CN1118448C - 苄基-醚的制备方法 - Google Patents
苄基-醚的制备方法 Download PDFInfo
- Publication number
- CN1118448C CN1118448C CN97199819A CN97199819A CN1118448C CN 1118448 C CN1118448 C CN 1118448C CN 97199819 A CN97199819 A CN 97199819A CN 97199819 A CN97199819 A CN 97199819A CN 1118448 C CN1118448 C CN 1118448C
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- China
- Prior art keywords
- acid
- group
- reaction
- alkyl
- general formula
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 46
- 238000002360 preparation method Methods 0.000 title claims abstract description 13
- 230000008569 process Effects 0.000 title claims abstract description 9
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical class C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 title description 4
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 107
- -1 methylenedioxy Chemical group 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims abstract description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 14
- 239000001257 hydrogen Substances 0.000 claims abstract description 14
- 239000002253 acid Substances 0.000 claims abstract description 12
- 150000001875 compounds Chemical class 0.000 claims abstract description 12
- 125000003118 aryl group Chemical group 0.000 claims abstract description 10
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 8
- 150000002367 halogens Chemical class 0.000 claims abstract description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 8
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims abstract description 7
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims abstract description 6
- 125000005843 halogen group Chemical group 0.000 claims abstract description 6
- 229910052751 metal Inorganic materials 0.000 claims abstract description 6
- 239000002184 metal Substances 0.000 claims abstract description 6
- 229910044991 metal oxide Inorganic materials 0.000 claims abstract description 6
- 150000004706 metal oxides Chemical class 0.000 claims abstract description 6
- 239000002841 Lewis acid Substances 0.000 claims abstract description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 5
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 5
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 4
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 45
- 239000000243 solution Substances 0.000 claims description 24
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 18
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 14
- 239000002585 base Substances 0.000 claims description 12
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical group ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 10
- 239000011787 zinc oxide Substances 0.000 claims description 9
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 8
- 239000000010 aprotic solvent Substances 0.000 claims description 7
- 239000011592 zinc chloride Substances 0.000 claims description 7
- 235000005074 zinc chloride Nutrition 0.000 claims description 7
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 claims description 6
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- 239000002904 solvent Substances 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 claims description 4
- 150000003839 salts Chemical class 0.000 claims description 4
- FMRLDPWIRHBCCC-UHFFFAOYSA-L Zinc carbonate Chemical compound [Zn+2].[O-]C([O-])=O FMRLDPWIRHBCCC-UHFFFAOYSA-L 0.000 claims description 3
- JXLHNMVSKXFWAO-UHFFFAOYSA-N azane;7-fluoro-2,1,3-benzoxadiazole-4-sulfonic acid Chemical compound N.OS(=O)(=O)C1=CC=C(F)C2=NON=C12 JXLHNMVSKXFWAO-UHFFFAOYSA-N 0.000 claims description 3
- AMAICRYCMCVAHT-UHFFFAOYSA-K calcium;sodium;trichloride Chemical compound [Na+].[Cl-].[Cl-].[Cl-].[Ca+2] AMAICRYCMCVAHT-UHFFFAOYSA-K 0.000 claims description 3
- 239000003112 inhibitor Substances 0.000 claims description 3
- 229910017053 inorganic salt Inorganic materials 0.000 claims description 3
- 229910001629 magnesium chloride Inorganic materials 0.000 claims description 3
- 230000003647 oxidation Effects 0.000 claims description 3
- 238000007254 oxidation reaction Methods 0.000 claims description 3
- 239000011667 zinc carbonate Substances 0.000 claims description 3
- 235000004416 zinc carbonate Nutrition 0.000 claims description 3
- 229910000010 zinc carbonate Inorganic materials 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 2
- 239000011260 aqueous acid Substances 0.000 claims description 2
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 150000007522 mineralic acids Chemical class 0.000 claims description 2
- 150000007524 organic acids Chemical class 0.000 claims 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 claims description 2
- 239000012267 brine Substances 0.000 claims 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 claims 2
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical group C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 10
- 125000002723 alicyclic group Chemical group 0.000 abstract description 4
- 125000000304 alkynyl group Chemical group 0.000 abstract description 4
- 125000001424 substituent group Chemical group 0.000 abstract description 3
- 239000003963 antioxidant agent Substances 0.000 abstract description 2
- 230000003078 antioxidant effect Effects 0.000 abstract description 2
- 125000005842 heteroatom Chemical group 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 2
- 125000003342 alkenyl group Chemical group 0.000 abstract 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000006656 (C2-C4) alkenyl group Chemical group 0.000 abstract 1
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 abstract 1
- 235000006708 antioxidants Nutrition 0.000 abstract 1
- 150000002170 ethers Chemical class 0.000 abstract 1
- WVDDGKGOMKODPV-UHFFFAOYSA-N hydroxymethyl benzene Natural products OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 37
- 239000000203 mixture Substances 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 26
- 239000000047 product Substances 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 238000003756 stirring Methods 0.000 description 17
- 229960004217 benzyl alcohol Drugs 0.000 description 15
- 238000001704 evaporation Methods 0.000 description 15
- 235000019445 benzyl alcohol Nutrition 0.000 description 14
- 230000008020 evaporation Effects 0.000 description 14
- 238000005406 washing Methods 0.000 description 12
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 11
- 238000001035 drying Methods 0.000 description 11
- 239000002994 raw material Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 9
- 239000012071 phase Substances 0.000 description 9
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 8
- 239000013256 coordination polymer Substances 0.000 description 8
- 229910052760 oxygen Inorganic materials 0.000 description 8
- 239000012074 organic phase Substances 0.000 description 7
- 239000001301 oxygen Substances 0.000 description 7
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 6
- 229960005069 calcium Drugs 0.000 description 6
- 239000011575 calcium Substances 0.000 description 6
- 229910052791 calcium Inorganic materials 0.000 description 6
- 239000001110 calcium chloride Substances 0.000 description 6
- 229960002713 calcium chloride Drugs 0.000 description 6
- 229910001628 calcium chloride Inorganic materials 0.000 description 6
- 239000000284 extract Substances 0.000 description 6
- 238000011049 filling Methods 0.000 description 6
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 5
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XNMQEEKYCVKGBD-UHFFFAOYSA-N 2-butyne Chemical compound CC#CC XNMQEEKYCVKGBD-UHFFFAOYSA-N 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 238000006471 dimerization reaction Methods 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 239000000706 filtrate Substances 0.000 description 4
- 239000010410 layer Substances 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000007086 side reaction Methods 0.000 description 4
- 239000000758 substrate Substances 0.000 description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 230000008859 change Effects 0.000 description 3
- 239000003153 chemical reaction reagent Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- 239000003480 eluent Substances 0.000 description 3
- OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical compound CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 238000006386 neutralization reaction Methods 0.000 description 3
- 239000012434 nucleophilic reagent Substances 0.000 description 3
- OEGPRYNGFWGMMV-UHFFFAOYSA-N (3,4-dimethoxyphenyl)methanol Chemical compound COC1=CC=C(CO)C=C1OC OEGPRYNGFWGMMV-UHFFFAOYSA-N 0.000 description 2
- DSSYKIVIOFKYAU-XCBNKYQSSA-N (R)-camphor Chemical compound C1C[C@@]2(C)C(=O)C[C@@H]1C2(C)C DSSYKIVIOFKYAU-XCBNKYQSSA-N 0.000 description 2
- GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 description 2
- DBAMUTGXJAWDEA-UHFFFAOYSA-N Butynol Chemical compound CCC#CO DBAMUTGXJAWDEA-UHFFFAOYSA-N 0.000 description 2
- 101150065749 Churc1 gene Proteins 0.000 description 2
- 241000723346 Cinnamomum camphora Species 0.000 description 2
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- 102100038239 Protein Churchill Human genes 0.000 description 2
- RHQDFWAXVIIEBN-UHFFFAOYSA-N Trifluoroethanol Chemical compound OCC(F)(F)F RHQDFWAXVIIEBN-UHFFFAOYSA-N 0.000 description 2
- 238000007171 acid catalysis Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 125000005133 alkynyloxy group Chemical group 0.000 description 2
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 2
- KCXMKQUNVWSEMD-UHFFFAOYSA-N benzyl chloride Chemical compound ClCC1=CC=CC=C1 KCXMKQUNVWSEMD-UHFFFAOYSA-N 0.000 description 2
- 125000001743 benzylic group Chemical group 0.000 description 2
- 239000006227 byproduct Substances 0.000 description 2
- 229960000846 camphor Drugs 0.000 description 2
- 229930008380 camphor Natural products 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000003550 marker Substances 0.000 description 2
- 239000002609 medium Substances 0.000 description 2
- 230000007935 neutral effect Effects 0.000 description 2
- ZYURHZPYMFLWSH-UHFFFAOYSA-N octacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCC ZYURHZPYMFLWSH-UHFFFAOYSA-N 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 239000012747 synergistic agent Substances 0.000 description 2
- QMXXECONCBMFQU-UHFFFAOYSA-N (1-methyl-2h-naphthalen-1-yl)methanol Chemical compound C1=CC=C2C(C)(CO)CC=CC2=C1 QMXXECONCBMFQU-UHFFFAOYSA-N 0.000 description 1
- FTNJQNQLEGKTGD-UHFFFAOYSA-N 1,3-benzodioxole Chemical compound C1=CC=C2OCOC2=C1 FTNJQNQLEGKTGD-UHFFFAOYSA-N 0.000 description 1
- ZHKALZZEGVFZQA-UHFFFAOYSA-N 1-(1,3-benzodioxol-5-yl)ethanol Chemical compound CC(O)C1=CC=C2OCOC2=C1 ZHKALZZEGVFZQA-UHFFFAOYSA-N 0.000 description 1
- UJBOGVMFJDOUDP-UHFFFAOYSA-N 1-(3,4-diethoxyphenyl)ethanol Chemical compound CCOC1=CC=C(C(C)O)C=C1OCC UJBOGVMFJDOUDP-UHFFFAOYSA-N 0.000 description 1
- NMYXSFKGIICIIM-UHFFFAOYSA-N 1-(3,4-dimethoxyphenyl)propan-1-ol Chemical compound CCC(O)C1=CC=C(OC)C(OC)=C1 NMYXSFKGIICIIM-UHFFFAOYSA-N 0.000 description 1
- HNZOLCDWNWTGFJ-UHFFFAOYSA-N 1-(4,5-dimethoxy-2-propylphenyl)ethanol Chemical compound CCCC1=CC(OC)=C(OC)C=C1C(C)O HNZOLCDWNWTGFJ-UHFFFAOYSA-N 0.000 description 1
- 241000238421 Arthropoda Species 0.000 description 1
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- 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 1
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical class CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 1
- OUUQCZGPVNCOIJ-UHFFFAOYSA-M Superoxide Chemical compound [O-][O] OUUQCZGPVNCOIJ-UHFFFAOYSA-M 0.000 description 1
- ACIAHEMYLLBZOI-ZZXKWVIFSA-N Unsaturated alcohol Chemical compound CC\C(CO)=C/C ACIAHEMYLLBZOI-ZZXKWVIFSA-N 0.000 description 1
- 238000006959 Williamson synthesis reaction Methods 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 150000001447 alkali salts Chemical class 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical class OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 1
- 238000010719 annulation reaction Methods 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 238000007068 beta-elimination reaction Methods 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- LLSDKQJKOVVTOJ-UHFFFAOYSA-L calcium chloride dihydrate Chemical compound O.O.[Cl-].[Cl-].[Ca+2] LLSDKQJKOVVTOJ-UHFFFAOYSA-L 0.000 description 1
- 229940052299 calcium chloride dihydrate Drugs 0.000 description 1
- VDDRNXHIJFHESZ-UHFFFAOYSA-L calcium dichloride hydrochloride Chemical compound Cl.[Cl-].[Cl-].[Ca+2] VDDRNXHIJFHESZ-UHFFFAOYSA-L 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 125000002091 cationic group Chemical group 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- AQEFLFZSWDEAIP-UHFFFAOYSA-N di-tert-butyl ether Chemical compound CC(C)(C)OC(C)(C)C AQEFLFZSWDEAIP-UHFFFAOYSA-N 0.000 description 1
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 1
- 229940028356 diethylene glycol monobutyl ether Drugs 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000008151 electrolyte solution Substances 0.000 description 1
- 238000007336 electrophilic substitution reaction Methods 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000004880 explosion Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 1
- 125000005462 imide group Chemical group 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 1
- 238000005648 named reaction Methods 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 230000000269 nucleophilic effect Effects 0.000 description 1
- 238000010534 nucleophilic substitution reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- JCGNDDUYTRNOFT-UHFFFAOYSA-N oxolane-2,4-dione Chemical compound O=C1COC(=O)C1 JCGNDDUYTRNOFT-UHFFFAOYSA-N 0.000 description 1
- NWVVVBRKAWDGAB-UHFFFAOYSA-N p-methoxyphenol Chemical compound COC1=CC=C(O)C=C1 NWVVVBRKAWDGAB-UHFFFAOYSA-N 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 229960003742 phenol Drugs 0.000 description 1
- LYKMMUBOEFYJQG-UHFFFAOYSA-N piperoxan Chemical compound C1OC2=CC=CC=C2OC1CN1CCCCC1 LYKMMUBOEFYJQG-UHFFFAOYSA-N 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- TVDSBUOJIPERQY-UHFFFAOYSA-N prop-2-yn-1-ol Chemical compound OCC#C TVDSBUOJIPERQY-UHFFFAOYSA-N 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 238000007614 solvation Methods 0.000 description 1
- 238000005728 strengthening Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- ABDKAPXRBAPSQN-UHFFFAOYSA-N veratrole Chemical compound COC1=CC=CC=C1OC ABDKAPXRBAPSQN-UHFFFAOYSA-N 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/44—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D317/46—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 ortho- or peri-condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D317/48—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring
- C07D317/50—Methylenedioxybenzenes or hydrogenated methylenedioxybenzenes, unsubstituted on the hetero ring with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to atoms of the carbocyclic ring
- C07D317/54—Radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C41/00—Preparation of ethers; Preparation of compounds having groups, groups or groups
- C07C41/01—Preparation of ethers
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Abstract
本发明涉及通式I的混合醚制造方法,式I中Ar代表一个脂环族、芳族或含一或多个杂原子的杂环部分,任选被一或多个C1-4烷氧基、亚甲二氧基、C1-4烷基、卤素、C1-4卤代烷基或硝基取代,和/或与一个苯环缩合;R1和R2独立表示氢、C1-4烷基、C1-4卤代烷基、C2-4链烯基、苯基、取代苯基、C3-6环烷基基团;R3表示C1-6烷基、C3-6链烯基或C3-6链炔基,任意被一或多个C1-6烷基、C3-6链烯基、C3-6链炔基、C1-6卤代烷基或卤原子取代;或是一个C1-4烷氧基-C1-4烷氧基-C1-4烷基基团,本方法的特征在于将通式II化合物与1-3摩尔当量的通式III醇在酸、路易斯酸、金属氧化物或金属碳酸盐存在下反应,式II中X是指羟基,卤素或磺酸酯离去基团,式III中各取代基定义同上,得到的通式I的醚分离出来,若需要,可通过加入碱和/或抗氧剂来稳定,且若需要的话,回收过量醇。
Description
本发明涉及通式I的混合醚制备方法,其中
Ar代表一个脂环族、芳族或含一或多个杂原子的杂环部分,任选被一或多个C1-4烷氧基、亚甲二氧基、C1-4烷基、卤素、C1-4卤代烷基或硝基取代,和/或与一个苯环缩合;
R1和R2独立表示氢、C1-4烷基、C1-4卤代烷基、C2-4链烯基、苯基、取代苯基、C3-6环烷基基团;
R3表示C3-6链炔基,任意被一个或多个C1-6烷基、C3-6链烯基、C3-6链炔基、C1-6卤代烷基或卤原子取代;或是一个C1-4烷氧基-C1-4烷氧基-C1-4烷基基团,在酸性条件下,将通式II化合物与通式III化合物反应来制备式I化合物,通式II中
X表示羟基、卤素或磺酸酯离去基团,
通式III中R3的定义同上;
Ar为芳族基团时,最好是苯基或萘基基团;
Ar为杂环部分时可含有一或多个O、S、N杂原子,最好是苯并间二氧杂环戊烯、苯并二氧杂环已烷、2-苯并呋喃、T-苯并呋喃部分;脂环族基团最好是与苯环缩合,例如可以是1,2-二氢茚基或1,2,3,4-四氢萘基;酰亚胺类基团可以是邻苯二甲酰亚胺部分;
芳族、杂环类和脂环族Ar基团任意被C1-4烷氧基、亚甲二氧基、C1-4烷基、卤素、C1-4卤代烷基或硝基取代。通式I的醚是许多化学产品的原料或活性组分,有很大的开发潜力。其中一些有代表性的醚是有显著活性的杀虫(节肢动物)增效剂(匈牙利专利申请号3318/95),除了已知的带饱和侧链的亚甲二氧基(MDP)类增效剂(例如PSO,即5-[2-(2-丁氧乙氧基)乙基氧甲基]-6-丙基-1,3-苯并间二氧杂环戊烯)外,这些化合物都是新化合物,尽管它们的结构简单,由于其效果明显,故它们的制备和经济合成是至关重要的。
上述醚可用已知的醚合成常用方法来制造(Gy,Matolcey,M.Nadasdy,V.Anderiska;农药化学,Akademia(1988);匈牙利专利说明书No.3318/95)。这些方法的要点是醇的碱性盐组分与作用物按亲核取代机理反应。作用物含一个离去基团,通常是卤原子,优选为溴原子。根据分子那部分作为亲核试剂,反应可按两个途径进行。由于苄基卤化物的活性较大,实际上通常是侧链的醇化物与苄基溴化物反应。但是,当由于某种原因醇化物的合成很困难时,这种方法就受到一定限制。在这样的情况下,只能用相反的方法解决这个问题,但可以预料,反应通常很不理想。此类制醚方法在有机化学中是非常熟悉的,属于Williamson合成法(B.P Mundy,M.G.Elled,有机合成的人名反应和试剂,Wiley(1988))。但是,该反应有一些不利因素,工业上醇化物的形成费用很高,需要昂贵的试剂,以及在无水条件下保护或有干燥步骤的精制技术(匈牙利专利申请号180500 190842)。卤化物或称含离去基团的作用物的制备需分离步骤且所用试剂的费用更高。在α碳原子含有另外的取代基(R1和/或R2不同于氢)时,由于产物易于发生消去反应或副反应,如芳族亲电取代反应,故活化的例如卤代衍生物的合成有困难。偶合物的收率很大程度上取决于作用物的反应活性,且得到的产物需进一步提纯。
对于普通醚的制备来说,还有一些方法也是为人们熟知的。其中最老且最著名的方法是酸催化的醇二聚反应(H0uben Weyl 6/3 11-19)。按照文献,反应通常需要高温,且为避免分解,产物必须不断从反应混合物中移出,酸作用下形成的氧翁阳离子很易参加重排反应,或可能过相邻碳原子中氢原子的所谓β消去反应形成相应的烯烃而得以稳定。这会形成大量的分解产物,因反应过程中有水生成的情况使反应过程缓慢而更加复杂化。因此,反应的效能(收率、纯度)很低。所以,可以理解,当打算合成时,该方法并不在考虑范围,倒不如当作酸催化方法的副反应(化学与药物通报(日).31,3024(1983))。
在二苄醚的情况中,为消除不利因素,已开发出甲基亚砜引发的二聚方法(有机化学杂志.42,2012,(1977))。但由于所用试剂和高温(1750℃)缘故,该方法不能工业规划应用。
据报道,除了可用路易斯酸催化成醚的情况外,反应也可在相对温和的条件下用二氯化锌在二氯乙烷中进行(有机化学杂志.52,3917,(1987)),这是一个突破性发现。但该方法实际上只能有效用于二聚和分子内成环反应。对于混合醚来说,反应的再现性以及产品的质量和产率较差。用含有芳族取代基的苄基(对甲氧基苄基)醇则由于聚合反应,反应的产率很低;带有不饱和链的混合醚(α-苄基烯丙基醚)-不同于它的饱和类似物-也可获得,但由于二聚反应产率却很差。在一个公开的反应方案中,苄基卤化物在氧化锌存在下与亲核试剂反应(四面体38,1843,(1982)),但该反应是否能应用于通式I化合物不得而知。
酸催化成醚反应通过适当的阳离子中间体进行。已研究了环取代的1-苯乙基碳阳离子稳定性和它们在三氟乙醇/水=1/1的模型***中与亲核试剂的反应(美国化学会志.106,1361,(1984);106,1373,(1984)。但是在这两篇资料中,并未给出制备通式I化合物的实例,而且也未提及反应介质对它们的合成影响(极性,溶剂化作用),如两篇文献中所示,反应介质在反应中起很重要的作用,甚至微小的改动都会干扰灵敏的平衡。上述两篇资料的作者在以后的理论工作中指出,类似于通式I的醚与其它醚不太一样,意外地发现对酸敏感。成醚过程以可逆反应方式进行,会增加形成副产物的可能性,使产品的纯度和产率变差。如所公开的数据显示,烷氧基醇如乙二醇单甲基醚反应性较差,不饱和醇如炔丙醇的反应活性中等,但都远不及易反应的简单饱和醇如甲醇、乙醇和丁醇的反应活性。芳环上的吸电子取代基和供电子取代基分别会提高和降低成醚反应的平衡常数。提高水/三氟乙醇之比会对直接醚合成产生不利影响。
工业上,生产醚是一个极其困难的任务,不仅因为试剂昂贵和可能的副反应,还因为起始原料醇和得到的醚易形成过氧化物,存在***隐患。此外,炔基化合物因有三键缘故对热敏感。只有在反应能在温和条件下进行且最终产品(绝大部分为液体)不必进一步提纯、蒸馏的情况下,才有可能大规模(1000吨/年)安全生产。
鉴于以上情况,我们仔细研究了通式I的不对称醚制备可能性。根据我们的实验结果,我们开发出一种方法,其要点是通过式II化合物(其中X是指羟基、卤或磺酸酯离去基团)与1-3摩尔当量的式III化合物(其中的取代基定义同上)在酸、路易斯酸、金属氧化物或金属碳酸盐存在下反应,可以很好地制备式I化合物(其中各取代基定义同上)。得到的通式I的醚被分离出来,过量醇被回收,若需要的话,可加入碱和/或抗氧剂来稳定产品。在通式I、II和III中,Ar、R1、R2和R3的定义与前文所给定义相同。
至于酸,最好使用0.01-3摩尔当量的强无机或有机酸,优选盐酸、硫酸、高氯酸或芳族磺酸。反应在盐溶液,优选在氯化钠、氯化钙、氯化镁、氯化锌溶液中进行,优选为10%(w/w)酸的水溶液,优选用无机盐饱和,反应温度在(-20)-(+30)℃。
至于路易斯酸,优选用0.01-3摩尔当量的二氯化锌或芳族磺酸,优选苯磺酸或对甲苯磺酸,反应在一种非极性的非质子溶剂中,于(-30)-(+40)℃下进行。
至于金属氧化物,优选使用0.01-3摩尔当量的氧化锌,金属碳酸盐则优选用碳酸锌,且反应在无溶剂或在一种非极性的非质子溶剂存在下进行。
至于有机溶剂,卤代溶剂被证明是较好的,其中二氯乙烷最好。在这种情况下,也可以用路易斯酸。据文献反道,二氯化锌被证实其不能很好地用于制备与通式I非常相似的结构,所得产品产率低且含有杂质(有机化学杂志52,3917,(1987)),然而在我们发明的最佳反应体系中,反应以很好的产率进行,且得到产品纯度也很适合。类似地,用氧化锌时,反应也能很好进行。在此情况中,卤化锌副产物也不会引起聚合反应。反应不要求无水溶剂和条件,反应中形成的水不会妨碍反应的完成,它与催化剂结合。得到的乳液或悬浮液可用简单的沉淀或过滤方法分离,在后面操作步骤中得以再利用。
在工业生产中用水作为溶剂是非常方便的。本方案的独特之处不仅在于先前从未采用,而且由于成醚反应-一种平衡反应-被认为在水性介质中受到抑制(美国化学会志107,1340(1985))而使用水作溶剂的方案出人意料。对照文献数据,本方法甚至可很好地用于制备带有给电子取代基(羟基、甲氧基、乙氧基、亚甲二氧基基团)的苄基炔基醚。含有酚式羟基的苄基醚,尽管含有多于一个亲核中心,也可直接选择性合成。介质极性的增加有利于反应。因此,使用辅助原料,优选各种盐也有利于反应。选定正确参数,反应可向生成产物方向移动。酸催化剂的用量在1-2mol%足以。反应甚至在低温下也可快速进行,因而避免了不期望的副反应。优选醇过量使用,这样反应时间就可大大缩短。产物可通过简单的沉积法从反应混合物中分离出来,电解液可再用。从过程中回收的原料醇可再使用。因此,本方法实际上对每一组分都是定量的。反应得到的粗产物品质很好,纯度达到93-95%。当然,也可通过蒸馏或重结晶(若可能)方法将其进一步提纯,而不是直接使用。为增强其稳定性并阻止它的酸性水解,适合将产品洗涤至中性或在碱性PH范围内的缓冲液。为更安全输送起见,推荐加入各类抗氧剂。
至于抗氧剂,优选用例如TMQ;BHT;氢醌;氢醌单甲基醚;2,2,6,6-四甲基-4-哌啶醇-N-氧化物。
为说明我们的方法,下面将给出一些非限定实例,但这并不全面覆盖本发明方法。
实施例1.)1-[1-(丁-2-炔氧基)乙基]-3-羟基-4-甲氧基苯A.)
1.7g(10.7mmol)1-(3-羟基-4-甲氧基苯基)乙醇溶解于1.4g 2-丁炔醇中,于室温搅拌下,向该溶液中加入1.5ml 1%HCl-50%CaCl2溶液。混合物搅拌过夜。反应通过TLC(洗脱剂:正乙烷-乙酸乙酯7∶3;Rf=0.19)跟踪。向反应混合物中加入***,直到油状有机相溶解。然后用1M NaOH溶液中和混合物,分离两相,水层用***萃取两次,合并有机相层,依次用水和饱和氯化钠溶液洗涤,经MgSO4干燥后,过滤并蒸发。产率:2.08g(94%),无色稠油。GC(CP 9000,CP-SIL-5CB 60mx 0.53mm,5ml/min N2 FID,250℃):tR=4.44min,>93%.IR(CHCl3,cm-1)υ:3601,3541,2972,2924,2857,1728,1615,1596,1507,
1457,1443,1372,1308,1288,1271,1235,1164,1132,
1110,1084,1043,1030,1004,934,877,841,808,644,
611.1H-NMR(200MHz,CDCl3)δ:1.44(3H,d,J=6.4Hz,CH-CH3),1.84(3H,t,
J=2.2Hz≡C-CH3),3.81和4.01(2H,
ABX3,JAB=1.50Hz,JAX=JBX=2.34Hz,
≡C-CH2O),3.87(3H,s,OCH3),4.52(2H,
q,J=6.4Hz,Ar-CHO),5.80(1H,OH),
6.82(2H,d,J=1.12Hz芳族5,6-CH)
6.91(1H,t,芳族-CH).13C-NMR(50MHz,CDEl3)δ:3.56(≡C-CH3),23.65(CH-CH3),55.84
(OCH3),55.89(≡C-CH2O),75.35(≡C-CH2
),76.06(Ar-CH-CH3),81.98(≡C-CH3
),81.89(≡C-CH3),110.47(C-2),
112.66(C-5),118.08(C-6),135.93(C-1),
145.65(C-4),146.08(C-3).B.)按照上一实施例所述步骤,不同处在于用二氯化锌溶液代替氯化钙溶液,得到的产物与上一方法所得产物相同。2.)1-[1-(丁-2-炔氧基)乙基]-3,4-二甲氧基苯(1-(3’,4’-二甲氧基苯基)乙基丁-2-炔基醚)。A.)准备阶段
在250ml水中,搅拌下溶入125g氯化钙二水合物,按照其密度(d=1.33g/m1),该溶液等同于约35w/w%氯化钙溶液。若需要,将溶液过滤。在容量瓶中用上述溶液将7.6ml(9.0g)浓盐酸稀释至250ml。制备阶段:
在强力搅拌的500.0gα-甲基-3,4-二甲氧基苄醇和192.3g 2-丁炔-1-醇的混合物中快速加入由250ml氯化钙-盐酸溶液和192.3g2-丁炔-1-醉组成的混合物。反应用GC和TLC分析跟踪。6小时后,产物的相对量为92-93%,如GC分析所示,而原料量减少为小于2%。此后,搅拌下用500ml***稀释,搅拌下用1M氢氧钠溶液中和。分离后,水层用2×100ml***萃取。合并的有机相用饱和氯化钠溶液洗涤(检测水相层的PH为中性),将其干燥。大气压下蒸发溶液,在水抽气减压下蒸出过量丁炔醇。回收的182g丁炔醇可再用于下面的纯度研究(GC,折光指数)。产物:650g无色油。纯度:直接积分法为93%,二十八烷内标法为95%,产率:94%,n20 D1.5280。IR(CHCl3 cm-1)υ:
2976,2855,2837,1605,1595,1514,1465,1419,1371,
1353,1311,1260,1164,1141,1086,1027,8641H-NMR(200MHz,CDCl3)δ:
1.46(3H,d,J=6.5Hz,CH-CH3),1.85(3h,t,
J=2.3Hz,≡C-CH3),3.83和4.01(2H,
ABX3,JAB=15.0Hz,JAX=JBX=2.3Hz,≡C-CH2-O
),3.87和3.89(共6H,每峰,
O-CH3),4.55(2H q,J=6.5Hz,Ar-CH-O),
6.80-6.89(3H,m,芳氢).13C-NMR(50MHz,CDCl3)δ:
3.61,(≡C-CH3),23.76(CH-CH3),55.87(
O-CH3),55.96(≡C-CH2-O),75.36(≡C-CH2),
76.40(Ar-CH-O),81.91(≡C-CH3),109.06(C-
2),110.86(C-5),118.94(C-6),135.30(C-1),
148.52(C-3),149.19(C-4).B.)
在装有磁搅拌器、冷凝器和装填氯化钙的干燥管的烧瓶中,加入α-甲基-3,4-二甲氧基苄醇(8.72g,0.0478mol)和2-丁炔-1-醇(4.36g,0.0623mol),然后溶解于100ml二氯乙烷。室温搅拌条件下,向混合物加入二氯化锌(1.97g,0.0145mol)。反应伴有颜色特征变。反应2小时后,分离反应中形成的水相部分,有机相用3×30ml饱和氯化钠溶液洗涤,干燥并蒸发。粗产物(12.1g)借助真空泵减压蒸馏。产率:9.2g(0.0393mol,82.2%)。GC(用内标法)98.2%。该物质与前一方法所得化合物相同。3.)1-[1-(丁-3-炔氧基)乙基]-3,4-二甲氧基苯
在装有搅拌器的烧瓶中加入3.0g(0.0164mol)α-甲基-3,4-二甲氧基苄醇和2.3g(0.0329mol)3-丁炔-1-醇,向该混合物中快速加入1.5ml由50w/v%氯化钙-1w/w%盐酸组成的溶液。混合物室温下搅拌过夜。然后用***稀释,混合物用几滴1M氢氧化钠溶液中和。分离两相,水相用***充分萃取,合并的有机层用饱和氧化钠溶液洗涤,干燥并蒸发。产率:3.5g(93%)。纯度:92%。IR(CHCl3,cm-1)υ:3307,3027,2958,2933,2869,2838,2120,1607,
1595,1509,1465,1443,1259,1163,1142,1098,
1027,861.1H-NMR(200MHz,CDCl3)δ:1.45(3H,d,J=6.5Hz,CH-CH3),1.96(1H,
t,J=2.7Hz,≡CH),2.44(2H,td,J=7,
2.7Hz,CH2-C≡),3.43(2H,t,J=7Hz),
3.87和3.89(共6H,每峰,OCH3),
4.38(2H,q,J=6.5Hz,Ar-CHO),6.83(2H,
d,芳氢),6.90(1H,s,芳氢).13C-NMR(50MHz,CDCl3)δ:19.95(OCH2-CH2),24.0(CH-CH3),55.77
和55.82(OCH3),66.33(OCH2-CH2),
69.09(≡CH),77.87(Ar-CH-H3),81.43(≡C-CH2
),108.87(C-2),110.81(C-5),
118.49(C-6),136.12(C-1),148.34(C-3),
149.12(C-4)4.)1-{1-[(z)-3-氯-丁-2-炔氧基]乙基}-3,4-二甲氧基苯
在装有搅拌器的烧瓶中加入4.27g(0.02345mol)α-甲基-3,4-二甲氧基苄醇和5.0g(0.0469mol)2-氯丁-2-烯-1-醇(主要由Z几何异构体组成),向该混合物中快速加入5.0ml由50w/v%氯化钙-1w/w%盐酸组成的溶液。混合物室温下搅拌过夜。然后用***稀释,混合物用几滴1M氢氧化钠溶液中和。分离两相,水相用***充分萃取,合并的有机层用饱和氧化钠溶液洗涤,干燥并蒸发。得到5.6g无色油,产率:9%,纯度(GC)约88.5%。GC(CP9000,CP-SIL-5CB,60mx 0.53mm,5ml/min N2,FID,250℃):IR(CHCl3,cm-1)υ:2973,2931,2862,2839,1659,1606,1595,1511,1465,
1443,1261,1164,1141,1093,1028.
1H-NMR(200MHz,CDCl3)δ:1.43(3H,d,J=6.5Hz,CH-CH3),1.97
(3H,t,J=0.5Hz,=CCl-CH3),3.80(2H,
m,OCH2),3.87和3.89(共6H,每
峰,O-CH3),4.38(2H q,J=6.5Hz,Ar-CHO
),5.78(1H,m,CH=CCl),
6.83(2H,d,Ar),6.87(1H,d,Ar).
13C-NMR(50MHz,CDCl3)δ:21.32,(=CC1-CH3),24.08(CH-CH3),
55.84(OCH3),64.10(OCH2),77.05(Ar-CHO
),108.92(C-2),110.91(C-5),
118.74(C-6)124.43(CH=CCl)134.0
(CH=CCl),135.89(C-1),148.49和
149.23(C-3和C-4).5.)1-[1-(丁-2-炔氧基乙基)-3-甲氧基-4-羟基苯
4.0g(23.6mmol)1-(3-甲氧基-4-羟基苯基)乙醇溶解于4.0g 2-丁炔醇中,于室温搅拌下,向该溶液中加入8.0ml 1w/w%HCl-50w/w%CaCl2溶液。混合物搅拌过夜。反应通过TLC(洗脱剂:正乙烷-乙酸乙酯7∶3;Rf=0.19)跟踪。向反应混合物中加入***,直到油状有机相溶解。然后用1M NaOH溶液中和混合物,分离两相,水层用***萃取两次,合并有机相层,依次用水和饱和氯化钠溶液洗涤,经MgSO4干燥后,过滤并蒸发。产率4.8g(92.0%),稠油GC(CP 9000,CP-SIL-5CB 60mx 0.53mm,5ml/min N2 FID,250℃):tR=4.3min,<93%IR(CHCl3,cm-1)υ:3668,3540,2973,2923,2858,2424,2376,2233,
1729,1610,1512,1465,1453,1433,1372,1344,1320,
1268,1235,1186,1162,1128,1111,1082,1036,1005,
970,913,886,859,822,698,645,598.1H-NMR(200MHz,CDCl3)δ:1.45(3H,d,J=6.5Hz,CH-CH3),1.84(3H,t,
J=2.2Hz≡C-CH3),3.82和4.01(2H,ABX3,
JAB=15.0Hz,JAX=JBX=2.3Hz,≡C-CH2-O),
3.88(3H,s,OCH3),4.53(2H q,J=6.5Hz,
Ar-CHO),6.76-6.89(3H,m,芳氢).13C-NMR(50MHz,CDCl3)δ:3.57(≡C-CH3),23.76(CH-CH3),55.83(
O-CH3),55.89(≡C-CH2O),75.35(≡C-CH2),
76.40(Ar-CH-CH3),81.91(≡C-CH3),
108.39(C-2),114.03(C-5),119.73(C-6),
134.60(C-1),145.15(C-4),146.75(C-3).6.)3,4-二甲氧基-1-[1-(戊-3-炔氧基)乙基]苯
在装有搅拌器的烧瓶中,放入1.5g(8.23mmol)α-甲基-3,4-二甲氧基苄醇和1.4g(16.46mmol)3-戊炔-1-醇,向该混合物中快速加入3.0ml 50w/v%氧化钙-1w/w%盐酸溶液。混合物室温下搅拌过夜,然后用***稀释,混合物用几滴1M氢氧化钠溶液中和。分离两相,水相用***充分萃取,合并的有权相用饱和氯化钠溶液洗涤,干燥并蒸发。产率:1.9g(93%)GC(CP 9000,CP-SIL-5CB,60mx 0.53mm,5ml/min N2,FID,250℃)tR=5.0min,约.93.2%IR(CHCl3,cm-1)υ:2995,2974,2957,2864,2838,1607,1595,1510,1465,
1260,1163,1142,1098,1027.1H-NMR(200MHz,CDCl3)δ:1.44(3H,d,J=6.4Hz,CH-CH3),1.75(3H,t,
J=2.5Hz,CH3-C≡),2.37(2H,m,CH2-C≡)
3.38(2H,t,J=7.2Hz)3.87和3.89(共6H,
每峰,OCH3),4.38(2H,q,J=6.4Hz,Ar-CHO
),6.83(2H,d,芳氢),
6.90(1H,s,芳氢).13C-NMR(50MHz,CDCl30δ:3.42,(CH3-C≡),20.27(OCH2-CH2),24.07
(CH-CH3),55.78és55.85(OCH3),67.04
(OCH2-CH2),75.93和77.78(Ar-CH-CH3,
C≡C两个信号重叠),108.92(C-2),110.83
(C-5)118.52(C-6),13634(C-1),148.33(C-
3),149.13(C-4).7.)1-[1-(3-丁炔-2-基氧基)乙基]-3,4-二甲氧基苯
在装有搅拌器的烧瓶中,放入3.0g(0.0164mmol)α-甲基-3,4-二甲氧基苄醇和3.46g(0.0493mmol)3-丁炔-1-醇,向该混合物中快速加入1.5ml 50w/v%氧化钙-1w/w%盐酸溶液。混合物室温下搅拌过夜,然后用10ml***稀释,混合物用几滴1M氢氧化钠溶液中和。分离两相,水相用***充分萃取,合并的有权相用饱和氯化钠溶液洗涤,干燥并蒸发。残留物用色谱柱提纯(洗脱剂:己烷-乙酸乙酯4∶1Rf=0.41和0.36)两种非对映异构体(苏式-赤式)被部分分离:非极性(主要)为α-异构体,1.9g,60-40混合物0.76g,极性为β-异构体,0.32g,两异构体比例,根据分离量计算:约3.7∶1.产率:2.98g(0.0127mol,77.6%)GC(CP 9000,CP-SIL-5CB,60mx 0.53mm,5ml/min N2,FID 250℃):α-异构体tR=3.4min,约97.27%,β异构体:tR=3.58min,约94.26%。α异构体:IR(CHCl3,cm-1)υ:3306,2981,2934,2838,1608,1595,1509,1465,
1464,1260,1168,1141,1098,1048,963,910,860,
635.1H-NMR(200MHz,CDCl3)δ:1.39(3H,d,J=6.6Hz,≡CH-CH3),1.46(3H,
d,J=6.5Hz,Ar-CH-CH3),2.41(1H,d,
J=2Hz≡CH),3.87和3.89(共6H,每峰,
OCH3),3.89(1H,qd,J=2,6.6Hz,≡CCH),
4.75(2H,q,J=6.5Hz,Ar-CH-CH3),6.80-
6.89(3H,m,芳氢).13C-NMR(50MHz,CDCl3)δ:22.19,(≡CCH-CH3),24.15(Ar-CH-CH3),
55.82(OCH3),61.78(≡C-CHO),72.44和
75.17(≡CH和Ar-CHO),84.11(≡C-CH),
109.06(C-2),110.89(C-5),118.94(C-6),
135.50(C-1),148.49(C-3)149.14(C-4).β-异构体:IR(CHCl3,cm-1)υ:3307,2975,2935,2838,1607,1595,1511,1466,1454,
1261,1165,1142,1094,1041,961,910,862,638.1H-NMR(200MHz,CDCl3)δ:1.44(6H,d,J=6.5Hz,≡CH-CH3和Ar-CH-CH3
),2.355(1H,d,J=2Hz≡CH),3.87和
3.89(共6H,每峰,OCH3),4.23(1H,qd,
J=2,6.5Hz,≡CCH),4.66(2H,q,J=6.5Hz,
Ar-CH-CH3),6.79-6.96(3H,m,芳氢).13C-NMR(50MHz,CDCl3)δ:21.83,(≡CCH-CH3),22.64(Ar-CH-CH3),
55.79和55.86(OCH3),62.53(≡CH-CHO)
72.26和75.10(≡CH和Ar-CHO),84.40
(C-CH),109.43(C-2),110.79(C-5),
118.51(C-6),136.19(C-1),148.33(C-3),
148.96(C-4).8.)1-[1-(丙-2-烯氧基)乙基]-3,4-二甲氧基苯,(1-(3’,4’-二甲氧基苯基)乙基烯丙基醚)
在装有搅拌器的烧瓶中放入3.0g(0.0164mol)2-甲基-3,4-二甲氧基苄醇和1.9克烯丙醇,向该混合物中快速加入1.5ml 50w/v%氯化钙-1w/w%盐酸溶液。混合物室温下搅拌过夜,用***稀释,并用几滴1M氢氧化钠溶液中和,分离两相,水相用***充分萃取。合并的有机相用饱和氯化钠溶液洗涤,干燥并蒸发。产率:3.0g(82.4%)GC(CP 9000,CP-SIL-5CB,60mx 0.53mm,5ml/min N2,FID,250℃)tR=3.4min约90.3%。IR(CHCl3,cm-1)υ:3079,2996,2973,2933,2860,2838,1607,1595,1510,
1465,1443,1419,1311,1260,1164,1141,1089,1027,
996,928,860.1H-NMR(200MHz,CDCl3)δ:1.45(3H,d,J=6.4Hz,CH3),3.83AB
mid.(2H,ABdt,JAB=12.7Hz,J=1.3,6.0Hz,
OCH2CH=),3.89和3.87(共6H,每峰,
OCH3),4.41(2H,qd,J=2,6.4Hz,CH-O),
5.11-5.29(2H,m),5.81-6.0(1H,m),6.83(2H,
s),6.89(1H,s)。13C-NMR(50MHz,CDCl3)δ:24.0(CH-CH3),55.77(OCH3),69.17
(OCH2=),108.94(C-2),110.82(C-5),
116.58(CH-CH2),118.58(C-6),135.0(C-1),
136.26(CH=CH2),148.29和149.11(C-3和
C-4)。9.)1-[1-(丁-2-炔氧基)乙基]萘(1-(1-萘基)乙基丁-2-炔基醚)
在装有磁搅拌器、冷凝器和装填氯化钙的干燥管的烧瓶中,加入α-甲基-1-萘基甲醇(0.86g,5mol)和2-丁炔-1-醇(0.7g,10mol),然后溶解于15ml二氯乙烷。室温搅拌条件下,向混合物加入二氯化锌(0.68g,5mol)。反应伴有颜色特征变。反应24小时后,分离反应中形成的水相部分,有机相用3×30ml饱和氯化钠溶液洗涤,干燥并蒸发。粗产物(1.2g)用色谱柱提纯。产率:0.8g(3.57mmol,71%).GC 95%.IR(CHCl3,cm-1)υ:3052,2977,2921,2856,1596,1509,1444,1371,1095,
1078.1H-NMR(200MHz,CDCl3)δ:1.67(3H,d,J=6.5Hz,CH3-CH),1.87(3H,t,
J=2.3Hz,≡C-CH3),2.96和4.15(共
2H,ABX,JAB=15.0Hz,JAX=JAB=2.3Hz,
OCH2-C≡C),5.40(1H,q,J=6.5Hz,C10H7-CH-O
),7.51(3H,m),7.61(1H,d,J=6.8Hz),
7.79(1H,d,J=8.1Hz),7.89(1H,dd,J=7.9,
1.8Hz),8.22(1H,d,J=8.1Hz)13C-NMR(50MHz,CDCl3)δ:3.64(C≡CH-CH3),22.96(CH3-CH),56.37
(O-CH2-C≡C),74.29(CH3-CH),75.36和
82.14(C≡C),123.26(C-8),123.52,125.50,
125.85,127.92,128.83,130.78(C-8a),
133.88(C-4a),138.42(C-1)。10.)制备丁-2-炔基苄基醚的通用步骤
在装有搅拌器的烧瓶中放入10mmol下列苄醇和1.2g(20mmol)-丁炔-1-醇,向该混合物中快速加入1.5ml 50w/v%氯化钙-1w/w%盐酸溶液。混合物室温下搅拌过夜,反应用TLC跟踪。混合物用***稀释,并用几滴1M氢氧化钠溶液中和,分离两相,水相用***充分萃取。合并的有机相用饱和氯化钠溶液洗涤,干燥并蒸发。得到的产物用色谱柱提纯a.)原料苄醇:3,4-二甲氧基苄醇产物:(3,4-二甲氧基苄基)丁-2-炔基醚产率:85%纯度(GC)94%IR(CHCl3,cm-1)υ:3025,3000,2956,2937,2921,2855,2839,
1607,1595,1512,1466,1443,1420,1158,
1140,1070,1028。1H-NMR(200MHz,CDCl3)δ:1.84(3H,t,J=2.3Hz,C≡CH3),3.83和3.85
(共6H,CH3O),4.08(2H,q,J=2.3Hz,
OCH2C≡C-),4.48(2H,s,芳基-CH2),6.77-
6.88(3H,m,芳基)13C-NMR(50MHz,CDCl3)δ:3.45(C≡CH-CH3),55.67和55.71(CH3O),
57.31(OCH2C≡C-),71.22(芳基-CH2),75.0
(C≡C-CH3),82.42(C≡C-CH3),110.76(C-2),
111.23(C-5),120.54(C-6),130.05(C-1),
148.58(C-4),148.88(C-3)。b.)原料苄醇:(3,4-二甲氧基苯基)二甲基甲醇产物:1-(3,4-二甲氧基苯基)-1-甲基乙基2-(丁-2-炔基)醚产率:85%纯度(GC):94%c.)原料苄醇:1-[1-羟基丙基]-3,4-二甲氧基苯产物:1-[1-(2-丁炔氧基)-丙基]-3,4二甲氧基苯产率:87%纯度(GC):CP 9000,CP-SIL-5CB,60mx 0.53μm,5ml/minN2,FID,220℃ tR=13.0min,>95%.IR(CHCl3,cm-1)υ:2999,2959,2935,2875,2856,2839,2240,1608,1595,
1513,1465,1261,1234,1162,1142,1061,1028.1H-NMR(200MHz,CDCl3)δ:0.84(3H,t,J=7.4Hz,CH2CH3),1.65和1.83
(共2H,每峰m,CH2CH3),1.82(3H,t,
J=2.3Hz,C≡CCH3),3.84和3.86(总共6H,
s,CH3O),3.78和3.99(总共2H,ABX3
JAB=15.0Hz,JAX=JBX=2.3Hz OCH2),4.22
(1H,t,J=6.8Hz,CH-O),6.80-6.83(3H,m,
芳基)(乙醇乙酯信号在1.22(t),2.01(s)和
4.08(q)ppm).13C-NMR(50MHz,CDCl3)δ:3.55(C≡CH-CH3),10.23(CH2CH3),30.58
(CH2CH3),55.77(OCH3),56.03(OCH2),
75.41(C≡C-CH3),81.71(C≡C-CH3),82.24
(CH-O),109.34,110.64(C-2,C-5),119.63(C-
6),133.95(C-1),148.44和149.09(C-3,C-
4).d.)原料苄醇:1-[1-羟基-2-甲基丙基]-3,4-二甲氧基苯产物:1-[1-(2-丁炔氧基)-2-甲基丙基]-3,4-二甲氧基
苯产率:85%纯度(GC):CP 9000,CP-SIL-5CB,60mx 0.53μm,5ml/minN2,FID,220℃ tR=14.0.0min,>91%。IR(CHCl3,cm-1)υ:3029,2995,2958,2937,2871,2857,2839,2238,1606,
1595,1510,1466,1443,1420,1263,1238,1157,1142,
1062,1028.1H-NMR(400MHz,CDCl3)δ:0.65和0.97(共6H,每峰d,J=6.8Hz,
CH(CH3)2),1.77(3H,t,J=2.3Hz,C≡C-CH3),
1.87(1H,m,CH(CH3)2),3.80和3.81(共6H,
每峰,OCH3)2),3.71和3.95(共2H,ABX3,
JBX3,JAB=15.0Hz,JAX=JBX=2.3Hz,OCH2),
3.90(1H,d,J=8.1Hz,CH-O),6.68-6.78
(3H,m,芳氢).13C-NMR(50MHz,CDCl3)δ:3.39(C≡C-CH3),18.87和19.16((CH(CH3)2),
34.32(CH2(CH3)2),55.61(OCH3),
56.11(OCH2),75.44(C≡C-CH3),81.37
(C≡C-CH3),86.25(CHO),109.76(C-5),
110.32(C-2),120.19(C-6),132.91(C-1),
148.24(C-4)és 148.80(C-3).e.)原料苄醇:5-[1-羟基乙基]-1,3-苯并间二氧杂环戊烯产物:5-[1-(2-丁炔氧基)乙基]-1,3-苯并间二氧杂环戊烯产率:84%纯度(GC):94%IR(CHCl3,cm-1)υ:2979,2921,2882,1609,1502,1486,1441,1079,1041,
9411H-NMR(400MHz,CDCl3)δ:1.41(3H,d,J=6.5Hz,CHCH3),1.83(3H,t,
J=2.3Hz,C≡C-CH3),3.80和3.99(共,2H,
ABX3,JAB=15Hz,JAX=JBX=2.3Hz,OCH2),
4.51(1H,q,J=6.5Hz,CHCH3),5.92(2H,
AB,OCH2O),6.74(2H,AB,H-6,H-7),
6.83(1H,s,H-4).13C-NMR(50MHz,CDCl3)δ:3.50(C≡C-CH3),23.67CHCH3),55.80
(OCH2)75.18(C≡C-CH3),76.16(CH-O),
81.93(C≡C-CH3),100.84(OCH2O),106.74
107.88(C-4,7),119.90(C-6),136.63(C-5),
146.94和147.77(C-3a,7a)f.)原料苄醇:1-[1-羟基乙基]-3,4-二乙氧基苯产物:1-[1-(2-丁炔氧基)-3,4-二乙氧基苯产率:86%纯度:93%g.)原料苄醇:1-[1-羟基乙基]-3,4-二甲氧基-6-丙基苯产物:1-[1-(2-丁炔氧基)-3,4-二甲氧基-6-基苯产率:73%纯度(GC):CP 9000,CP-SIL-5CB,60mx 0.53μm,5ml/min N2,
FID,250℃ tR=6.7min,kb>95.4%.IR(CHCl3,cm-1)υ:2961,2933,2873,2331,1610,1511,1466,1261,1132,
1098,1047.1H-NMR(400MHz,CDCl3)δ:0.96(3H,t,J=7.3Hz,CH3),1.41(3H,d,
J=6.4Hz,CH3CHO),1.58((2H,六重峰,
J=7.4Hz,CH2-CH3),1.81(3H,t,J=2.5
Hz,CH3-C≡),2.54(2H,m,CH2-Ar),2.78和
3.98(2H,ABX3,JAB=15.0Hz,JAX=JBX-2.3
Hz,≡C-CH2O),3.83(6H,s,OCH3),4.86(H,
q,J=6.5Hz,Ar-CHO),6.60and 6.91(2H,s,
芳氢).13C-NMR(50MHz,CDCl3)δ:3.46(≡C-CH3),14.05(CH3,23.70和
24.97(CH2-CH3)和CH3CHOH),34.03(芳
基-CH2),55.62 55.69和55.80(OCH3和
≡C-CH2O)71.60(Ar-CH-CH3),75.46(≡C-CH2
),81.84(≡C-CH3),108.45,112.32(C-2,
C-5),132.29,132.33(C-6,C-1),147.60,
147.79(C-4,C-3).11).5-[(2-丁炔氧基)甲基]-1,3-苯并间二氧杂环戊烯
在装有磁搅拌器、冷凝器和装填氯化钙的干燥管的烧瓶中放入3.0g(13.95mmol)3,4-亚甲二氧基苄溴、2.0g(27.9mmol)-2-丁炔-1-醇和50ml二氯乙烷。加入氧化锌(II)(1.1g,13.5mmol)后,悬浮液室温下搅拌1小时。反应们有颜色特征变化。随后过滤混合物,滤液蒸发。残留油溶于50ml***,用2×10ml水洗涤,干燥并蒸发。
产率:2.3g(11.2mmol,80.7%),GC 82%IR(CHCl3,cm-1)υ:2997,2964,2921,2888,2376,1609,1503,1491,1445,
1251,1099,1070,1042,937,865,8101H-NMR(400MHz,CDCl3)δ:1.87(3H,t,J=2.3Hz,Me),4.10(2H,q,
J=2.3Hz,O-CH2-C≡),4.47((2H,s,O-CH2-Ar
),5.94(2H,s,O-CH2O),6.76(1H,d,
J=8Hz,H-7),6.81(1H,dd,J=8.15Hz,H-
6),6.86(1H,J=1.5Hz,H-4).13C-NMR(100MHz,CDCl3)δ:3.52(Me),57.29(O-CH2-C≡),71.15(
O-CH2-Ar),82.54(CH3-C≡),100.9C-2,
107.95,108.71(C-4,7),121.66,(C-6),
131.39(C-5),147.15 147.66(C3a,c-7a).12).1-[(2-丁炔氧基)甲基]萘
在装有磁搅拌器、冷凝器和装填氯化钙的干燥管的烧瓶中放入1.0g(4.52mmol)溴甲基萘、0.63g(9mmol)2-丁炔-1-醇和10ml二氯乙烷。加入氧化锌(II)(4.01g,4.52mmol)后,悬浮液室温下搅拌1小时然后,回流1小时。反应们有颜色特征变化。随后过滤混合物,滤液蒸发。残留油溶于15ml之醚,用2×50ml水洗涤,干燥并蒸发。产物用色谱柱提纯。纯度(GC)59%IR(CHCl3,cm-1)υ:3044,3001,2945,2920,2854,1598,1509,1356,1166,
1086,10671H-NMR(400MHz,CDCl3)δ:1.93(3H,t,J=2.3Hz,C≡C-CH3),4.22(2H,
q,J=2.1Hz,O-CH2-C≡C),5.06((2H,s,
C10H7-CH2-O),7.45(1H,t,J=8Hz),7.53
(3H,m),7.84(1H,d,J=8.1Hz),7.88(3H,m),
7.88(1H,d,J=7.7Hz),8.19(1H,d,
J=8.2Hz)13C-NMR(100MHz,CDCl3δ:3.6(C≡CH3),57.71(O-CH2-C≡C),69.72
C10H7-CH2-O),75.10(O-CH2-C≡C),82.76
(O-CH2-C≡C),124.03,125.10,125.72,
126.19,126.85,128.43,128.72,131.79,(C-
8a),133.06,133.70.13.)5-[2-(2-丁氧乙氧基)乙氧基甲基]-6-丙基-1,3-苯并间二氧杂环戊烯,PBOa).
在装有磁搅拌器、冷凝器和装填氯化钙的干燥管的烧瓶中放入2.98g(14.02mmol)5-氯甲基二氢基樟脑、2.72g(16.82mmol)二甘醇单丁基醚和20ml二氯乙烷。加入氧化锌(II)(1.22g,15.0mmol)后,悬浮液室温下搅拌24小时。反应用TLC法跟踪,原料苄氯消失后,过滤混合物,蒸发滤液。残留油浮于25ml***,用2×50ml水洗涤,干燥并蒸发。产物真空蒸馏,BP:180℃/1Hgmm。本物质与标示的PBO相同。产率4.0g(90%),纯度(GC)98%。b).
在装有磁搅拌器、冷凝器和装填氯化钙的干燥管的烧瓶中放入2.12g(10.0mmol)5-氯甲基二氢基樟脑、2.42g(15.0mmol)二甘醇一丁基醚。加入氧化锌(II)(0.97g,15.0mmol)后,悬浮液室温下搅拌24小时。反应用TLC法跟踪,原料苄氯消失后,用***稀释混合物,过滤,滤液,用2×50ml水洗涤,干燥并蒸发。产物真空蒸馏,BP:180℃/1Hgmm。本物质与标示的PBO相同。产率2.8g(91%),纯度(GC)98%。
Claims (17)
其中Ar代表芳族或含一或多个杂原子的杂环部分,任选被一或多个C1-4烷氧基、亚甲二氧基、C1-4烷基、卤素、C1-4卤代烷基或硝基取代,和/或与一个苯环稠合;
R1和R2独立表示氢、C1-4烷基、C1-4卤代烷基、C2-4链烯基、苯基、取代苯基、C3-6环烷基基团;
R3表示C3-6链炔基,任意被一或多个C1-6烷基、C3-6链烯基、C3-6链炔基、C1-6卤代烷基或卤原子取代;或是一个C1-4烷氧基-C1-4烷氧基-C1-4烷基基团,包括将通式II化合物与1-3摩尔当量的通式III醇在酸、路易斯酸、金属氧化物或金属碳酸盐存在下反应,
其中X是指羟基,卤素或磺酸酯离去基团,
R3-OH III其中各取代基定义同上,得到的通式I的醚分离出来,若需要,可通过加入碱和/或抗氧剂来稳定。
2.按权利要求1的方法,其特征在于所述酸用0.01-3摩尔当量强无机或有机酸。
3.按权利要求1的方法,其特征在于所述酸是盐酸、硫酸、高氯酸或芳族磺酸。
4.按权利要求1的方法,其特征在于反应在盐水溶液中进行。
5.按权利要求4的方法,其特征在于所述盐水溶液是氯化钠、氯化钙、氯化镁、氯化锌溶液。
6.按权利要求1的方法,其特征在于反应在用无机盐饱和的10w/w%酸的水溶液中进行,反应温度为-20到+30℃。
7.按权利要求1的方法,其特征在于所述路易酸是用0.01-3摩尔当量的氯化锌(II)或芳族磺酸,且反应在非极性的非质子溶剂中进行。
8.按权利要求7的方法,所述芳族磺酸是苯磺酸或对甲苯磺酸。
9.按权利要求7的方法,其特征在于所述非极性非质子溶剂是二氯乙烷,反应在-30到+40℃下进行。
10.按权利要求1的方法,其特征在于所述金属氧化物是用0.01-3摩尔当量的氧化锌,反应在无溶剂下进行。
11.按权利要求1的方法,其中所述金属氧化物是0.01-3摩尔当量的氧化锌且反应是在非极性非质子溶剂存在下进行的。
12.按权利要求11的方法,其中非极性非质子溶剂是二氯乙烷。
13.按权利要求1的方法,其中所述金属碳酸盐是碳酸锌且反应在无溶剂存在下进行。
14.按权利要求1的方法,其中所述金属碳酸盐是碳酸锌且反应在非极性质子溶剂存在下进行。
15.按权利要求14的方法,其中非极性非质子溶剂是二氯乙烷。
16.按权利要求1的方法,还包括回收过量的醇。
17.按权利要求6的方法,其中无机盐是氯化钠、氯化钙或氯化镁。
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HUP9603179 | 1996-11-18 |
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FR2788269B1 (fr) | 1999-01-08 | 2001-02-09 | Rhodia Chimie Sa | Procede de preparation d'un ether de type benzylique |
US7838708B2 (en) | 2001-06-20 | 2010-11-23 | Grt, Inc. | Hydrocarbon conversion process improvements |
WO2005021468A1 (en) | 2003-07-15 | 2005-03-10 | Grt, Inc. | Hydrocarbon synthesis |
US20050171393A1 (en) | 2003-07-15 | 2005-08-04 | Lorkovic Ivan M. | Hydrocarbon synthesis |
US8642822B2 (en) | 2004-04-16 | 2014-02-04 | Marathon Gtf Technology, Ltd. | Processes for converting gaseous alkanes to liquid hydrocarbons using microchannel reactor |
US8173851B2 (en) | 2004-04-16 | 2012-05-08 | Marathon Gtf Technology, Ltd. | Processes for converting gaseous alkanes to liquid hydrocarbons |
US20080275284A1 (en) | 2004-04-16 | 2008-11-06 | Marathon Oil Company | Process for converting gaseous alkanes to liquid hydrocarbons |
US7244867B2 (en) | 2004-04-16 | 2007-07-17 | Marathon Oil Company | Process for converting gaseous alkanes to liquid hydrocarbons |
US7674941B2 (en) | 2004-04-16 | 2010-03-09 | Marathon Gtf Technology, Ltd. | Processes for converting gaseous alkanes to liquid hydrocarbons |
US20060100469A1 (en) | 2004-04-16 | 2006-05-11 | Waycuilis John J | Process for converting gaseous alkanes to olefins and liquid hydrocarbons |
US20060229228A1 (en) * | 2005-04-11 | 2006-10-12 | Zachary John Anthony Komon | Method of making alkoxylates |
JP5275817B2 (ja) | 2006-02-03 | 2013-08-28 | ジーアールティー,インコーポレイティド | ハロゲンからの軽質ガスの分離 |
CA2641348C (en) | 2006-02-03 | 2014-12-23 | Grt, Inc. | Continuous process for converting natural gas to liquid hydrocarbons |
US8921625B2 (en) | 2007-02-05 | 2014-12-30 | Reaction35, LLC | Continuous process for converting natural gas to liquid hydrocarbons |
WO2008148113A1 (en) | 2007-05-24 | 2008-12-04 | Grt, Inc. | Zone reactor incorporating reversible hydrogen halide capture and release |
US8282810B2 (en) * | 2008-06-13 | 2012-10-09 | Marathon Gtf Technology, Ltd. | Bromine-based method and system for converting gaseous alkanes to liquid hydrocarbons using electrolysis for bromine recovery |
WO2010121975A1 (en) * | 2009-04-22 | 2010-10-28 | Akzo Nobel Chemicals International B.V. | Method for preparation of and compositions of low foam, non-gelling, surfactants |
EP2289889A1 (en) | 2009-08-18 | 2011-03-02 | Endura S.p.a. | Substituted alkynyl phenoxy compounds and their uses |
US8367884B2 (en) | 2010-03-02 | 2013-02-05 | Marathon Gtf Technology, Ltd. | Processes and systems for the staged synthesis of alkyl bromides |
US8198495B2 (en) | 2010-03-02 | 2012-06-12 | Marathon Gtf Technology, Ltd. | Processes and systems for the staged synthesis of alkyl bromides |
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US8815050B2 (en) | 2011-03-22 | 2014-08-26 | Marathon Gtf Technology, Ltd. | Processes and systems for drying liquid bromine |
US8436220B2 (en) | 2011-06-10 | 2013-05-07 | Marathon Gtf Technology, Ltd. | Processes and systems for demethanization of brominated hydrocarbons |
US8829256B2 (en) | 2011-06-30 | 2014-09-09 | Gtc Technology Us, Llc | Processes and systems for fractionation of brominated hydrocarbons in the conversion of natural gas to liquid hydrocarbons |
US8802908B2 (en) | 2011-10-21 | 2014-08-12 | Marathon Gtf Technology, Ltd. | Processes and systems for separate, parallel methane and higher alkanes' bromination |
US9193641B2 (en) | 2011-12-16 | 2015-11-24 | Gtc Technology Us, Llc | Processes and systems for conversion of alkyl bromides to higher molecular weight hydrocarbons in circulating catalyst reactor-regenerator systems |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4434823A1 (de) * | 1994-09-29 | 1996-04-04 | Merck Patent Gmbh | Verfahren zur Herstellung von Hydroxybenzylalkylethern |
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BE1007421A3 (nl) | 1993-08-20 | 1995-06-13 | Tessenderlo Chem Nv | Werkwijze voor het selectief alkyleren van een alifatische alcohol tegenover een fenolverbinding. |
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Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4434823A1 (de) * | 1994-09-29 | 1996-04-04 | Merck Patent Gmbh | Verfahren zur Herstellung von Hydroxybenzylalkylethern |
Non-Patent Citations (2)
Title |
---|
JORG.CHEM.1988.VOL 53,NO.18,P.4263-4273 1988-01-01 josem.saa,etc,metalation of phinols,synthesis of benzqhuinones by the oxidative degradation approac * |
JORGCHEM1987-VOL 52.NO,17P3917-3919 1987-01-01 DIRECT SYNTHESIS OF ETHERS VIA ZINC CHLORIDE MEDIATED ETHERIFICATION OF ALCOHOLS IN DICHLOROETHANE * |
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