CN114874167A - Preparation method of 5-hydroxyfuranone derivative - Google Patents
Preparation method of 5-hydroxyfuranone derivative Download PDFInfo
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- CN114874167A CN114874167A CN202210729446.2A CN202210729446A CN114874167A CN 114874167 A CN114874167 A CN 114874167A CN 202210729446 A CN202210729446 A CN 202210729446A CN 114874167 A CN114874167 A CN 114874167A
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- BDMAPVZUIINOIJ-UHFFFAOYSA-N 5-hydroxy-3h-furan-2-one Chemical class OC1=CCC(=O)O1 BDMAPVZUIINOIJ-UHFFFAOYSA-N 0.000 title claims abstract description 22
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- -1 alpha-keto acid compound Chemical class 0.000 claims abstract description 48
- 238000006243 chemical reaction Methods 0.000 claims abstract description 35
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000003960 organic solvent Substances 0.000 claims abstract description 7
- 238000004440 column chromatography Methods 0.000 claims abstract description 5
- 238000000746 purification Methods 0.000 claims abstract description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 84
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 60
- KZMGYPLQYOPHEL-UHFFFAOYSA-N Boron trifluoride etherate Chemical compound FB(F)F.CCOCC KZMGYPLQYOPHEL-UHFFFAOYSA-N 0.000 claims description 54
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 54
- 239000003208 petroleum Substances 0.000 claims description 20
- 239000003480 eluent Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000006727 (C1-C6) alkenyl group Chemical group 0.000 claims description 5
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 5
- GETTZEONDQJALK-UHFFFAOYSA-N (trifluoromethyl)benzene Chemical compound FC(F)(F)C1=CC=CC=C1 GETTZEONDQJALK-UHFFFAOYSA-N 0.000 claims description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-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
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 claims description 4
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 4
- 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 claims description 4
- 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
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- HIYUMYXSGIKHHE-UHFFFAOYSA-M bismuth trifluoromethanesulfonate Chemical compound [Bi+3].[O-]S(=O)(=O)C(F)(F)F HIYUMYXSGIKHHE-UHFFFAOYSA-M 0.000 claims description 2
- 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 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 claims description 2
- 125000001624 naphthyl group Chemical group 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 125000001544 thienyl group Chemical group 0.000 claims description 2
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 2
- 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 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 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 claims description 2
- ZMLPZCGHASSGEA-UHFFFAOYSA-M zinc trifluoromethanesulfonate Chemical compound [Zn+2].[O-]S(=O)(=O)C(F)(F)F ZMLPZCGHASSGEA-UHFFFAOYSA-M 0.000 claims description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 3
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 1
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000009776 industrial production Methods 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 32
- 150000001875 compounds Chemical class 0.000 description 27
- 238000005481 NMR spectroscopy Methods 0.000 description 24
- 239000012043 crude product Substances 0.000 description 16
- 239000011259 mixed solution Substances 0.000 description 16
- UQQMNAKUWQWIMD-UHFFFAOYSA-N 2-naphthalen-2-yl-2-oxoacetic acid Chemical compound C1=CC=CC2=CC(C(=O)C(=O)O)=CC=C21 UQQMNAKUWQWIMD-UHFFFAOYSA-N 0.000 description 14
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 14
- JHIVVAPYMSGYDF-UHFFFAOYSA-N cyclohexyloxide Natural products O=C1CCCCC1 JHIVVAPYMSGYDF-UHFFFAOYSA-N 0.000 description 9
- 238000004458 analytical method Methods 0.000 description 8
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 8
- 238000004364 calculation method Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 8
- 238000005259 measurement Methods 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 238000002390 rotary evaporation Methods 0.000 description 8
- 238000007789 sealing Methods 0.000 description 8
- 238000010898 silica gel chromatography Methods 0.000 description 8
- 238000003756 stirring Methods 0.000 description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 238000000605 extraction Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000010355 oscillation Effects 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 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 6
- FAQJJMHZNSSFSM-UHFFFAOYSA-N phenylglyoxylic acid Chemical compound OC(=O)C(=O)C1=CC=CC=C1 FAQJJMHZNSSFSM-UHFFFAOYSA-N 0.000 description 6
- 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
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 125000000524 functional group 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
- 239000002253 acid Substances 0.000 description 2
- 125000004429 atom Chemical group 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 125000003844 furanonyl group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 206010011224 Cough Diseases 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 101100001674 Emericella variicolor andI gene Proteins 0.000 description 1
- 244000194828 Ligularia tussilaginea Species 0.000 description 1
- 125000000217 alkyl group Chemical group 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
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000017531 blood circulation Effects 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
- 238000004587 chromatography analysis Methods 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- VCKBXFCIXKWWAI-UHFFFAOYSA-N eremophilanolide Natural products CC1CCCC2=CC3(O)OC(=O)C(=C3CC12C)C VCKBXFCIXKWWAI-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 241000411851 herbal medicine Species 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 239000000543 intermediate Substances 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
- 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
- 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
- 229930014626 natural product Natural products 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
- 230000001737 promoting effect Effects 0.000 description 1
- 125000004368 propenyl group Chemical group C(=CC)* 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 229920006395 saturated elastomer Chemical class 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
- 239000000243 solution Substances 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
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 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
- C07D307/77—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
- C07D307/02—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
- C07D307/60—Two oxygen atoms, e.g. succinic anhydride
-
- 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
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/02—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains two hetero rings
- C07D493/04—Ortho-condensed systems
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention relates to the technical field of organic synthesis, in particular to a preparation method of a 5-hydroxyfuranone derivative, which comprises the following steps: the alpha-keto acid compound, the aliphatic ketone compound and the catalyst are sequentially added into an organic solvent, the reaction is carried out at a certain reaction temperature, and the 5-hydroxyfuranone derivative can be prepared by column chromatography purification. The invention takes the alpha-keto acid compound and the aliphatic ketone compound as raw materials, and prepares the 5-hydroxyfuranone derivative by using the cheap and easily available catalyst. The invention provides a new synthetic route for the preparation of the 5-hydroxyfuranone derivative, and has greater 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-hydroxyfuranone derivative.
Background
Furanone structures are widely found in biologically active natural product structural molecules. For example: eremophilanolide (eremophilanoids) separated from ligularia plant contains furanone structure (chem.biodiversity 2016,13, 645; nat.prod.rep.2006,23,699), and the compound is also used as Chinese herbal medicine for relieving cough and promoting blood circulation to remove blood stasis (Mini-Rev.Med.chem.2014,14,664). Therefore, the method for preparing the 5-hydroxyfuranone derivative structure, which is simple and efficient to develop, has important industrial production and scientific research values.
The existing method for preparing 5-hydroxyfuranone derivatives mainly comprises a cyclic aliphatic ketone compound and 2-chloro-2-methoxy methyl acetate or 1, 1-dimethoxyacetone, wherein the 2-chloro-2-methoxy methyl acetate or 1, 1-dimethoxyacetone is prepared through 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 material obtaining, more side reactions and the like. At present, no efficient and simple method for preparing 5-hydroxyfuranone derivatives exists.
Disclosure of Invention
Aiming at the problems, the invention provides a preparation method of the 5-hydroxyfuranone derivative, which has the advantages of mild reaction conditions, simple operation, easily available raw materials, good functional group compatibility and wide substrate application range.
In order to achieve the purpose, the technical scheme adopted by the invention is as follows:
a preparation method of a 5-hydroxyfuranone derivative specifically comprises the following steps: adding an alpha-keto acid compound shown in a formula (II), a fatty ketone compound shown in a formula (III) and a catalyst into an organic solvent in sequence, reacting at a certain reaction temperature, and purifying by column chromatography to obtain a 5-hydroxyfuranone 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 2 And R 3 Independently selected from any one of hydrogen atom, C1-C6 alkyl and C1-C6 alkenyl.
Wherein C1-C6 alkyl refers to straight or branched chain alkyl groups having 1-6 carbon atoms, including: methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, tert-butyl, n-pentyl, isopentyl, n-hexylcyclohexyl, and the like.
C1-C6 alkenyl refers to straight or branched chain carbon-carbon double bond containing substituents having 1-6 carbon atoms, including: ethenyl, propenyl, butenyl, pentenyl, hexenyl, cyclohexenyl.
Preferably, the organic solvent comprises: toluene, fluorobenzene, trifluorotoluene, 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 and titanium tetrachloride.
Preferably, the molar ratio of the alpha-keto acid compound (II) to the aliphatic ketone compound (III) is 1 (1-3); the mol 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 reaction 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 the petroleum ether to the ethyl acetate is (1-10): 1.
The invention has the beneficial effects that:
1. the invention adopts cheap and easily obtained alpha-keto acid compound and aliphatic ketone compound as raw materials and boron trifluoride diethyl etherate as a catalyst to prepare the 5-hydroxyfuranone derivative.
2. The method 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 functional group compatibility, simple post-treatment, high atom economy and the like.
4. The invention provides a new synthetic route for the preparation of the 5-hydroxyfuranone derivative, and the prepared 5-hydroxyfuranone derivative can play an important role in the field of active drug intermediates and has greater application value and potential in industrial production and scientific research.
Detailed Description
The technical solutions of the present invention are further illustrated and described below by specific embodiments, but the embodiments of the present invention are not limited thereto.
Example 1:
adding the above benzoyl formic acid (II), cyclohexanone compound (III) and trifluoroboric acid ethyl ether (BF) into toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the benzoylformic acid (II) to the cyclohexanone compound (III) is 1: 2; benzoylcarboxylic acid (II) with boron trifluoride etherate (BF) 3 ·Et 2 O) in a molar ratio of 1: 0.2; the ratio of benzoylcarboxylic acid (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated salt water in an equal volume ratio into a reaction system, oscillating and extracting for 3 times, collecting an organic layer, drying, carrying out rotary evaporation and concentration to obtain a crude product, carrying out chromatography on the crude product by a 300-mesh silica gel column chromatography, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely a compound (C) of a formula (I) with a white solid appearance 14 H 14 O 3 )。
For the compound (C) of the formula (I) obtained in this example 14 H 14 O 3 ) The nuclear magnetic resonance analysis was carried out, and the results were: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.44-7.34(m,5H),4.31(s,1H),2.97-2.94(m,1H),2.53-2.45(m,2H),2.03-1.91(m,1H),1.86-1.74(m,2H),1.64-1.55(m,1H),1.37-1.24(m,1H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ170.9,162.2,129.2,128.9(2C),128.6,128.5(2C),124.4,103.2,38.3,26.9,25.6,22.0.
HRMS m/z(ESI)calcd for C 14 H 14 O 3 ,(M+H) + 231.1016；found 231.1014.
Through measurement and calculation: a compound of formula (I) (C) 14 H 14 O 3 ) Yield of 86%, melting point: 102-104 ℃.
Example 2:
adding benzoylformic acid (II), tetrahydropyranone compound (III), and trifluoroboric acid diethyl ether (BF) into toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the benzoylformic acid (II) to the tetrahydropyranone compound (III) is 1: 2; benzoylcarboxylic acid (II) with boron trifluoride etherate (BF) 3 ·Et 2 O) in a molar ratio of 1: 0.2; the ratio of benzoylcarboxylic acid (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline water in an equal volume ratio into a reaction system, performing oscillation extraction for 3 times, collecting an organic layer, drying, performing rotary evaporation and concentration to obtain a crude product, performing 300-mesh silica gel column chromatography on the crude product, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely the compound (C) of the formula (I) with a colorless oily liquid appearance 13 H 12 O 4 )。
For the compound (C) of the formula (I) obtained in this example 13 H 12 O 4 ) The nuclear magnetic resonance analysis was carried out, and the results were: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.45-7.31(m,5H),4.75(d,J＝13.2Hz,1H),4.41-4.38(m,2H),4.00-3.96(m,1H),3.86-3.80(m,1H),2.37(d,J＝13.4Hz,1H),2.10-1.99(m,1H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ170.3,154.8,129.5,128.9(2C),128.7(2C),128.1,126.1,100.9,64.6,62.7,40.0.
HRMS m/z(ESI)calcd for C 13 H 12 O 4 ,(M+H) + 233.0808；found 233.0806.
Through measurement and calculation: a compound of formula (I) (C) 13 H 12 O 4 ) The yield of (a) was 60%.
Example 3:
adding benzoylformic acid (II), cycloheptanone compound (III), and trifluoroboric acid diethyl ether (BF) into toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the benzoylformic acid (II) to the cycloheptanone compound (III) is 1: 2; benzoylcarboxylic acid (II) with boron trifluoride etherate (BF) 3 ·Et 2 O) in a molar ratio of 1: 0.2; the ratio of benzoylcarboxylic acid (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline water in an equal volume ratio into a reaction system, performing oscillation extraction for 3 times, collecting an organic layer, drying, performing rotary evaporation and concentration to obtain a crude product, performing 300-mesh silica gel column chromatography on the crude product, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely the compound (C) of the formula (I) with a white solid appearance 15 H 16 O 3 )。
For the compound (C) of the formula (I) obtained in this example 15 H 16 O 3 ) Nuclear magnetic resonance analysis was performed, with the results: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.44-7.32(m,5H),4.55(s,1H),2.84-2.63(m,2H),2.34(ddd,J＝14.2,6.1,2.7Hz,1H),1.99-1.55(m,6H),1.46-1.34(m,1H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ171.3,164.2,129.6,128.9(2C),128.5,128.3(2C),127.1,107.7,38.0,28.5,26.6,25.6,23.5.
HRMS m/z(ESI)calcd for C 15 H 16 O 3 ,(M+H) + 245.1172；found 245.1171.
Through measurement and calculation: a compound of formula (I) (C) 15 H 16 O 3 ) Yield of 79%, melting point: 84-86 ℃.
Example 4:
adding 4-methylbenzoylcarboxylic acid (II) of the above formula, acetonide (III), trifluoroboric acid ethyl ether (BF) to toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the 4-methylbenzoyl formic acid (II) to the acetonide (III) is 1: 2; 4-Methylbenzoylcarboxylic acid (II) with boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) in a molar ratio of 1: 0.2; the ratio of 4-methylbenzoylcarboxylic acid (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline water in an equal volume ratio into a reaction system, performing oscillation extraction for 3 times, collecting an organic layer, drying, performing rotary evaporation and concentration to obtain a crude product, performing 300-mesh silica gel column chromatography on the crude product, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely the compound (C) of the formula (I) with a white solid appearance 11 H 10 O 3 )。
For the compound (C) of the formula (I) obtained in this example 11 H 10 O 3 ) The nuclear magnetic resonance analysis was carried out, and the results were: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.78-7.75(m,2H),7.40-7.33(m,3H),7.30(s,1H),4.41(s,1H),1.73(s,3H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ170.0,146.4,132.5,129.8,128.6(3C),127.4(2C),103.7,24.7.
HRMS m/z(ESI)calcd for C 11 H 10 O 3 ,(M+H) + 191.0703；found 191.0705.
Through measurement and calculation: a compound of formula (I) (C) 11 H 10 O 3 ) Is/are as followsYield 59%, melting point: 91-93 ℃.
Example 5:
adding the above formula 2- (naphthalen-2-yl) -2-oxoacetic acid (II), cyclohexanone compound (III), and trifluoroboric acid diethyl ether (BF) to toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the 2- (naphthalene-2-yl) -2-oxoacetic acid (II) to the haloalkyne compound (III) is 1: 2; 2- (Naphthalen-2-yl) -2-oxoacetic acid (II) with boron trifluoride etherate (BF) 3 ·Et 2 O) in a molar ratio of 1: 0.2; the ratio of 2- (naphthalen-2-yl) -2-oxoacetic acid (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline water in an equal volume ratio into a reaction system, performing oscillation extraction for 3 times, collecting an organic layer, drying, performing rotary evaporation and concentration to obtain a crude product, performing 300-mesh silica gel column chromatography on the crude product, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely the compound (C) of the formula (I) with a white solid appearance 18 H 16 O 3 )。
For the compound (C) of the formula (I) obtained in this example 18 H 16 O 3 ) The nuclear magnetic resonance analysis was carried out, and the results were: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.89(s,1H),7.78-7.73(m,3H),7.51-7.38(m,3H),4.70(s,1H),2.98(d,J＝13.7Hz,1H),2.60-2.44(m,2H),2.00-1.89(m,1H),1.82-1.75(m,2H),1.63-1.55(m,1H),1.37-1.17(m,1H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ171.3,162.7,133.0,132.9,128.6,128.2,128.0,127.6,126.6,126.6,126.2,126.1,124.3,103.5,38.2,26.9,25.8,22.0.
HRMS m/z(ESI)calcd for C 18 H 16 O 3 ,(M+H) + 281.1172；found 281.1170.
Through measurement and calculation: formula (A), (B) andI) compound (C) 18 H 16 O 3 ) Yield of 85%, melting point: 135 ℃ and 137 ℃.
Example 6:
adding 4-methylphenylglyoxylic acid compound (II) of the above formula, cyclohexanone compound (III), and trifluoroboric acid diethyl ether (BF) to toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the 4-methyl phenyl glyoxylic acid compound (II) to the cyclohexanone compound (III) is 1: 2; 4-Methylphenylglyoxylic acid compound (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) is 1: 0.2; the ratio of the 4-methylphenylglyoxylic acid compound (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline water in an equal volume ratio into a reaction system, performing oscillation extraction for 3 times, collecting an organic layer, drying, performing rotary evaporation and concentration to obtain a crude product, performing 300-mesh silica gel column chromatography on the crude product, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely the compound (C) of the formula (I) with a white solid appearance 15 H 16 O 3 )。
For the compound (C) of the formula (I) obtained in this example 15 H 16 O 3 ) Nuclear magnetic resonance analysis was performed, with the results: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.32(d,J＝8.0Hz,2H),7.19(d,J＝7.8Hz,2H),4.23(s,1H),2.95(d,J＝13.7Hz,1H),2.52-2.42(m,2H),2.00-1.94(m,1H),1.82-1.75(m,2H),1.62-1.55(m,1H),1.35-1.24(m,1H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ171.0,161.5,138.6,129.1(2C),128.8(2C),126.3,124.3,103.2,38.2,26.9,25.6,22.1,21.3.
HRMS m/z(ESI)calcd for C 15 H 16 O 3 ,(M+H) + 245.1172；found 245.1175.
Through measurement and calculation: a compound of formula (I) (C) 15 H 16 O 3 ) Yield of (b) 84%, melting point: 131 ℃ and 133 ℃.
Example 7:
adding the above 4-bromophenyl glyoxylic acid compound (II), cyclohexanone compound (III), and trifluoroboric acid ethyl ether (BF) to toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the 4-bromophenyl glyoxylic acid compound (II) to the cyclohexanone compound (III) is 1: 2; 4-bromophenyl glyoxylic acid compound (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) in a molar ratio of 1: 0.2; the ratio of 4-bromophenyl glyoxylic acid compound (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline water in an equal volume ratio into a reaction system, performing oscillation extraction for 3 times, collecting an organic layer, drying, performing rotary evaporation and concentration to obtain a crude product, performing 300-mesh silica gel column chromatography on the crude product, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely the compound (C) of the formula (I) with a white solid appearance 14 H 13 BrO 3 )。
For the compound (C) of the formula (I) obtained in this example 14 H 13 BrO 3 ) The nuclear magnetic resonance analysis was carried out, and the results were: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.55-7.49(m,2H),7.32-7.25(m,2H),3.95(s,1H),2.96-2.87(m,1H),2.56-2.43(m,2H),2.08-1.96(m,1H),2.04-1.99(m,2H),1.68-1.57(m,1H),1.42-1.25(m,1H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ170.5,162.6,131.7(2C),130.5(2C),128.0,123.5,123.1,103.3,38.3,26.9,25.7,22.0.
HRMS m/z(ESI)calcd for C 14 H 13 BrO 3 ,(M+H) + 309.0121；found 309.0119.
Through measurement and calculation: a compound of formula (I) (C) 14 H 13 BrO 3 ) 80% yield, melting point: 168 ℃ and 170 ℃.
Example 8:
adding the above 2-thiophene glyoxylic acid compound (II), cyclohexanone compound (III) and trifluoroboric acid ethyl ether (BF) into toluene 3 ·Et 2 O), followed by a sealing reaction with stirring at a temperature of 40 ℃ for 2 hours.
Wherein the molar ratio of the 2-thiophene glyoxylic acid compound (II) to the cyclohexanone compound (III) is 1: 2; 2-Thiophenemethylenoic acid compound (II) and boron trifluoride diethyl etherate (BF) 3 ·Et 2 O) in a molar ratio of 1: 0.2; the ratio of the 2-thiopheneacetic acid compound (II) to toluene was 1mmol:4 mL.
After the reaction is finished, adding a mixed solution of ethyl acetate and saturated saline water in an equal volume ratio into a reaction system, performing oscillation extraction for 3 times, collecting an organic layer, drying, performing rotary evaporation and concentration to obtain a crude product, performing 300-mesh silica gel column chromatography on the crude product, and using a mixed solution of ethyl acetate and petroleum ether as an eluent, wherein the volume ratio of ethyl acetate to petroleum ether is 1:20, so as to obtain a target product, namely the compound (C) of the formula (I) with a white solid appearance 12 H 12 SO 3 )。
For the compound (C) of the formula (I) obtained in this example 12 H 12 SO 3 ) The nuclear magnetic resonance analysis was carried out, and the results were: 1 h NMR (400MHz, deuterated chloroform CDCl 3 )δ7.64(d,J＝3.7Hz,1H),7.39(d,J＝5.1Hz,1H),7.08(dd,J＝4.9,3.8Hz,1H),3.92(s,1H),3.28-3.23(m,1H),2.61-2.42(m,2H),2.07-2.02(m,1H),1.89-1.72(m,2H),1.67-1.52(m,1H),1.46-1.29(m,1H).
13 C NMR (100MHz, deuterated chloroform CDCl 3 )δ169.8,158.5,130.7,128.5,127.3,126.9,118.2,103.3,38.3,26.7,26.2,22.0.
HRMS m/z(ESI)calcd for C 12 H 12 SO 3 ,(M+H) + 237.0580；found 237.0582.
Through measurement and calculation: a compound of formula (I) (C) 12 H 12 SO 3 ) Yield of (b) 72%, melting point: 70-72 ℃.
In conclusion, the invention takes the alpha-keto acid compound and the aliphatic ketone compound as raw materials, and takes the cheap and easily available acid as the catalyst to prepare the 5-hydroxyfuranone derivative, and the method has the advantages of high reaction yield, simple operation, high atom economy, good functional group compatibility and wide substrate application range. The invention provides a brand new route for preparing the 5-hydroxyfuranone derivative.
It is to be noted that the present invention is not described in detail, and is well known to those skilled in the art.
The above examples are only for further illustrating the preparation method of a 5-hydroxyfuranone derivative according to the present invention, but the present invention is not limited to the examples, and all equivalent changes and modifications made to the above examples according to the technical spirit of the present invention are included in the scope of the present invention.
Claims (6)
1. A preparation method of a 5-hydroxyfuranone derivative is characterized by comprising the following steps: adding an alpha-keto acid compound shown in a formula (II), a fatty ketone compound shown in a formula (III) and a catalyst into an organic solvent in sequence, reacting at a certain reaction temperature, and purifying by column chromatography to obtain a 5-hydroxyfuranone 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 2 And R 3 Independently selected from any one of hydrogen atom, C1-C6 alkyl and C1-C6 alkenyl.
2. The method according to claim 1, wherein the organic solvent comprises: toluene, fluorobenzene, trifluorotoluene, chlorobenzene, benzene, xylene, tetrahydrofuran, dichloromethane, 1, 2-dichloroethane, ethanol, acetonitrile, N-dimethylformamide, N-dimethylacetamide, dimethylsulfoxide, and N-methylpyrrolidone.
3. The method of claim 1, wherein the catalyst comprises: boron trifluoride diethyl etherate, trifluoromethanesulfonic anhydride, p-toluenesulfonic acid, ferric chloride, bismuth trifluoromethanesulfonate, zinc trifluoromethanesulfonate, yttrium trifluoromethanesulfonate, copper trifluoromethanesulfonate, aluminum chloride and titanium tetrachloride.
4. The method 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 mol 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.
5. The method of claim 1, wherein the reaction temperature is 25-120 ℃ and the reaction time is 0.5-12 hours.
6. The preparation method of the 5-hydroxyfuranone derivative according to claim 1, wherein an eluent used for the column chromatography purification is a mixed solvent of petroleum ether and ethyl acetate, and the volume ratio of the petroleum ether to the ethyl acetate is (1-10): 1.
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| JPH09110853A (en) * | 1995-10-12 | 1997-04-28 | Kikkoman Corp | 4-acyloxyfuranone derivative or its salt and its production |
| CN106565644A (en) * | 2016-10-28 | 2017-04-19 | 上海大学 | 3- alkyl-5-hydroxy-4-aryl furanone derivative and preparation method thereof |
| WO2019083001A1 (en) * | 2017-10-27 | 2019-05-02 | 住友化学株式会社 | Method for producing benzoyl formic acid compound and pyridazine compound |
| CN110294725A (en) * | 2019-07-03 | 2019-10-01 | 广东医科大学 | A kind of derivative and its process for catalytic synthesis of sponge furanone |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPH09110853A (en) * | 1995-10-12 | 1997-04-28 | Kikkoman Corp | 4-acyloxyfuranone derivative or its salt and its production |
| CN106565644A (en) * | 2016-10-28 | 2017-04-19 | 上海大学 | 3- alkyl-5-hydroxy-4-aryl furanone derivative and preparation method thereof |
| WO2019083001A1 (en) * | 2017-10-27 | 2019-05-02 | 住友化学株式会社 | Method for producing benzoyl formic acid compound and pyridazine compound |
| CN110294725A (en) * | 2019-07-03 | 2019-10-01 | 广东医科大学 | A kind of derivative and its process for catalytic synthesis of sponge furanone |
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