JPH0544951B2 - - Google Patents
Info
- Publication number
- JPH0544951B2 JPH0544951B2 JP60239291A JP23929185A JPH0544951B2 JP H0544951 B2 JPH0544951 B2 JP H0544951B2 JP 60239291 A JP60239291 A JP 60239291A JP 23929185 A JP23929185 A JP 23929185A JP H0544951 B2 JPH0544951 B2 JP H0544951B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- compound
- catalyst
- groups
- reaction
- 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.)
- Expired - Fee Related
Links
- -1 ether compound Chemical class 0.000 claims description 28
- 239000003054 catalyst Substances 0.000 claims description 24
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 22
- 150000002440 hydroxy compounds Chemical class 0.000 claims description 15
- 229910052751 metal Inorganic materials 0.000 claims description 14
- 239000002184 metal Substances 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000010949 copper Substances 0.000 claims description 13
- 229910052802 copper Inorganic materials 0.000 claims description 13
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 238000006243 chemical reaction Methods 0.000 description 14
- 125000001072 heteroaryl group Chemical group 0.000 description 11
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 238000000034 method Methods 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 9
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- 238000005695 dehalogenation reaction Methods 0.000 description 9
- 239000002994 raw material Substances 0.000 description 9
- 229910021595 Copper(I) iodide Inorganic materials 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 8
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000000217 alkyl group Chemical group 0.000 description 6
- 125000000304 alkynyl group Chemical group 0.000 description 6
- 150000002390 heteroarenes Chemical class 0.000 description 6
- 239000003960 organic solvent Substances 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- ORTQZVOHEJQUHG-UHFFFAOYSA-L copper(II) chloride Chemical compound Cl[Cu]Cl ORTQZVOHEJQUHG-UHFFFAOYSA-L 0.000 description 5
- 150000002170 ethers Chemical class 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 229910021591 Copper(I) chloride Inorganic materials 0.000 description 4
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 4
- 229940045803 cuprous chloride Drugs 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- 150000002367 halogens Chemical group 0.000 description 4
- 238000007086 side reaction Methods 0.000 description 4
- TUCRZHGAIRVWTI-UHFFFAOYSA-N 2-bromothiophene Chemical compound BrC1=CC=CS1 TUCRZHGAIRVWTI-UHFFFAOYSA-N 0.000 description 3
- RFSKGCVUDQRZSD-UHFFFAOYSA-N 3-methoxythiophene Chemical compound COC=1C=CSC=1 RFSKGCVUDQRZSD-UHFFFAOYSA-N 0.000 description 3
- 229910021589 Copper(I) bromide Inorganic materials 0.000 description 3
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- 150000001340 alkali metals Chemical group 0.000 description 3
- 150000001502 aryl halides Chemical class 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- ODWXUNBKCRECNW-UHFFFAOYSA-M bromocopper(1+) Chemical compound Br[Cu+] ODWXUNBKCRECNW-UHFFFAOYSA-M 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- NKNDPYCGAZPOFS-UHFFFAOYSA-M copper(i) bromide Chemical compound Br[Cu] NKNDPYCGAZPOFS-UHFFFAOYSA-M 0.000 description 3
- 238000004821 distillation Methods 0.000 description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
- 229910052708 sodium Inorganic materials 0.000 description 3
- 239000011734 sodium Substances 0.000 description 3
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 2
- XCMISAPCWHTVNG-UHFFFAOYSA-N 3-bromothiophene Chemical compound BrC=1C=CSC=1 XCMISAPCWHTVNG-UHFFFAOYSA-N 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- QTMDXZNDVAMKGV-UHFFFAOYSA-L copper(ii) bromide Chemical compound [Cu+2].[Br-].[Br-] QTMDXZNDVAMKGV-UHFFFAOYSA-L 0.000 description 2
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 description 2
- 238000004817 gas chromatography Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001256 steam distillation Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 229930192474 thiophene Natural products 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 description 1
- APWZAIZNWQFZBK-UHFFFAOYSA-N 1-ethoxynaphthalene Chemical compound C1=CC=C2C(OCC)=CC=CC2=C1 APWZAIZNWQFZBK-UHFFFAOYSA-N 0.000 description 1
- 125000004974 2-butenyl group Chemical group C(C=CC)* 0.000 description 1
- OKEHURCMYKPVFW-UHFFFAOYSA-N 2-methoxythiophene Chemical compound COC1=CC=CS1 OKEHURCMYKPVFW-UHFFFAOYSA-N 0.000 description 1
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 1
- 125000004975 3-butenyl group Chemical group C(CC=C)* 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- 229910021593 Copper(I) fluoride Inorganic materials 0.000 description 1
- 229910021590 Copper(II) bromide Inorganic materials 0.000 description 1
- 229910021594 Copper(II) fluoride Inorganic materials 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000003905 agrochemical Substances 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- HOPRXXXSABQWAV-UHFFFAOYSA-N anhydrous collidine Natural products CC1=CC=NC(C)=C1C HOPRXXXSABQWAV-UHFFFAOYSA-N 0.000 description 1
- 125000003710 aryl alkyl group Chemical group 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000004618 benzofuryl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 description 1
- 125000004196 benzothienyl group Chemical group S1C(=CC2=C1C=CC=C2)* 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- GWFAVIIMQDUCRA-UHFFFAOYSA-L copper(ii) fluoride Chemical compound [F-].[F-].[Cu+2] GWFAVIIMQDUCRA-UHFFFAOYSA-L 0.000 description 1
- GBRBMTNGQBKBQE-UHFFFAOYSA-L copper;diiodide Chemical compound I[Cu]I GBRBMTNGQBKBQE-UHFFFAOYSA-L 0.000 description 1
- 229960003280 cupric chloride Drugs 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 125000004663 dialkyl amino group Chemical group 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
- 125000004705 ethylthio group Chemical group C(C)S* 0.000 description 1
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 1
- 125000002541 furyl group Chemical group 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 125000001041 indolyl group Chemical group 0.000 description 1
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000000555 isopropenyl group Chemical group [H]\C([H])=C(\*)C([H])([H])[H] 0.000 description 1
- 125000000842 isoxazolyl group Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N methyl monoether Natural products COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 150000002790 naphthalenes Chemical class 0.000 description 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 150000004707 phenolate Chemical class 0.000 description 1
- ZMRUPTIKESYGQW-UHFFFAOYSA-N propranolol hydrochloride Chemical compound [H+].[Cl-].C1=CC=C2C(OCC(O)CNC(C)C)=CC=CC2=C1 ZMRUPTIKESYGQW-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000002568 propynyl group Chemical group [*]C#CC([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- 125000003226 pyrazolyl group Chemical group 0.000 description 1
- 125000005495 pyridazyl group Chemical group 0.000 description 1
- 125000004076 pyridyl group Chemical group 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000000168 pyrrolyl group Chemical group 0.000 description 1
- 125000005493 quinolyl group Chemical group 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
- SUBJHSREKVAVAR-UHFFFAOYSA-N sodium;methanol;methanolate Chemical compound [Na+].OC.[O-]C SUBJHSREKVAVAR-UHFFFAOYSA-N 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 125000005017 substituted alkenyl group Chemical group 0.000 description 1
- 125000000547 substituted alkyl group Chemical group 0.000 description 1
- 125000004426 substituted alkynyl group Chemical group 0.000 description 1
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/52—Improvements relating to the production of bulk chemicals using catalysts, e.g. selective catalysts
Landscapes
- Catalysts (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Description
〔産業上の利用分野〕
本発明は、ハロゲン化銅を用いて、複素芳香環
を有するエーテル化合物を選択性良く、なおかつ
高収率で製造する方法に関する。
〔従来の技術及び発明が解決しようとする問題
点〕
複素芳香環を有するエーテル化合物は農薬や医
薬の中間体として広範囲に利用し得る有用な化合
物である。しかしながら、複素芳香環を有するエ
ーテル化合物の合成反応は、現在までほとんど研
究されていない。その数少ない反応例として、ア
ルキブ ケミ（AIKiv Kemi）23巻、239頁
（1958年）に、触媒として酸化第１銅を用いた３
−メトキシチオフエンの合成法が記載されてい
る。この報告によると、１当量の３−ブロムチオ
フエンに対し、2.8当量のナトリウムメチラート
及び触媒として0.5当量の酸化第１銅を用い、100
時間加熱還流し、収率81％で３−メトキシチオフ
エンを得ている。この合成法では原料である３−
ブロムチオフエンが残存し、３−ブロムチオフエ
ンと生成物である３−メトキシチオフエンの沸点
が近似しているために煩雑な分離精製工程が必要
となるばかりではなく、反応時間が極めて長く、
しかも収率も良くないという欠点があつた。
他方、アリールアルキルエーテル化合物を合成
する際の触媒としてハロゲン化銅を用いること
が、ジヤーナル オブ ケミカル ソサイアテイ
ー(C)〔（Journal of chemical Society(C)）〕312
頁、1969年にアール・ジー・アール・ベーコン
（Ｒ，Ｇ，Ｒ，Bacon）らによつて報告されてい
る。該報告によると、触媒としてヨウ化第一銅を
用いた場合、１−臭化ナフタレン１当量に対し、
沃化第１銅0.5〜1.0当量、ナトリウムエチラート
２〜３当量及び溶媒にエタノールと２，３，６−
コリジンを用いると、ほぼ定量的に１−エトキシ
ナフタレンを得ている。しかし、ヨウ化第１銅の
使用量を低下させると、収率の低下ばかりでな
く、副反応である脱ハロゲン化反応が起きてい
る。又、触媒として臭化第１銅または塩化第１銅
を用いた場合、副反応として脱ハロゲン化反応及
びハロゲン交換反応が起きており、このために目
的物であるエーテル化合物の収率が低い。
〔問題を解決するための手段〕
本発明者らは、種々の複素芳香環を有するエー
テル化合物が医農薬中間体として有用であること
に鑑み、ハロゲン化複素環式芳香族化合物と有機
ヒドロキシ化合物の金属塩を反応させてエーテル
化合物と製造する方法について鋭意検討してき
た。その結果、意外にも低触媒量のハロゲン化銅
を用いた場合でも、ハロゲン交換反応や脱ハロゲ
ン化反応の副反応が全く進行せず、短時間に、選
択性よくエーテル化合物を製造できることを見い
出し、本発明を完成させるに至つた。
即ち、本発明はハロゲン化複素環式芳香族化合
物と有機ヒドロキシ化合物の金属塩を触媒の存在
下に反応させてエーテル化合物を製造するに際
し、触媒としてハロゲン化銅を用いることを特徴
とするエーテル化合物の製造方法である。
本発明に於いて、原料として用いられるハロゲ
ン化複素環式芳香族化合物は、複素芳香環に結合
した水素がハロゲン原子で置換した化合物であ
り、一般式で次のように表わされる。
R1−X1
（但し、R1は置換もしくは非置換の複素芳香
環基であり、X1はハロゲン原子である。）上記一
般式(1)中、R1で示される複素芳香環は、いかな
るものも使用でき、何ら制限されない。該複素芳
香環基の具体例としては、フリル基、チエニル
基、ピロリル基、イミダゾリル基、ピラゾリル
基、ピリジル基、ベンゾフリル基、ベンゾチエニ
ル基、インドリル基、キノリル基、ピラジニル
基、ピリミジル基、ピリダジル基、キノキサリニ
ル基、チアゾリル基、ベンゾチアゾリル基、イソ
オキサゾリル基等が挙げられる。さらに又、上記
一般式(1)中、X1で示されるハロゲン原子はフツ
素、塩素、臭素、沃素のいずれでも使用できる
が、反応性の良さから好ましくは臭素又は沃素が
用いられる。
さらに又、前記一般式(1)中、R1で示される置
換複素芳香環基の置換基としては、反応に用いら
れる試剤と反応しないものであれば、あらゆる置
換基が特に制限されず、用いられる。該置換基の
具体例としては、メチル基、エチル基、プロピル
基等のアルキル基；ビニル基、アリル基等のアル
ケニル基；プロピニル基等のアルキニル基；メト
キシ基、エトキシ基等のアルコキシ基；メチルチ
オ基、エチルチオ基等のアルキルチオ基；メトキ
シメチル基等のアルコキシアルキル基；フエニル
基；ニトロ基；シアノ基；アミノ基；アルコキシ
カルボニル基；スルホニル基；ホルミル基；ジア
ルキルアミノ基；トリフルオロメチル基等のポリ
フルオロアルキル基等が挙げられる。また、エー
テル化反応を阻害しなければ、ハロゲン原子又は
ヒドロキシ基が置換されていても良い。
本発明で用いられるもう一方の原料は、有機ヒ
ドロキシ化合物の金属塩である。有機ヒドロキシ
化合物の金属塩は、アルコラート或いはフエノラ
ートとして知られており、本発明では、このよう
な公知の有機ヒドロキシ化合物の金属塩が何ら制
限されず使用し得る。本発明に於いて特に好適に
用いることのできる有機ヒドロキシ化合物の金属
塩は一般式で次のように示される。
R2−Ｏ−Ｍ (2)
（但し、R2は置換もしくは非置換のアルキル
基、置換もしくは非置換のアルケニル基、置換も
しくは非置換のアルキニル基、置換もしくは非置
換のフエニル基を示し、Ｍはアルカリ金属原子を
示す。）で示される有機ヒドロキシ化合物の金属
塩である。
上記一般式(2)中、R2で示されるアルキル基は
直鎖状、分枝状のいずれであつてもよく、炭素数
も特に制限されない。しかしながら、原料入手の
容易さから炭素数１〜６個であることが好適であ
る。該アルキル基の具体例としては、メチル基，
エチル基，ｎ−プロピル基iso−プロピル基、ｎ
−ブチル基、iso−ブチル基、ｔ−ブチル基、ｎ
−ペンチル基ｎ−ヘキシル基等が挙げられる。ま
た、上記一般式(2)中、R2で示されるアルケニル
基は直鎖状、分枝状のいずれであつてもよく、炭
素数も特に制限されない。しかしながら、原料入
手の容易さから、炭素数２〜４個であることが好
適である。該アルケニル基の具体例としては、ビ
ニル基、アリル基、iso−プロペニル基、２−ブ
テニル基，３−ブテニル基等が挙げられる。
又、上記一般式(2)中、R2で示されるアルキニ
ル基は、直鎖状、分枝状を問わず、炭素数も特に
制限されないが、前記と同様の理由により炭素数
２〜４個であることが好適である。該アルキニル
基の具体例としては、エチニル基、２−プロピニ
ル基等が挙げられる。
前記一般式(2)中、R2で示される置換アルキル
基、置換アルケニル基、置換アルキニル基の置換
基としては、前記一般式(1)について説明した置換
複素芳香環基の置換基のうち、アルキル基、アル
ケニル基、アルキニル基を除いて用いることがで
きる。また、置換フエニル基の置換基としては、
前述の置換複素芳香環基の置換基をそのまま適用
することができる。
又、前記一般式(2)中、Ｍで示されるアルカリ金
属原子としてはリチウム、ナトリウム、カリウム
等が挙げられるが、取扱い上から、ナトリウム及
びカリウムが好適に使用される。
前記一般式(2)で示される有機ヒドロキシ化合物
の金属塩の中でも、R2がアルキル基、アルケニ
ル基，アルキニル基又は置換基を有するこれらの
基の場合は、目的物であるエーテル化合物の収率
が高くなるため、本発明では特に好適である。
本発明で用いられる触媒であるハロゲン化銅は
公知な化合物であり、特に限定されず使用でき
る。好適に使用されるハロゲン化銅としては、沃
化第１銅、臭化第１銅、臭化第２銅、塩化第１
銅、塩化第２銅、フツ化第１銅、フツ化第２銅等
が挙げられる。就中、沃化第１銅、臭化第１銅及
び塩化第１銅は、上記のハロゲン化複素環式芳香
族化合物と有機ヒドロキシ化合物の金属塩の反応
時間を短縮し、しかも生成するエーテル化合物の
収率及び選択性を高める効果が高いため、本発明
で好適に使用される。
本発明により、触媒としてハロゲン化銅を用
い、上記ハロゲン化複素環式芳香族化合物と有機
ヒドロキシ化合物の金属塩からエーテル化合物を
製造する際、通常は不活性有機溶媒を用いるのが
好ましい。該不活性有機溶媒としては、あらゆる
種類の不活性有機溶媒が適用でき、具体例として
はベンゼン、ヘキサン、シクロヘキサン、デカリ
ン、トルエン、キシレン、Ｎ，Ｎ−ジメチルホル
ムアミド（DMF）、ジメチルスルホキシド
（DMSO），ジエチルエーテル，ジブチルエーテ
ル，ジメトキシエタン、ジエチレングリコールジ
メチルエーテル、アルコール等が挙げられる。ア
ルコールを溶媒として用いる場合には上記一般式
(2)で示されるR2−Ｏ−Ｍに対応するアルコール，
すなわち、一般式R2−OHで表わされるアルコー
ルを用いることが望ましい。例えばR2がメチル
基であればメタノール、エチル基であればエタノ
ール、イソプロピル基であればイソプロピルアル
コールを用いることが収率、選択性の面から好適
となる。
本発明を実施する際、反応操作の手順として、
不活性有機溶媒中へのハロゲン化複素環芳香族化
合物、有機ヒドロキシ化合物の金属塩及びハロゲ
ン化銅の添加順序は特に限定されるものではない
が、特に有機ヒドロキシ化合物が、メタノール又
はエタノール等の低級アルコールである場合、直
接アルカリ金属と反応させ、有機ヒドロキシ化合
物の金属塩を含む有機ヒドロキシ化合物溶液を調
製し、該溶液にハロゲン化複素環式芳香族化合物
とハロゲン化銅を添加してもよい。
また、ハロゲン化複素環式芳香族化合物と有機
ヒドロキシ化合物の金属塩のモル比は特に限定さ
れるものではないが、一般には１：0.1〜１：
100、好ましくはハロゲン化複素環式芳香族化合
物に対し、有機ヒドロキシ化合物の金属塩を多量
に加えることにより、短時間に、より選択性にし
かも高収率でエーテル化合物を得ることができる
点から、モル比１：1.1〜１：10の範囲で使用す
るのがよい。
また、触媒であるハロゲン化銅は、ハロゲン化
複素還式芳香族化合物に対して0.01〜80モルパー
セント、好ましくは１〜40モルパーセントの範囲
から選ぶのが好適である。更にまた、ハロゲン化
複素環式芳香族化合物と不活性有機溶媒の重量比
は一般に１：１〜１：20、好ましくは１：１〜
１：10の範囲から選べばよい。本発明の反応にお
ける反応温度は特に限定されず、広い温度範囲で
選びうるが、一般には50〜180℃、好ましくは80
〜150℃の範囲から選ぶと良い。
本発明で得られるエーテル化合物の精製方法
は、特に限定されるものではない。一般には、触
媒を口別した後、反応液を中和し、ベンゼン、ト
ルエン、塩化メチレン、クロロホルム、四塩化炭
素、エーテル等の不活性有機溶媒で押出、乾燥
し、常圧蒸留、減圧蒸留、再結晶、またはクロマ
トグラフイーによつて精製することができる。特
に本反応では触媒の除去法により、収率に大きく
影響する場合もあり、一つの除去法として、反応
液を中和後、水蒸気蒸留にて、触媒を分離する方
法も採用することもできる。
〔効果〕
以上に述べた本発明の方法によれば、原料とし
てハロゲン化アリールを用いた従来の方法に比べ
て、ハロゲン化複素環式芳香族化合物に対して40
モルパーセント以下という、少量の触媒で目的と
するエーテル化合物を90％以上の高収率で得るこ
とができる。しかも、本発明の方法に於いては触
媒量を少量としたにもかかわらず、ハロゲン化ア
リールを用いた従来の方法に於けるような脱ハロ
ゲン化反応等の副反応を生じることもない。この
ため、目的とするエーテル化合物の選択性が良好
であり、精製が容易になる。
また、触媒として塩化銅又は臭化銅を用いた場
合、ハロゲン化アリールを原料として用いた従来
の方法では、上記の脱ハロゲン化反応の他に、原
料であるハロゲン化アリールと触媒との間でハロ
ゲン交換が生じ、目的とするエーテル化合物の収
率が低いものであつた。しかし、本発明の方法に
於いては、触媒として塩化銅又は臭化銅を用いて
も、ハロゲン交換反応は見られず、目的物がヨウ
化銅を触媒としたときと同程度の高い収率で得ら
れている。従つて、本発明に於いては、触媒とし
て塩化銅又は臭化銅を用いたときに、目的とする
エーテル化合物の収率が飛躍的に向上するのであ
る。
以上のように、本発明の方法は、エーテル化合
物を低触媒量で且つ高収率で、しかも選択性良く
製造する方法であり、その工業的な価値は著しい
ものである。
以下に、本発明を具体的に説明するために実施
例を挙げるが、本発明はこれらの実施例に限定さ
れるものではない。
実施例 １
還流冷却器、撹拌器を備えた200mlの三つ口フ
ラスコに、２−ブロムチオフエン20ｇ（120ｍ
mole）、ナトリウムメチラート13.2ｇ（250ｍ
mole）、塩化第１銅0.9ｇ（９ｍmole）及びメタ
ノール40mlを仕込み、窒素雰囲気下、加熱還流状
態で、17時間、激しく撹拌した。反応液を室温ま
で戻し、希塩酸で中和した後、水蒸気蒸留を行な
つた。得られた油層をガスクロマトグラフイーに
より分析した結果、チオフエンは生成しておら
ず、脱ハロゲン化反応が生起していないことが確
認できた。その後、油層を分離し、常圧蒸留を行
なうことにより、沸点159℃の無色液体である２
−メトキシチオフエンを13.1ｇ得た。収率は原料
である２−ブロムチオフエンに対し、93.1％であ
つた。
実施例 ２
還流冷却器、撹拌器を備えた200mlの三つ口フ
ラスコに、メタノール100mlと金属ナトリウム
12.3ｇ（530ｍmole）を加え、予め、ナトリウム
メチラート−メタノール溶液を調製した。該溶液
に、３−プロムチオフエン34.9ｇ（214ｍmole）
と沃化第１銅7.6ｇ（40ｍmole）を順次加え、加
熱還流状態で３時間、激しく撹拌した。その後、
反応液は室温まで戻し、希塩酸で中和した後、水
蒸気蒸留を行なつた。得られた油層をガスクロマ
トグラフイーにより分析した結果、チオフエンの
存在が認められず、脱ハロゲン化反応が生起して
いないことが確認できた。得られた油層は塩化メ
チレン50mlで抽出し、塩化カルシウムで乾燥し
た。塩化メチレンを留去した後、常圧蒸留を行な
い、沸点159℃の無色液体である３−メトキシチ
オフエンを22ｇ得た。収率は原料である３−ブロ
ムチオフエンに対し90.0％であつた。
実施例 ３
実施例２と同様な実験操作に従い、触媒として
沃化第１銅を用いた実験結果を表１に示す。
いずれの実験においても、実施例２と同様に脱
ハロゲン化反応の生起は認められなかつた。
但し、表中のDMFは、Ｎ，Ｎ−ジメチルホル
ムアミドを、またDMSOは、ジメチルスルホキ
シドを夫々示す。
[Industrial Application Field] The present invention relates to a method for producing an ether compound having a heteroaromatic ring with good selectivity and high yield using copper halide. [Prior art and problems to be solved by the invention] Ether compounds having a heteroaromatic ring are useful compounds that can be widely used as intermediates for agricultural chemicals and medicines. However, the synthesis reaction of ether compounds having a heteroaromatic ring has hardly been studied to date. As one of the few examples of such reactions, in AIKiv Kemi, vol. 23, p. 239 (1958), there is a
A method for synthesizing -methoxythiophene is described. According to this report, 100
The mixture was heated under reflux for a period of time to obtain 3-methoxythiophene in a yield of 81%. In this synthesis method, the raw material 3-
Since bromothiophene remains and the boiling points of 3-bromothiophene and the product 3-methoxythiophene are similar, not only is a complicated separation and purification step required, but the reaction time is extremely long.
Moreover, it had the disadvantage that the yield was not good. On the other hand, the use of copper halide as a catalyst in the synthesis of aryl alkyl ether compounds has been reported in Journal of Chemical Society (C) [(Journal of Chemical Society (C)) 312
Page, 1969 by R.G.R. Bacon et al. According to this report, when cuprous iodide is used as a catalyst, for 1 equivalent of 1-brominated naphthalene,
0.5 to 1.0 equivalents of cuprous iodide, 2 to 3 equivalents of sodium ethylate, and ethanol and 2,3,6-
When collidine is used, 1-ethoxynaphthalene is obtained almost quantitatively. However, when the amount of cuprous iodide used is reduced, not only the yield is reduced, but also a dehalogenation reaction, which is a side reaction, occurs. Furthermore, when cuprous bromide or cuprous chloride is used as a catalyst, dehalogenation reactions and halogen exchange reactions occur as side reactions, and therefore the yield of the target ether compound is low. [Means for Solving the Problem] In view of the fact that ether compounds having various heteroaromatic rings are useful as pharmaceutical and agricultural intermediates, the present inventors developed a combination of halogenated heteroaromatic compounds and organic hydroxy compounds. We have been intensively studying methods for producing ether compounds by reacting metal salts. As a result, it was surprisingly discovered that even when a low catalyst amount of copper halide was used, side reactions of halogen exchange reactions and dehalogenation reactions did not proceed at all, and ether compounds could be produced in a short time and with good selectivity. , we have completed the present invention. That is, the present invention provides an ether compound characterized in that copper halide is used as a catalyst when producing an ether compound by reacting a halogenated heterocyclic aromatic compound with a metal salt of an organic hydroxy compound in the presence of a catalyst. This is a manufacturing method. In the present invention, the halogenated heteroaromatic compound used as a raw material is a compound in which hydrogen bonded to a heteroaromatic ring is replaced with a halogen atom, and is represented by the following general formula. R 1 −X 1 (However, R 1 is a substituted or unsubstituted heteroaromatic ring group, and X 1 is a halogen atom.) In the above general formula (1), the heteroaromatic ring represented by R 1 is: You can use anything, there are no restrictions. Specific examples of the heteroaromatic group include furyl group, thienyl group, pyrrolyl group, imidazolyl group, pyrazolyl group, pyridyl group, benzofuryl group, benzothienyl group, indolyl group, quinolyl group, pyrazinyl group, pyrimidyl group, and pyridazyl group. , quinoxalinyl group, thiazolyl group, benzothiazolyl group, isoxazolyl group, and the like. Furthermore, in the above general formula (1), the halogen atom represented by X 1 can be any of fluorine, chlorine, bromine, and iodine, but bromine or iodine is preferably used because of its good reactivity. Furthermore, in the general formula (1), any substituent for the substituted heteroaromatic group represented by R 1 is not particularly limited as long as it does not react with the reagent used in the reaction. It will be done. Specific examples of the substituent include alkyl groups such as methyl, ethyl and propyl groups; alkenyl groups such as vinyl and allyl groups; alkynyl groups such as propynyl; alkoxy groups such as methoxy and ethoxy groups; methylthio alkylthio groups such as ethylthio groups; alkoxyalkyl groups such as methoxymethyl groups; phenyl groups; nitro groups; cyano groups; amino groups; alkoxycarbonyl groups; sulfonyl groups; formyl groups; dialkylamino groups; trifluoromethyl groups, etc. Examples include polyfluoroalkyl groups. Further, a halogen atom or a hydroxy group may be substituted as long as the etherification reaction is not inhibited. The other raw material used in the present invention is a metal salt of an organic hydroxy compound. Metal salts of organic hydroxy compounds are known as alcoholates or phenolates, and in the present invention, such known metal salts of organic hydroxy compounds can be used without any restriction. A metal salt of an organic hydroxy compound that can be particularly preferably used in the present invention is represented by the following general formula. R 2 -O-M (2) (However, R 2 represents a substituted or unsubstituted alkyl group, a substituted or unsubstituted alkenyl group, a substituted or unsubstituted alkynyl group, a substituted or unsubstituted phenyl group, represents an alkali metal atom). In the above general formula (2), the alkyl group represented by R 2 may be linear or branched, and the number of carbon atoms is not particularly limited. However, from the viewpoint of easy availability of raw materials, it is preferable that the number of carbon atoms is 1 to 6. Specific examples of the alkyl group include methyl group,
Ethyl group, n-propyl group iso-propyl group, n
-butyl group, iso-butyl group, t-butyl group, n
-pentyl group, n-hexyl group, etc. Furthermore, in the above general formula (2), the alkenyl group represented by R 2 may be either linear or branched, and the number of carbon atoms is not particularly limited. However, from the viewpoint of easy availability of raw materials, it is preferable that the number of carbon atoms is 2 to 4. Specific examples of the alkenyl group include vinyl group, allyl group, iso-propenyl group, 2-butenyl group, and 3-butenyl group. In addition, in the above general formula (2), the alkynyl group represented by R 2 may be linear or branched, and the number of carbon atoms is not particularly limited. It is preferable that Specific examples of the alkynyl group include ethynyl group and 2-propynyl group. In the general formula (2), the substituted alkyl group, substituted alkenyl group, and substituted alkynyl group represented by R 2 include the substituents of the substituted heteroaromatic ring group explained for the general formula (1), It can be used except for alkyl groups, alkenyl groups, and alkynyl groups. In addition, as a substituent of the substituted phenyl group,
The substituents of the above-mentioned substituted heteroaromatic ring group can be applied as they are. Further, in the general formula (2), examples of the alkali metal atom represented by M include lithium, sodium, potassium, etc., but sodium and potassium are preferably used from the viewpoint of handling. Among the metal salts of organic hydroxy compounds represented by the general formula (2), when R 2 is an alkyl group, an alkenyl group, an alkynyl group, or any of these groups having a substituent, the yield of the target ether compound is particularly suitable in the present invention because of its high value. Copper halide, which is a catalyst used in the present invention, is a known compound and can be used without particular limitation. Copper halides suitably used include cuprous iodide, cuprous bromide, cupric bromide, cuprous chloride, etc.
Examples include copper, cupric chloride, cuprous fluoride, cupric fluoride, and the like. Among them, cuprous iodide, cuprous bromide, and cuprous chloride shorten the reaction time of the above-mentioned halogenated heteroaromatic compound and the metal salt of an organic hydroxy compound, and also reduce the ether compound produced. It is preferably used in the present invention because it is highly effective in increasing the yield and selectivity of. According to the present invention, when an ether compound is produced from the halogenated heteroaromatic compound and the metal salt of an organic hydroxy compound using copper halide as a catalyst, it is usually preferable to use an inert organic solvent. All kinds of inert organic solvents can be used as the inert organic solvent, and specific examples include benzene, hexane, cyclohexane, decalin, toluene, xylene, N,N-dimethylformamide (DMF), and dimethyl sulfoxide (DMSO). , diethyl ether, dibutyl ether, dimethoxyethane, diethylene glycol dimethyl ether, alcohol and the like. When alcohol is used as a solvent, the above general formula
Alcohol corresponding to R 2 -O-M shown in (2),
That is, it is desirable to use an alcohol represented by the general formula R 2 -OH. For example, in terms of yield and selectivity, it is preferable to use methanol if R 2 is a methyl group, ethanol if it is an ethyl group, and isopropyl alcohol if it is an isopropyl group. When carrying out the present invention, as a reaction procedure,
The order of addition of the halogenated heteroaromatic compound, the metal salt of the organic hydroxy compound, and the copper halide into the inert organic solvent is not particularly limited. In the case of alcohol, it may be directly reacted with an alkali metal to prepare an organic hydroxy compound solution containing a metal salt of the organic hydroxy compound, and a halogenated heterocyclic aromatic compound and a copper halide may be added to the solution. Further, the molar ratio of the halogenated heterocyclic aromatic compound and the metal salt of the organic hydroxy compound is not particularly limited, but is generally 1:0.1 to 1:
100, preferably from the point that by adding a large amount of a metal salt of an organic hydroxy compound to a halogenated heterocyclic aromatic compound, an ether compound can be obtained in a short time, with more selectivity, and in a high yield. , preferably in a molar ratio of 1:1.1 to 1:10. Further, the amount of copper halide used as a catalyst is preferably selected from the range of 0.01 to 80 mol percent, preferably 1 to 40 mol percent, based on the halogenated heterocyclic aromatic compound. Furthermore, the weight ratio of the halogenated heteroaromatic compound to the inert organic solvent is generally from 1:1 to 1:20, preferably from 1:1 to
You can choose from a range of 1:10. The reaction temperature in the reaction of the present invention is not particularly limited and can be selected within a wide temperature range, but is generally 50 to 180°C, preferably 80°C.
It is best to choose from a range of ~150℃. The method for purifying the ether compound obtained in the present invention is not particularly limited. Generally, after separating the catalyst, the reaction solution is neutralized, extruded with an inert organic solvent such as benzene, toluene, methylene chloride, chloroform, carbon tetrachloride, ether, etc., dried, followed by atmospheric distillation, reduced pressure distillation, It can be purified by recrystallization or chromatography. Particularly in this reaction, the yield may be greatly affected by the catalyst removal method, and one removal method may be to neutralize the reaction solution and then separate the catalyst by steam distillation. [Effect] According to the method of the present invention described above, compared to the conventional method using a halogenated aryl as a raw material, 40
The desired ether compound can be obtained in a high yield of over 90% with a small amount of catalyst, less than mol percent. Moreover, in the method of the present invention, although the amount of catalyst is small, side reactions such as dehalogenation reactions, which occur in conventional methods using aryl halides, do not occur. Therefore, the selectivity of the target ether compound is good and purification becomes easy. In addition, when copper chloride or copper bromide is used as a catalyst, in the conventional method using an aryl halide as a raw material, in addition to the dehalogenation reaction described above, there is a reaction between the aryl halide and the catalyst. Halogen exchange occurred and the yield of the desired ether compound was low. However, in the method of the present invention, even when copper chloride or copper bromide is used as a catalyst, no halogen exchange reaction is observed, and the yield of the target product is as high as when copper iodide is used as a catalyst. It is obtained by Therefore, in the present invention, when copper chloride or copper bromide is used as a catalyst, the yield of the target ether compound is dramatically improved. As described above, the method of the present invention is a method for producing an ether compound with a low catalyst amount, high yield, and good selectivity, and its industrial value is significant. Examples are given below to specifically explain the present invention, but the present invention is not limited to these Examples. Example 1 In a 200 ml three-necked flask equipped with a reflux condenser and a stirrer, 20 g of 2-bromothiophene (120 ml
mole), sodium methylate 13.2g (250m
0.9 g (9 mmole) of cuprous chloride, and 40 ml of methanol were added, and the mixture was vigorously stirred under heating under reflux for 17 hours under a nitrogen atmosphere. The reaction solution was returned to room temperature, neutralized with dilute hydrochloric acid, and then steam distilled. As a result of analyzing the obtained oil layer by gas chromatography, it was confirmed that thiophene was not produced and no dehalogenation reaction occurred. After that, the oil layer is separated and distilled under atmospheric pressure to produce 2, a colorless liquid with a boiling point of 159℃.
-13.1g of methoxythiophene was obtained. The yield was 93.1% based on the raw material 2-bromothiophene. Example 2 In a 200 ml three-necked flask equipped with a reflux condenser and a stirrer, 100 ml of methanol and metallic sodium were added.
12.3 g (530 mmole) was added to prepare a sodium methylate-methanol solution in advance. Add 34.9 g (214 mmole) of 3-promthiophene to the solution.
and 7.6 g (40 mmole) of cuprous iodide were added one after another, and the mixture was vigorously stirred under heating under reflux for 3 hours. after that,
The reaction solution was returned to room temperature, neutralized with dilute hydrochloric acid, and then subjected to steam distillation. As a result of analyzing the obtained oil layer by gas chromatography, the presence of thiophene was not observed, and it was confirmed that no dehalogenation reaction occurred. The obtained oil layer was extracted with 50 ml of methylene chloride and dried over calcium chloride. After distilling off the methylene chloride, atmospheric distillation was performed to obtain 22 g of 3-methoxythiophene, a colorless liquid with a boiling point of 159°C. The yield was 90.0% based on the raw material 3-bromothiophene. Example 3 Table 1 shows the experimental results using cuprous iodide as a catalyst according to the same experimental procedure as in Example 2. In any of the experiments, as in Example 2, no dehalogenation reaction was observed. However, DMF in the table indicates N,N-dimethylformamide, and DMSO indicates dimethyl sulfoxide.
【表】【table】
【表】
実施例 ４
実施例１と同様な実験操作に従い、触媒として
沃化第１銅以外のハロゲン化銅を用いた実験結果
を表２に示す。
いずれの実験に於いても、実施例１と同様に脱
ハロゲン化反応の生起は認められなかつた。[Table] Example 4 Table 2 shows the results of an experiment in which a copper halide other than cuprous iodide was used as a catalyst according to the same experimental procedure as in Example 1. In any of the experiments, as in Example 1, no dehalogenation reaction was observed.
【表】【table】
【表】【table】
【表】【table】
Claims (1)
ロキシ化合物の金属塩を触媒の存在下に反応させ
てエーテル化合物を製造するに際し、触媒として
ハロゲン化銅を用いることを特徴とするエーテル
化合物の製造方法。1. A method for producing an ether compound, which comprises using copper halide as a catalyst in producing an ether compound by reacting a halogenated heterocyclic aromatic compound and a metal salt of an organic hydroxy compound in the presence of a catalyst.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60239291A JPS6299383A (en) | 1985-10-28 | 1985-10-28 | Production of ether compound |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP60239291A JPS6299383A (en) | 1985-10-28 | 1985-10-28 | Production of ether compound |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS6299383A JPS6299383A (en) | 1987-05-08 |
| JPH0544951B2 true JPH0544951B2 (en) | 1993-07-07 |
Family
ID=17042546
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP60239291A Granted JPS6299383A (en) | 1985-10-28 | 1985-10-28 | Production of ether compound |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPS6299383A (en) |
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|---|---|---|---|---|
| CN103201262B (en) * | 2010-08-20 | 2016-06-01 | 艾米拉医药股份有限公司 | Autotaxin inhibitors and application thereof |
| GB201522179D0 (en) * | 2015-12-16 | 2016-01-27 | Autifony Therapeutics Ltd | Novel compounds |
-
1985
- 1985-10-28 JP JP60239291A patent/JPS6299383A/en active Granted
Also Published As
| Publication number | Publication date |
|---|---|
| JPS6299383A (en) | 1987-05-08 |
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