CN116947636A - 一种2-酰基-4-氧代丁酸酯衍生物的制备方法 - Google Patents
一种2-酰基-4-氧代丁酸酯衍生物的制备方法 Download PDFInfo
- Publication number
- CN116947636A CN116947636A CN202310928529.9A CN202310928529A CN116947636A CN 116947636 A CN116947636 A CN 116947636A CN 202310928529 A CN202310928529 A CN 202310928529A CN 116947636 A CN116947636 A CN 116947636A
- Authority
- CN
- China
- Prior art keywords
- oxo
- lambda
- dimethyl
- sulfadimide
- methyl
- 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.)
- Pending
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 20
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 34
- 239000012074 organic phase Substances 0.000 claims abstract description 19
- 238000001035 drying Methods 0.000 claims abstract description 16
- 238000001914 filtration Methods 0.000 claims abstract description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 15
- 239000002841 Lewis acid Substances 0.000 claims abstract description 9
- 150000007517 lewis acids Chemical class 0.000 claims abstract description 9
- 239000003960 organic solvent Substances 0.000 claims abstract description 9
- RWSOTUBLDIXVET-UHFFFAOYSA-O sulfonium Chemical compound [SH3+] RWSOTUBLDIXVET-UHFFFAOYSA-O 0.000 claims abstract description 9
- 239000000463 material Substances 0.000 claims abstract description 4
- 238000007865 diluting Methods 0.000 claims abstract description 3
- 238000002156 mixing Methods 0.000 claims abstract description 3
- 238000005406 washing Methods 0.000 claims abstract description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 51
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- -1 ethyl benzoyl imide Chemical class 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- 150000002367 halogens Chemical class 0.000 claims description 6
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 claims description 6
- 125000003118 aryl group Chemical group 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- AMXOYNBUYSYVKV-UHFFFAOYSA-M lithium bromide Chemical compound [Li+].[Br-] AMXOYNBUYSYVKV-UHFFFAOYSA-M 0.000 claims description 4
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 claims description 4
- HSZCZNFXUDYRKD-UHFFFAOYSA-M lithium iodide Chemical compound [Li+].[I-] HSZCZNFXUDYRKD-UHFFFAOYSA-M 0.000 claims description 4
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 4
- 125000001424 substituent group Chemical group 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- 239000001211 (E)-4-phenylbut-3-en-2-one Substances 0.000 claims description 3
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical group CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 claims description 3
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims description 3
- LWDDRIZJCLYGJZ-UHFFFAOYSA-N methyl 3-(3-methoxyphenyl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC=CC(OC)=C1 LWDDRIZJCLYGJZ-UHFFFAOYSA-N 0.000 claims description 3
- OXXOTNVLAORSGM-UHFFFAOYSA-N methyl 3-(3-methylphenyl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC=CC(C)=C1 OXXOTNVLAORSGM-UHFFFAOYSA-N 0.000 claims description 3
- SNZLRGHNGDZHTB-UHFFFAOYSA-N methyl 3-(4-bromophenyl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC=C(Br)C=C1 SNZLRGHNGDZHTB-UHFFFAOYSA-N 0.000 claims description 3
- VXXOASOINNOPGR-UHFFFAOYSA-N methyl 3-(4-methoxyphenyl)-3-oxopropanoate Chemical compound COC(=O)CC(=O)C1=CC=C(OC)C=C1 VXXOASOINNOPGR-UHFFFAOYSA-N 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- YKYONYBAUNKHLG-UHFFFAOYSA-N n-Propyl acetate Natural products CCCOC(C)=O YKYONYBAUNKHLG-UHFFFAOYSA-N 0.000 claims description 3
- 125000003107 substituted aryl group Chemical group 0.000 claims description 3
- 229960002135 sulfadimidine Drugs 0.000 claims description 3
- BYEAHWXPCBROCE-UHFFFAOYSA-N 1,1,1,3,3,3-hexafluoropropan-2-ol Chemical compound FC(F)(F)C(O)C(F)(F)F BYEAHWXPCBROCE-UHFFFAOYSA-N 0.000 claims description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
- IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 claims description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 2
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
- 125000003342 alkenyl group Chemical group 0.000 claims description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 2
- 229910052794 bromium Inorganic materials 0.000 claims description 2
- 229910052801 chlorine Inorganic materials 0.000 claims description 2
- 239000000460 chlorine Substances 0.000 claims description 2
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 229910052731 fluorine Inorganic materials 0.000 claims description 2
- 239000011737 fluorine Substances 0.000 claims description 2
- 229910052740 iodine Inorganic materials 0.000 claims description 2
- 239000011630 iodine Substances 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 229940090181 propyl acetate Drugs 0.000 claims description 2
- FEONEKOZSGPOFN-UHFFFAOYSA-K tribromoiron Chemical compound Br[Fe](Br)Br FEONEKOZSGPOFN-UHFFFAOYSA-K 0.000 claims description 2
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims 1
- 150000002431 hydrogen Chemical class 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 3
- 230000035484 reaction time Effects 0.000 abstract description 2
- 239000000758 substrate Substances 0.000 abstract description 2
- 238000011097 chromatography purification Methods 0.000 abstract 1
- 239000000126 substance Substances 0.000 abstract 1
- 238000004440 column chromatography Methods 0.000 description 13
- 230000005311 nuclear magnetism Effects 0.000 description 13
- 229960004306 sulfadiazine Drugs 0.000 description 10
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 9
- GKKZMYDNDDMXSE-UHFFFAOYSA-N Ethyl 3-oxo-3-phenylpropanoate Chemical compound CCOC(=O)CC(=O)C1=CC=CC=C1 GKKZMYDNDDMXSE-UHFFFAOYSA-N 0.000 description 4
- 150000001875 compounds Chemical class 0.000 description 4
- 238000003786 synthesis reaction Methods 0.000 description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- PNMLOOBLEBXYGE-UHFFFAOYSA-N ethyl 2-benzoyl-4-oxo-4-phenylbutanoate Chemical compound C=1C=CC=CC=1C(=O)C(C(=O)OCC)CC(=O)C1=CC=CC=C1 PNMLOOBLEBXYGE-UHFFFAOYSA-N 0.000 description 2
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 2
- HXUIDZOMTRMIOE-UHFFFAOYSA-M 3-oxo-3-phenylpropionate Chemical compound [O-]C(=O)CC(=O)C1=CC=CC=C1 HXUIDZOMTRMIOE-UHFFFAOYSA-M 0.000 description 1
- BZKFMUIJRXWWQK-UHFFFAOYSA-N Cyclopentenone Chemical compound O=C1CCC=C1 BZKFMUIJRXWWQK-UHFFFAOYSA-N 0.000 description 1
- 238000006086 Paal-Knorr synthesis reaction Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 238000003889 chemical engineering Methods 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- HJAAQGWRRFXKKN-UHFFFAOYSA-N ethyl 2-acetyl-4-(4-methoxyphenyl)-4-oxobutanoate Chemical compound CCOC(=O)C(C(C)=O)CC(=O)C1=CC=C(OC)C=C1 HJAAQGWRRFXKKN-UHFFFAOYSA-N 0.000 description 1
- 239000012847 fine chemical Substances 0.000 description 1
- 238000007306 functionalization reaction Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 230000001766 physiological effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/24—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明公开了一种2‑酰基‑4‑氧代丁酸酯衍生物的制备方法，包括如下步骤：(1)将β‑羰基酯、锍叶立德、路易斯酸和有机溶剂混合后，在空气氛围下于85‑95℃反应20‑25h；(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；(3)将步骤(2)所得的有机相一次经干燥、过滤、浓缩和色谱纯化，得到所述2‑酰基‑4‑氧代丁酸酯衍生物。本发明具有良好的化学选择性，所用原料易得，收率高，反应条件温和，反应时间短，底物范围广，反应专一性强，后处理简便。
Description
技术领域
本发明属于有机合成技术领域，具体涉及一种2-酰基-4-氧代丁酸酯衍生物的制备方法。
背景技术
2-酰基-4-氧代丁酸酯衍生物是重要的含羰基化合物，其子结构1,4-二酮化合物是重要的有机合成中间体，可以合成许多具有生理活性的五元杂环诸如呋喃、噻吩、吡咯等系，也是合成具有环戊烯酮型天然产物的重要原料或前体化合物，被广泛用于药物合成、组合化学、材料科学、精细化工等领域。同时，现有技术中，最常见的1,4-二酮化合物的应用是通过paal-knorr方法合成。因此，1,4-二酮化合物的有效合成和功能化一直是国内外研究的热点。
发明内容
本发明目的在于克服现有技术缺陷，提供一种2-酰基-4-氧代丁酸酯衍生物的制备方法。
本发明的反应式如下：
本发明的技术方案如下：
一种2-酰基-4-氧代丁酸酯衍生物的制备方法，包括如下步骤：
(1)将β-羰基酯、锍叶立德、路易斯酸和有机溶剂混合后，在空气氛围下于85-95℃反应20-25h；
(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相一次经干燥、过滤、浓缩和色谱纯化，得到所述2-酰基-4-氧代丁酸酯衍生物；
上述β-羰基酯的结构式为其中R1为氢、烷氧基、烷基、取代或未取代的芳香基，该取代的芳香基上的取代基为烷基、烷氧基或卤素；
上述锍叶立德的结构式为其中R2为氢、烷氧基、烷基、烯基、取代或未取代的芳香基，该取代的芳香基上的取代基为烷基、烷氧基或卤素。
在本发明的一个优选实施方案中，所述卤素为氟、氯、溴或碘。
在本发明的一个优选实施方案中，所述锍叶立德为2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮、2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-苯基乙烷-1-酮、1-(4-溴苯基)-2-(二甲基(氧代)-λ6-磺胺酰亚胺)乙烷-1-酮、2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(2-噻吩基)乙烷-1-酮、2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(2-苯氧基苯基)乙烷-1-酮、(E)-1-(二甲基(氧代)-λ6-磺胺酰亚胺)-4-苯基丁-3-烯-2-酮或2-(二甲基(氧代)-λ6-磺胺酰亚胺)乙酸丙酯。
在本发明的一个优选实施方案中，所述路易斯酸为溴化钾、氯化锂、氯化锌、氯化铝、碘化钾、碘化锂、氯化铁或溴化铁。
进一步优选的，所述路易斯酸为溴化锂。
在本发明的一个优选实施方案中，所述有机溶剂为N,N－二甲基甲酰胺、N,N－二甲基乙酰胺、1,2-二氯乙烷、甲苯、1,4-二氧六环、四氢呋喃、六氟异丙醇、异丙醇或乙腈。
进一步优选的，所述有机溶剂为乙腈。
在本发明的一个优选实施方案中，所述β-羰基酯为丙二酸二乙酯、乙酰乙酸乙酯、3-氧代-3-(对甲苯基)丙酸甲酯、3-氧代-3-(间甲苯基)丙酸甲酯、3-(4-甲氧基苯基)-3-氧代丙酸甲酯、3-(3-甲氧基苯基)-3-氧代丙酸甲酯或3-(4-溴苯基)-3-氧代丙酸甲酯。
在本发明的一个优选实施方案中，所述β-羰基酯、锍叶立德、路易斯酸的摩尔比为1:1:1，且每0.01mmol苯甲酰亚胺乙酯或其衍生物对应所述有机溶剂0.1mL。
进一步优选的，所述步骤(1)中，于90℃反应24h。
本发明的有益效果是：
1、本发明在构建2-酰基-4-氧代丁酸酯衍生物时具有良好的化学选择性。
2、本发明所用原料易得，收率高，反应条件温和，反应时间短，底物范围广，反应专一性强，后处理简便。
具体实施方式
以下通过具体实施方式对本发明的技术方案进行进一步的说明和描述。
实施例1
2-苯甲酰基-4-氧代-4-苯基丁酸乙酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮(0.1mmol)、丙二酸二乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到18.8mg的目标产物，收率为61％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.99–7.95(m,2H),6.94(d,J＝8.8Hz,2H),4.27–4.20(m,4H),4.05(t,J＝7.1Hz,1H),3.88(s,3H),3.59(d,J＝7.1Hz,2H),1.29(t,J＝7.1Hz,6H).13C NMR(126MHz,CDCl3)δ195.1,169.3,163.9,130.5,129.3,113.9,61.8,55.6,47.4,37.5,14.1.
实施例2
2-乙酰基-4-(4-甲氧基苯基)-4-氧代丁酸乙酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮(0.1mmol)、乙酰乙酸乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到14.7mg的目标产物，收率为53％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.96(d,J＝8.9Hz,2H),6.94(d,J＝8.9Hz,2H),4.22(q,J＝7.1Hz,3H),3.87(s,3H),3.68(dd,J＝18.2,8.3Hz,1H),3.48(dd,J＝18.2,5.6Hz,1H),2.45(s,3H),1.29(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ202.7,195.6,169.1,163.8,130.5,129.2,113.8,61.8,55.6,54.0,37.2,30.4,14.1.
实施例3
4-(4-甲氧基苯基)-2-(4-甲基苯甲酰基)-4-氧代丁酸甲酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮(0.1mmol)、3-氧代-3-(对甲苯基)丙酸甲酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到25.8mg的目标产物，收率为76％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.01–7.95(m,4H),7.30(d,J＝7.9Hz,2H),6.93(d,J＝8.9Hz,2H),5.12(t,J＝6.8Hz,1H),3.86(s,3H),3.71(d,J＝11.0Hz,5H),2.42(s,3H).13C NMR(126MHz,CDCl3)δ195.4,194.5,170.1,163.9,144.7,133.5,130.6,129.6,129.2,129.2,113.9,55.6,52.8,48.5,38.1,21.8.HRMS(ESI-TOF)m/z:calcd forC20H21O5+:341.1384(M+H)+,found:341.1384.
实施例4
4-(4-甲氧基苯基)-2-(3-甲基苯甲酰基)-4-氧代丁酸甲酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮(0.1mmol)、3-氧代-3-(间甲苯基)丙酸甲酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到24.1mg的目标产物，收率为71％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.00–7.95(m,2H),7.90(dd,J＝6.7,1.8Hz,2H),7.44–7.37(m,2H),6.95–6.91(m,2H),5.13(dd,J＝7.4,6.3Hz,1H),3.86(s,3H),3.78–3.67(m,5H),2.43(s,3H).13C NMR(126MHz,CDCl3)δ195.4,195.2,170.1,163.9,138.7,136.2,134.6,130.6,129.5,129.3,128.7,126.3,113.9,55.6,52.9,48.7,38.1,21.5.HRMS(ESI-TOF)m/z:calcd for C20H21O5 +:341.1384(M+H)+,found:341.1384.
实施例5
2-(4-甲氧基苯甲酰基)-4-(4-乙氧基苯基)-4-氧代丁酸甲酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮(0.1mmol)、3-(4-甲氧基苯基)-3-氧代丙酸甲酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到26.0mg的目标产物，收率为73％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.14–8.07(m,2H),8.02–7.95(m,2H),7.03–6.90(m,4H),5.11(d,J＝6.3Hz,1H),3.88(dd,J＝7.4,5.0Hz,6H),3.76–3.67(m,5H).13C NMR(126MHz,CDCl3)δ195.5,193.3,170.2,164.1,163.9,131.5,130.6,129.3,129.0,114.1,113.9,55.6,55.6,52.8,48.4,38.1.
实施例6
2-(3-甲氧基苯甲酰基)-4-(4-甲氧基苯基)-4-氧代丁酸甲酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮(0.1mmol)、3-(3-甲氧基苯基)-3-氧代丙酸甲酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到28.2mg的目标产物，收率为79％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.01–7.94(m,2H),7.70(dt,J＝7.7,1.3Hz,1H),7.59(dd,J＝2.7,1.5Hz,1H),7.41(t,J＝7.9Hz,1H),7.15(ddd,J＝8.2,2.6,1.0Hz,1H),6.98–6.90(m,2H),5.11(dd,J＝7.6,6.1Hz,1H),3.85(d,J＝1.2Hz,6H),3.78(dd,J＝18.0,7.7Hz,1H),3.73–3.65(m,4H).13C NMR(126MHz,CDCl3)δ195.3,194.8,170.0,163.9,160.0,137.4,130.6,129.8,129.2,121.7,120.4,113.9,113.0,55.6,55.5,52.8,48.8,38.1.HRMS(ESI-TOF)m/z:calcd for C20H21O6 +:357.1333(M+H)+,found:357.1333.
实施例7
2-(4-溴苯甲酰基)-4-(4-甲氧基苯基)-4-氧代丁酸甲酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮(0.1mmol)、3-(4-溴苯基)-3-氧代丙酸甲酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到30.1mg的目标产物，收率为75％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ7.97(t,J＝2.4Hz,2H),7.96(t,J＝2.5Hz,2H),7.67–7.62(m,2H),6.95–6.91(m,2H),5.06(dd,J＝8.3,5.4Hz,1H),3.88–3.80(m,4H),3.70(s,4H).13C NMR(126MHz,CDCl3)δ195.3,194.1,169.6,164.0,135.0,132.2,130.6,130.6,129.1,129.0,113.9,55.6,53.0,48.5,38.2.HRMS(ESI-TOF)m/z:calcd forC19H18BrO5 +:405.0332(M+H)+,found:405.0332.
实施例8
2-苯甲酰基-4-氧代-4-苯基丁酸乙酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-苯基乙烷-1-酮(0.1mmol)、3-氧代-3-苯基丙酸乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到22.5mg的目标产物，收率为73％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.10(dt,J＝8.2,1.0Hz,2H),8.00(dq,J＝8.1,1.5Hz,2H),7.63–7.55(m,2H),7.53–7.44(m,4H),5.13(dd,J＝7.6,6.0Hz,1H),4.16(qd,J＝7.1,1.1Hz,2H),3.82(dd,J＝18.2,7.5Hz,1H),3.73(dd,J＝18.1,6.1Hz,1H),1.17(td,J＝7.0,1.0Hz,3H).13C NMR(126MHz,CDCl3)δ197.0,194.9,169.4,136.1,133.7,133.6,129.0,128.8,128.7,128.3,61.9,48.9,38.2,14.0.
实施例9
2-苯甲酰基-4-(4-溴苯基)-4-氧代丁酸乙酯的制备
将1-(4-溴苯基)-2-(二甲基(氧代)-λ6-磺胺酰亚胺)乙烷-1-酮(0.1mmol)、3-氧代-3-苯基丙酸乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到27.6mg的目标产物，收率为71％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.12–8.07(m,2H),7.89–7.84(m,2H),7.64–7.59(m,3H),7.51(dd,J＝8.4,7.1Hz,2H),5.11(dd,J＝7.7,5.9Hz,1H),4.16(q,J＝7.1Hz,2H),3.78(dd,J＝18.2,7.7Hz,1H),3.67(dd,J＝18.2,6.0Hz,1H),1.17(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ196.1,194.7,169.2,136.1,134.9,133.8,132.1,129.8,129.1,128.9,128.8,62.0,48.9,38.2,14.0.
实施例10
2-苯甲酰基-4-氧代-4-(2-噻吩基)丁酸乙酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(2-噻吩基)乙烷-1-酮(0.1mmol)、3-氧代-3-苯基丙酸乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到19.9mg的目标产物，收率为63％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.11–8.06(m,2H),7.83(dd,J＝3.8,1.2Hz,1H),7.66(dd,J＝4.9,1.1Hz,1H),7.63–7.57(m,1H),7.50(dd,J＝8.4,7.2Hz,2H),7.15(dd,J＝5.0,3.8Hz,1H),5.12(dd,J＝7.5,6.2Hz,1H),4.16(q,J＝7.1Hz,2H),1.16(t,J＝7.1Hz,3H).13CNMR(126MHz,CDCl3)δ194.8,189.9,169.2,143.2,136.1,134.2,133.8,132.7,129.1,128.8,128.4,62.0,48.9,38.6,14.0.
实施例11
2-苯甲酰基-4-氧代-4-(2-苯氧基苯基)丁酸乙酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(2-苯氧基苯基)乙烷-1-酮(0.1mmol)、3-氧代-3-苯基丙酸乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到28.6mg的目标产物，收率为71％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.08–8.01(m,2H),7.86(dd,J＝7.9,1.8Hz,1H),7.62–7.55(m,1H),7.48(dd,J＝8.4,7.1Hz,2H),7.42(ddd,J＝8.3,7.3,1.8Hz,1H),7.39–7.35(m,2H),7.19–7.12(m,2H),7.07–7.02(m,2H),6.87(dd,J＝8.4,1.0Hz,1H),5.08(dd,J＝7.5,6.1Hz,1H),4.12(q,J＝7.1Hz,2H),3.86(dd,J＝18.8,7.5Hz,1H),3.78(dd,J＝18.8,6.1Hz,1H),1.12(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ197.9,195.0,169.6,157.0,156.0,136.2,134.1,133.6,130.9,130.2,129.0,129.0,128.8,124.3,123.4,119.6,118.8,61.7,49.5,43.0,14.0.HRMS(ESI-TOF)m/z:calcd for C25H22O5Na+:425.1359(M+Na)+,found:425.1359.
实施例12
(E)-2-苯甲酰基-4-氧代-6-苯基己基-5-烯酸乙酯的制备
将(E)-1-(二甲基(氧代)-λ6-磺胺酰亚胺)-4-苯基丁-3-烯-2-酮(0.1mmol)、3-氧代-3-苯基丙酸乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到15.5mg的目标产物，收率为46％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.11–8.05(m,2H),7.63(d,J＝16.3Hz,1H),7.60(d,J＝7.4Hz,1H),7.57–7.53(m,2H),7.50(dd,J＝8.4,7.2Hz,2H),7.43–7.39(m,3H),6.77(d,J＝16.2Hz,1H),5.06(dd,J＝7.4,6.3Hz,1H),4.16(q,J＝7.1Hz,2H),3.54–3.41(m,2H),1.17(t,J＝7.1Hz,3H).13C NMR(126MHz,CDCl3)δ196.8,195.0,169.4,143.8,136.2,134.4,133.7,130.8,129.1,129.1,128.8,128.5,125.6,61.9,48.9,39.8,14.1.HRMS(ESI-TOF)m/z:calcd for C21H21O4+:337.1434(M+H)+,found:337.1434.
实施例13
1-乙基-4-丙基-2-苯甲酰基琥珀酸酯的制备
将2-(二甲基(氧代)-λ6-磺胺酰亚胺)乙酸丙酯(0.1mmol)、3-氧代-3-苯基丙酸乙酯(0.1mmol)和乙腈1mL加入到15mL的反应管中，在空气氛围下置于90℃的油浴中，反应24h；冷却至室温，反应液用乙酸乙酯稀释，水洗三次，有机相用无水Na2SO4干燥，过滤，浓缩，柱层析色谱纯化得到14.0mg的目标产物，收率为48％。该目标产物的核磁表征如下：1H NMR(500MHz,CDCl3)δ8.07–8.02(m,2H),7.63–7.58(m,1H),7.49(dd,J＝8.5,7.1Hz,2H),4.87(dd,J＝7.9,6.6Hz,1H),4.14(q,J＝7.1Hz,2H),4.03(td,J＝6.7,1.2Hz,2H),3.11(dd,J＝17.4,7.8Hz,1H),3.03(dd,J＝17.4,6.6Hz,1H),1.62(q,J＝7.0Hz,2H),1.16(t,J＝7.1Hz,3H),0.91(t,J＝7.4Hz,3H).13C NMR(126MHz,CDCl3)δ194.3,171.5,168.8,136.0,133.8,129.0,128.8,66.8,61.9,49.7,33.4,22.0,14.0,10.4.HRMS(ESI-TOF)m/z:calcd forC16H20O5Na+:315.1203(M+Na)+,found:315.1203.
以上所述，仅为本发明的较佳实施例而已，故不能依此限定本发明实施的范围，即依本发明专利范围及说明书内容所作的等效变化与修饰，皆应仍属本发明涵盖的范围内。
Claims (10)
1.一种2-酰基-4-氧代丁酸酯衍生物的制备方法，其特征在于：包括如下步骤：
(1)将β-羰基酯、锍叶立德、路易斯酸和有机溶剂混合后，在空气氛围下于85-95℃反应20-25h；
(2)将步骤(1)所得的物料经乙酸乙酯稀释后，再经水洗，分离得有机相；
(3)将步骤(2)所得的有机相一次经干燥、过滤、浓缩和色谱纯化，得到所述2-酰基-4-氧代丁酸酯衍生物；
上述β-羰基酯的结构式为其中R1为氢、烷氧基、烷基、取代或未取代的芳香基，该取代的芳香基上的取代基为烷基、烷氧基或卤素；
上述锍叶立德的结构式为其中R2为氢、烷氧基、烷基、烯基、取代或未取代的芳香基，该取代的芳香基上的取代基为烷基、烷氧基或卤素。
2.如权利要求1所述的制备方法，其特征在于：所述卤素为氟、氯、溴或碘。
3.如权利要求1所述的制备方法，其特征在于：所述锍叶立德为2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(4-甲氧基苯基)乙烷-1-酮、2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-苯基乙烷-1-酮、1-(4-溴苯基)-2-(二甲基(氧代)-λ6-磺胺酰亚胺)乙烷-1-酮、2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(2-噻吩基)乙烷-1-酮、2-(二甲基(氧代)-λ6-磺胺酰亚胺)-1-(2-苯氧基苯基)乙烷-1-酮、(E)-1-(二甲基(氧代)-λ6-磺胺酰亚胺)-4-苯基丁-3-烯-2-酮或2-(二甲基(氧代)-λ6-磺胺酰亚胺)乙酸丙酯。
4.如权利要求1所述的制备方法，其特征在于：所述路易斯酸为溴化钾、氯化锂、氯化锌、氯化铝、碘化钾、碘化锂、氯化铁或溴化铁。
5.如权利要求4所述的制备方法，其特征在于：所述路易斯酸为溴化锂。
6.如权利要求1所述的制备方法，其特征在于：所述有机溶剂为N,N－二甲基甲酰胺、N,N－二甲基乙酰胺、1,2-二氯乙烷、甲苯、1,4-二氧六环、四氢呋喃、六氟异丙醇、异丙醇或乙腈。
7.如权利要求6所述的制备方法，其特征在于：所述有机溶剂为乙腈。
8.如权利要求1所述的制备方法，其特征在于：所述β-羰基酯为丙二酸二乙酯、乙酰乙酸乙酯、3-氧代-3-(对甲苯基)丙酸甲酯、3-氧代-3-(间甲苯基)丙酸甲酯、3-(4-甲氧基苯基)-3-氧代丙酸甲酯、3-(3-甲氧基苯基)-3-氧代丙酸甲酯或3-(4-溴苯基)-3-氧代丙酸甲酯。
9.如权利要求1至8中任一权利要求所述的制备方法，其特征在于：所述β-羰基酯、锍叶立德、路易斯酸的摩尔比为1:1:1，且每0.01mmol苯甲酰亚胺乙酯或其衍生物对应所述有机溶剂0.1mL。
10.如权利要求9所述的制备方法，其特征在于：所述步骤(1)中，于90℃反应24h。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310928529.9A CN116947636A (zh) | 2023-07-27 | 2023-07-27 | 一种2-酰基-4-氧代丁酸酯衍生物的制备方法 |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202310928529.9A CN116947636A (zh) | 2023-07-27 | 2023-07-27 | 一种2-酰基-4-氧代丁酸酯衍生物的制备方法 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN116947636A true CN116947636A (zh) | 2023-10-27 |
Family
ID=88461517
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202310928529.9A Pending CN116947636A (zh) | 2023-07-27 | 2023-07-27 | 一种2-酰基-4-氧代丁酸酯衍生物的制备方法 |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN116947636A (zh) |
-
2023
- 2023-07-27 CN CN202310928529.9A patent/CN116947636A/zh active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| AU2004236085B2 (en) | Processes for producing 3-substituted 2-chloro-5-fluoropyridine or salt thereof | |
| CN110183378B (zh) | 一种烟酰胺的衍生物及其催化合成方法 | |
| CN105801575A (zh) | 一种咪唑并[1,2-a]吡啶的合成方法 | |
| CN110790763A (zh) | 吡啶并二嘧啶及吡啶并二吡唑衍生物的制备方法 | |
| JP2964041B2 (ja) | フエニル―１ジエチルアミノカルボニル―１フタールイミドメチル―２シクロプロパンｚの新規な製造方法 | |
| CN111285881B (zh) | 一种噻吩并[3,4-b]吲哚衍生物及其合成方法 | |
| CN110204533B (zh) | 一种4-(异色烯-1-基)异喹啉衍生物的制备方法 | |
| CN116947636A (zh) | 一种2-酰基-4-氧代丁酸酯衍生物的制备方法 | |
| CN114573512B (zh) | 一种合成c2-二氟烷基苯并咪唑衍生物的方法 | |
| CN109535140A (zh) | 一种基于肟酯与吲哚构建双吲哚取代二氢吡咯酮类衍生物的方法 | |
| CN113563328B (zh) | 一种1,3-二取代-2-氟中氮茚衍生物的制备方法 | |
| KR870001922B1 (ko) | 이미다졸 유도체의 제조방법 | |
| CN108218758B (zh) | 一种2，4-二取代吡咯衍生物的制备方法 | |
| KR101894091B1 (ko) | 크로마논 유도체의 신규한 제조방법 | |
| CN113603694A (zh) | 一种1,2-二酮类化合物及其制备方法和应用 | |
| JPH047346B2 (zh) | ||
| CN105801328B (zh) | 一种晕苯的制备方法 | |
| WO2004083213A1 (fr) | Derives de 4,6-dihydrofuro[3,4-d]imidazole-6-one, sels de ceux-ci ainsi que procede de preparation associe | |
| CN111892582B (zh) | 一种苯并呋喃香豆素化合物的制备方法 | |
| CN115260122B (zh) | 一种萘并噻唑类衍生物及其合成方法 | |
| JP2007099744A (ja) | テトラアザポルフィリン化合物の製造法 | |
| CN115974879B (zh) | 一种多取代的咪唑并杂环类化合物的制备方法 | |
| Wu et al. | CuLi2Cl4 catalysed cross-coupling strategy for the formal synthesis of the diterpenoid (+)-subersic acid from (–)-sclareol | |
| CN114957097B (zh) | 一种吲哚啉类化合物的制备方法 | |
| CN114875433B (zh) | 一种多氟芳基硒醚衍生物的制备方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |