CN106431824A - Industrial production method of 3,3'-difluorobiphenyl - Google Patents
Industrial production method of 3,3'-difluorobiphenyl Download PDFInfo
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- CN106431824A CN106431824A CN201610653088.6A CN201610653088A CN106431824A CN 106431824 A CN106431824 A CN 106431824A CN 201610653088 A CN201610653088 A CN 201610653088A CN 106431824 A CN106431824 A CN 106431824A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C17/00—Preparation of halogenated hydrocarbons
- C07C17/26—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton
- C07C17/263—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions
- C07C17/2632—Preparation of halogenated hydrocarbons by reactions involving an increase in the number of carbon atoms in the skeleton by condensation reactions involving an organo-magnesium compound, e.g. Grignard synthesis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/50—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom condensed with carbocyclic rings or ring systems
- C07D333/76—Dibenzothiophenes
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/20—Air quality improvement or preservation, e.g. vehicle emission control or emission reduction by using catalytic converters
Abstract
The invention relates to a novel, safe, economical and environment-friendly production method of a useful chemical 3,3'-difluorobiphenyl. High-purity 3,3'-difluorobiphenyl can be prepared and obtained in a high-yield manner by making 3-fluorophenyl halogenated magnesium react with 1,2-dihalogenethane under the catalytic action of a trivalent ferric salt, and then treating a product by using an alkali or an acid. In addition, the method comprises a step of using and recycling an ethylene gas released in the reaction to prepare the initial raw material 1,2-dihalogenethane of the reaction, wherein the ethylene gas is a potential air pollutant.
Description
Technical field
The present invention relates to a kind of industrial production high-purity 3, the method for the compound of 3 '-DfBP, this compound is system
Standby electrophilic trifluoromethyl reagent 2,8-bis-fluoro-S-(trifluoromethyl) benzothiophene salt and 2,6-bis-fluoro-S-(trifluoromethyl) benzene
The key intermediate of bithiophene salt.
Background technology
Owing to trifluoromethyl functional group is at the effective medicine of exploitation, most important when agricultural chemicals and other useful materials, three
The practical system Preparation Method of fluoromethylation compound attracts great attention and (for example, sees, J.Fluorine Chem.2006,127,1013-
1029；Chem.Soc.Rev.,2008,37,230-330；“Fluorine and the environment”,Vol.2,
Chapter 4,“Fluorine-Containing Agrochemicals:An Overview of Recent
Development”,pp 121-175(2006)(ISSN 1872-0358)).Thus new highly active electrophilic trifluoromethylation
Reagent, 2,8-bis-fluoro-S-(trifluoromethyl) benzothiophene fluoroform sulphonates (A) and 2,6-bis-fluoro-S-(trifluoromethyl) benzo
Thiophene fluoroform sulphonate (B) has been synthesized, and is effectively applied to prepare trifluoromethyl compound and (for example, sees ginseng
Examine embodiment 2 and 3 and WO2016107578).As shown in reaction equation 1, trifluoromethyl reagent (A) and (B) are by 3,3 '-two
Fluorine biphenyl one kettle way prepares.Therefore, 3,3 '-DfBP is to produce in the middle of the key of useful trifluoromethyl reagent
Body.
[equation 1]
The production method of disclosed 3,3 '-DfBP is as described below：
(1) coupling reaction that 3-fluorochlorobenzene and 3-fluorobenzoic boric acid occur under palladium chtalyst effect prepares (Beilstein
Journal of Organic Chemistry, 2007,3, No 18)；
(2) 3-fluorobenzoic boric acid is at Cu2HOMO coupling is occurred to prepare under-β-CD catalytic action
(Eur.J.Org.Chem.2011,6656-6662)；
(3) 3-fluorobenzoic boric acid is at CuSO4Under catalytic action occur HOMO coupling prepare (Synthesis.2011,
No.1,91-96)；
(4) 3-fluorobenzoic boric acid is at Fe3O4-Cu2HOMO coupling is occurred to prepare (Green under-β-CD catalytic action
Chem,2013,15,2266-2274)；
(5) 3-fluorine iodobenzene occurs HOMO coupling to prepare (CN 101745385) under Pd/Shell catalytic action；
(6) 3-fluorine iodobenzene occurs HOMO coupling to prepare under sulfur-bearing ring palladium complex (containing palladium) catalytic action
(Tetrahedron Lett.,43(2002)2327-2329)；
(7) 3-fluorine iodobenzene occur under Pd/PCMS catalytic action HOMO coupling prepare (Green Chem., 2011,
13,350-356and Journal of Organometallic Chemistry 704(2012)29-37)；
(8) 3-fluorine iodobenzene is at Pd (dppf) Cl2Under catalytic action occur HOMO coupling prepare (J.Org.Chem.,
2010,75,2556-2563)；
(9) 3-fluorophenyl diazonium tetrafluoroborate occurs HOMO coupling to prepare under frerrous chloride effect
(Tetrahedron Lett.,53(2012)6269-6272and Journal of Chemical Research,2012,
672-674)；
(10) 3-bromofluorobenzene and 3-fluorobenzoic boric acid occur coupling to prepare under perfluoroalkyl phosphate/palladium effect
(Organometallics2012,31,1329-1334)；
But, in commercial Application, there is obvious shortcoming in these conventional methods.If desired for the palladium catalyst using costliness
The raw material such as 3-fluorobenzoic boric acid (method 1,2,3,4 and 10) or potential explosive of (method 1,5,6,7,8 and 10) or high cost
Initiation material such as 3-fluorophenyl diazol (method 9).
On the other hand, document discloses 4-flourophenyl magnesium bromide at FeCl3Catalytic action under, with 1,2-dichloroethanes is anti-
Should prepare 4,4 '-DfBP, yield 78% (Org.Lett., 2005,7,1943-1946).Disclosed reaction is 4-
The reaction of fluorophenyhnagnesium halide.But, this report does not has any data not have any enlightenment to show that 3-fluorophenyhnagnesium halide exists yet
This reaction can obtain identical result.It is known that 4-fluorine (contraposition) and 3-fluorine (meta) substitution reaction activity have huge
Difference.Reaction on phenyl ring, contraposition fluorine replace have strong to electro, but meta fluorine replaces to electro (example
As seen, Journal of Chemical Education, 2003,80,679-690).Therefore, the substituted system of actually 3-fluorine
Row compound is it could not be expected that obtain identical result with 4-fluorine substituted series.
Content of the invention
The invention provides a kind of 3, the novel safety of 3 '-DfBP, economic and environment-friendly production method, this is useful for producing
The important intermediate of electrophilic trifluoromethyl reagent.
For solving the problems referred to above, the comprehensive in-depth study of the present inventor 3, the industry of 3 '-DfBP a kind of novelty is raw
Product method.As a result, they successfully develop 3, this novel safety of 3 '-DfBP, economic and environment-friendly production method, the method
Overcome all problems discussed above.
The present invention relates to the production method of the biphenyl of key intermediate 3,3 '-tetrafluoro shown in Formulas I.
Molecule formula (I):
The invention provides the preparation method (technique I) of 3,3 '-DfBP shown in formula (I)：This method is formula (II)
Shown 3-fluorophenyl halo magnesium and the 1,2-dihalo-ethane shown in formula (III) react under the effect of the molysite shown in formula (IV)
Prepare；
X′CH2CH2X′--------------------------(III)
Fe(X″)3--------------------------(IV)
Wherein said X, X ', X " it each is independently expressed as chlorine, bromine, atomic iodine.
The present invention further provides and prepares highly purified 3, the purification process (technique II) of 3 '-DfBP, we
Method is technique I gained crude product alkali lye or acid solution processes and prepares.
The present invention comprises ethylene gas and the chlorine (Cl discharging in technique I further2), bromine (Br2) or iodine (I2) anti-
Should prepare 1 described in formula (III), 2-dihalo-ethane, gained 1,2-dihalo-ethane can make as the initiation material of technique I
With.
Technique I of the present invention, II, III, as shown in Table 2.
[equation 2]：
(wherein said X, X ', X " it is expressed as chlorine, bromine, atomic iodine)
[technique I]
Technique I by the 3-fluorophenyhnagnesium halide shown in formula (II) under the molysite effect shown in formula (IV) with formula (III) institute
Show that the reaction of 1,2-dihalo-ethane prepares the described product of formula (I).
3-fluorophenyl halo magnesium used in technique I, can be by many institutes as using one of more popular RMgBr
Prepared by known grignard reaction, i.e. 3-fluorine halobenzene easily prepares with reactive magnesium.Preparation 3-fluorophenyhnagnesium halide, typically
Technique be 3-fluorine halobenzene at ether solvents such as ether, with reactive magnesium in oxolane；Also can be by 3-fluorine halobenzene and alkyl halide magnesium
Grignard exchange prepares, and conventional alkyl halide magnesium has methyl-magnesium-halide, isopropyl magnesium halide.
3-fluorine halobenzene described in technique I has 3-fluorochlorobenzene, 3-bromofluorobenzene, 3-fluorine iodobenzene.These all can be commercially available.Examine
Consider and arrive Cost Problems, preferably 3-fluorochlorobenzene or 3-bromofluorobenzene.
In technique I used 1,2-dihalo-ethane is 1,2-dichloroethanes, 1,2-Bromofume, 1,2-ethylidene periodide.These
All can be commercially available.Wherein consider availability, preferably 1,2-dichloroethanes, 1,2-Bromofume, it is contemplated that yield and
Cost, more preferably 1,2-dichloroethanes.On the basis of 1mol 3-fluorophenyl halo magnesium, selected scope is about 0.4mol---and is about
1.0mol, preferably scope are about 0.5mol---and are about 0.7mol.
The molysite shown in formula (IV) described in technique I has FeF3,FeCl3,FeBr3,FeI3.Consider can supply and valency
Lattice, preferably FeCl3Or FeBr3, more preferably FeCl3.These molysite are commercially available.Molysite amount used is compared to 3-fluorophenyl halogen
It is catalytic amount for magnesium.On the basis of 1mol 3-difluorophenyl halo magnesium, selected scope is about 0.5mol%---and is about 20%, excellent
Select scope to be about 0.5mol%---and be about 10%, more preferably from about 1mol%---about 5mol%.
Reaction described in technique I is preferably used solvent.In reaction, solvent for use has ethers, such as ether, propyl ether, isopropyl ether,
Methyl tertiary butyl ether(MTBE), oxolane, 2-methyltetrahydrofuran, 1,2-dimethoxy-ethane, dioxane etc.；Aromatic series kind solvent
Such as benzene, toluene, dimethylbenzene etc.；Alkane solvents such as pentane, hexane, heptane and octane etc.；And their mixture.Consider to produce
The yield of product, preferably ethers such as ether and oxolane, it is contemplated that safety operation, more preferably oxolane in ether.
Reaction temperature range of choice described in technique I can be from about-60 DEG C---and about+100 DEG C.For making to obtain high yield product,
Preferably-20 DEG C---about+65 DEG C.Operate and economy due to easy, more preferably from about 0 DEG C---about+50 DEG C.
Reaction time is as the criterion completely to react, and scope is 1 hour to several days, preferably several days.
For safety operation, reacting described in technique I, preferably 3-fluorophenyhnagnesium halide is slowly dropped to 1,2-dihalo-ethane and
In iron halide mixed liquor.
In reacting described in technique I, 3 shown in Formulas I, 3 '-DfBP preparation process can produce ethylene gas.Discharge this
Gas will cause atmosphere pollution.
After reaction terminates described in technique I, use the post-processing operation of standard.For example, reactant mixture acid solution is for example dilute
In hydrochloric acid and/or acidifying, in and/or acidifying after reactant liquor with organic solvent such as ethyl acetate extraction.Organic layer magnesium sulfate or
The desiccant dryness such as sodium sulphate.Filtering, filtrate is evaporated, and distillation leftover obtains 3,3 '-DfBP.This product may still contain
Some impurity, detect the compound 1-ethyoxyl-4-NBB determining, dibromobutane, 1-second including GC-MS and NMR
Epoxide-4-chloroethanes, 1,2-bis-(fluorobenzene) ethane and other impurity.In this case, gained crude product can be with buck or acid
Water liquid processes (technique II) and obtains highly purified 3,3 '-DfBP.Above-mentioned residue before it is distilled can be directly with alkali lye or acid
Liquid processes and obtains highly purified product.
[technique II]
Technique II be for purifying process I obtained by product, obtain highly purified 3,3 '-DfBP because according to
The product that technique I is obtained contains impurity.
The product alkali lye of technique I gained or acid solution process and obtain the high-purity 3,3 '-DfBP shown in formula (I).
Alkali lye used by technique II is that alkali is dissolved in the water, and described alkali is metal hydroxides such as lithium hydroxide, hydroxide
Sodium, potassium hydroxide, cesium hydroxide etc.；Metal alcoholate such as lithium methoxide, lithium ethoxide, sodium methoxide, caustic alcohol, potassium methoxide, potassium ethoxide,
Potassium tert-butoxide etc.；Tetraalkylphosphonium hydroxide ammonia such as tetramethyl aqua ammonia, tetraethyl aqua ammonia, tetrabutylammonium hydroxide ammonia and benzyl
Trimethyl aqua ammonia etc.；Or their mixture；Wherein, preferred metal hydroxides, owing to price is low, more preferably hydroxide
Sodium or potassium hydroxide.
Described aqueous alkali, alkali consumption in water is preferably from about 1wt% to about 50wt%, and even more preferably about 1wt%---is about
30wt%.
The consumption of aqueous slkali described in technique II depends on removing impurity.For example, in technique I, the volume of products therefrom is base
Standard, alkali lye volume used is preferably less than about 2 volumes.
Being preferably added to a small amount of phase transfer catalyst in alkali lye, therefore reaction can carry out (see embodiment 4) at low temperatures.Excellent
Phase selection transfer catalyst has quaternary alkylammonium halides such as tetramethyl ammonium chloride, 4 bromide, etamon chloride, tetrapropyl chlorine
Change ammonium, tetrabutylammonium chloride, benzyltrimethylammonium chloride etc.；Halophosphines salt has tetraphenylphosphonium chloride, tetraphenylphosphonibromide bromide etc..
When using tetraalkylphosphonium hydroxide amine described above as alkali, phase transfer catalyst can not be used, because tetra-alkyl ammonium hydroxide
Itself can be as phase transfer catalyst.
On the basis of alkali used by 1mol, the amount ranges of catalyst is preferably from about 1mol%---about 10mol%, more preferably
About 2mol%---about 5mol%.
Acid solution used by technique II is that acid is dissolved in the water.Acid is preferably sulfuric acid, hydrogen chloride, hydrochloric acid, hydrogen bromide, hydrogen bromine
Acid, hydrogen iodide, hydroiodic acid etc..Wherein, due to availability, preferably hydrochloric acid and sulfuric acid.
Described acid solution, the consumption of the acid being dissolved in water is preferably about 1wt%---50wt%, more preferably 1wt%---
30wt%.
The consumption of acid solution described in technique II depends on removing impurity.For example, in technique I, the volume of products therefrom is base
Standard, acid solution volume used is preferably less than about 2 volumes.
Reaction described in technique II is technique I products obtained therefrom alkali lye or acid solution process.This reaction can use and also can not use
Solvent.Suitable solvent can at least select one, alcohols such as methyl alcohol, ethanol, propyl alcohol, isopropanol, the tert-butyl alcohol, ethylene glycol etc.；Ethers
Such as ether, isopropyl ether, methyl tertiary butyl ether(MTBE), oxolane, dioxane, 1,2-dimethoxy-ethane etc.；Aromatics has benzene, first
Benzene, chlorobenzene, dimethylbenzene etc..Most cases, does not needs solvent, and technique I products obtained therefrom directly mixes with alkali lye or acid solution.
Range of reaction temperature described in technique II selects to be about 0 DEG C---and about+150 DEG C.Produce to effectively obtain high-purity
Product, preferably from about room temperature to about+120 DEG C.Till reaction time selects to react completely, can be 0.5 hour to several days, preferably 24 is little
When interior.
For effectively preparing highly purified product, comparing aqueous acid, preferably aqueous alkali is (see embodiment 2-4 aqueous alkali
Process, embodiment 5 aqueous acid process).Process with pure water solution and can not obtain highly purified product (see comparative example 1).
[technique III]
The present invention also comprises technique III, which is ethylene gas produced by technique I and chlorine (Cl2), bromine (Br2) or iodine
(I2) reaction.Wherein, it is contemplated that availability and cost, preferably chlorine or bromine.Relative to the ethylene gas collected by technique I
Amount, chlorine used in technique III, the consumption of bromine and iodine is excessive.But, it is contemplated that cost, preferably from about 1.0 equivalents arrive
About 1.2 equivalents.Described in technique III, ethylene gas collected by selection process I for the reaction is passed into chloride gas, the solution of bromine or iodine
In.When selecting chlorine or bromine absorbs, it is possible to ethylene gas collected with technique I to chlorine or bromine is passed through simultaneously
In solvent.Described solvent, preferably water and carbon halide compound such as dichloromethane, chloroform etc.；Or the mixed solvent of its any ratio.
Ethylene gas collected in technique I can effective reactor transfer from technique I with the help of inert gas such as nitrogen
Moving on in another reactor, at this reactor, chlorine, bromine or iodine react (technique III) with ethylene gas.
The optional scope of reaction temperature of technique III is about-20 DEG C---it is about+50 DEG C.Have to make this react more economical
Effect, preferably about 0 DEG C---it is about room temperature.
The reaction time of technique III is as the criterion completely to react.Substantially, ethylene gas and halogen are swift in response, Ji Ge little
When interior can react complete.But, in fact, the reaction time of technique I is depended in the reaction of technique III.It is preferably technique I anti-
Completely then technique III should also react complete.Therefore, the actual finish time of technique III for being about than the reaction time of technique I more
Several hours or more.
Product 1 obtained in technique III, 2-dihalo-ethane, as one of them in three initiation materials, Ke Yiyong
In technique 1.(being shown in Table lattice 2)
3,3 '-DfBP is the key intermediate producing the electrophilic trifluoromethyl reagent of high activity, this trifluoromethylation
Reagent is widely used in producing all kinds of and chemical association area trifluoromethylation organic compound.The invention provides economy has
Effect 3,3 '-DfBP economical and effective, the production method of high-purity high-yield.The more important thing is, the present invention comprises to prevent ethene
Gas enters air, and reclaims initiation material by reacting the ethylene gas generating.No matter economically or environmental, exist
The industrial society of present or future, this is of crucial importance.Therefore, the invention provides the eco-friendly industrialized production of economical and effective
The method of key intermediate 3,3 '-DfBP.
Detailed description of the invention
It in order to be better understood from present disclosure, is described further below in conjunction with specific embodiment, but specifically
Embodiment be not the restriction that present disclosure is done.
Embodiment 1. technique I:The preparation of 3,3 '-DfBP
In being equipped with dropping funel, thermometer, in the four-hole bottle of the 500ml of magnetic stir bar, add the anhydrous tetrahydrochysene of 200ml
Furans, 3.75 grams of (154mmol) magnesium metals.24.5g (140mmol) 3-bromofluorobenzene is added in dropping funel.Reaction bulb adds
Enter micro iodine and a small amount of 3-bromofluorobenzene, then heat reactant mixture and cause grignard reaction to about 50 DEG C.After grignard reaction causes,
It is 45 DEG C-52 DEG C that 3-bromofluorobenzene in dropping funel is slowly added dropwise in reactant liquor the interior temperature of control.Dripping and finishing, reactant liquor continues stirring
3 hours are until reaction is complete.
It is equipped with thermometer in another, the four-hole bottle of dropping funel and magnetic stir bar adds 84ml be dried tetrahydrochysene furan
Mutter, 8.3g (83.8mmol) 1,2-dichloroethanes, and 0.7g (4.3mmol) i.e. 3mol%FeCl3.The above-mentioned grignard preparing
Liquid is placed in a dropping funel, and is slowly dropped to the 1 of stirring, 2-dichloroethanes/FeCl3In/THF reaction mixture, the used time
About 1.5 hours.Dripping after finishing, reaction temperature is 49 DEG C.Reactant mixture is stirred for 2 hours at room temperature.19FNMR analytical reactions are mixed
Closing liquid, with fluorobenzene as internal standard, product 3, the yield of 3 '-DfBP is 96%.The post processing of reactant mixture is as follows：Reaction is mixed
Compound is acidified by watery hydrochloric acid, and ethyl acetate extracts.Water layer ethyl acetate extracts, and merges organic layer, and saturated sodium-chloride water solution is washed
Washing, magnesium sulfate is dried, and filters, and filtrate is evaporated.The remaining residue of decompression distillation, GC-Mass and NMR analyzes display gained crude product and is
Product contains a small amount of 1-bromo-4-acetonyl ester butane and other impurity.
Embodiment 2. technique II:Under the effect of tetrabutylammonium chloride, products obtained therefrom sodium hydrate aqueous solution in technique I
Process.
Obtained technique I product by standard post processing after the reaction of technique I.Standard post processing is watery hydrochloric acid acidifying, acetic acid
Ethyl ester extracts, and magnesium sulfate is dried, and decompression distillation after concentration, products obtained therefrom 3 in GC analysis process I, the purity of 3 '-DfBP is
97.0% (NMR purity assay is 95%).
In the bottle of a 1L, adding the product that the preparation of 200g technique I is obtained, 196ml contains 5mol% (relative to hydroxide
Sodium) the sodium hydrate aqueous solution of 2.5N (mol/L) of phase transfer catalyst tetrabutylammonium chloride.Under nitrogen protection, mixture
It is heated to reflux 3 hours, then drop to room temperature.Reactant mixture is acidified by watery hydrochloric acid, separates organic layer.Water layer is extracted by ether,
Mixing organic layer saturated sodium-chloride water solution washs, and magnesium sulfate dry filter, filtrate is evaporated, then distillation of reducing pressure obtains 174g
(87%) highly purified product, NMR purity assay ＞ 99% (GC purity assay is 99.4%).Product boiling point is 92-93 DEG C/
2.3Torr.Result is as shown in Table 1.
Embodiment 3-5. technique II：Under the effect of phase transfer catalyst, in technique I, gained thick product alkali or sour water are molten
Liquid process.
As in Example 2, the raw material used by embodiment 3-5 is the product that technique I obtains.In phase transfer catalyst effect
Descend or not under phase transfer catalyst effect, the impure product alkali obtained by technique I or aqueous acid process.Form 1 shows
Alkali, acid and their consumption, reaction condition and result are shown.High yield, highly purified product can be obtained.
Form I. technique 1 products therefrom buck, aqueous acid or Pure water preparation
*NMR purity assay. ＞ 99% means NMR detection free from admixture.
*GC purity assay (fid detector).
+ oil bath pan temperature is 120 DEG C
Comparative example 1：The product that technique 1 prepares water process
As embodiment 2-5, technique 1 products obtained therefrom is used in this reaction.Product water process, refluxes 3 hours, locates afterwards
Reason mode is in the same manner as in Example 2.Condition and result are as shown in Table 1.It is 97% (GC analysis that products obtained therefrom NMR detects its purity
Its purity is 98.0%), purity is inadequate, and this shows that neutrallty condition is not suitable for products obtained therefrom in purifying process 1.
Embodiment 6. technique I and technique III:The preparation of (technique I) 3,3 '-DfBP and (technique III) technique I are produced
The absorption of raw ethylene gas and be converted into 1,2-dihalo-ethane.
In the same manner as in Example 1,24.5g (140mmol) 3-bromofluorobenzene, 3.75 grams of (154mmol) magnesium metals, 200ml is anhydrous
Oxolane, prepares the tetrahydrofuran solution of 3-fluorophenyhnagnesium halide.
On the other hand, it is equipped with thermometer, dropping funel, the four of the 500ml of nitrogen access port and nitrogen exit in one
In mouth bottle.Nitrogen exit connects another flask equipped with bromine (14.7g) dichloromethane (100ml) solution.In a 500ml tetra-
Mouth bottle adds 84ml dry tetrahydrofuran, 8.3g (83.8mmol) 1,2-dichloroethanes, and 0.7g (4.3mmol) FeCl3.On
Stating the Grignard solution preparing to be placed in a dropping funel, and being slowly dropped in the reaction mixture of stirring, the used time about 2.5 is little
When.Drip after finishing, be passed through several hours nitrogen, nitrogen flow rate 100ml/min.
Main reactant mixture watery hydrochloric acid is acidified to Ph=2, and ethyl acetate (250ml) extracts.Aqueous layer with ethyl acetate
Extraction, merges organic layer, and with the washing of 200ml saturated nacl aqueous solution, magnesium sulfate is dried, and filters.Filtrate is evaporated, and residue reduces pressure
Distillation obtains 10.4g 3,3 '-DfBP (oil bath temperature 100-120 DEG C/0.2mmHg).Yield 79%.GC assay products is pure
Degree is 98.9%.NMR analyzes and shows containing other impurity a small amount of in product, therefore, for obtaining purer product, and can be according to technique
II process.
Bromine excessive in bromine solutions is with chilled solution of sodium bisulfite process.NMR analysis of mixtures, shows to generate
5mmol1,2-Bromofume.This shows that the ethylene gas producing in technique I is absorbed, and the 1 of recovery, 2-Bromofume can
Reuse using one of them initiation material as technique I.
Reference implementation example 2：3,3 '-DfBP is used to prepare trifluoromethyl reagent (A) and (B)
At room temperature, 3,3 '-DfBP (28.3g, 149mmol) is joined dry fluoroform sulphur by nitrogen protection
It in acid sodium (32.9g, 211mmol) and dry 100mL nitromethane mixed liquor, is placed in water-bath cooling.Then by trifluoro
Methanesulfonic acid acid anhydride (65.1g, 231mmol) adds in mixed liquor, within 40 minutes, drips and finishes, and keeps being stirred for 2 hours in ice bath, then removes
Ice bath, this mixed liquor is stirred at room temperature 3 hours, adds TFAA (37.8g, 180mmol), and reactant liquor maintains room temperature to stir
Mix 17 hours.Solvent evaporated, gained adds 130ml toluene, again solvent evaporated, adds 130ml toluene and 130ml water, stirring
20 minutes.Gained solid filters, and obtains the 2 of 50.4g (77%), the fluoro-S-of 8-bis-(trifluoromethyl)-dibenzothiophenes fluoroform sulphur
Hydrochlorate (A) is with the fluoro-S-of 2,6-bis-(trifluoromethyl)-(ratio is 91 to dibenzothiophenes fluoroform sulphonate (B):9) mixture.
Through being recrystallized to give the fluoro-S-of 2,8-bis-(the trifluoromethyl)-dibenzothiophenes TFMS of pure crystal habit
Salt,
Degraded initial temperature is that 204 DEG C (TGA/DSC detections) (recrystallization solvent is CH3CN-ether).
The spectral data of this product and physicochemical data are as follows：
19F NMR(1H irradiates) (376.5MHz, DMSO-d6)δ-53.25(3F,s,CF3),-77.78(3F,s,
SO2CF3),-101.81ppm(2F,s,2,8-F)；
1H-NMR(400.2MHz,DMSO-d6) δ 8.76 (2H, dd, J=9.0,4.8Hz, 4,6-H), 8.56 (2H, dd, J=
8.8,2.8Hz, 1,9-H), 7.84ppm (2H, dt, J=2.8,9.0Hz, 3,7–H)
13C-NMR(100.6MHz,DMSO-d6) δ 66.9 (d, J=261.6Hz), 143.8 (dd, J=11.6,2.5Hz),
132.9 (d, J=10.1Hz), 123.4 (quartet, J=332.3Hz), 123.0 (d, J=2.0Hz), 121.1 (quartet,
J=321.9Hz), 120.1 (d, J=24.1Hz), 113.7ppm (d, J=27.2Hz)；
IR(KBr)3112,3057,1593,1584,1583,1263,1237,1178,1157,1090,1029,903,
838,757,636,571,517,492,465cm-1；
Mass spectral analysis (ESI method) m/z, 289 (M+-OSO2CF3)；
High resolution mass spectrum (ESI method) C13H6F5S(M-OSO2CF3)+, calculated value 289.0105. measured value 289.0129.
Elementary analysis C14H6F8O3S2:Calculated value：C, 38.36%；H, 1.38%. measured value：C, 38.45%；
H.1.67%.
In mixture, the fluoro-S-of 2,6-bis-(trifluoromethyl) dibenzothiophenes fluoroform sulphonate NMR detection data are as follows：
19F NMR(1H irradiates) (376.5MHz, DMSO-d6) δ-52.45 (3F, d, J=6.6Hz, CF3),-77.78(s,
CF3SO2) ,-100.76 (1F, s, 2-F) ,-108.23ppm (1F, quartet, J=6.6Hz, 6-F).
Another tests the pure 2,6-of isolated as follows bis-fluoro-S-(trifluoromethyl) dibenzothiophenes three
Fluorine mesylate. being evaporated reactant liquor, adding water and dichloromethane, filter out the solid of precipitation, filtrate isolates organic layer, dense
Contracting, (eluting solvent is dichloromethane to cross post separation:Methyl alcohol=10:1) the pure fluoro-S-of solid 2,6-bis-(trifluoromethyl) two is obtained
Benzothiophene fluoroform sulphonate.
Degraded initial temperature is that 135 DEG C (TGA/DSC detections) (recrystallization solvent is CH3CN-ether).
19F NMR(1H irradiates) (376.5MHz, DMSO-d6)δ-53.25(3F,s,CF3),-77.78(3F,s,
SO2CF3),-101.81ppm(2F,s,2,8-F)；
1H-NMR(400.2MHz,DMSO-d6) δ 8.77 (1H, dd, J=8.9,4.6Hz, 4-H), 8.67 (1H, dd, J=
8.9,2.6Hz, 1-H), 8.47 (1H, d, J=8.4Hz, 9-H), 8.26 (1H, dt, J=5.2,8.4Hz, 8-H), 7.95 (1H,
T, J=8.4Hz, 7-H), 7.88ppm (1H, dt, J=2.6,8.9Hz, 3-H)；
13C NMR(100.6MHz,DMSO-d6) δ 163.3 (d, J=255.9Hz, 2-C), 159.5 (d, J=257.5Hz,
6-C), 144.1 (dd, J=11.2,1.9Hz), 143.0 (d, J=2.5Hz), 140.2 (d, J=8.3Hz), 133.2 (d, J=
10.8Hz), 123.5 (quartet, J=333.1Hz, CF3), 122.5 (d, J=2.8Hz), 121.1 (quartet, J=
322.2Hz,SO2CF3), 120.8 (d, J=2.1Hz), 120.6 (d, J=24.8Hz), 119.7 (d, J=18.0Hz), 114.5
(d, J=26.8Hz), 113.3ppm (d, J=17.1Hz)；
IR(KBr)3059,1603,1583,1490,1474,1447,1267,1224,1169,1155,1103,1075,
1027,904,838,815,804,758,733,665,634,573,516,495,454,435,404cm-1.
Elementary analysis C14H6F8O3S2:Calculated value：C, 38.36%；H, 1.38%. measured value：C, 38.28%；
H.1.45%.
Reference implementation example 3：Trifluoromethyl reagent (A) and the example of (B) trifluoromethylation organic compound
At ambient temperature, 1-oxo-2-indane carboxylate methyl ester (190mg, 1mmol), K to stirring2CO3(430mg,
It 3mmol) with additional proportion in N,N-dimethylformamide (10mL) solution of tetrabutylammonium iodide (20mg, 0.05mmol) is
97:The fluoro-S-of 2,8-bis-(the trifluoromethyl)-dibenzothiophenes fluoroform sulphonate of 3 and the fluoro-S-of 2,6-bis-(trifluoromethyl)-two
The mixed liquor (650mg, 1.5mmol) of benzothiophene fluoroform sulphonate, this reactant mixture stirs 3 hours, with benzotrifluoride
For standard, warp19Trifluoromethylation product in F NMR detection mixed liquor, i.e. 1-oxo-2-(trifluoromethyl)-indan-2-carboxylic acids first
Ester yield 94%, product is i.e. available through routine post processing, e.g., and extraction and column chromatography, identify through spectrum analysis19F NMR
(CDCl3)δ-69.3(s,CF3).
Although having been incorporated with detailed description of the invention sufficient description has been carried out to the present invention, it shall be noted that be for this
For skilled person, its variations and modifications are apparent from.Such changing and modifications it will be appreciated that as including
By in the scope of the present invention defined in claims.
Claims (10)
1. the preparation method of 3,3 '-DfBP with below formula (I) structure：
The method is the 3-fluorophenyhnagnesium halide shown in formula (II) and the molysite shown in formula (IV) and the dihalo-second shown in formula (III)
Alkane reacts：
X'CH2CH2X'(III)
Fe(X")3(IV)
Wherein X, X ', X " each stand alone as chlorine, bromine or iodine atom.
2. preparation method according to claim 1, it is characterised in that 1,2-dihalo-ethane rubs with 3-fluorophenyhnagnesium halide
You are 0.4～1 than scope：1.
3. preparation method according to claim 1, it is characterised in that the molar ratio range of molysite and 3-fluorophenyhnagnesium halide
It is 0.5%～20%：1.
4. preparation method according to claim 1, it is characterised in that described solvent is oxolane.
5. preparation method according to claim 1, it is characterised in that reaction temperature controls at-20 DEG C～+65 DEG C.
6. the preparation method according to claim 1-5, it is characterised in that further comprise claim 1-5 gained
Compound alkali shown in formula (I) or the step of acid treatment.
7. the preparation method according to claim 1-5, it is characterised in that further comprise claim 1-5 gained
The step that compound shown in formula (I) is processed by aqueous alkali.
8. preparation method according to claim 7, described aqueous alkali includes phase transfer catalyst.
9. the preparation method according to claim 1-5 any claim, comprises to reclaim 1 further, 2-dihalo-ethane, institute
State 1,2-dihalo-ethane, it is possible to use ethylene gas and chlorine, bromine, or the Iod R of the reaction release of claim 1-5 are prepared into
Arrive.
10. preparation method according to claim 1, wherein said X, X ', X " each stand alone as Cl or Br.
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| CHRISTOPHE CHABOCHE等: "Iron-Catalyzed Homo-Coupling of Simple and Functionalized Arylmagnesium Reagents", 《ORG. LETT.》 * |
| MINFENG ZENG ET AL.: "Palladium-Catalyzed Reductive Homocoupling of Aromatic Halides and Oxidation of Alcohols", 《J. ORG. CHEM.》 * |
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| CN110698686B (en) * | 2019-10-25 | 2021-11-30 | 江西师范大学 | Terbium coordination polymer for separating propyne/propylene mixed gas and preparation method thereof |
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