CN107337572A - 一种制备β,γ‑不饱和羧酸类化合物的方法 - Google Patents
一种制备β,γ‑不饱和羧酸类化合物的方法 Download PDFInfo
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- CN107337572A CN107337572A CN201710401044.9A CN201710401044A CN107337572A CN 107337572 A CN107337572 A CN 107337572A CN 201710401044 A CN201710401044 A CN 201710401044A CN 107337572 A CN107337572 A CN 107337572A
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- unsaturated carboxylic
- alkyl
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- 238000000034 method Methods 0.000 title claims abstract description 57
- 150000001875 compounds Chemical class 0.000 title claims abstract description 16
- 150000001732 carboxylic acid derivatives Chemical class 0.000 title claims description 14
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 67
- 238000006243 chemical reaction Methods 0.000 claims abstract description 44
- -1 allyl alcohol compound Chemical class 0.000 claims abstract description 42
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims abstract description 34
- 229910052763 palladium Inorganic materials 0.000 claims abstract description 32
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims abstract description 28
- XXROGKLTLUQVRX-UHFFFAOYSA-N hydroxymethylethylene Natural products OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 claims abstract description 20
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims abstract description 17
- 235000019253 formic acid Nutrition 0.000 claims abstract description 17
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims abstract description 14
- 150000008065 acid anhydrides Chemical class 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 13
- 239000003446 ligand Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims description 47
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 8
- IVSZLXZYQVIEFR-UHFFFAOYSA-N m-xylene Chemical group CC1=CC=CC(C)=C1 IVSZLXZYQVIEFR-UHFFFAOYSA-N 0.000 claims description 8
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 7
- GPAYUJZHTULNBE-UHFFFAOYSA-N diphenylphosphine Chemical compound C=1C=CC=CC=1PC1=CC=CC=C1 GPAYUJZHTULNBE-UHFFFAOYSA-N 0.000 claims description 7
- 125000003118 aryl group Chemical group 0.000 claims description 6
- 125000001072 heteroaryl group Chemical group 0.000 claims description 6
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims description 5
- SHPHYIMDOLOPIB-UHFFFAOYSA-N 2,3-dibenzylidene-1H-indene Chemical class C(C1=CC=CC=C1)=C1C(C2=CC=CC=C2C1)=CC1=CC=CC=C1 SHPHYIMDOLOPIB-UHFFFAOYSA-N 0.000 claims description 5
- CHIHQLCVLOXUJW-UHFFFAOYSA-N benzoic anhydride Chemical compound C=1C=CC=CC=1C(=O)OC(=O)C1=CC=CC=C1 CHIHQLCVLOXUJW-UHFFFAOYSA-N 0.000 claims description 5
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 claims description 5
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 5
- 125000001424 substituent group Chemical group 0.000 claims description 5
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 4
- 125000003320 C2-C6 alkenyloxy group Chemical group 0.000 claims description 4
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 4
- 239000004305 biphenyl Substances 0.000 claims description 4
- 235000010290 biphenyl Nutrition 0.000 claims description 4
- 239000004327 boric acid Substances 0.000 claims description 4
- 125000004185 ester group Chemical group 0.000 claims description 4
- 150000002170 ethers Chemical class 0.000 claims description 4
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 claims description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 125000002541 furyl group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 claims description 3
- 230000002194 synthesizing effect Effects 0.000 claims description 3
- 125000001544 thienyl group Chemical group 0.000 claims description 3
- 125000006267 biphenyl group Chemical group 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 claims 2
- OTEKOJQFKOIXMU-UHFFFAOYSA-N 1,4-bis(trichloromethyl)benzene Chemical compound ClC(Cl)(Cl)C1=CC=C(C(Cl)(Cl)Cl)C=C1 OTEKOJQFKOIXMU-UHFFFAOYSA-N 0.000 claims 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 239000005864 Sulphur Substances 0.000 claims 1
- 230000037429 base substitution Effects 0.000 claims 1
- 150000004820 halides Chemical class 0.000 claims 1
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims 1
- 239000001294 propane Substances 0.000 claims 1
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 8
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 abstract description 6
- 229910002091 carbon monoxide Inorganic materials 0.000 abstract description 6
- 238000010189 synthetic method Methods 0.000 abstract description 3
- 230000001988 toxicity Effects 0.000 abstract description 3
- 231100000419 toxicity Toxicity 0.000 abstract description 3
- 229910052751 metal Inorganic materials 0.000 abstract description 2
- 239000002184 metal Substances 0.000 abstract description 2
- 231100000614 poison Toxicity 0.000 abstract description 2
- 230000007096 poisonous effect Effects 0.000 abstract description 2
- 150000001735 carboxylic acids Chemical class 0.000 abstract 2
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 84
- 150000007513 acids Chemical class 0.000 description 42
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 41
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 21
- 238000005160 1H NMR spectroscopy Methods 0.000 description 21
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- 239000007787 solid Substances 0.000 description 21
- 238000004458 analytical method Methods 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 6
- CXNIUSPIQKWYAI-UHFFFAOYSA-N xantphos Chemical compound C=12OC3=C(P(C=4C=CC=CC=4)C=4C=CC=CC=4)C=CC=C3C(C)(C)C2=CC=CC=1P(C=1C=CC=CC=1)C1=CC=CC=C1 CXNIUSPIQKWYAI-UHFFFAOYSA-N 0.000 description 5
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 4
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
- 150000002118 epoxides Chemical class 0.000 description 4
- 239000007789 gas Substances 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 0 CC([C@@](C)C1*CCC1)C1CCCC1 Chemical compound CC([C@@](C)C1*CCC1)C1CCCC1 0.000 description 3
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- ONDPGJBEBGWAKI-UHFFFAOYSA-N diphenylphosphane;propane Chemical compound CCC.C=1C=CC=CC=1PC1=CC=CC=C1 ONDPGJBEBGWAKI-UHFFFAOYSA-N 0.000 description 3
- 239000002994 raw material Substances 0.000 description 3
- OOCCDEMITAIZTP-QPJJXVBHSA-N (E)-cinnamyl alcohol Chemical compound OC\C=C\C1=CC=CC=C1 OOCCDEMITAIZTP-QPJJXVBHSA-N 0.000 description 2
- 125000006276 2-bromophenyl group Chemical group [H]C1=C([H])C(Br)=C(*)C([H])=C1[H] 0.000 description 2
- 125000004801 4-cyanophenyl group Chemical group [H]C1=C([H])C(C#N)=C([H])C([H])=C1* 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 150000004808 allyl alcohols Chemical class 0.000 description 2
- 229910052786 argon Inorganic materials 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 229910002092 carbon dioxide Inorganic materials 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 235000013399 edible fruits Nutrition 0.000 description 2
- 150000002240 furans Chemical class 0.000 description 2
- 239000011521 glass Substances 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- 125000004430 oxygen atom Chemical group O* 0.000 description 2
- 229920001084 poly(chloroprene) Polymers 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 125000004646 sulfenyl group Chemical group S(*)* 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 description 1
- WFLOTYSKFUPZQB-UHFFFAOYSA-N 1,2-difluoroethene Chemical group FC=CF WFLOTYSKFUPZQB-UHFFFAOYSA-N 0.000 description 1
- PQPVYEDTTQIKIA-UHFFFAOYSA-N 1,2-dimethyl-9h-xanthene Chemical compound C1=CC=C2CC3=C(C)C(C)=CC=C3OC2=C1 PQPVYEDTTQIKIA-UHFFFAOYSA-N 0.000 description 1
- LVEYOSJUKRVCCF-UHFFFAOYSA-N 1,3-Bis(diphenylphosphino)propane Substances C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCP(C=1C=CC=CC=1)C1=CC=CC=C1 LVEYOSJUKRVCCF-UHFFFAOYSA-N 0.000 description 1
- SJWIOZSGMUJDFJ-UHFFFAOYSA-N 1-benzylideneindene Chemical class C1=CC2=CC=CC=C2C1=CC1=CC=CC=C1 SJWIOZSGMUJDFJ-UHFFFAOYSA-N 0.000 description 1
- PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
- UCFSYHMCKWNKAH-UHFFFAOYSA-N 4,4,5,5-tetramethyl-1,3,2-dioxaborolane Chemical class CC1(C)OBOC1(C)C UCFSYHMCKWNKAH-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 229910014033 C-OH Inorganic materials 0.000 description 1
- JNQWXIYXMPKHDM-UHFFFAOYSA-N C=CC(c1ccc[o]1)O Chemical compound C=CC(c1ccc[o]1)O JNQWXIYXMPKHDM-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 229910014570 C—OH Inorganic materials 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- 229910002666 PdCl2 Inorganic materials 0.000 description 1
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 1
- RYXZOQOZERSHHQ-UHFFFAOYSA-N [2-(2-diphenylphosphanylphenoxy)phenyl]-diphenylphosphane Chemical compound C=1C=CC=C(P(C=2C=CC=CC=2)C=2C=CC=CC=2)C=1OC1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RYXZOQOZERSHHQ-UHFFFAOYSA-N 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000004414 alkyl thio group Chemical group 0.000 description 1
- OOCCDEMITAIZTP-UHFFFAOYSA-N allylic benzylic alcohol Natural products OCC=CC1=CC=CC=C1 OOCCDEMITAIZTP-UHFFFAOYSA-N 0.000 description 1
- 239000012300 argon atmosphere Substances 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 230000006315 carbonylation Effects 0.000 description 1
- 238000005810 carbonylation reaction Methods 0.000 description 1
- 230000021523 carboxylation Effects 0.000 description 1
- 238000006473 carboxylation reaction Methods 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 229940126678 chinese medicines Drugs 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000004927 clay Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 125000001047 cyclobutenyl group Chemical group C1(=CCC1)* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- AIGRXSNSLVJMEA-FQEVSTJZSA-N ethoxy-(4-nitrophenoxy)-phenyl-sulfanylidene-$l^{5}-phosphane Chemical compound O([P@@](=S)(OCC)C=1C=CC=CC=1)C1=CC=C([N+]([O-])=O)C=C1 AIGRXSNSLVJMEA-FQEVSTJZSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 238000003760 magnetic stirring Methods 0.000 description 1
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical group COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- CWKLZLBVOJRSOM-UHFFFAOYSA-N methyl pyruvate Chemical compound COC(=O)C(C)=O CWKLZLBVOJRSOM-UHFFFAOYSA-N 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 239000003208 petroleum Substances 0.000 description 1
- RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000002390 rotary evaporation Methods 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 230000000707 stereoselective effect Effects 0.000 description 1
- 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 235000012773 waffles Nutrition 0.000 description 1
- 150000003732 xanthenes Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B37/00—Reactions without formation or introduction of functional groups containing hetero atoms, involving either the formation of a carbon-to-carbon bond between two carbon atoms not directly linked already or the disconnection of two directly linked carbon atoms
- C07B37/04—Substitution
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/57—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and carboxyl groups, other than cyano groups, bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
- C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
- C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
- C07C323/50—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton
- C07C323/62—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and carboxyl groups bound to the same carbon skeleton having the sulfur atom of at least one of the thio groups bound to a carbon atom of a six-membered aromatic ring of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/347—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups
- C07C51/353—Preparation of carboxylic acids or their salts, halides or anhydrides by reactions not involving formation of carboxyl groups by isomerisation; by change of size of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C57/00—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms
- C07C57/30—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings
- C07C57/42—Unsaturated compounds having carboxyl groups bound to acyclic carbon atoms containing six-membered aromatic rings having unsaturation outside the rings
-
- C—CHEMISTRY; METALLURGY
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Abstract
本发明提供一种制备β,γ‑不饱和羧酸类化合物的方法,所述方法包括在钯催化剂、膦配体、酸酐和有机溶剂存在下,使式1或式2的烯丙基醇化合物与甲酸进行反应,得到式3或式4的β,γ‑不饱和羧酸类化合物,其中R1、R2和R3如本文所定义。本发明的方法利用甲酸作为羧基化试剂,价格低廉,安全稳定,毒性低;产率高,操作容易,经济性好;与现有合成方法相比,本发明方法避免了毒性气体一氧化碳和/或当量活性金属试剂的使用,符合绿色环境友好化学的要求;此外,本发明方法中催化剂用量少,反应条件温和,而且反应物转化率高、产物收率高,具有很好的工业前景。
Description
技术领域
本发明涉及化合物合成领域,具体涉及钯催化甲酸和烯丙基醇反应制备β,γ-不饱和羧酸类化合物的方法。
背景技术
β,γ-不饱和羧酸化合物在生物医药、有机合成以及化学工业中是一类非常重要的中间体。
关于β,γ-不饱和羧酸化合物的合成方法,Ruth Naigre和Howard Alper的文章(Palladium clay catalyzed regio-and stereospecific synthesis ofβ,γ-unsaturated acids by the carbonylation of allylic alcohols,Ruth Naigre andHoward Alper,Journal of Molecular Catalysis A:Chemical 111(1996)1l-15)中公开的方法利用一氧化碳为羧基化原料,其反应体系中需要高的一氧化碳压力,同时一氧化碳毒性大,操作危险困难。
此外,Manuel van Gemmeren等人(Switchable Site-Selective CatalyticCarboxylation of Allylic Alcohols with CO2,Manuel van Gemmeren,MarinoAndreu Tortajada,Shang-Zheng Sun,Keisho Okura,and Ruben Martin,Angew.Chem.Int.Ed.2017,DOI:10.1002/anie.201702857)提供的方法是采用二氧化碳气体为羧基化原料,而且反应体系中需要加入4倍当量的活性有机金属锌粉作为还原剂,原子经济性低,不符合绿色有机化学的发展方向。
发明内容
鉴于此,本发明的目的在于解决现有合成β,γ-不饱和羧酸类化合物工艺中的一个或多个问题或缺陷。
为此,本发明提供了一种用于合成β,γ-不饱和羧酸类化合物的方法,所述方法包括在钯催化剂、膦配体、酸酐和有机溶剂存在下,使式1或式2的烯丙基醇化合物与甲酸进行反应,得到式3或式4的β,γ-不饱和羧酸类化合物,
其中,R1、R2和R3各自独立地为氢原子、C1-6烷基、C1-6卤代烷基或任选地被一个或多个取代基取代的芳基或杂芳基,并且其中所述取代基选自C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代烷氧基、氰基、卤素、C2-6烯基、C2-6卤代烯基、C2-6烯氧基、C1-6烷硫基、C1-6卤代烷硫基、C1-6烷基取代的硼酸酯基、C1-6烷基C1-6烷酸酯基或苄氧基,所述芳基是苯基或萘基,所述杂芳基是噻吩基或呋喃基。
在一个优选实施方案中,所述甲酸与所述烯丙基醇类化合物的摩尔比为1:1-4:1。
在一个优选实施方案中,所述钯催化剂与所述膦配体的摩尔比为1:1-1:5。
在一个优选实施方案中,所述钯催化剂与所述烯丙基醇类化合物的摩尔比为0.001:1-0.05:1。
在一个优选实施方案中,所述酸酐与所述烯丙基醇类化合物的摩尔比0.5:1-4:1。
在一个优选实施方案中,所述反应的温度为60-150℃并且时间为1-30小时。
在一个优选实施方案中,所述钯催化选自醋酸钯、三(二亚苄基茚丙酮)二钯、四(三苯基膦)钯和氯化钯中的至少一种。
在一个优选实施方案中,所述膦配体选自1,3-双(二苯基膦)丙烷、4,5-双二苯基膦-9,9-二甲基氧杂蒽、双(2-二苯基磷苯基)醚和4,6-二(二苯基膦)吩嗪中的至少一种。
在一个优选实施方案中,所述酸酐选自乙酸酐、新戊酸酐和苯甲酸酐中的至少一种。
在一个优选实施方案中,所述有机溶剂选自苯、甲苯、间二甲苯、均三甲苯、环己烷和1,4-二氧六环中的至少一种。
本发明的方法利用甲酸作为羧基化试剂,价格低廉,安全稳定,毒性低;产率高,操作容易,经济性好;与现有合成方法相比,本发明方法避免了毒性气体一氧化碳和/或当量活性金属试剂的使用,符合绿色环境友好化学的要求;此外,本发明方法中催化剂用量少,反应条件温和,而且反应物转化率高、产物收率高,具有很好的工业前景。
具体实施方式
本发明提供了一种用于合成β,γ-不饱和羧酸类化合物的方法,本发明的方法通过利用甲酸为原料并使用酸酐代替传统方法中使用的一氧化碳,同时利用钯催化插羰反应实现烯丙基醇的C-OH键断裂,从而得到所需的β,γ-不饱和羧酸类化合物。
更具体地,本发明的方法是在钯催化剂、膦配体、酸酐和有机溶剂存在下,使式1或式2的烯丙基醇化合物与甲酸进行反应,得到式3或式4的β,γ-不饱和羧酸类化合物,
其中,R1、R2和R3各自独立地为氢原子、C1-6烷基、C1-6卤代烷基或任选地被一个或多个取代基取代的芳基或杂芳基,并且其中所述取代基选自C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代烷氧基、氰基、卤素、C2-6烯基、C2-6卤代烯基、C2-6烯氧基、C1-6烷硫基、C1-6卤代烷硫基、C1-6烷基取代的硼酸酯基、C1-6烷基C1-6烷酸酯基或苄氧基(BnO),所述芳基是苯基或萘基,所述杂芳基是噻吩基或呋喃基。
在本发明中,C1-6烷基的实例包括甲基、乙基、丙基、丁基、戊基、己基及其异构体。C1-6卤代烷基是指上述C1-6烷基被一个或多个卤素取代形成的基团如三氟甲基。C1-6烷氧基是指上述C1-6烷基与氧原子连接形成的基团,如甲氧基、乙氧基、丙氧基、丁氧基等。C1-6卤代烷氧基是上述C1-6烷氧基被一个或多个卤素取代形成的基团如三氟甲氧基。卤素是指氟、氯、溴或碘。C2-6烯基的实例包括乙烯基、丙烯基、丁烯基、戊烯基、己烯基及其异构体。C2-6卤代烯基是指上述C2-6烯基被一个或多个卤素取代形成的基团如二氟乙烯基。C2-6烯氧基是指上述C2-6烯基与氧原子连接形成的基团,如乙烯氧基、丙烯氧基、丁烯氧基等。C1-6烷硫基的实例包括甲硫基、乙硫基、丙硫基、丁硫基、戊硫基、己硫基及其异构体。C1-6卤代烷硫基是指上述C1-6烷硫基被一个或多个卤素取代形成的基团如三氟甲硫基。C1-6烷基取代的硼酸酯基的实例包括3,4-四甲基二氧杂戊硼烷基等。C1-6烷基C1-6烷酸酯基的实例包括甲酸甲酯基团等。
本发明的镍催化烯丙基醇和甲酸反应制备β,γ-不饱和羧酸类化合物方法,优选在惰性气氛如氩气气氛中进行。在钯催化烯丙基醇和甲酸反应实现β,γ-不饱和羧酸的制备中,合理的钯催化剂、配体种类、烯丙基醇与甲酸的摩尔比以及烯丙基醇与酸酐的摩尔比是进行该反应重要的工艺条件。
优选地,在本发明中,甲酸与烯丙基醇类化合物的摩尔比为1.0:1-4.0:1,更优选为3:1。
优选地,在本发明中,钯催化剂与膦配体的摩尔比为1:1-1:5,更优选为1:4。
优选地,在本发明中,钯催化剂与烯丙基醇类化合物的摩尔比为0.001:1-0.05:1,更优选为0.005:1。
优选地,在本发明中,酸酐与烯丙基醇类化合物的摩尔比0.5:1-4:1,更优选为3:1。
优选地,在本发明中,反应的温度为60-150℃并且时间为1-30小时,更优选反应温度为80℃,时间12小时。
优选地,在本发明中,钯催化选自醋酸钯、三(二亚苄基茚丙酮)二钯、四(三苯基膦)钯和氯化钯中的至少一种,更优选为三(二亚苄基茚丙酮)二钯。
优选地,在本发明中,膦配体选自1,3-双(二苯基膦)丙烷、4,5-双二苯基膦-9,9-二甲基氧杂蒽、双(2-二苯基磷苯基)醚和4,6-二(二苯基膦)吩嗪中的至少一种,更优选为4,5-双二苯基膦-9,9-二甲基氧杂蒽。
优选地,在本发明中,酸酐选自乙酸酐、新戊酸酐和苯甲酸酐中的至少一种,更优选为乙酸酐。
优选地,在本发明中,有机溶剂选自苯、甲苯、间二甲苯、均三甲苯、环己烷和1,4-二氧六环中的至少一种,更优选为甲苯。
为了进一步阐明本发明,下面结合实施例对本发明优选实施方案进行描述,但是应当理解,这些描述只是为了进一步说明本发明的特征和优点,而不是对本发明权利要求的限制,本领域普通技术人员在没有作出创造性劳动前提下所获得的所有其他实施例,都属于本发明保护的范围。
除非另行定义,本文中所使用的所有专业与科学用语与本领域熟练人员所熟悉的意义相同。此外,任何与所记载内容相似或均等的方法及材料皆可应用于本发明方法中。文中所述的较佳实施方法与材料仅作示范之用。
本发明下述实施例中用于钯催化甲酸和烯丙基醇反应所使用的试剂分别在以下试剂公司购买:
苯(C6H6,99.7%)、甲苯(C7H8,99.5%)、环己烷(C6H12,99.9%)等均从百灵威化学试剂公司购买。
间二甲苯(C8H10,99.0%)、均三甲苯(C9H12,98.0%)、氯化钯(PdCl2,98%)、三(二亚苄基茚丙酮)二钯(Pd2(dba)3,98%)、醋酸钯(Pd(OAc)2,98%)、四(三苯基膦)钯(Pd(PPh3)4,97%)、4,5-双二苯基膦-9,9-二甲基氧杂蒽(xantphos,98%)等均从TCI公司购买。
乙酸酐(Ac2O,C4H6O3,98.5%)、1,4-二氧六环(C4H8O2,99.8%)、新戊酸酐(Piv2O,C10H18O3,99%)、苯甲酸酐(Bz2O,C14H10O3,98%)等均从国药集团化学试剂公司购买。
1,3-双(二苯基膦)丙烷(dppp,C27H26P2,95%)、双(2-二苯基磷苯基)醚(DPE-phos,O[C6H4P(C6H5)2]2,98%)、4,6-二(二苯基膦)吩嗪(Ni-xantphos,C36H27NOP2,98%)等均从Sigma-Aldrich公司购买。
实施例1:制备(E)-4-苯基丁-3-烯酸
反应条件如下:
操作过程如下:
在10mL的Schlenk反应管(北京欣维尔玻璃仪器有限公司,F891410反应管,容量10mL,磨口14/20)中加入三(二亚苄基茚丙酮)二钯(Pd2(dba)3,0.5mol%,2.3mg)、4,5-双二苯基膦-9,9-二甲基氧杂蒽(xantphos,2.0mol%,5.8mg)。用氩气完全置换管内空气三次,然后在氩气氛围下加1mL甲苯,肉桂醇(0.50mmol,67mg)、甲酸(1.5mmol,69mg)和乙酸酐(1.5mmol,152mg)。反应管密封后将该反应体系在油浴下加热到80℃并连续搅拌12小时(使用IKA磁力搅拌器,RCT基本型,搅拌速度500转/分钟)。反应完毕后,将体系冷却至室温。用乙酸乙酯稀释反应液,再将稀释过的反应液用旋转蒸发的方式浓缩(瑞士步琦有限公司,BUCHI旋转蒸发仪R-3)。浓缩残渣通过色谱柱(北京欣维尔玻璃仪器有限公司,C383040C具砂板存储球层析柱,35/20,有效长:500mL,洗脱剂为石油醚:乙酸乙酯=5:1~1:1))层析分离得到产物。产物为白色固体,共72mg,产率89%。
利用核磁共振(Bruker公司,400MHz)对实施例1中得到的(E)-4-苯基丁-3-烯酸进行分析,得到以下结果:
1H NMR(400MHz,CDCl3)δ10.02(br,1H),7.37(d,J=7.3Hz,2H),7.31(t,J=7.7Hz,2H),7.27–7.21(m,1H),6.52(d,J=15.9Hz,1H),6.34–6.23(m,1H),3.30(dd,J=7.1,1.2Hz,2H);
13C NMR(101MHz,CDCl3)δ178.1,136.8,134.1,128.7,127.8,126.5,121.0,38.2。
实施例2:制备(E)-4-(4-甲氧基苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率78%,纯度>99%。
利用核磁共振对实施例2中得到的(E)-4-(4-甲氧基苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.31(d,J=8.8Hz,2H),6.85(d,J=8.8Hz,2H),6.46(d,J=15.9Hz,1H),6.14(dt,J=15.8,7.1Hz,1H),3.80(s,3H),3.27(dd,J=7.2,1.4Hz,2H);
13C NMR(101MHz,CDCl3)δ177.8,159.4,133.5,129.6,127.6,118.7,114.1,55.4,38.1。
实施例3:制备(E)-4-(4-氟苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率85%,纯度>99%。
利用核磁共振对实施例3中得到的(E)-4-(4-氟苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.34(m,2H),7.00(m,2H),6.48(d,J=15.9Hz,1H),6.20(dt,J=15.8,7.1Hz,1H),3.29(dd,J=7.1,1.2Hz,2H);
13C NMR(101MHz,CDCl3)δ178.2,162.5,133.0,132.9,128.0,120.6,115.62,38.1。
实施例4:制备5.(E)-4-(2-溴苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率50%,纯度>99%。
利用核磁共振对实施例4中得到的(E)-4-(2-溴苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.53(d,J=7.9Hz,2H),7.26(dd,J=9.2,6.0Hz,1H),7.10(td,J=7.8,1.5Hz,1H),6.86(d,J=15.8Hz,1H),6.24(dt,J=15.7,7.1Hz,1H),3.36(dd,J=7.1,1.3Hz,2H);
13C NMR(101MHz,CDCl3)δ177.8,136.4,132.9,132.7,129.0,127.5,127.1,123.8,123.4,38.0。
实施例5:制备(E)-4-(2-氯苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率91%,纯度>99%。
利用核磁共振对实施例5中得到的(E)-4-(2-氯苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.55(dd,J=7.5,1.7Hz,1H),7.34(dd,J=7.6,1.5Hz,1H),7.25–7.14(m,2H),6.91(d,J=15.9Hz,1H),6.28(dt,J=15.7,7.2Hz,1H),3.36(dd,J=7.1,1.3Hz,2H);
13C NMR(101MHz,CDCl3)δ177.9,134.7,132.9,130.2,129.7,128.8,126.9,123.7,38.1。
实施例6、4,4-二苯基丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率96%,纯度>99%。
利用核磁共振对实施例6中得到的4,4-二苯基丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.45–7.14(m,10H),6.23(t,J=7.4Hz,1H),3.21(d,J=7.4Hz,2H);
13C NMR(101MHz,CDCl3)δ178.2,145.3,141.7,139.0,129.7,128.4,128.2,127.5,127.4,119.4,35.1。
实施例7:制备4,4-双(4-氟苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率89%,纯度>99%。
利用核磁共振对实施例7中得到的4,4-双(4-氟苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ10.06(br,1H),7.23–7.04(m,6H),6.96(t,J=8.7Hz,2H),6.16(t,J=7.4Hz,1H),3.19(d,J=7.5Hz,2H);
13C NMR(101MHz,CDCl3)δ178.3,162.4,162.4,143.4,137.8,134.7,131.4,129.1,119.6,115.4,35.2。
实施例8:制备(E)-4-(4-(苄氧基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率70%,纯度>99%。
利用核磁共振对实施例8中得到的(E)-4-(4-(苄氧基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.46–7.28(m,7H),6.92(d,J=8.5Hz,2H),6.46(d,J=15.7Hz,1H),6.27–6.03(m,1H),5.06(s,2H),3.27(d,J=7.1Hz,2H);
13C NMR(101MHz,CDCl3)δ176.9,158.5,136.9,133.4,129.7,128.6,128.0,127.5,127.5,118.7,114.9,70.0,37.9。
实施例9:制备(E)-4-(4-(三氟甲基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率85%,纯度>99%。
利用核磁共振对实施例9中得到的(E)-4-(4-(三氟甲基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.56(d,J=8.2Hz,2H),7.46(d,J=8.1Hz,2H),6.55(d,J=16.0Hz,1H),6.46–6.23(m,1H),3.33(d,J=7.0Hz,2H);
13C NMR(101MHz,CDCl3)δ177.8,140.2,132.9,129.7,126.6,125.7,124.2,123.7,38.1。
实施例10:制备(E)-4-(4-(甲氧基羰基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率78%,纯度>99%。
利用核磁共振对实施例10中得到的(E)-4-(4-(甲氧基羰基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.98(d,J=8.4Hz,2H),7.43(d,J=8.4Hz,2H),6.55(d,J=15.9Hz,1H),6.41(dt,J=15.9,7.0Hz,1H),3.91(s,3H),3.33(dd,J=7.0,1.1Hz,2H);
13C NMR(101MHz,CDCl3)δ177.2,166.9,141.1,133.1,123.0,129.1,126.2,123.7,52.1,38.0。
实施例11:制备(E)-4-(4-氰基苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,浅黄色固体,产率70%,纯度>99%。
利用核磁共振对实施例11中得到的(E)-4-(4-氰基苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.60(d,J=7.5Hz,2H),7.45(d,J=7.8Hz,2H),6.54(d,J=16.6Hz,1H),6.43(dt,J=14.9,8.6Hz,1H),3.35(d,J=6.9Hz,2H);
13C NMR(101MHz,CDCl3)δ176.1,141.0,132.5,126.8,125.0,118.8,111.0,37.7。
实施例12:制备(E)-4-(4-(甲硫基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率73%,纯度>99%。
利用核磁共振对实施例12中得到的(E)-4-(4-(甲硫基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.29(d,J=8.4Hz,2H),7.19(d,J=8.4Hz,2H),6.47(d,J=15.9Hz,1H),6.24(dt,J=15.8,7.1Hz,1H),3.29(dd,J=7.1,1.2Hz,2H),2.48(s,3H);
13C NMR(101MHz,CDCl3)δ177.5,137.9,133.6,133.4,126.7,126.6,120.2,38.0,15.8。
实施例13:制备(E)-4-(4-((三氟甲基)硫基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率78%,纯度>99%。
利用核磁共振对实施例13中得到的(E)-4-(4-((三氟甲基)硫基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.59(d,J=8.1Hz,2H),7.41(d,J=8.2Hz,2H),6.53(d,J=16.0Hz,1H),6.47–6.10(m,1H),3.33(d,J=7.0Hz,2H);
13C NMR(101MHz,CDCl3)δ177.3,139.2,136.6,132.7,123.0,129.5,127.2,123.2,37.9。
实施例14:制备(E)-4-(4-(三氟甲氧基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率49%,纯度>99%。
利用核磁共振对实施例14中得到的(E)-4-(4-(三氟甲氧基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.38(d,J=8.7Hz,2H),7.16(d,J=8.0Hz,2H),6.50(d,J=15.9Hz,1H),6.26(dt,J=15.9,7.1Hz,1H),3.31(dd,J=7.1,1.4Hz,2H);
13C NMR(101MHz,CDCl3)δ177.7,148.6,135.4,132.6,127.6,121.9,121.1,120.5,37.9。
实施例15:制备(E)-4-(4-(4,4,5,5-四甲基-1,3,2-二氧杂环戊硼烷-2-基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率84%,纯度>99%。
利用核磁共振对实施例15中得到的(E)-4-(4-(4,4,5,5-四甲基-1,3,2-二氧杂环戊硼烷-2-基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.75(d,J=7.4Hz,2H),7.37(d,J=7.6Hz,2H),6.52(d,J=15.9Hz,1H),6.41–6.28(m,1H),3.31(d,J=7.0Hz,2H),1.34(s,12H);
13C NMR(101MHz,CDCl3)δ177.3,139.3,135.1,134.0,125.6,121.9,83.8,38.0,24.9。
实施例16:制备(E)-4-(萘-2-基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率67%,纯度>99%。
利用核磁共振对实施例16中得到的(E)-4-(萘-2-基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.88–7.76(m,3H),7.72(s,1H),7.60(d,J=8.6Hz,1H),7.50–7.38(m,2H),6.69(d,J=16.0Hz,1H),6.55–6.35(m,1H),3.37(d,J=6.0Hz,2H);
13C NMR(101MHz,CDCl3)δ176.4,134.1,133.5,133.0,128.2,128.0,127.7,126.3,125.9,123.5,121.2,37.9。
实施例17:制备(E)-4-(4-(新戊酰氧基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率50%,纯度>99%。
利用核磁共振对实施例17中得到的(E)-4-(4-(新戊酰氧基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.37(d,J=8.6Hz,2H),7.00(d,J=8.6Hz,2H),6.50(d,J=15.9Hz,1H),6.23(dt,J=15.9,7.1Hz,1H),3.29(dd,J=7.1,1.4Hz,2H),1.35(s,9H);
13C NMR(101MHz,CDCl3)δ177.3,177.1,150.6,134.2,133.1,127.2,121.6,120.9,39.1,38.0,27.1。
实施例18:制备(E)-4-(噻吩-3-基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,浅黄色固体,产率78%,纯度>99%。
利用核磁共振对实施例18中得到的(E)-4-(噻吩-3-基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.34–7.08(m,3H),6.53(d,J=15.8Hz,1H),6.27–5.98(m,1H),3.26(d,J=7.0Hz,2H);
13C NMR(101MHz,CDCl3)δ178.0,139.2,128.2,126.1,124.9,122.1,120.6,37.9。
实施例19:制备(E)-4-(呋喃-2-基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,浅黄色固体,产率66%,纯度>99%。
利用核磁共振对实施例19中得到的(E)-4-(呋喃-2-基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.64–7.10(m,1H),6.62–6.01(m,4H),3.25(d,J=7.1Hz,2H);
13C NMR(101MHz,CDCl3)δ177.8,152.1,142.0,122.3,119.4,111.2,107.9,37.8。
实施例20:制备(E)-4-(4-(4-氯丁氧基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率76%,纯度>99%。
利用核磁共振对实施例20中得到的(E)-4-(4-(4-氯丁氧基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.30(d,J=8.7Hz,2H),6.83(d,J=8.7Hz,2H),6.45(d,J=15.9Hz,1H),6.13(dt,J=15.8,7.1Hz,1H),3.99(t,J=5.8Hz,2H),3.62(t,J=6.2Hz,2H),3.27(d,J=7.1Hz,2H),2.29–1.61(m,4H);
13C NMR(101MHz,CDCl3)δ177.9,158.6,133.4,129.5,127.5,118.6,114.5,67.0,44.8,38.0,29.3,26.7。
实施例21:制备(E)-4-(4-(己-5-烯-1-基氧基)苯基)丁-3-烯酸
反应条件如下:
操作过程与实施例1相同,白色固体,产率60%,纯度>99%。
利用核磁共振对实施例21中得到的(E)-4-(4-(己-5-烯-1-基氧基)苯基)丁-3-烯酸进行分析,结果如下:
1H NMR(400MHz,CDCl3)δ7.29(d,J=8.7Hz,2H),6.83(d,J=8.7Hz,2H),6.45(d,J=15.9Hz,1H),6.13(dt,J=15.8,7.1Hz,1H),5.83(ddt,J=16.9,10.2,6.7Hz,1H),5.00(ddd,J=13.6,11.1,1.3Hz,2H),3.95(t,J=6.5Hz,2H),3.27(dd,J=7.1,1.2Hz,2H),2.12(dd,J=14.3,7.2Hz,2H),1.89–1.71(m,2H),1.56(dq,J=15.0,7.6Hz,2H);
13C NMR(101MHz,CDCl3)δ178.0,158.8,138.5,133.5,129.3,127.5,118.4,114.8,114.5,67.8,38.0,33.4,28.7,25.3。
以上对本发明所提供的一种钯催化烯丙基醇和甲酸反应制备β,γ-不饱和羧酸类化合物的方法进行了详细介绍。本文中利用具体实例对发明的原理及实施方式进行了阐述,以上实施例的说明只是用于帮助理解本发明的方法及其核心思想。应当指出,对于本技术领域的普通技术人员来说,再不脱离本发明原理的前提下,还可以对本发明进行若干改进和修饰,这些改进和修饰也落入本发明权利要求的保护范围内。
Claims (10)
1.一种用于合成β,γ-不饱和羧酸类化合物的方法,所述方法包括在钯催化剂、膦配体、酸酐和有机溶剂存在下,使式1或式2的烯丙基醇化合物与甲酸进行反应,得到式3或式4的β,γ-不饱和羧酸类化合物,
其中,R1、R2和R3各自独立地为氢原子、C1-6烷基、C1-6卤代烷基或任选地被一个或多个取代基取代的芳基或杂芳基,并且其中所述取代基选自C1-6烷基、C1-6卤代烷基、C1-6烷氧基、C1-6卤代烷氧基、氰基、卤素、C2-6烯基、C2-6卤代烯基、C2-6烯氧基、C1-6烷硫基、C1-6卤代烷硫基、C1-6烷基取代的硼酸酯基、C1-6烷基C1-6烷酸酯基或苄氧基,所述芳基是苯基或萘基,所述杂芳基是噻吩基或呋喃基。
2.根据权利要求1所述的方法,其特征在于,所述甲酸与所述烯丙基醇类化合物的摩尔比为1:1-4:1。
3.根据权利要求1所述的方法,其特征在于,所述钯催化剂与所述膦配体的摩尔比为1:1-1:5。
4.根据权利要求1所述的方法,其特征在于,所述钯催化剂与所述烯丙基醇类化合物的摩尔比为0.001:1-0.05:1。
5.根据权利要求1所述的方法,其特征在于,所述酸酐与所述烯丙基醇类化合物的摩尔比0.5:1-4:1。
6.根据权利要求1所述的方法,其特征在于,所述反应的温度为60-150℃并且时间为1-30小时。
7.根据权利要求1至6中任一项所述的方法,其特征在于,所述钯催化选自醋酸钯、三(二亚苄基茚丙酮)二钯、四(三苯基膦)钯和氯化钯中的至少一种。
8.根据权利要求1至6中任一项所述的方法,其特征在于,所述膦配体选自1,3-双(二苯基膦)丙烷、4,5-双二苯基膦-9,9-二甲基氧杂蒽、双(2-二苯基磷苯基)醚和4,6-二(二苯基膦)吩嗪中的至少一种。
9.根据权利要求1至6中任一项所述的方法,其特征在于,所述酸酐选自乙酸酐、新戊酸酐和苯甲酸酐中的至少一种。
10.根据权利要求1至6中任一项所述的方法,其特征在于,所述有机溶剂选自苯、甲苯、间二甲苯、均三甲苯、环己烷和1,4-二氧六环中的至少一种。
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JING HOU,ET AL: ""Palladium-Catalyzed Hydrocarboxylation of Alkynes with Formic Acid"", 《ANGEW. CHEM. INT. ED.》 * |
RUTH NAIGRE AND HOWARD ALPER: ""Palladium clay catalyzed regio-and stereospecific synthesis of β,γ-unsaturated acids by the carbonylation of allylic alcohols"", 《JOURNAL OF MOLECULAR CATALYSIS A:CHEMICAL》 * |
TETSUYA SATOH,ET AL.: ""Palladium-Catalyzed Carbonylation of Allyl Alcohols in the Presence of Phenols"", 《J. ORG. CHEM.》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
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JP7483818B2 (ja) | 2017-02-24 | 2024-05-15 | ビーエーエスエフ ソシエタス・ヨーロピア | アリルアルコール及びそれらのアシル化生成物のカルボニル化による不飽和カルボン酸の調製のための方法 |
CN108727179A (zh) * | 2018-07-18 | 2018-11-02 | 信阳师范学院 | 一种α-烯丙基取代的α,β-不饱和酮、酯或腈化合物的合成方法 |
CN108727179B (zh) * | 2018-07-18 | 2021-04-30 | 信阳师范学院 | 一种α-烯丙基取代的α,β-不饱和酮、酯或腈化合物的合成方法 |
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