JP4924863B2 - Method for producing difluorobenzene derivative - Google Patents
Method for producing difluorobenzene derivative Download PDFInfo
- Publication number
- JP4924863B2 JP4924863B2 JP2005316169A JP2005316169A JP4924863B2 JP 4924863 B2 JP4924863 B2 JP 4924863B2 JP 2005316169 A JP2005316169 A JP 2005316169A JP 2005316169 A JP2005316169 A JP 2005316169A JP 4924863 B2 JP4924863 B2 JP 4924863B2
- Authority
- JP
- Japan
- Prior art keywords
- general formula
- group
- carbon atoms
- represent
- same meaning
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000004519 manufacturing process Methods 0.000 title claims description 17
- GOYDNIKZWGIXJT-UHFFFAOYSA-N 1,2-difluorobenzene Chemical class FC1=CC=CC=C1F GOYDNIKZWGIXJT-UHFFFAOYSA-N 0.000 title description 7
- 150000001875 compounds Chemical class 0.000 claims description 79
- 125000004432 carbon atom Chemical group C* 0.000 claims description 47
- -1 p-toluenesulfonyloxy group Chemical group 0.000 claims description 28
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 12
- 125000003342 alkenyl group Chemical group 0.000 claims description 12
- 239000000460 chlorine Substances 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 11
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 11
- 125000003545 alkoxy group Chemical group 0.000 claims description 11
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 11
- 229910052794 bromium Inorganic materials 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000005948 methanesulfonyloxy group Chemical group 0.000 claims description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 10
- AZFQCTBZOPUVOW-UHFFFAOYSA-N methyl(triphenyl)phosphanium Chemical class C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 AZFQCTBZOPUVOW-UHFFFAOYSA-N 0.000 claims description 10
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 10
- SDMCZCALYDCRBH-UHFFFAOYSA-N methoxymethyl(triphenyl)phosphanium Chemical class C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SDMCZCALYDCRBH-UHFFFAOYSA-N 0.000 claims description 9
- ISWSIDIOOBJBQZ-UHFFFAOYSA-M phenolate Chemical compound [O-]C1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-M 0.000 claims description 8
- 229940031826 phenolate Drugs 0.000 claims description 8
- 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 claims description 8
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 claims description 6
- 239000007800 oxidant agent Substances 0.000 claims description 6
- WGOPGODQLGJZGL-UHFFFAOYSA-N lithium;butane Chemical compound [Li+].CC[CH-]C WGOPGODQLGJZGL-UHFFFAOYSA-N 0.000 claims description 5
- RPEPGIOVXBBUMJ-UHFFFAOYSA-N 2,3-difluorophenol Chemical compound OC1=CC=CC(F)=C1F RPEPGIOVXBBUMJ-UHFFFAOYSA-N 0.000 claims description 4
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 4
- KFSLWBXXFJQRDL-UHFFFAOYSA-N Peracetic acid Chemical compound CC(=O)OO KFSLWBXXFJQRDL-UHFFFAOYSA-N 0.000 claims description 4
- 239000003153 chemical reaction reagent Substances 0.000 claims description 4
- 125000002524 organometallic group Chemical group 0.000 claims description 4
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 claims description 3
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims 1
- 150000002978 peroxides Chemical class 0.000 claims 1
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 44
- 239000002904 solvent Substances 0.000 description 42
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- 239000004973 liquid crystal related substance Substances 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 19
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 238000006243 chemical reaction Methods 0.000 description 17
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 17
- 239000000203 mixture Substances 0.000 description 14
- 239000004210 ether based solvent Substances 0.000 description 13
- 238000001819 mass spectrum Methods 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- 239000012044 organic layer Substances 0.000 description 11
- 238000005160 1H NMR spectroscopy Methods 0.000 description 10
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 10
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 10
- 239000003849 aromatic solvent Substances 0.000 description 10
- 239000004215 Carbon black (E152) Substances 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 230000015572 biosynthetic process Effects 0.000 description 9
- 229930195733 hydrocarbon Natural products 0.000 description 9
- 150000002430 hydrocarbons Chemical class 0.000 description 9
- 239000002798 polar solvent Substances 0.000 description 9
- 238000003786 synthesis reaction Methods 0.000 description 9
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 8
- CKKAZWYLHGNVDZ-UHFFFAOYSA-N 2,3-difluoro-4-methoxyphenol Chemical compound COC1=CC=C(O)C(F)=C1F CKKAZWYLHGNVDZ-UHFFFAOYSA-N 0.000 description 7
- DUTIYVOXQFBHJK-NUUBBLISSA-N C(=O)[C@@H]1CC[C@H](CC1)C1=C(C(=C(C=C1OC)OC[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)CC)F)F Chemical compound C(=O)[C@@H]1CC[C@H](CC1)C1=C(C(=C(C=C1OC)OC[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)CC)F)F DUTIYVOXQFBHJK-NUUBBLISSA-N 0.000 description 7
- APDMJKMEPZFWKQ-QAQDUYKDSA-N CCCC[C@H]1CC[C@H](COC(C=C(C(C(CC2)CCC2=O)=C2F)OC)=C2F)CC1 Chemical compound CCCC[C@H]1CC[C@H](COC(C=C(C(C(CC2)CCC2=O)=C2F)OC)=C2F)CC1 APDMJKMEPZFWKQ-QAQDUYKDSA-N 0.000 description 7
- CORPKQWSUJIUEA-HDJSIYSDSA-N CCCC[C@H]1CC[C@H](COC(C=CC(OC)=C2F)=C2F)CC1 Chemical compound CCCC[C@H]1CC[C@H](COC(C=CC(OC)=C2F)=C2F)CC1 CORPKQWSUJIUEA-HDJSIYSDSA-N 0.000 description 7
- 239000007810 chemical reaction solvent Substances 0.000 description 7
- RDOGTTNFVLSBKG-UHFFFAOYSA-N 1,2-difluoro-3-methoxybenzene Chemical compound COC1=CC=CC(F)=C1F RDOGTTNFVLSBKG-UHFFFAOYSA-N 0.000 description 6
- VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 6
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
- QXVWHHVNWXGCQG-OPMHRUBESA-N COC1=C(C(=C(C=C1)OC[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)CC)F)F Chemical compound COC1=C(C(=C(C=C1)OC[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)CC)F)F QXVWHHVNWXGCQG-OPMHRUBESA-N 0.000 description 6
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 6
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- 238000004440 column chromatography Methods 0.000 description 6
- 238000001816 cooling Methods 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000008096 xylene Substances 0.000 description 6
- CHEWJFZUNBFWOB-UBBSCCEASA-N C(=O)[C@@H]1CC[C@H](CC1)C1=C(C(=C(C=C1OC)OC[C@@H]1CC[C@H](CC1)CCCC)F)F Chemical compound C(=O)[C@@H]1CC[C@H](CC1)C1=C(C(=C(C=C1OC)OC[C@@H]1CC[C@H](CC1)CCCC)F)F CHEWJFZUNBFWOB-UBBSCCEASA-N 0.000 description 5
- KFUYZYUUVCBHFY-IFSQOONMSA-N CC[C@H](CC1)CC[C@@H]1[C@H]1CC[C@H](COC(C=C(C(C(CC2)CCC2=O)=C2F)OC)=C2F)CC1 Chemical compound CC[C@H](CC1)CC[C@@H]1[C@H]1CC[C@H](COC(C=C(C(C(CC2)CCC2=O)=C2F)OC)=C2F)CC1 KFUYZYUUVCBHFY-IFSQOONMSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000007710 freezing Methods 0.000 description 5
- 230000008014 freezing Effects 0.000 description 5
- 238000002955 isolation Methods 0.000 description 5
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 5
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 5
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 5
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- ZYGIGCGQXNTERG-IFSQOONMSA-N FC1=C(C=C(C(=C1F)[C@@H]1CC[C@H](CC1)C=C)OC[C@@H]1CC[C@H](CC1)CCCC)OC Chemical compound FC1=C(C=C(C(=C1F)[C@@H]1CC[C@H](CC1)C=C)OC[C@@H]1CC[C@H](CC1)CCCC)OC ZYGIGCGQXNTERG-IFSQOONMSA-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
- 229910000318 alkali metal phosphate Inorganic materials 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
- LWIHDJKSTIGBAC-UHFFFAOYSA-K tripotassium phosphate Chemical compound [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 4
- DYLIWHYUXAJDOJ-OWOJBTEDSA-N (e)-4-(6-aminopurin-9-yl)but-2-en-1-ol Chemical compound NC1=NC=NC2=C1N=CN2C\C=C\CO DYLIWHYUXAJDOJ-OWOJBTEDSA-N 0.000 description 3
- 0 *C1(CCC(C*C=C)CC1)O* Chemical compound *C1(CCC(C*C=C)CC1)O* 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- BNIPVJNRPRBAQL-NYUFXJCHSA-N FC1=C(C=C(C(=C1F)[C@@H]1CC[C@H](CC1)C=C)OC[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)CC)OC Chemical compound FC1=C(C=C(C(=C1F)[C@@H]1CC[C@H](CC1)C=C)OC[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)CC)OC BNIPVJNRPRBAQL-NYUFXJCHSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- 239000002253 acid Substances 0.000 description 3
- 229910000288 alkali metal carbonate Inorganic materials 0.000 description 3
- 150000008041 alkali metal carbonates Chemical class 0.000 description 3
- 229910000102 alkali metal hydride Inorganic materials 0.000 description 3
- 150000008046 alkali metal hydrides Chemical class 0.000 description 3
- 150000001639 boron compounds Chemical class 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 238000001953 recrystallisation Methods 0.000 description 3
- 239000012312 sodium hydride Substances 0.000 description 3
- 229910000104 sodium hydride Inorganic materials 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 2
- OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 2
- 229910052783 alkali metal Inorganic materials 0.000 description 2
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 2
- 230000005595 deprotonation Effects 0.000 description 2
- 238000010537 deprotonation reaction Methods 0.000 description 2
- 229940117389 dichlorobenzene Drugs 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 239000005453 ketone based solvent Substances 0.000 description 2
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 229940098779 methanesulfonic acid Drugs 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 2
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- 230000007704 transition Effects 0.000 description 2
- 229910000404 tripotassium phosphate Inorganic materials 0.000 description 2
- 235000019798 tripotassium phosphate Nutrition 0.000 description 2
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 1
- 229910015900 BF3 Inorganic materials 0.000 description 1
- VXGDOXAULQMWOI-UBBSCCEASA-N C(=O)[C@@H]1CC[C@H](CC1)C=1C(=C(C(=C(C1)OC[C@@H]1CC[C@H](CC1)CCCC)F)F)OC Chemical compound C(=O)[C@@H]1CC[C@H](CC1)C=1C(=C(C(=C(C1)OC[C@@H]1CC[C@H](CC1)CCCC)F)F)OC VXGDOXAULQMWOI-UBBSCCEASA-N 0.000 description 1
- FHRLWJCMWHBUBH-UBBSCCEASA-N C(C)[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)COC1=CC=CC=C1 Chemical compound C(C)[C@@H]1CC[C@H](CC1)[C@@H]1CC[C@H](CC1)COC1=CC=CC=C1 FHRLWJCMWHBUBH-UBBSCCEASA-N 0.000 description 1
- MVMZKLKIUWBNCA-XYPYZODXSA-N CCCC[C@H]1CC[C@H](CBr)CC1 Chemical compound CCCC[C@H]1CC[C@H](CBr)CC1 MVMZKLKIUWBNCA-XYPYZODXSA-N 0.000 description 1
- DQEODYVEJBBEIO-VVPTUSLJSA-N CC[C@H](CC1)CC[C@@H]1[C@H](CC1)CC[C@@H]1C(C=CC=C1)=C1OC Chemical compound CC[C@H](CC1)CC[C@@H]1[C@H](CC1)CC[C@@H]1C(C=CC=C1)=C1OC DQEODYVEJBBEIO-VVPTUSLJSA-N 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 241000336896 Numata Species 0.000 description 1
- QRLSPZHITUKTDH-UHFFFAOYSA-N OC1(CCC(COc(cccc2F)c2F)CC1)O Chemical compound OC1(CCC(COc(cccc2F)c2F)CC1)O QRLSPZHITUKTDH-UHFFFAOYSA-N 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000004327 boric acid Substances 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
- 229910000024 caesium carbonate Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 238000007697 cis-trans-isomerization reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000000062 cyclohexylmethoxy group Chemical group [H]C([H])(O*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- 230000005684 electric field Effects 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 239000011521 glass Substances 0.000 description 1
- 150000004678 hydrides Chemical class 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- SIAPCJWMELPYOE-UHFFFAOYSA-N lithium hydride Chemical compound [LiH] SIAPCJWMELPYOE-UHFFFAOYSA-N 0.000 description 1
- 229910000103 lithium hydride Inorganic materials 0.000 description 1
- UBJFKNSINUCEAL-UHFFFAOYSA-N lithium;2-methylpropane Chemical compound [Li+].C[C-](C)C UBJFKNSINUCEAL-UHFFFAOYSA-N 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229910000000 metal hydroxide Inorganic materials 0.000 description 1
- 150000004692 metal hydroxides Chemical class 0.000 description 1
- 229910001463 metal phosphate Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 0.000 description 1
- SJFNDMHZXCUXSA-UHFFFAOYSA-M methoxymethyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(COC)C1=CC=CC=C1 SJFNDMHZXCUXSA-UHFFFAOYSA-M 0.000 description 1
- QRPRIOOKPZSVFN-UHFFFAOYSA-M methyl(triphenyl)phosphanium;chloride Chemical compound [Cl-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(C)C1=CC=CC=C1 QRPRIOOKPZSVFN-UHFFFAOYSA-M 0.000 description 1
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 1
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 1
- 239000012046 mixed solvent Substances 0.000 description 1
- CZFNISFYDPIDNM-UHFFFAOYSA-N n,n-dimethylformamide;oxolane Chemical compound CN(C)C=O.C1CCOC1 CZFNISFYDPIDNM-UHFFFAOYSA-N 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 235000015497 potassium bicarbonate Nutrition 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- 235000011181 potassium carbonates Nutrition 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 229940086066 potassium hydrogencarbonate Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 1
- 239000010409 thin film Substances 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
本発明はジフルオロベンゼン誘導体の製造方法に関する。 The present invention relates to a method for producing a difluorobenzene derivative.
液晶表示素子は、低電圧作動、薄型表示等の優れた特徴から現在広く用いられている。従来の液晶表示素子の表示方式にはTN（ねじれネマチック）、STN（超ねじれネマチック）、又はTNをベースにしたアクティブマトリックス（TFT：薄膜トランジスタ）等があり、これらは誘電率異方性値が正の液晶組成物を利用するものである。しかし、これら表示方式の欠点の一つとして視野角の狭さがあり、近年高まっている液晶パネルの大型化の要求に伴い、その改善が大きな課題となっている。 Liquid crystal display elements are currently widely used because of their excellent features such as low voltage operation and thin display. Conventional liquid crystal display element display methods include TN (twisted nematic), STN (super twisted nematic), or active matrix (TFT: thin film transistor) based on TN, and these have positive dielectric anisotropy values. The liquid crystal composition is used. However, one of the disadvantages of these display methods is a narrow viewing angle, and with the increasing demand for larger liquid crystal panels in recent years, the improvement has become a major issue.
この解決策として近年、垂直配向方式、IPS（インプレインスイッチング）等の表示方式が新たに実用化されてきた。垂直配向方式は液晶分子の垂直配向を利用して視野角の改善を図った方式であり、誘電異方性値が負の液晶組成物が使用される。またIPSは、ガラス基板に対して水平方向の横電界を用いて液晶分子をスイッチングさせることで視野角の改善を図った方法であり、誘電異方性値が正又は負の液晶組成物が使用される。このように、視野角改善のために有効な表示方式である垂直配向方式及びIPSには誘電率異方性値が負である液晶化合物ならびに液晶組成物が必要であり、強く要望されるようになってきた。 In recent years, display methods such as vertical alignment and IPS (in-plane switching) have been newly put to practical use as a solution. The vertical alignment method is a method in which the viewing angle is improved by utilizing the vertical alignment of liquid crystal molecules, and a liquid crystal composition having a negative dielectric anisotropy value is used. IPS is a method of improving viewing angle by switching liquid crystal molecules using a horizontal electric field in the horizontal direction with respect to a glass substrate, and a liquid crystal composition having a positive or negative dielectric anisotropy value is used. Is done. As described above, the vertical alignment method and the IPS, which are effective display methods for improving the viewing angle, require a liquid crystal compound and a liquid crystal composition having a negative dielectric anisotropy value. It has become.
誘電率異方性が負の液晶組成物に使用される液晶化合物としては、2,3-ジフルオロベンゼン誘導体が挙げられる（特許文献１参照）。しかしながら、特許文献１は側鎖がアルキル基の化合物のみが開示されており、側鎖にビニル基を有する化合物の開示は全くなく、製造方法は知られていなかった。また、ベンゼン環の1位および4位にシクロヘキシルメトキシ基を有する化合物は化学的に不安定で液晶材料として使用できないとの知見（非特許文献１参照）により、当該化合物の製造方法の開発は進行していなかった。 Examples of the liquid crystal compound used in the liquid crystal composition having a negative dielectric anisotropy include 2,3-difluorobenzene derivatives (see Patent Document 1). However, Patent Document 1 discloses only a compound having an alkyl group in the side chain, and no disclosure of a compound having a vinyl group in the side chain, and the production method has not been known. In addition, the development of a method for producing the compound has progressed due to the knowledge that a compound having a cyclohexylmethoxy group at the 1-position and 4-position of the benzene ring is chemically unstable and cannot be used as a liquid crystal material (see Non-Patent Document 1). I did not.
側鎖にビニル基を有するジフルオロベンゼン誘導体の製造方法を提供することである。また、側鎖にビニル基を有するジフルオロベンゼン誘導体の製造に有用な中間体化合物を提供することである。 It is to provide a method for producing a difluorobenzene derivative having a vinyl group in a side chain. Moreover, it is providing the intermediate compound useful for manufacture of the difluorobenzene derivative which has a vinyl group in a side chain.
本発明者は、上記課題を解決するために鋭意検討した結果、本件発明を完成するに至った。
本発明は、一般式(1)
As a result of intensive studies in order to solve the above problems, the present inventors have completed the present invention.
The present invention relates to general formula (1)
（式中、R1およびR2はそれぞれ独立的にメチル基、エチル基またはプロピル基を表すか、R1およびR2は-CH2CH2-、-CH2CH2CH2-または-CH2C(CH3)2CH2-を表し、X1は塩素、臭素、よう素、ベンゼンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基又はトリフルオロメタンスルホニルオキシ基を表す。）で表される化合物を2,3-ジフルオロフェノールより調製されるフェノラートを反応させることにより一般式(2) (Wherein R 1 and R 2 each independently represent a methyl group, an ethyl group or a propyl group, or R 1 and R 2 are —CH 2 CH 2 —, —CH 2 CH 2 CH 2 — or —CH 2 C (CH 3 ) 2 CH 2 —, and X 1 represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group. By reacting a phenolate prepared from 2,3-difluorophenol with the compound represented by the general formula (2)
（式中、R3およびnは一般式(4)と同じ意味を表す。）で表される化合物とし、この化合物をメトキシメチルトリフェニルホスホニウム塩より調製されるイリドと反応させた後加水分解することにより一般式(7) (Wherein R 3 and n represent the same meaning as in the general formula (4)), and this compound is reacted with an ylide prepared from a methoxymethyltriphenylphosphonium salt and then hydrolyzed. General formula (7)
本発明の製造方法は、ジフルオロベンゼン誘導体を効率的に製造することができることから当該化合物の製造方法として有用である。また、本発明の化合物を使用することにより、ジフルオロベンゼン誘導体を効率的に製造することが可能であり、製造中間体として有用である。 Since the production method of the present invention can produce a difluorobenzene derivative efficiently, it is useful as a production method of the compound. In addition, by using the compound of the present invention, a difluorobenzene derivative can be produced efficiently and is useful as a production intermediate.
2,3-ジフルオロフェノールを塩基を用いてフェノラートとし、その後一般式(1)で表される化合物と反応させることによって一般式(2)で表される化合物を得るが、使用する塩基としては金属水素化物、金属炭酸塩、金属リン酸塩、金属水酸化物、金属カルボン酸塩、金属アミドおよび金属等を挙げることができ、中でもアルカリ金属水素化物、アルカリ金属リン酸塩、アルカリ金属リン酸塩、アルカリ金属炭酸塩、アルカリ金属水酸化物、アルカリ金属アミドおよびアルカリ金属が好ましく、アルカリ金属リン酸塩、アルカリ金属水素化物およびアルカリ金属炭酸塩は更に好ましい。アルカリ金属水素化物としては水素化リチウム、水素化ナトリウムおよび水素化カリウムを、アルカリ金属リン酸塩としてはリン酸三カリウムを、アルカリ金属炭酸塩としては炭酸ナトリウム、炭酸水素ナトリウム、炭酸セシウム、炭酸カリウムおよび炭酸水素カリウムをそれぞれ好ましく挙げることができる。 2,3-Difluorophenol is converted into phenolate using a base, and then reacted with a compound represented by general formula (1) to obtain a compound represented by general formula (2). Examples include hydrides, metal carbonates, metal phosphates, metal hydroxides, metal carboxylates, metal amides and metals, among which alkali metal hydrides, alkali metal phosphates, alkali metal phosphates. Alkali metal carbonates, alkali metal hydroxides, alkali metal amides and alkali metals are preferred, and alkali metal phosphates, alkali metal hydrides and alkali metal carbonates are more preferred. Lithium hydride, sodium hydride and potassium hydride as alkali metal hydrides, tripotassium phosphate as alkali metal phosphates, sodium carbonate, sodium hydrogen carbonate, cesium carbonate, potassium carbonate as alkali metal carbonates And potassium hydrogen carbonate can be preferably mentioned.
反応溶媒としては、反応を好適に進行させるものであればいずれでも構わないが、エーテル系溶媒、塩素系溶媒、炭化水素系溶媒、芳香族系溶媒および極性溶媒等を好ましく用いることができる。エーテル系溶媒としては、1,4-ジオキサン、1,3-ジオキサン、テトラヒドロフラン、ジエチルエーテルおよびｔ-ブチルメチルエーテル等を、塩素系溶媒としてはジクロロメタン、1,2-ジクロロエタンおよび四塩化炭素等を、炭化水素系溶媒としてはペンタン、ヘキサン、シクロヘキサン、ヘプタンおよびオクタン等を、芳香族系溶媒としてはベンゼン、トルエン、キシレン、メシチレン、クロロベンゼンおよびジクロロベンゼン等を、極性溶媒としてはN,N-ジメチルホルムアミド、N-メチルピロリドン、ジメチルスルホキシドおよびスルホラン等を好例として挙げることができる。中でも、テトラヒドロフラン、ジエチルエーテル等のエーテル系溶媒およびN,N-ジメチルホルムアミド等の極性溶媒がより好ましい。また、前記の各溶媒を単独で使用しても、2種もしくはそれ以上の溶媒を混合して使用してもよい。 Any reaction solvent may be used as long as it allows the reaction to proceed suitably. Ether solvents, chlorine solvents, hydrocarbon solvents, aromatic solvents, polar solvents, and the like can be preferably used. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether and t-butyl methyl ether. Examples of chlorine solvents include dichloromethane, 1,2-dichloroethane and carbon tetrachloride. Examples of hydrocarbon solvents include pentane, hexane, cyclohexane, heptane and octane, aromatic solvents such as benzene, toluene, xylene, mesitylene, chlorobenzene and dichlorobenzene, and polar solvents such as N, N-dimethylformamide, Preferable examples include N-methylpyrrolidone, dimethyl sulfoxide, and sulfolane. Among these, ether solvents such as tetrahydrofuran and diethyl ether and polar solvents such as N, N-dimethylformamide are more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
反応温度は溶媒の凝固点から還流温度範囲で行うことができるが、0℃から150℃が好ましく、30℃から120℃がより好ましい。なお、生成したフェノラートを一度単離してから一般式(1)で表される化合物と反応させてもよく、単離せずに反応させてもよいが、作業の煩雑さから単離せずに反応させたほうがよい。 The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably from 0 ° C to 150 ° C, more preferably from 30 ° C to 120 ° C. The generated phenolate may be isolated once and then reacted with the compound represented by the general formula (1), or may be reacted without isolation, but it is allowed to react without isolation due to the complexity of work. Better.
なお、R1およびR2はそれぞれ独立的にメチル基、エチル基またはプロピル基を表すかまたは、R1およびR2は-CH2CH2-、-CH2CH2CH2-または-CH2C(CH3)2CH2-を表すが、R1およびR2が共にメチル基であるか、R1およびR2が-CH2CH2-または-CH2CH2CH2-であることが好ましい。X1は塩素、臭素、よう素、ベンゼンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基又はトリフルオロメタンスルホニルオキシ基を表すが、臭素またはメタンスルホニルオキシ基が好ましい。 R 1 and R 2 each independently represent a methyl group, an ethyl group or a propyl group, or R 1 and R 2 are —CH 2 CH 2 —, —CH 2 CH 2 CH 2 — or —CH 2 C (CH 3 ) 2 CH 2 — represents that R 1 and R 2 are both methyl groups, or R 1 and R 2 are —CH 2 CH 2 — or —CH 2 CH 2 CH 2 —. Is preferred. X 1 represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, preferably bromine or methanesulfonyloxy group.
一般式(2)で表される化合物の酸化は、有機金属試薬により脱プロトン化した後ほう酸トリアルキルと反応させてほう素化合物とし、その後酸化剤を作用させることによって行うことができる。反応溶媒としては、反応を好適に進行させるものであればいずれでも構わないが、エーテル系溶媒および炭化水素系溶媒等を挙げることができる。エーテル系溶媒としては、1,4-ジオキサン、1,3-ジオキサン、テトラヒドロフラン、ジエチルエーテルおよびｔ-ブチルメチルエーテル等を、炭化水素系溶媒としてはペンタン、ヘキサン、シクロヘキサン、ヘプタンおよびオクタン等が挙げられ、中でもテトラヒドロフランが好ましい。有機金属試薬としてはn-ブチルリチウム、sec-ブチルリチウム、tert-ブチルリチウム、メチルリチウムおよびリチウムジイソプロピルアミド等を挙げることができ、入手および取り扱いの容易さからn-ブチルリチウムおよびsec-ブチルリチウムが好ましく、効率的にリチオ化が可能であるsec-ブチルリチウムがより好ましい。脱プロトン化の際の反応温度は-100℃から-20℃が好ましく、-78℃から-40℃がより好ましい。 The oxidation of the compound represented by the general formula (2) can be carried out by deprotonation with an organometallic reagent, reacting with a trialkyl borate to form a boron compound, and then allowing an oxidizing agent to act. Any reaction solvent may be used as long as it allows the reaction to proceed suitably, and examples thereof include ether solvents and hydrocarbon solvents. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of hydrocarbon solvents include pentane, hexane, cyclohexane, heptane, and octane. Of these, tetrahydrofuran is preferred. Examples of the organometallic reagent include n-butyllithium, sec-butyllithium, tert-butyllithium, methyllithium and lithium diisopropylamide, and n-butyllithium and sec-butyllithium are Preferably, sec-butyllithium that can be efficiently lithiated is more preferable. The reaction temperature at the time of deprotonation is preferably -100 ° C to -20 ° C, more preferably -78 ° C to -40 ° C.
ほう酸トリアルキルとしては、ほう酸トリメチルを用いるのが好ましい。ほう素化の際の反応温度は-100℃から-20℃が好ましく、-78℃から-40℃がより好ましい。得られたほう素化合物は一度単離してもよく、単離せずそのまま酸化剤と反応させてもよい。また、得られたほう素化合物を加水分解してほう酸化合物へと変換した後に酸化剤と反応させても構わない。 Trimethyl borate is preferably used as the trialkyl borate. The reaction temperature during boriding is preferably from -100 ° C to -20 ° C, more preferably from -78 ° C to -40 ° C. The obtained boron compound may be isolated once or may be reacted with an oxidizing agent without isolation. Further, the obtained boron compound may be hydrolyzed and converted into a boric acid compound and then reacted with an oxidizing agent.
酸化剤としては、過酸化水素水、過酢酸または過ギ酸を用いるのが好ましい。反応温度は-78℃から70℃が好ましく、0℃から50℃がより好ましい。また、酸化剤との反応時には、溶媒に水が含まれていても構わない。 As the oxidizing agent, it is preferable to use hydrogen peroxide, peracetic acid or performic acid. The reaction temperature is preferably -78 ° C to 70 ° C, more preferably 0 ° C to 50 ° C. Moreover, water may be contained in the solvent at the time of reaction with an oxidizing agent.
一般式(3)で表される化合物を一般式(5)で表される化合物に変換する反応は、一般式(1)で表される化合物を一般式(2)へ変換する反応（前述）と同様に行うことができる。この際X2は塩素、臭素、よう素、ベンゼンスルホニルオキシ基、p-トルエンスルホニルオキシ基、メタンスルホニルオキシ基又はトリフルオロメタンスルホニルオキシ基を表すが、臭素またはメタンスルホニルオキシ基が好ましい。 The reaction for converting the compound represented by the general formula (3) into the compound represented by the general formula (5) is a reaction for converting the compound represented by the general formula (1) into the general formula (2) (described above). Can be done as well. X 2 represents chlorine, bromine, iodine, benzenesulfonyloxy group, p-toluenesulfonyloxy group, methanesulfonyloxy group or trifluoromethanesulfonyloxy group, preferably bromine or methanesulfonyloxy group.
一般式(5)で表される化合物の脱保護は、酸性条件下で行うことが好ましい。使用する酸としては、ギ酸、酢酸、トリフルオロ酢酸、しゅう酸、p-トルエンスルホン酸等のプロトン酸および三フッ化ほう素等のルイス酸等が挙げられるが、ギ酸を用いるのが好ましい。 The deprotection of the compound represented by the general formula (5) is preferably performed under acidic conditions. Examples of the acid used include protonic acids such as formic acid, acetic acid, trifluoroacetic acid, oxalic acid, and p-toluenesulfonic acid, and Lewis acids such as boron trifluoride. Formic acid is preferably used.
反応溶媒としては、反応を好適に進行させるものであればいずれでも構わないが、エーテル系溶媒、塩素系溶媒、ケトン系溶媒、炭化水素系溶媒、芳香族系溶媒および極性溶媒等を好ましく用いることができ、無溶媒で反応させてもよい。エーテル系溶媒としては、1,4-ジオキサン、1,3-ジオキサン、テトラヒドロフラン、ジエチルエーテルおよびｔ-ブチルメチルエーテル等を、塩素系溶媒としてはジクロロメタン、1,2-ジクロロエタン、クロロホルムおよび四塩化炭素等を、ケトン系溶媒としてはアセトンおよび2-ブタノン等を、炭化水素系溶媒としてはペンタン、ヘキサン、シクロヘキサン、ヘプタンおよびオクタン等を、芳香族系溶媒としてはベンゼン、トルエン、キシレン、メシチレン、クロロベンゼンおよびジクロロベンゼン等を、極性溶媒としてはアセトニトリルおよびジメチルスルホキシド等を好例として挙げることができる。中でも、ペンタン、ヘキサン、シクロヘキサン、ヘプタンおよびオクタン等の炭化水素系溶媒およびベンゼン、トルエン、キシレン等の芳香族系溶媒等がより好ましい。また、前記の各溶媒を単独で使用しても、2種もしくはそれ以上の溶媒を混合して使用してもよい。 Any reaction solvent may be used as long as it allows the reaction to proceed suitably, but ether solvents, chlorine solvents, ketone solvents, hydrocarbon solvents, aromatic solvents, polar solvents, and the like are preferably used. And may be reacted without solvent. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of chlorine solvents include dichloromethane, 1,2-dichloroethane, chloroform, and carbon tetrachloride. Acetone, 2-butanone and the like as ketone solvents, pentane, hexane, cyclohexane, heptane and octane as hydrocarbon solvents, and benzene, toluene, xylene, mesitylene, chlorobenzene and dibenzene as aromatic solvents. Preferable examples include chlorobenzene and acetonitrile, dimethyl sulfoxide and the like as polar solvents. Of these, hydrocarbon solvents such as pentane, hexane, cyclohexane, heptane and octane, and aromatic solvents such as benzene, toluene and xylene are more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
反応温度は溶媒の凝固点から還流温度範囲で行うことができるが、0℃から100℃が好ましく、30℃から60℃がより好ましい。 The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably 0 ° C to 100 ° C, more preferably 30 ° C to 60 ° C.
一般式(6)で表される化合物をメトキシメチルトリフェニルホスホニウム塩より調製されるイリドと反応させた後加水分解することにより一般式(7)で表される化合物を得ることができる。イリドの調製はメトキシメチルトリフェニルホスホニウム塩に塩基を作用させて行うが、使用する塩基としてはカリウム-t-ブトキシド、n-ブチルリチウム、フェニルリチウム、水素化ナトリウム等が好ましく、カリウム-t-ブトキシドがより好ましい。反応溶媒はエーテル系溶媒、芳香族系溶媒および極性溶媒等を好ましく用いることができる。エーテル系溶媒としては、1,4-ジオキサン、1,3-ジオキサン、テトラヒドロフラン、ジエチルエーテルおよびｔ-ブチルメチルエーテル等を、芳香族系溶媒としてはベンゼン、トルエン、キシレン、メシチレン等を、極性溶媒としてはN,N-ジメチルホルムアミド等を好例として挙げることができる。中でもテトラヒドロフランおよびトルエンがより好ましい。また、前記の各溶媒を単独で使用しても、2種もしくはそれ以上の溶媒を混合して使用してもよい。 A compound represented by the general formula (7) can be obtained by reacting a compound represented by the general formula (6) with an ylide prepared from a methoxymethyltriphenylphosphonium salt, followed by hydrolysis. The ylide is prepared by reacting a methoxymethyltriphenylphosphonium salt with a base. As the base to be used, potassium tert-butoxide, n-butyllithium, phenyllithium, sodium hydride, etc. are preferable. Potassium tert-butoxide Is more preferable. As the reaction solvent, ether solvents, aromatic solvents, polar solvents and the like can be preferably used. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of aromatic solvents include benzene, toluene, xylene, mesitylene, and the like as polar solvents. A good example is N, N-dimethylformamide. Of these, tetrahydrofuran and toluene are more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
反応温度は溶媒の凝固点から還流温度範囲で行うことができるが、-40℃から30℃が好ましく、-20℃から20℃がより好ましい。得られたイリドは単離することなく一般式(6)で表される化合物と反応させるのが好ましい。また、メトキシメチルトリフェニルホスホニウム塩および一般式(6)で表される化合物の混合物に対して塩基を加えてもよい。 The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably -40 ° C to 30 ° C, more preferably -20 ° C to 20 ° C. The obtained ylide is preferably reacted with the compound represented by the general formula (6) without isolation. Further, a base may be added to the mixture of the compound represented by the methoxymethyltriphenylphosphonium salt and the general formula (6).
加水分解は酸触媒下で行うことができる。使用する酸としては、希塩酸、硫酸水溶液等を好例として挙げることができる。反応溶媒としては、反応を好適に進行させるものであればいずれでも構わないが、エーテル系溶媒、炭化水素系溶媒、芳香族系溶媒等を好ましく用いることができ、無溶媒で反応させてもよい。エーテル系溶媒としては、1,4-ジオキサン、1,3-ジオキサン、テトラヒドロフラン、ジエチルエーテルおよびｔ-ブチルメチルエーテル等を、炭化水素系溶媒としてはペンタン、ヘキサン、シクロヘキサン、ヘプタンおよびオクタン等を、芳香族系溶媒としてはベンゼン、トルエン、キシレン、メシチレン、クロロベンゼンおよびジクロロベンゼン等を好例として挙げることができる。中でも、テトラヒドロフランがより好ましい。また、前記の各溶媒を単独で使用しても、2種もしくはそれ以上の溶媒を混合して使用してもよい。 Hydrolysis can be carried out under an acid catalyst. Examples of the acid to be used include dilute hydrochloric acid and sulfuric acid aqueous solution. Any reaction solvent may be used as long as it allows the reaction to proceed suitably, but ether solvents, hydrocarbon solvents, aromatic solvents and the like can be preferably used, and the reaction may be performed without solvent. . Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of hydrocarbon solvents include pentane, hexane, cyclohexane, heptane, and octane. Examples of the group solvent include benzene, toluene, xylene, mesitylene, chlorobenzene, dichlorobenzene and the like. Of these, tetrahydrofuran is more preferable. Each of the above solvents may be used alone, or two or more solvents may be mixed and used.
反応温度は溶媒の凝固点から還流温度範囲で行うことができるが、0℃から80℃が好ましい。 The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably from 0 ° C to 80 ° C.
こうして得られる一般式(7)で表される化合物は、シクロヘキサン環に関するシス体およびトランス体の混合物として得られるが、一般に液晶化合物として使用するためにはトランス体であることが好ましい。一般式(7)で表される化合物のホルミル基が結合した側のシクロヘキサン環に関しては、塩基を作用させることによりシス−トランス異性化を行うことができ、トランス体を過剰に得ることができる。この際使用する塩基としては水酸化ナトリウム、水酸化カリウム等が好ましく、反応溶媒はメタノール、エタノールおよびテトラヒドロフラン等が好ましく、反応温度は-40℃から20℃が好ましく、-20℃から10℃がより好ましい。 The compound represented by the general formula (7) thus obtained is obtained as a mixture of a cis isomer and a trans isomer relating to the cyclohexane ring, but is generally preferably a trans isomer for use as a liquid crystal compound. With respect to the cyclohexane ring to which the formyl group of the compound represented by the general formula (7) is bonded, cis-trans isomerization can be performed by acting a base, and an excess of the trans isomer can be obtained. The base used at this time is preferably sodium hydroxide, potassium hydroxide or the like, the reaction solvent is preferably methanol, ethanol or tetrahydrofuran, the reaction temperature is preferably -40 ° C to 20 ° C, more preferably -20 ° C to 10 ° C. preferable.
一般式(7)で表される化合物にメチルトリフェニルホスホニウム塩より調製されるイリドを反応させることによって一般式(8)で表される化合物を得ることができる。イリドの調製はメチルトリフェニルホスホニウム塩に塩基を作用させて行うが、使用する塩基としてはカリウム-t-ブトキシド、n-ブチルリチウム、フェニルリチウム、水素化ナトリウム等が好ましく、カリウム-t-ブトキシドがより好ましい。反応溶媒はエーテル系溶媒、芳香族系溶媒および極性溶媒等を好ましく用いることができる。エーテル系溶媒としては、1,4-ジオキサン、1,3-ジオキサン、テトラヒドロフラン、ジエチルエーテルおよびｔ-ブチルメチルエーテル等を、芳香族系溶媒としてはベンゼン、トルエン、キシレン、メシチレン等を、極性溶媒としてはN,N-ジメチルホルムアミド等を好例として挙げることができる。テトラヒドロフランおよびトルエンがより好ましい。また、前記の各溶媒を単独で使用しても、2種もしくはそれ以上の溶媒を混合して使用してもよい。反応温度は溶媒の凝固点から還流温度範囲で行うことができるが、-40℃から30℃が好ましく、-20℃から20℃がより好ましい。得られたイリドは単離することなく一般式(7)で表される化合物と反応させるのが好ましい。また、メチルトリフェニルホスホニウム塩および一般式(7)で表される化合物の混合物に対して塩基を加えてもよい。 The compound represented by the general formula (8) can be obtained by reacting the compound represented by the general formula (7) with an ylide prepared from a methyltriphenylphosphonium salt. Preparation of ylide is carried out by allowing a base to act on methyltriphenylphosphonium salt. As the base to be used, potassium-t-butoxide, n-butyllithium, phenyllithium, sodium hydride and the like are preferable, and potassium-t-butoxide is preferred. More preferred. As the reaction solvent, ether solvents, aromatic solvents, polar solvents and the like can be preferably used. Examples of ether solvents include 1,4-dioxane, 1,3-dioxane, tetrahydrofuran, diethyl ether, and t-butyl methyl ether. Examples of aromatic solvents include benzene, toluene, xylene, mesitylene, and the like as polar solvents. A good example is N, N-dimethylformamide. Tetrahydrofuran and toluene are more preferred. Each of the above solvents may be used alone, or two or more solvents may be mixed and used. The reaction temperature can be in the range from the freezing point of the solvent to the reflux temperature, but is preferably -40 ° C to 30 ° C, more preferably -20 ° C to 20 ° C. The obtained ylide is preferably reacted with the compound represented by the general formula (7) without isolation. Further, a base may be added to a mixture of the methyltriphenylphosphonium salt and the compound represented by the general formula (7).
一般式(8)において、R3は炭素原子数1から12のアルキル基、炭素原子数2から12のアルケニル基、炭素原子数1から12のアルコキシ基、炭素原子数3から12のアルケニルオキシ基を表すが、炭素原子数1から12のアルキル基または炭素原子数2から12のアルケニル基が好ましく、炭素原子数1から7のアルキル基を表す化合物の製造が特に好ましい。 In the general formula (8), R 3 is an alkyl group having 1 to 12 carbon atoms, an alkenyl group having 2 to 12 carbon atoms, an alkoxy group having 1 to 12 carbon atoms, and an alkenyloxy group having 3 to 12 carbon atoms. However, an alkyl group having 1 to 12 carbon atoms or an alkenyl group having 2 to 12 carbon atoms is preferable, and production of a compound representing an alkyl group having 1 to 7 carbon atoms is particularly preferable.
以下、実施例を挙げて本発明を更に詳述するが、本発明はこれらの実施例に限定されるものではない。化合物の構造は、核磁気共鳴スペクトル(NMR)、質量スペクトル(MS)等により確認した。
化合物記載に下記の略号を使用する。
EXAMPLES Hereinafter, although an Example is given and this invention is further explained in full detail, this invention is not limited to these Examples. The structure of the compound was confirmed by nuclear magnetic resonance spectrum (NMR), mass spectrum (MS) and the like.
The following abbreviations are used in compound descriptions.
THF ：テトラヒドロフラン
DMF ：N, N-ジメチルホルムアミド
Me ：メチル基
Et ：エチル基
Bu ：ブチル基
Ph ：フェニル基
Ms ：メタンスルホニル基
（実施例１）1-((4’, 4’-エチレンジオキシ)シクロヘキシル)メトキシ-2,3-ジフルオロベンゼン(Ia)の合成
THF: tetrahydrofuran
DMF: N, N-dimethylformamide
Me: methyl group
Et: ethyl group
Bu: Butyl group
Ph: phenyl group
Ms: Methanesulfonyl group (Example 1) Synthesis of 1-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluorobenzene (Ia)
メタンスルホン酸 ((4’, 4’-エチレンジオキシ)シクロヘキシル)メチル721 g、2,3-ジフルオロフェノール393 g、炭酸ナトリウム320 gおよびDMF 2.1 Lを混合し、130℃で2時間攪拌した。水4.2 Lを加え、ヘキサン／トルエン＝１／１で抽出し、有機層を水および飽和食塩水で洗浄後、カラムクロマトグラフィーに付し、溶媒を減圧留去した。残渣を再結晶により精製し、1-((4’, 4’-エチレンジオキシ)シクロヘキシル)メトキシ-2,3-ジフルオロベンゼン(Ia)493 gを得た。化合物(Ia)は、液晶化合物の製造中間体として有用である。
MS m/z : 284 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 1.3 2.0 (m, 9 H), 3.8 4.0 (m, 6 H), 6.4 6.6 (m, 2 H), 6.8 7.0 (m, 1 H)
（実施例２）4-((4’, 4’-エチレンジオキシ)シクロヘキシル)メトキシ-2,3-ジフルオロフェノール(Ib)の合成
Methanesulfonic acid ((4 ′, 4′-ethylenedioxy) cyclohexyl) methyl (721 g), 2,3-difluorophenol (393 g), sodium carbonate (320 g) and DMF (2.1 L) were mixed and stirred at 130 ° C. for 2 hours. After adding 4.2 L of water and extracting with hexane / toluene = 1/1, the organic layer was washed with water and saturated brine and then subjected to column chromatography, and the solvent was distilled off under reduced pressure. The residue was purified by recrystallization to obtain 493 g of 1-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluorobenzene (Ia). Compound (Ia) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 284 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 1.3 2.0 (m, 9 H), 3.8 4.0 (m, 6 H), 6.4 6.6 (m, 2 H), 6.8 7.0 (m, 1 H)
Example 2 Synthesis of 4-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluorophenol (Ib)
MS m/z : 300 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 1.3 2.0 (m, 9 H), 3.8 4.0 (m, 6 H), 4.0 6.0 (s, 1 H), 6.3 6.4 (m, 2 H)
（実施例３）4-((4’, 4’-エチレンジオキシ)シクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-(トランス-4-エチルシクロヘキシル)シクロヘキシル)メトキシベンゼン(Ic)の合成
MS m / z: 300 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 1.3 2.0 (m, 9 H), 3.8 4.0 (m, 6 H), 4.0 6.0 (s, 1 H), 6.3 6.4 (m, 2 H)
Example 3 4-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Ic )
MS m/z : 506 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 0.9 2.0 (m, 34 H), 3.8 4.0 (m, 8 H), 6.3 6.5 (m, 2 H)
（実施例４）4-(4-オキソシクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-(トランス-4-エチルシクロヘキシル)シクロヘキシル)メトキシベンゼン(Id)の合成
MS m / z: 506 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 0.9 2.0 (m, 34 H), 3.8 4.0 (m, 8 H), 6.3 6.5 (m, 2 H)
Example 4 Synthesis of 4- (4-oxocyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Id)
MS m/z : 462 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 0.9 2.0 (m, 29 H), 2.1 2.4 (m, 5 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H)
（実施例５）4-(トランス-4-ホルミルシクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-(トランス-4-エチルシクロヘキシル)シクロヘキシル)メトキシベンゼン(Ie)の合成
MS m / z: 462 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 0.9 2.0 (m, 29 H), 2.1 2.4 (m, 5 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H)
Example 5 Synthesis of 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Ie)
MS m/z : 476 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 0.9 2.0 (m, 34 H), 2.2 2.4 (m, 1 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H), 9.6 9.8 (m, 1 H)
（実施例６）2,3-ジフルオロ-1-(トランス-4-(トランス-4-エチルシクロヘキシル)シクロヘキシル)メトキシ-4-(トランス-4-ビニルシクロヘキシル)メトキシベンゼン（If）の合成
MS m / z: 476 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 0.9 2.0 (m, 34 H), 2.2 2.4 (m, 1 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H), 9.6 9.8 (m, 1 H)
Example 6 Synthesis of 2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (If)
相転移温度 : C 75.6 N 195.2 I
MS m/z : 474 (M+), 146 (100)
1H-NMR (400 MHz, CDCl3)
δ: 0.75 1.25 (m, 17 H), 0.86 (t, J = 7.2 Hz, 3 H), 1.65 2.00 (m, 15 H), 3.75 (d, J = 6.8 Hz, 2 H), 3.78 (d, J = 6.4 Hz, 2 H), 4.87 5.03 (m, 2 H), 5.79 (ddd, J = 6.8 Hz, J = 10.4 Hz, J = 17.2 Hz, 1 H), 6.59 (d, J = 5.2 Hz, 2 H)
（実施例７）4-((4’, 4’-エチレンジオキシ)シクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシベンゼン(IIc)の合成
Phase transition temperature: C 75.6 N 195.2 I
MS m / z: 474 (M + ), 146 (100)
1 H-NMR (400 MHz, CDCl 3 )
δ: 0.75 1.25 (m, 17 H), 0.86 (t, J = 7.2 Hz, 3 H), 1.65 2.00 (m, 15 H), 3.75 (d, J = 6.8 Hz, 2 H), 3.78 (d, J = 6.4 Hz, 2 H), 4.87 5.03 (m, 2 H), 5.79 (ddd, J = 6.8 Hz, J = 10.4 Hz, J = 17.2 Hz, 1 H), 6.59 (d, J = 5.2 Hz, 2 H)
Example 7 Synthesis of 4-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IIc)
MS m/z : 452 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 0.9 2.0 (m, 28 H), 3.8 4.0 (m, 8 H), 6.3 6.5 (m, 2 H)
（実施例８）4-(4-オキソシクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシベンゼン(IId)の合成
MS m / z: 452 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 0.9 2.0 (m, 28 H), 3.8 4.0 (m, 8 H), 6.3 6.5 (m, 2 H)
Example 8 Synthesis of 4- (4-oxocyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IId)
実施例４において、4-((4’, 4’-エチレンジオキシ)シクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-(トランス-4-エチルシクロヘキシル)シクロヘキシル)メトキシベンゼン(Ic)の代わりに4-((4’, 4’-エチレンジオキシ)シクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシベンゼン(IIc)を用い、同様の操作を行うことにより、4-(4-オキソシクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシベンゼン(IId)を得た。化合物(IId)は、液晶化合物の製造中間体として有用である。
MS m/z : 408 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 0.9 2.0 (m, 23 H), 2.1 2.4 (m, 5 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H)
（実施例９）4-(トランス-4-ホルミルシクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシベンゼン(IIe)の合成
In Example 4, 4-((4 ′, 4′-ethylenedioxy) cyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Ic ) 4-((4 ', 4'-ethylenedioxy) cyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IIc) instead of By performing, 4- (4-oxocyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IId) was obtained. Compound (IId) is useful as an intermediate for producing a liquid crystal compound.
MS m / z: 408 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 0.9 2.0 (m, 23 H), 2.1 2.4 (m, 5 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H)
Example 9 Synthesis of 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IIe)
MS m/z : 422 (M+)
1H-NMR (60 MHz, CDCl3)
δ: 0.9 2.0 (m, 28 H), 2.2 2.4 (m, 1 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H), 9.6 9.8 (m, 1 H)
（実施例１０）2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシ-4-(トランス-4-ビニルシクロヘキシル)メトキシベンゼン（IIf）の合成
MS m / z: 422 (M + )
1 H-NMR (60 MHz, CDCl 3 )
δ: 0.9 2.0 (m, 28 H), 2.2 2.4 (m, 1 H), 3.8 4.0 (m, 4 H), 6.3 6.5 (m, 2 H), 9.6 9.8 (m, 1 H)
Example 10 Synthesis of 2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (IIf)
実施例６において、4-(トランス-4-ホルミルシクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-(トランス-4-エチルシクロヘキシル)シクロヘキシル)メトキシベンゼン(Ie)の代わりに4-(トランス-4-ホルミルシクロヘキシル)メトキシ-2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシベンゼン(IIe)を用い、同様の操作を行うことにより、2,3-ジフルオロ-1-(トランス-4-ブチルシクロヘキシル)メトキシ-4-(トランス-4-ビニルシクロヘキシル)メトキシベンゼン(IIf)を得た。
相転移温度 : C 55.2 N 95.8 I
MS m/z : 420 (M+), 146 (100)
1H-NMR (400 MHz, CDCl3)
δ: 0.80 1.35 (m, 15 H), 0.889 (t, J = 6.8 Hz, 3 H), 1.65 2.00 (m, 11 H), 3.76 (d, J = 6.4 Hz, 2 H), 3.78 (d, J = 6.4 Hz, 2 H), 4.85 5.05 (m, 2 H), 5.79 (ddd, J = 6.8 Hz, J = 10.4 Hz, J = 17.2 Hz, 1 H), 6.59 (d, J = 5.6 Hz, 2 H)
In Example 6, instead of 4- (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4- (trans-4-ethylcyclohexyl) cyclohexyl) methoxybenzene (Ie) By performing the same operation using (trans-4-formylcyclohexyl) methoxy-2,3-difluoro-1- (trans-4-butylcyclohexyl) methoxybenzene (IIe), 2,3-difluoro-1- (Trans-4-butylcyclohexyl) methoxy-4- (trans-4-vinylcyclohexyl) methoxybenzene (IIf) was obtained.
Phase transition temperature: C 55.2 N 95.8 I
MS m / z: 420 (M + ), 146 (100)
1 H-NMR (400 MHz, CDCl 3 )
δ: 0.80 1.35 (m, 15 H), 0.889 (t, J = 6.8 Hz, 3 H), 1.65 2.00 (m, 11 H), 3.76 (d, J = 6.4 Hz, 2 H), 3.78 (d, J = 6.4 Hz, 2 H), 4.85 5.05 (m, 2 H), 5.79 (ddd, J = 6.8 Hz, J = 10.4 Hz, J = 17.2 Hz, 1 H), 6.59 (d, J = 5.6 Hz, 2 H)
本発明の製造方法は、液晶化合物の製造方法として有用である。また、本発明の化合物は、液晶化合物の製造中間体として有用である。 The production method of the present invention is useful as a production method of a liquid crystal compound. Moreover, the compound of this invention is useful as a manufacturing intermediate of a liquid crystal compound.
Claims (17)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005316169A JP4924863B2 (en) | 2005-10-31 | 2005-10-31 | Method for producing difluorobenzene derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2005316169A JP4924863B2 (en) | 2005-10-31 | 2005-10-31 | Method for producing difluorobenzene derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JP2007119423A JP2007119423A (en) | 2007-05-17 |
| JP4924863B2 true JP4924863B2 (en) | 2012-04-25 |
Family
ID=38143641
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2005316169A Active JP4924863B2 (en) | 2005-10-31 | 2005-10-31 | Method for producing difluorobenzene derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JP4924863B2 (en) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP4894226B2 (en) * | 2005-10-31 | 2012-03-14 | Ｄｉｃ株式会社 | Method for producing fluorine-containing liquid crystal compound having hydroquinone skeleton |
| JP5061466B2 (en) * | 2006-01-31 | 2012-10-31 | Ｄｉｃ株式会社 | Method for producing fluorine-containing liquid crystal compound having hydroquinone skeleton |
| JP4882395B2 (en) * | 2006-01-31 | 2012-02-22 | Ｄｉｃ株式会社 | Method for producing difluorobenzene derivative |
| JP5056118B2 (en) * | 2006-03-31 | 2012-10-24 | Ｄｉｃ株式会社 | Method for producing difluorobenzene derivative |
| JP4993183B2 (en) * | 2006-11-29 | 2012-08-08 | Ｄｉｃ株式会社 | Method for producing difluorobenzene derivative and production intermediate |
| JP5187025B2 (en) * | 2008-06-26 | 2013-04-24 | Ｄｉｃ株式会社 | Method for producing fluoronaphthol derivative |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP3772351B2 (en) * | 1994-06-30 | 2006-05-10 | 大日本インキ化学工業株式会社 | Bicyclohexane-4-one derivative |
| TWI429732B (en) * | 2005-03-17 | 2014-03-11 | Dainippon Ink & Chemicals | A difluorobenzene derivative and a nematic liquid crystal composition using the same |
| JP4876420B2 (en) * | 2005-03-31 | 2012-02-15 | Ｄｉｃ株式会社 | Difluorobenzene derivative |
| JP4894226B2 (en) * | 2005-10-31 | 2012-03-14 | Ｄｉｃ株式会社 | Method for producing fluorine-containing liquid crystal compound having hydroquinone skeleton |
| JP4882395B2 (en) * | 2006-01-31 | 2012-02-22 | Ｄｉｃ株式会社 | Method for producing difluorobenzene derivative |
-
2005
- 2005-10-31 JP JP2005316169A patent/JP4924863B2/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| JP2007119423A (en) | 2007-05-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4876420B2 (en) | Difluorobenzene derivative | |
| JP4872121B2 (en) | Method for producing difluorobenzene derivative | |
| JP4924863B2 (en) | Method for producing difluorobenzene derivative | |
| JP5604809B2 (en) | Fluorobenzene derivative and liquid crystal composition containing the compound | |
| JP4691893B2 (en) | Liquid crystal composition, display element and compound containing trifluoronaphthalene derivative. | |
| JP4882395B2 (en) | Method for producing difluorobenzene derivative | |
| JP5056118B2 (en) | Method for producing difluorobenzene derivative | |
| JP4993183B2 (en) | Method for producing difluorobenzene derivative and production intermediate | |
| JP5051418B2 (en) | Cyclohexyl methanol derivative and method for producing the same | |
| JP4983009B2 (en) | Method for producing difluorobenzene derivative | |
| TW200918517A (en) | 2,5-selenophene derivatives and 2,5-tellurophene derivatives | |
| JP4835032B2 (en) | Trifluoronaphthalene derivative | |
| JP2012116780A (en) | Compound having fluorinated bicyclooctane structure and liquid crystal composition thereof | |
| TWI481695B (en) | Liquid crystal compounds and method for preparing the same | |
| TW200540261A (en) | As-indacene derivatives | |
| JP4655197B2 (en) | Difluorochroman derivative | |
| JP5061466B2 (en) | Method for producing fluorine-containing liquid crystal compound having hydroquinone skeleton | |
| JP3841178B2 (en) | Alkenylbenzene derivative and method for producing the same | |
| JP5407145B2 (en) | 4'-dialkoxymethylbicyclohexyl-4-ylmethanol and process for producing the same | |
| CN102344434B (en) | Method for preparing difluorobenzene derivatives | |
| JP6489369B2 (en) | Process for producing compound having difluoromethyl ether skeleton and intermediate compound for producing the same | |
| JP5240494B2 (en) | Difluorobenzene derivative and method for producing the same | |
| JP5433996B2 (en) | Method for producing fluorophenol derivative | |
| JP2015131785A (en) | New compound having negative dielectric anisotropy and ring structure, production method of the same, liquid crystal composition, and liquid crystal electro-optic element | |
| JP4905764B2 (en) | Bicyclohexane derivative and process for producing the same |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20080929 |
|
| A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20110928 |
|
| A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20111025 |
|
| A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20111214 |
|
| TRDD | Decision of grant or rejection written | ||
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20120112 |
|
| A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 |
|
| A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20120125 |
|
| FPAY | Renewal fee payment (event date is renewal date of database) |
Free format text: PAYMENT UNTIL: 20150217 Year of fee payment: 3 |
|
| R150 | Certificate of patent or registration of utility model |
Ref document number: 4924863 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
| S111 | Request for change of ownership or part of ownership |
Free format text: JAPANESE INTERMEDIATE CODE: R313113 |
|
| R350 | Written notification of registration of transfer |
Free format text: JAPANESE INTERMEDIATE CODE: R350 |