CN115636775B - Preparation method of sulfur-containing biphenyl liquid crystal compound - Google Patents
Preparation method of sulfur-containing biphenyl liquid crystal compound Download PDFInfo
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- 238000002360 preparation method Methods 0.000 title claims abstract description 48
- 239000004973 liquid crystal related substance Substances 0.000 title claims abstract description 41
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 title claims abstract description 40
- 150000001875 compounds Chemical class 0.000 title claims abstract description 30
- 235000010290 biphenyl Nutrition 0.000 title claims abstract description 27
- 239000004305 biphenyl Substances 0.000 title claims abstract description 25
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 229910052717 sulfur Inorganic materials 0.000 title claims abstract description 22
- 239000011593 sulfur Substances 0.000 title claims abstract description 22
- 238000006243 chemical reaction Methods 0.000 claims description 67
- -1 biphenyl compound Chemical class 0.000 claims description 42
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical group [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 21
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 18
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 12
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 12
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 12
- 239000003054 catalyst Substances 0.000 claims description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 10
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 10
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical group C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- 238000005859 coupling reaction Methods 0.000 claims description 8
- CYPYTURSJDMMMP-WVCUSYJESA-N (1e,4e)-1,5-diphenylpenta-1,4-dien-3-one;palladium Chemical compound [Pd].[Pd].C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1.C=1C=CC=CC=1\C=C\C(=O)\C=C\C1=CC=CC=C1 CYPYTURSJDMMMP-WVCUSYJESA-N 0.000 claims description 6
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 claims description 6
- 229960000583 acetic acid Drugs 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 5
- 239000003153 chemical reaction reagent Substances 0.000 claims description 5
- 239000012362 glacial acetic acid Substances 0.000 claims description 5
- 239000001301 oxygen Substances 0.000 claims description 5
- 229910052760 oxygen Inorganic materials 0.000 claims description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 229910052731 fluorine Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical class OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 3
- 239000011737 fluorine Substances 0.000 claims description 3
- 230000008569 process Effects 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- CJQWLNNCQIHKHP-UHFFFAOYSA-N Ethyl 3-mercaptopropanoic acid Chemical group CCOC(=O)CCS CJQWLNNCQIHKHP-UHFFFAOYSA-N 0.000 claims description 2
- 150000004074 biphenyls Chemical class 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 238000006266 etherification reaction Methods 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 239000003513 alkali Substances 0.000 claims 2
- 239000002253 acid Substances 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 125000005619 boric acid group Chemical group 0.000 claims 1
- 239000003795 chemical substances by application Substances 0.000 claims 1
- 230000032050 esterification Effects 0.000 claims 1
- 238000005886 esterification reaction Methods 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 230000003647 oxidation Effects 0.000 claims 1
- 238000007254 oxidation reaction Methods 0.000 claims 1
- 238000009776 industrial production Methods 0.000 abstract description 2
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 53
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 48
- 239000012074 organic phase Substances 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 31
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- 239000002904 solvent Substances 0.000 description 22
- 238000001035 drying Methods 0.000 description 20
- 238000010438 heat treatment Methods 0.000 description 20
- 238000010992 reflux Methods 0.000 description 19
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 18
- 238000000605 extraction Methods 0.000 description 18
- 235000019441 ethanol Nutrition 0.000 description 17
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
- 238000004321 preservation Methods 0.000 description 16
- 238000000746 purification Methods 0.000 description 16
- 230000007935 neutral effect Effects 0.000 description 15
- 229910001873 dinitrogen Inorganic materials 0.000 description 13
- 238000001914 filtration Methods 0.000 description 13
- 239000000463 material Substances 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 238000005406 washing Methods 0.000 description 12
- 239000011259 mixed solution Substances 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- 239000012046 mixed solvent Substances 0.000 description 10
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 10
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
- 238000004458 analytical method Methods 0.000 description 7
- 239000012141 concentrate Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 238000005070 sampling Methods 0.000 description 6
- 238000007789 sealing Methods 0.000 description 6
- 238000010907 mechanical stirring Methods 0.000 description 5
- FKRCODPIKNYEAC-UHFFFAOYSA-N propionic acid ethyl ester Natural products CCOC(=O)CC FKRCODPIKNYEAC-UHFFFAOYSA-N 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- 239000000243 solution Substances 0.000 description 5
- 125000003396 thiol group Chemical group [H]S* 0.000 description 5
- 229960000549 4-dimethylaminophenol Drugs 0.000 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 230000018109 developmental process Effects 0.000 description 4
- 239000012535 impurity Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
- WVAXIJZYVPNCKJ-UHFFFAOYSA-N 4-(4-ethoxy-2,3-difluorophenyl)-2,3-difluorophenol Chemical compound FC1=C(F)C(OCC)=CC=C1C1=CC=C(O)C(F)=C1F WVAXIJZYVPNCKJ-UHFFFAOYSA-N 0.000 description 3
- RWSOTUBLDIXVET-UHFFFAOYSA-N Dihydrogen sulfide Chemical compound S RWSOTUBLDIXVET-UHFFFAOYSA-N 0.000 description 3
- LXXNWCFBZHKFPT-UHFFFAOYSA-N Ethyl 2-mercaptopropionate Chemical compound CCOC(=O)C(C)S LXXNWCFBZHKFPT-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910000037 hydrogen sulfide Inorganic materials 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- SZYXKFKWFYUOGZ-UHFFFAOYSA-N (2,3-difluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC(F)=C1F SZYXKFKWFYUOGZ-UHFFFAOYSA-N 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- RDHPKYGYEGBMSE-UHFFFAOYSA-N bromoethane Chemical compound CCBr RDHPKYGYEGBMSE-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 238000005516 engineering process Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000012265 solid product Substances 0.000 description 2
- 125000000446 sulfanediyl group Chemical group *S* 0.000 description 2
- QCSLIRFWJPOENV-UHFFFAOYSA-N (2-fluorophenyl)boronic acid Chemical compound OB(O)C1=CC=CC=C1F QCSLIRFWJPOENV-UHFFFAOYSA-N 0.000 description 1
- OJZVBJOHBGYINN-UHFFFAOYSA-N 1-bromo-4-ethoxy-2,3-difluorobenzene Chemical compound CCOC1=CC=C(Br)C(F)=C1F OJZVBJOHBGYINN-UHFFFAOYSA-N 0.000 description 1
- CYNYIHKIEHGYOZ-UHFFFAOYSA-N 1-bromopropane Chemical compound CCCBr CYNYIHKIEHGYOZ-UHFFFAOYSA-N 0.000 description 1
- WZFUQSJFWNHZHM-UHFFFAOYSA-N 2-[4-[2-(2,3-dihydro-1H-inden-2-ylamino)pyrimidin-5-yl]piperazin-1-yl]-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)ethanone Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)N1CCN(CC1)CC(=O)N1CC2=C(CC1)NN=N2 WZFUQSJFWNHZHM-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- KFFDFOYKRCZONP-UHFFFAOYSA-N CCCC1CCC(C1)C1=C(F)C(F)=C(Br)C=C1 Chemical compound CCCC1CCC(C1)C1=C(F)C(F)=C(Br)C=C1 KFFDFOYKRCZONP-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229920000271 Kevlar® Polymers 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Chemical compound CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 239000004760 aramid Substances 0.000 description 1
- 229920003235 aromatic polyamide Polymers 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical compound OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
- XYZUWOHEILWUID-UHFFFAOYSA-N bromomethylcyclopentane Chemical compound BrCC1CCCC1 XYZUWOHEILWUID-UHFFFAOYSA-N 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000001887 cyclopentyloxy group Chemical group C1(CCCC1)O* 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 239000004761 kevlar Substances 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 239000003444 phase transfer catalyst Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 239000011232 storage material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
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- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a preparation method of a sulfur-containing biphenyl liquid crystal compound, wherein the liquid crystal compound is a compound with a general formula I, and the general formula I is
Description
Technical Field
The invention relates to a preparation method of a liquid crystal compound, in particular to a preparation method of a sulfur-containing biphenyl liquid crystal compound.
Background
In the 60 s of the 20 th century, RCA corporation discovered for the first time that the light transmission mode of liquid crystals was changed by electric stimulation, and then after the liquid crystal display technology was released by applying this property, liquid crystals gradually attracted high attention and rapidly developed to various fields. In 1966, duPont had synthesized Kevlar fibers using aramid liquid crystals, and the liquid crystal materials began the industrialization process. Through rapid development for decades, the liquid crystal material has been widely applied to various fields such as display technology, optical storage equipment, solar cells and the like by virtue of the special properties, and the research scope is more over the fields such as chemistry, biology, information science and the like, so that the liquid crystal material becomes one of the favored and indispensable novel materials in the current society.
The development of liquid crystal materials today is mainly focused on the following aspects: (1) The new process for preparing the existing liquid crystal material is explored, the generation of byproducts and harmful substances is reduced, and the production cost is reduced; (2) The performance of the existing liquid crystal material is modified, such as reducing the requirement on the environmental temperature, improving the color richness and diversity of the liquid crystal material for display, etc.; (3) The novel functional liquid crystal material is prepared to meet the high standard use requirements of multiple fields, such as novel liquid crystal material for display, novel photoelectric liquid crystal storage material in the field of information engineering, novel medicinal liquid crystal material in the field of bioengineering and the like. These developments have left no place for the development of methods for the preparation of liquid crystal materials.
In an improvement over existing liquid crystal materials, there is a direction to replace the corresponding moiety in existing liquid crystal compounds (e.g. replacing bromine with chlorine, oxygen with sulfur) with groups or elements having similar properties in order to obtain unexpected property changes. However, the relatively mature preparation method of the existing liquid crystal compound cannot be directly applied to the liquid crystal compound after replacement, and the problems of large pollution, low cost, low yield, difficult purification and the like of the preparation of the new compound are inevitably encountered in the exploration process of the new liquid crystal compound.
Disclosure of Invention
The invention aims to provide a preparation method of a sulfur-containing biphenyl liquid crystal compound, which is simple and convenient to operate, has little pollution, high yield and is easy to purify.
The technical scheme is as follows: in order to achieve the above object, according to one aspect of the present invention, there is provided a method for preparing a sulfur-containing biphenyl-based liquid crystal compound.
The liquid crystal compound synthesized by the invention has a general formula I, wherein the general formula I is as follows:
wherein R is 1 Is a C1-C10 linear alkyl group, a linear alkoxy group, a naphthene group, an oxygen-containing naphthene group, or a combination thereof, R 2 Is a C1-C10 linear alkyl group, a cycloalkane group or a combination of a cycloalkane group and a linear alkyl group, X 1 、X 2 、X 3 、X 4 、X 5 、X 6 、X 7 、X 8 Each independently hydrogen or fluorine;
the preparation method comprises the following steps:
(1) Preparation of the derivatives by means of a boronic acid-halohydrocarbon coupling reactionA biphenyl compound of structure;
(2) Oxidizing the biphenyl compound prepared in the step 1 under the low-temperature condition to prepare the biphenyl compound with a structurePhenol compounds of (2);
(3) Sulfonylating the phenol compound obtained in the step 2 to obtain a phenol compound having the following structureSulfonate of structure;
(4) Combining the sulfonate prepared in the step 3 with a sulfur source to prepare the catalystStructural ethyl sulfanyl propionate;
(5) The ethyl sulfanyl propionate prepared in the step 4 is subjected to etherification reaction to prepare the catalyst with the following componentsSulfur-containing biphenyls;
advantageous effects
Compared with the prior art, the invention has the following advantages:
in the preparation method provided by the invention, impurities contained in the products obtained in the steps 2,3 and 4 do not participate in the reaction, so that the products can be directly put into the next reaction without purification, and the products can be purified once after the reaction in the step is finished. The advantage of disposable purification is that
1. The preparation process can be simplified, and the time required by industrial production can be shortened;
2. the use of organic solvents in the purification process is reduced, the cost is saved, and the pollution to the environment is reduced;
3. avoiding the necessary loss during the gradual purification and effectively improving the final yield.
Detailed description of the preferred embodiments
It should be noted that, in the case of no conflict, the embodiments and features in the embodiments may be combined with each other. The advantageous effects of the present invention will be further described below with reference to examples.
The specification and sources of part of raw materials and reagents used in the invention are as follows:
the invention provides a preparation method of a sulfur-containing biphenyl liquid crystal compound, which is characterized in that the prepared liquid crystal compound has a structure shown in a general formula I, wherein the general formula I is as follows:
wherein R is 1 Is a C1-C10 linear alkyl group, a linear alkoxy group, a naphthene group, an oxygen-containing naphthene group, or a combination thereof, R 2 Is a C1-C10 linear alkyl group, a cycloalkane group or a combination of a cycloalkane group and a linear alkyl group, X 1 、X 2 、X 3 、X 4 、X 5 、X 6 、X 7 、X 8 Each independently hydrogen or fluorine;
the preparation method comprises the following steps:
(1) To have the followingThe structural compound is used as raw materialToluene, ethanol and pure water are used as mixed solvents, anhydrous potassium carbonate is used for providing an alkaline environment, a phase transfer catalyst (usually tetrabutylammonium bromide) is added, and a coupling catalyst is stirred and refluxed under the anhydrous and anaerobic condition. After the reaction is finished, adding ethyl acetate, normal hexane and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases by anhydrous magnesium sulfate, filtering, concentrating and removing the dry solvent, and recrystallizing the organic phases by using a mixed solvent of ethyl acetate and ethanol to obtain a compound->The synthetic route of step 1 is shown below:
(2) Dissolving the product obtained in the step 1 by 8-10 times of anhydrous tetrahydrofuran, and reducing the reaction system to-75+/-5 ℃ under the protection of nitrogen; dripping 1-1.1 equivalent of n-butyllithium to pull hydrogen, and preserving heat for 1-1.5 h after dripping; after the heat preservation is finished, 1.3 to 1.5 equivalents of mixed solution of trimethyl borate and tetrahydrofuran is dripped into the system, the temperature is controlled between-70 ℃ and-80 ℃, and the heat preservation is carried out for 1 to 1.5 hours after the dripping is finished; after the heat preservation is finished, removing nitrogen, naturally heating the reaction system to room temperature, and dropwise adding 3-4 equivalents of glacial acetic acid and water solution into the reaction system to enable the reactants to be fully acidolyzed; after acidolysis, 3-4 equivalents of 30% hydrogen peroxide is dripped into the reaction system, and the temperature is controlled below 45 ℃; after the reactants are fully oxidized, adding ethyl acetate, normal hexane and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases by anhydrous magnesium sulfate, filtering, concentrating and removing the dry solvent to obtain the compoundThe obtained product was directly used in the next step after drying without purification. The synthetic route for step 2 is shown below:
(3) Dissolving the product obtained in the step 2 by using 6-8 times of dichloromethane, adding 0.04-0.06 equivalent of DMAP as a catalyst, reducing the temperature of a reaction system to below 0 ℃ by using an ice salt bath, sequentially adding 1.4-1.6 equivalent of triethylamine and 1.1-1.3 equivalent of trifluoromethanesulfonic anhydride into the reaction system, keeping the temperature between-5 ℃ and 5 ℃, and preserving the temperature for 2 hours; sampling GC after the heat preservation is finished, diluting a reaction system with dichloromethane after the completion of the reaction, directly passing through a short silica gel column, concentrating and removing the dry solvent to obtain a compoundThe obtained product was used directly in the next reaction without purification. The synthetic route of step 3 is shown below:
(4) Mixing the product obtained in the step 3 with 1.1-1.3 equivalent of 3-mercaptopropionic acid ethyl ester, dissolving with 5-10 times of toluene, introducing nitrogen for protection, erecting a condenser tube, heating to micro reflux, adding 2-3 equivalent of anhydrous sodium carbonate, 0.09-0.11 equivalent of bis (2-diphenylphosphinophenyl) ether and 0.04-0.06 equivalent of tris (dibenzylideneacetone) dipalladium into the system, continuing heating to reflux, reacting for 1.5-2 hours, and sampling GC; after confirming that the reaction is finished, adding ethyl acetate and water into the system for layered extraction, combining the organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate, filtering, concentrating and removing the dry solvent to obtain the compoundThe obtained product was used in the next reaction without purification. The synthetic route of step 4 is shown below:
(5) Mixing the product obtained in the step 4 with 2 to 3 equivalents of a compound with a general formula of Br-R 2 Mixing the compound of (2) with 3 to 3.5 equivalents of potassium hydroxide, dissolving the mixture with 5 to 10 times of acetone, and introducing nitrogen for protection; heating reverseAfter the reaction is performed for micro reflux, removing nitrogen, sealing the system, performing heat preservation reaction for 2 hours, and then sampling and analyzing by TLC until the raw materials are basically reacted; adding toluene and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate, filtering, concentrating and removing the dry solvent to obtain a solid product, and recrystallizing and purifying the solid product by using a mixed solution of toluene and ethanol to obtain the compoundThe synthetic route of step 5 is shown below:
the advantageous effects of the present invention will be further described below with reference to examples.
Example 11 preparation of- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluoro-4- (propylsulfanyl) benzene the preparation scheme is as follows:
step 1, preparation of 4-ethoxy-2, 2',3' -tetrafluoro-1, 1' -biphenyl
10000ml four-mouth bottle, 0-100 ℃ thermometer, mechanical stirring, spherical condenser, constant pressure dropping funnel, nitrogen gas; 474g of 4-ethoxy-2, 3-difluorobromobenzene, 552g of anhydrous potassium carbonate, 600ml of pure water, 32g of tetrabutylammonium bromide, 1500ml of toluene and 300ml of absolute ethyl alcohol are added into the system, the mixture is stirred and heated to about 45 ℃, 1.5g of coupling catalyst is added, and the temperature is continuously raised to micro reflux; dripping the prepared boric acid solution (316 g of mixed solution of 2, 3-difluorophenylboronic acid and 1200ml of absolute ethyl alcohol) into the system, and after the dripping is finished, carrying out heat preservation reaction for 2 hours at 70-75 ℃ and sampling GC; after the reaction is finished, adding ethyl acetate, normal hexane and water into the system for layered extraction, combining organic phases, washing the organic phases to be neutral, drying the organic phases by anhydrous magnesium sulfate, filtering, concentrating and removing the dry solvent, and recrystallizing the mixed solvent of ethyl acetate and ethanol to obtain 388g of refined 4-ethoxy-2, 2',3' -tetrafluoro-1, 1' -biphenyl (GC is more than or equal to 99.85 percent), wherein the yield is 72 percent.
Step 2, preparation of 4- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluorophenol
10000ml four-mouth bottle, installing a low-temperature thermometer, mechanically stirring, dropping a funnel at constant pressure, introducing nitrogen, adding the 4-ethoxy-2, 2',3' -tetrafluoro-1, 1' -biphenyl 3838 g obtained in the step 1 and 4000ml tetrahydrofuran into the system, and cooling the system to-78 ℃ after dissolving; 632ml of n-butyllithium n-hexane solution (2.5 mol/L) is added dropwise into the system, and the temperature is controlled to be minus 75 plus or minus 5 ℃; after dripping, the mixture is reacted for 1 to 1.5 hours at the temperature of minus 75 plus or minus 5 ℃; after heat preservation, 224g of mixed solution of trimethyl borate and 250ml of tetrahydrofuran is dropwise added into the system, and the temperature is controlled to be 75+/-5 ℃; after the dripping is finished, the temperature is kept at-75+/-5 ℃ for reaction for 1 to 1.5 hours, and then the temperature is naturally raised to the room temperature; dripping a mixed solution of 258.7g of glacial acetic acid and 388ml of water into the system, and measuring the pH value of the reaction system by using broad-spectrum pH test paper after dripping; after the acidity is displayed, 491g of hydrogen peroxide with the concentration of 30 percent is dripped into the system, and the temperature is controlled below 45 ℃; after the dripping is finished, the reaction is carried out for 2 hours at the temperature of 40-45 ℃, GC is sampled, after the reaction is finished, ethyl acetate, normal hexane and water are added into the system for layered extraction, the organic phase is combined and washed to be neutral by water, anhydrous magnesium sulfate is dried, and the solvent is filtered, concentrated and removed to obtain 420g of the product, wherein the content of 4- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluorophenol measured by GC is about 85 percent. The main impurity is 4-ethoxy-2, 2',3' -tetrafluoro-1, 1' -biphenyl, which does not participate in the subsequent reaction, so the obtained product is not purified, and 403g is obtained after drying and is directly used in the next step.
Step 3 preparation of 4- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluorophenyl trifluoromethanesulfonate
5000ml four-port flask, equipped with a low temperature thermometer, magnetic stirrer, constant pressure dropping funnel, nitrogen gas, to the reaction system were added all at once, to the last step of obtaining 403g 4- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluorophenol (estimated as 1.2 mol), 2400ml dichloromethane, 7.3g DMAP; after the dissolution, cooling the system to below 0 ℃ by using an ice salt bath, sequentially dropwise adding 182g of triethylamine and 406g of trifluoromethanesulfonic anhydride into the system, and controlling the temperature to be 0+/-5 ℃; after the dripping is finished, the temperature is kept between 0 and 10 ℃ for 2 hours, and GC is sampled; after confirming that the reaction was completed, the reaction system was diluted with methylene chloride and then directly subjected to short silica gel, and the solvent was concentrated and dried to obtain 820g of a concentrate of 4- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluorophenyl trifluoromethanesulfonate, which was used directly in the next reaction without purification.
Step 4, preparation of ethyl 3- { [4' - (4 "-ethoxy-2", 3 "-difluorophenyl) -2',3' -difluorophenyl ] sulfanyl } propanoate
5000ml four-mouth bottle, installing 0-00 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, introducing nitrogen, adding 4- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluorophenyl trifluoro methane sulfonate obtained in the previous step, 194g ethyl mercaptopropionate, 3000ml toluene into the reaction system; after heating to slight reflux, 318g of anhydrous sodium carbonate, 64.6g of bis (2-diphenylphosphinophenyl) ether and 55g of tris (dibenzylideneacetone) dipalladium are added into the system, the mixture is continuously heated to reflux, and after heat preservation reaction is carried out for 2 hours, GC is sampled; after confirming that the reaction was completed, ethyl acetate and water were added to the system for the layered extraction, and the organic phases were combined, washed with water to neutrality, dried over anhydrous magnesium sulfate for 0.5h, and then filtered, concentrated and the solvent was removed to obtain 720g of ethyl 3- { [4' - (4 "-ethoxy-2", "-difluorophenyl) -2',3' -difluorophenyl ] sulfanyl } propionate concentrate, which was used directly in the next reaction without purification.
Step 5 preparation of 1- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluoro-4- (propylsulfanyl) benzene
10000ml four-mouth bottle, 0-100 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, nitrogen gas, 295g bromopropane, 202g potassium hydroxide, 4000ml acetone and ethyl 3- { [4' - (4 "ethoxy-2", "-difluorophenyl) -2',3' -difluorophenyl ] sulfanyl } propionate obtained in the previous step are added into the reaction system at one time; heating to start micro reflux, sealing the reaction system, preserving heat for 2h, and performing TLC analysis until the raw materials are basically reacted; adding toluene and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate for 0.5h, filtering, concentrating and removing the dry solvent to obtain 600g of orange yellow solid, crystallizing the mixed solvent of toluene and ethanol to obtain 276g of 1- (4 ' -ethoxy-2 ',3' -difluorophenyl) -2, 3-difluoro-4- (propylsulfanyl) benzene fine product (GC content is more than or equal to 99.813%), wherein the fine product yield is about 67%.
Example 21 preparation of- {4' - [ (cyclopentyl) sulfanyl ] -2',3' -difluorophenyl } -4-ethoxy-2, 3-difluorobenzene the preparation scheme is as follows:
step 1, step 2, step 3, and step 4 are the same as embodiment 1, and will not be repeated here.
Step 5, preparation of 1- {4' - [ (cyclopentyl) sulfanyl ] -2',3' -difluorophenyl } -4-ethoxy-2, 3-difluorobenzene
10000ml four-mouth bottle, 0-100 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, nitrogen gas, 536g of bromocyclopentane, 204g of potassium hydroxide, 4000ml of acetone and 3- { [4'- (4' -ethoxy-2 ',3' -difluorophenyl) -2',3' -difluorophenyl ] sulfanyl } ethyl propionate obtained in the previous step are added into the reaction system at one time; heating to start micro reflux, sealing the reaction system, preserving heat for 2h, and performing TLC analysis until the raw materials are basically reacted; adding toluene and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate for 0.5h, filtering, concentrating and removing the dry solvent to obtain 600g of orange yellow solid, crystallizing the mixed solvent of toluene and ethanol to obtain 348 g of 1- {4' - [ (cyclopentyl) sulfanyl ] -2',3' -difluorophenyl } -4-ethoxy-2, 3-difluorobenzene fine product (GC content is more than or equal to 99.853%), wherein the fine product yield is about 77%;
example 31 preparation of- {4' - [ (cyclopentylmethyl) sulfanyl ] -2',3' -difluorophenyl } -4-ethoxy-2, 3-difluorobenzene the preparation scheme is as follows:
step 1, step 2, step 3, and step 4 are the same as embodiment 1, and will not be repeated here.
Step 5, preparation of 1- {4' - [ (cyclopentylmethyl) sulfanyl ] -2',3' -difluorophenyl } -4-ethoxy-2, 3-difluorobenzene
10000ml four-mouth bottle, 0-100 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, nitrogen gas, 588g bromomethyl cyclopentane, 204g potassium hydroxide, 4000ml acetone and ethyl 3- { [4'- (4' -ethoxy-2 ',3' -difluorophenyl) -2',3' -difluorophenyl ] sulfanyl } propionate obtained in the previous step are added into the reaction system at one time; heating to start micro reflux, sealing the reaction system, preserving heat for 2h, and performing TLC analysis until the raw materials are basically reacted; adding toluene and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate for 0.5h, filtering, concentrating and removing the dry solvent to obtain 620g of orange yellow solid, crystallizing the mixed solvent of toluene and ethanol to obtain 312g of 1- {4' - [ (cyclopentylmethyl) sulfanyl ] -2',3' -difluorophenyl } -4-ethoxy-2, 3-difluorobenzene fine product (GC content is more than or equal to 99.803%), wherein the fine product yield is about 70%;
example 4 1 preparation of- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -4- (ethylsulfanyl) -2, 3-difluorobenzene, the preparation scheme is as follows:
step 1, preparation of 1- (cyclopentyloxy) -4- (2, 3-difluorophenyl) -2, 3-difluorobenzene
3000ml four-mouth bottle, 0-100 ℃ thermometer, mechanical stirring, constant pressure dropping funnel, nitrogen gas, 138g 2, 3-difluoro-4-cyclopentyloxy bromobenzene, 138g potassium carbonate, 200ml pure water, 8g tetrabutylammonium bromide, 500ml toluene, 100ml ethanol; heating to 45 ℃, and adding a coupling catalyst and 50ml of ethanol into the system; continuously heating to slightly reflux, and dropwise adding a mixed solution of 79g of 2, 3-difluorophenylboronic acid and 500ml of ethanol; after dripping, continuously heating to reflux; after the reaction is completed, ethyl acetate and water are added into the system for layered extraction, the organic phase is combined and washed to be neutral by water, anhydrous magnesium sulfate is dried for 0.5h, 198g of crude product is obtained by filtering, concentrating and removing the dry solvent, and 124g of mixed solvent of ethyl acetate and ethanol is obtained after crystallization and drying, and the yield is 80 percent and the GC content is 99.85 percent.
Step 2, preparation of 4- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -2, 3-difluorophenol
3000ml four-port bottle, thermometer at-100-50 deg.C, mechanical stirring, constant pressure dropping funnel, introducing nitrogen, adding 124g of 1- (cyclopentyloxy) -4- (2, 3-difluorophenyl) -2, 3-difluorobenzene into the system, 1200ml tetrahydrofuran; after dissolution, the system is cooled to-78+/-5 ℃; 176ml of n-butyllithium n-hexane solution (2.5 mol/L) is added into the system dropwise, and the temperature is controlled to be minus 75 plus or minus 5 ℃; after dripping, the mixture is reacted for 1 to 1.5 hours at the temperature of minus 75 plus or minus 5 ℃; after heat preservation, dropwise adding a mixed solution of 62.3g of trimethyl borate and 100ml of tetrahydrofuran into the system, and controlling the temperature to be 75+/-5 ℃; after dripping, the mixture is reacted for 1h at the temperature of minus 75 plus or minus 5 ℃; after heat preservation, naturally heating to room temperature overnight; dropwise adding a mixed solution consisting of 72g of glacial acetic acid and 108g of water into the system; after dripping, stirring for 0.5h at room temperature, dripping 137g of 30% hydrogen peroxide into the system, and controlling the temperature below 45 ℃; after the dripping is finished, the reaction is carried out for 1 hour at the temperature of 40-45 ℃ and TLC analysis is carried out until the reaction of the raw materials is finished; adding ethyl acetate and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate for 0.5h, filtering, concentrating and removing the dry solvent to obtain 130g of a product, wherein the GC content is 80%, and the main impurity of the product is 1- (cyclopentyloxy) -4- (2, 3-difluorophenyl) -2, 3-difluorobenzene which does not participate in the subsequent reaction is determined, 110g is obtained after drying, and the product is directly used in the next step without purification;
step 3, preparation of 4- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -2, 3-difluorophenyl trifluoromethanesulfonate
2000ml four-port bottle, thermometer at-100-50 ℃, magnetic stirrer, constant pressure dropping funnel, nitrogen gas, 110g of 4- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -2, 3-difluorophenol (estimated as 0.3 mol) obtained in the previous step, 750ml of dichloromethane were added to the system; 1.95g of DMAP is added into the system after ice salt bath, 46.5g of triethylamine and 102g of trifluoromethanesulfonic anhydride are sequentially added into the system after the addition, and the temperature is controlled to be 0+/-5 ℃; after the dripping is finished, carrying out heat preservation reaction for 2 hours at 0-10 ℃, and sampling GC; after confirming that the reaction was completed, the reaction system was diluted with methylene chloride, followed by directly passing through a short silica gel, concentrating and drying the solvent to obtain 207g of a concentrate, which was used directly in the next reaction without purification.
Step 4, preparation of ethyl 3- ({ 4' - [4"- (cyclopentyloxy) -2",3 "-difluorophenyl ] -2',3' -difluorophenyl } sulfanyl) propanoate
2000ml four-port bottle, installing 0-100 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, introducing nitrogen, adding 4- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -2, 3-difluorophenyl trifluoro methane sulfonate obtained in the previous step, 48g ethyl mercaptopropionate, 1000ml toluene; after heating to slight reflux, 79.5g of anhydrous sodium carbonate, 16.5g of bis (2-diphenylphosphinophenyl) ether and 13.8g of tris (dibenzylideneacetone) dipalladium are added into the system, the mixture is continuously heated to reflux, and after heat preservation reaction is carried out for 2 hours, GC is sampled; after confirming that the reaction was completed, ethyl acetate and water were added to the system to conduct layered extraction, the organic phases were combined and washed with water to neutrality, dried over anhydrous magnesium sulfate for 0.5h, and then the resultant was filtered, concentrated and the solvent was removed to obtain 232.5g of concentrate, which was directly used for the next reaction without purification.
Step 5, preparation of 1- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -4- (ethylsulfanyl) -2, 3-difluorobenzene
5000ml four-mouth bottle, 0-100 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, nitrogen gas, adding 98g bromoethane, 51g potassium hydroxide, 1200ml acetone and 3- ({ 4'- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -2',3' -difluorophenyl } sulfanyl) ethyl propionate obtained in the previous step into the reaction system at one time; heating to start micro reflux, sealing the reaction system, preserving heat for 2h, and performing TLC analysis until the raw materials are basically reacted; adding toluene and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate for 0.5h, filtering, concentrating and removing the dry solvent to obtain 165g of orange yellow solid, crystallizing the mixed solvent of toluene and ethanol to obtain 76.5g of 1- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -4- (ethylsulfanyl) -2, 3-difluorobenzene (GC content is more than or equal to 99.815%), wherein the refined yield is about 71%;
example 5 preparation of propyl (2 ',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-yl) sulfane, the preparation scheme is as follows:
step 1, preparation of 2,3 '-trifluoro-4- (3-propylcyclopentyl) -1,1' -biphenyl
3000ml four-mouth bottle, 0-100 ℃ thermometer, mechanical stirring, constant pressure dropping funnel, nitrogen gas charging, 196g 1-bromo-2, 3-difluoro-4- (3-propylcyclopentyl) benzene, 138g potassium carbonate, 200ml pure water, 8g tetrabutylammonium bromide, 500ml toluene, 100ml ethanol are added into the system; heating to 45 ℃, and adding a coupling catalyst and 50ml of ethanol into the system; continuously heating to slightly reflux, and dropwise adding a mixed solution of 70g of 2-fluorobenzeneboronic acid and 500ml of ethanol; after dripping, continuously heating to reflux; after the reaction is completed, ethyl acetate and water are added into the system for layered extraction, the organic phase is combined and washed to be neutral by water, anhydrous magnesium sulfate is dried for 0.5h, the mixture is filtered, concentrated and the solvent is removed to obtain 212g of crude product, the mixed solvent of ethyl acetate and ethanol is crystallized, 145g is obtained after drying, the yield is 90%, and the GC content is 99.87%.
Step 2, preparation of 2',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-ol
3000ml four-mouth bottle, 100-50 ℃ thermometer, mechanical stirring, constant pressure dropping funnel, nitrogen gas charging, adding 145g of 2,3 '-trifluoro-4- (3-propylcyclopentyl) -1,1' -biphenyl obtained in the previous step and 1200ml of tetrahydrofuran into the system; after dissolution, the system is cooled to-78+/-5 ℃; 198ml of n-butyllithium n-hexane solution (2.5 mol/L) is added into the system dropwise, and the temperature is controlled to be minus 75 plus or minus 5 ℃; after dripping, the mixture is reacted for 1 to 1.5 hours at the temperature of minus 75 plus or minus 5 ℃; after heat preservation, 70g of mixed solution of trimethyl borate and 100ml of tetrahydrofuran is dropwise added into the system, and the temperature is controlled to be-75+/-5 ℃; after dripping, the mixture is reacted for 1h at the temperature of minus 75 plus or minus 5 ℃; after heat preservation, naturally heating to room temperature overnight; dropwise adding a mixed solution consisting of 81g of glacial acetic acid and 122g of water into the system; after the dripping is finished, stirring for 0.5h at room temperature, dripping 154g of 30% hydrogen peroxide into the system, and controlling the temperature below 45 ℃; after the dripping is finished, the reaction is carried out for 1 hour at the temperature of 40-45 ℃ and TLC analysis is carried out until the reaction of the raw materials is finished; adding ethyl acetate and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate for 0.5h, filtering, concentrating and removing the dry solvent to obtain 181g of product, wherein the GC content is 85%, and the main impurity of the product is 1- (cyclopentyloxy) -4- (2, 3-difluorophenyl) -2, 3-difluorobenzene which does not participate in the subsequent reaction, and 155g of product is obtained after drying and is directly used in the next step without purification;
step 3, preparation of 2',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-ylmethane sulfonate
3000ml four-port bottle, thermometer at-100-50 ℃, magnetic stirrer, constant pressure dropping funnel, nitrogen gas, 155g of 4- [4' - (cyclopentyloxy) -2',3' -difluorophenyl ] -2, 3-difluorophenol (estimated as 0.4 mol) obtained in the previous step, 1000ml of dichloromethane are added into the system; 2.6g of DMAP is added into the system after the ice salt bath, 62g of triethylamine and 136g of trifluoromethanesulfonic anhydride are sequentially added into the system in a dropwise manner after the addition, and the temperature is controlled to be 0+/-5 ℃; after the dripping is finished, carrying out heat preservation reaction for 2 hours at 0-10 ℃, and sampling GC; after confirming that the reaction was completed, the reaction system was diluted with methylene chloride, followed by directly passing through a short silica gel, concentrating and drying the solvent to obtain 280g of concentrate, which was used directly in the next reaction without purification.
Step 4, preparation of ethyl 3- ((2 ',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-yl) thio) propionate
3000ml four-port bottle, 0-100 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, nitrogen gas, 2',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-yl methanesulfonate obtained in the previous step, 64g ethyl mercaptopropionate, 1200ml toluene; after heating to slight reflux, 106g of anhydrous sodium carbonate, 22g of bis (2-diphenylphosphinophenyl) ether and 18.4g of tris (dibenzylideneacetone) dipalladium are added into the system, the mixture is continuously heated to reflux, and after heat preservation reaction is carried out for 2 hours, GC is sampled; after confirming that the reaction was completed, ethyl acetate and water were added to the system for layered extraction, the organic phases were combined and washed with water to neutrality, dried over anhydrous magnesium sulfate for 0.5h, and then filtered, concentrated and the solvent was removed to obtain 312g of concentrate, which was directly used for the next reaction without purification.
Step 5 preparation of propyl (2 ',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-yl) sulfane
5000ml four-mouth bottle, 0-100 ℃ thermometer, constant temperature magnetic stirrer, spherical condenser tube, nitrogen gas, adding 148g bromoethane, 68g potassium hydroxide, 1500ml acetone, 3- ((2 ',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-yl) thio) ethyl propionate obtained in the previous step into the reaction system at one time; heating to start micro reflux, sealing the reaction system, preserving heat for 2h, and performing TLC analysis until the raw materials are basically reacted; adding toluene and water into the system for layered extraction, combining organic phases, washing the organic phases with water to be neutral, drying the organic phases with anhydrous magnesium sulfate for 0.5h, filtering, concentrating and removing the dry solvent to obtain 250g of orange-yellow solid, crystallizing the mixed solvent of toluene and ethanol to obtain 114g of propyl (2 ',3' -trifluoro-4 '- (3-propylcyclopentyl) - [1,1' -biphenyl ] -4-yl) sulfane (GC content is more than or equal to 99.834%), and the refined yield is about 73%;
by combining the above examples 1 to 5, the method provided by the invention can prepare the biphenyl liquid crystal compound containing sulfur with a relatively simple flow, relatively less organic solvent consumption and relatively high yield.
The following liquid crystal compounds can be conveniently prepared with reference to the similar preparation methods using examples 1 to 5:
in addition, although the preparation method of the sulfur-containing biphenyl liquid crystal compounds is not exhaustive, it is anticipated by those skilled in the art that other similar compounds can be prepared without any creative effort by combining the specific knowledge of the workers based on the disclosed examples. Only representative embodiments are listed herein.
The above description is only of the preferred embodiments of the present invention and is not intended to limit the present invention, but various modifications and variations can be made to the present invention by those skilled in the art. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention should be included in the protection scope of the present invention.
Claims (6)
1. The preparation method of the sulfur-containing biphenyl liquid crystal compound comprises the following steps:
wherein R is 1 Is a C1-C10 linear alkyl group, a linear alkoxy group, a naphthene group, an oxygen-containing naphthene group, or a combination thereof, R 2 Is a C1-C10 linear alkyl group, a cycloalkane group or a combination of a cycloalkane group and a linear alkyl group, X 1 、X 2 、X 3 、X 4 、X 5 、X 6 、X 7 、X 8 Each independently hydrogen or fluorine;
the preparation method comprises the following steps:
(1) Preparation of the derivatives by means of a boronic acid-halohydrocarbon coupling reactionA biphenyl compound of structure;
(2) Oxidizing the biphenyl compound prepared in the step 1 under the low-temperature condition to prepare the biphenyl compound with a structurePhenol compounds of (2);
(3) Sulfonylating the phenol compound obtained in the step 2 to obtain a phenol compound having the following structureSulfonate of structure;
(4) Combining the sulfonate prepared in the step 3 with a sulfur source to prepare the catalyst havingStructural ethyl sulfanyl propionate;
(5) The ethyl sulfanyl propionate prepared in the step 4 is subjected to etherification reaction to prepare the catalyst with the following componentsSulfur-containing biphenyls;
wherein the reactants of the coupling reaction in the step 1 areWherein R is 1 Is a C1-C10 linear alkyl group, a linear alkoxy group, a naphthene group, an oxygen-containing naphthene group, or a combination thereof, Y 1 Is a boric acid group, namely-B (OH) 2 ，Y 2 Is halogen group, selected from one of F, cl or Br;
wherein, the step 2 is that the biphenyl compound obtained in the step 1 is firstly extracted with strong alkali reagent n-butyl lithium under the low temperature condition, then added with trimethyl borate for esterification, and after the low temperature is kept for 1 to 1.5 hours, the reaction system is naturally warmed to room temperature, diluted glacial acetic acid is added for acidolysis, and after acidolysis, hydrogen peroxide with volume concentration of 30 percent is added dropwise for oxidation, thus obtaining the biphenyl compound with the following characteristics ofPhenol compounds of the structure;
wherein in the step 4, the sulfur source is 3-mercaptopropionic acid ethyl ester, and the catalyst used is bis (2-diphenylphosphinophenyl) ether and tris (dibenzylideneacetone) dipalladium;
in the step 5, the reaction system is an alkaline environment, and the reagent providing the alkaline environment is potassium hydroxide.
2. The method for preparing a sulfur-containing biphenyl liquid crystal compound according to claim 1, wherein the reaction system of the coupling reaction in step 1 is an alkaline environment, and the reagent providing the alkaline environment is anhydrous potassium carbonate.
3. The method for preparing a sulfur-containing biphenyl liquid crystal compound according to claim 1, wherein the molar ratio of the biphenyl compound obtained in step 1 to the strong alkali reagent n-butyllithium in step 2 is 1:1-1.1, and the molar ratio of the biphenyl compound to trimethyl borate is 1:1.3-1.5.
4. The method for preparing a sulfur-containing biphenyl liquid crystal compound according to claim 1, wherein in the step 3, the catalyst used is 4-Dimethylaminopyridine (DMAP), the sulfonylating agent used is trifluoromethanesulfonic anhydride, and the acid-binding agent used is triethylamine.
5. The process for producing a sulfur-containing biphenyl liquid crystal compound according to claim 4, wherein in step 3, the molar ratio of the phenol compound obtained in step 2 to trifluoromethanesulfonic anhydride is 1:1.1 to 1.3 and the molar ratio of the phenol compound to triethylamine is 1:1.4 to 1.6.
6. The method for preparing a sulfur-containing biphenyl liquid crystal compound according to claim 1, wherein in step 4, the molar ratio of sulfonate obtained in step 3 to sulfur source is 1:1.1-1.3, the molar ratio of sulfonate to bis (2-diphenylphosphinophenyl) ether is 1:0.09-0.11, and the molar ratio of sulfonate to tris (dibenzylideneacetone) dipalladium is 1:0.04-0.06.
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| CN111100048A (en) * | 2018-10-25 | 2020-05-05 | 沈阳中化农药化工研发有限公司 | Preparation method of diphenyl sulfide compound |
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| CN103571498A (en) * | 2013-10-16 | 2014-02-12 | 西安彩晶光电科技股份有限公司 | CF2S bridged bond-containing liquid crystal monomeric compound and synthesis method |
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