CN107043396B - 一种三十烷醇的制备方法 - Google Patents
一种三十烷醇的制备方法 Download PDFInfo
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- CN107043396B CN107043396B CN201710406865.1A CN201710406865A CN107043396B CN 107043396 B CN107043396 B CN 107043396B CN 201710406865 A CN201710406865 A CN 201710406865A CN 107043396 B CN107043396 B CN 107043396B
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- triacontanol
- tertiary butyl
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- REZQBEBOWJAQKS-UHFFFAOYSA-N triacontan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO REZQBEBOWJAQKS-UHFFFAOYSA-N 0.000 title claims abstract description 103
- 238000002360 preparation method Methods 0.000 title claims description 24
- HFJRKMMYBMWEAD-UHFFFAOYSA-N dodecanal Chemical compound CCCCCCCCCCCC=O HFJRKMMYBMWEAD-UHFFFAOYSA-N 0.000 claims abstract description 41
- MEIYNORBWAYVQZ-UHFFFAOYSA-M [PH4+].[Br-].C(CCCCCCCCCCCCCCCCC)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1.[Br-] Chemical compound [PH4+].[Br-].C(CCCCCCCCCCCCCCCCC)[P+](C1=CC=CC=C1)(C1=CC=CC=C1)C1=CC=CC=C1.[Br-] MEIYNORBWAYVQZ-UHFFFAOYSA-M 0.000 claims abstract description 23
- LQZZUXJYWNFBMV-UHFFFAOYSA-N dodecan-1-ol Chemical compound CCCCCCCCCCCCO LQZZUXJYWNFBMV-UHFFFAOYSA-N 0.000 claims abstract description 23
- GHLKSLMMWAKNBM-UHFFFAOYSA-N dodecane-1,12-diol Chemical compound OCCCCCCCCCCCCO GHLKSLMMWAKNBM-UHFFFAOYSA-N 0.000 claims abstract description 23
- NLAGNNORBYGNAV-UHFFFAOYSA-N isotriacontane Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCC(C)C NLAGNNORBYGNAV-UHFFFAOYSA-N 0.000 claims abstract description 18
- 239000002994 raw material Substances 0.000 claims abstract description 13
- GDOPTJXRTPNYNR-UHFFFAOYSA-N methyl-cyclopentane Natural products CC1CCCC1 GDOPTJXRTPNYNR-UHFFFAOYSA-N 0.000 claims abstract description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 42
- 239000000243 solution Substances 0.000 claims description 37
- 239000002904 solvent Substances 0.000 claims description 35
- 239000002585 base Substances 0.000 claims description 32
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 29
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 27
- 239000000047 product Substances 0.000 claims description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 22
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- 239000003208 petroleum Substances 0.000 claims description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 13
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 12
- 238000010992 reflux Methods 0.000 claims description 12
- WSULSMOGMLRGKU-UHFFFAOYSA-N 1-bromooctadecane Chemical compound CCCCCCCCCCCCCCCCCCBr WSULSMOGMLRGKU-UHFFFAOYSA-N 0.000 claims description 11
- 239000012074 organic phase Substances 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 claims description 10
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 9
- 239000003054 catalyst Substances 0.000 claims description 9
- 238000001816 cooling Methods 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 9
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 claims description 9
- 239000007787 solid Substances 0.000 claims description 9
- 238000003756 stirring Methods 0.000 claims description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 claims description 8
- 239000003513 alkali Substances 0.000 claims description 8
- 238000012544 monitoring process Methods 0.000 claims description 8
- 238000002390 rotary evaporation Methods 0.000 claims description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 8
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 7
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 7
- 235000019441 ethanol Nutrition 0.000 claims description 7
- 239000003921 oil Substances 0.000 claims description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- 239000012230 colorless oil Substances 0.000 claims description 6
- 150000002460 imidazoles Chemical class 0.000 claims description 6
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 claims description 6
- 239000011574 phosphorus Substances 0.000 claims description 6
- 229910052698 phosphorus Inorganic materials 0.000 claims description 6
- 238000001953 recrystallisation Methods 0.000 claims description 6
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 6
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims description 6
- LGZDNJBUAAXEMN-UHFFFAOYSA-N 1,2,2,3-tetramethyl-1-oxidopiperidin-1-ium Chemical class CC1CCC[N+](C)([O-])C1(C)C LGZDNJBUAAXEMN-UHFFFAOYSA-N 0.000 claims description 5
- 238000007239 Wittig reaction Methods 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 239000005457 ice water Substances 0.000 claims description 5
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 claims description 5
- 229910052943 magnesium sulfate Inorganic materials 0.000 claims description 5
- 238000005406 washing Methods 0.000 claims description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 claims description 4
- 239000005708 Sodium hypochlorite Substances 0.000 claims description 4
- 239000000460 chlorine Substances 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 235000019341 magnesium sulphate Nutrition 0.000 claims description 4
- 239000000203 mixture Substances 0.000 claims description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 claims description 4
- 230000003647 oxidation Effects 0.000 claims description 4
- 238000007254 oxidation reaction Methods 0.000 claims description 4
- 238000001556 precipitation Methods 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 3
- 239000006227 byproduct Substances 0.000 claims description 3
- 238000010828 elution Methods 0.000 claims description 3
- 239000011521 glass Substances 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 3
- 239000003223 protective agent Substances 0.000 claims description 3
- 238000010791 quenching Methods 0.000 claims description 3
- 230000000171 quenching effect Effects 0.000 claims description 3
- 239000013557 residual solvent Substances 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 239000011780 sodium chloride Substances 0.000 claims description 3
- 238000001291 vacuum drying Methods 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 239000002253 acid Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims description 2
- 239000004519 grease Substances 0.000 claims description 2
- 238000005984 hydrogenation reaction Methods 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 125000006239 protecting group Chemical group 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 239000000725 suspension Substances 0.000 claims description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical group C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 2
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Substances C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 2
- 238000010792 warming Methods 0.000 claims description 2
- 229960000549 4-dimethylaminophenol Drugs 0.000 claims 2
- 239000003463 adsorbent Substances 0.000 claims 2
- 239000003960 organic solvent Substances 0.000 claims 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N alpha-methyl toluene Natural products CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 claims 1
- 230000003197 catalytic effect Effects 0.000 claims 1
- 239000002024 ethyl acetate extract Substances 0.000 claims 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims 1
- 235000017557 sodium bicarbonate Nutrition 0.000 claims 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 1
- 239000008096 xylene Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 17
- 238000003786 synthesis reaction Methods 0.000 abstract description 10
- 230000008569 process Effects 0.000 abstract description 8
- 239000000126 substance Substances 0.000 abstract description 7
- -1 and simple process Substances 0.000 abstract description 6
- 239000003317 industrial substance Substances 0.000 abstract 1
- 238000011031 large-scale manufacturing process Methods 0.000 abstract 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
- 238000001460 carbon-13 nuclear magnetic resonance spectrum Methods 0.000 description 13
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 11
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 9
- 238000001157 Fourier transform infrared spectrum Methods 0.000 description 9
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 241000196324 Embryophyta Species 0.000 description 6
- 238000012790 confirmation Methods 0.000 description 6
- CNNRPFQICPFDPO-UHFFFAOYSA-N octacosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCO CNNRPFQICPFDPO-UHFFFAOYSA-N 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 235000013871 bee wax Nutrition 0.000 description 4
- 239000012166 beeswax Substances 0.000 description 4
- 230000000694 effects Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 229960002666 1-octacosanol Drugs 0.000 description 3
- 239000000284 extract Substances 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 238000006722 reduction reaction Methods 0.000 description 3
- QOEHNLSDMADWEF-UHFFFAOYSA-N I-Dotriacontanol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO QOEHNLSDMADWEF-UHFFFAOYSA-N 0.000 description 2
- 150000001299 aldehydes Chemical class 0.000 description 2
- 150000001336 alkenes Chemical class 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 238000010511 deprotection reaction Methods 0.000 description 2
- 238000006073 displacement reaction Methods 0.000 description 2
- QHMGJGNTMQDRQA-UHFFFAOYSA-N dotriacontane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCC QHMGJGNTMQDRQA-UHFFFAOYSA-N 0.000 description 2
- 229960004756 ethanol Drugs 0.000 description 2
- 238000000605 extraction Methods 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- IRHTZOCLLONTOC-UHFFFAOYSA-N hexacosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCO IRHTZOCLLONTOC-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 230000001965 increasing effect Effects 0.000 description 2
- 230000028161 membrane depolarization Effects 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- ZYURHZPYMFLWSH-UHFFFAOYSA-N octacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCCCCC ZYURHZPYMFLWSH-UHFFFAOYSA-N 0.000 description 2
- 230000004224 protection Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- TTZQKNSUDZZDJV-UHFFFAOYSA-N tert-butyl-chloro-dimethoxysilane Chemical compound CO[Si](Cl)(OC)C(C)(C)C TTZQKNSUDZZDJV-UHFFFAOYSA-N 0.000 description 2
- BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 2
- TYWMIZZBOVGFOV-UHFFFAOYSA-N tetracosan-1-ol Chemical compound CCCCCCCCCCCCCCCCCCCCCCCCO TYWMIZZBOVGFOV-UHFFFAOYSA-N 0.000 description 2
- KULACDNYICFKDP-UHFFFAOYSA-N CCCCCCCCCCCCCCCCCCC(C=CC=C1)=C1P(C1=CC=CC=C1)C1=CC=CC=C1.Br Chemical compound CCCCCCCCCCCCCCCCCCC(C=CC=C1)=C1P(C1=CC=CC=C1)C1=CC=CC=C1.Br KULACDNYICFKDP-UHFFFAOYSA-N 0.000 description 1
- DCSOPUDOZMRWRP-UHFFFAOYSA-N Cc1cc(C)cc([SiH2]Cl)c1 Chemical compound Cc1cc(C)cc([SiH2]Cl)c1 DCSOPUDOZMRWRP-UHFFFAOYSA-N 0.000 description 1
- ZNZYKNKBJPZETN-WELNAUFTSA-N Dialdehyde 11678 Chemical compound N1C2=CC=CC=C2C2=C1[C@H](C[C@H](/C(=C/O)C(=O)OC)[C@@H](C=C)C=O)NCC2 ZNZYKNKBJPZETN-WELNAUFTSA-N 0.000 description 1
- SNRUBQQJIBEYMU-UHFFFAOYSA-N Dodecane Natural products CCCCCCCCCCCC SNRUBQQJIBEYMU-UHFFFAOYSA-N 0.000 description 1
- 206010013786 Dry skin Diseases 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 206010020649 Hyperkeratosis Diseases 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
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000012271 agricultural production Methods 0.000 description 1
- 150000001298 alcohols Chemical class 0.000 description 1
- 125000001931 aliphatic group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000008827 biological function Effects 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- 230000019522 cellular metabolic process Effects 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- 238000005660 chlorination reaction Methods 0.000 description 1
- 229930002875 chlorophyll Natural products 0.000 description 1
- 235000019804 chlorophyll Nutrition 0.000 description 1
- ATNHDLDRLWWWCB-AENOIHSZSA-M chlorophyll a Chemical compound C1([C@@H](C(=O)OC)C(=O)C2=C3C)=C2N2C3=CC(C(CC)=C3C)=[N+]4C3=CC3=C(C=C)C(C)=C5N3[Mg-2]42[N+]2=C1[C@@H](CCC(=O)OC\C=C(/C)CCC[C@H](C)CCC[C@H](C)CCCC(C)C)[C@H](C)C2=C5 ATNHDLDRLWWWCB-AENOIHSZSA-M 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 229960000935 dehydrated alcohol Drugs 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
- 230000004069 differentiation Effects 0.000 description 1
- 125000000532 dioxanyl group Chemical group 0.000 description 1
- 239000002019 doping agent Substances 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 235000013399 edible fruits Nutrition 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002191 fatty alcohols Chemical class 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 108700039708 galantide Proteins 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 1
- 239000003630 growth substance Substances 0.000 description 1
- SKGCQRZZTHOERR-UHFFFAOYSA-N hexatriacontyl alcohol Natural products CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO SKGCQRZZTHOERR-UHFFFAOYSA-N 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000006317 isomerization reaction Methods 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- LGZXYFMMLRYXLK-UHFFFAOYSA-N mercury(2+);sulfide Chemical compound [S-2].[Hg+2] LGZXYFMMLRYXLK-UHFFFAOYSA-N 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- 230000029553 photosynthesis Effects 0.000 description 1
- 238000010672 photosynthesis Methods 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 230000008635 plant growth Effects 0.000 description 1
- 239000005648 plant growth regulator Substances 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
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- 230000004044 response Effects 0.000 description 1
- 239000004170 rice bran wax Substances 0.000 description 1
- 235000019384 rice bran wax Nutrition 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 150000004756 silanes Chemical class 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- MCJUNPPODVYJBD-UHFFFAOYSA-N triacontan-1-ol Chemical group CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO.CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO MCJUNPPODVYJBD-UHFFFAOYSA-N 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C29/00—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring
- C07C29/17—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds
- C07C29/175—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom not belonging to a six-membered aromatic ring by hydrogenation of carbon-to-carbon double or triple bonds with simultaneous reduction of an oxo group
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
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Abstract
一种利用有机合成制备高纯度三十烷醇的方法,属于有机合成领域。提供一种原料来源可靠、工艺简单、收率与纯度高、易于规模化生产的制备三十烷醇的方法。以1,12‑十二烷二醇为原料制备12‑叔丁基二甲基硅氧基十二醇,用TEMPO氧化成12‑叔丁基二甲基硅氧基十二醛,制备十八烷基三苯基溴化膦鎓盐,制备叔丁基二甲氧基三十烷氧基硅烷‑12‑烯,制备三十烷醇。原料全部是工业化学品,工艺简单、化学收率高、产品纯度高、易于工业化和对环境较友好。
Description
技术领域
本发明涉及一种三十烷醇的制备方法,属于有机合成领域。
背景技术
三十烷醇(Triacontanol)又称蜂花醇(Myricylalcohol),化学名称为1-三十烷醇(1-Triacontanol),分子量438,化学式C30H62O,是一种长链饱和脂肪醇。对光、空气、碱稳定,易于保存,几乎不溶于水,也难溶于冷乙醇、甲醇、苯,溶于氯仿、正己烷、乙醚和热苯等。1977年美国密斯根州立大学S. Ries教授等发现并证实三十烷醇对植物生长具有特殊的调节和控制作用,是一种天然存在的、适用范围相当广泛的植物生长调节剂。三十烷醇能促进作物生根、发芽、开花、结实,增强光合作用、提高叶绿素含量,可促进愈伤组织的生长分化,促进吸收矿物质,具有明显的增产效果。适用于多种作物、花卉、果树的种植。三十烷醇作为新型的天然植物生长调节剂,具有作用浓度低、生理效应强、反应速度快、低残留、无公害的优异特点。虽然到目前为止人类还未完全理解掌握三十烷醇的作用机制,M. Naeem等在2011年总结了三十烷醇的生物学功能,主要有以下几点:1)提高植物细胞的酶活性;2)促进植物细胞新陈代谢;3)诱导植物体内第二信使产生(M. Naeem et al.,Journal of PlantInteractions [J],2011,2:33-36)。
得到三十烷醇有两种途径:一是从天然产物中提取,二是通过化学合成。三十烷醇在自然界中广泛存在于米糠蜡、蔗蜡、蜂蜡等天然蜡质中,资源十分丰富,所以亦今为止工业制备三十烷醇都是采用从天然蜂蜡中提取。提取法主要有两个缺点,一是产量受原料来源限制,蜂蜡属于自然资源,产量不稳定,使用用途多样化,包括化妆品、中药等很多产业都需要这种原料。第二个缺点是提取得到的产物中含有较高含量的二十八烷醇和三十二烷醇等杂质。三十烷醇在自然界总是与其它长链醇共存,如二十八烷醇,三十二烷醇等,这些化合物的物理化学性质同三十烷醇非常接近,单纯的重结晶等工艺很难把它们从产品中完全除去,事实上在目前工业条件下采用提取法得不到到大批量的高纯度三十烷醇产品。而早在1979年,J. Jones等就报道了二十八烷醇等其他高级脂肪醇对三十烷醇发挥促进植物生长活性的功能起到抑制作用(J. Jones etal., Planta[J],1979,144:277-282)。这也是到目前为止工业提取得到的三十烷醇(最高可以达到95%含量)无法在农业生产中发挥出完全的促进农作物生长的功效,从而提高农产品产量和品质的最主要原因。我国学者邓道利等也专门指出:从天然产物中提取分离得到纯的三十烷醇是极其困难的,从蜂蜡中提取得到的三十烷醇产品中含有大量的同系物: 二十四烷醇、二十六烷醇、二十八烷醇、、三十二烷醇、、三十四烷醇及三十六醇等。而有机合成得到的产品中杂质种类很少,经纯化后即可除去,从而得到高纯度三十烷醇(邓道利等,有机化学 [J],1980,4:71-72.)。因此,研究利用有机合成法制备高纯度三十烷醇对于促进三十烷醇的研究和应用有显著意义。
亦今已经报道的通过有机合成方法制备三十烷醇的方法有:氯化烷基锌法(钱长涛等,植物学报[J],1981,23:423-426.)、KAPA炔烃异构化法(Kang S & Cho J S.,Bulletin of the Korean Chemical Society[J],1989,10: 479-480.)、格氏偶合反应(吴明光等,厦门大学学报:自然科学版[J],1996,35: 560-563.)、酰氯-烯胺反应(Welebir JA. 美国专利,US4167641.)以及烯烃合成法(Tran-Thi N H & Falk H., Monatshefte fürChemie/Chemical Monthly[J],1995,126:565-568.)等。虽然用化学合成法比较容易制得纯度较高的产品,但由于三十烷醇的碳链很长,化学合成法普遍存在反应步骤多,工艺路线长,原料昂贵,选择性差,副反应多等缺点,而且很多化学反应的条件比较苛刻,收率也不高。
发明内容
本发明的目的在于提供一种原料来源丰富、工艺简单、收率与纯度高、易于规模化生产的三十烷醇的制备方法。
本发明的反应步骤(化学方程式)如下:
步骤(1):
步骤(2):
步骤(3):
其中,TBDMS是叔丁基二甲基硅基,PPh3是三苯磷。
本发明的技术方案是将1,12-十二烷二醇(1)的一个羟基用叔丁基二甲氧基硅基进行保护,得到单取代的硅醚(3),对(3)进行选择性氧化,得到12-叔丁基二甲基硅氧基十二醛(4)。溴代十八烷(5)与三苯磷(6)反应得到十八烷基三苯基溴化膦鎓盐(7)。(4)和(7)在强碱作用下进行维蒂希反应,得到叔丁基二甲基三十烷氧基硅烷-12-烯(8),催化加氢还原,脱保护基,得到三十烷醇(9)。
本发明的具体步骤如下:
(a)制备12-叔丁基二甲基硅氧基十二醇(3)
将1,12-十二烷二醇(1)溶于二氯甲烷等溶剂,加入1-2倍摩尔量的咪唑,控温20~35℃间,缓慢滴加1.0~1.5摩尔倍数的叔丁基二甲基氯硅烷(TBDMSCl,2)溶于二氯甲烷等溶剂的溶液,加入0.05-0.1摩尔倍数的4-二甲氨基吡啶(DMAP),维持该温度搅拌反应1~5小时。TLC监测(石油醚:乙酸乙酯=15:1)反应进程,当监测到双保护基取代的副产物开始出现时,加入冰水混合物淬灭反应。分离有机相,无水硫酸镁干燥。抽滤,旋蒸浓缩得无色油状物。柱层析纯化,除去极性大的咪唑和DMAP,旋蒸浓缩,得无色油状物12-叔丁基二甲基硅氧基十二醇(3)。
(b)12-叔丁基二甲基硅氧基十二醛(4)的制备
将12-叔丁基二甲基硅氧基十二醇(3)溶于二氯甲烷等溶剂中,室温搅拌条件下,加入由0.1摩尔倍数NaBr、0.1摩尔倍数四甲基哌啶氧化物(TEMPO试剂)和2.0摩尔倍数碳酸氢钠配成的pH约为8.6的饱和水溶液,控温20~35℃之间,搅拌,缓慢滴加1.5~2.0摩尔倍数的次氯酸钠水溶液(浓度在5~10%之间即可,使用前临时测定其有效摩尔浓度)。滴毕,TLC监测(石油醚:乙酸乙酯=15:1)原料反应完全,冰浴降温至0~5℃,加入含有0.01摩尔倍数KI的盐酸溶液(10%),调节溶液pH值7~8。分离有机相,用10%Na2S2O3溶液洗涤1次,饱和NaCl溶液洗涤1次,无水MgSO4干燥,过滤,减压旋蒸除去溶剂,得油状物12-叔丁基二甲基硅氧基十二醛(4)。
(c)十八烷基三苯基溴化膦鎓盐(7)的制备:
1-溴代十八烷(5)和1.5摩尔倍数的三苯磷(6)溶于甲苯等溶剂中,缓慢加热升温至甲苯开始回流,保持回流状态反应12 ~72小时。停止加热,旋蒸除去溶剂,得黄色油状物残余。降至室温,搅拌下加入甲基叔丁基醚,冰水浴冷却,析出类白色固体。抽滤,甲基叔丁基醚洗涤,室温真空干燥除去残余溶剂,得到十八烷基三苯基溴化膦鎓盐(7),m.p. 96-97℃。
(d)叔丁基二甲基三十烷氧基硅烷-12-烯(8)的制备:
干燥、密闭的玻璃反应器中加入2.0摩尔倍数(以12-叔丁基二甲基硅氧基十二醛的量计)的十八烷基三苯基溴化膦鎓盐(7),加入无水溶剂,形成悬浊液。多次抽真空,并用惰性气体N2置换,赶除反应器内的空气。冰盐浴降温-10~0℃之间,用注射器抽取4.0-5.0摩尔倍数的有机强碱溶于无水溶剂的溶液,缓慢加入玻璃反应器中,加料完毕后升至室温,再用油浴加热至溶剂回流,保持回流1小时。降温至室温,搅拌下使用注射器缓慢加入1.0摩尔倍数的12-叔丁基二甲基硅氧基十二醛(4)溶于无水溶剂的溶液,室温反应3~6小时,TLC监测(纯石油醚)12-叔丁基二甲基硅氧基十二醛反应完全。冰水浴降温至5℃左右,缓慢滴加等体积饱和NH4Cl溶液,用3%稀盐酸调节pH值至中性。加入乙酸乙酯萃取2次,合并有机相,用饱和NH4Cl溶液洗涤有机相,无水MgSO4干燥,旋蒸除去溶剂,柱层析纯化,石油醚洗脱,减压旋蒸除去石油醚,得叔丁基二甲基三十烷氧基硅烷-12-烯(8)。
(e)三十烷醇(9)的制备
叔丁基二甲基三十烷氧基硅烷-12-烯(8)溶于甲醇,加入0.1摩尔倍数的10% 钯碳催化剂(Pd/C),接通氢气,搅拌,常压氢化1~5小时。TLC监测(纯石油醚)反应完全。抽滤除去钯碳催化剂,溶液中加入1/3量的盐酸溶液(浓度15%),加热回流0.2~3小时,冷却,有白色固体析出,抽滤得白色固体,苯重结晶,真空干燥,得到产品三十烷醇(9)。收率90%以上,m.p.86~87℃。
在步骤(a)中,溶剂选自二氯甲烷、氯仿、甲苯、DMF中的至少一种。1,12-十二烷二醇的羟基保护剂是三甲基氯硅烷、二甲基苯基氯硅烷、叔丁基二甲氧基氯硅烷中的至少一种。羟基保护剂与1,12-十二烷二醇的摩尔数比例在1.0~1.5:1之间。
在步骤(b)中,选择性氧化采用TEMPO催化氧化,其中四甲基哌啶氧化物(TEMPO试剂)是催化剂,次氯酸钠是氧化剂。反应体系是有机相水相双相体系,12-叔丁基二甲基硅氧基十二醇溶于二氯甲烷、乙酸乙酯、苯、甲苯等与水不互溶的溶剂。
在步骤(c)中,加热回流时间不短于12小时。反应溶剂是甲苯或二甲苯中的至少一种。
在步骤(d)中,维蒂希反应所采用的无水溶剂是THF或二氧六环,且溶剂需进行无水处理。用于催化维蒂希反应的有机强碱的碱性强度不低于叔丁醇钾。优选地有机强碱为叔丁醇钾或叔丁醇钾与正丁基锂的混合物,其中,叔丁醇钾与正丁基锂的摩尔比为4-9:1
在步骤(e)中,溶解烯烃叔丁基二甲基三十烷氧基硅烷-12-烯的溶剂选自甲醇或乙醇。还原反应结束后,过滤除去Pd/C催化剂,羟基保护的中间体叔丁基二甲氧基三十烷醚(或其他硅烷保护的三十烷醚)不进行纯化,直接在溶剂中加入强酸,如稀盐酸、稀硫酸、稀硝酸中的一种,搅拌加热,脱除保护基,三十烷醇以沉淀形式析出。过滤分离,重结晶纯化一次,产物纯度98.5%以上。
本发明具有以下突出优点:
(1)原料易得:所用原料1,12-十二烷二醇(1)和溴代十八烷(5)都是工业化学产品,可以规模采购。
(2)工艺简单:从原料1,12-十二烷二醇(1)和溴代十八烷(5)出发,经过5步骤反应得到三十烷醇(9)。
(3)化学收率高:一般而言,按照每步收率80%计算,4步骤的有机合成路线总收率在40%左右。本发明的总收率以1,12-十二烷二醇计算可达55%以上,甚至更高。
(4)产品纯度高:经气相色谱分析,重结晶一次后的产品纯度在98.5%以上。
(5)易于工业化:本发明中各步骤所使用的试剂均为常用化学试剂,毒性低,对环境友好;所采用的的反应条件在工业化生产中都能达到,对设备无特殊高温高压要求,适合工业化生产。
附图说明
图1. 12-叔丁基二甲基硅氧基十二醇(3)的1H NMR谱图;
图2. 12-叔丁基二甲基硅氧基十二醇(3)的13C NMR谱图;
图3. 12-叔丁基二甲基硅氧基十二醇(3)的FT-IR谱图;
图4. 12-叔丁基二甲基硅氧基十二醛(4)的1H NMR谱图;
图5. 12-叔丁基二甲基硅氧基十二醛(4)的13C NMR谱图;
图6. 12-叔丁基二甲基硅氧基十二醛(4)的FT-IR谱图;
图7. 十八烷基三苯基溴化膦鎓盐(7)的1H NMR谱图;
图8. 十八烷基三苯基溴化膦鎓盐(7)的13C NMR谱图;
图9. 十八烷基三苯基溴化膦鎓盐(7)的FT-IR谱图;
图10. 叔丁基二甲基三十烷氧基硅烷-12-烯(8)的1H NMR谱图;
图11. 叔丁基二甲基三十烷氧基硅烷-12-烯(8)的13C NMR谱图;
图12. 叔丁基二甲基三十烷氧基硅烷-12-烯(8)的FT-IR谱图;
图13. 1-三十烷醇(9)的1H NMR谱图;
图14. 1-三十烷醇(9)的13C NMR谱图;
图15. 1-三十烷醇(9)的FT-IR谱图;
具体实施方式
实施例1
步骤一:
12-叔丁基二甲基硅氧基十二醇(3)
将10.0 g1,12-十二烷二醇(1)和6.7 g咪唑置于50 mL DMF和160 mL CH2Cl2中,冰浴控温25℃左右,滴加8.4 g 叔丁基二甲氧基氯硅烷(TBDMSCl,2)的50 mL CH2Cl2溶液,滴毕加入0.3 g 4-二甲氨基吡啶(DMAP),维持该温度搅拌反应。TLC监测(PE:EA=15:1)当监测到双保护的副产物出现时,冰浴降温,加入100 mL水淬灭反应。分出有机相,无水硫酸镁干燥。抽滤,旋蒸浓缩得无色油状物。柱层析纯化(石油醚:乙酸乙酯=100:1,采取梯度洗脱,流动相调至石油醚:乙酸乙酯=10:1)除去极性大的咪唑和DMAP,收集产物,旋蒸浓缩除去溶剂,得无色油状产物15.4g(理论产量15.7g,收率98%)。
中间体(3)的结构确认:
本发明中每一步骤中间体都通过1H NMR、13C NMR和FT-IR光谱得到结构确证,图1、图2、图3分别是12-叔丁基二甲基硅氧基十二醇(3)的1H NMR、13C NMR和FT-IR谱图。
IR(film,cm-1) νmax:3341(-OH),2972,2855(-CH2),720[(CH2)11];
1H NMR(500MHz, CDCl3):δ:3.58-3.65(m,4H,-OCH2,-OCH2),1.47-1.63(m,4H,-OCH2CH2,-OCH2CH2),1.26-1.313(m,16H,-CH2),0.89(s,9H,-CH3),0.04(s,6H,-CH3);
13C NMR(125MHz, CDCl3):δ:63.4,63.1,32.9,32.8,29.6,29.4,26.0,25.8,25.7,18.4,-5.2。
步骤二:12-叔丁基二甲基硅氧基十二醛(4)的制备
称取10g12-叔丁基二甲基硅氧基十二醇(3),加入60 mL CH2Cl2,室温搅拌待溶解完全。加入0.26g NaBr和0.12 g 四甲基哌啶氧化物(TEMPO试剂),称取3.0 g NaHCO3于50mL水中,配成pH约为8.6的饱和溶液,水浴控温25℃左右,缓慢滴加1.5摩尔倍数的NaClO溶液(注:由于NaClO溶液久置浓度易发生变化,故在使用前需要进行标定,以便确定其浓度,决定滴加的实际体积量)。滴加过程中溶液颜色有变化,滴毕TLC监测(PE:EA=15:1)原料反应完全,冰浴降温至0℃,滴加含有0.1 g KI的稀HCl溶液(3M,10%),调节pH值7~8。分液,有机相用10%Na2S2O3溶液(100 mL)洗涤2次,饱和NaCl 100 mL洗涤1次,无水MgSO4干燥,抽滤,旋蒸浓缩得油状产物6.4g(理论8 g),收率80%。
中间体(4)的结构确认:
图4、图5、图6分别是12-叔丁基二甲基硅氧基十二醛(4)的1H NMR、13C NMR和FT-IR谱图。
IR(film,cm-1) νmax:2927.6,2855.4(-CH2),1729.0(-CHO);
1H NMR(500MHz, CDCl3):δ:9.76-9.75(t,1H,-CHO),3.60-3.58 (t,2H,-OCH2),2.39-2.43(m,2H,-OCH2),1.59-1.65(m,2H,-OCH2CH2),1.47-1.52(m,2H,-OCH2CH2),1.26-1.29(m,16H,-CH2),0.89(s,9H,-CH3),0.04(s,6H,-CH3);
13C NMR(125MHz, CDCl3):δ:202.8,63.3,43.9,32.9,29.6,29.5,29.4,29.3,29.2,26.0,25.8,22.1,18.4,-5.2。
步骤三:十八烷基三苯基溴化膦鎓盐(7)的制备
称取60 g溴代十八烷(5)和71 g三苯磷(6)于1000mL单口瓶中,加入420 mL甲苯,缓慢升温至甲苯回流,保持回流反应48 h,TLC监测(石油醚100%),反应完全,旋蒸除去甲苯,残余物为黄色油状物,室温搅拌下加入500mL甲基叔丁基醚,冰水浴冷却下析出类白色固体。抽滤,少量叔丁基醚洗涤。室温真空干燥除去残余溶剂,得到十八烷基三苯基溴化膦鎓盐(7),称重94g,收率87%,熔点为96-97℃。
中间体(7)的结构确认:
图7、图8、图9分别是十八烷基三苯基溴化膦鎓盐(7)的1H NMR、13C NMR和FT-IR谱图。
IR(film,cm-1) νmax:2918.6,2848.6(-CH2),1437.1,1468.5 (-PhH),720[(CH2)15];
1H NMR(500MHz, CDCl3):δ:7.67-7.87(m,15H,-PhH),3.81-3.84 (t,2H,BrCH2),1.72(m,2H,BrCH2CH2),1.17-1.23(m,28H,-CH2),0.86(t,3H,-CH3);
13C NMR(125MHz, CDCl3):δ:135.0,133.7,133.6,130.6,130.5,118.8,118.1,31.9,30.5,30.4,29.7,29.6,29.3,29.2,23.0,22.7,22.6,14.1。
步骤四:叔丁基二甲基三十烷氧基硅烷-12-烯(8)的制备
称取14.2 g 十八烷基三苯基溴化膦鎓盐(7)试剂于250 mL密闭干燥的三口瓶中,加入50 mL新鲜制备的无水THF。多次抽真空,并用惰性气体N2置换反应瓶内空气。冰盐浴控温-10℃左右,用注射器抽取5.7 g叔丁醇钾溶于50 mL无水THF的溶液,缓慢注入三口瓶中,注射过程中出现橘红色现象,加料完毕,逐渐升至室温反应,后转为油浴加热回流1 h后,自然升温至室温,搅拌下使用注射器缓慢注入12-叔丁基二甲基硅氧基十二醛(4,2.0 g溶于30 mL无水THF)溶液,加料过程中溶液变为深棕色,TLC监测(纯石油醚)原料反应完全。冰浴降温至5℃左右,缓慢滴加50mL饱和NH4Cl溶液,调节pH近中性,反应液转入分液漏斗。分离有机相,加入50mL 乙酸乙酯,50mL饱和NH4Cl溶液洗涤2次,有机相用无水MgSO4干燥。抽滤,滤液旋蒸除大部分溶剂,转入冰箱静置,抽滤除去固体,滤液浓缩,柱层析进一步,石油醚洗脱,合并产物,旋蒸浓缩得叔丁基二甲基三十烷氧基硅烷-12-烯(8,无色液体),称重5.5 g,收率约80%。
中间体(8)的结构确认:
图10、图11、图12分别是叔丁基二甲基三十烷氧基硅烷-12-烯(8)的1H NMR、13CNMR和FT-IR谱图。
IR(film,cm-1) νmax:3004.3(=CH),2924.1,2853.8(-CH2),1463.8(C=C),720[(CH2)15];
1H NMR(500MHz, CDCl3):δ:5.32-5.40(m,2H,=CH),3.59-3.62 (t,2H,OCH2),1.96-2.04(m,4H,=CHCH2),1.50-1.53(m,2H,-OCH2CH2),1.27(m,48H,-CH2),0.90(m,12H,-CH3),0.06(s,6H,-CH3);
13C NMR(125MHz, CDCl3):δ:130.4,129.9,63.3,32.9,32.6,32.0,29.8,29.75,29.71,29.6,29.5,29.4,29.37,29.2,27.2,26.0,25.9,22.7,18.4,14.1,-5.2。
步骤五:1-三十烷醇的制备和纯化
称取0.5 g 10% 钯碳催化剂(Pd-C)于250 ml三口瓶中,加入溶于100 ml甲醇的叔丁基二甲基三十烷氧基硅烷-12-烯(中间体8,2.5 g),接通氢气,室温搅拌反应,TLC监测(纯石油醚)反应完全。抽滤除去钯碳催化剂,溶液中加入30ml 浓盐酸(15%浓度),加热回流20分钟,冷却,有白色固体析出,抽滤得白色固体,苯重结晶,真空干燥后称重为1.77 g,收率90%,熔点86~87℃,GC色谱纯度98.7%。
产品结构确认:
图13、图14、图15分别是1-三十烷醇(9)的1H NMR、13C NMR和FT-IR谱图,三十烷醇的1H NMR、13C NMR和FT-IR光谱与文献报道完全一致。
IR(film,cm-1) νmax:3227.4(-OH),2917.5,2848.8(-CH2) 720[(CH2)29];
1H NMR(500MHz, CDCl3):δ:3.62-3.65 (m,2H,-OCH2),1.55-1.59 (m,2H,OCH2CH2),1.28-1.35(m,56H,-CH2),0.86-0.89(t,3H,-CH3);
13C NMR(125MHz, CDCl3):δ:63.1,32.9,31.9,29.7,29.6,29.4,29.3,25.8,22.7,14.1。
GC-MS(EI,m/z):422[M-15(CH3)]
实施例2
与实施例1类似,其区别在于步骤(a)中所用溶剂为氯仿和DMF,叔丁基二甲氧基氯硅烷与1,12-十二烷二醇摩尔比是1.5:1。产品通过1H NMR、13C NMR和FT-IR光谱得到结构确证,其谱图与文献报道完全一致;GC色谱纯度98.6%。
实施例3
与实施例1类似,其区别在于步骤(b)中所用溶剂是乙酸乙酯。产品通过1H NMR、13C NMR和FT-IR光谱得到结构确证,其谱图与文献报道完全一致;GC色谱纯度98.5%。
实施例4
与实施例1类似,其区别在于步骤(c)中所用溶剂是二甲苯,回流温度140℃,回流反应时间24小时。产品通过1H NMR、13C NMR和FT-IR光谱得到结构确证,其谱图与文献报道完全一致;GC色谱纯度98.7%。
实施例5
与实施例1类似,其区别在于步骤(d)中所用溶剂是二氧六环。产品通过1H NMR、13C NMR和FT-IR光谱得到结构确证,其谱图与文献报道完全一致;GC色谱纯度98.6%。
实施例6
与实施例1类似,其区别在于催化维蒂希反应的有机强碱选择摩尔比为1:4正丁基锂和叔丁醇钾混合强碱,总碱量摩尔数5倍于12-叔丁基二甲基硅氧基十二醛。产品通过1HNMR、13C NMR和FT-IR光谱得到结构确证,其谱图与文献报道完全一致;GC色谱纯度98.9%。
实施例7
与实施例1类似,其区别在还原反应溶剂选择无水乙醇。还原完毕,除去Pd/C催化剂后,用30%的硫酸溶液进行酸化,加热回流0.5小时后,降至室温,三十烷醇从溶液中析出。产品通过1H NMR、13C NMR和FT-IR光谱得到结构确证,其谱图与文献报道完全一致;GC色谱纯度98.6%。
Claims (8)
1.一种三十烷醇的制备方法,其特征在于,反应方程式如下:
步骤(1):
步骤(2):
步骤(3):
其中,TBDMS是叔丁基二甲基硅基,PPh3是三苯磷;
包括以下步骤:
(a)制备12-叔丁基二甲基硅氧基十二醇
将1,12-十二烷二醇溶于有机溶剂,加入1-2倍数摩尔量的咪唑,控温20~35℃间,向有机溶剂的溶液中滴加1.0~1.5摩尔倍数的羟基保护剂叔丁基二甲基氯硅烷,再加入0.05~0.1摩尔倍数的4-二甲氨基吡啶DMAP,维持该温度搅拌反应1~5小时;监测反应进程,当监测到双保护基取代的副产物开始出现时,加入冰水混合物淬灭反应,分离有机相,无水硫酸镁干燥,抽滤,旋蒸浓缩得无色油状物,柱层析纯化,除去咪唑和DMAP,旋蒸浓缩,得无色油状物12-叔丁基二甲基硅氧基十二醇;
(b)12-叔丁基二甲基硅氧基十二醛的制备
将12-叔丁基二甲基硅氧基十二醇溶于溶剂中,室温搅拌条件下,加入由0.1~0.2摩尔倍数的NaBr、0.1~0.2摩尔倍数的四甲基哌啶氧化物TEMPO和1.5-2.0摩尔倍数碳酸氢钠配成的饱和水溶液,控温20~35℃之间,搅拌,滴加1.5~2.0摩尔倍数的次氯酸钠水溶液,滴毕,监测原料反应完全,冰浴降温至0~5℃,加入含有0.01摩尔倍数KI的盐酸溶液,调节溶液pH值7~8,分离有机相,用Na2S2O3溶液洗涤,然后用饱和NaCl溶液洗涤,无水MgSO4干燥,过滤,减压旋蒸除去溶剂,得油状物12-叔丁基二甲基硅氧基十二醛;
(c)十八烷基三苯基溴化膦鎓盐的制备:
1-溴代十八烷和1.5摩尔倍数的三苯磷溶于溶剂中,缓慢加热升温至溶剂开始回流,保持回流状态反应12 ~72小时,停止加热,旋蒸除去溶剂,得黄色油状物残余,降至室温,搅拌下加入甲基叔丁基醚,冰水浴冷却,析出白色固体,抽滤,甲基叔丁基醚洗涤,室温真空干燥除去残余溶剂,得到十八烷基三苯基溴化膦鎓盐;
(d)叔丁基二甲基三十烷氧基硅烷-12-烯的制备:
干燥、密闭的玻璃反应器中,以12-叔丁基二甲基硅氧基十二醛的量计,加入2.0摩尔倍数的十八烷基三苯基溴化膦鎓盐,加入无水溶剂,形成悬浊液,抽真空并用惰性气体N2置换,赶除反应器内的空气,降温-40~-20℃之间,加入4.0-5.0摩尔倍数的有机强碱,加料完毕后升至0~5℃,再用油浴加热至室温,搅拌下使用注射器缓慢加入12-叔丁基二甲基硅氧基十二醛溶于无水溶剂的溶液,室温反应3~6小时,监测12-叔丁基二甲基硅氧基十二醛反应完全;冰水浴降温至5℃以下,缓慢滴加等体积饱和NH4Cl溶液,用酸调节pH至中性,加入乙酸乙酯萃取2次,合并有机相,用饱和NH4Cl溶液洗涤有机相,无水MgSO4干燥,旋蒸除去溶剂,柱层析纯化,石油醚洗脱,减压旋蒸除去石油醚,得叔丁基二甲基三十烷氧基硅烷-12-烯;
(e)三十烷醇的制备
叔丁基二甲基三十烷氧基硅烷-12-烯溶于溶剂,加入0.1摩尔倍数的10% 钯碳催化剂Pd/C,接通氢气,搅拌,常压氢化1~5小时;监测反应完全,抽滤除去钯碳催化剂,溶液中加入1/3体积量的质量浓度15%的盐酸溶液,加热回流0.2~1小时,冷却,有白色固体析出,抽滤得白色固体,苯重结晶,真空干燥,得到产品三十烷醇。
2.如权利要求1所述的一种三十烷醇的制备方法,其特征在于,步骤(a)中,有机溶剂为二氯甲烷、氯仿、苯、甲苯、二甲苯、DMF中的至少一种。
3.如权利要求1所述的一种三十烷醇的制备方法,其特征在于,步骤(b)中,选择性氧化采用TEMPO催化氧化法,其中四甲基哌啶氧化物是催化剂,次氯酸钠是氧化剂;溶剂为与水不互溶的二氯甲烷、乙酸乙酯、苯或甲苯。
4.如权利要求1所述的一种三十烷醇的制备方法,其特征在于,步骤(c)中的溶剂是甲苯、二甲苯中的至少一种。
5.如权利要求1所述的一种三十烷醇的制备方法,其特征在于,步骤(d)中,维蒂希反应所采用的溶剂是四氢呋喃或二氧六环,且溶剂要进行无水处理。
6.如权利要求1所述的一种三十烷醇的制备方法,其特征在于,步骤(d)中,有机强碱为叔丁醇钾或叔丁醇钾与正丁基锂的混合物,其中,叔丁醇钾与正丁基锂的摩尔比为4-9:1。
7.如权利要求1所述的一种三十烷醇的制备方法,其特征在于,步骤(e)中的溶剂选自甲醇或乙醇。
8.如权利要求1所述的一种三十烷醇的制备方法,其特征在于,步骤(a)、(b)中采用TLC监测反应,其采用的吸附剂体积比组成为石油醚:乙酸乙酯=15:1;步骤(d)和步骤(e)中均采用TLC监测反应,其采用的吸附剂均为纯石油醚。
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