CN103145542A - Method for producing difluorobenzene derivative - Google Patents
Method for producing difluorobenzene derivative Download PDFInfo
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- CN103145542A CN103145542A CN2013100048735A CN201310004873A CN103145542A CN 103145542 A CN103145542 A CN 103145542A CN 2013100048735 A CN2013100048735 A CN 2013100048735A CN 201310004873 A CN201310004873 A CN 201310004873A CN 103145542 A CN103145542 A CN 103145542A
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Abstract
The invention relates to an effective method of producing difluorobenzene derivative containing thiazolinyl on a side chain and a producing intermediate used in the producing method. As the following shown steps, the invention provides a method for producing difluorobenzene derivative. Furthermore, the invention provides a producing intermediate compound. The method of the invention can effectively produce the liquid-crystal compounds shown by the formula (9). Furthermore, the producing method of the invention leads R4 in the final step so that a compound group only comprising R4 shown by different formulae () is easily produced. The compound can be used as the effective materials for consisting of the liquid-crystal compounds.
Description
The present invention is to be that March 30, application number in 2007 are 201010105726.3, 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 the advantages such as liquid crystal display device is low voltage operated due to it, slim demonstration are widely used.The display mode of liquid crystal display device had the TN(twisted-nematic in the past), the STN(supertwist is to row), or the active-matrix (active-matrix) that forms on substrate of TN (TFT: thin film transistor) etc., they are all 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 in recent years improves this problem and becomes larger problem.
As its solution, vertical orientation mode, IPS(In Plane Switching transverse electric field effect in recent years) etc. display mode begin to be practical.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, be to use transverse electric field conversion liquid crystal molecule to improve the method at visual angle on 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 negative liquid-crystal composition, can enumerate 2,3-difluorophenyl derivative (with reference to patent documentation 1).But, only disclose side chain in 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 preparation intermediate used in the effective preparation method of the difluoro bezene derivative that thiazolinyl is arranged on side chain and this preparation method.
The inventor attentively studies for solving above-mentioned problem, found that by compound shown in formula (1) being converted to the method for compound shown in formula (2), can effectively prepare the difluoro bezene derivative that has thiazolinyl on side chain, thereby complete 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 formula (13) after compound oxidation shown in this formula (2);
Shown in the phenates that is made by compound shown in this formula (13) and formula (7), compound reacts, and obtains compound shown in formula (16);
Obtain compound shown in formula (17) after compound deprotection shown in this formula (16);
Add water decomposition after reactant salt in compound and methoxymethyl phosphine shown in this formula (17) and obtain compound shown in formula (18);
In compound and alkylphosphines shown in this formula (18), reactant salt obtains the preparation method of compound shown in formula (9),
And,
Compound shown in formula (1) obtains compound shown in formula (2) with the phenates reaction that is made by 2,3-difluorophenol;
Obtain compound shown in formula (3) after compound deprotection shown in this formula (2);
Add water decomposition after reactant salt in compound and methoxymethyl phosphine shown in this formula (3) and obtain compound shown in formula (4);
In compound and alkylphosphines shown in this formula (4), reactant salt obtains compound shown in formula (5);
Obtain compound shown in formula (6) after compound oxidation shown in this formula (5);
Shown in the phenates that is made by compound shown in this formula (6) and formula (7), compound reacts, and obtains the preparation method of compound shown in formula (9).
R
4X
2 (7)
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 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 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 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 having introduced side chain R in final step
3Or R
4, can extremely easily synthesize and only have R
3Or R
4Compound group shown in different formula (9).
Embodiment
In preparation method of the present invention, 2,3-difluorophenol and alkali effect generate phenates, then obtain compound shown in formula (2) with the reaction of compound shown in formula (1), 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 sodium carbonate 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 Isosorbide-5-Nitrae-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 the example preferably such as DMF, N-Methyl pyrrolidone, dimethyl sulfoxide (DMSO), tetramethylene sulfone.Wherein be more preferably the polar solvent of the ether solvent, DMF etc. of tetrahydrofuran (THF), Anaesthetie Ether etc.In addition, each solvent of front 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 formula (1) after the phenates flash liberation of generation, also can not separate and react, but consider to react better under not separating from the difficulty or ease of operation.
Shown in formula (2) or formula (16), the deprotection of compound, preferably carry out under acidic conditions.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 react under solvent-free.Ether solvent can be enumerated Isosorbide-5-Nitrae-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 the 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 front 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 after reactant salt in compound and methoxymethyl phosphine shown in formula (3) or formula (17), can obtain compound shown in formula (4) from formula (3), can obtain compound shown in 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 Isosorbide-5-Nitrae-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 DMF etc.Wherein be more preferably tetrahydrofuran (THF), toluene.In addition, each solvent of front 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 formula (3) under unseparated situation.In addition, also can add alkali in the mixture of compound shown in methoxymethyl triphenylphosphine salt, 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 react under solvent-free.Ether solvent can be enumerated Isosorbide-5-Nitrae-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 front 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 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 formula (18), by can make its cis-trans isomerization 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 alkylphosphines shown in formula (4) or formula (18) can obtain formula (5) from formula (4), obtains compound shown in 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 Isosorbide-5-Nitrae-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 DMF etc., wherein is more preferably tetrahydrofuran (THF), toluene.In addition, each solvent of front 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 formula (4) under unseparated situation.In addition, also can add alkali in the mixture of compound shown in alkyl triphenylphosphine salt, formula (4).The alkyl triphenylphosphine salt is preferably used the methyl triphenyl phosphonium salt.
The oxidation of compound shown in formula (2) or formula (5) can utilize organometallic reagent to take off after 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 Isosorbide-5-Nitrae-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 preferred n-Butyl Lithium, s-butyl lithium are considered in operation difficulty or ease aspects, because effective deprotonation is more preferably s-butyl lithium.In addition, during deprotonation, also can add the potassium tert.-butoxide as additive together with above-mentioned organometallic reagent, the alkali such as tetramethylethylened.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 water decomposition after 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 formula (16) in 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 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 formula (2d) wherein.
R in formula (5)
3Be the alkyl of hydrogen atom or carbonatoms 1 to 5, preferred hydrogen atom or methyl, more preferably hydrogen atom.
R in 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 formula (13d) wherein.
The present invention's preparation intermediate as the formula (16) further is preferably as follows formula (16a) to compound shown in formula (16l).
In formula, R
6Thiazolinyl for carbonatoms 2 to 12.
Formula (16a) arrives in formula (16f), R
6Concrete is preferably 3-butenyl, 3-pentenyl, 4-pentenyl or 4-hexenyl, further preferred 3-butenyl or 4-pentenyl.
In 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 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, the particularly preferably thiazolinyl of the alkyl of carbonatoms 1 to 5 or carbonatoms 2 to 5 of further preferred carbonatoms 1 to 5.Thiazolinyl preferred vinyl, 1-propenyl, 3-butenyl or 3-pentenyl, particularly preferably vinyl.
The present invention's preparation intermediate as the formula (17) further specifically is preferably as follows compound shown in formula (17a) and formula (17b).
In 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 formula (17a), R
6Concrete is preferably 3-butenyl, 3-pentenyl, 4-pentenyl or 4-hexenyl, further preferred 3-butenyl or 4-pentenyl.
In 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, be particularly preferably the alkyl of carbonatoms 1 to 5 or the thiazolinyl of carbonatoms 2 to 5.Thiazolinyl preferred vinyl, 1-propenyl, 3-butenyl or 3-pentenyl, particularly preferably 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 formula (18b).
In 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 formula (17a), R
6Concrete is preferably 3-butenyl, 3-pentenyl, 4-pentenyl or 4-hexenyl, more preferably 3-butenyl or 4-pentenyl.
In 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, the particularly preferably thiazolinyl of the alkyl of carbonatoms 1 to 5 or carbonatoms 2 to 5 of carbonatoms 1 to 5.Thiazolinyl preferred vinyl, 1-propenyl, 3-butenyl or 3-pentenyl, particularly preferably 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 formula (1), can utilize for example following method preparation.
In 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-difluorobenzene (Ia) synthetic
Methanesulfonic (4, own-4 '-yl) methyl, 2 of 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 under 80 ℃.Filter reaction mixture, solid ingredient utilizes DMF to clean, and filters.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-difluorobenzene (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-difluorobenzene (Ia) is dissolved in the THF of 540mL.Add secondary BuLi(1.0M tetrahydrobenzene solution under Nei Wen-60 ℃) 260mL, stirred 2 hours.Add trimethyl borate 29g under Nei Wen-60 ℃, be warming up to 20 ℃.Add 15% hydrogen peroxide 72mL, stirred 5 hours under 35 ℃.Add and utilize 10% hydrochloric acid neutralization after 10% aqueous solution of sodium bisulfite, after minute getting 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 under 130 ℃.Add water, use methylbenzene extraction, after water and saturated aqueous common salt are cleaned organic layer, desolventizing is heated up in a steamer in decompression.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-4-ketone-4 '-yl) methoxyl group-2,3-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-(4-amylene oxygen) benzene (Ih), stirred 2 hours under 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-4-ketone-4 '-yl) methoxyl group-2,3-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-4-ketone-4 '-yl) methoxyl group-2,3-two fluoro-1-(4-amylene oxygen) benzene (Ii) and methoxymethyl triphenylphosphine muriate are scattered in THF, add the THF solution of potassium tert.-butoxide under 0～5 ℃ of interior temperature, stir 2 hours.After adding water, desolventizing is heated up in a steamer in decompression, adds hexene filtering separation solid ingredient in 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 residue, adds to reflux 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 after anhydrous sodium sulfate drying.Add triethylamine, THF and methyl alcohol in residue.Then add therein 30% aqueous sodium hydroxide solution, stirred 3 hours under 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 after 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 in THF, is adding potassium tert.-butoxide below 0 ℃, stirs stirring in 30 minutes.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.After adding acetone and water, desolventizing is heated up in a steamer in decompression, adds hexene leaching solid ingredient in 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 in embodiment 1, own-the 4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-1,2-difluorobenzene (Ia).
2-2:3-(dicyclo oneself-4-ketone-4 '-yl) methoxyl group-1,2-difluorobenzene (Ib) synthetic
3-[4, oneself-4 '-yl of 4-(ethylidene dioxy) dicyclo] methoxyl group-1,2-difluorobenzene (Ia) 111g is dissolved in toluene 330mL, stirs 2 hours under 50 ℃ after adding formic acid 270mL.After being cooled to room temperature, adding water 200mL and divide 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 after anhydrous magnesium sulfate drying.The residue recrystallize is refining obtain 3-(dicyclo oneself-4-ketone-4 '-yl) methoxyl group-1,2-difluorobenzene (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-difluorobenzene (Ic) synthetic
3-(dicyclo oneself-4-ketone-4 '-yl) methoxyl group-1,2-difluorobenzene (Ib) 95g and methoxymethyl triphenylphosphine muriate 132g are scattered in THF650mL, the THF(180mL that adds potassium tert.-butoxide 44g under 0～5 ℃ of interior temperature) solution, stirred 2 hours.After adding water 25mL, desolventizing is heated up in a steamer in decompression, adds hexene 700mL leaching solid ingredient in 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 THF 400mL in residue, reflux 1 hour.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 after anhydrous sodium sulfate drying.Add triethylamine 8mL, THF 250mL and methyl alcohol 400mL in residue.Wherein add again 30% aqueous sodium hydroxide solution 20mL, stirred 3 hours under 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 after anhydrous magnesium sulfate drying, obtain 3-(instead, own-4 '-yl) methoxyl group-1 of anti--4-formyloxy dicyclo, 2-difluorobenzene (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-difluorobenzene (Id) synthetic
Methyl triphenyl phosphine bromide 136g is scattered in THF340mL, is adding potassium tert.-butoxide 46g below 0 ℃, stirs 30 minutes.Drip 3-(anti-, own-4 '-yl) methoxyl group-1 of anti--4-formyloxy dicyclo, the THF(200mL of 2-difluorobenzene (Ic) 99g) solution, stirred 1 hour.After adding acetone 15mL and water 15mL, desolventizing is heated up in a steamer in decompression, adds hexene 500mL leaching solid ingredient in 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-difluorobenzene (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-difluorobenzene (Id) 39g is dissolved in THF 320mL.Add secondary BuLi(0.95M tetrahydrobenzene solution under Nei Wen-60 ℃) 196mL, stirred 2 hours.The THF(42mL that adds trimethyl borate 21g under Nei Wen-60 ℃) solution, be warming up to 0 ℃.Add water 7.2mL and stir after 10 minutes, add 30% hydrogen peroxide 34mL, stirred 5 hours under 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 after 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 under 130 ℃.Add water, utilize methylbenzene extraction, after organic layer utilizes water and saturated aqueous common salt to clean, desolventizing is heated up in a steamer in decompression.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 section 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
In 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
In embodiment 1 or 2, replace 5-bromo-1-amylene to use anti--4-(ethyl cyclohexyl) monobromethane, carry out same reaction, obtain 4-(anti-, own-4 '-yl) methoxyl group-2 of instead-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
In embodiment 1 or 2, replace 5-bromo-1-amylene use methanesulfonic anti--4-(vinyl cyclohexyl) methyl, carry out same reaction, obtain 4-(anti-, own-4 '-yl) methoxyl group-2 of instead-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 (2)
1. one kind suc as formula compound shown in (3),
2. one kind suc as formula compound shown in (4),
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| JPH11241068A (en) * | 1997-12-22 | 1999-09-07 | Dainippon Ink & Chem Inc | Nematic liquid crystal composition and liquid crystal display prepared by using same |
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