problems is technological progress, therefore, further develops Environmental Safety, succinct efficient, low in cost, is suitable for The β of large-scale production-chloroethyl substituted aromatic compound technology of preparing is of great significance.
Summary of the invention
The purpose of the present invention is to overcome the above shortcomings and to provide a kind of low in cost, simple process is easy to operate, production safety Chloroethyl substituted aromatic compound preparation method.
In order to realize the above goal of the invention, the technical solution of the application are as follows:
A kind of preparation method of chloroethyl substituted aromatic compound comprising following steps:
In reaction solution, under nitrogen atmosphere, using the bromo- 2- chloroethanes of 1- and aryl boric acid as raw material, in Raney nickel Under being acted on the catalyst system and weak base of bipyridyliums ligand, pyridined additives, after heating reaches reaction end, through separating Purification obtains β-chloroethyl substituted aromatic compound.
The step of specific preparation method are as follows:
1) under nitrogen atmosphere, alkali, pyridined additives, bipyridyliums ligand, Raney nickel are added into aryl boric acid And reaction dissolvent, it stirs evenly；
2) the bromo- 2- chloroethanes of 1- is added into above-mentioned solution, it, will be anti-after being heated after sealing, stirring arrival reaction end Liquid is answered to be cooled to room temperature；
3) reaction solution after cooling is obtained into β-chloroethyl substituted aromatic compound after separating-purifying.
Preferably, the ratio between amount of the bromo- 2- chloroethanes of 1- and aryl boric acid substance is 1:1-2.0；The bromo- 2- of 1- The ratio between amount of chloroethanes and alkaloid substance is 1:2.0-4.0；The ratio between the bromo- 2- chloroethanes of 1- and the amount of Raney nickel substance are 100:1-10；The ratio between amount of the bromo- 2- chloroethanes of 1- and bipyridyliums ligand substance is 100:1-10；The bromo- 2- chlorine of 1- The ratio between amount of ethane and pyridined additives substance is 10:1-3.0；The ratio between the bromo- 2- chloroethanes of 1- and reaction dissolvent volume For 1:1-15molL-1。
Preferably, heating and temperature control is 50-80 DEG C, heating time 12-24h.
Preferably, the Ar group of the aryl boric acid is phenyl, C1-4 alkyl-substituted phenyl, C1-4 alkoxy substituted Base, C1-4 acyl group substituted-phenyl, C1-4 alkoxy acyl substituted-phenyl, cyano substituted-phenyl, naphthalene, pyridyl group, dibenzothiophenes Any one or more in base, dibenzofuran group.
Preferably, the alkyl of the C1-4 is methyl, ethyl, propyl, butyl, tert-butyl；The alkane of the C1-4 Oxygroup refers to methoxyl group, ethyoxyl, tert-butoxy；The C1-4 acyl group refers to formoxyl, acetyl group, propiono, bytyry； The C1-4 alkoxy acyl refers to methoxy acyl group, ethoxy acyl group, the third oxygen acyl group, fourth oxygen acyl group.
Preferably, the alkali is sodium carbonate, potassium carbonate, cesium carbonate, potassium acetate, sodium phosphate, potassium phosphate, potassium fluoride, uncle Any one of sodium butoxide, potassium tert-butoxide.Preferably potassium phosphate.
Preferably, the bipyridyliums ligand be 2,2 '-bipyridyls, 4,4 '-dimethyl -2,2 '-bipyridyls, 4,4 ' - Di-t-butyl-bipy 2,2' bipyridyl, 4,4 '-dimethoxys-bipy 2,2' bipyridyl, Phen, α, α, α-terpyridyl are any It is a kind of；It is still more preferably 4,4 '-di-t-butyls-bipy 2,2' bipyridyl.
Preferably, the Raney nickel is Ni (cod)2、NiCl2、NiBr2、NiCl2、NiBr2、Ni(acac)2It is any One kind is still more preferably NiBr2。
Preferably, the pyridined additives are pyridine, 4-dimethylaminopyridine, 4-methoxypyridine, 4- cyano pyrrole Any one of pyridine is still more preferably 4-methoxypyridine.
Preferably, the reaction dissolvent be tetrahydrofuran, dioxane, glycol dimethyl ether, diethylene glycol dimethyl ether, Any one of triethylene glycol dimethyl ether, toluene, dimethyl sulfoxide, n,N-Dimethylformamide, n,N-dimethylacetamide, more into One step is preferably glycol dimethyl ether.
Preferably, the separating-purifying step are as follows: after reaction to terminal, cross the insoluble matter filtered out in reaction solution, ether Insoluble matter is washed, filtrate is collected；Filtrate is poured into water, and using ether aqueous phase extracted, merges organic phase, organic phase washed with water, Saturated sodium-chloride water solution washing, anhydrous sodium sulfate dry, filter, and rotary evaporation removes solvent, and residue is recrystallized or used The isolated β of silica gel column chromatography-chloroethyl substituted aromatic compound.
Compared with prior art, the present invention has the advantage that
(1), the present invention is using the bromo- 2- chloroethanes of the commercially available 1- cheap and easy to get of safety and stability and aryl boric acid as raw material, rich Under the catalyst system effect for producing metalNicatalyst and bipyridine ligand, aryl boric acid is activated using weak base, in glycol dinitrate It is stirred to react in ether solvents and generates β-chloroethyl substituted aromatic compound.The specific advantage of preparation method of the present invention is following several A aspect:
(2), preparation method of the present invention is not necessarily to the previously prepared beta-hydroxyethyl aromatic compound as existing preparation method, It is reacted again with thionyl chloride, but is directly realized by aromatic group and the combination of β-chloroethyl segment, aromatic group selectable range Extensively, reaction is efficient；
(3), preparation method of the present invention uses cheap high yield metallic nickel for catalyst, and bipyridyliums ligand is that support is matched Body, catalyst system is efficient, at low cost；
(4), preparation method reaction condition of the present invention is mild, aryl boric acid selectable range is wide, and reaction scale is easy to expand Greatly, product separation is easy, and no acidic exhaust gas generates more environmental protection, is conducive to industrialized production.
Detailed description of the invention
Fig. 1 is the carbon-13 nmr spectra figure of compound 2- (2- chloroethyl) naphthalene being prepared in embodiment 17；
Fig. 2 is the hydrogen nuclear magnetic resonance spectrogram of compound 2- (2- chloroethyl) naphthalene being prepared in embodiment 17；
Fig. 3 is the carbon-13 nmr spectra of compound 4- (2- chloroethyl) methyl benzoate being prepared in embodiment 20 Figure；
Fig. 4 is the nuclear magnetic resonance spectroscopy of compound 4- (2- chloroethyl) methyl benzoate being prepared in embodiment 20 Figure；
Fig. 5 is the carbon-13 nmr spectra figure of compound 4- (2- chloroethyl) benzonitrile being prepared in embodiment 25；
Fig. 6 is the hydrogen nuclear magnetic resonance spectrogram of compound 4- (2- chloroethyl) benzonitrile being prepared in embodiment 25；
Fig. 7 is the nuclear magnetic resonance carbon of compound 3- (2- the chloroethyl) -2- methoxypyridine being prepared in embodiment 26 Spectrogram；
Fig. 8 is the hydrogen nuclear magnetic resonance of compound 3- (2- the chloroethyl) -2- methoxypyridine being prepared in embodiment 26 Spectrogram.
Specific embodiment
In order to be more clear the objectives, technical solutions, and advantages of the present invention, below in conjunction with example, to the present invention carry out into One step is described in detail.It should be appreciated that specific example described herein is used only for explaining the present invention, rather than limit this hair It is bright.
Below with reference to concrete principle and preparation process to a kind of preparation side of β-chloroethyl substituted aromatic compound of the present invention Method is described in detail.
A kind of preparation method of β-chloroethyl substituted aromatic compound, the preparation method is that in reaction solution, nitrogen Under atmosphere, using the bromo- 2- chloroethanes of 1- and aryl boric acid as raw material, Raney nickel and bipyridyliums ligand catalyst system and Under weak base, pyridined additives effect, after heating reaches reaction end, β-chloroethyl substituted aroma chemical combination is obtained through separating-purifying Object.
β of the present invention-chloroethyl substituted aromatic compound reaction equation is as follows:
β of the present invention-chloroethyl substituted aromatic compound preparation method, under nitrogen atmosphere, with the bromo- 2- chloroethanes of 1- and virtue Ylboronic acid is raw material, in the catalyst system of Raney nickel and bipyridyliums ligand, activates aryl boric acid using weak base, and in pyrrole Under the action of pyridine class additive, heating stirring generates β-chloroethyl substituted aromatic compound in glycol dinitrate ether solvents.
Preparation method of the present invention is not necessarily to the previously prepared beta-hydroxyethyl aromatic compound as existing preparation method, then with two The reaction of chlorine sulfoxide, but it is directly realized by aromatic group and the combination of β-chloroethyl segment, aromatic group selectable range is wide, reaction Efficiently.
In preparation method of the present invention, nitrogen is inert gas, it does not have an effect with reaction substrate, catalyst, in inertia Under gas shield, transition metal-catalyzed species Oxidative inactivation can be effectively prevented.The effect of reaction dissolvent is to provide advantageous anti- Environment is answered, and plays dilution and peptizaiton, avoids the excessively high generation side reaction of local concentration.The effect of alkali is to provide orphan to electricity Son can be coordinated to form complex with the empty p track of boron atom on aryl boric acid, be conducive to the aryl group being connected with boron and turn gold Categoryization.The effect of Raney nickel is to provide catalytic reaction activity center can be significant after bipyridyliums ligand and Raney nickel are coordinated Improve reaction effect.
Further, the ratio between amount of the bromo- 2- chloroethanes of the 1- and aryl boric acid substance is 1:1-2.0；The bromo- 2- chlorine of 1- The ratio between amount of ethane and alkaloid substance is 1:2.0-4.0；The ratio between amount of the bromo- 2- chloroethanes of 1- and Raney nickel substance is 100: 1-10；The ratio between amount of the bromo- 2- chloroethanes of 1- and bipyridyliums ligand substance is 100:1-10；The bromo- 2- chloroethanes of 1- It is 10:1-3.0 with the ratio between the amount of pyridined additives substance；The ratio between the bromo- 2- chloroethanes of 1- and reaction dissolvent volume are 1: 1-15mol·L-1.Under the additional amount setting ratio of above-mentioned various substances, the atom utilization of each raw material is higher, substantially reduces Material loss, economic value are high.
Further, the Ar group of the aryl boric acid is phenyl, C1-4 alkyl-substituted phenyl, C1-4 alkoxy substituted Base, C1-4 acyl group substituted-phenyl, C1-4 alkoxy acyl substituted-phenyl, cyano substituted-phenyl, naphthalene, pyridyl group, dibenzothiophenes One of base, dibenzofuran group are a variety of.Further, the alkyl of the C1-4 be methyl, ethyl, propyl, butyl, Tert-butyl；The alkoxy of the C1-4 refers to methoxyl group, ethyoxyl, tert-butoxy；The C1-4 acyl group refer to formoxyl, Acetyl group, propiono, bytyry；The C1-4 alkoxy acyl refers to methoxy acyl group, ethoxy acyl group, the third oxygen acyl group, fourth oxygen acyl Base.
Further, the alkali is sodium carbonate, potassium carbonate, cesium carbonate, potassium acetate, sodium phosphate, potassium phosphate, potassium fluoride, tertiary fourth One kind of sodium alkoxide, potassium tert-butoxide.Weak base can promote aryl boric acid substrate boron removal, be conducive to the effect for turning metallization, greatly Fast transition-metal catalysis speed.
Further, the bipyridyliums ligand be 2,2 '-bipyridyls, 4,4 '-dimethyl -2,2 '-bipyridyls, 4,4 '-two Tert-butyl-bipy 2,2' bipyridyl, 4,4 '-dimethoxys-bipy 2,2' bipyridyl, Phen, α, α, α-terpyridyl one kind.Connection Pyridine plays the role of stable nickel metal catalytic activity center, can effectively adjust transition metal-catalyzed middle oxidation addition, Each primitive steps such as ligand exchange, reduction elimination.
Further, the Raney nickel is Ni (cod)2、NiCl2、NiBr2、NiCl2、NiBr2、Ni(acac)2One kind. Preferred nickelous bromide belongs to cheap metal catalyst, cheap, can be stabilized in air, with precious metal palladium of the same clan Catalyst is compared, and has the advantage for reducing catalytic reaction cost and charging process simplicity.
Further, the pyridined additives are pyridine, 4-dimethylaminopyridine, 4-methoxypyridine, 4- cyanopyridine One kind.Preferred 4-methoxypyridine, which is conducive to bipyridyliums ligand is cooperateed with to play adjusting, turns metallization processes.
Further, the separating-purifying step are as follows: after reaction to terminal, cross the insoluble matter filtered out in reaction solution, ether is washed Insoluble matter is washed, filtrate is collected；Filtrate is poured into water, and using ether aqueous phase extracted, merges organic phase, organic phase washed with water is satisfied It is washed with sodium-chloride water solution, anhydrous sodium sulfate dries, filters, and rotary evaporation removes solvent, and residue is recrystallized or used silicon The isolated β of plastic column chromatography-chloroethyl substituted aromatic compound.The step of separating-purifying of the present invention is according to the β-being prepared What the characteristic of chloroethyl substituted aromatic compound was designed, those skilled in the art can preferably other efficiently separate mention Pure method is to the separating-purifying of target product, as long as being able to achieve the purpose of product separating-purifying of the present invention.
Have combined with specific embodiments below to a kind of preparation method of β-chloroethyl substituted aromatic compound of the present invention Body explanation.
Embodiment 1: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickel chloride (0.1296g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) stir evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added afterwards, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution It is cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, with less Washed with ether is measured, filtrate is collected.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, Saturated common salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silicagel column After chromatography, product 0.9102g, yield 42% are obtained.
The structured data that product is prepared in this example is characterized as below:
1H NMR(600MHz,CDCl3) δ 7.55 (dd, J=18.6,7.7Hz, 4H), 7.42 (t, J=7.7Hz, 2H), 7.33 (t, J=7.4Hz, 1H), 7.28 (d, J=8.0Hz, 2H), 3.73 (t, J=7.4Hz, 2H), 3.09 (t, J=7.4Hz, 2H)；13C NMR(151MHz,CDCl3)δ140.83,139.89,137.17,129.29,128.82,127.36,127.30, 127.08,44.97,38.84.
Embodiment 2: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) stir evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added afterwards, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution It is cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, on a small quantity Washed with ether collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, satisfies Primary with brine It organic phase, anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column layer After analysis separation, product 1.4953g, yield 69% are obtained.
Embodiment 3: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickel iodide (0.3125g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) stir evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added afterwards, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution It is cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, on a small quantity Washed with ether collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, satisfies Primary with brine It organic phase, anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column layer After analysis separation, product 0.9535g, yield 44% are obtained.
Embodiment 4: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 2,2 '-bipyridyls (0.1562g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) are stirring evenly and then adding into the bromo- 2- of 1- Chloroethanes (1.4341g, 10mmol) is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, and reaction solution is cooled to room temperature, and is made Reaction end is monitored with GC-MS, then filters out insoluble matter in reaction solution with diatomite sand core funnel, a small amount of washed with ether is collected Filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, and saturated common salt water washing has Machine is mutually primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is produced after silica gel column chromatography separates Object 1.1052g, yield 51%.
Embodiment 5: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-dimethoxy -2,2 '-connection Pyridine (0.2162g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) stir evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added afterwards, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution It is cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, on a small quantity Washed with ether collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, satisfies Primary with brine It organic phase, anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column layer After analysis separation, product 0.9969g, yield 46% are obtained.
Embodiment 6: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), Anhydrous potassium carbonate are sequentially added into tube sealing (4.1463g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) stir evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added afterwards, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution It is cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, on a small quantity Washed with ether collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, satisfies Primary with brine It organic phase, anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column layer After analysis separation, product 1.1919g, yield 55% are obtained.
Embodiment 7: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent dioxane (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.2569g, yield 58% are obtained.
Embodiment 8: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvents tetrahydrofurane (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.3869g, yield 64% are obtained.
Embodiment 9: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent acetonitrile (20mL) are stirring evenly and then adding into 1- Bromo- 2- chloroethanes (1.4341g, 10mmol) is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, and reaction solution is cooled to room Temperature monitors reaction end using GC-MS, then filters out insoluble matter in reaction solution with diatomite sand core funnel, a small amount of washed with ether, Collect filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturated common salt washing It is primary to wash organic phase, anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue obtains after silica gel column chromatography separates To product 0.6501g, yield 30%.
Embodiment 10: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent n,N-Dimethylformamide (20mL) stirring The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added after uniformly, is stirred to react 24 hours after sealing in 70 DEG C of oil bath again, instead It answers liquid to be cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, A small amount of washed with ether collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic Phase, saturated common salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel After column chromatography for separation, product 1.3434g, yield 62% are obtained.
Embodiment 11: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), pyridine (0.0791g, 1.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) are stirring evenly and then adding into the bromo- 2- of 1- Chloroethanes (1.4341g, 10mmol) is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, and reaction solution is cooled to room temperature, and is made Reaction end is monitored with GC-MS, then filters out insoluble matter in reaction solution with diatomite sand core funnel, a small amount of washed with ether is collected Filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, and saturated common salt water washing has Machine is mutually primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is produced after silica gel column chromatography separates Object 1.2567g, yield 58%.
Embodiment 12: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), 4- cyanopyridine (0.1041g, 1.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.3000g, yield 60% are obtained.
Embodiment 13: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.6467g, yield 76% are obtained.
Embodiment 14: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
This example is that the comparative example of example 13 is ground with example 13 the difference is that bromination Raney nickel is not added Study carefully influence of the presence to product yield of Raney nickel.The chemistry of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl Reaction equation is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) be stirring evenly and then adding into the bromo- 2- chloroethanes of 1- (1.4341g, 10mmol), it is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooled to room temperature, and is not had using GC-MS monitoring It was found that target product generates.
Embodiment 15: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
This example is the comparative example of example 13, with example 13 the difference is that 4,4 '-di-t-butyl -2 are not added, 2 '-bipyridine ligands study influence of the addition to product yield of the ligand.This example prepare compound 4- (2- chloroethyl)- The chemical equation of 1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent second Glycol dimethyl ether (20mL) is stirring evenly and then adding into the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, 70 DEG C of oil again after sealing It is stirred to react in bath 24 hours, reaction solution is cooled to room temperature, and is monitored reaction end using GC-MS, is then leaked with diatomite sand core Bucket filters out insoluble matter in reaction solution, and a small amount of washed with ether collects filtrate.20mL water, ether aqueous phase extracted three are added into filtrate Secondary (20mL X 3) merges organic phase, and saturated common salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation Recycling design, residue obtain product 0.1517g, yield 7% after silica gel column chromatography separates.
Embodiment 16: the preparation of compound 4- (2- chloroethyl) -1,1'- biphenyl
This example is the comparative example of example 13, is carried out the difference is that not being added to 4- biphenylboronic acid with example 13 The weak base anhydrous phosphoric acid potassium of activation, studies influence of the addition to product yield of weak base.This example prepare compound 4- (2- chloroethene Base) -1,1'- biphenyl chemical equation it is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- biphenylboronic acid (2.9705g, 15.0mmol), 4- methoxyl group pyrrole are sequentially added into tube sealing Pyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) be stirring evenly and then adding into the bromo- 2- chloroethanes of 1- (1.4341g, 10mmol), it is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooled to room temperature, and uses GC-MS monitoring reaction Terminal, then filters out insoluble matter in reaction solution with diatomite sand core funnel, and a small amount of washed with ether collects filtrate.Add into filtrate Enter 20mL water, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturated common salt water washing organic phase is primary, anhydrous sulphur Sour sodium dries, filters, rotary evaporation recycling design, and residue obtains product 0.0867g, yield after silica gel column chromatography separates It is 4%.
Embodiment 17: the preparation of compound 2- (2- chloroethyl) naphthalene
The chemical equation of this example prepare compound 2- (2- chloroethyl) naphthalene is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 2- naphthalene boronic acids (2.5799g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.3919g, yield 73% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 7.83-7.76 (m, 3H), 7.65 (s, 1H), 7.45 (dq, J=6.8,5.4Hz, 2H), 7.32 (dd, J=8.4,1.7Hz, 1H), 3.78 (t, J=7.4Hz, 2H), 3.21 (t, J=7.4Hz, 2H)；13C NMR (151MHz,CDCl3)δ135.56,133.52,132.44,128.28,127.70,127.62,127.46,127.04, 126.21,125.72,44.92,39.33.
Embodiment 18: the preparation of compound 4- (2- chloroethyl) benzaldehyde
The chemical equation of this example prepare compound 4- (2- chloroethyl) benzaldehyde is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- formylphenylboronic acid (2.2491g, 15.0mmol), anhydrous phosphorus are sequentially added into tube sealing Sour potassium (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.0960g, yield 65% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR (600MHz, CDCl3) δ 10.00 (s, 1H), 7.85 (d, J=8.1Hz, 2H), 7.40 (d, J=8.0Hz, 2H), 3.77 (t, J=7.1Hz, 2H), 3.16 (t, J=7.1Hz, 2H)；13C NMR(151MHz,CDCl3)δ191.86, 145.13,135.29,130.06,129.57,44.22,39.03.
Embodiment 19: the preparation of compound 1- (4- (2- chloroethyl) phenyl) ethyl ketone
The chemical equation of this example prepare compound 1- (4- (2- chloroethyl) phenyl) ethyl ketone is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- acetylbenzene boric acid (2.4596g, 15.0mmol), anhydrous phosphorus are sequentially added into tube sealing Sour potassium (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.0046g, yield 55% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 7.93 (d, J=8.2Hz, 2H), 7.33 (d, J=8.1Hz, 2H), 3.75 (t, J =7.2Hz, 2H), 3.14 (t, J=7.2Hz, 2H), 2.60 (s, 3H)；13C NMR(151MHz,CDCl3)δ197.75, 143.58,135.91,129.11,128.70,44.37,38.89,26.63.
Embodiment 20: the preparation of compound 4- (2- chloroethyl) methyl benzoate
The chemical equation of this example prepare compound 4- (2- chloroethyl) methyl benzoate is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- methoxycarbonyl group phenyl boric acid (2.7006g, 15.0mmol), anhydrous is sequentially added into tube sealing Potassium phosphate (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-connection pyrroles Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) is after mixing evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reacts liquid cooling But to room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, Shao Liangyi with diatomite sand core funnel Ether rinses, and collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation Brine It organic phase is primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column chromatography After separation, product 1.3906g, yield 70% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 8.00 (d, J=8.2Hz, 2H), 7.30 (d, J=8.2Hz, 2H), 3.91 (s, 3H), 3.74 (t, J=7.2Hz, 2H), 3.12 (t, J=7.2Hz, 2H)13C NMR(151MHz,CDCl3)δ166.92, 143.33,129.90,128.90,128.87,52.10,44.38,38.95.
Embodiment 21: the preparation of compound 4- (2- chloroethyl) dibenzo [b, d] furans
The chemical equation of this example prepare compound 4- (2- chloroethyl) dibenzo [b, d] furans is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- dibenzofurans boric acid (3.1802g, 15.0mmol), anhydrous is sequentially added into tube sealing Potassium phosphate (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-connection pyrroles Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) is after mixing evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reacts liquid cooling But to room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, Shao Liangyi with diatomite sand core funnel Ether rinses, and collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation Brine It organic phase is primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column chromatography After separation, product 1.0612g, yield 46% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 7.95 (d, J=7.7Hz, 1H), 7.86 (d, J=8.7Hz, 1H), 7.58 (s, 1H), 7.46 (t, J=8.2Hz, 1H), 7.32 (ddd, J=18.2,14.8,7.4Hz, 3H), 3.93 (t, J=7.5Hz, 2H), 3.45 (t, J=7.5Hz, 2H)13C NMR(151MHz,CDCl3)δ156.02,154.66,127.98,127.22,124.36, 124.21,122.85,122.81,121.99,120.78,119.47,111.74,43.52,33.76.
Embodiment 22: the preparation of compound 4- (2- chloroethyl) dibenzo [b, d] thiophene
The chemical equation of this example prepare compound 4- (2- chloroethyl) dibenzo [b, d] thiophene is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- dibenzothiophenes boric acid (3.4211g, 15.0mmol), anhydrous is sequentially added into tube sealing Potassium phosphate (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-connection pyrroles Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) is after mixing evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reacts liquid cooling But to room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, Shao Liangyi with diatomite sand core funnel Ether rinses, and collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation Brine It organic phase is primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column chromatography After separation, product 1.2388g, yield 53% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 8.17-8.11 (m, 1H), 8.06 (d, J=7.8Hz, 1H), 7.88-7.84 (m, 1H), 7.50-7.41 (m, 3H), 7.33 (d, J=7.3Hz, 1H), 3.90 (t, J=7.5Hz, 2H), 3.36 (t, J=7.5Hz, 2H).13C NMR(151MHz,CDCl3)δ139.29,138.85,136.06,136.02,132.29,127.10,126.90, 124.92,124.59,122.87,121.83,120.40,42.89,38.42.
Embodiment 23: the preparation of compound 1- (tert-butyl) -4- (2- chloroethyl) benzene
The chemical equation of this example prepare compound 1- (tert-butyl) -4- (2- chloroethyl) benzene is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- tert-butylbenzeneboronic acid (2.6706g, 15.0mmol), anhydrous phosphorus are sequentially added into tube sealing Sour potassium (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 0.9049g, yield 46% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 7.34 (d, J=8.3Hz, 2H), 7.16 (d, J=8.2Hz, 2H), 3.70 (t, J =7.6Hz, 2H), 3.04 (t, J=7.6Hz, 2H), 1.31 (s, 3H)；13C NMR(151MHz,CDCl3)δ149.78, 135.05,128.49,125.52,45.03,38.76,34.47,31.37.
Embodiment 24: the preparation of compound 1- (2- chloroethyl) -4- methoxybenzene
The chemical equation of this example prepare compound 1- (2- chloroethyl) -4- methoxybenzene is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- methoxyphenylboronic acid (2.2790g, 15.0mmol), anhydrous phosphorus are sequentially added into tube sealing Sour potassium (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 0.8020g, yield 47% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 7.14 (d, J=8.5Hz, 2H), 6.86 (d, J=8.5Hz, 2H), 3.79 (s, 3H), 3.67 (t, J=7.5Hz, 2H), 3.01 (t, J=7.5Hz, 2H)；13C NMR(151MHz,CDCl3)δ158.54, 130.19,129.83,114.00,55.27,45.31,38.36.
Embodiment 25: the preparation of compound 4- (2- chloroethyl) benzonitrile
The chemical equation of this example prepare compound 4- (2- chloroethyl) benzonitrile is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- cyanophenylboronic acid (2.2041g, 15.0mmol), anhydrous phosphoric acid are sequentially added into tube sealing Potassium (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 1.6556g, yield 61% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 7.62 (d, J=8.1Hz, 2H), 7.35 (d, J=8.1Hz, 2H), 3.74 (t, J =6.9Hz, 2H), 3.13 (t, J=6.9Hz, 2H)；13C NMR(151MHz,CDCl3)δ143.51,132.38,129.71, 118.79,110.92,44.07,38.85.
Embodiment 26: the preparation of compound 3- (2- chloroethyl) -2- methoxypyridine
The chemical equation of this example prepare compound 3- (2- chloroethyl) -2- methoxypyridine is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 2- methoxypyridine -3- boric acid (2.5644g, 15.0mmol), nothing are sequentially added into tube sealing Water potassium phosphate (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) stir evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added afterwards, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution It is cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, on a small quantity Washed with ether collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, satisfies Primary with brine It organic phase, anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column layer After analysis separation, product 1.0984g, yield 64% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 8.09 (dd, J=5.0,1.8Hz, 1H), 7.46 (d, J=8.8Hz, 1H), 6.86 (dd, J=7.1,5.1Hz, 1H), 3.98 (s, 3H), 3.74 (t, J=7.1Hz, 2H), 3.04 (t, J=7.1Hz, 2H)；13C NMR(151MHz,CDCl3)δ162.00,145.18,139.31,120.67,116.74,53.63,43.06,33.80.
Embodiment 27: compound 3- (2- chloroethyl) -1,1'- biphenyl
The chemical equation of this example prepare compound 4- (2- chloroethyl) -1,1'- biphenyl is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 3- biphenylboronic acid (2.9705g, 15.0mmol), anhydrous phosphoric acid potassium are sequentially added into tube sealing (6.3681g, 30mmol), DMAP (4-dimethylaminopyridine) (0.2443g, 2.0mmol), 4,4 '-di-t-butyl -2,2 '-connection Pyridine (0.2684g, 1.0mmol), nickel chloride (0.1296g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) stir evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added afterwards, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution It is cooled to room temperature, monitors reaction end using GC-MS, then filter out insoluble matter in reaction solution with diatomite sand core funnel, on a small quantity Washed with ether collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, satisfies Primary with brine It organic phase, anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column layer After analysis separation, product 1.3867g, yield 46% are obtained.
The structured data that product is prepared in this example is characterized as below:
1H NMR(600MHz,CDCl3) δ 7.58 (d, J=7.7Hz, 2H), 7.48 (d, J=7.7Hz, 1H), 7.44 (t, J =7.7Hz, 3H), 7.39 (t, J=7.6Hz, 1H), 7.35 (d, J=14.8Hz, 1H), 7.20 (d, J=7.5Hz, 1H), 3.76 (t, J=7.5Hz, 2H), 3.13 (t, J=7.4Hz, 2H)；13C NMR(151MHz,CDCl3)δ141.64,141.01, 138.59,129.03,128.80,127.76,127.72,127.40,127.21,125.80,44.97,39.27.
Embodiment 28: the preparation of compound 3- (2- chloroethyl) methyl benzoate
The chemical equation of this example prepare compound 3- (2- chloroethyl) methyl benzoate is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 4- methoxycarbonyl group phenyl boric acid (2.7006g, 15.0mmol), anhydrous is sequentially added into tube sealing Potassium phosphate (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-connection pyrroles Pyridine (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) is after mixing evenly The bromo- 2- chloroethanes (1.4341g, 10mmol) of 1- is added, is stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reacts liquid cooling But to room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, Shao Liangyi with diatomite sand core funnel Ether rinses, and collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation Brine It organic phase is primary, and anhydrous sodium sulfate dries, filters, and rotary evaporation recycling design, residue is through silica gel column chromatography After separation, product 0.8940g, yield 45% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 7.94 (d, J=7.5Hz, 1H), 7.91 (s, 1H), 7.43 (d, J=7.5Hz, 1H), 7.40 (t, J=7.5Hz, 1H), 3.92 (s, 3H), 3.74 (t, J=7.6Hz, 2H), 3.12 (t, J=7.2Hz, 2H)；13C NMR(151MHz,CDCl3)δ166.97,138.42,133.50,130.50,129.92,128.64,128.17,52.17, 44.66,38.77.
Embodiment 29: the preparation of compound 3- (2- chloroethyl) benzaldehyde
The chemical equation of this example prepare compound 4- (2- chloroethyl) benzaldehyde is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 3- formylphenylboronic acid (2.2491g, 15.0mmol), anhydrous phosphorus are sequentially added into tube sealing Sour potassium (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 0.8599g, yield 51% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3) δ 10.02 (s, 1H), 7.80-7.77 (m, 1H), 7.76 (s, 1H), 7.51 (d, J= 5.5Hz, 2H), 3.76 (t, J=7.1Hz, 2H), 3.16 (t, J=7.1Hz, 2H)；13C NMR(151MHz,CDCl3)δ 192.25,139.20,136.73,135.07,129.68,129.28,128.73,44.55,38.59.
Embodiment 30: the preparation of compound 1- (3- (2- chloroethyl) phenyl) ethyl ketone
The chemical equation of this example prepare compound 1- (3- (2- chloroethyl) phenyl) ethyl ketone is as follows:
Specific preparation process is as follows:
Under nitrogen atmosphere, 3- acetylbenzene boric acid (2.4596g, 15.0mmol), anhydrous phosphorus are sequentially added into tube sealing Sour potassium (4.2454g, 20mmol), 4-methoxypyridine (0.3273g, 3.0mmol), 4,4 '-di-t-butyl -2,2 '-bipyridyls (0.2684g, 1.0mmol), nickelous bromide (0.2185g, 1.0mmol), solvent ethylene glycol dimethyl ether (20mL) add after mixing evenly Enter the bromo- 2- chloroethanes (1.4341g, 10mmol) of 1-, be stirred to react 24 hours in 70 DEG C of oil bath again after sealing, reaction solution is cooling To room temperature, reaction end is monitored using GC-MS, then filters out insoluble matter in reaction solution, a small amount of ether with diatomite sand core funnel It rinses, collects filtrate.20mL water is added into filtrate, ether aqueous phase extracted three times (20mL X 3), merges organic phase, saturation food Salt water washing organic phase is primary, and anhydrous sodium sulfate dries, filters, rotary evaporation recycling design, and residue is through silica gel column chromatography point From rear, product 0.9498g, yield 52% are obtained.
The product structure data characterization that this example obtains is as follows:
1H NMR(600MHz,CDCl3)δ7.86–7.84(m,1H),7.83(s,1H),7.45–7.40(m,2H),3.75 (t, J=7.2Hz, 2H), 3.13 (t, J=7.2Hz, 2H), 2.61 (s, 3H)；13C NMR(151MHz,CDCl3)δ198.06, 138.67,137.45,133.66,128.83,128.55,127.09,44.69,38.80,26.69.
The bromo- 2- chloroethanes needs of reaction raw materials 1- are eventually adding in the present invention, otherwise conversion ratio can be made to reduce.System of the present invention The addition sequence of reactant and preparation step are that inventor passes through long-term experiment in Preparation Method, obtained in conjunction with yield optimization, Product yield can effectively be obtained.
The foregoing is merely certain embodiments of the invention, are not intended to limit the invention, all in spirit and original of the invention Made any modifications, equivalent replacements, and improvements etc., should all be included in the protection scope of the present invention within then.

Claims (9)

1. a kind of β-chloroethyl substituted aromatic compound preparation method, it is characterised in that the following steps are included: in reaction dissolvent And under the atmosphere of nitrogen, using the bromo- 2- chloroethanes of 1- and aryl boric acid as raw material, in the catalysis of Raney nickel and bipyridyliums ligand Under the action of system and weak base, pyridined additives, after heating reaches reaction end, β-chloroethyl is obtained through separating-purifying and is taken For aromatic compound；The ratio between amount of the bromo- 2- chloroethanes of 1- and aryl boric acid substance is 1:1-2.0；The bromo- 2- chloroethene of 1- The ratio between amount of alkane and alkaloid substance is 1:2.0-4.0；The ratio between amount of the bromo- 2- chloroethanes of 1- and Raney nickel substance is 100:1- 10；The ratio between amount of the bromo- 2- chloroethanes of 1- and bipyridyliums ligand substance is 100:1-10；The bromo- 2- chloroethanes of 1- with The ratio between amount of pyridined additives substance is 10:1-3.0；The ratio between the bromo- 2- chloroethanes of 1- and reaction dissolvent volume are 1:1- 15mol·L-1。
2. β as described in claim 1-chloroethyl substituted aromatic compound preparation method, which is characterized in that the aryl boric acid Ar group be phenyl, C1-4 alkyl-substituted phenyl, C1-4 alkoxy substituted phenyl, C1-4 acyl group substituted-phenyl, C1-4 alcoxyl Acyl group substituted-phenyl, cyano substituted-phenyl, naphthalene, pyridyl group, dibenzothiophene, in dibenzofuran group any one or It is a variety of.
3. β as described in claim 1-chloroethyl substituted aromatic compound preparation method, which is characterized in that the alkali is carbon It is any one in sour sodium, potassium carbonate, cesium carbonate, potassium acetate, sodium phosphate, potassium phosphate, potassium fluoride, sodium tert-butoxide and potassium tert-butoxide Kind.
4. β as described in claim 1-chloroethyl substituted aromatic compound preparation method, which is characterized in that the bipyridyliums Ligand is bipy 2,2' bipyridyl, 4,4 '-dimethyl-bipy 2,2' bipyridyl, 4,4 '-di-t-butyls-bipy 2,2' bipyridyl, 4,4 '-diformazans Oxygroup-bipy 2,2' bipyridyl, Phen and α, α, any one in α-terpyridyl.
5. β as described in claim 1-chloroethyl substituted aromatic compound preparation method, which is characterized in that the Raney nickel For Ni (cod)2、NiCl2、NiBr2、NiCl2、NiBr2、Ni(acac)2In any one.
6. β as described in claim 1-chloroethyl substituted aromatic compound preparation method, which is characterized in that the pyridines add Adding agent is any one in pyridine, 4-dimethylaminopyridine, 4-methoxypyridine and 4- cyanopyridine.
7. β as described in claim 1-chloroethyl substituted aromatic compound preparation method, which is characterized in that the reaction is molten Agent is tetrahydrofuran, dioxane, glycol dimethyl ether, diethylene glycol dimethyl ether, triethylene glycol dimethyl ether, toluene, diformazan Asia Any one in sulfone, N,N-dimethylformamide and DMAC N,N' dimethyl acetamide.
8. β as described in claim 1-chloroethyl substituted aromatic compound preparation method, which is characterized in that the separating-purifying Step are as follows: after reaction to terminal, cross the insoluble matter filtered out in reaction solution, ether washs insoluble matter, collects filtrate；Filtrate pours into water In, using ether aqueous phase extracted, merge organic phase, organic phase washed with water, saturated sodium-chloride water solution washing, anhydrous sodium sulfate It dries, filters, rotary evaporation removes solvent, and residue is recrystallized or replaces virtue with the isolated β of silica gel column chromatography-chloroethyl Aroma compounds.
9. β as claimed in claim 2-chloroethyl substituted aromatic compound preparation method, which is characterized in that the C1-4's Alkyl is methyl, ethyl, propyl, butyl or tert-butyl；The alkoxy of the C1-4 is methoxyl group, ethyoxyl or tertiary fourth oxygen Base；The C1-4 acyl group is formoxyl, acetyl group, propiono, bytyry；The C1-4 alkoxy acyl be methoxy acyl group, Ethoxy acyl group, the third oxygen acyl group or fourth oxygen acyl group.
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CN106748638A (en) * 2016-11-17 2017-05-31 四川理工学院 A kind of preparation method of trifluoroethyl substituted arene compound
CN107628926A (en) * 2017-09-29 2018-01-26 四川理工学院 A kind of preparation method of single fluoro ethyl substituted aromatic compound

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CN106748638A (en) * 2016-11-17 2017-05-31 四川理工学院 A kind of preparation method of trifluoroethyl substituted arene compound
CN107628926A (en) * 2017-09-29 2018-01-26 四川理工学院 A kind of preparation method of single fluoro ethyl substituted aromatic compound

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XIAO Y L ET AL.: "Nickel‐Catalyzed Difluoroalkylation of (Hetero)Arylborons with Unactivated 1‐Bromo‐1,1‐difluoroalkanes", 《ANGEWANDTE CHEMIE》 *
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