CN103086850B - Preparation method of CF2O-containing compound, and intermediate compound and preparation method thereof - Google Patents
Preparation method of CF2O-containing compound, and intermediate compound and preparation method thereof Download PDFInfo
- Publication number
- CN103086850B CN103086850B CN201310049647.9A CN201310049647A CN103086850B CN 103086850 B CN103086850 B CN 103086850B CN 201310049647 A CN201310049647 A CN 201310049647A CN 103086850 B CN103086850 B CN 103086850B
- Authority
- CN
- China
- Prior art keywords
- preparation
- bromo
- difluoro
- methoxy
- trifluoro
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of a CF2O-containing compound, and an intermediate compound and a preparation method thereof. The preparation method of a CF2O-containing compound, provided by the invention, comprises the following step: in solvent, in the presence of a catalyst, performing coupling reaction on 5-(bromo-difluoro-methoxy)-1,2,3-trifluorobenzene shown as Formula 1 and a Grignard reagent 3,5-difluoro-4'-propylbiphenyl-4-magnesium bromide shown as Formula 2, thus obtaining 4-(4-n-propyl)phenyl-3,5-difluoro-1',1'-difluorobenzyl-3,4,5-trifluorophenyl ether shown as Formula 3. The preparation method provided by the invention is simple to operate, mild in reaction conditions, convenient in posttreatment steps, high in reaction conversion rate, high in atom economy, friendly to environment, favorable in product purity and suitable for industrial production.
Description
Technical field
The present invention relates to containing CF
2the preparation method, intermediate and preparation method thereof of O compound.
Background technology
Difluoro methoxy bridge bond (CF
2o) monomer liquid crystal compound has high dielectric anisotropy and low viscous feature, this compound liquid crystal is widely used in TFT-LCD mixed liquid crystal, due to the monomer liquid crystal compound complicated process of preparation containing difluoro-methoxy center bridged bond, price is high, industrialization difficulty.A kind of new method of such searching prepares difluoro-methoxy center bridged bond (CF
2o) monomer liquid crystal compound, just becomes very urgent task.
Compound 4-(difluoro (3,4, the 5-trifluoromethoxy phenoxy base) methyl related in the present invention))-3,5-bis-fluoro-4 '-propyl group-1,1 '-biphenyl is a kind of monomer of representative difluoro-methoxy center bridged bond.Containing CF
2the difficult point of the synthesis of O compound how to introduce difluoro-methoxy center bridged bond (CF easily in the molecule
2o).At present, the synthetic method of bibliographical information mainly contains following three kinds:
1, dibromodifluoromethane method: utilize the Grignard reagent of alkyl or phenyl or lithium reagent and dibromodifluoromethane to react, obtain alkyl or phenyl difluoro monobromethane, then with fortified phenol etherificate under the effect of alkali, thus obtain the liquid crystalline cpd containing difluoro-methoxy.The method subject matter is the low conversion rate to polycyclic system reaction, and post-processing operation is loaded down with trivial details, and product yield is lower, and alkyl or phenyl difluoro monobromethane consumption causes greatly cost higher.
2, DAST method: ester compound and Lawson (Lawesson) reagent react are generated monothioester, then with DAST(fluorination reagent, diethylin sulfur trifluoride) react at low temperatures, thus ester group is converted into difluoro-methoxy center bridged bond.The method subject matter is the price is rather stiff of DAST, and yield is lower, causes the preparation cost of compound higher.
3, dimercaptopropane-trifluoromethayl sulfonic acid method: alkyl or phenyl formic acid and dimercaptopropane, trifluoromethayl sulfonic acid are obtained by reacting trifluoro-methanyl sulfonate, then are obtained by reacting containing CF with fortified phenol
2the target product of O.The method subject matter is to synthesize in two steps, and the purification loss of trifluoro-methanyl sulfonate is comparatively large, and the salt recrystallization difficulty of low melting point, cause overall yield lower, the preparation cost of compound is higher.
Chinese patent CN1733676 (invalidated patent), publication date 2006-02-15, report with 4 '-propyl group-3,5-DfBP be raw material successively with butyllithium and CF
2br
2be obtained by reacting 4-(4-n-propyl) phenyl-3,5-bis-fluoro-1 ', 1 '-two fluorobenzyl bromide, then 4-(4-n-propyl) phenyl-3,5-bis-fluoro-1 ', Williamson etherification reaction is there is again and obtains target product 4-(4-n-propyl in 1 '-two fluorobenzyl bromide with 3,4,5-trifluoromethyl phenol) phenyl-3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3,4,5-trifluorophenyl ether.
The people such as Matsui (Matsui, Shuichi; Kondo, Tomoyuki; S ago, Kouki; Molecular Crystals and Liquid Crystals; Vol.411; (2004); P.127 – 138.) report compound 4 '-propyl group-3,5-DfBP and n-Butyl Lithium, THF under-70 DEG C of conditions, the phenyl lithium solution reaction with difluorodibromomethane, obtains intermediate CF
2br-form, this intermediate with DMF (DMF) for solvent, at K
2cO
3under alkaline condition, there is Williamson etherification reaction with halogenated phenol, be separated and obtain target product 4-(4-n-propyl) phenyl-3,5-bis-fluoro-1 ', the yield of 1 '-difluorobenzyl-3,4,5-trifluorophenyl ether is 35%.
Summary of the invention
In order to overcome existing 4-(4-n-propyl) phenyl-3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3,4, in the preparation method of 5-trifluorophenyl ether, reaction conversion ratio is low, and product yield is low, and Atom economy is poor, production cost is high, is unfavorable for amplifying the defects such as production, and provides containing CF
2the preparation method, intermediate and preparation method thereof of O compound.Of the present invention containing CF
2the preparation method of O compound is simple to operate, and reaction conditions is gentle, and post-processing step is easy, and reaction conversion ratio is high, and Atom economy is high, environmental friendliness, and good product purity is suitable for suitability for industrialized production.
The invention provides a kind of containing CF
2the preparation method of O compound, it comprises the following steps: in a solvent, under catalyzer existent condition, by bromo-for 5-(as shown in Equation 1 difluoro-methoxy)-1,2,3-trifluoro-benzene carries out linked reaction with the fluoro-4 '-pentylbiphenyl-4-magnesium bromide of grignard reagent 3,5-bis-as shown in Equation 2, obtains 4-(4-n-propyl as shown in Equation 3) phenyl-3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3,4,5-trifluorophenyl ether;
In the present invention, described linked reaction is preferably carried out under the condition of protection of inert gas.Described rare gas element can be the conventional inert gas carrying out such linked reaction in this area, one or more in preferred nitrogen, argon gas, helium, neon, Krypton and xenon.
In the present invention, described solvent can be the Conventional solvents carrying out such linked reaction in this area, preferred ether solvent, one or more in the preferred ether of described ether solvent, methyltetrahydrofuran and tetrahydrofuran (THF), further preferred tetrahydrofuran (THF).
In the present invention, the bromo-difluoro-methoxy of described 5-() the preferred 1:1 ~ 1:10 of mass ratio of-1,2,3-trifluoro-benzenes 1 and solvent, further preferred 1:2 ~ 1:7.
In the present invention, the bromo-difluoro-methoxy of described 5-() the preferred 1:0.5 ~ 1:3 of mol ratio of-1,2,3-trifluoro-benzenes 1 and the fluoro-4 '-pentylbiphenyl-4-magnesium bromide 2 of described grignard reagent 3,5-bis-, further preferred 1:1.0 ~ 1:2.2.
In the present invention, described catalyzer can be the conventional catalyst carrying out such linked reaction in this area, preferred Ni (acac)
2(acetylacetonate nickel, CAS:3264-82-2), NiCl
2(PCy
3)
2(molybdenyl dichloride (tricyclohexyl phosphine) nickel (II), CAS:19999-87-2), NiCl
2two (diphenylphosphine propane) Nickel Chloride of-dppp(1,3-, CAS:15629-92-2) and anhydrous NiCl
2in one or more, further preferred anhydrous NiCl
2.
Dehydrated nickel chloride described in the present invention can adopt commercial anhydrous nickelous chloride reagent, and in the present invention, spy particularly preferably adopts document Dong Ya to put down, Lang Yi, Peng Guangzhi, " salt lake research ", 1997,5,2,57 ~ 63.Dehydrated nickel chloride prepared by the method reported.
In the present invention, described catalyzer and the bromo-difluoro-methoxy of 5-() the preferred 0.001:1 ~ 0.100:1 of mass ratio of-1,2,3-trifluoro-benzenes 1, further preferred 0.0050:1 ~ 0.0100:1.
In the present invention, the temperature of described linked reaction can be in this area the ordinary temperature carrying out such reaction, preferably 20 DEG C ~ 90 DEG C, preferably 50 DEG C ~ 70 DEG C further.
In the present invention, the process of described linked reaction can according to traditional test methods monitoring (as GC) in this area, with the bromo-difluoro-methoxy of 5-()-1,2,3-trifluoro-benzenes 1 disappear for reaction end, the time preferred 1h ~ 18h of reaction, preferred 2h ~ 8h further.
The bromo-difluoro-methoxy of 5-(described in the present invention)-1,2,3-trifluoro-benzene 1 can be obtained by following preparation method, and it comprises the following steps: in a solvent, under alkali existent condition, by 3,4,5-trifluoromethyl phenol and difluorodibromomethane carry out Williamson etherification reaction, obtain the bromo-difluoro-methoxy of 5-()-1,2,3-trifluoro-benzene 1;
Again according to described preparation 4-(4-n-propyl as shown in Equation 3) phenyl-3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3, the method of 4,5-trifluorophenyl ether obtains 4-(4-n-propyl as shown in Equation 3) phenyl-3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3,4,5-trifluorophenyl ether.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, described Williamson etherification reaction preferably carries out under the condition of protection of inert gas.Described rare gas element can be the conventional inert gas carrying out such linked reaction in this area, one or more in preferred nitrogen, argon gas, helium, neon, Krypton and xenon.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, described solvent can be the Conventional solvents carrying out such Williamson etherification reaction in this area, preferred amide kind solvent, preferred N,N-dimethylacetamide (DMAC) further.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the volume mass of 3,4,5-described trifluoromethyl phenols and described solvent than preferred 1:1 ~ 1:20, preferred 1:2 ~ 1:10 further.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the preferred 1:1 ~ 1:4 of mol ratio of 3,4,5-described trifluoromethyl phenols and described difluorodibromomethane, further preferred 1:1 ~ 1:2.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, described alkali is the conventional alkali carrying out such Williamson etherification reaction in this area, preferred sodium and/or sodium hydride.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the preferred 2:1 ~ 2:3 of mol ratio of 3,4,5-described trifluoromethyl phenols and described alkali, further preferred 2:1 ~ 10:7.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, when described alkali adopts sodium and sodium hydride, described sodium hydride and the preferred 1:1 ~ 1:5 of the mol ratio of sodium, further preferred 1:2 ~ 1:3.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the temperature of described Williamson etherification reaction can be in this area the ordinary temperature carrying out such reaction, preferably-20 DEG C ~ 50 DEG C, and preferably 10 DEG C ~ 30 DEG C further.
At the bromo-difluoro-methoxy of preparation 5-()-1,2, in the method for 3-trifluoro-benzene 1, the process of described Williamson etherification reaction can adopt traditional test methods in this area to carry out monitoring (as GC), disappear for reaction end with 3,4,5-trifluoromethyl phenol, reaction times preferred 4h ~ 30h, further preferred 6h ~ 15h.
The fluoro-4 '-pentylbiphenyl-4-magnesium bromide 2 of grignard reagent 3,5-bis-described in the present invention can be obtained by following preparation method, and it comprises the following steps:
Step 1: in a solvent, reacts with lithium reagent and bromine successively by 4 '-propyl group-3,5-DfBP, obtains bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of 4-;
Step 2: in a solvent, by bromo-3,5-bis-fluoro-4 '-pentylbiphenyl and the reactive magnesiums of 4-obtained in step 1, obtains the fluoro-4 '-pentylbiphenyl-4-magnesium bromide 2 of grignard reagent 3,5-bis-;
Again according to the bromo-difluoro-methoxy of described 5-() preparation method of-1,2,3-trifluoro-benzenes 1 obtains 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1; Again according to described preparation 4-(4-n-propyl as shown in Equation 3) phenyl-3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3, the method of 4,5-trifluorophenyl ether obtains 4-(4-n-propyl as shown in Equation 3) phenyl-3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3,4,5-trifluorophenyl ether.
In step 1, described solvent is the Conventional solvents carrying out such reaction in this area, particularly preferably ether solvent in the present invention, the preferred tetrahydrofuran (THF) of described ether solvent.
In step 1, the preferred 1:1 ~ 1:10 of mass ratio of described 4 '-propyl group-3,5-DfBP and described solvent, further preferred 1:2 ~ 1:6.
In step 1, described lithium reagent is the conventional lithium reagent carrying out such reaction in this area, particularly preferably n-Butyl Lithium in the present invention.
In step 1, the preferred 1:1 ~ 1:3 of mol ratio of described 4 '-propyl group-3,5-DfBP and described lithium reagent, further preferred 1:1.1 ~ 1:1.4.
In step 1, the preferred 1:1 ~ 1:4 of mol ratio of described 4 '-propyl group-3,5-DfBP and described bromine, further preferred 1:1.1 ~ 1:2.0.
In step 1, the temperature of described reaction can for carrying out the ordinary temperature of such reaction in this area, in the present invention particularly preferably-60 DEG C ~-20 DEG C, preferably-50 DEG C ~-30 DEG C further.
In step 1, the process of described reaction can adopt the traditional test methods in this area (as GC) to monitor, with the bromo-difluoro-methoxy of 5-()-1,2,3-trifluoro-benzenes disappear for reaction end, reaction times preferred 2h ~ 8h, preferred 3h ~ 6h further.
In step 2, described solvent is the Conventional solvents carrying out such reaction in this area, particularly preferably ether solvent in the present invention, the preferred tetrahydrofuran (THF) of described ether solvent.
In step 2, the volume mass of bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of described 4-and described solvent than preferred 1:1.0 ~ 1:6.0, preferred 1:1.5 ~ 1:3.0 further.
In step 2, the preferred 1.0:1.0 ~ 1.0:2.0 of mol ratio of bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of described 4-and described magnesium, further preferred 1.0:1.2 ~ 1.0:1.8.
In step 2, the temperature of described reaction can for carrying out the ordinary temperature of such reaction in this area, in the present invention particularly preferably 10 DEG C ~ 60 DEG C, preferably 20 DEG C ~ 40 DEG C further.
In step 2, the process of described reaction can adopt the traditional test methods in this area (as GC) to monitor, and disappears for reaction end with bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of 4-, particularly preferably reaction times 1h ~ 12h in the present invention, further preferred 4h ~ 8h.
In step 2, the reaction of bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of described 4-and magnesium is preferably carried out under initiator existent condition.
Described step 2 is preferably in reactions steps, and described initiator is the normal starter carrying out such reaction in this area, particularly preferably iodine in the present invention.
Described step 2 is preferably in reactions steps, the preferred 20000:1 ~ 500:1 of mass ratio of bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of described 4-and described initiator, further preferred 15000:1 ~ 800:1.
The invention provides the bromo-difluoro-methoxy of a kind of 5-(as shown in Equation 1)-1,2,3-trifluoro-benzenes,
Present invention also offers the described bromo-difluoro-methoxy of 5-(as shown in Equation 1)-1,2, the preparation method of 3-trifluoro-benzene, it comprises the following steps: in a solvent, under alkali existent condition, by 3,4,5-trifluoromethyl phenol and difluorodibromomethane carry out Williamson etherification reaction, obtain the bromo-difluoro-methoxy of 5-()-1,2,3-trifluoro-benzene 1;
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, described Williamson etherification reaction preferably carries out under the condition of protection of inert gas.Described rare gas element can be the conventional inert gas carrying out such linked reaction in this area, one or more in preferred nitrogen, argon gas, helium, neon, Krypton and xenon.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, described solvent can be the Conventional solvents carrying out such Williamson etherification reaction in this area, preferred amide kind solvent, preferred N,N-dimethylacetamide (DMAC) further.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the volume mass of 3,4,5-described trifluoromethyl phenols and described solvent than preferred 1:1 ~ 1:20, preferred 1:2 ~ 1:10 further.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the preferred 1:1 ~ 1:4 of mol ratio of 3,4,5-described trifluoromethyl phenols and described difluorodibromomethane, further preferred 1:1 ~ 1:2.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, described alkali is the conventional alkali carrying out such Williamson etherification reaction in this area, preferred sodium and/or sodium hydride.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the preferred 2:1 ~ 2:3 of mol ratio of 3,4,5-described trifluoromethyl phenols and described alkali, further preferred 2:1 ~ 10:7.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, when described alkali adopts sodium and sodium hydride, described sodium hydride and the preferred 1:1 ~ 1:5 of the mol ratio of sodium, further preferred 1:2 ~ 1:3.
At preparation 5-(bromo-difluoro-methoxy) in the method for-1,2,3-trifluoro-benzenes 1, the temperature of described Williamson etherification reaction can be in this area the ordinary temperature carrying out such reaction, preferably-20 DEG C ~ 50 DEG C, and preferably 10 DEG C ~ 30 DEG C further.
At the bromo-difluoro-methoxy of preparation 5-()-1,2, in the method for 3-trifluoro-benzene 1, the process of described Williamson etherification reaction can adopt traditional test methods in this area to carry out monitoring (as GC), disappear for reaction end with 3,4,5-trifluoromethyl phenol, reaction times preferred 4h ~ 30h, further preferred 6h ~ 15h.
Without prejudice to the field on the basis of common sense, above-mentioned each optimum condition, can arbitrary combination, obtains the preferred embodiments of the invention.
Agents useful for same of the present invention and raw material are all commercially.
Positive progressive effect of the present invention is:
1, the invention provides a kind of be different from completely prior art containing CF
2the preparation method, intermediate and preparation method thereof of O compound.
2, of the present invention containing CF
2the preparation method of O compound is simple to operate, and reaction conditions is gentle, and post-processing step is easy, and reaction conversion ratio is high, and Atom economy is high, environmental friendliness, and good product purity is suitable for suitability for industrialized production.
3, of the present invention containing CF
2one of them preferred embodiment of the preparation method of O compound, first by CF
2o combines with fortified phenol, the bromo-difluoro-methoxy of obtained reaction 5-()-1,2,3-trifluoro-benzene 1, and then react with the grignard reagent of biphenyl compound, reduce the usage quantity of biphenyl compound, improve atom utilization, effectively reduce production cost, be beneficial to suitability for industrialized production.
4, of the present invention containing CF
2the preparation method of O compound intermediate is simple to operate, and reaction conditions is gentle, and post-processing step is easy, and reaction conversion ratio is high, and Atom economy is high, environmental friendliness, and good product purity is suitable for suitability for industrialized production.
Embodiment
Mode below by embodiment further illustrates the present invention, but does not therefore limit the present invention among described scope of embodiments.The experimental technique of unreceipted actual conditions in the following example, conventionally and condition, or selects according to catalogue.
The preparation of bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of embodiment 14-
Add in the four-hole bottle of 2000mL, the fluoro-4 '-pentylbiphenyl 185g(0.80mol of tetrahydrofuran (THF) (THF) 420g and 3,5-bis-), nitrogen replacement 3 times, under agitation be cooled to-50 DEG C after being replaced, cooling is finished, and slowly drips the hexane solution 400mL(1.00mol of n-Butyl Lithium, 2.5mol/L), dropwise rear insulation 3 hours, insulation drips bromine 160.0g(1.00mol after finishing), dropwise rear insulation 2 hours, after insulation, be naturally warming up to room temperature.Add salt aqueous acid (described mass percent refers to that the quality of hydrogenchloride accounts for the per-cent of the total mass of the salt aqueous acid) 365g that mass percent is 10%, steaming desolventizes, use 200g × 3 petroleum ether extraction again, merge organic layer, add anhydrous magnesium sulfate 50g, stir after 10 minutes and cross 40g silicagel column, with the sherwood oil drip washing silicagel column of 20g × 2.Steam except after sherwood oil (can recovery) bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl crude product 246.8g of 4-, GC purity 99.2%, yield 95.9%.
The preparation of bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl grignard reagents of embodiment 24-
In the four-hole bottle of 1000mL, add magnesium chips 21.2g(0.88mol), iodine 0.0227g and tetrahydrofuran (THF) (THF) 200g, after nitrogen replacement 3 times, stir at 20 DEG C, drip bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl crude product 23.8g(0.074mol of 4-) and tetrahydrofuran (THF) (THF) 100g mixed solution.Dropwise rear stirring, after solution colour is decorporated, at 20 DEG C, drip bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl crude product 212.6g(0.661mol of 4-) and 200g tetrahydrofuran (THF) (THF) mixed solution.Dropwise rear insulation, time for adding and soaking time amount to 4 hours.Then bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl Grignard reagents of 4-are obtained.Next step reaction is directly used in without purification.
The bromo-difluoro-methoxy of embodiment 35-() preparation of-1,2,3-trifluoro-benzenes
N,N-dimethylacetamide (DMAC) 600g is added in the four-hole bottle of 2000mL.Sodium 11.5g (0.5mol) and sodium hydride 4.8g (0.2mol) is added successively at 20 DEG C.Stir 1 hour, start to drip 3,4,5-trifluoromethyl phenol 200g(1.35mol) and the mixed solution of N,N-dimethylacetamide (DMAC) 200g, after dropwising, insulated and stirred 2 hours.Start to pass into difluorodibromomethane 337g(1.62mol), after dropwising, insulated and stirred 6 hours, insulation is complete pours out reaction solution in 5000mL glass reaction still, add 1000g methyl tertiary butyl ether and the stirring of 2000g water, with the extraction of 200g × 2 methyl tertiary butyl ether after separatory, merge organic layer, wash with 200g × 3 water, steam after washing except methyl tertiary butyl ether (methyl tertiary butyl ether is recyclable to be applied mechanically), add sherwood oil 800g and anhydrous magnesium sulfate 50g, stir after 10 minutes and cross 40g silicagel column, with the sherwood oil drip washing silicagel column of 20g × 2.Steam except after sherwood oil (sherwood oil can recovery) the bromo-difluoro-methoxy of crude product 5-()-1,2,3-trifluoro-benzene 327.8g, GC purity 96%, yield 79.3%.GC-MS：MS（m/z）=275.8。
Embodiment 44-(difluoro (3,4,5-trifluoromethoxy phenoxy base) methyl))-3, the 5-bis-fluoro-4 ' preparations of-propyl group-1,1 '-biphenyl
The bromo-difluoro-methoxy of tetrahydrofuran (THF) (THF) 500g, 5-(is added in the four-hole bottle of 2000mL)-1,2,3-trifluoro-benzene crude product 225g(0.735mol) and anhydrous NiCl
21.87g (0.0147mol), after nitrogen replacement 3 times, start to be warming up to about 65 DEG C, start to drip 4-bromo-3, the fluoro-4 '-pentylbiphenyl Grignard reagent of 5-bis-, dropwise rear insulation backflow 2 hours, backflow Bi Jiangzhi room temperature, drip salt aqueous acid (described mass percent refers to that the quality of hydrogenchloride accounts for the per-cent of the total mass of the salt aqueous acid) 268g that mass percent is 10%, stir after 30 minutes, filter, steam except after tetrahydrofuran (THF) (THF), add sherwood oil 800g, stir 30 minutes, separatory, aqueous phase 200g × 3 petroleum ether extractions, merge organic layer, add anhydrous magnesium sulfate 50g, stir after 10 minutes and cross 40g silicagel column, with the sherwood oil drip washing silicagel column of 20g × 2.Steam except sherwood oil (sherwood oil can recovery) 4-(difluoro (3,4,5-trifluoromethoxy phenoxy base) methyl))-3,5-bis-fluoro-4 '-propyl group-1,1 '-biphenyl 352.8g, GC purity 82.24%, yields 81.02%.GC-MS：MS（m/z）=428。
Claims (24)
1. one kind contains CF
2the preparation method of O compound, it is characterized in that comprising the following steps: in a solvent, under catalyzer existent condition, by 5-(bromo-difluoro-methoxy)-1 as shown in Equation 1,2,3-trifluoro-benzene carries out linked reaction with the fluoro-4 '-pentylbiphenyl-4-magnesium bromide of Grignard reagent 3,5-bis-as shown in Equation 2, obtains 4-(4-n-propyl) phenyl-3 as shown in Equation 3,5-bis-fluoro-1 ', 1 '-difluorobenzyl-3,4,5-trifluorophenyl ether;
2. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: described linked reaction is carried out under the condition of protection of inert gas; Described rare gas element is one or more in nitrogen, argon gas, helium, neon, Krypton and xenon.
3. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: described solvent is ether solvent.
4. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: described ether solvent is one or more in ether, methyltetrahydrofuran and tetrahydrofuran (THF).
5. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: described 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1 is 1:0.5 ~ 1:3 with the mol ratio of the fluoro-4 '-pentylbiphenyl-4-magnesium bromide 2 of described Grignard reagent 3,5-bis-.
6. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: described catalyzer is acetylacetonate nickel, molybdenyl dichloride (tricyclohexyl phosphine) nickel (II), 1,3-two (diphenylphosphine propane) Nickel Chlorides and anhydrous NiCl
2in one or more.
7. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: the mass ratio of described catalyzer and 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1 is 0.001:1 ~ 0.100:1.
8. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: the temperature of described linked reaction is 20 DEG C ~ 90 DEG C.
9. as claimed in claim 1 containing CF
2the preparation method of O compound, it is characterized in that: described 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1 is obtained by following preparation method, it comprises the following steps: in a solvent, under alkali existent condition, by 3,4,5-trifluoromethyl phenol and difluorodibromomethane carry out Williamson etherification reaction, obtain 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1;
Prepare 4-(4-n-propyl) phenyl-3,5-bis-fluoro-1 ' as shown in Equation 3 more in accordance with the method for claim 1,1 '-difluorobenzyl-3,4,5-trifluorophenyl ether.
10. as claimed in claim 9 containing CF
2the preparation method of O compound, is characterized in that: in the method for preparation 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1, and described Williamson etherification reaction carries out under the condition of protection of inert gas; Described rare gas element is one or more in nitrogen, argon gas, helium, neon, Krypton and xenon.
11. as claimed in claim 9 containing CF
2the preparation method of O compound, is characterized in that: in the method for preparation 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1, described solvent is amide solvent.
12. as claimed in claim 11 containing CF
2the preparation method of O compound, is characterized in that: described amide solvent is N,N-dimethylacetamide.
13. as claimed in claim 9 containing CF
2the preparation method of O compound, is characterized in that: in the method for preparation 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1,3,4,5-described trifluoromethyl phenols and the mol ratio of described difluorodibromomethane are 1:1 ~ 1:4.
14. as claimed in claim 9 containing CF
2the preparation method of O compound, is characterized in that: in the method for preparation 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1, described alkali is sodium and/or sodium hydride.
15. as claimed in claim 9 containing CF
2the preparation method of O compound, is characterized in that: in the method for preparation 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1,3,4,5-described trifluoromethyl phenols and the mol ratio of described alkali are 2:1 ~ 2:3.
16. as claimed in claim 1 containing CF
2the preparation method of O compound, is characterized in that: the fluoro-4 '-pentylbiphenyl-4-magnesium bromide 2 of described Grignard reagent 3,5-bis-is obtained by following preparation method, and it comprises the following steps:
Step 1: in a solvent, reacts with lithium reagent and bromine successively by 4 '-propyl group-3,5-DfBP, and obtain bromo-3, the 5-bis-fluoro-4 '-pentylbiphenyl of 4-, described lithium reagent is n-Butyl Lithium;
Step 2: in a solvent, by bromo-3,5-bis-fluoro-4 '-pentylbiphenyl and the reactive magnesiums of 4-obtained in step 1, obtains the fluoro-4 '-pentylbiphenyl-4-magnesium bromide 2 of Grignard reagent 3,5-bis-;
5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1 is obtained again according to preparation method according to claim 9; 4-(4-n-propyl) phenyl-3,5-bis-fluoro-1 ' as shown in Equation 3,1 '-difluorobenzyl-3,4,5-trifluorophenyl ether is obtained again according to preparation method according to claim 1.
17. 1 kinds of 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzenes as shown in Equation 1,
18. 5-(bromo-difluoro-methoxy)-1 as shown in Equation 1 as claimed in claim 17,2, the preparation method of 3-trifluoro-benzene, is characterized in that comprising the following steps: in a solvent, under alkali existent condition, by 3,4,5-trifluoromethyl phenol and difluorodibromomethane carry out Williamson etherification reaction, obtain 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzene 1;
19. 5-(bromo-difluoro-methoxy)-1 as shown in Equation 1 as claimed in claim 18,2, the preparation method of 3-trifluoro-benzene, it is characterized in that: in preparation 5-(bromo-difluoro-methoxy)-1,2, in the method for 3-trifluoro-benzene 1, described Williamson etherification reaction carries out under the condition of protection of inert gas; Described rare gas element is one or more in nitrogen, argon gas, helium, neon, Krypton and xenon.
The preparation method of 20. 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzenes as shown in Equation 1 as claimed in claim 18, it is characterized in that: preparation 5-(bromo-difluoro-methoxy)-1, in the method for 2,3-trifluoro-benzene 1, described solvent is amide solvent.
The preparation method of 21. 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzenes as shown in Equation 1 as claimed in claim 20, is characterized in that: described amide solvent is N,N-dimethylacetamide.
22. 5-(bromo-difluoro-methoxy)-1 as shown in Equation 1 as claimed in claim 18,2, the preparation method of 3-trifluoro-benzene, it is characterized in that: preparation 5-(bromo-difluoro-methoxy)-1, in the method for 2,3-trifluoro-benzene 1, described 3, the mol ratio of 4,5-trifluoromethyl phenol and described difluorodibromomethane is 1:1 ~ 1:4.
The preparation method of 23. 5-(bromo-difluoro-methoxy)-1,2,3-trifluoro-benzenes as shown in Equation 1 as claimed in claim 18, it is characterized in that: preparation 5-(bromo-difluoro-methoxy)-1, in the method for 2,3-trifluoro-benzene 1, described alkali is sodium and/or sodium hydride.
24. 5-(bromo-difluoro-methoxy)-1 as shown in Equation 1 as claimed in claim 18,2, the preparation method of 3-trifluoro-benzene, it is characterized in that: preparation 5-(bromo-difluoro-methoxy)-1, in the method for 2,3-trifluoro-benzene 1, described 3, the mol ratio of 4,5-trifluoromethyl phenol and described alkali is 2:1 ~ 2:3.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310049647.9A CN103086850B (en) | 2013-02-07 | 2013-02-07 | Preparation method of CF2O-containing compound, and intermediate compound and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201310049647.9A CN103086850B (en) | 2013-02-07 | 2013-02-07 | Preparation method of CF2O-containing compound, and intermediate compound and preparation method thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN103086850A CN103086850A (en) | 2013-05-08 |
| CN103086850B true CN103086850B (en) | 2014-12-24 |
Family
ID=48200043
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201310049647.9A Active CN103086850B (en) | 2013-02-07 | 2013-02-07 | Preparation method of CF2O-containing compound, and intermediate compound and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN103086850B (en) |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104513145B (en) * | 2013-09-29 | 2016-05-18 | 江苏和成新材料有限公司 | The fluoro-4-difluoro of 2,3,5-tri-(3,4,5-trifluoro-benzene phenolic group) methyl-benzaldehyde and synthetic method thereof and in the application of preparing in liquid-crystal compounds |
| CN103756688B (en) * | 2014-01-27 | 2015-05-27 | 北京八亿时空液晶科技股份有限公司 | Pentafluoropropylene ether liquid crystal compound as well as preparation method and application thereof |
| CN105294492B (en) * | 2015-09-15 | 2017-06-16 | 联化科技股份有限公司 | A kind of preparation method of substituted biphenyl |
| CN108002989A (en) * | 2017-12-04 | 2018-05-08 | 武汉药明康德新药开发有限公司 | A kind of preparation method of the fluoro- 2- trifluomethoxybenzenes of the bromo- 1- of 4- |
| CN109704915A (en) * | 2018-12-24 | 2019-05-03 | 西安彩晶光电科技股份有限公司 | A kind of polyhalo biphenyl compound and preparation method |
Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4377711A (en) * | 1981-11-04 | 1983-03-22 | Rhone-Poulenc Industries | Novel aromatic bromopolyfluoroalkyl ethers and method for the preparation thereof |
| US5105021A (en) * | 1989-04-18 | 1992-04-14 | Mitsui Toatsu Chemicals, Incorporated | Preparation of a difluorohalomethoxybenzene |
| CN1733676A (en) * | 2004-08-10 | 2006-02-15 | 上海康鹏化学有限公司 | 4-(4-n-alkyl)phenyl-3,5(or2,3)-difluoro-1',1'-difluorobenzyl-3,4,5-trifluorophenyl ether preparation method |
| US7105708B2 (en) * | 2000-12-12 | 2006-09-12 | Merck Patentgesellschaft | Method for producing compounds having a CF2O bridge |
| EP1845147A2 (en) * | 2006-04-13 | 2007-10-17 | Merck Patent GmbH | Liquid-crystalline compounds |
| CN102675062A (en) * | 2012-04-27 | 2012-09-19 | 石家庄诚志永华显示材料有限公司 | Method for preparing difluoromethoxy bridge type liquid crystal |
-
2013
- 2013-02-07 CN CN201310049647.9A patent/CN103086850B/en active Active
Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4377711A (en) * | 1981-11-04 | 1983-03-22 | Rhone-Poulenc Industries | Novel aromatic bromopolyfluoroalkyl ethers and method for the preparation thereof |
| US5105021A (en) * | 1989-04-18 | 1992-04-14 | Mitsui Toatsu Chemicals, Incorporated | Preparation of a difluorohalomethoxybenzene |
| US7105708B2 (en) * | 2000-12-12 | 2006-09-12 | Merck Patentgesellschaft | Method for producing compounds having a CF2O bridge |
| CN1733676A (en) * | 2004-08-10 | 2006-02-15 | 上海康鹏化学有限公司 | 4-(4-n-alkyl)phenyl-3,5(or2,3)-difluoro-1',1'-difluorobenzyl-3,4,5-trifluorophenyl ether preparation method |
| EP1845147A2 (en) * | 2006-04-13 | 2007-10-17 | Merck Patent GmbH | Liquid-crystalline compounds |
| CN102675062A (en) * | 2012-04-27 | 2012-09-19 | 石家庄诚志永华显示材料有限公司 | Method for preparing difluoromethoxy bridge type liquid crystal |
Non-Patent Citations (1)
| Title |
|---|
| 1-取代-2,4-二氟苯类液晶的合成;任惜寒 等;《河南师范大学学报》;20100531;第34卷(第3期);第322-324页 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN103086850A (en) | 2013-05-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN103086850B (en) | Preparation method of CF2O-containing compound, and intermediate compound and preparation method thereof | |
| CN102924243B (en) | Liquid crystal compound containing cyclopentyl and difluorometheneoxy linking group, preparation method and applications thereof | |
| CN103086848B (en) | Dicyclohexylalkyl ether terminal olefines liquid crystal compound and preparation method thereof | |
| TW201307534A (en) | Compound containing 2-fluorophenyloxymethan structure | |
| CN103980098B (en) | Containing difluoromethoxy ether bridged bond (CF2The preparation method of monomer liquid crystal compound O) | |
| CN102153441A (en) | Fluorinated terphenyl liquid crystal compound containing two 3-butenyls and preparation method thereof | |
| CN100509724C (en) | Multifluoro substituted diphenyl acetylene derivative, composition containing multifluoro substituted diphenyl acetylene derivatire, preparation method and use thereof | |
| CN103058836A (en) | Liquid crystal compound containing indan and difluoro methylenedioxy bridge, as well as preparation method and application thereof | |
| CN102888227A (en) | Liquid crystal compound and preparation method and application thereof | |
| JP2746711B2 (en) | Fluorinated 4 ″ -cyano substituted terphenyl | |
| CN103333697A (en) | Nematic negative liquid crystal containing 2,3,5,6-tetrafluorotolane, synthetic method and application | |
| CN103086843A (en) | Liquid crystal compound containing bicyclooctane as well as preparation method and application thereof | |
| CN103214353B (en) | End alkene polyfluoro diaryl ethine liquid crystal compound and preparation method thereof | |
| CN112939715A (en) | Synthesis method of 4-alkyl biphenyl acetylene | |
| CN102992972B (en) | Liquid crystal compound and preparation and application thereof | |
| CN103145525B (en) | Synthesis method of 1 - fluoro - 3 - [2 - (trans- 4 - alkyl cyclohexyl) ethyl] benzene | |
| CN101503625B (en) | Preparation method of 1,2-diaryl ethine liquid crystal | |
| CN101704724B (en) | Novel method for preparing high-proportion trans, trans-4-(4'-alkyl cyclohexyl) cyclohexyl alcohol liquid crystal intermediate compound | |
| CN101712654A (en) | Liquid crystal compound containing fluoropyrimidine and application thereof | |
| CN103242133B (en) | Synthesis method of 4-[2-(trans-4-alkylcyclohexyl)ethyl] bromobenzene | |
| CN101565343B (en) | Preparation method of difluoro methoxy bridge bond compound | |
| JP2010248138A (en) | Compound having octafluorobutylene structure and method for producing the same | |
| CN107244662B (en) | A kind of preparation method of bis- (fluorosulfonyl) imides | |
| CN101973869B (en) | Method for synthesis of flurbiprofen | |
| CN102093257B (en) | Method for preparing 2,2-diisopropylpropionitrile |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |