CN102344434B - Method for preparing difluorobenzene derivatives - Google Patents
Method for preparing difluorobenzene derivatives Download PDFInfo
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- CN102344434B CN102344434B CN 201110208203 CN201110208203A CN102344434B CN 102344434 B CN102344434 B CN 102344434B CN 201110208203 CN201110208203 CN 201110208203 CN 201110208203 A CN201110208203 A CN 201110208203A CN 102344434 B CN102344434 B CN 102344434B
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- VEPUCJFILGUFGJ-WAYWQWQTSA-N C=C/C(/F)=C(\C(O)=C)/F Chemical compound C=C/C(/F)=C(\C(O)=C)/F VEPUCJFILGUFGJ-WAYWQWQTSA-N 0.000 description 1
- CUEWKLBLDSVIKV-UHFFFAOYSA-N Fc1cccc(OCC(CC2)CCC2C(CC2)CCC22OCCO2)c1F Chemical compound Fc1cccc(OCC(CC2)CCC2C(CC2)CCC22OCCO2)c1F CUEWKLBLDSVIKV-UHFFFAOYSA-N 0.000 description 1
Abstract
To provide a method for efficiently producing conventionally hardly producible difluorobenzene derivatives having alkenyl on a side chain thereof, and to provide an intermediate usable for the production method. The production method for difluorobenzene comprises steps represented by general formulae (2a), (2b) and (2c). And each production intermediate compound thereof is provided.
Description
The present invention is to be that March 30, application number in 2007 are 200710091376.8, denomination of invention is divided an application for " preparation method's of difluoro bezene derivative " the applying date.
Technical field
The present invention relates to a kind of preparation method and preparation intermediate thereof of difluoro bezene derivative.
Background technology
Nowadays advantages such as liquid crystal display device is low voltage operated owing to it, slim demonstration are widely used.The display mode of liquid crystal display device had TN (twisted-nematic) in the past, STN (supertwist is to row), or the active-matrix (active-matrix) that forms at substrate of TN (TFT: thin film transistor) etc., they all are that to utilize the dielectric constant anisotropy value be positive liquid-crystal composition.It is that its visual angle is narrower that but these display modes have a shortcoming, and the raising of maximizing and requiring along with liquid crystal board improves this problem and becomes bigger problem in recent years.
As its solution, vertical orientation mode, IPS display modes such as (In Plane Switching transverse electric field effects) began to be practical in recent years.Vertical orientation mode is utilize liquid crystal molecule vertical orientated improving the method at visual angle, use be that the dielectric constant anisotropy value is negative liquid-crystal composition.IPS is to use transverse electric field conversion liquid crystal molecule to improve the method at visual angle in the horizontal direction of relative glass substrate in addition, and what use is that the dielectric constant anisotropy value is the liquid-crystal composition of negative or positive.So, all need the dielectric constant anisotropy value to be negative liquid crystalline cpd and liquid-crystal composition in the vertical orientation mode of the effective display mode that can improve the visual angle and IPS, urgent hope can be achieved.
As the liquid crystalline cpd of dielectric constant anisotropy value for using in the negative liquid-crystal composition, can enumerate 2,3-difluorophenyl derivative (with reference to patent documentation 1).But, only disclose side chain in the patent documentation 1 and be amino compound, not disclosing side chain fully is the compound of thiazolinyl, its preparation method is not known yet.In addition, have the compound of alkoxyl group on 1 and 4 of known phenyl ring because therefore chemically unstable does not use (with reference to non-patent literature 1) as liquid crystal material, therefore the exploitation of this compounds process for production thereof is not carried out.
Patent documentation 1: special public table 2-503568 communique
Non-patent literature 1: field, natural pond, " trend of liquid crystal material ", monthly magazine デ イ ス プ レ イ, in March, 1998, the 4th volume, No. 3 (page 5)
Summary of the invention
The invention provides used preparation intermediate among the effective preparation method of the difluoro bezene derivative that thiazolinyl is arranged on the side chain and this preparation method.
The inventor attentively studies for solving above-mentioned problem, found that by compound shown in the formula (1) being converted to the method for compound shown in the formula (2), can effectively prepare the difluoro bezene derivative that has thiazolinyl at side chain, thereby finish the present invention.
The present invention relates to,
The compound represented by formula (1) reacts compound shown in the formula of obtaining (2) with the phenates that is made by 2,3-difluorophenol;
Obtain compound shown in the formula (13) after the compound oxidation shown in this formula (2);
Compound reacts shown in the phenates that is made by compound shown in this formula (13) and the formula (7), obtains compound shown in the formula (16);
Obtain compound shown in the formula (17) after the compound deprotection shown in this formula (16);
Add water decomposition behind the reactant salt in compound and the methoxymethyl phosphine shown in this formula (17) and obtain compound shown in the formula (18);
Reactant salt obtains the preparation method of compound shown in the formula (9) in compound and the alkylphosphines shown in this formula (18),
And,
Compound shown in the formula (1) obtains compound shown in the formula (2) with the phenates reaction that is made by 2,3-difluorophenol;
Obtain compound shown in the formula (3) after the compound deprotection shown in this formula (2);
Add water decomposition behind the reactant salt in compound and the methoxymethyl phosphine shown in this formula (3) and obtain compound shown in the formula (4);
Reactant salt obtains compound shown in the formula (5) in compound and the alkylphosphines shown in this formula (4);
Obtain compound shown in the formula (6) after the compound oxidation shown in this formula (5);
Compound reacts shown in the phenates that is made by compound shown in this formula (6) and the formula (7), obtains the preparation method of compound shown in the formula (9).
Wherein,
In formula (1), (2), (13), (16), R
1And R
2Expression is independently methyl, ethyl or propyl group separately, or, R
1And R
2Expression-CH
2CH
2-,-CH
2CH
2CH
2-or-CH
2C (CH
3)
2CH
2-;
In the formula (1), X
1Expression chlorine, bromine, iodine, phenylsulfonyloxy, tolysulfonyl oxygen base, methanesulfonyloxy group or trifluoromethane sulfonyloxy;
In formula (5), (6), (9), R
3The alkyl of expression hydrogen atom or carbonatoms 1 to 5;
In the formula (7), X
2Expression chlorine, bromine, iodine, phenylsulfonyloxy, tolysulfonyl oxygen base, methanesulfonyloxy group or trifluoromethane sulfonyloxy;
In formula (7), (9), (16), (17), (18), R
4Thiazolinyl or the expression (8) of expression carbonatoms 2 to 12;
In the formula (8), R
5Be the alkyl of carbonatoms 1 to 12, the thiazolinyl of carbonatoms 2 to 12, the alkoxyl group of carbonatoms 1 to 12, the alkene oxygen base of carbonatoms 2 to 12.
Further, the invention provides preparation intermediate used in preparation process of the present invention, by compound shown in formula (2), (3), (4), (5), (6), (13), (16), (17) and (18).
Preparation method of the present invention, as the preparation method of difluoro bezene derivative of great use.In addition, preparation method of the present invention is owing to introduced side chain R in final step
3Or R
4, can synthesize extremely easily and have only R
3Or R
4Compound group shown in the different formula (9).
Embodiment
Among the preparation method of the present invention, 2,3-difluorophenol and alkali effect generate phenates, obtain compound shown in the formula (2) with the reaction of compound shown in the formula (1) then, the alkali that uses can be enumerated metal hydride, metal carbonate, metal phosphate, metal hydroxides, metal carboxylate, metal amide and metal etc., wherein preferred as alkali hydride, alkali metal phosphate, alkali metal phosphate, alkaline carbonate, alkali metal hydroxide, alkali metal amide, basic metal; Further preferred as alkali phosphoric acid salt, alkalimetal hydride, alkaline carbonate.The preferred lithium hydride of alkalimetal hydride, sodium hydride, potassium hydride KH, alkali metal phosphate preferably phosphoric acid tripotassium, the preferred yellow soda ash of alkaline carbonate, sodium bicarbonate, cesium carbonate, salt of wormwood, saleratus.
As reaction solvent, if be fit to reaction carry out any all can, but preferably use ether solvent, chlorine kind solvent, varsol, aromatic series kind solvent, polar solvent etc.As ether solvent, can enumerate 1,4-two
Alkane, 1,3-two
Alkane, tetrahydrofuran (THF), Anaesthetie Ether, t-butyl methyl ether etc., can enumerate methylene dichloride, 1 as the chlorine kind solvent, 2-ethylene dichloride, four salinization carbon etc., can enumerate amylene, hexene, tetrahydrobenzene, heptane, octane etc. as varsol, can enumerate benzene,toluene,xylene, trimethylbenzene, chlorobenzene, dichlorobenzene etc. as the aromatic series kind solvent, polar solvent can be enumerated N, and dinethylformamide, N-Methyl pyrrolidone, dimethyl sulfoxide (DMSO), tetramethylene sulfone etc. are example preferably.Wherein be more preferably ether solvent, the N of tetrahydrofuran (THF), Anaesthetie Ether etc., the polar solvent of dinethylformamide etc.In addition, each solvent of preceding note can use separately, also can 2 kinds or above mixing use.
Though temperature of reaction can be carried out in reflow temperature range in the zero pour from solvent, preferred 0 ℃ to 150 ℃, further preferred 30 ℃ to 120 ℃.In addition, but react with compound shown in the formula (1) after the phenates flash liberation of generation, also can not separate and react, but consider under not separating, to react better from the difficulty or ease of operation.
The deprotection of compound preferably carries out under acidic conditions shown in formula (2) or the formula (16).The acid of using can be enumerated the protonic acid of formic acid, acetic acid, trifluoroacetic acid, oxalic acid, tosic acid etc., the Lewis acid of boron trifluoride element etc. etc., but preferably use formic acid.
Reaction solvent, any as long as the carrying out that is fit to react can be used, preferably use ether solvent, chlorine kind solvent, ketones solvent, varsol, aromatic series kind solvent, polar solvent etc., also can under solvent-free, react.Ether solvent can be enumerated 1,4-two
Alkane, 1,3-two
Alkane, tetrahydrofuran (THF), Anaesthetie Ether, t-butyl methyl ether etc., the chlorine kind solvent has methylene dichloride, 1,2-ethylene dichloride, chloroform, four salinization carbon etc., ketones solvent can be enumerated acetone, 2-butanone etc., varsol can be enumerated amylene, hexene, tetrahydrobenzene, heptane, octane etc., the aromatic series kind solvent can be enumerated benzene,toluene,xylene, trimethylbenzene, chlorobenzene, dichlorobenzene etc., and polar solvent can be enumerated example preferably such as acetonitrile, dimethyl sulfoxide (DMSO).Wherein, be more preferably the varsol of amylene, hexene, tetrahydrobenzene, heptane, octane etc., the aromatic series kind solvent of benzene,toluene,xylene etc. etc.In addition, each solvent of preceding note can use separately, also can 2 kinds or above solvent use.
Though temperature of reaction can be carried out in reflow temperature range in the zero pour from solvent, preferred 0 ℃ to 100 ℃, further preferred 30 ℃ to 60 ℃.
Add water decomposition behind the reactant salt in compound and the methoxymethyl phosphine shown in formula (3) or the formula (17), can obtain compound shown in the formula (4) from formula (3), can obtain compound shown in the formula (18) from formula (17).Methoxymethyl phosphine inner salt can make from phosphonium salt, phosphoric acid ester etc., preferably makes from the methoxymethyl triphenylphosphine salt.
When using the methoxymethyl triphenylphosphine salt to prepare inner salt and the alkali effect, the preferred potassium tert.-butoxide of the alkali of use, n-Butyl Lithium, phenyl lithium, sodium hydride etc. are more preferably potassium tert.-butoxide.Reaction solvent preferably uses ether solvent, aromatic series kind solvent, polar solvent etc.Ether solvent can be enumerated 1,4-two
Alkane, 1,3-two
Alkane, tetrahydrofuran (THF), Anaesthetie Ether, t-butyl methyl ether etc., the aromatic series kind solvent can be enumerated benzene,toluene,xylene, trimethylbenzene etc., and polar solvent can be enumerated N, dinethylformamide etc.Wherein be more preferably tetrahydrofuran (THF), toluene.In addition, each solvent of preceding note can use separately, also can 2 kinds or above solvent use.
Temperature of reaction can be carried out in reflow temperature range from the zero pour of solvent, but preferred-40 ℃ to 30 ℃, further preferred-20 ℃ to 20 ℃.The inner salt that obtains preferably reacts with compound shown in the formula (3) under unseparated situation.In addition, also can add alkali in the mixture of compound shown in methoxymethyl triphenylphosphine salt, the formula (3).
Adding water decomposition can carry out under acid catalyst.The acid of using can be enumerated dilute hydrochloric acid, aqueous sulfuric acid etc.Reaction solvent, any as long as the carrying out that is fit to react can be used, preferably use ether solvent, varsol, aromatic series kind solvent etc., also can under solvent-free, react.Ether solvent can be enumerated 1,4-two
Alkane, 1,3-two
Alkane, tetrahydrofuran (THF), Anaesthetie Ether, t-butyl methyl ether etc., varsol can be enumerated amylene, hexene, tetrahydrobenzene, heptane, octane etc., and the aromatic series kind solvent can be enumerated benzene,toluene,xylene, trimethylbenzene, chlorobenzene, dichlorobenzene etc.Wherein, be more preferably tetrahydrofuran (THF).In addition, each solvent of preceding note can use separately, also can 2 kinds or above solvent use.
Temperature of reaction can be carried out in reflow temperature range from the zero pour of solvent, preferred 0 ℃ to 80 ℃.
Compound shown in the formula that so obtains (4) or the formula (18), what obtain for cyclohexene ring is cis and trans mixture, but uses preferably trans as the intermediate of liquid crystalline cpd.For the cyclohexene ring in conjunction with the formyloxy side of compound shown in formula (4) or the formula (18), by can making its cis-trans isomerizationization with the alkali effect, thereby make trans surplus.The preferred sodium hydroxide of alkali that uses this moment, potassium hydroxide etc., reaction solvent particular methanol, ethanol, tetrahydrofuran (THF) etc., preferred-40 ℃ to 20 ℃ of temperature of reaction, further preferred-20 ℃ to 10 ℃.
Reactant salt in compound and the alkylphosphines shown in formula (4) or the formula (18) can obtain formula (5) from formula (4), obtains compound shown in the ultimate aim product formula (9) from formula (18).In this reaction, the alkylphosphines inner salt can make from phosphonium salt, phosphoric acid ester etc., preferably makes from the alkyl triphenylphosphine salt.
When using the alkyl triphenylphosphine salt to make inner salt and the alkali effect, the preferred potassium tert.-butoxide of the alkali of use, n-Butyl Lithium, phenyl lithium, sodium hydride etc. are more preferably potassium tert.-butoxide.Reaction solvent preferably uses ether solvent, aromatic series kind solvent, polar solvent etc.Ether solvent can be enumerated 1,4-two
Alkane, 1,3-two
Alkane, tetrahydrofuran (THF), Anaesthetie Ether, t-butyl methyl ether etc., the aromatic series kind solvent can be enumerated benzene,toluene,xylene, trimethylbenzene etc., and polar solvent can be enumerated N, and dinethylformamides etc. wherein are more preferably tetrahydrofuran (THF), toluene.In addition, each solvent of preceding note can use separately, also can 2 kinds or above solvent use.Temperature of reaction can be carried out in reflow temperature range from the zero pour of solvent, preferably from-40 ℃ to 30 ℃, and further preferred-20 ℃ to 20 ℃.The inner salt of gained preferably reacts with compound shown in the formula (4) under unseparated situation.In addition, also can add alkali in the mixture of compound shown in alkyl triphenylphosphine salt, the formula (4).The alkyl triphenylphosphine salt is preferably used the methyl triphenyl phosphonium salt.
The oxidation of compound shown in formula (2) or the formula (5) can utilize organometallic reagent to take off behind the proton and obtain boron compound with the trialkyl borate reaction, then with the oxygenant effect.Reaction solvent as long as carrying out of being fit to react is any all passable, can be enumerated ether solvent, varsol etc.As ether solvent, can enumerate 1,4-two
Alkane, 1,3-two
Alkane, tetrahydrofuran (THF), Anaesthetie Ether, t-butyl methyl ether etc., varsol can be enumerated amylene, hexene, tetrahydrobenzene, heptane, octane etc., wherein preferred tetrahydrofuran (THF).Organometallic reagent can be enumerated n-Butyl Lithium, s-butyl lithium, tert-butyl lithium, lithium methide, lithium diisopropylamide etc., from obtain and operation difficulty or ease aspect consider preferred n-Butyl Lithium, s-butyl lithium, since effectively deprotonation be more preferably s-butyl lithium.In addition, during deprotonation, also can add potassium tert.-butoxide as additive, alkali such as tetramethylethylened with above-mentioned organometallic reagent.Preferred-100 ℃ to-20 ℃ of temperature of reaction during deprotonation, further preferred-78 ℃ to-40 ℃.
Trialkyl borate preferably uses trimethyl borate.Preferred-100 ℃ to-20 ℃ of temperature of reaction during boronation, further preferred-78 ℃ to-40 ℃.The boron compound that obtains can flash liberation, also can not separate directly and oxidant reaction.In addition, the boron compound that obtains add change into after the water decomposition behind the boronic acid compounds also passable with oxidant reaction again.
Oxygenant preferably uses hydrogen peroxide, peracetic acid or peroxyformic acid.Preferred-78 ℃ to 70 ℃ of temperature of reaction, further preferred 0 ℃ to 50 ℃.In addition, during with oxidant reaction, solvent comprises water also has no relations.
Shown in formula (1), formula (2), formula (13) and the formula (16) in the compound carbonyl utilize R
1And R
2Protect.R
1And R
2Independent separately is methyl, ethyl or propyl group, perhaps, and R
1And R
2Expression-CH
2CH
2-,-CH
2CH
2CH
2-or-CH
2C (CH
3)
2CH
2-, work as R
1And R
2For-CH
2CH
2-,-CH
2CH
2CH
2-or-CH
2C (CH
3)
2CH
2In-time, the concrete formula that formula (1) is put down in writing is as follows.
In the formula (1), preferred R
1And R
2Be methyl, or R
1And R
2For-CH
2CH
2-or-CH
2CH
2CH
2-.X
1And X
2Be chlorine, bromine, iodine, phenylsulfonyloxy, tolysulfonyl oxygen base, methanesulfonyloxy group or trifluoromethane sulfonyloxy, preferred bromine or methanesulfonyloxy group.R
4Be the thiazolinyl of carbonatoms 2 to 12, preferred 3-butenyl and 4-pentenyl.R
5Alkyl for carbonatoms 1 to 12, the thiazolinyl of carbonatoms 2 to 12, the alkoxyl group of carbonatoms 1 to 12, the alkene oxygen base of carbonatoms 2 to 12, the alkyl of preferred carbonatoms 1 to 12 or the thiazolinyl of carbonatoms 2 to 12, the alkyl of further preferred carbonatoms 1 to 7.
The present invention further specifically is preferably as follows described compound suc as formula the preparation intermediate of (2).
Further compound shown in preferred formula (2a), formula (2b) or the formula (2d) wherein.
R in the formula (5)
3Be the alkyl of hydrogen atom or carbonatoms 1 to 5, preferred hydrogen atom or methyl, more preferably hydrogen atom.
R in the formula (6)
3Be the alkyl of hydrogen atom or carbonatoms 1 to 5, preferred hydrogen atom or methyl, more preferably hydrogen atom.
Compound shown in the present invention further specifically is preferably as follows suc as formula the preparation intermediate of (13).
Further compound shown in preferred formula (13a), formula (13b) or the formula (13d) wherein.
The present invention's preparation intermediate as the formula (16) further is preferably as follows formula (16a) to compound shown in the formula (16l).
In the formula, R
6Thiazolinyl for carbonatoms 2 to 12.
Formula (16a) arrives in the formula (16f), R
6Concrete is 3-butenyl, 3-pentenyl, 4-pentenyl or 4-hexenyl preferably, further preferred 3-butenyl or 4-pentenyl.
In the formula, R
5Be the alkyl of carbonatoms 1 to 12, the thiazolinyl of carbonatoms 2 to 12, the alkoxyl group of carbonatoms 1 to 12 or the alkene oxygen base of carbonatoms 2 to 12.
Formula (16g) arrives in the formula (16l), R
5Be preferably the alkyl of carbonatoms 1 to 7, the thiazolinyl of carbonatoms 2 to 7, the alkoxyl group of carbonatoms 1 to 7 or the alkene oxygen base of carbonatoms 2 to 7, alkyl, the thiazolinyl of carbonatoms 2 to 5, the alkoxyl group of carbonatoms 1 to 5 or the alkene oxygen base of carbonatoms 2 to 5 of further preferred carbonatoms 1 to 5, the alkyl of preferred especially carbonatoms 1 to 5 or the thiazolinyl of carbonatoms 2 to 5.Thiazolinyl preferred vinyl, 1-propenyl, 3-butenyl or 3-pentenyl, special preferred vinyl.
The present invention's preparation intermediate as the formula (17) further specifically is preferably as follows compound shown in formula (17a) and the formula (17b).
In the formula, R
6Be the thiazolinyl of carbonatoms 2 to 12, R
5Be the alkyl of carbonatoms 1 to 12, the thiazolinyl of carbonatoms 2 to 12, the alkoxyl group of carbonatoms 1 to 12 or the alkene oxygen base of carbonatoms 2 to 12.
In the formula (17a), R
6Concrete is 3-butenyl, 3-pentenyl, 4-pentenyl or 4-hexenyl preferably, further preferred 3-butenyl or 4-pentenyl.
In the formula (17b), R
5Be preferably the alkyl of carbonatoms 1 to 7, the thiazolinyl of carbonatoms 2 to 7, the alkoxyl group of carbonatoms 1 to 7 or the alkene oxygen base of carbonatoms 2 to 7, more preferably the alkene oxygen base of the alkoxyl group of the thiazolinyl of the alkyl of carbonatoms 1 to 5, carbonatoms 2 to 5, carbonatoms 1 to 5 or carbonatoms 2 to 5 is preferably the alkyl of carbonatoms 1 to 5 or the thiazolinyl of carbonatoms 2 to 5 especially.Thiazolinyl preferred vinyl, 1-propenyl, 3-butenyl or 3-pentenyl, special preferred vinyl.
Compound shown in the formula that is preferably as follows (18a) that the present invention's preparation intermediate as the formula (18) is concrete and the formula (18b).
In the formula, R
6Thiazolinyl, R for carbonatoms 2 to 12
5Be the alkyl of carbonatoms 1 to 12, the thiazolinyl of carbonatoms 2 to 12, the alkoxyl group of carbonatoms 1 to 12 or the alkene oxygen base of carbonatoms 2 to 12.
In the formula (17a), R
6Concrete is 3-butenyl, 3-pentenyl, 4-pentenyl or 4-hexenyl preferably, more preferably 3-butenyl or 4-pentenyl.
In the formula (17b), R
5Be preferably the alkene oxygen base of the alkoxyl group of thiazolinyl, carbonatoms 1 to 7 of alkyl, the carbonatoms 2 to 7 of carbonatoms 1 to 7 or carbonatoms 2 to 7, more preferably alkyl, the thiazolinyl of carbonatoms 2 to 5, the alkoxyl group of carbonatoms 1 to 5 or the alkene oxygen base of carbonatoms 2 to 5 of carbonatoms 1 to 5, the alkyl of preferred especially carbonatoms 1 to 5 or the thiazolinyl of carbonatoms 2 to 5.Thiazolinyl preferred vinyl, 1-propenyl, 3-butenyl or 3-pentenyl, special preferred vinyl.
Embodiment
Below, enumerate embodiment and be described in further detail the present invention, but the present invention is not restricted to these embodiment.The structure of compound can be utilized nucleus magnetic resonance (NMR), and mass spectroscopy (MS) etc. is confirmed.
Utilize following abbreviation to describe compound.
THF: tetrahydrofuran (THF)
DMF:N, dinethylformamide
Me: methyl
Et: ethyl
Bu: butyl
Ph: phenyl
Ms: methane sulfonyl
Reference example
Initial substance of the present invention is compound shown in the formula (1), can utilize for example following method preparation.
In the formula, R
1And R
2Be the expression meaning identical with formula (1), Ms is methane sulfonyl.
Embodiment 1:4-(anti-, own-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, synthetic 1 of 3-two fluoro-1-(4-amylene oxygen) benzene (If)
1-1:3-[4, oneself-4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-1,2-two fluorobenzene (Ia) synthetic
Methanesulfonic (own-4 '-yl) methyl, 2 of 4,4-(ethylidene dioxy) dicyclo, 3-methylene fluoride sulfonic acid (4, own-4 '-yl) the methyl esters 122.9g of 4-(ethylidene dioxy) dicyclo, 2,3-difluorophenol 49.5g, Tripotassium phosphate 235.4g and DMF 690mL mix, and 3 stir hour down at 80 ℃.Filter reaction mixture, solid ingredient utilize DMF to clean, and filter.Merging filtrate adds frozen water, and solid is separated out in leaching, dissolves in the mixed solvent of acetic acid ethyl, hexene, toluene.In its column chromatography of packing into, desolventizing is heated up in a steamer in decompression, the refining 3-[4 that obtains 111.6g of residue recrystallize, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-1,2-two fluorobenzene (Ia).Compound (Ia), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：366(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.3-2.0(m，19H)，3.8-4.0(m，6H)，6.4-6.6(m，2H)，6.8-7.0(m，1H)
1-2:4-[4, oneself-4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-2,3-difluorophenol (Ig) synthetic
With the 3-[4 of 90g, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-1,2-two fluorobenzene (Ia) are dissolved among the THF of 540mL.Add secondary BuLi (1.0M tetrahydrobenzene solution) 260mL down at Nei Wen-60 ℃, stirred 2 hours.Add trimethyl borate 29g down at Nei Wen-60 ℃, be warming up to 20 ℃.Add 15% hydrogen peroxide 72mL, stirred 5 hours down at 35 ℃.Utilize the neutralization of 10% hydrochloric acid after adding 10% aqueous solution of sodium bisulfite, after branch is got organic layer, with 400mL methylbenzene extraction water layer, merge organic layer and utilize 10% salt solution 250mL and water 250mL to clean, utilize anhydrous sodium sulfate drying.Desolventizing is heated up in a steamer in decompression, the refining 4-[4 that obtains of residue recrystallize, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-2,3-difluorophenol (Ib) 87.9g.Compound (Ib), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：382(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.3-2.2(m，19H)，3.8-4.0(m，6H)，4.0-6.0(s，1H)，6.3-6.5(m，2H)
1-3:4-[4, oneself-4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-2,3-two fluoro-1-(4-amylene oxygen) benzene (Ih) synthetic
With 5-bromo-1-amylene, 4-[4, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-2,3-difluorophenol (Ig), Tripotassium phosphate and DMF mix, and stir 2 hours down at 130 ℃.Add water, use methylbenzene extraction, desolventizing was heated up in a steamer in decompression after water and saturated aqueous common salt were cleaned organic layer.Residue utilizes column chromatography and recrystallize to make with extra care, and obtains 4-[4, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-2,3-two fluoro-1-(4-amylene oxygen) benzene (Ih).Compound (Ih), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：450(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.3-2.2(m，23H)，3.8-4.0(m，8H)，4.9-5.1(m，2H)，5.6-5.8(m，1H)，6.3-6.5(m，2H)
1-4:4-(dicyclo oneself-methoxyl group-2 of 4-ketone-4 '-yl), 3-two fluoro-1-(4-amylene oxygen) benzene (Ii) synthetic
4-[4, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-2, add toluene and formic acid in 3-two fluoro-1-(the 4-amylene oxygen) benzene (Ih), stirred 2 hours down at 50 ℃.After being cooled to room temperature, adding moisture and get organic layer, utilize the methylbenzene extraction water layer.After merging organic layer and utilizing water, saturated sodium bicarbonate aqueous solution and saturated aqueous common salt to clean, utilize anhydrous magnesium sulfate drying after decompression heat up in a steamer desolventizing.The residue recrystallize is refining obtain 4-(dicyclo oneself-methoxyl group-2 of 4-ketone-4 '-yl), 3-two fluoro-1-(4-amylene oxygen) benzene (Ii).Compound (Ii), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：406(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.6-2.0(m，19H)，2.0-2.4(m，4H)，3.8-4.0(m，4H)，4.9-5.1(m，2H)，5.6-5.8(m，1H)，6.3-6.5(m，2H)
1-5:4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-formyloxy dicyclo, 3-two fluoro-1-(4-amylene oxygen) benzene (Ij) synthetic
4-(dicyclo oneself-methoxyl group-2 of 4-ketone-4 '-yl), 3-two fluoro-1-(4-amylene oxygen) benzene (Ii) and methoxymethyl triphenylphosphine muriate are scattered among the THF, at 0～5 ℃ of THF solution that adds potassium tert.-butoxide down of interior temperature, stir 2 hours.Desolventizing is heated up in a steamer in decompression after adding water, adds hexene filtering separation solid ingredient in the residue.Filtrate is utilized 50% methanol aqueous solution, and water and saturated aqueous common salt are cleaned, and use anhydrous magnesium sulfate drying.Desolventizing is heated up in a steamer in decompression, adds 10% hydrochloric acid and THF in the residue, adds and refluxes 1 hour.Divide and get organic layer, utilize the methylbenzene extraction water layer.Merge organic layer and utilize saturated aqueous common salt to clean, heat up in a steamer desolventizing with decompression behind the anhydrous sodium sulfate drying.Add triethylamine, THF and methyl alcohol in the residue.Add 30% aqueous sodium hydroxide solution then therein, stirred 3 hours down at 5 ℃.Neutralize with 10% hydrochloric acid after adding water, add THF and toluene.Divide and get organic layer, heat up in a steamer desolventizing with decompression behind the anhydrous magnesium sulfate drying, obtain 4-(instead, own-4 '-yl) methoxyl group-2 of anti--4-formyloxy dicyclo, 3-two fluoro-1-(4-amylene oxygen) benzene (Ij).Compound (Ij), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：420(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.3-2.0(m，23H)，2.2-2.4(m，1H)，3.8-4.0(m，4H)，4.9-5.1(m，2H)，5.6-5.8(m，1H)，6.4-6.6(m，2H)，9.6-9.8(m，1H)
1-6:4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(4-amylene oxygen) benzene (If) synthetic
Methyl triphenyl phosphine bromide is scattered among the THF, is adding potassium tert.-butoxide below 0 ℃, stirs stirring in 30 fens.Splash into 4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-formyloxy dicyclo, the THF solution of 3-two fluoro-1-(4-amylene oxygen) benzene (Ij) stirred 1 hour.Desolventizing is heated up in a steamer in decompression after adding acetone and water, adds hexene leaching solid ingredient in the residue.Filtrate utilizes 50% methanol aqueous solution, water and saturated aqueous common salt to clean, and uses anhydrous magnesium sulfate drying.Desolventizing is heated up in a steamer in decompression, and residue utilizes column chromatography and recrystallize to make with extra care, and obtains 4-(instead, own-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(4-amylene oxygen) benzene (If).Compound (If), as the component parts of liquid-crystal composition of great use.
Embodiment 2:4-(anti-, own-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, synthetic 2 of 3-two fluoro-1-(4-amylene oxygen) benzene (If)
2-1: adopt with the synthetic 3-[4 of the same method of 1-1 among the embodiment 1, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-1,2-two fluorobenzene (Ia).
2-2:3-(dicyclo oneself-methoxyl group-1 of 4-ketone-4 '-yl), 2-two fluorobenzene (Ib) synthetic
3-[4, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-1,2-two fluorobenzene (Ia) 111g is dissolved among the toluene 330mL, stirs 2 hours down at 50 ℃ behind the adding formic acid 270mL.After being cooled to room temperature, adding water 200mL branch and get organic layer, extract water layer with toluene 300mL.Utilize water, saturated sodium bicarbonate aqueous solution and saturated aqueous common salt to clean after merging organic layer, heat up in a steamer desolventizing with decompression behind the anhydrous magnesium sulfate drying.The residue recrystallize is refining obtain 3-(dicyclo oneself-methoxyl group-1 of 4-ketone-4 '-yl), 2-two fluorobenzene (Ib) 95g.Compound (Ib), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：322(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.6-2.0(m，15H)，2.0-2.4(m，4H)，3.8-4.0(m，2H)，6.4-6.6(m，2H)，6.8-7.0(m，1H)
2-3:3-(anti-, oneself-4 '-yl) methoxyl group-1 of anti--4-formyloxy dicyclo, 2-two fluorobenzene (Ic) synthetic
3-(dicyclo oneself-methoxyl group-1 of 4-ketone-4 '-yl), 2-two fluorobenzene (Ib) 95g and methoxymethyl triphenylphosphine muriate 132g are scattered among the THF 650mL, at 0～5 ℃ of THF (180mL) solution that adds potassium tert.-butoxide 44g down of interior temperature, stir 2 hours.Desolventizing is heated up in a steamer in decompression after adding water 25mL, adds hexene 700mL leaching solid ingredient in the residue.Filtrate is utilized 50% methanol aqueous solution, and water and saturated aqueous common salt are cleaned, and use anhydrous magnesium sulfate drying.Desolventizing is heated up in a steamer in decompression, adds 10% hydrochloric acid 300mL and THF400mL, reflux 1 hour in the residue.Divide and get organic layer, utilize toluene 300mL to extract water layer.Utilize saturated aqueous common salt to clean after merging organic layer, heat up in a steamer desolventizing with decompression behind the anhydrous sodium sulfate drying.Add triethylamine 8mL, THF 250mL and methyl alcohol 400mL in the residue.Wherein add 30% aqueous sodium hydroxide solution 20mL again, stirred 3 hours down at 5 ℃.Neutralize with 10% hydrochloric acid after adding water 600mL, add THF 300mL and toluene 700mL.Divide and get organic layer, heat up in a steamer desolventizing with decompression behind the anhydrous magnesium sulfate drying, obtain 3-(instead, own-4 '-yl) methoxyl group-1 of anti--4-formyloxy dicyclo, 2-two fluorobenzene (Ic) 99g.Compound (Ic), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：336(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.3-2.0(m，19H)，2.2-2.4(m，1H)，3.8-4.0(m，2H)，6.4-6.6(m，2H)，6.8-7.0(m，1H)，9.6-9.8(m，1H)
2-4:3-(anti-, oneself-4 '-yl) methoxyl group-1 of anti--4-vinyl dicyclo, 2-two fluorobenzene (Id) synthetic
Methyl triphenyl phosphine bromide 136g is scattered among the THF 340mL, adding potassium tert.-butoxide 46g below 0 ℃, stirs 30 fens.Dropping 3-(anti-, own-4 '-yl) methoxyl group-1 of anti--4-formyloxy dicyclo, THF (200mL) solution of 2-two fluorobenzene (Ic) 99g stirred 1 hour.Desolventizing is heated up in a steamer in decompression after adding acetone 15mL and water 15mL, adds hexene 500mL leaching solid ingredient in the residue.Filtrate utilizes 50% methanol aqueous solution, water and saturated aqueous common salt to clean, and uses anhydrous magnesium sulfate drying.Desolventizing is heated up in a steamer in decompression, and residue utilizes column chromatography and recrystallize to make with extra care, and obtains 3-(instead, own-4 '-yl) methoxyl group-1 of anti--4-vinyl dicyclo, 2-two fluorobenzene (Id) 81g.Compound (Id), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：334(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.3-2.2(m，20H)，3.8-4.0(m，2H)，4.8-5.0(m，2H)，5.7-5.9(m，1H)，6.4-6.6(m，2H)，6.8-7.0(m，1H)
2-5:4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-difluorophenol (Ie) synthetic
3-(anti-, own-4 '-yl) methoxyl group-1 of anti--4-vinyl dicyclo, 2-two fluorobenzene (Id) 39g is dissolved among the THF 320mL.Add secondary BuLi (0.95M tetrahydrobenzene solution) 196mL down at Nei Wen-60 ℃, stirred 2 hours.At Nei Wen-60 ℃ of THF (42mL) solution that adds trimethyl borate 21g down, be warming up to 0 ℃.Add water 7.2mL and stir after 10 minutes, add 30% hydrogen peroxide 34mL, stirred 5 hours down at 35 ℃.Neutralize with 10% hydrochloric acid after adding 10% aqueous solution of sodium bisulfite, divide and get organic layer.Utilize 120mL methylbenzene extraction water layer, utilize 10% salt solution to clean behind the merging organic layer, utilize anhydrous sodium sulfate drying.Desolventizing is heated up in a steamer in decompression, refining 4-(instead, own-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-difluorophenol (Ie) 36g of obtaining of residue recrystallize.Compound (Ie), as the preparation intermediate of liquid crystalline cpd of great use.
MS?m/z：350(M
+)
1H-NMR(60MHz，CDCl
3)
δ：1.3-2.2(m，20H)，3.8-4.0(m，2H)，4.8-5.0(m，2H)，5.7-5.9(m，1H)，6.3-6.5(m，2H)，4.0-6.0(s，1H)
2-6:4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(4-amylene oxygen) benzene (If) synthetic
5-bromo-1-amylene, 4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-difluorophenol (Ie), Tripotassium phosphate and DMF mix, and stir 2 hours down at 130 ℃.Add water, utilize methylbenzene extraction, desolventizing was heated up in a steamer in decompression after organic layer utilized water and saturated aqueous common salt to clean.Residue utilizes column chromatography and recrystallize to make with extra care, and obtains 4-(instead, own-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(4-amylene oxygen) benzene (If).Compound (If), as the formation portion material of liquid-crystal composition of great use.
Phase inversion temperature: C 75.6 N 195.2 I
MS?m/z：418(M
+)
1H-NMR(400MHz，CDCl
3)
δ：0.95-1.15(m，10H)，1.65-2.00(m，12H)，2.20-2.30(m，2H)，3.76(d，J＝6.4Hz，2H)，3.98(t，J＝6.8Hz，2H)，4.87(d，J＝10.0Hz，1H)，4.95(d，J＝17.2Hz，1H)，5.00(d，J＝10.4Hz，1H)，5.05(d，J＝17.2Hz，1H)，5.77(ddd，J＝17.2Hz，J＝10.4Hz，J＝6.4Hz，1H)，5.84(ddt，J＝16.8Hz，J＝13.6Hz，J＝6.8Hz，1H)，6.55-6.65(m，2H)
Embodiment 3:4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(3-butylene oxygen) benzene (IIf) synthetic
Among the embodiment 1 or 2, replace 5-bromo-1-amylene to use 4-bromo-1-butylene, carry out same reaction, obtain 4-(instead, own-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(3-butylene oxygen) benzene (IIf).
Phase inversion temperature C 64.5 N 119.5 I
MS?m/z：404(M
+)，55(100)
1H-NMR(400MHz，CDCl
3)
δ：0.95-1.15(m，10H)，1.65-2.00(m，10H)，2.50-2.60(m，2H)，3.76(d，J＝6.4Hz，2H)，4.03(t，J＝6.8Hz，2H)，4.80-5.30(m，4H)，5.79(ddd，J＝17.2Hz，J＝10.4Hz，J＝6.4Hz，1H)，5.83-5.95(m，1H)，6.55-6.70(m，2H)
Embodiment 4:4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(anti--4-ethyl cyclohexyl) anisole (IIIf) synthetic
Among the embodiment 1 or 2, replace 5-bromo-1-amylene to use anti--4-(ethyl cyclohexyl) monobromethane, carry out same reaction, it is (anti-to obtain 4-, instead-and own-4 '-yl) methoxyl group-2 of 4-vinyl dicyclo, 3-two fluoro-1-(anti--4-ethyl cyclohexyl) anisole (IIIf).
Phase inversion temperature C 94.1 N 197.5 I
MS?m/z：474(M
+)，146(100)
1H-NMR(400MHz，CDCl
3)
δ：0.88(t，J＝7.2Hz，3H)，0.90-1.30(m，17H)，1.65-2.00(m，15H)，3.70-3.80(m，4H)，4.80-5.00(m，2H)，5.77(ddd，J＝16.8Hz，J＝10.4Hz，J＝6.4Hz，1H)，6.59(d，J＝5.6Hz，2H)
Embodiment 5:4-(anti-, oneself-4 '-yl) methoxyl group-2 of anti--4-vinyl dicyclo, 3-two fluoro-1-(anti--4-vinyl cyclohexyl) anisole (IVf) synthetic
Among the embodiment 1 or 2, replace 5-bromo-1-amylene use methanesulfonic anti--4-(vinyl cyclohexyl) methyl, carry out same reaction, it is (anti-to obtain 4-, instead-and own-4 '-yl) methoxyl group-2 of 4-vinyl dicyclo, 3-two fluoro-1-(anti--4-vinyl cyclohexyl) anisole (IVf).
Phase inversion temperature C 86.5 N 205.8 I
MS?m/z：472(M
+)，146(100)
1H-NMR(400MHz，CDCl
3)
δ：0.95-1.25(m，14H)，1.65-2.00(m，16H)，3.77(t，J＝7.2Hz，4H)，4.85-5.05(m，4H)，5.70-5.85(m，2H)，6.60(d，J＝5.6Hz，2H)
Industrial utilizability
The inventive method as the preparation method of liquid crystalline cpd of great use.Compound of the present invention as the preparation intermediate of liquid crystalline cpd also of great use in addition.
Claims (3)
1. compound as the formula (2),
In the formula, R
1And R
2Expression is independently methyl, ethyl or propyl group separately, or, the concrete formula of formula (2) shown in following formula (2a), formula (2b) or formula (2c),
2. compound as the formula (13):
In the formula, R
1And R
2Expression is independently methyl, ethyl or propyl group separately, or, the concrete formula of formula (13) shown in following formula (13a), formula (13b) or formula (13c),
3. compound as the formula (16),
In the formula (16), R
1And R
2Expression is independently methyl, ethyl or propyl group separately, or, the concrete formula of formula (16) shown in following formula (16a), formula (16b) or formula (16c), R
4Thiazolinyl or the expression (8) of expression carbonatoms 2 to 12,
In the formula, R
6Implication and R
4It is identical,
In the formula (8), R
5Be the alkyl of carbonatoms 1 to 12, the thiazolinyl of carbonatoms 2 to 12, the alkoxyl group of carbonatoms 1 to 12, the alkene oxygen base of carbonatoms 2 to 12.
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