CN104250236B - γ hydrocarbon oxygen sulfonylmethyl gamma butyrolactone, the synthetic method of δ hydrocarbon oxygen sulfonylmethyl δ valerolactone - Google Patents
γ hydrocarbon oxygen sulfonylmethyl gamma butyrolactone, the synthetic method of δ hydrocarbon oxygen sulfonylmethyl δ valerolactone Download PDFInfo
- Publication number
- CN104250236B CN104250236B CN201410332641.7A CN201410332641A CN104250236B CN 104250236 B CN104250236 B CN 104250236B CN 201410332641 A CN201410332641 A CN 201410332641A CN 104250236 B CN104250236 B CN 104250236B
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- China
- Prior art keywords
- sulfonylmethyl
- hydrosilicon
- unsaturated carboxylic
- hydrocarbon oxygen
- 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.)
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- 239000004215 Carbon black (E152) Substances 0.000 title claims abstract description 54
- -1 sulfonylmethyl Chemical group 0.000 title claims abstract description 50
- 239000001301 oxygen Substances 0.000 title claims abstract description 10
- 229910052760 oxygen Inorganic materials 0.000 title claims abstract description 10
- 238000010189 synthetic method Methods 0.000 title claims abstract description 10
- 229930195733 hydrocarbon Natural products 0.000 title claims abstract description 8
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 title claims abstract description 6
- YEJRWHAVMIAJKC-UHFFFAOYSA-N 4-Butyrolactone Chemical compound O=C1CCCO1 YEJRWHAVMIAJKC-UHFFFAOYSA-N 0.000 title abstract description 12
- OZJPLYNZGCXSJM-UHFFFAOYSA-N 5-valerolactone Chemical compound O=C1CCCCO1 OZJPLYNZGCXSJM-UHFFFAOYSA-N 0.000 title abstract description 10
- 150000002430 hydrocarbons Chemical class 0.000 title abstract 4
- 238000006243 chemical reaction Methods 0.000 claims abstract description 48
- 150000004754 hydrosilicons Chemical class 0.000 claims abstract description 34
- 238000000034 method Methods 0.000 claims abstract description 34
- 229930194542 Keto Natural products 0.000 claims abstract description 32
- 150000001875 compounds Chemical class 0.000 claims abstract description 30
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 24
- 150000002148 esters Chemical class 0.000 claims abstract description 21
- 239000005749 Copper compound Substances 0.000 claims abstract description 12
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 150000001880 copper compounds Chemical class 0.000 claims abstract description 12
- 239000003446 ligand Substances 0.000 claims abstract description 12
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 12
- 150000001735 carboxylic acids Chemical class 0.000 claims abstract description 9
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 8
- 238000003756 stirring Methods 0.000 claims description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 39
- 239000000243 solution Substances 0.000 claims description 32
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 25
- CROQKTJSIKXCPR-UHFFFAOYSA-N S(=O)(=O)=CC1C(=O)OCC1.[O] Chemical compound S(=O)(=O)=CC1C(=O)OCC1.[O] CROQKTJSIKXCPR-UHFFFAOYSA-N 0.000 claims description 22
- JRQVQYWVSZZRBZ-UHFFFAOYSA-N S(=O)(=O)=CC1C(=O)OCCC1.[O] Chemical compound S(=O)(=O)=CC1C(=O)OCCC1.[O] JRQVQYWVSZZRBZ-UHFFFAOYSA-N 0.000 claims description 20
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 19
- DDFHBQSCUXNBSA-UHFFFAOYSA-N 5-(5-carboxythiophen-2-yl)thiophene-2-carboxylic acid Chemical compound S1C(C(=O)O)=CC=C1C1=CC=C(C(O)=O)S1 DDFHBQSCUXNBSA-UHFFFAOYSA-N 0.000 claims description 17
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- 239000000203 mixture Substances 0.000 claims description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 14
- 238000004440 column chromatography Methods 0.000 claims description 13
- 239000002904 solvent Substances 0.000 claims description 13
- 125000003118 aryl group Chemical group 0.000 claims description 12
- 125000002252 acyl group Chemical group 0.000 claims description 11
- 238000003786 synthesis reaction Methods 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 claims description 8
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 239000000376 reactant Substances 0.000 claims description 7
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 6
- 239000001257 hydrogen Substances 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 238000012805 post-processing Methods 0.000 claims description 6
- 238000000746 purification Methods 0.000 claims description 6
- 125000003107 substituted aryl group Chemical group 0.000 claims description 6
- 238000005292 vacuum distillation Methods 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000010949 copper Substances 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- 229910052740 iodine Inorganic materials 0.000 claims description 5
- 238000001953 recrystallisation Methods 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 4
- 239000012047 saturated solution Substances 0.000 claims description 4
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 3
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 239000000463 material Substances 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- JUJWROOIHBZHMG-UHFFFAOYSA-N pyridine Substances C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- 150000003839 salts Chemical class 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000004417 unsaturated alkyl group Chemical group 0.000 claims description 3
- LZDKZFUFMNSQCJ-UHFFFAOYSA-N 1,2-diethoxyethane Chemical compound CCOCCOCC LZDKZFUFMNSQCJ-UHFFFAOYSA-N 0.000 claims description 2
- DURPTKYDGMDSBL-UHFFFAOYSA-N 1-butoxybutane Chemical compound CCCCOCCCC DURPTKYDGMDSBL-UHFFFAOYSA-N 0.000 claims description 2
- RRQYJINTUHWNHW-UHFFFAOYSA-N 1-ethoxy-2-(2-ethoxyethoxy)ethane Chemical compound CCOCCOCCOCC RRQYJINTUHWNHW-UHFFFAOYSA-N 0.000 claims description 2
- JPVYNHNXODAKFH-UHFFFAOYSA-N Cu2+ Chemical class [Cu+2] JPVYNHNXODAKFH-UHFFFAOYSA-N 0.000 claims description 2
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 2
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 125000005428 anthryl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C3C(*)=C([H])C([H])=C([H])C3=C([H])C2=C1[H] 0.000 claims description 2
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
- 150000007942 carboxylates Chemical class 0.000 claims description 2
- 238000007600 charging Methods 0.000 claims description 2
- 239000012295 chemical reaction liquid Substances 0.000 claims description 2
- 238000002425 crystallisation Methods 0.000 claims description 2
- 229940019778 diethylene glycol diethyl ether Drugs 0.000 claims description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 claims description 2
- 150000002170 ethers Chemical group 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 239000012298 atmosphere Substances 0.000 claims 3
- 239000011261 inert gas Substances 0.000 claims 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 2
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims 1
- 239000007809 chemical reaction catalyst Substances 0.000 claims 1
- 239000013078 crystal Substances 0.000 claims 1
- 150000002576 ketones Chemical class 0.000 claims 1
- 238000000926 separation method Methods 0.000 abstract description 9
- 238000010523 cascade reaction Methods 0.000 abstract description 3
- 238000005516 engineering process Methods 0.000 abstract description 3
- 239000000126 substance Substances 0.000 abstract description 3
- 238000006459 hydrosilylation reaction Methods 0.000 abstract description 2
- 239000013067 intermediate product Substances 0.000 abstract description 2
- 239000000047 product Substances 0.000 description 14
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 9
- 150000001721 carbon Chemical group 0.000 description 9
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- 239000012071 phase Substances 0.000 description 7
- 238000005406 washing Methods 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- 208000035126 Facies Diseases 0.000 description 6
- BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 6
- DFEMJYIRAXUQQB-UHFFFAOYSA-N 3-ethyloxolan-2-one Chemical compound CCC1CCOC1=O DFEMJYIRAXUQQB-UHFFFAOYSA-N 0.000 description 5
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 5
- 238000006555 catalytic reaction Methods 0.000 description 5
- 238000001035 drying Methods 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 150000002596 lactones Chemical class 0.000 description 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 3
- 238000006668 aldol addition reaction Methods 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 239000012141 concentrate Substances 0.000 description 3
- 238000007796 conventional method Methods 0.000 description 3
- 229910052756 noble gas Inorganic materials 0.000 description 3
- 150000002835 noble gases Chemical class 0.000 description 3
- 238000007363 ring formation reaction Methods 0.000 description 3
- 229910052710 silicon Inorganic materials 0.000 description 3
- 239000010703 silicon Substances 0.000 description 3
- HSJKGGMUJITCBW-UHFFFAOYSA-N 3-hydroxybutanal Chemical compound CC(O)CC=O HSJKGGMUJITCBW-UHFFFAOYSA-N 0.000 description 2
- ONSWFYLALGXCIQ-UHFFFAOYSA-N 5-oxooxolane-3-carboxylic acid Chemical compound OC(=O)C1COC(=O)C1 ONSWFYLALGXCIQ-UHFFFAOYSA-N 0.000 description 2
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 2
- ZQVZYZVRVFBTDG-UHFFFAOYSA-N Lycoperdic acid Chemical compound OC(=O)C(N)CC1(C(O)=O)CCC(=O)O1 ZQVZYZVRVFBTDG-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical class OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical compound [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 description 2
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 2
- MWPLVEDNUUSJAV-UHFFFAOYSA-N anthracene Chemical compound C1=CC=CC2=CC3=CC=CC=C3C=C21 MWPLVEDNUUSJAV-UHFFFAOYSA-N 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- PWLNAUNEAKQYLH-UHFFFAOYSA-N butyric acid octyl ester Natural products CCCCCCCCOC(=O)CCC PWLNAUNEAKQYLH-UHFFFAOYSA-N 0.000 description 2
- 229910052802 copper Inorganic materials 0.000 description 2
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 description 2
- VDCSGNNYCFPWFK-UHFFFAOYSA-N diphenylsilane Chemical compound C=1C=CC=CC=1[SiH2]C1=CC=CC=C1 VDCSGNNYCFPWFK-UHFFFAOYSA-N 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- XVRCVKWYKYJEIG-UHFFFAOYSA-N methyl 4-oxo-4-phenylbutanoate Chemical compound COC(=O)CCC(=O)C1=CC=CC=C1 XVRCVKWYKYJEIG-UHFFFAOYSA-N 0.000 description 2
- UUIQMZJEGPQKFD-UHFFFAOYSA-N n-butyric acid methyl ester Natural products CCCC(=O)OC UUIQMZJEGPQKFD-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 229920001843 polymethylhydrosiloxane Polymers 0.000 description 2
- 229920006395 saturated elastomer Polymers 0.000 description 2
- 229910000077 silane Inorganic materials 0.000 description 2
- YZCRACGZKLIGLZ-DTWKUNHWSA-N (2s,3r)-4-methylidene-5-oxo-2-pentyloxolane-3-carboxylic acid Chemical compound CCCCC[C@@H]1OC(=O)C(=C)[C@H]1C(O)=O YZCRACGZKLIGLZ-DTWKUNHWSA-N 0.000 description 1
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 description 1
- SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- MNMHTBMXCUARLR-UHFFFAOYSA-N 3-ethyloxan-2-one Chemical compound CCC1CCCOC1=O MNMHTBMXCUARLR-UHFFFAOYSA-N 0.000 description 1
- 235000001674 Agaricus brunnescens Nutrition 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- 206010006187 Breast cancer Diseases 0.000 description 1
- 208000026310 Breast neoplasm Diseases 0.000 description 1
- DILLGYXHRXDYAT-UHFFFAOYSA-N C1(CCCCO1)=O.C(=O)(O)C1CC(=O)OC1 Chemical compound C1(CCCCO1)=O.C(=O)(O)C1CC(=O)OC1 DILLGYXHRXDYAT-UHFFFAOYSA-N 0.000 description 1
- IAMFZSSKDOOBEU-UHFFFAOYSA-N C1(CCCCO1)=O.C(=O)(O)CC1CC(=O)OC1 Chemical compound C1(CCCCO1)=O.C(=O)(O)CC1CC(=O)OC1 IAMFZSSKDOOBEU-UHFFFAOYSA-N 0.000 description 1
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- 241000294162 Lycoperdon perlatum Species 0.000 description 1
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- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 1
- 241000857105 Pestalotiopsis photiniae Species 0.000 description 1
- 230000004103 aerobic respiration Effects 0.000 description 1
- 150000001335 aliphatic alkanes Chemical class 0.000 description 1
- 238000005937 allylation reaction Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 201000008275 breast carcinoma Diseases 0.000 description 1
- 125000001246 bromo group Chemical group Br* 0.000 description 1
- IAQRGUVFOMOMEM-UHFFFAOYSA-N butene Natural products CC=CC IAQRGUVFOMOMEM-UHFFFAOYSA-N 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- BKFAZDGHFACXKY-UHFFFAOYSA-N cobalt(II) bis(acetylacetonate) Chemical compound [Co+2].CC(=O)[CH-]C(C)=O.CC(=O)[CH-]C(C)=O BKFAZDGHFACXKY-UHFFFAOYSA-N 0.000 description 1
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- 230000006837 decompression Effects 0.000 description 1
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- 238000004821 distillation Methods 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
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- 239000000284 extract Substances 0.000 description 1
- 238000000855 fermentation Methods 0.000 description 1
- 230000004151 fermentation Effects 0.000 description 1
- KTWOOEGAPBSYNW-UHFFFAOYSA-N ferrocene Chemical compound [Fe+2].C=1C=C[CH-]C=1.C=1C=C[CH-]C=1 KTWOOEGAPBSYNW-UHFFFAOYSA-N 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 239000003823 glutamate receptor agonist Substances 0.000 description 1
- 125000005843 halogen group Chemical group 0.000 description 1
- YWGHUJQYGPDNKT-UHFFFAOYSA-N hexanoyl chloride Chemical compound CCCCCC(Cl)=O YWGHUJQYGPDNKT-UHFFFAOYSA-N 0.000 description 1
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
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- 230000002438 mitochondrial effect Effects 0.000 description 1
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- 238000012544 monitoring process Methods 0.000 description 1
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- HNBDRPTVWVGKBR-UHFFFAOYSA-N n-pentanoic acid methyl ester Natural products CCCCC(=O)OC HNBDRPTVWVGKBR-UHFFFAOYSA-N 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
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- 239000002243 precursor Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
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- 238000002390 rotary evaporation Methods 0.000 description 1
- 235000002639 sodium chloride Nutrition 0.000 description 1
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- ISXSCDLOGDJUNJ-UHFFFAOYSA-N tert-butyl prop-2-enoate Chemical compound CC(C)(C)OC(=O)C=C ISXSCDLOGDJUNJ-UHFFFAOYSA-N 0.000 description 1
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- IPSRAFUHLHIWAR-UHFFFAOYSA-N zinc;ethane Chemical compound [Zn+2].[CH2-]C.[CH2-]C IPSRAFUHLHIWAR-UHFFFAOYSA-N 0.000 description 1
- 150000007934 α,β-unsaturated carboxylic acids Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
- C07D307/33—Oxygen atoms in position 2, the oxygen atom being in its keto or unsubstituted enol form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D309/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings
- C07D309/16—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D309/28—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D309/30—Oxygen atoms, e.g. delta-lactones
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Abstract
The invention belongs to chemical technology field is and in particular to the synthetic method of a kind of γ hydrocarbon oxygen sulfonylmethyl gamma butyrolactone, δ hydrocarbon oxygen sulfonylmethyl δ valerolactone.With CuH compound as reducing agent and keto ester, α, β esters of unsaturated carboxylic acids reacts；With CuH compound as catalyst, keto ester, α, react between β esters of unsaturated carboxylic acids, hydrosilicon or hydroboron；Generation catalyst, direct catalyzed hydrosilation compound or hydroboron and keto ester, α are reacted by other copper compounds, Phosphine ligands, hydrosilicon or hydroboron, these three methods of the reaction of β esters of unsaturated carboxylic acids carry out synthetic reaction.The inventive method is synthesized by cascade reaction, is carried out continuously three-step reaction it is not necessary to separating intermediate product, avoiding middle separation process and the loss thereby resulting in same reaction vessel, easy and simple to handle, improves reaction efficiency, has good using value.
Description
Technical field
The invention belongs to chemical technology field is and in particular to a kind of γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen acyl
The synthetic method of ylmethyl-δ-valerolactone.
Background technology
Gamma-butyrolacton and δ-valerolactone compound are important organic synthesis intermediate and bioactive substance.From plant
Separate in endophyte Pestalotiopsis photiniae and obtain gamma-butyrolacton material 1 and 2, to breast carcinoma cell strain MDA-
MB-231 strain inhibited (Ding, G.; Zheng, Z. H.; Liu, S. C.; Zhang, H.; Guo, L.
D.; Che, Y. S.J. Nat. Prod., 2009, 72, 942).From lichensPunctelia microsticta(Muell.Arg.)KrogIn detached Paraconic acid 3 and its derivative
Thing 4 has antiinflammatory, anti-tumor activity (Maier, M. S.； Marimon, D. I. G..; Stortz, C. A.;
Adler, M. T. J.Nat.Prod. 1999, 62, 1565; Park, B. K.; Nakagawa, M.; Hirota,
A.; Nakayama, M. J.Antibiot. 1988, 41, 751.).Ester type compound 5 can suppress fungal cell's center line
Mitochondrial respiratory chain electron transfer, disturbs mitochondrial aerobic respiration (van Tamelen, E. E.; Dickie, J. P.;
Loomans, M. E.; Dewey, R. S.; Strong, F. M. J.Am.Chem.Soc.1961,83,1639).Carboxyl
The compound being connected by saturated carbon atom with lactone equally has biological activity.From mushroom Lycoperdon perlatum
Detached lactone compound Lycoperdic acid 6 be one kind potentially non-NMDA type glutamate receptor agonists (Kaname,
M.; Yoshifuji, S. Tetrahedron Lett.1992,33,8103).
The gamma-butyrolacton of anamorphic zone β-carboxyl or β-oxyl acyl group, the method for δ-valerolactone compound include chemistry conjunction
One-tenth method and living things catalysis, fermentation method.Chemical synthesiss include replaced succinate ester deprotonation-to the addition of carbonyl compound-
Cyclization (Pohmakotr, M.; Issaree, A.; Sampaongoen, L.; Tuchinda, P.;
Reutrakul, V. Tetrahedron Lett.2003, 44, 7937; Pohmakotr, M.; Soorukram, D.;
Tuchinda, P.; Prabpai, S.; Kongsaeree, P.; Reutrakul, V. Tetrahedron Lett.,
2004, 45, 4315; Barros, M. T.; Maycock, C. D.; Ventura, M. R. Org. Lett.2003,
5,4097), the reduction to esters of unsaturated carboxylic acids-intramolecular aldol addition cyclization (Lam, H. W.; Joensuu, P.
M.Org.Lett.2005,7, 4225), the Reformatsky of halo dicarboxylic ester reaction-right
Addition (Muniz Machado Rodrigues, the S. of carbonyl; da Silva, G. V. J.; Gomes
Constantino, M. Planta Medica2012,78,1285), substituted epoxy ethane and malonic acid condensation etc. method all
Can be used to prepare δ-valerolactone, gamma-butyrolacton skeleton.But needed low using saturated carboxylic acid ester deprotonation method synthesis cyclic lactone
Carry out under temperature, and generate a large amount of aldol addition compound products, need to be cyclized further and just can obtain cyclic lactone.Reformatsky reacts
Pre-synthesis bromo dicarboxylic ester and a large amount of organometallic reagent need to be used.Blanc et al. synthesizes keto ester, warp with caproyl chloride
Ru-SYNPHOS catalysis reduction ketone carbonyl, allylation, cyclisation, generate after seven steps such as ester hydrolysis compound 4 (-)-
Methylenolactocin, reaction needs to use noble metal Ru, low temperature and condition of high voltage, and complex steps (Blanc, D.;
Madec, J.; Popowyck, F.; Ayad, T.; Phanavath, P.; Ratovelomanana-Vidal, V.;
Genêt, J.-P. Adv. Synth. Catal.2007, 349, 943).Lam etc. adopts the reduction of copper catalysis silane unsaturated
Carboxylate-intramolecular aldol addition cyclization, obtains cyclic lactone, reaction condition gentle but require to contain in reactant ester group and
Contain carbonyl in position, only give and in molecule, introduce hydrogen atom (Lam, H. W.; Joensuu, P. M.
Org.Lett.2005, 7, 4225).Lam etc. utilizes Co (acac)2 .2H2O- is catalyzed Et2Zn, α, β-unsaturation monoamides list
Gamma-butyrolacton (Lumby, R. J. R. has been synthesized between ester, carbonyl compound; Joensuu, P. M.; Lam, H.
W. Org. Lett.2007, 9, 4367).We are recently reported copper catalysis silane reduction unsaturated dicarboxylic ester-to carbonyl
Between compound molecule, aldol addition-lactonize cascade reaction, and high productivity obtains cyclic lactone (Li, Z. C.; Zhang, Z.
L.; Yuan, L.; Jiang, L.; Li, Z. S.; Li, Z. N. Synlett. 2004, 25, 724).These sides
The lactone of method synthesis carries β -ester base, as β-hydrocarbon oxygen acyl group-gamma-butyrolacton.
Bandβ- carboxymethyl-gamma-butyrolacton (δ-valerolactone) and its precursorβ- hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton (δ-penta
Lactone) structure withβ- carboxy-y-butyrolactone (δ-valerolactone) closely, has important biological activity, is also synthesis
Otherβ- carboxy-y-butyrolactone,βThe intermediate of-carboxyl-δ-valerolactone.But not yet have so far by one pot reaction easily
Anamorphic zoneβThe method of-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, the method for document report need to be synthesized by multistep stepwise reaction, its
In be related to complexity the process isolating and purifying intermediate compound.The convenient, fast method synthesizing such compound of research has
Significance.
Content of the invention
For the problems referred to above, the present invention will provide one kind in a mild condition, succinct, efficient, easy and simple to handle, with low cost
Synthesis γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, the method for δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone.
γ-hydrocarbon oxygen sulfonylmethyl-the gamma-butyrolacton of present invention synthesis, the structure of δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone are divided
Shown in not following structure A, B：
The present invention includes three kinds of methods：
Method 1：
With stable, pure CuH compound such as [CuHPPh3]6For reducing agent and keto ester and alpha, beta-unsaturated carboxylic acid
Ester is synthesized γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone；
Method 2：
With stable, pure CuH compound as catalyst, keto ester, α, beta-unsaturated carboxylic acid ester and hydrosilicon
Or hydroboron is synthesized γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone.
Method 3：
During the course of the reaction catalysis is generated by the reaction of other copper compounds, Phosphine ligands, hydrosilicon or hydroboron
Agent, is not required to isolate and purify, direct catalyzed hydrosilation compound or hydroboron and keto ester, α, beta-unsaturated carboxylic acid ester anti-
, γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone should be synthesized.
Synthesis γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone reaction equation are respectively as formula
(1), shown in (2).
Keto ester in the present invention refers to γ -one acid esters in formula (1) or the δ -one acid esters in formula (2), wherein ketone carbonyl and ester
It is respectively separated 2,3 carbon atoms between base.
R therein1For aryl or substituted aryl or the aliphatic alkyl not being conjugated with carbonyl.Aryl include phenyl, naphthyl,
Anthryl, furyl, thienyl, pyrrole radicals, pyridine radicals etc.；Substituted aryl refers to that in aryl, one is taken to all H atom by other
The aryl replacing for base, other substituent groups can independently for C1- C8Alkyl, C3- C8Cycloalkyl, halogen, alkane (C1
- C8) epoxide ,-OPh ,-O- substituted-phenyl (substituent group C1- C4) ,-OCO- alkyl (C1- C8), containing 1-8 carbon atom
Acyl group ,-NO2、-NH2, containing single hydrocarbylamino of 1-8 carbon atom or Dialkylamino, the ester group containing 1-8 carbon atom ,-
CONH2,-CONH- alkyl (C1- C8) ,-CON- dialkyl (C1- C8) etc. group；Aliphatic alkyl refers to former containing 1-18 carbon
The saturation of straight or branched of son or unsaturated alkyl；
R2、R3、R5、R6、R7Can independently for H, F, Cl, Br, I, C1- C10Alkyl, phenyl, halohydrocarbyl or 1
The groups such as the oxyl of -4 carbon atoms；
R4、R8For C1- C10Alkyl or substituted hydrocarbon radical.
Described CuH compound refers to the compound containing Cu-H key, wherein generally also contains the Phosphine ligands of coordination, has
[CuHPL]aComposition (a=1,2,3 ..., 10).L therein can be Phosphine ligands L1-L12.R in L9、R10、R11Can
Independently for C1- C10Alkyl, phenyl, the group such as halohydrocarbyl; R9、R10Can also have (CH2)cShown knot
Structure, c=1,2,3 ..., 10.
Described other copper compounds refer to not contain the copper compound of Cu-H key, including CuF (PPh3)3 .2MeOH、CuLdX、
CuLdX2, containing 0-3 water of crystallization C2-C18Copper (II) salt of carboxylic acid or halogenated carboxylic acid or (I) salt, C1-C18Alcohol or replacement C1-C18
Cu (I) compound of alcohol etc., L therein is Phosphine ligands, and halogen is F, Cl, Br, I, and substituent group is halogen or alkoxyl, d=0,
1,2,3, X=F, Cl, Br, I, the oxyl containing 1-18 carbon atom.
Described hydrosilicon be molecule at least the compound containing a Si -- H bond, can be structure single silicon hydrogen
Compound or the mixture of hydrosilicon.Corresponding hydrosilicon has below formula：R12 dHeSiX4-d-e(X generation
Table halogen；E=1,2,3 arbitrary integer；And d and e sum 4).Or R12R13R14Si(OSiHR15)fOSiR12R13R14
Or R12(OSiHR13)fOR12(f=1,2,3 ..., 1000 integer)；Or HgR12 3-gSiOSi R12 3-gHg(g =
1,2,3).
Described hydroboron contains at least one B-H key, has BH2R12Or BHR12R13Structure composition or they
Mixture.
Above-mentioned R12、R13、R14、R15For aryl or substituted aryl or aliphatic alkyl.Wherein aryl includes phenyl, naphthyl, anthracene
Base, furyl, thienyl, pyrrole radicals, pyridine radicals etc.；Above-mentioned substituted aryl refers to that in aryl, one is substituted to all H atom
The aryl that base replaces.Substituent group can independently for C1- C8Alkyl, C1- C8Cycloalkyl, halogen, alkoxyl (C1-
C8)、-OPh、C1- C4The phenoxy group of replacement ,-OCO alkyl (C1- C8), containing the acyl group of 1-8 carbon atom ,-NO2、-NH2、
A hydrocarbylamino containing 1-8 carbon atom or Dialkylamino, the ester group containing 1-8 carbon atom ,-CONH2,-CONH- hydrocarbon
Base (C1- C8) ,-CON- dialkyl (C1- C8) etc. group；Aliphatic alkyl refers to the straight or branched of 1-8 carbon atom
Saturation or unsaturated alkyl.
The reactions steps of the present invention are as follows：
Reaction dissolvent can be ethers or aromatic hydrocarbons, including methyl ether, ether, butyl ether, oxolane, Isosorbide-5-Nitrae-dioxane,
Glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, benzene,toluene,xylene etc., also may be used
Think water or alcohols, nitrile, halogenated alkyl solvent etc..Described solvent can be the mixing of single solvent or above-mentioned solvent
Thing.The volumetric usage (mL) of solvent is 1-1000 times of the weight (g) of substrate keto ester.
Method 1：Using stable, pure CuH compound such as [CuHPPh3]6For reducing agent
(1a). under noble gases such as argon, nitrogen atmosphere, in -78 DEG C of -70 DEG C of temperature ranges, add pure CuH
Compound and reaction dissolvent, stir 1- 60 min.
With molar amount, the consumption of CuH is α, 1-5 times of beta-unsaturated carboxylic acid ester.
(1b). by keto ester and α, beta-unsaturated carboxylic acid ester is mixed and stirred for the solution of (1a), at -78 DEG C -70 DEG C
Temperature range is reacted.
With molar amount, α, the consumption of beta-unsaturated carboxylic acid ester is 1-50 times of keto ester.
(1c). reaction process is monitored by TLC or GC or HPLC, as keto ester or α, beta-unsaturated carboxylic acid ester relative
When amount no longer substantially reduces, to addition ammonium fluoride solution or dilute hydrochloric acid terminating reaction, stirring reaction liquid 1-60 in reaction system
After min, separate through conventional post processing, using the conventional method such as column chromatography or vacuum distillation or recrystallization and purification obtains target and produces
Thing γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone.
The molar concentration of ammonium fluoride solution is 0.001 mol/L saturated solution, solvent be methanol or ethanol or methanol-
Water or alcohol-water, alcohol is 0 with the volume ratio of water:100 to 100:0.With molar amount, the consumption of ammonium fluoride is the 1- 20 of CuH
Times.The concentration of dilute hydrochloric acid is 0.01 mol/L 6 mol/L, and with molar amount, the consumption of hydrochloric acid is CuH in (1a)
0.01-50 times.
Method 2：Using stable, pure CuH compound such as [CuHPPh3]6For catalyst, hydrosilicon or boron hydrogen
Compound is reducing agent
(2a). under noble gases such as argon, nitrogen atmosphere, add CuH and reaction dissolvent, stir 1-60 min.
With molar amount, the consumption of CuH is α, 0.0001-1 times of beta-unsaturated carboxylic acid ester.
(2b). in -78 DEG C of -70 DEG C of temperature ranges, by keto ester, α, beta-unsaturated carboxylic acid ester, hydrosilicon or boron
Hydrogen compound adds in any order in the solution of (2a) and stirs, or in other orders by keto ester, α, beta-unsaturated carboxylic acid
Ester, hydrosilicon or hydroboron, (2a) solution mixing, stirring reaction, by TLC or GC or HPLC monitoring react into
Journey.
With molar amount, α, the consumption of beta-unsaturated carboxylic acid ester is 1-50 times of keto ester；Hydrosilicon or hydroboration
Compound is 15 times of esters of alpha, beta, unsaturated carboxylic acids.
(2c). as keto ester or α, beta-unsaturated carboxylic acid ester relative quantity when no longer substantially reducing, by ammonium fluoride solution
Or dilute hydrochloric acid adds in the reactant mixture of step (2b), after stirring 1-60 min, through conventional post processing, column chromatography or decompression
The conventional method such as distillation or recrystallization separates and purification obtains target product γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen
Sulfonylmethyl-δ-valerolactone.
The composition of ammonium fluoride solution, concentration with identical in (1c), with molar amount, the consumption of ammonium fluoride is that silicon hydrogenation is closed
Thing or hydroboron 20 times of 1-.The concentration of dilute hydrochloric acid also with identical in step (1c), with molar amount, dilute hydrochloric acid
Consumption be 0.01-50 times of hydrosilicon or hydroboron.
Method 3 is catalyst, hydrosilicon or hydroboron for reducing using the CuH generating in reaction system
Agent
(3a). under noble gases such as argon, nitrogen atmosphere, in -78 DEG C of -70 DEG C of temperature ranges, add other copper
Compound, Phosphine ligands, reaction dissolvent, stir 1-60 min；Add hydrosilicon or hydroboron, stir 1-60
Min, prepares CuH catalyst.Also by other any charging sequences, above-mentioned several material mixings can be formed CuH catalyst.
(3b). in -78 DEG C of -70 DEG C of temperature ranges, by keto ester, α, the solution of beta-unsaturated carboxylic acid ester and step (3a)
Mixing, the relative quantity of stirring reaction to keto ester or esters of unsaturated carboxylic acids no longer substantially reduces.
With molar amount, the consumption of other copper compounds is α, 1 times of the 0.0001- of beta-unsaturated carboxylic acid ester, Phosphine ligands
Consumption is α, 0.0001 1 times of beta-unsaturated carboxylic acid ester, and the consumption of hydrosilicon or hydroboron is α, β-unsaturation
1-5 times of carboxylate.
With molar amount, α, the consumption of beta-unsaturated carboxylic acid ester is 1 to 50 times of keto ester.
(3c). ammonium fluoride solution or dilute hydrochloric acid are mixed with the reactant mixture of step (3b), stirs 1-60 min
Afterwards, separate through conventional methods such as conventional post processing, column chromatography or vacuum distillation or recrystallization and purification obtains target product γ-hydrocarbon
Oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone.
The composition of ammonium fluoride solution, concentration, consumption with identical in (2c).The concentration of dilute hydrochloric acid, consumption also with step
(2c) identical in.
The inventive method passes through cascade reaction synthetic gamma butyrolactone, δ-valerolactone, is carried out continuously in same reaction vessel
Three-step reaction is it is not necessary to separating intermediate product, avoiding middle separation process and the loss thereby resulting in, easy and simple to handle, improves
Reaction efficiency, has good using value.
Specific embodiment
In conjunction with specific experiment, the present invention is further detailed.
Embodiment 1
Reacted as follows by method 1, obtained product.
Reacted as follows by method 1, obtained product.
[CuHPPh is added in the reaction bulb of the drying crossed to nitrogen displacement3]6(4.890 g, 15 mmol CuH), toluene
(30 mL), stirring and dissolving, it is cooled to -30 DEG C, and maintain this temperature in follow-up reaction.To instillation 4- oxygen in above-mentioned solution
Generation -4-phenylbutyrate methyl ester (2.300 g, 12.0 mmol) and 2-butylene acid methyl ester (1.6 mL, 15.1 mmol) are in toluene
The solution of (10 mL), about 20 min drip off, and continue stirring reaction and react 0.5 h.It is warming up to room temperature, stir 0.5 h, Ran Houjia
Enter 20 mL saturations NH4Cl aqueous solution, and continue to stir 0.5 h.Standing split-phase.With toluene aqueous phase extracted (3 × 10 mL), close
And after organic faciess through saturated common salt water washing, anhydrous sodium sulfate drying, concentrate after, then obtain γ-benzene through column chromatography for separation
Base-γ-(1- methoxyl group acyl group) propyl group-gamma-butyrolacton (3.02 g, yield 96%).Also target can be obtained by vacuum distillation
Product.
Embodiment 2
Reacted as follows by method 2, obtained product.
To dried reaction bulb evacuation, nitrogen injection, repeatedly for three times, add [CuHPPh3]6(16 mg, 0.049
Mmol CuH) and toluene (1 mL), stirring 2 min at 25 DEG C makes [CuHPPh3]6Quan Rong.Add poly- (first in above-mentioned solution
Base hydrogen siloxane) (120 mL, 2.00 mmol SiH), 4- oxo -4-phenylbutyrate methyl ester (0.193 g, 1.00 mmol),
The toluene solution (2 mL) of acrylic acid methyl ester. (137 mL, 0.152 mmol) is added after stirring 2 min.After stirring reaction 2.0 h
Add the NH of 2 mL 1.5 mol/L4Methanol-water solution (the methanol of F：Water=3:1), split-phase, aqueous phase are stood after stirring 0.5 h
Filtrate extracts (3 × 10 mL) with dichloromethane, the organic faciess after merging through saturated common salt water washing, anhydrous sodium sulfate drying,
After concentration, then obtain product γ-phenyl-γ-(1- methoxyl group acyl group) ethyl-gamma-butyrolacton (0.203 through column chromatography for separation
G, yield 82%).
Embodiment 3 is carried out by method 3 and arrives embodiment 7, obtain product.
Embodiment 3
Under nitrogen atmosphere, to addition CuF (5.0 mg, 0.060 mmol) in the reaction bulb being dried, 1,1'- pair (two-
Phenyl phosphino-) ferrocene, (33.2 mg, 0.060 mmol), ethyl acetate (3mL), stirs 30 min at 40 DEG C.To above-mentioned molten
Add diphenyl silane (2.22 mL, 24.0 mmol SiH) in liquid, stir 30 min, then add 4- oxo -4- phenyl
Methyl butyrate (2.30 g, 12 mmol), instills the ethyl acetate solution (10 of acrylic acid methyl ester. (2.20 mL, 24 mmol)
ML), about 10 min drip off, and stir 5 h.To the NH adding 30 mL 1.5 mol/L in reactant mixture4The methanol-water solution of F
(methanol：Water=3:1), stand split-phase after stirring 0.5 h.Aqueous phase is extracted with ethyl acetate (3 × 30 mL).Organic after merging
Through saturated common salt water washing, anhydrous sodium sulfate drying, concentration, column chromatography for separation obtains product γ-phenyl-γ-(1- methoxyl group
Acyl group) ethyl-gamma-butyrolacton (1.63 g, yield 55%).
Embodiment 4
Under nitrogen atmosphere, in the reaction bulb being dried, add CuF (PPh3)32MeOH (28 mg, 0.032 mmol), double
(2- diphenylphosphine phenyl) ether (16 mg, 0.030 mmol), toluene (1 mL), stirs 15 min, is subsequently adding poly- under room temperature
(methyl hydrogen siloxane) (0.36 mL, 6.0 mmol), and stir 30 min.Then give in above-mentioned reaction mixture and instill 4-
Oxo -4-phenylbutyrate methyl ester (0.576 g, 3.00 mmol) and acrylic acid methyl ester. (0.40 mL, 4.4 mmol) are in toluene
Solution in (5 mL).The NH of 5 mL 1.5 mol/L is added after continuing stirring 4.0 h4The aqueous solution of F, after being stirred for 0.5 h
Standing split-phase.With toluene aqueous phase extracted (3 × 10 mL), the organic faciess after merging are done through saturated common salt water washing, anhydrous sodium sulfate
Dry, concentration, column chromatography for separation obtains product γ-phenyl-γ-(1- methoxyl group acyl group) ethyl-gamma-butyrolacton, and (0.700 g produces
Rate 94%).
Embodiment 5
Under nitrogen atmosphere, add CuF (PPh in dry reaction bottle3)32MeOH (4.7 mg, 0.0054 mmol), 4,
Double (diphenylphosphine) -9,9- dimethyl xanthene (2.9 mg, 0.0050 mmol) of 5-, toluene (1mL).15 are stirred under room temperature
Min, adds diphenyl silane (0.20 mL, 4.9 mmol H), stirs 30 min.It is slowly added to 4- oxo -4- (4- bromophenyl)
Methyl butyrate (0.678 g, 2.50 mmol) and the toluene solution (2 mL) of tert-butyl acrylate (0.43 ml, 3.0 mmol),
5 mL NH are added after stirring 6.0 h4Methanol-water solution (1.5 mol/L, the solvent methanol of F：Water=3:1), it is stirred for 1 h
Stand split-phase afterwards, with toluene aqueous phase extracted (3 × 10 mL), the organic faciess after merging are through saturated common salt water washing, anhydrous magnesium sulfate
It is dried, concentrates, column chromatography for separation obtains product γ-p-bromophenyl-γ-(1- tert-butoxy acyl group) ethyl-gamma-butyrolacton
(0.783 g, yield 85%).
Embodiment 6
Under 25 DEG C, nitrogen atmosphere, in the reaction bulb being dried, add CuF (PPh3)32MeOH (4.7 mg, 0.0054
Mmol), Isosorbide-5-Nitrae-bis- (diphenylphosphine) butane (2.1 mg, 0.0050 mmol), benzene (0.5 mL), stirs 15 min；Add poly-
(methyl hydrogen siloxane) (45 mL, 0.75 mmol SiH), stirs 30 min.To addition 4- oxo -4- in reactant mixture
(2- methoxyphenyl) methyl butyrate (56 mg, 0.25 mmol) and 2- methyl methacrylate (42 mL, 0.39 mmol)
Benzole soln (1 mL).2 mL NH are added after stirring 16 h4Methanol-water solution (the methanol of F：Water=3:1) (1.5 mol/L),
It is stirred for after 0.5 h standing split-phase, with benzene aqueous phase extracted (3 × 3 mL), the organic faciess after merging are through saturated common salt water washing, no
Water magnesium sulfate is dried, concentrates, and column chromatography for separation obtains product γ-o-methoxyphenyl-γ-(1- methyl isophthalic acid-methoxyl group acyl group)
Ethyl-gamma-butyrolacton (43 mg, yield 59%).
Embodiment 7
Under nitrogen atmosphere, in the reaction bulb being dried, add Cu (O2CCH3)2.H2O (5 mg, 0.025 mmol), 4,5-
Double (diphenylphosphine) -9,9- dimethyl xanthenes (14 mg, 0.024 mmol), methyl tertiary butyl ether(MTBE) (3 mL), stirs at 0 DEG C
Add 1,1,3,3- tetramethyl two silicon ether (90 mL, 1.02 mmol SiH) after mixing 15 min, be stirred for 2 h.Anti- to stirring
Answer and in system, add 5- oxo -5- (3- methoxyphenyl) methyl valerate (0.139 g, 0.589 mmol) and the tertiary fourth of acrylic acid
The t-butyl methyl ether solution (1 mL) of ester (100 mL, 0.690 mmol), adds 5 mL NH after stirring 6.0h4The methanol of F-
Aqueous solution (1.5 mol/L, solvent methanol：Water=3:1), it is stirred for 1 h.Standing, filtration, filtrate split-phase, aqueous phase methyl- tert
Butyl ether washs (3 × 5 mL), merges organic faciess.Saturated common salt water washing organic faciess, anhydrous sodium sulfate drying.Concentrated by rotary evaporation,
Column chromatography for separation obtains product δ-m-methoxyphenyl-δ-(1- tert-butoxy acyl group) ethyl-δ-valerolactone, and (0.122 g produces
Rate 74%).
.
Claims (4)
1. γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone synthetic method it is characterised in that
Structure is：
Its synthetic method is：
Method 1：With CuH compound as reducing agent and keto ester, esters of alpha, beta, unsaturated carboxylic acids are synthesized γ-hydrocarbon oxygen acyl group first
Base-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone；
Method 2：With CuH compound as catalyst, keto ester, α, be synthesized between beta-unsaturated carboxylic acid ester, hydrosilicon γ-
Hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone；
Method 3：During the course of the reaction catalyst is generated by other copper compounds, Phosphine ligands, hydrosilicon reaction, be directly catalyzed
Hydrosilicon and keto ester, the reaction of esters of alpha, beta, unsaturated carboxylic acids, synthesis γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon
Oxygen sulfonylmethyl-δ-valerolactone；Synthesis γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone reaction
Formula is respectively as shown in formula (1), (2)：
Wherein, R1For phenyl, the phenyl of halogen substiuted and C1-C8The phenyl that alkoxyl replaces, R2、R3It is hydrogen, R4For methyl,
R5、R6、R7It is hydrogen or methyl, R8For C1-C10 alkyl；
Described CuH compound refers to the compound containing Cu-H key, the Phosphine ligands containing coordination, has [CuHL]aComposition a=1,
2,3 ..., 10, L therein are Phosphine ligands L1-L3, L5-L12：
R in L9、R10、R11For C1-C10Alkyl or phenyl；
Described other copper compounds refer to not contain the copper compound of Cu-H key, are CuF (PPh3)3.2MeOH、CuLdX、CuLdX2,
D=1,2,3, X=F, Cl, Br, I, containing 1-18 carbon atom oxyl, other copper compounds are the C containing 0-3 water of crystallization2-
C18Copper (II) salt of carboxylic acid or halogenated carboxylic acid or (I) salt, C1-C18Alcohol or replacement C1-C18Cu (I) compound of alcohol, halogen therein
Element is F, Cl, Br, I, and substituent group is halogen.
2. γ according to claim 1-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone
Synthetic method it is characterised in that described hydrosilicon is at least compound containing a Si -- H bond in molecule, structure list
One hydrosilicon or the mixture of hydrosilicon, corresponding hydrosilicon has below formula：R12 dHeSiX4-d-e, X representative
Halogen, e=1,2,3 arbitrary integers, and d and e sum 4；Or R12R13R14Si(OSiHR15)fOSiR12R13R14Or R12
(OSiHR13)fOR12, f=1,2,3 ..., 1000 integer, or HgR12 3-gSiOSi R12 3-gHg, g=1,2,3；R12、R13、R14、
R15For aryl or substituted aryl or aliphatic alkyl, wherein aryl be phenyl, naphthyl, anthryl, furyl, thienyl, pyrrole radicals,
Pyridine radicals, substituted aryl refers to an aryl being substituted with a substituent to all H atom in aryl, and substituent group is C1-C8Hydrocarbon
Base, C1-C8Cycloalkyl, halogen, alkoxyl (C1-C8)、-OPh、C1-C4The phenoxy group of replacement ,-OCO alkyl (C1-C8), contain 1-8
The acyl group of individual carbon atom ,-NO2、-NH2, containing a hydrocarbylamino of 1-8 carbon atom or Dialkylamino, contain 1-8 carbon atom
Ester group ,-CONH2,-CONH- alkyl (C1-C8) ,-CON- dialkyl (C1-C8), aliphatic alkyl refers to the straight chain of 1-8 carbon atom
Or the saturation of side chain or unsaturated alkyl.
3. γ according to claim 1 and 2-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone
Synthetic method it is characterised in that the step of synthetic method is：
Method 1：It is reducing agent using CuH compound
(1a). under inert gas atmosphere, in -78 DEG C of -70 DEG C of temperature ranges, add CuH compound and reaction dissolvent, stir 1-
60min, with molar amount, the consumption of CuH is α, 1-5 times of beta-unsaturated carboxylic acid ester,
(1b). by keto ester and α, beta-unsaturated carboxylic acid ester is mixed and stirred for the solution of (1a), -78 DEG C of -70 DEG C of humidity provinces
Between react, with molar amount, α, the consumption of beta-unsaturated carboxylic acid ester is 1-50 times of keto ester,
(1c). reaction process is monitored by TLC or GC or HPLC, when the relative quantity of keto ester or esters of unsaturated carboxylic acids is no longer obvious
During reduction, add ammonium fluoride solution in reaction system, or dilute hydrochloric acid terminating reaction, after stirring reaction liquid 1-60min, through routine
Post processing, separated using column chromatography or vacuum distillation or recrystallization method and purification obtain target product γ-hydrocarbon oxygen sulfonylmethyl-
Gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone,
The molar concentration of ammonium fluoride solution is 0.001mol/L saturated solution, and solvent is methanol or ethanol or methanol-water or second
Alcohol-water, alcohol is 0 with the volume ratio of water:100 to 100:0, with molar amount, the consumption of ammonium fluoride is 1-20 times of CuH, dilute salt
The concentration of acid is 0.01mol/L 6mol/L, and with molar amount, the consumption of hydrochloric acid is 0.01-50 times of CuH in (1a)；
Method 2：Using CuH compound be catalyst, hydrosilicon be reducing agent
(2a). under inert gas atmosphere, add CuH and reaction dissolvent, stir 1-60min, with molar amount, the consumption of CuH
For α, 0.0001-1 times of beta-unsaturated carboxylic acid ester,
(2b). in -78 DEG C of -70 DEG C of temperature ranges, by keto ester, α, beta-unsaturated carboxylic acid ester, hydrosilicon are in any order
Add in the solution of (2a) and stir, or in other orders by keto ester, α, beta-unsaturated carboxylic acid ester, hydrosilicon, (2a)
Solution mixing, stirring reaction, reaction process is monitored by TLC or GC or HPLC, with molar amount, α, beta-unsaturated carboxylic acid ester
Consumption be 1-50 times of keto ester；Hydrosilicon is α, 15 times of beta-unsaturated carboxylic acid ester,
(2c). when keto ester or esters of unsaturated carboxylic acids relative quantity no longer substantially reduce when, by ammonium fluoride solution or dilute hydrochloric acid
Add in the reactant mixture of step (2b), after stirring 1-60min, tie through conventional post processing, column chromatography or vacuum distillation or again
Crystal method separates and purification obtains target product γ-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, in δ-hydrocarbon oxygen sulfonylmethyl-δ-penta
Ester,
The molar concentration of ammonium fluoride solution is 0.001mol/L saturated solution, and solvent is methanol or ethanol or methanol-water or second
Alcohol-water, alcohol is 0 with the volume ratio of water:100 to 100:0, with molar amount, the consumption of ammonium fluoride is the 1-20 of hydrosilicon
Times, the concentration of dilute hydrochloric acid is 0.01mol/L 6mol/L, and with molar amount, the consumption of dilute hydrochloric acid is the 0.01- of hydrosilicon
50 times；
Method 3：Using in reaction system generate CuH be catalyst, hydrosilicon be reducing agent
(3a). under inert gas atmosphere, in -78 DEG C of -70 DEG C of temperature ranges, add other copper compounds, Phosphine ligands, reaction molten
Agent, stirs 1-60min；Add hydrosilicon, stir 1-60min, prepare CuH catalyst, or by other any chargings
Above-mentioned several material mixings are formed CuH catalyst by order, and with molar amount, the consumption of other copper compounds is α, β-unsaturation
0.0001-1 times of carboxylate, the consumption of Phosphine ligands is α, 0.0001 1 times of beta-unsaturated carboxylic acid ester, the use of hydrosilicon
Measure as α, 1-5 times of beta-unsaturated carboxylic acid ester,
(3b). in -78 DEG C of -70 DEG C of temperature ranges, by keto ester, α, beta-unsaturated carboxylic acid ester is mixed with the solution of step (3a),
Stirring reaction no longer reduces to keto ester or α, the relative quantity of beta-unsaturated carboxylic acid ester, with molar amount, α, beta-unsaturated carboxylic acid
The consumption of ester is 1 to 50 times of keto ester, and the consumption of hydrosilicon is α, 1-5 times of beta-unsaturated carboxylic acid ester,
(3c). ammonium fluoride solution or dilute hydrochloric acid are mixed with the reactant mixture of step (3b), after stirring 1-60min, through routine
Post processing, column chromatography or vacuum distillation or recrystallization method separate and purification obtain target product γ-hydrocarbon oxygen sulfonylmethyl-γ-
Butyrolactone, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone,
The molar concentration of ammonium fluoride solution is 0.001mol/L saturated solution, and solvent is methanol or ethanol or methanol-water or second
Alcohol-water, alcohol is 0 with the volume ratio of water:100 to 100:0, with molar amount, the consumption of ammonium fluoride is the 1-20 of hydrosilicon
Times, the concentration of dilute hydrochloric acid is 0.01mol/L 6mol/L, and with molar amount, the consumption of hydrochloric acid is the 0.01-50 of hydrosilicon
Times.
4. γ according to claim 3-hydrocarbon oxygen sulfonylmethyl-gamma-butyrolacton, δ-hydrocarbon oxygen sulfonylmethyl-δ-valerolactone
Synthetic method it is characterised in that described reaction dissolvent is ethers or aromatic hydrocarbons, including methyl ether, ether, butyl ether, oxolane,
1,4- dioxane, glycol dimethyl ether, ethylene glycol diethyl ether, diethylene glycol dimethyl ether, diethylene glycol diethyl ether, benzene, toluene,
The mixture of one or more of dimethylbenzene, water or alcohols, nitrile or halogenated alkyl solvent, the volumetric usage of solvent is substrate ketone
1-1000 times of the weight of acid esters.
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