CN115043799B - Preparation method of 5, 6-dihydrobenzofuranone derivative - Google Patents
Preparation method of 5, 6-dihydrobenzofuranone derivative Download PDFInfo
- Publication number
- CN115043799B CN115043799B CN202210862570.6A CN202210862570A CN115043799B CN 115043799 B CN115043799 B CN 115043799B CN 202210862570 A CN202210862570 A CN 202210862570A CN 115043799 B CN115043799 B CN 115043799B
- Authority
- CN
- China
- Prior art keywords
- dihydrobenzofuranone
- derivative
- compound
- formula
- alpha
- 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.)
- Active
Links
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- MLMMUMDAZISJQU-UHFFFAOYSA-N C1CC=C2C(=C1)CC(=O)O2 Chemical class C1CC=C2C(=C1)CC(=O)O2 MLMMUMDAZISJQU-UHFFFAOYSA-N 0.000 title abstract description 23
- -1 alpha-keto acid compound Chemical class 0.000 claims abstract description 36
- 238000006243 chemical reaction Methods 0.000 claims abstract description 33
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 238000000034 method Methods 0.000 claims abstract description 8
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000004440 column chromatography Methods 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 75
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical group FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 61
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 44
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 36
- 239000003208 petroleum Substances 0.000 claims description 18
- 239000003480 eluent Substances 0.000 claims description 9
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims 2
- 238000011097 chromatography purification Methods 0.000 claims 1
- 125000003944 tolyl group Chemical group 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 6
- 125000000524 functional group Chemical group 0.000 abstract description 4
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000000758 substrate Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 28
- 150000001875 compounds Chemical class 0.000 description 23
- 238000005481 NMR spectroscopy Methods 0.000 description 21
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 20
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 17
- 239000012043 crude product Substances 0.000 description 14
- 239000011259 mixed solution Substances 0.000 description 14
- 239000005711 Benzoic acid Substances 0.000 description 10
- 235000010233 benzoic acid Nutrition 0.000 description 10
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexyloxide Natural products O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000004458 analytical method Methods 0.000 description 7
- 238000004364 calculation method Methods 0.000 description 7
- 238000001035 drying Methods 0.000 description 7
- 238000001704 evaporation Methods 0.000 description 7
- 239000012044 organic layer Substances 0.000 description 7
- 239000000047 product Substances 0.000 description 7
- 238000010898 silica gel chromatography Methods 0.000 description 7
- 238000000605 extraction Methods 0.000 description 6
- 238000002844 melting Methods 0.000 description 6
- 230000008018 melting Effects 0.000 description 6
- 230000010355 oscillation Effects 0.000 description 6
- VTESCYNPUGSWKG-UHFFFAOYSA-N (4-tert-butylphenyl)hydrazine;hydrochloride Chemical compound [Cl-].CC(C)(C)C1=CC=C(N[NH3+])C=C1 VTESCYNPUGSWKG-UHFFFAOYSA-N 0.000 description 5
- RSAXVDMWQCQTDT-UHFFFAOYSA-N 2-(4-chlorophenyl)-2-oxoacetic acid Chemical compound OC(=O)C(=O)C1=CC=C(Cl)C=C1 RSAXVDMWQCQTDT-UHFFFAOYSA-N 0.000 description 4
- UIIIPQVTXBPHTI-UHFFFAOYSA-N 2-(4-methylphenyl)-2-oxoacetic acid Chemical compound CC1=CC=C(C(=O)C(O)=O)C=C1 UIIIPQVTXBPHTI-UHFFFAOYSA-N 0.000 description 4
- SMJRBWINMFUUDS-UHFFFAOYSA-N 2-thienylacetic acid Chemical compound OC(=O)CC1=CC=CS1 SMJRBWINMFUUDS-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000004429 atom Chemical group 0.000 description 3
- ULVSHNOGEVXRDR-UHFFFAOYSA-N 1,1-dimethoxypropan-2-one Chemical compound COC(OC)C(C)=O ULVSHNOGEVXRDR-UHFFFAOYSA-N 0.000 description 2
- 241000132012 Atractylodes Species 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- BGTOWKSIORTVQH-UHFFFAOYSA-N cyclo-pentanone Natural products O=C1CCCC1 BGTOWKSIORTVQH-UHFFFAOYSA-N 0.000 description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 description 2
- DCOWHZYIFORKFC-UHFFFAOYSA-N methyl 2-chloro-2-methoxyacetate Chemical compound COC(Cl)C(=O)OC DCOWHZYIFORKFC-UHFFFAOYSA-N 0.000 description 2
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 2
- ZTVSGQPHMUYCRS-SWLSCSKDSA-N (4as,8as)-3,8a-dimethyl-5-methylidene-4a,6,7,8-tetrahydro-4h-benzo[f][1]benzofuran-2-one Chemical compound C=C([C@@H]1C2)CCC[C@]1(C)C=C1C2=C(C)C(=O)O1 ZTVSGQPHMUYCRS-SWLSCSKDSA-N 0.000 description 1
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 description 1
- GIWRVUADKUVEGU-UHFFFAOYSA-N 2-oxo-2-thiophen-2-ylacetic acid Chemical compound OC(=O)C(=O)C1=CC=CS1 GIWRVUADKUVEGU-UHFFFAOYSA-N 0.000 description 1
- OQYBLUDOOFOBPO-UHFFFAOYSA-N Asterolide Natural products C1C2C(=C)CCCC2(C)CC2C1=C(C)C(=O)O2 OQYBLUDOOFOBPO-UHFFFAOYSA-N 0.000 description 1
- 229910021578 Iron(III) chloride Inorganic materials 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- HIYUMYXSGIKHHE-UHFFFAOYSA-M bismuth trifluoromethanesulfonate Chemical compound [Bi+3].[O-]S(=O)(=O)C(F)(F)F HIYUMYXSGIKHHE-UHFFFAOYSA-M 0.000 description 1
- 125000004369 butenyl group Chemical group C(=CCC)* 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000007661 gastrointestinal function Effects 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002596 lactones Chemical class 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 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
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 235000015816 nutrient absorption Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 230000001737 promoting effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 125000001424 substituent group Chemical group 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- JPJIEXKLJOWQQK-UHFFFAOYSA-K trifluoromethanesulfonate;yttrium(3+) Chemical compound [Y+3].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F JPJIEXKLJOWQQK-UHFFFAOYSA-K 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
- CITILBVTAYEWKR-UHFFFAOYSA-L zinc trifluoromethanesulfonate Substances [Zn+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F CITILBVTAYEWKR-UHFFFAOYSA-L 0.000 description 1
- ZMLPZCGHASSGEA-UHFFFAOYSA-M zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F ZMLPZCGHASSGEA-UHFFFAOYSA-M 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
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members 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
- C07D307/58—One oxygen atom, e.g. butenolide
-
- 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
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/78—Benzo [b] furans; Hydrogenated benzo [b] furans
- C07D307/82—Benzo [b] furans; Hydrogenated benzo [b] furans 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 carbon atoms of the hetero ring
- C07D307/83—Oxygen atoms
-
- 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
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/93—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems condensed with a ring other than six-membered
- C07D307/935—Not further condensed cyclopenta [b] furans or hydrogenated cyclopenta [b] furans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a 5, 6-dihydrobenzofuranone derivative, which comprises the following steps: sequentially adding an alpha-keto acid compound, a fatty ketone compound and a catalyst into an organic solvent, reacting at a certain reaction temperature, and purifying by column chromatography to obtain the 5, 6-dihydrobenzofuranone derivative. The invention takes the alpha-keto acid compound and the aliphatic ketone compound as raw materials, and prepares the 5, 6-dihydrobenzofuranone derivative by using a cheap and easily available catalyst, and the method has the advantages of simple reaction operation, high yield and atom economy, good functional group compatibility and wide substrate application range, provides a new synthetic route for preparing the 5, 6-dihydrobenzofuranone derivative, and has great application value and potential in industrial production and scientific research.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a 5, 6-dihydrobenzofuranone derivative.
Background
The 5, 6-dihydrobenzofuranone structure is widely present in naturally occurring structural molecules with biological activity. For example: bighead atractylodes lactone I (Atractylenolide I) isolated from dried rhizome of bighead atractylodes rhizome is a sesquiterpenoid compound containing 5, 6-dihydrobenzofuranone structure (Tetrahedron Lett.2015,56,5545), and has anti-inflammatory and antitumor effects, and the compound is also applied to regulating gastrointestinal functions and promoting nutrient absorption. Therefore, the development of a simple and efficient method for preparing the 5, 6-dihydrobenzofuranone derivative structure has important industrial production and scientific research values.
The existing method for preparing the 5, 6-dihydrobenzofuranone derivative mainly comprises the steps of preparing the cyclic aliphatic ketone compound and 2-chloro-2-methoxyacetic acid methyl ester or 1, 1-dimethoxyacetone, wherein the 2-chloro-2-methoxyacetic acid methyl ester or the 1, 1-dimethoxyacetone is prepared by a multi-step reaction (Synthesis 1979,434;Tetrahedron Lett.2015,56,5545;J.Org.Chem.2004,69,9100), and has the defects of low yield, difficult raw materials, multiple side reactions and the like. There is no efficient and simple method for preparing 5, 6-dihydrobenzofuranone derivative, and in order to expand the availability of 5, 6-dihydrobenzofuranone derivative, a novel preparation method of 5, 6-dihydrobenzofuranone derivative is developed, which has a great application value, and the method has the advantages of easily available reaction raw materials, high efficiency, simplicity, high atom economy and the like.
Disclosure of Invention
Aiming at the problems, the invention provides a preparation method of a 5, 6-dihydrobenzofuranone derivative, which has the advantages of mild reaction conditions, simple operation, easily available raw materials, good compatibility of functional groups and wide application range of substrates.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
the preparation method of the 5, 6-dihydrobenzofuranone derivative specifically comprises the following steps: sequentially adding an alpha-keto acid compound shown in a formula (II), an aliphatic ketone compound shown in a formula (III) and a catalyst into an organic solvent, reacting at a certain reaction temperature, and purifying by column chromatography to obtain a 5, 6-dihydrobenzofuranone derivative (I), wherein the reaction structural formula is shown as follows;
wherein R is 1 Independently selected from any one of phenyl, substituted phenyl, naphthyl, thienyl, C1-C6 alkyl and C1-C6 alkenyl; r is R 2 And R is 3 Independently selected from any one of hydrogen atom, C1-C6 alkyl and C1-C6 alkenyl.
Wherein C1-C6 alkyl refers to a straight or branched alkyl group having 1 to 6 carbon atoms, comprising: methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexylcyclohexyl, and the like.
C1-C6 alkenyl means a straight or branched carbon-carbon double bond containing substituent having 1 to 6 carbon atoms comprising: ethenyl, propenyl, butenyl, pentenyl, hexenyl, cyclohexenyl.
Preferably, the organic solvent comprises: toluene, fluorobenzene, benzotrifluoride, chlorobenzene, benzene, xylene, tetrahydrofuran, methanol, ethanol, acetonitrile, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide and N-methylpyrrolidone.
Preferably, the catalyst comprises: boron trifluoride diethyl etherate, trifluoromethanesulfonic anhydride, p-toluenesulfonic acid, ferric chloride, bismuth trifluoromethanesulfonate, zinc trifluoromethanesulfonate, yttrium trifluoromethanesulfonate, copper trifluoromethanesulfonate, aluminum chloride, titanium tetrachloride.
Preferably, the molar ratio of the alpha-keto acid compound (II) to the aliphatic ketone compound (III) shown is 1 (1-3); the molar ratio of the alpha-keto acid compound (II) to the catalyst is 1 (0.05-1); the dosage ratio of the alpha-keto acid compound (II) to the organic solvent is 1mmol (2-15) mL.
Preferably, the reaction temperature is 25-120 ℃ and the time is 0.5-12 hours.
Preferably, the eluent used for the column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (1-10): 1.
The invention has the beneficial effects that:
1. the invention adopts an alpha-keto acid compound and a fatty ketone compound which are cheap and easy to obtain as raw materials and boron trifluoride diethyl ether as a catalyst to prepare the 5, 6-dihydrobenzofuranone derivative.
2. The invention can be operated under the air condition, is insensitive to oxygen, and has mild reaction condition and simple operation.
3. The invention has the advantages of good compatibility of functional groups, simple post-treatment, high atom economy and the like.
4. The invention provides a new synthetic route for the preparation of the 5, 6-dihydrobenzofuranone derivative, and the prepared 5, 6-dihydrobenzofuranone derivative can play an important role in the field of active pharmaceutical intermediates, and has great application value and potential in industrial production and scientific research.
Detailed Description
The technical scheme of the present invention is further illustrated and described below by means of specific embodiments, but the embodiments of the present invention are not limited thereto.
Example 1:
adding the above-mentioned benzoylformic acid (II), cyclohexanone compound (III) and boron trifluoride diethyl etherate (BF) into toluene 3 ·Et 2 O), and then the reaction was stirred and sealed at a temperature of 70 ℃ for 4 hours.
Wherein the molar ratio of the benzoic acid (II) to the cyclohexanone compound (III) is 1:2; benzoic acid (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1:0.5; the ratio of benzoic acid (II) to toluene was 1mmol:4mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline in equal volume ratio into a reaction system, carrying out oscillation extraction for 3 times, collecting an organic layer, drying, rotationally evaporating and concentrating to obtain a crude product, carrying out 300-mesh silica gel column chromatography on the crude product, and taking a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1:20, thus obtaining a target product of the formula (I) compound (C 14 H 12 O 2 )。
For the compound (C) of formula (I) obtained in this example 14 H 12 O 2 ) Nuclear magnetic resonance analysis was performed, with the following results: 1 h NMR (400 MHz, deuterated chloroform CDCl) 3 )δ7.69-7.61(m,2H),7.45-7.41(m,2H),7.39-7.32(m,1H),5.93(t,J＝4.7Hz,1H),2.91(t,J＝6.5Hz,2H),2.44(dd,J＝10.9,5.8Hz,2H),1.93-1.85(m,2H)
13 C NMR (100 MHz, deuterated chloroform CDCl) 3 )δ169.2,149.2,147.7,130.0,128.5(2C),128.4,128.3(2C),121.5,110.8,24.3,23.6,22.7
HRMS m/z(ESI)calcd for C 14 H 12 O 2 ,(M+H) + 213.0910；found 213.0913.
Through calculation: compounds of formula (I) (C 14 H 12 O 2 ) Yield of 82%, melting point: 102-104 ℃.
Example 2:
adding 4-methyl phenyl glyoxylic acid (II), cyclohexanone compound (III) and boron trifluoride diethyl etherate (BF) into toluene 3 ·Et 2 O) and then at a temperature of 70 DEG CThe reaction was stirred under sealed conditions for 4 hours.
Wherein, the mol ratio of the 4-methyl phenyl glyoxylic acid (II) to the cyclohexanone compound (III) is 1:2; 4-Methylphenylglyoxylic acid (II) with boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1:0.5; the ratio of 4-methylphenyl glyoxylic acid (II) to toluene was 1 mmol/4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline in equal volume ratio into a reaction system, carrying out oscillation extraction for 3 times, collecting an organic layer, drying, rotationally evaporating and concentrating to obtain a crude product, carrying out 300-mesh silica gel column chromatography on the crude product, and taking a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1:20, thus obtaining a target product of the formula (I) compound (C 15 H 14 O 2 )。
For the compound (C) of formula (I) obtained in this example 15 H 14 O 2 ) Nuclear magnetic resonance analysis was performed, with the following results: 1 h NMR (400 MHz, deuterated chloroform CDCl) 3 )δ7.55(d,J＝8.2Hz,2H),7.24(d,J＝8.1Hz,2H),5.90(t,J＝4.7Hz,1H),2.89(t,J＝6.5Hz,2H),2.43(dd,J＝10.9,5.7Hz,2H),2.38(s,3H),1.92-1.84(m,2H).
13 C NMR (100 MHz, deuterated chloroform CDCl) 3 )δ169.3,149.3,146.9,138.5,129.2(2C),128.3(2C),127.1,121.5,110.3,24.3,23.6,22.7,21.3
HRMS m/z(ESI)calcd for C 15 H 14 O 2 ,(M+H) + 227.1067；found 227.1065.
Through calculation: compounds of formula (I) (C 15 H 14 O 2 ) Yield of 80%, melting point: 96-98 ℃.
Example 3:
adding 4-chlorophenyl glyoxylic acid (II), cyclohexanone compound (III) and boron trifluoride diethyl etherate (BF) into toluene 3 ·Et 2 O) and then stirring at 70 DEG CThe reaction was blocked for 4 hours.
Wherein, the mol ratio of the 4-chlorophenyl glyoxylic acid (II) to the cyclohexanone compound (III) is 1:2; 4-Chlorophenylglyoxylic acid (II) with boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1:0.5; the ratio of 4-chlorophenyl glyoxylic acid (II) to toluene was 1 mmol/4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline in equal volume ratio into a reaction system, carrying out oscillation extraction for 3 times, collecting an organic layer, drying, rotationally evaporating and concentrating to obtain a crude product, carrying out 300-mesh silica gel column chromatography on the crude product, and taking a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1:20, thus obtaining a target product of the formula (I) compound (C 14 H 11 ClO 2 )。
For the compound (C) of formula (I) obtained in this example 14 H 11 ClO 2 ) Nuclear magnetic resonance analysis was performed, with the following results: 1 h NMR (400 MHz, deuterated chloroform CDCl) 3 )δ7.65-7.59(m,2H),7.43-7.38(m,2H),5.97(t,J＝4.7Hz,1H),2.89(t,J＝6.5Hz,2H),2.46(dd,J＝10.8,5.8Hz,2H),1.96-1.87(m,2H).
13 C NMR (100 MHz, deuterated chloroform CDCl) 3 )δ168.9,149.1,147.9,134.5,129.7(2C),128.8(2C),128.5,120.5,111.4,24.3,23.6,22.6.
HRMS m/z(ESI)calcd for C 14 H 11 ClO 2 ,(M+H) + 247.0520；found 247.0521.
Through calculation: compounds of formula (I) (C 14 H 11 ClO 2 ) The yield of (2) was 73%, melting point: 174-176 ℃.
Example 4:
adding 2-thiopheneacetic acid (II), cyclohexanone compound (III) and boron trifluoride diethyl etherate (BF) into toluene 3 ·Et 2 O), and then the reaction was stirred and sealed at a temperature of 70 ℃ for 4 hours.
Wherein, the mol ratio of the 2-thiophene glyoxylic acid (II) to the cyclohexanone compound (III) is 1:2; 2-thiopheneacetic acid (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1:0.5; the ratio of 2-thiopheneacetic acid (II) to toluene was 1 mmol/4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline in equal volume ratio into a reaction system, oscillating and extracting for 3 times, collecting an organic layer, drying, rotationally evaporating and concentrating to obtain a crude product, subjecting the crude product to 300-mesh silica gel column chromatography, and taking a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1:20, thus obtaining a target product of a compound (I) (C 12 H 10 SO 2 )。
For the compound (C) of formula (I) obtained in this example 12 H 10 SO 2 ) Nuclear magnetic resonance analysis was performed, with the following results: 1 h NMR (400 MHz, deuterated chloroform CDCl) 3 )δ7.77(d,J＝3.5Hz,1H),7.44(dd,J＝5.0,0.7Hz,1H),7.15-7.13(m,1H),5.93(t,J＝4.7Hz,1H),2.95(t,J＝6.6Hz,2H),2.45(dd,J＝10.9,5.9Hz,2H),2.02-1.90(m,2H).
13 C NMR (100 MHz, deuterated chloroform CDCl) 3 )δ168.2,149.3,143.6,132.2,127.7,127.6,127.2,116.5,110.9,24.2,23.4,22.3。
HRMS m/z(ESI)calcd for C 12 H 10 SO 2 ,(M+H) + 219.0474；found 219.0471.
Through calculation: compounds of formula (I) (C 12 H 10 SO 2 ) Yield of 61%, melting point: 56-58 ℃.
Example 5:
adding the above-mentioned benzoylformic acid (II), cyclopentanone compound (III) and boron trifluoride diethyl etherate (BF) to toluene 3 ·Et 2 O), and then the reaction was stirred and sealed at a temperature of 70 ℃ for 4 hours.
Wherein,the molar ratio of the benzoic acid (II) to the cyclopentanone compound (III) is 1:2; benzoic acid (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1:0.5; the ratio of benzoic acid (II) to toluene was 1mmol:4mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline in equal volume ratio into a reaction system, carrying out oscillation extraction for 3 times, collecting an organic layer, drying, rotationally evaporating and concentrating to obtain a crude product, carrying out 300-mesh silica gel column chromatography on the crude product, and taking a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1:20, thus obtaining a target product of the formula (I) compound (C 13 H 10 O 2 )。
For the compound (C) of formula (I) obtained in this example 13 H 10 O 2 ) Nuclear magnetic resonance analysis was performed, with the following results: 1 h NMR (400 MHz, deuterated chloroform CDCl) 3 )δ7.91-7.85(m,2H),7.43(dd,J＝10.7,4.7Hz,2H),7.32(t,J＝7.4Hz,1H),5.84(t,J＝3.0Hz,1H),3.11-3.05(m,2H),2.99-2.96(m,2H).
13 C NMR (100 MHz, deuterated chloroform CDCl) 3 )δ172.6,161.6,153.9,130.4,128.6(2C),128.1,127.0(2C),116.3,112.4,33.4,25.3.
HRMS m/z(ESI)calcd for C 13 H 10 O 2 ,(M+H) + 199.0754；found 199.0757.
Through calculation: compounds of formula (I) (C 13 H 10 O 2 ) Yield of 48%, melting point: 78-80 ℃.
Example 6:
adding the above formula of benzoic acid (II), acetonide (III), boron trifluoride diethyl etherate (BF) into toluene 3 ·Et 2 O), and then the reaction was stirred and sealed at a temperature of 70 ℃ for 4 hours.
Wherein the molar ratio of the benzoyl formic acid (II) to the acetonide (III) is 1:2; benzoyl compoundsFormic acid (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1:0.5; the ratio of benzoic acid (II) to toluene was 1mmol:4mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline in equal volume ratio into a reaction system, carrying out oscillation extraction for 3 times, collecting an organic layer, drying, rotationally evaporating and concentrating to obtain a crude product, carrying out 300-mesh silica gel column chromatography on the crude product, and taking a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1:20, thus obtaining a target product of the formula (I) compound (C 11 H 8 O 2 )。
For the compound (C) of formula (I) obtained in this example 11 H 8 O 2 ) Nuclear magnetic resonance analysis was performed, with the following results: 1 h NMR (400 MHz, deuterated chloroform CDCl) 3 )δ7.92-7.87(m,2H),7.51(s,1H),7.45-7.38(m,3H),5.23(d,J＝2.5Hz,1H),4.94(d,J＝2.6Hz,1H).
13 C NMR (100 MHz, deuterated chloroform CDCl) 3 )δ168.4,153.4,134.3,131.9,129.9,128.9,128.7(2C),127.2(2C),97.4.
HRMS m/z(ESI)calcd for C 11 H 8 O 2 ,(M+H) + 173.0597；found 173.0595.
Through calculation: compounds of formula (I) (C 11 H 8 O 2 ) Yield of 48%, melting point: 68-70 ℃.
Example 7:
adding the above-mentioned benzoylformic acid (II), 3-pentanone compound (III) and boron trifluoride diethyl etherate (BF) into toluene 3 ·Et 2 O), and then the reaction was stirred and sealed at a temperature of 70 ℃ for 4 hours.
Wherein the molar ratio of the benzoyl formic acid (II) to the 3-pentanone compound (III) is 1:2; benzoic acid (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1:0.5; benzoic acid (II) with tolueneThe ratio was 1mmol:4mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline in equal volume ratio into a reaction system, carrying out oscillation extraction for 3 times, collecting an organic layer, drying, rotationally evaporating and concentrating to obtain a crude product, carrying out 300-mesh silica gel column chromatography on the crude product, and taking a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of the ethyl acetate to the petroleum ether is 1:20, thus obtaining a target product (a compound shown as a formula (I) with oily liquid appearance 13 H 12 O 2 )。
For the compound (C) of formula (I) obtained in this example 13 H 12 O 2 ) Nuclear magnetic resonance analysis was performed, with the following results: 1 h NMR (400 MHz, deuterated chloroform CDCl) 3 )δ7.54-7.51(m,2H),7.47-7.41(m,2H),7.39-7.34(m,1H),5.45(q,J＝7.4Hz,1H),2.23(s,3H),2.00(d,J＝7.4Hz,3H).
13 C NMR (100 MHz, deuterated chloroform CDCl) 3 )δ169.0,150.6,146.6,129.9,129.0(2C),128.5,128.4(2C),126.3,107.7,11.8,10.8.
HRMS m/z(ESI)calcd for C 13 H 12 O 2 ,(M+H) + 201.0910；found 201.0913.
Through calculation: compounds of formula (I) (C 13 H 12 O 2 ) The yield of (2) was 79%.
In conclusion, the method takes the alpha-keto acid compound and the aliphatic ketone compound as raw materials, and prepares the 5, 6-dihydrobenzofuranone derivative by using a cheap and easily available catalyst, and has the advantages of high reaction yield, simple operation, high atom economy, good functional group compatibility and wide substrate application range, thereby providing a brand-new route for preparing the 5, 6-dihydrobenzofuranone derivative.
It should be noted that, not described in detail, the present invention is well known to those skilled in the art.
The above examples are only for further illustrating a preparation method of 5, 6-dihydrobenzofuranone derivatives of the present invention, but the present invention is not limited to the examples, and all equivalent changes and modifications of the above examples are included in the scope of the present invention according to the technical spirit of the present invention.
Claims (5)
1. The preparation method of the 5, 6-dihydrofuranone derivative is characterized by comprising the following steps of: sequentially adding an alpha-keto acid compound shown in a formula (II), an aliphatic ketone compound shown in a formula (III) and a catalyst into an organic solvent, reacting at a certain reaction temperature, and purifying by column chromatography to obtain the 5, 6-dihydrofuranone derivative shown in the formula (I), wherein the reaction structural formula is shown as follows;
wherein R is 1 Independently selected from any one of phenyl, substituted phenyl, naphthyl, thienyl, C1-C6 alkyl and C1-C6 alkenyl; r is R 2 And R is 3 Independently selected from any one of hydrogen atom, C1-C6 alkyl and C1-C6 alkenyl;
the catalyst is boron trifluoride diethyl etherate.
2. The method for producing a 5, 6-dihydrofuranone derivative according to claim 1, wherein the organic solvent is toluene.
3. The process for producing a 5, 6-dihydrofuranone derivative according to claim 1, wherein the molar ratio of the α -keto acid compound (II) to the aliphatic ketone compound (III) is 1 (1-3); the molar ratio of the alpha-keto acid compound (II) to the catalyst is 1 (0.05-1); the dosage ratio of the alpha-keto acid compound (II) to the organic solvent is 1mmol (2-15) mL.
4. The process for preparing a 5, 6-dihydrofuranone derivative according to claim 1, wherein the reaction temperature is 25 to 120 ℃ for 0.5 to 12 hours.
5. The method for preparing 5, 6-dihydrofuranone derivatives according to claim 1, wherein the eluent used for the chromatographic purification of the column is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of petroleum ether to ethyl acetate is (1-10): 1.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210862570.6A CN115043799B (en) | 2022-07-20 | 2022-07-20 | Preparation method of 5, 6-dihydrobenzofuranone derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210862570.6A CN115043799B (en) | 2022-07-20 | 2022-07-20 | Preparation method of 5, 6-dihydrobenzofuranone derivative |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN115043799A CN115043799A (en) | 2022-09-13 |
| CN115043799B true CN115043799B (en) | 2024-02-23 |
Family
ID=83167409
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210862570.6A Active CN115043799B (en) | 2022-07-20 | 2022-07-20 | Preparation method of 5, 6-dihydrobenzofuranone derivative |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115043799B (en) |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108727316A (en) * | 2018-06-28 | 2018-11-02 | 武汉大学 | A kind of benzofuran-2-ones and the preparation method and application thereof |
-
2022
- 2022-07-20 CN CN202210862570.6A patent/CN115043799B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN108727316A (en) * | 2018-06-28 | 2018-11-02 | 武汉大学 | A kind of benzofuran-2-ones and the preparation method and application thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN115043799A (en) | 2022-09-13 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN112142694A (en) | Polysubstituted tetrahydrofuran and tetrahydropyrane diene compound and preparation method thereof | |
| CN115043799B (en) | Preparation method of 5, 6-dihydrobenzofuranone derivative | |
| CN111620808B (en) | 2-aldehyde indole compound and preparation method thereof | |
| Kido et al. | Stereoselective synthesis of contiguously substituted butyrolactones based on the cyclic allylsulfonium ylide rearrangement | |
| Zhao et al. | FeCl3· 6H2O-catalyzed synthesis of β-ketothioesters from chain α-oxo ketene dithioactals | |
| WO2011003300A1 (en) | Method for preparing hydroxymethylfurfural | |
| Dai et al. | Synthetic Studies on (+)‐Biotin, Part 11: Application of Cinchona Alkaloid‐Mediated Asymmetric Alcoholysis of meso‐Cyclic Anhydride in the Total Synthesis of (+)‐Biotin | |
| CN111303096B (en) | Synthesis method of polysubstituted 1, 3-dihydronaphtho [2,3-c ] furan derivative | |
| CN111233707B (en) | Synthesis and refining method of 4-fluorobenzoylacetonitrile | |
| Lemus et al. | Lewis acid catalyzed enlargement of cyclic β‐alkoxyenals and one‐pot synthesis of polyfunctional enoxysilanes derived from aucubin with trimethylsilyldiazomethane | |
| CN114956927B (en) | Preparation method of beta-halogenated olefine acid ester derivative | |
| CN109608323B (en) | Beta-trifluoromethyl-beta-hydroxy substituted cyclohexanone derivative and synthesis method thereof | |
| CN112194608A (en) | Synthesis method of visible light promoted 3-methyl-3-difluoroethyl-2-oxindole compound | |
| CN109384753B (en) | Synthetic method of 2-phenyl-3-methylbenzofuran compound | |
| CN114874167A (en) | Preparation method of 5-hydroxyfuranone derivative | |
| CN111559993A (en) | Preparation method of furan methanol compound | |
| CN112125843B (en) | Preparation method of 3-hydroxymethyl-4-phenyl-3, 4-dihydroquinolinone compound | |
| CN113264972B (en) | Method for preparing obeticholic acid | |
| CN110669046A (en) | Polysubstituted tetrahydro-gamma-carboline derivative with multiple chiral centers and preparation method of stereo diversity of polysubstituted tetrahydro-gamma-carboline derivative | |
| CN114989132B (en) | Method for synthesizing spiro compounds through lithium iodide catalysis | |
| CN114933516B (en) | Method for synthesizing deuterated compound in ionic liquid medium | |
| CN112159344B (en) | Synthesis method of 1, 3-dimethyl-3-hydroxymethyl indoline-2-ketone compound | |
| CN116162052B (en) | Preparation method of 2-benzylidene indoline-3-ketone compound | |
| Sharma et al. | An abbreviated synthesis of 7, 12-dimethylbenz [a] anthracene and benzo [c] chrysene metabolites using the Suzuki reaction | |
| CN113214199B (en) | Synthetic method of benzofuran-3-oxocarboxylate compound |
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 | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |