CN103553878B - A kind of novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound - Google Patents
A kind of novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound Download PDFInfo
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Abstract
The invention discloses a kind of novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound, it is reacted with magnesium chips in a solvent by benzyloxy bromobenzene compounds, obtains benzyloxy-phenyl magnesium bromide, then react with raw material A, then acidic hydrolysis is carried out, obtained compd B; Compd B carries out the series of processes such as reflux dewatering and obtains Compound C in organic solvent and Organic Acid System; Under PH 6.5-7.5, in organic solvent, Compound C in the presence of a catalyst, carries out hydrogenation, obtains along anti-Compound D; Along anti-Compound D isomerization reaction in organic solvent and strong basicity system, obtain trans product, then obtain cyclohexyl phenol class liquid crystal intermediates compound through series of processes.Present invention process is simple, yield is high, purity is high, and operational path is simple, and cost is low, can meet the requirement of TFT-LCD to liquid crystal intermediates high purity, high-quality, low cost.
Description
Technical field
The present invention relates to a kind of novel preparation method preparing fluorine-containing ethers monomer liquid crystal midbody compound used, more specifically relate to the novel preparation method containing 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 one 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 material forming liquid-crystal display (LCD), and along with the difference of display format, required liquid crystal material is also different.Therefore, liquid crystal material as display also grows along with the development of liquid-crystal display, there is a large amount of novel liquid crystalline cpd, as: cyclohexyl (connection) benzene class, ethane bridged bond class, end alkene class and containing fluorobenzene class liquid crystalline cpd etc., constantly meet the requirement of the display devices such as TN-LCD, STN-LCD, TFT-LCD to performance.
Be used widely in the liquid-crystal display that fluorinated liquid crystal material drives at thin film transistor (TFT) in recent years, become field of liquid crystals study hotspot gradually.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 also called difluoromethyl ethers liquid crystal, is developed at the initial stage the 90's of 20th century.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 all be mentioned to the fluorine-containing ethers monomer liquid crystal compound with the phenol intermediate synthesis containing alkyl and cyclohexyl in the patents such as EP2199270, US55364429, CN102344815:
Be configured to the mixed liquid crystal material of STN-LCD and TFT-LCD together with other monomer liquid crystal compound, and become wherein very important integral part! Have in TFT-LCD and apply widely, become wherein indispensable composition!
In the patent of Merck company, report and carried out etherificate by amphyl prepare difluoro methyl ether with monochlorodifluoromethane, but lack complete synthetic route.The preparation report of 4-［ 4'-(4 "-alkyl cyclohexyl)-cyclohexyl ］ phenol liquid crystal intermediates is few, only have report Xi'an Inst. of Modern Chemistry Lee < fine chemistry industry > the 21st volume the 12nd phase in 2004 to build, one section of article that An Zhongwei etc. deliver, with the Grignard reagent of aryl bromide and 4-(4'-alkyl-cyclohexyl) pimelinketone coupling, dewater through Catalyzed by Potassium Bisulfate again, catalytic hydrogenation, isomerization, demethylating reaction, synthesize trans-alkyl bicyclic hexane phenol, further etherificate obtains the phenyl dicyclic hexane liquid crystal that end group is difluoro-methoxy, wherein do trans-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) and palladium charcoal has been used in process, cost is very high, and can aluminum chloride be used 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 patent discloses a kind of adjacent difluoro alkoxy benzene derivative liquid crystal monomer of CN102826966, it first uses 1,2-bis-fluoro-3-(4-propyl-cyclohexyl base)-benzene is under ultra low temperature state, lithium reagent is prepared with n-Butyl Lithium, then 1 is made, 2-bis-fluoro-3-(4-propyl-cyclohexyl base)-phenylo boric acid, finally in oxidation preparation 1,2-bis-fluoro-3-(4-propyl-cyclohexyl base)-phenol, danger is used and expensive n-Butyl Lithium in its preparation process, severe reaction conditions, cost is higher.
Summary of the invention
Based on above-mentioned the deficiencies in the prior art, the object of this invention is to provide the novel preparation method of simple, the high yield of a kind of technique, highly purified cyclohexyl phenol class liquid crystal intermediates compound, to shorten operational path, reduce production cost, meet the requirement of TFT-LCD to liquid crystal intermediates high purity, high-quality, low cost, adapt to the needs of TFT-LCD liquid crystal material fast development.
The midbody compound prepared needed for ether type monomer of the present invention---cyclohexyl phenol class liquid crystal intermediates compound, this compound has the structure shown in general formula (I):
（I）
Wherein:
R is C
1-C
10alkyl; Further, R is preferably C
1-C
10straight chained alkyl;
More preferably, R is more preferably C
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 any one in-H or-F.
For realizing object of the present invention, provide a kind of novel preparation method of cyclohexyl phenol class liquid crystal intermediates compound (general formula (I)), 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, obtains 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 is more preferably C
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 any one in-H or-F.
2.. compd B carries out reflux dewatering in organic solvent and Organic Acid System, obtains corresponding product (C), washes obtained corresponding product (C), after precipitation is extremely dry, then carries out recrystallization, obtained 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 is more preferably C
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 any one in-H or-F.
3.. in organic solvent, Compound C in the presence of a catalyst, carries 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 is more preferably C
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 any one in-H or-F.
4.. in organic solvent and strong basicity system, carry out isomerization reaction along anti-compound (D), obtain trans product, then acidic hydrolysis is carried out to trans product, after extraction, be washed till neutrality, precipitation to 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 is more preferably C
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 any one in-H or-F.
Step of the present invention 1. described in benzyloxy bromobenzene compounds have multiple, as: benzyloxy bromobenzene, 3,5-bis-fluoro-4-benzyloxy bromobenzenes, 2 can be adopted, 3-bis-fluoro-4-benzyloxy bromobenzene is medium, according to L1, L2, the difference of L3, corresponding different benzyloxy bromobenzene compounds.
Step of the present invention 1. described in raw material (A) be amyl group dicyclo ketone.
Step of the present invention 1. described in organic solvent be at least one in ether, tetrahydrofuran (THF), methyltetrahydrofuran, benzene, toluene and dimethylbenzene, 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.
Step of the present invention 1. described in hydrolysis implement in the presence of acid, preferably hydrochloric acid, sulfuric acid, the glacial acetic acid of optionally dilute with water, be more preferably concentrated hydrochloric acid, most preferably be 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 DEG C to 100 DEG C, is preferably 20 DEG C to 90 DEG C, is more preferably 30 DEG C to 80 DEG C, most preferably reaction initiation reaction at 60 DEG C to 75 DEG C in step (1), further reaction is carried out to 85 DEG C at 70 DEG C, then, then carries out acidic hydrolysis at 50 DEG C to 60 DEG C.
1., the reaction times is not critical step of the present invention, can select according to the number of production lot in wider scope.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 used is generally 0.7mol to 1.8mol, is preferably 0.9mol to 1.5mol, is more preferably 1.0mol to 1.1mol; The amyl group dicyclo ketone (A) used is generally 0.6mol to 1.6mol, is more preferably 0.8mol to 1.5mol, most preferably is 0.8mol to 1.0mol.
Step of the present invention 2. described in reflux dewatering dewatering agent used be any one in tosic acid, the vitriol oil, sal enixum, concentrated hydrochloric acid, be preferably tosic acid, sal enixum, most preferably be tosic acid.
Step of the present invention 2. described in organic solvent be any one in ethyl acetate, toluene, dimethylbenzene, methylene dichloride, be preferably toluene, dimethylbenzene, most preferably be toluene.
Step of the present invention 2. described in Organic Acid System be toluene+tosic acid.
Step of the present invention 2. described in recrystallization organic solvent used be ethanol.
2. step of the present invention can be implemented within the scope of relatively wide temperature and pressure.Typical temperature is 50 DEG C to 150 DEG C.Preferable temperature is 100 DEG C to 150 DEG C.More preferably temperature is 110 DEG C to 130 DEG C.Most preferred temperature is: step 2. in the temperature of reaction of each reactive component be divided into two stages: first carry out at temperature is 75 DEG C to 110 DEG C, until temperature rises to 110 DEG C, then, continue to heat up, carry out at temperature is 110 DEG C to 120 DEG C.The product of gained is by purifying with the re crystallization from toluene of 1 times of quality.
2., the reaction times is not critical step of the present invention, can select according to the number of production lot in wider scope.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, preferably control to carry out under 6.5-7.5 at PH.
Step of the present invention 3. in, described catalyzer is any one 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.
Step of the present invention 3. described in organic solvent be any one in ethyl acetate, ethanol, methyl alcohol, Virahol, toluene, dimethylbenzene, methylene dichloride, be preferably ethanol and methyl alcohol, most preferably be ethanol.
3. step of the present invention can be implemented within the scope of relatively wide temperature and pressure.Typical temperature is 50 DEG C to 200 DEG C, pressure is 0 Mpa to 0.5 Mpa, and preferable temperature is 60 DEG C to 180 DEG C, pressure is 0.1 Mpa to 0.3Mpa, and more preferably temperature is 80 DEG C to 150 DEG C, pressure is 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 select according to the number of production lot in wider scope.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.
Step of the present invention 4. described in isomerization reaction highly basic used be any one in sodium hydroxide, potassium hydroxide, sodium hydride, potassium tert.-butoxide, sodium methylate, be preferably potassium hydroxide and potassium tert.-butoxide, be more preferably potassium hydroxide.And for the compound of 1mol
(d), the add-on (molal amount) of alkali is generally the 90-100% of the amount (molal amount) of Compound D, is preferably 60-70%, most preferably is 40-50%.
Step of the present invention 4. described in organic solvent be dimethyl formamide (DMF), N-Methyl pyrrolidone (NMP), toluene, diglyme, 1, any one in 4 — dioxs, be preferably DMF, toluene, 1, any one in 4 — dioxs, most preferably be DMF.
4. step of the present invention can be implemented in relatively wide temperature range.Typical temperature is 60 DEG C to 150 DEG C, is preferably 80 DEG C to 140 DEG C, is more preferably 90 DEG C to 130 DEG C, most preferably is 100 DEG C to 120 DEG C.
4., the reaction times is not critical step of the present invention, can select according to the number of production lot in wider scope.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 adopt gas chromatograph GC to monitor to follow the tracks of reaction always.
Step of the present invention 4. in, described acidic hydrolysis, preferably hydrochloric acid, sulfuric acid, the glacial acetic acid of optionally dilute with water, be more preferably concentrated hydrochloric acid, most preferably be 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 obtained product B of the first step reaction, do not purify, not discharging, prepare at second step in the process of product (C), adopt and first carries out under the cold condition of 75 DEG C to 100 DEG C, after the reaction process of carrying out under the high temperature of temperature 110 DEG C to 120 DEG C (previous stage is desolvation process, the latter half is reaction process), solvent lower boiling in system can be steamed like this, directly do second step reaction, to shorten preparation cycle.
(2) in the 3rd step, synthesis along anti-product (D) (suitable+anti-) adopts a step catalytic hydrogenation, on the one hand hydrogenation is carried out to the double bond on cyclohexyl, benzyl can be removed again on the other hand, this is advantage maximum in this preparation process, one step hydrogenation solves two problems, and by recrystallization, obtains the white crystal product that purity can reach more than 99%.
Cyclohexyl phenol class liquid crystal intermediates compound is prepared according to method of the present invention, its design and synthesis route is unique, operational path is shorter, processing condition are reasonable, production cost reduces, treatment process is suitable, and product quality is excellent, reaches the requirement of TFT-LCD liquid crystal material to liquid crystal intermediates high purity, high-quality, low cost.
Embodiment
Below in conjunction with specific embodiment, further detailed description is done to the present invention, but 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, when n=2, 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).
The synthesis of step 1:4-［ 4'-(4 "-n-pentyl cyclohexyl) cyclohexyl-l'-hydroxyl ］ benzene benzyl oxide (B):
Under nitrogen protection, add 113 grams of magnesium chips and 600ml tetrahydrofuran (THF) in 5L there-necked flask after, start stirring, heating in water bath, when temperature rises to 60 DEG C, first drip 10ml benzyloxy bromobenzene, the mixing solutions (in mixing solutions, the content of three kinds of materials is: 1124 grams of benzyloxy bromobenzenes+1000 grams of tetrahydrofuran (THF)s+1000 grams of toluene) of tetrahydrofuran (THF) and toluene composition, now, reaction causes automatically, heat release, then continue to drip, be warming up to 75 DEG C, backflow drips, rate of addition and return velocity are consistent, within about 1.5 hours, dropwise, reflux after 1.5 hours, starting toluene solution (that is: 930 grams of amyl group dicyclo ketone (A)+1050 grams of toluene) dropping temperature dripped containing amyl group dicyclo ketone (A) is 80 DEG C, within 1 hour, dropwise, after being incubated 1 hour at this temperature, sampling is followed the tracks of, when amyl group dicyclo ketone is less than 1%, add the hydrochloric acid (namely add 540 grams of tap water in 270 grams of concentrated hydrochloric acids and dilute the hydrochloric acid obtained) of dilution, acidic hydrolysis is carried out at 50 DEG C, 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) synthesis of-l'-cyclohexenyl benzene benzyl oxide (C)
Above-mentioned organic phase is transferred in 5L there-necked flask, reflux water-dividing device is installed, add 30 grams of tosic acid and add 1 gram of stopper (BHT) 2 simultaneously, 6-di-tert-butyl-4-methy phenol, add 1L toluene, start stirring, electric mantle heats, when temperature rises to 65 DEG C, solvent is had to steam, continue to be warming up to 110 DEG C, 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(is suitable+anti-)≤0.1% time, stop heating, be cooled to 40 DEG C, add 1L and be washed to neutrality, precipitation is to dry, recrystallization is done with 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%.
The synthesis of step 3:4-［ 4'-(4 "-n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D)
To in 10L hydrogenation still, add 4-4'-(4 "-n-pentyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C) 1000 grams, neutral Raney's nickel 200 grams, 5000ml ethanol, build kettle cover, after nitrogen replacement air 3 times, logical hydrogen hydrogenation, pressure is 0.2Mpa, temperature is 80 DEG C, hydrogenation is after 5 hours, pressure release, sampling detects, when raw material 4-4'-(4 "-n-pentyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C)≤0.01% time, stop hydrogenation, filtering catalyst, filtrate takes off dry solvent, obtain faint yellow solid 775 grams, GC detects, 4-4'-(4 " and-n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D) (suitable+instead) be 99.47%, yield 98%.
The synthesis of step 4:4-［ 4'-(4 "-n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans) (D)
To in 5L there-necked flask, add 800 grams of 4-［ 4'-(4 "-n-pentyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D) and 2400mlDMF, start stirring, 137 grams of potassium hydroxide are added under whipped state, electric mantle is warming up to 110 DEG C, now system is complete molten state, timing is incubated 6 hours, sampling is followed the tracks of, when cis-product≤1%, stopped reaction, cooling, in reaction system, drip the hydrochloric acid soln be made up of 200ml concentrated hydrochloric acid and 400ml tap water be hydrolyzed, after the extraction of 1500ml toluene, be washed till neutrality, then precipitation is to dry, the mixed solution of the toluene of three times of quality and Virahol (mass ratio of toluene and Virahol is 1:1) is used to carry out recrystallization again, obtain 696 grams, white plates crystal, its fusing point is: 206.2 DEG C, 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, when n=2, L1=L2=-F, 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).
The synthesis of the fluoro-4-of step 1:2,3-bis-［ 4'-(4 "-n-propyl cyclohexyl) cyclohexyl-l'-hydroxyl ］ benzene benzyl oxide (B):
Under nitrogen protection, add 113 grams of magnesium chips and 600ml tetrahydrofuran (THF) in 5L there-necked flask after, start stirring, heating in water bath, when temperature rises to 60 DEG C, first drip 10ml2, 3-bis-fluoro-4-benzyloxy bromobenzene, (in mixing solutions, the content of three kinds of materials is the mixing solutions of tetrahydrofuran (THF) and toluene composition: 1279 gram 2, 3-bis-fluoro-4-benzyloxy bromobenzene+1000 grams of tetrahydrofuran (THF)s+1000 grams of toluene), now, reaction causes automatically, heat release, then continue to drip, be warming up to 75 DEG C, backflow drips, rate of addition and return velocity are consistent, within about 1.5 hours, dropwise, reflux after 1.5 hours, starting toluene solution (that is: 804 grams of propyl group dicyclo ketone (A)+1050 grams of toluene) dropping temperature dripped containing propyl group dicyclo ketone (A) is 80 DEG C, within 1 hour, dropwise, after being incubated 1 hour at this temperature, sampling is followed the tracks of, when propyl group dicyclo ketone is less than 1%, add the hydrochloric acid (adding 540 grams of tap water dilutions in 270 grams of concentrated hydrochloric acids) of dilution, acidic hydrolysis is carried out at 50 DEG C, layering, retain organic phase, GC detects 2, 3-bis-fluoro-4-4'-(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 2:2,3-bis-fluoro-4-4'-(4 " and-n-propyl cyclohexyl) synthesis of-l'-cyclohexenyl benzene benzyl oxide (C)
Above-mentioned organic phase is transferred in 5L there-necked flask, reflux water-dividing device is installed, add 30 grams of tosic acid and add 1 gram of stopper (BHT) 2 simultaneously, 6-di-tert-butyl-4-methy phenol, add 1L toluene, start stirring, electric mantle heats, when temperature rises to 65 DEG C, solvent is had to steam, continue to be warming up to 110 DEG C, 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(is suitable+anti-)≤0.1% time, stop heating, be cooled to 40 DEG C, add 1L and be washed to neutrality, precipitation is to dry, recrystallization is done with after 3 times of dissolve with ethanol, filter to obtain 1388 grams of faint yellow solids, GC detects, 2, 3-bis-fluoro-4-4'-(4 " and-n-propyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C) reaches 99.5%, yield is 90%.
The synthesis of the fluoro-4-of step 3:2,3-bis-［ 4'-(4 "-n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D)
To in 10L hydrogenation still, add 2, 3-bis-fluoro-4-4'-(4 " and-n-propyl cyclohexyl)-l'-cyclohexenyl benzene benzyl oxide (C) 1000 grams, neutral Raney's nickel 200 grams, 5000ml ethanol, build kettle cover, after nitrogen replacement air 3 times, logical hydrogen hydrogenation, pressure is 0.2Mpa, temperature is 80 DEG C, hydrogenation is after 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 faint yellow solid 780 grams, GC detects, 2, 3-bis-fluoro-4-4'-(4 " and-n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans+cis) (D) (suitable+instead) be 99.5%, yield 98.4%.
The synthesis of the fluoro-4-of step 4:2,3-bis-［ 4'-(4 "-n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans) (D)
To 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, 130 grams of potassium hydroxide are added under whipped state, electric mantle is warming up to 110 DEG C, now system is complete molten state, timing is incubated 6 hours, sampling is followed the tracks of, when cis-product≤1%, stopped reaction, be cooled to 50 DEG C, in reaction system, drip the hydrochloric acid soln be made up of 200ml concentrated hydrochloric acid and 400ml tap water be hydrolyzed, after the extraction of 1500ml toluene, be washed till neutrality, then precipitation is to dry, the mixed solution of the toluene of three times of quality and Virahol (mass ratio of toluene and Virahol is 1:1) is used to carry out recrystallization again, obtain 690 grams, white plates crystal, its fusing point is: 195.2 DEG C, GC detects, 2, 3-bis-fluoro-4-4'-(4 " and-n-propyl cyclohexyl)-cyclohexyl ］ phenol (trans) (D) >=99.85%, yield is 86%.
embodiment 3
The present embodiment is 2, the preparation of the fluoro-4-of 3-bis-［ 4'-(4 "-n-pentyl cyclohexyl)-cyclohexyl ］-phenol (trans) (I-3); its preparation process is with embodiment 1; difference be by step 1 by benzyloxy bromobenzene instead of 2; 3-bis-fluoro-4-benzyloxy bromobenzene, prepare target product (I-3).
Experimental result is as follows: target product (I-3) fusing point: 213.5 DEG C, and 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; 5-bis-fluoro-4-benzyloxy bromobenzene, prepares target product (I-4).
Experimental result is as follows: target product (I-4) fusing point: 209.3 DEG C, and 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 amendment made, equivalent replacement, improvement etc. all should be included within protection scope of the present invention.
Claims (1)
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, obtained compd B;
Described raw material A is:
A
Obtained compd B is:
In raw material A and compd B:
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 any one in-H or-F;
2. compd B carries out reflux dewatering in dewatering agent and organic solvent, obtains corresponding product C, washes obtained corresponding product C, after precipitation is extremely dry, then carries out recrystallization, obtained Compound C; Dewatering agent used is any one in tosic acid, the vitriol oil, sal enixum, concentrated hydrochloric acid, and described organic solvent is any one in ethyl acetate, toluene, dimethylbenzene, methylene dichloride;
Described Compound C is:
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 any one in-H or-F;
3. in organic solvent, Compound C in the presence of a catalyst, carries out hydrogenation, obtains along anti-Compound D; Described catalyzer is any one in Raney's nickel catalyst, active nickel catalyst, palladium charcoal Pd/C, platinum charcoal Pt/C;
Described suitable anti-Compound D is:
D （trans、cis）
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 any one in-H or-F;
4. in organic solvent and strong basicity system, isomerization reaction is carried out along anti-Compound D, obtain trans product, then acidic hydrolysis is carried out to trans product, after extraction, be washed till neutrality, precipitation to dry, then after recrystallization purifying, obtains final product-cyclohexyl phenol class liquid crystal intermediates compound;
D （trans）
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 any one in-H or-F.
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| CN110790650B (en) * | 2019-11-14 | 2023-09-29 | 西安瑞联新材料股份有限公司 | Synthesis method of trans-4 '- (4-alkylphenyl) (1, 1' -dicyclohexyl) -4-ketone |
| 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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