CN103553878A - New preparation method of alkylcyclohexylphenol liquid crystal intermediate compound - Google Patents
New preparation method of alkylcyclohexylphenol liquid crystal intermediate compound Download PDFInfo
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- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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Abstract
The invention discloses a new preparation method of an alkylcyclohexylphenol liquid crystal intermediate compound, which comprises the following steps of enabling a benzyloxybromobenzene compound to react with magnesium chips in a solvent to obtain benzyloxyphenylmagnesium bromide which then reacts with a raw material A; performing acidic hydrolysis to obtain a compound B; performing a series of processes such as backflow dehydration and the like on the compound B in an organic solvent and an organic acid system to obtain a compound C; at the pH of 6.5-7.5 and in an organic solvent, performing a hydrogenation reaction on the compound C in the presence of a catalyst to obtain a cis-trans compound D; performing an isomerization reaction on the cis-trans compound D in an organic solvent and a strong-alkaline system to obtain a trans product; performing a series of processes to obtain the alkylcyclohexylphenol liquid crystal intermediate compound. The method disclosed by the invention has the advantages of simple process, high yield, high purity, simple process path and low cost, and can meet the requirements of a TFT-LCD (thin film transistor-liquid crystal display) for the high purity, high quality and low cost of a liquid crystal intermediate.
Description
Technical field
The present invention relates to a kind of novel preparation method of preparing fluorine-containing ethers monomer liquid crystal midbody compound used, more specifically relate to the novel preparation method that contains alkyl and phenylcyclohexane phenols liquid crystal intermediates compound, belong to liquid crystal material compound field.
Background technology
Thin Film Transistor-LCD (TFT-LCD) is most important a kind of in liquid-crystal display (LCD), and its output value and influence power have very important status in liquid-crystal display family.Be widely used in all respects such as televisor, notebook computer, watch-dog, mobile phone.
Liquid crystal material is one of several large materials that form by liquid-crystal display (LCD), and is accompanied by the difference of display format, and required liquid crystal material is also different.Therefore, as the liquid crystal material that shows use, be also accompanied by the development of liquid-crystal display and grow, a large amount of novel liquid crystalline cpds have been there are, as: cyclohexyl (connection) benzene class, ethane bridged bond class, end alkene class with containing fluorobenzene class liquid crystalline cpd etc., constantly meet the requirements of display device to performance such as TN-LCD, STN-LCD, TFT-LCD.
In the liquid-crystal display that fluorinated liquid crystal material drives at thin film transistor (TFT) in recent years, be used widely, become gradually field of liquid crystals study hotspot.It is low that fluoro liquid crystals has viscosity, and response is fast, can improve the advantages such as mixed liquid crystal specific inductivity.End group is the liquid crystalline cpd of difluoro-methoxy, is called again difluoromethyl ethers liquid crystal, at the initial stage the 90's of 20th century, is developed.This compounds has the characteristic that dielectric anisotropy is high, voltage retention is high, is suitable for TFT liquid-crystal display, has good market outlook.
Publication number is in the patents such as EP2199270, US55364429, CN102344815, to be all mentioned to the synthetic fluorine-containing ethers monomer liquid crystal compound of the phenol intermediate that contains alkyl and cyclohexyl:
With the mixed liquid crystal material that is configured to STN-LCD and TFT-LCD together with other monomer liquid crystal compound and uses, and become wherein very important integral part! In TFT-LCD, have application widely, become wherein indispensable composition!
In the patent of Merck company, reported that by amphyl, with monochlorodifluoromethane, carrying out etherificate prepares difluoro methyl ether, but lacked complete synthetic route.The preparation report of 4-［ 4'-(4 " alkyl cyclohexyl)-cyclohexyl ］ phenol liquid crystal intermediates is few, only have reported that Lee of Xi'an Inst. of Modern Chemistry builds < fine chemistry industry > the 21st the 12nd phase of volume in 2004, one piece of article that An Zhongwei etc. deliver, Grignard reagent and 4-(4'-alkyl-cyclohexyl with aryl bromide) pimelinketone coupling, again through Catalyzed by Potassium Bisulfate dehydration, catalytic hydrogenation, isomerization, demethylating reaction, synthesize trans-alkyl bis cyclohexane phenol, further etherificate has obtained the phenyl dicyclic hexane liquid crystal that end group is difluoro-methoxy, wherein doing transly-4-［ 4'-(4 " n-propyl cyclohexyl)-cyclohexyl ］ phenol has shared five steps reactions, total recovery only has 53%, a large amount of expensive tetrahydrofuran (THF)s and palladium charcoal in process, have been used, cost is very high, and can use aluminum chloride in preparation process, Hydrogen bromide, Glacial acetic acid, discharge a large amount of sour gas, contaminate environment, can not meet and adapt to the theory that current environmental protection is produced! notification number is the preparation method that the patent of CN102826966 discloses a kind of adjacent difluoro alkoxy benzene derivative liquid crystal monomer, it is first to use 1, the fluoro-3-(4-propyl group-cyclohexyl of 2-bis-)-benzene is under very low temperature state, with n-Butyl Lithium, prepare lithium reagent, then make 1, the fluoro-3-(4-propyl group-cyclohexyl of 2-bis-)-phenylo boric acid, finally in oxidation preparation 1, the fluoro-3-(4-propyl group-cyclohexyl of 2-bis-)-phenol, in its preparation process, use dangerous and expensive n-Butyl Lithium, severe reaction conditions, cost is higher.
Summary of the invention
Based on above-mentioned the deficiencies in the prior art, the novel preparation method that the object of this invention is to provide simple, the high yield of a kind of technique, highly purified cyclohexyl phenol class liquid crystal intermediates compound, to shorten operational path, reduce production costs, meet TFT-LCD to liquid crystal intermediates high purity, high-quality, requirement cheaply, adapt to the needs of liquid crystal material fast development for TFT-LCD.
The required midbody compound of ethers monomer of preparing of the present invention---cyclohexyl phenol class liquid crystal intermediates compound, this compound has the structure shown in general formula (I):
Wherein:
R is C
1-C
10alkyl; Further, R is preferably C
1-C
10straight chained alkyl;
More preferably, R C more preferably
1-C
7straight chained alkyl;
Most preferably, R is-CH
3,-C
2h
5,-C
3h
7,-C
4h
9or-C
5h
11, C
7h
15.
N is the arbitrary numerical value in 0,1,2,3,4,5, and further, n is preferably the arbitrary numerical value in 1,2,3.
L
1, L
2, L
3for-H or-any in F.
For realizing object of the present invention, the novel preparation method of a kind of cyclohexyl phenol class liquid crystal intermediates compound (general formula (I)) is provided, its syntheti c route is as follows:
(A)
The technical scheme of technical solution problem of the present invention is as follows:
1.. benzyloxy bromobenzene compounds is reacted with magnesium chips in organic solvent, obtain grignard reagent-benzyloxy phenyl-magnesium-bromide, then react with raw material (A), then carry out acidic hydrolysis, obtain corresponding compd B;
In above formula:
R is C
1-C
10alkyl; Further, R is preferably C
1-C
10straight chained alkyl;
More preferably, R C more preferably
1-C
7straight chained alkyl;
Most preferably, R is-CH
3,-C
2h
5,-C
3h
7,-C
4h
9or-C
5h
11, C
7h
15.
N is the arbitrary numerical value in 0,1,2,3,4,5, and further, n is preferably the arbitrary numerical value in 1,2,3
L
1, L
2, L
3for-H or-any in F.
2.. compd B carries out reflux dewatering in organic solvent and Organic Acid System, obtains corresponding product (C), and resulting corresponding product (C) is washed, and after precipitation is extremely dry, then carries out recrystallization, makes high-purity compound (C);
(high purity is generally more than 99%)
In above formula:
R is C
1-C
10alkyl; Further, R is preferably C
1-C
10straight chained alkyl;
More preferably, R C more preferably
1-C
7straight chained alkyl;
Most preferably, R is-CH
3,-C
2h
5,-C
3h
7,-C
4h
9or-C
5h
11,-C
7h
15.
N is the arbitrary numerical value in 0,1,2,3,4,5, and further, n is preferably the arbitrary numerical value in 1,2,3;
L
1, L
2, L
3for-H or-any in F.
3.. in organic solvent, Compound C, under catalyzer exists, is carried out hydrogenation, obtains along anti-compound (D).
In above formula:
R is C
1-C
10alkyl; Further, R is preferably C
1-C
10straight chained alkyl;
More preferably, R C more preferably
1-C
7straight chained alkyl;
Most preferably, R is-CH
3,-C
2h
5,-C
3h
7,-C
4h
9or-C
5h
11,-C
7h
15.
N is the arbitrary numerical value in 0,1,2,3,4,5, and further, n is preferably the arbitrary numerical value in 1,2,3;
L
1, L
2, L
3for-H or-any in F.
4.. along anti-compound (D), in organic solvent and strong basicity system, carry out isomerization reaction, obtain trans product, then trans product is carried out to acidic hydrolysis, after extraction, be washed till neutrality, precipitation is extremely dry, then after recrystallization purifying, obtains highly purified compound---cyclohexyl phenol class liquid crystal intermediates compound.
(high purity is generally more than 99%)
In above formula:
R is C
1-C
10alkyl; Further, R is preferably C
1-C
10straight chained alkyl;
More preferably, R C more preferably
1-C
7straight chained alkyl;
Most preferably, R is-CH
3,-C
2h
5,-C
3h
7,-C
4h
9or-C
5h
11,-C
7h
15.
N is the arbitrary numerical value in 0,1,2,3,4,5, and further, n is preferably the arbitrary numerical value in 1,2,3;
L
1, L
2, L
3for-H or-any in F.
The benzyloxy bromobenzene compounds of step of the present invention described in 1. has multiple, as: can adopt benzyloxy bromobenzene, 3, the fluoro-4-benzyloxy of 5-bis-bromobenzene, 2, the fluoro-4-benzyloxy of 3-bis-bromobenzene is medium, according to L1, and L2, the difference of L3, corresponding different benzyloxy bromobenzene compounds.
The raw material (A) of step of the present invention described in is 1. amyl group dicyclo ketone.
The organic solvent of step of the present invention described in is 1. at least one in ether, tetrahydrofuran (THF), methyltetrahydrofuran, benzene, toluene and dimethylbenzene, and it is preferably the mixture of tetrahydrofuran (THF) and toluene.Described organic solvent total mass is 2-5 times of raw material A quality, is preferably 4 times.
The hydrolysis of step of the present invention described in 1. implemented under sour existence, preferably optionally hydrochloric acid, sulfuric acid, the glacial acetic acid of dilute with water, and concentrated hydrochloric acid more preferably, most preferably is the mixture (concentration is 10%) of concentrated hydrochloric acid and water.
1. step of the present invention can be implemented in relatively wide temperature range.Typical temperature is 10 ℃ to 100 ℃, is preferably 20 ℃ to 90 ℃, more preferably 30 ℃ to 80 ℃, most preferably reaction initiation reaction at 60 ℃ to 75 ℃ in step (1), further reaction is carried out at 70 ℃ to 85 ℃, then, then carries out acidic hydrolysis at 50 ℃ to 60 ℃.
1., the reaction times is not critical step of the present invention, can in wider scope, select according to the number of production lot.Generally speaking, each reactant combines and reaches 10 hours most, and preferably the longest is 8 hours, and most preferably the longest is 6 hours.
In step of the present invention enforcement 1., for the benzyloxy bromobenzene compounds of 1mol, the magnesium chips using is generally 0.7mol to 1.8mol, is preferably 0.9mol to 1.5mol, more preferably 1.0mol to 1.1mol; The amyl group dicyclo ketone (A) using is generally 0.6mol to 1.6mol, and more preferably 0.8mol to 1.5mol, most preferably is 0.8mol to 1.0mol.
The reflux dewatering used dewatering agent of step of the present invention described in is 2. any in tosic acid, the vitriol oil, sal enixum, concentrated hydrochloric acid, is preferably tosic acid, sal enixum, most preferably is tosic acid.
The organic solvent of step of the present invention described in is 2. any in ethyl acetate, toluene, dimethylbenzene, methylene dichloride, is preferably toluene, dimethylbenzene, most preferably is toluene.
The Organic Acid System of step of the present invention described in is 2. toluene+tosic acid.
The recrystallization used organic solvent of step of the present invention described in is 2. ethanol.
2. step of the present invention can be implemented within the scope of relatively wide temperature and pressure.Typical temperature is 50 ℃ to 150 ℃.Preferably temperature is 100 ℃ to 150 ℃.More preferably temperature is 110 ℃ to 130 ℃.Most preferred temperature is: step 2. in the temperature of reaction of each reactive component be divided into two stages: in temperature, being first to carry out at 75 ℃ to 110 ℃, until temperature rises to 110 ℃, then, continuing to heat up, is to carry out at 110 ℃ to 120 ℃ in temperature.The product of gained is purified by the toluene recrystallization by 1 times of quality.
2., the reaction times is not critical step of the present invention, can in wider scope, select according to the number of production lot.Generally speaking, each reactant combines and reaches 10 hours most, and preferably the longest is 9 hours, and more preferably the longest is 8 hours.More specifically the first stage is 1 to 3 hour, and subordinate phase is 3 to 7 hours.
Step of the present invention 3. in, be preferably in PH and be controlled under 6.5-7.5 and carry out.
Step of the present invention 3. in, described catalyzer is any in Raney's nickel catalyst, active nickel catalyst, palladium charcoal Pd/C, palladium charcoal Pt/C.Be preferably Raney's nickel catalyst and Pd/C, most preferably be neutral Raney's nickel catalyst.
The organic solvent of step of the present invention described in is 3. any in ethyl acetate, ethanol, methyl alcohol, Virahol, toluene, dimethylbenzene, methylene dichloride, is preferably ethanol and methyl alcohol, most preferably is ethanol.
3. step of the present invention can be implemented within the scope of relatively wide temperature and pressure.Typical temperature is that 50 ℃ to 200 ℃, pressure are 0 Mpa to 0.5 Mpa, and preferably temperature is that 60 ℃ to 180 ℃, pressure are 0.1 Mpa to 0.3Mpa, and more preferably temperature is that 80 ℃ to 150 ℃, pressure are 0.15 Mpa to 0.2 Mpa.This step is not purified.
3., the reaction times is not critical step of the present invention, can in wider scope, select according to the number of production lot.Generally speaking, each reactant combines and reaches 12 hours most, and preferably the longest is 10 hours, and more preferably the longest is 8 hours.
The isomerization reaction used highly basic of step of the present invention described in is 4. any in sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert.-butoxide, sodium methylate, is preferably potassium hydroxide and potassium tert.-butoxide, more preferably potassium hydroxide.And for the compound of 1mol
(d), the add-on of alkali (weight molar weight) is generally the 90-100% of the amount (weight molar weight) of Compound D, is preferably 60-70%, most preferably is 40-50%.
The organic solvent of step of the present invention described in is 4. any in dimethyl formamide (DMF), N-Methyl pyrrolidone (NMP), toluene, diglyme, 1,4 — dioxs, be preferably any in DMF, toluene, 1,4 — dioxs, most preferably be DMF.
4. step of the present invention can be implemented in relatively wide temperature range.Typical temperature is 60 ℃ to 150 ℃, is preferably 80 ℃ to 140 ℃, more preferably 90 ℃ to 130 ℃, most preferably is 100 ℃ to 120 ℃.
4., the reaction times is not critical step of the present invention, can in wider scope, select according to the number of production lot.Generally speaking, each reactant combines and reaches 10 hours most, and preferably the longest is 8 hours, and most preferably the longest is 6 hours.More efficiently be to adopt gas chromatograph GC to monitor to follow the tracks of reaction always.
Step of the present invention 4. in, described acidic hydrolysis, preferably optionally hydrochloric acid, sulfuric acid, the glacial acetic acid of dilute with water, concentrated hydrochloric acid more preferably, most preferably is the mixture (concentration is 10%) of concentrated hydrochloric acid and water.
Step of the present invention 4. in, described extraction, the solvent of employing is toluene.
Step of the present invention 4. in, carrying out last recrystallization organic solvent used is at least one in acetone, butanone, pimelinketone, ethyl acetate, ethanol, methyl alcohol, Virahol, toluene, dimethylbenzene, be preferably butanone, pimelinketone, ethyl acetate, ethanol, toluene, Virahol, most preferably be the mixture of toluene and Virahol.
Advantage of the present invention is as follows:
(1) the first step reaction makes product B, do not purify, not discharging, at second step, prepare in the process of product (C), adopt and first under the cold condition of 75 ℃ to 100 ℃, to carry out, after the reaction process of carrying out under the high temperature of 110 ℃ to 120 ℃ of temperature (be desolvation process previous stage, the latter half is reaction process), lower boiling solvent in system can have been steamed like this, directly do second step reaction, to shorten preparation cycle.
(2) in the 3rd step, synthetic employing one step catalytic hydrogenation along anti-product (D) (suitable+anti-), on the one hand the two keys on cyclohexyl are carried out to hydrogenation, can remove benzyl again on the other hand, this is advantage maximum in this preparation process, one step hydrogenation solves two problems, and by recrystallization, obtains the more than 99% white crystal product of purity.
According to method of the present invention, prepare cyclohexyl phenol class liquid crystal intermediates compound, its design synthetic route is unique, operational path is shorter, processing condition are reasonable, production cost reduces, treatment process is suitable, and product quality is excellent, reaches TFT-LCD liquid crystal material to liquid crystal intermediates high purity, high-quality, requirement cheaply.
Embodiment
Below in conjunction with specific embodiment, the present invention is done to further detailed description, yet described embodiment, only for explaining the present invention, is not intended to limit scope of the present invention.
Embodiment 1
General formula
Work as R=5, n=2, during L1=L2=L3=-H, product is 4-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans).
The present embodiment is the preparation (I-1) of 4-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans).
Step 1:4-［ 4'-(4 " n-pentyl cyclohexyl) cyclohexyl-l'-hydroxyl ］ benzene benzyl oxide (B) synthetic:
Under nitrogen protection, in 5L there-necked flask, add after 113 grams of magnesium chips and 600ml tetrahydrofuran (THF), start stirring, heating in water bath, when temperature rises to 60 ℃, first drip 10ml benzyloxy bromobenzene, (in mixing solutions, the content of three kinds of materials is the mixing solutions that tetrahydrofuran (THF) and toluene form: gram tetrahydrofuran (THF)+1000,1124 grams of benzyloxy bromobenzene+1000 gram toluene), now, reaction causes automatically, heat release, then continue to drip, be warming up to 75 ℃, reflux and drip, rate of addition and return velocity are consistent, within about 1.5 hours, dropwise, reflux after 1.5 hours, starting to drip toluene solution (that is: 930 grams of amyl group dicyclo ketone (A)+1050 gram toluene) dropping temperature that contains amyl group dicyclo ketone (A) is 80 ℃, within 1 hour, dropwise, at this temperature, be incubated after 1 hour, sampling is followed the tracks of, when amyl group dicyclo ketone is less than 1%, the hydrochloric acid (adding 540 grams of tap water to dilute the hydrochloric acid obtaining in 270 grams of concentrated hydrochloric acids) that adds dilution, at 50 ℃, carry out acidic hydrolysis, layering, retain organic phase, GC detection 4-4'-(4 " and n-pentyl cyclohexyl) cyclohexyl-l'-hydroxyl ］ benzene benzyl oxide (B) (cis+trans) >=98%, now, do not process, directly enter next step dehydration procedure.
Step 2:4-4'-(4 " and n-pentyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C) synthetic
Above-mentioned organic phase is transferred in 5L there-necked flask, reflux water-dividing device is installed, add 30 grams of tosic acid to add 1 gram of stopper (BHT) 2 simultaneously, 6-di-tert-butyl-4-methy phenol, add 1L toluene, start stirring, electric mantle heating, when temperature rises to 65 ℃, there is solvent to steam, continue to be warming up to 110 ℃, change distillation for reflux water-dividing, divide water after 6 hours, see and do not have water droplet to fall, sampling is followed the tracks of, when raw material B(suitable+anti-)≤0.1% time, stop heating, be cooled to 40 ℃, add 1L to be washed to neutrality, precipitation is to dry, with doing recrystallization after 3 times of dissolve with ethanol, filter to obtain 1400 grams of faint yellow solids, GC detects, 4-4'-(4 " and n-pentyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C) reaches 99.5%, yield is 90%.
(D) synthetic of step 3:4-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis)
In 10L hydrogenation still, add 4-4'-(4 " n-pentyl cyclohexyl) 1000 grams of-l'-cyclohexenyl benzene benzyl oxides (C), 200 grams of neutral Raney's nickels, 5000ml ethanol, build kettle cover, with after nitrogen replacement air 3 times, logical hydrogen hydrogenation, pressure is 0.2Mpa, temperature is 80 ℃, after hydrogenation 5 hours, pressure release, sampling detects, when raw material 4-4'-(4 " n-pentyl cyclohexyl) during-l'-cyclohexenyl benzene benzyl oxide (C)≤0.01%, stop hydrogenation, filtering catalyst, filtrate takes off dry solvent, obtain 775 grams of faint yellow solids, GC detects, 4-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D) (suitable+anti-) is 99.47%, yield 98%.
(D) synthetic of step 4:4-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans)
In 5L there-necked flask, add 800 grams of 4-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D) and 2400mlDMF, start stirring, under whipped state, add 137 grams of potassium hydroxide, electric mantle is warming up to 110 ℃, now system is complete molten state, timing insulation 6 hours, sampling is followed the tracks of, when cis-product≤1%, stopped reaction, cooling, to dripping the hydrochloric acid soln of being made by 200ml concentrated hydrochloric acid and 400ml tap water in reaction system, be hydrolyzed, with after the extraction of 1500ml toluene, be washed till neutrality, then precipitation is to dry, use again the toluene of three times of quality and the mixed solution of Virahol (mass ratio of toluene and Virahol is 1:1) to carry out recrystallization, obtain 696 grams, white plates crystal, its fusing point is: 206.2 ℃, GC detects, 4-4'-(4 " and n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans) (D) >=99.85%, yield is 87%.
embodiment 2
General formula
Work as R=3, n=2, L1=L2=-F, during L3=-H, product is the fluoro-4-of 2,3-bis-［ 4'-(4 " n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans).
The present embodiment is the preparation (I-2) of the fluoro-4-of 2,3-bis-［ 4'-(4 " n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans).
Step 1:2, the fluoro-4-of 3-bis-［ 4'-(4 " n-propyl cyclohexyl) cyclohexyl-l'-hydroxyl ］ benzene benzyl oxide (B) synthetic:
Under nitrogen protection, in 5L there-necked flask, add after 113 grams of magnesium chips and 600ml tetrahydrofuran (THF), start stirring, heating in water bath, when temperature rises to 60 ℃, first drip 10ml2, the fluoro-4-benzyloxy of 3-bis-bromobenzene, (in mixing solutions, the content of three kinds of materials is the mixing solutions that tetrahydrofuran (THF) and toluene form: 1279 gram 2, gram tetrahydrofuran (THF)+1000, the fluoro-4-benzyloxy of 3-bis-bromobenzene+1000 gram toluene), now, reaction causes automatically, heat release, then continue to drip, be warming up to 75 ℃, reflux and drip, rate of addition and return velocity are consistent, within about 1.5 hours, dropwise, reflux after 1.5 hours, starting to drip toluene solution (that is: 804 grams of propyl group dicyclo ketone (A)+1050 gram toluene) dropping temperature that contains propyl group dicyclo ketone (A) is 80 ℃, within 1 hour, dropwise, at this temperature, be incubated after 1 hour, sampling is followed the tracks of, when propyl group dicyclo ketone is less than 1%, the hydrochloric acid (adding 540 grams of tap water dilutions in 270 grams of concentrated hydrochloric acids) that adds dilution, at 50 ℃, carry out acidic hydrolysis, layering, retain organic phase, GC detects 2, the fluoro-4-of 3-bis-4'-(4 " and n-propyl cyclohexyl) cyclohexyl-l'-hydroxyl ］-benzene benzyl oxide (B) (cis+trans) >=98%, now, do not process, directly enter next step dehydration procedure.
Step 2:2, the fluoro-4-of 3-bis-4'-(4 " and n-propyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C) synthetic
Above-mentioned organic phase is transferred in 5L there-necked flask, reflux water-dividing device is installed, add 30 grams of tosic acid to add 1 gram of stopper (BHT) 2 simultaneously, 6-di-tert-butyl-4-methy phenol, add 1L toluene, start stirring, electric mantle heating, when temperature rises to 65 ℃, there is solvent to steam, continue to be warming up to 110 ℃, change distillation for reflux water-dividing, divide water after 6 hours, see and do not have water droplet to fall, sampling is followed the tracks of, when raw material B(suitable+anti-)≤0.1% time, stop heating, be cooled to 40 ℃, add 1L to be washed to neutrality, precipitation is to dry, with doing recrystallization after 3 times of dissolve with ethanol, filter to obtain 1388 grams of faint yellow solids, GC detects, 2, the fluoro-4-of 3-bis-4'-(4 " and n-propyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C) reaches 99.5%, yield is 90%.
Step 3:2, (D) synthetic of the fluoro-4-of 3-bis-［ 4'-(4 " n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis)
In 10L hydrogenation still, add 2, the fluoro-4-of 3-bis-4'-(4 " and n-propyl cyclohexyl) 1000 grams of-l'-cyclohexenyl benzene benzyl oxides (C), 200 grams of neutral Raney's nickels, 5000ml ethanol, build kettle cover, with after nitrogen replacement air 3 times, logical hydrogen hydrogenation, pressure is 0.2Mpa, temperature is 80 ℃, after hydrogenation 5 hours, pressure release, sampling detects, when raw material 4-4'-(4 " n-propyl cyclohexyl)-l'-cyclohexenyl-2, during 3-difluorobenzene benzyl oxide (C)≤0.01%, stop hydrogenation, filtering catalyst, filtrate takes off dry solvent, obtain 780 grams of faint yellow solids, GC detects, 2, the fluoro-4-of 3-bis-［ 4'-(4 " n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D) (suitable+anti-) is 99.5%, yield 98.4%.
Step 4:2, (D) synthetic of the fluoro-4-of 3-bis-［ 4'-(4 " n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans)
In 5L there-necked flask, add 800 gram 2, the fluoro-4-of 3-bis-［ 4'-(4 " n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D) and 2400mlDMF, start stirring, under whipped state, add 130 grams of potassium hydroxide, electric mantle is warming up to 110 ℃, now system is complete molten state, timing insulation 6 hours, sampling is followed the tracks of, when cis-product≤1%, stopped reaction, be cooled to 50 ℃, to dripping the hydrochloric acid soln of being made by 200ml concentrated hydrochloric acid and 400ml tap water in reaction system, be hydrolyzed, with after the extraction of 1500ml toluene, be washed till neutrality, then precipitation is to dry, use again the toluene of three times of quality and the mixed solution of Virahol (mass ratio of toluene and Virahol is 1:1) to carry out recrystallization, obtain 690 grams, white plates crystal, its fusing point is: 195.2 ℃, GC detects, 2, the fluoro-4-of 3-bis-4'-(4 " and n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans) (D) >=99.85%, yield is 86%.
embodiment 3
The present embodiment is 2, the fluoro-4-of 3-bis-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］-phenol (trans) preparation (I-3); its preparation process is with embodiment 1; difference be by step 1 by benzyloxy bromobenzene instead of 2; the fluoro-4-benzyloxy of 3-bis-bromobenzene, prepare target product (I-3).
Experimental result is as follows: target product (I-3) fusing point: 213.5 ℃, purity is 99.82%, and yield is 86%.
embodiment 4
The present embodiment is 2, the preparation of the fluoro-4-of 6-bis-［ 4'-(4 " n-pentyl cyclohexyl)-cyclohexyl ］-phenol (trans) preparation (I-4); its preparation process is with embodiment 1; difference is that by the benzyloxy bromobenzene raw material substitution in step 1 be 3; the fluoro-4-benzyloxy of 5-bis-bromobenzene, prepares target product (I-4).
Experimental result is as follows: target product (I-4) fusing point: 209.3 ℃, purity is 99.85%, and yield is 89%.
The foregoing is only preferred embodiment of the present invention, be not limited to the present invention, within the spirit and principles in the present invention all, any modification of making, be equal within replacement, improvement etc. all should be included in protection scope of the present invention.
Claims (10)
1. a novel preparation method for cyclohexyl phenol class liquid crystal intermediates compound, is characterized in that: its syntheti c route is as follows:
1.. benzyloxy bromobenzene compounds is reacted with magnesium chips in organic solvent, obtain grignard reagent-benzyloxy phenyl-magnesium-bromide, then react with raw material A, then carry out acidic hydrolysis, make compd B;
In above formula:
R is C
1-C
10alkyl, n is the arbitrary numerical value in 0,1,2,3,4,5, L
1, L
2, L
3for-H or-any in F;
2.. compd B carries out reflux dewatering in organic solvent and Organic Acid System, obtains corresponding product C, and resulting corresponding product C is washed, and after precipitation is extremely dry, then carries out recrystallization, makes Compound C;
In above formula:
R is C
1-C
10alkyl, n is the arbitrary numerical value in 0,1,2,3,4,5, L
1, L
2, L
3for-H or-any in F;
3.. in organic solvent, Compound C, under catalyzer exists, is carried out hydrogenation, obtains along anti-Compound D;
In above formula:
R is C
1-C
10alkyl, n is the arbitrary numerical value in 0,1,2,3,4,5, L
1, L
2, L
3for-H or-any in F;
4.. along anti-Compound D, in organic solvent and strong basicity system, carry out isomerization reaction, obtain trans product, then trans product is carried out to acidic hydrolysis, after extraction, be washed till neutrality, precipitation is extremely dry, then after recrystallization purifying, obtains final product-cyclohexyl phenol class liquid crystal intermediates compound;
In above formula:
R is C
1-C
10alkyl, n is the arbitrary numerical value in 0,1,2,3,4,5, L
1, L
2, L
3for-H or-any in F.
2. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 1, it is characterized in that:
Step 1. in, described raw material A is amyl group dicyclo ketone; Described organic solvent is at least one in ether, tetrahydrofuran (THF), methyltetrahydrofuran, benzene, toluene and dimethylbenzene; Hydrochloric acid, sulfuric acid, glacial acetic acid that the acid used of described acidic hydrolysis is dilute with water;
Step 2. in, described reflux dewatering dewatering agent used is any in tosic acid, the vitriol oil, sal enixum, concentrated hydrochloric acid; Described organic solvent is any in ethyl acetate, toluene, dimethylbenzene, methylene dichloride; Described Organic Acid System is toluene+tosic acid; The organic solvent that described recrystallization is used is ethanol;
Step 3. in, described catalyzer is any in Raney's nickel catalyst, active nickel catalyst, palladium charcoal Pd/C, palladium charcoal Pt/C; Described organic solvent is any in ethyl acetate, ethanol, methyl alcohol, Virahol, toluene, dimethylbenzene, methylene dichloride;
Step 4. in, described isomerization reaction highly basic used is any in sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert.-butoxide, sodium methylate, and described organic solvent is any in dimethyl formamide, N-Methyl pyrrolidone, toluene, diglyme, 1,4 — dioxs; Described acidic hydrolysis is hydrochloric acid, sulfuric acid, the glacial acetic acid of dilute with water; The material that described extraction adopts is toluene; Described recrystallization organic solvent used is at least one in acetone, butanone, pimelinketone, ethyl acetate, ethanol, methyl alcohol, Virahol, toluene, dimethylbenzene.
3. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 2, it is characterized in that:
Step 1. in, described organic solvent is the mixture of tetrahydrofuran (THF) and toluene; The acid used of described acidic hydrolysis is the mixture of concentrated hydrochloric acid and water, and its concentration is 10%;
Step 2. in, described reflux dewatering dewatering agent used is tosic acid, sal enixum; Described organic solvent is toluene, dimethylbenzene;
Step 3. in, described catalyzer is Raney's nickel catalyst and Pd/C; Described organic solvent is ethanol and methyl alcohol;
Step 4. in, described isomerization reaction highly basic used is any in potassium hydroxide and potassium tert.-butoxide; Described organic solvent is any in dimethyl formamide, toluene, 1,4 — dioxs; The acid used of described acidic hydrolysis is the mixture of concentrated hydrochloric acid and water, and its concentration is 10%; Described recrystallization organic solvent used is any in butanone, pimelinketone, ethyl acetate, ethanol, toluene, Virahol.
4. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 1, it is characterized in that: step 1. in, for the benzyloxy bromobenzene class material of 1mol, the magnesium chips using is 0.7mol-1.8mol, and the amyl group dicyclo ketone using is 0.6mol-1.6mol.
5. according to the novel preparation method of the cyclohexyl phenol class liquid crystal intermediates compound described in claim 1, it is characterized in that: step 1. in, described organic solvent total mass be raw material amyl group dicyclo ketone quality 2-5 doubly.
6. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 1, it is characterized in that: step 1. in, initiation reaction at 60 ℃ to 75 ℃, further reaction is carried out at 70 ℃ to 85 ℃, then, then at 50 ℃ to 60 ℃ carry out acidic hydrolysis.
7. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 1, it is characterized in that: step 2. in, the temperature of reaction of each reactive component is divided into two stages: in temperature, be first to carry out at 75 ℃ to 110 ℃, until temperature rises to 110 ℃, then, continuing to heat up, is to carry out at 110 ℃ to 120 ℃ in temperature.
8. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 1, it is characterized in that: step 2. in, for precipitation to the product C obtaining after dry, then with the toluene recrystallization purification of 1 times of quality.
9. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 1, it is characterized in that: step 4. in, for the Compound D of 1mol, the weight molar weight that alkali adds is the 90-100% of the weight molar weight of Compound D.
10. according to the novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound claimed in claim 1, it is characterized in that: step 4. in, adopt gas chromatograph GC to monitor always and follow the tracks of reaction.
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| KR20190013740A (en) * | 2016-06-03 | 2019-02-11 | 디아이씨 가부시끼가이샤 | A self-orienting auxiliary for liquid crystal compositions, a compound suitable for the self-orienting auxiliary, a liquid crystal composition, |
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| CN110964538B (en) * | 2019-12-18 | 2022-01-04 | 江苏创拓新材料有限公司 | Transposition method of 1-cyclohexyl-2, 3-difluorobenzene |
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