CN117326922A - Synthesis method of 4-hydroxycyclopent-2-enone - Google Patents
Synthesis method of 4-hydroxycyclopent-2-enone Download PDFInfo
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- CN117326922A CN117326922A CN202311216463.7A CN202311216463A CN117326922A CN 117326922 A CN117326922 A CN 117326922A CN 202311216463 A CN202311216463 A CN 202311216463A CN 117326922 A CN117326922 A CN 117326922A
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- hydroxycyclopent
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- DHNDDRBMUVFQIZ-UHFFFAOYSA-N 4-hydroxycyclopent-2-en-1-one Chemical compound OC1CC(=O)C=C1 DHNDDRBMUVFQIZ-UHFFFAOYSA-N 0.000 title claims abstract description 38
- 238000001308 synthesis method Methods 0.000 title claims description 6
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 30
- VQKFNUFAXTZWDK-UHFFFAOYSA-N 2-Methylfuran Chemical compound CC1=CC=CO1 VQKFNUFAXTZWDK-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 24
- -1 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran Chemical compound 0.000 claims abstract description 20
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 20
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims abstract description 16
- 239000007800 oxidant agent Substances 0.000 claims abstract description 14
- 238000001035 drying Methods 0.000 claims abstract description 13
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical compound [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 claims abstract description 10
- 230000001590 oxidative effect Effects 0.000 claims abstract description 10
- 238000004440 column chromatography Methods 0.000 claims abstract description 9
- 239000008367 deionised water Substances 0.000 claims abstract description 8
- 229910021641 deionized water Inorganic materials 0.000 claims abstract description 8
- 238000002156 mixing Methods 0.000 claims abstract description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 claims abstract description 8
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 8
- 239000012043 crude product Substances 0.000 claims abstract description 5
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 239000012295 chemical reaction liquid Substances 0.000 claims abstract description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 claims description 10
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 claims description 6
- 239000002253 acid Substances 0.000 claims description 5
- 239000011230 binding agent Substances 0.000 claims description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 4
- YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 claims description 3
- MENYRYNFSIBDQN-UHFFFAOYSA-N 5,5-dibromoimidazolidine-2,4-dione Chemical compound BrC1(Br)NC(=O)NC1=O MENYRYNFSIBDQN-UHFFFAOYSA-N 0.000 claims description 3
- 229950009390 symclosene Drugs 0.000 claims description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 2
- 239000000047 product Substances 0.000 abstract description 19
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000009776 industrial production Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 15
- 239000003795 chemical substances by application Substances 0.000 description 10
- 239000003208 petroleum Substances 0.000 description 10
- XPFVYQJUAUNWIW-UHFFFAOYSA-N furfuryl alcohol Chemical compound OCC1=CC=CO1 XPFVYQJUAUNWIW-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 7
- ZSWFCLXCOIISFI-UHFFFAOYSA-N cyclopentadiene Chemical compound C1C=CC=C1 ZSWFCLXCOIISFI-UHFFFAOYSA-N 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- 230000015572 biosynthetic process Effects 0.000 description 4
- 230000003647 oxidation Effects 0.000 description 4
- 238000007254 oxidation reaction Methods 0.000 description 4
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 description 3
- VZSRBBMJRBPUNF-UHFFFAOYSA-N 2-(2,3-dihydro-1H-inden-2-ylamino)-N-[3-oxo-3-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propyl]pyrimidine-5-carboxamide Chemical compound C1C(CC2=CC=CC=C12)NC1=NC=C(C=N1)C(=O)NCCC(N1CC2=C(CC1)NN=N2)=O VZSRBBMJRBPUNF-UHFFFAOYSA-N 0.000 description 2
- 101001110286 Homo sapiens Ras-related C3 botulinum toxin substrate 1 Proteins 0.000 description 2
- 102100022122 Ras-related C3 botulinum toxin substrate 1 Human genes 0.000 description 2
- 238000013459 approach Methods 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052799 carbon Inorganic materials 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 238000010586 diagram Methods 0.000 description 2
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 2
- 229910052763 palladium Inorganic materials 0.000 description 2
- 150000004965 peroxy acids Chemical class 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 238000007363 ring formation reaction Methods 0.000 description 2
- 238000013341 scale-up Methods 0.000 description 2
- XYPISWUKQGWYGX-UHFFFAOYSA-N 2,2,2-trifluoroethaneperoxoic acid Chemical compound OOC(=O)C(F)(F)F XYPISWUKQGWYGX-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 230000004075 alteration Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000002837 carbocyclic group Chemical group 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 239000000084 colloidal system Substances 0.000 description 1
- KQAVUGAZLAPNJY-UHFFFAOYSA-N cyclopent-3-en-1-one Chemical compound O=C1CC=CC1 KQAVUGAZLAPNJY-UHFFFAOYSA-N 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- 235000019441 ethanol Nutrition 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 1
- 239000003999 initiator Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 229910000510 noble metal Inorganic materials 0.000 description 1
- 230000005311 nuclear magnetism Effects 0.000 description 1
- TWNQGVIAIRXVLR-UHFFFAOYSA-N oxo(oxoalumanyloxy)alumane Chemical compound O=[Al]O[Al]=O TWNQGVIAIRXVLR-UHFFFAOYSA-N 0.000 description 1
- 238000007867 post-reaction treatment Methods 0.000 description 1
- 230000035484 reaction time Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000006462 rearrangement reaction Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 150000003505 terpenes Chemical class 0.000 description 1
- 235000007586 terpenes Nutrition 0.000 description 1
- USFPINLPPFWTJW-UHFFFAOYSA-N tetraphenylphosphonium Chemical compound C1=CC=CC=C1[P+](C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 USFPINLPPFWTJW-UHFFFAOYSA-N 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
- C07C45/64—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by introduction of functional groups containing oxygen only in singly bound form
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/56—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds
- C07C45/57—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom
- C07C45/59—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds from heterocyclic compounds with oxygen as the only heteroatom in five-membered rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/26—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D307/30—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/32—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2601/00—Systems containing only non-condensed rings
- C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
- C07C2601/10—Systems containing only non-condensed rings with a five-membered ring the ring being unsaturated
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a method for synthesizing 4-hydroxycyclopent-2-enone, which comprises the steps of adding 2-methylfuran and sodium carbonate into an organic solvent, uniformly mixing, adding an oxidant, reacting at a temperature of minus 30 ℃ to 0 ℃ to obtain 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran, adding the 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into deionized water, adding acetic acid for reaction to obtain (Z) -4-pentanone-2-enaldehyde, adding the (Z) -4-pentanone-2-enaldehyde into disodium hydrogen phosphate solution for reaction, extracting, drying and concentrating the obtained reaction liquid to obtain a crude product, and performing column chromatography to obtain the product. Compared with the prior art, the method has the advantages of cheap and easily obtained raw materials, mild reaction conditions, simple operation, easy purification of products, high total yield and easy realization of industrial production.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 4-hydroxycyclopent-2-enone.
Background
The 4-hydroxycyclopent-2-enone (4-hydroxycyclopent-2-enone, 4-HCP, rac-1) belongs to an important synthetic building block, which has a five-membered carbocyclic skeleton, contains three functional groups of hydroxyl, alkenyl and carbonyl, and the carbon of the hydroxyl is a chiral center. Optically pure 4-HCP, including (R) -1 and (S) -1, can control the stereochemistry of the reaction to achieve asymmetric synthesis. Optically pure 4-HCP can be obtained by resolution of the racemate rac-1 (literature: kumaraguru, T.; babita, P.; shellu, G.; lavanya, K.; fadnavis, N.W. Org. Process Res. Dev.2013,17, 1526-1530.).
4-HCP and its hydroxy protected derivatives (4-HCPs) are an important raw material in the field of pharmaceutical synthesis and are widely used in the synthesis of prostaglandins, alkaloids, terpenes and other types of active natural products. For example, a series of prostaglandins were synthesized using (R) -1a as a starting material (literature: suzuki, M.; yanagisawa, A.; noyori, R.J. am. Chem. Soc.1988,110, 4718-426.).
At present, several methods for synthesizing 4-HCP have been reported. First, by the rearrangement reaction of furfuryl alcohol (furfuryl alcohol), two types of conditions have been reported: under the first type of conditions, 4-HCP was obtained by refluxing furfuryl alcohol in aqueous solution (literature) (a) Nanni, M.; tamachi, H.; moriyama, S.Jpn. Kokai TokkyoKoho 1982,57062236.; piancaielli, G.; D 'Auria, M.; D' Onofrio, F.Synthesis 1994, 867-889.; morgan, B.S.; hoenner, D.; evans, P.; roberts, S.M. tetrahedron asymmetry 2004,15,2807-2809.). The conditions have low reaction concentration, long reaction time and complex post-reaction treatment, raw materials and products are unstable under the reaction conditions to generate black colloid, and the products need to be purified by column chromatography; the second type of conditions, using microwaves and a pipeline reactor, is characterized by high temperatures (up to 240 ℃) and high pressures and short times (tens of seconds) with yields of over 80% (literature) (a) ullrich, k.; kreitmeier, p.; reiser, o.synlett2010, 2037-2040.; b.) Li Ning, li Anyi, zhang Tao, wang Aiqin, wang Xiaodong, cong: cn106866392 a.). Such conditions require high temperature and high pressure and high demands on the reaction equipment. On the other hand, in order to ensure rapid temperature change in a short time, the inner diameter of the pipe is narrow, and insoluble matters generated by the reaction are liable to clog the pipe.
Secondly, synthesizing 4-HCP by taking cyclopentadiene as a raw material has two ways: the first approach, in which cyclopentadiene is cyclized with singlet oxygen and then rearranged to 4-HCP by palladium tetraphenylphosphine (literature: suzuki, M.; oda, Y.; noyori, R.tetrahedron Lett.1981,22, 4413-4416.); the second route, oxidation of cyclopentadiene with peracid gives the monoepoxide which rearranges to 3-cyclopentenone under palladium catalysis, followed by epoxidation with trifluoroperacetic acid and finally rearrangement with aluminum oxide catalysis gives the 4-HCP (literature: suzuki, M.; oda, Y.; noyori, R.J.Am.chem.Soc).
1979,101,1623-1625.). These approaches have problems such as the use of singlet oxygen (singlet oxygen generation devices are difficult to scale up and have safety problems), noble metal catalysts, peracids, etc., and are not suitable for industrial scale up.
In addition, the synthesis of 4-HCP can be achieved by oxidation of 2-methylfuran, but this method requires the use of liquid bromine as the oxidant, followed by oxidation, hydrolysis, and cyclization reactions (literature: hamann, P.R., wissner, A. Synthetic Commun).
1989,19,1509-1518.). The liquid bromine is inconvenient to store and use, and has great potential safety hazard.
Disclosure of Invention
The invention aims to provide a synthesis method of 4-HCP, which solves the problems of harsh reaction conditions, potential safety hazards, high equipment requirements, complex process, low yield, high cost and adverse industrialized production in the synthesis method proposed in the background art.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a method for synthesizing 4-hydroxycyclopent-2-enone comprises the following steps:
s1, adding 2-methylfuran and an acid binding agent into an organic solvent, uniformly mixing, adding an oxidant, and reacting at a temperature of minus 30 ℃ to 0 ℃ to obtain 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran;
s2, adding 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into deionized water, and adding acetic acid to react to obtain (Z) -4-pentanone-2-enal;
s3, adding (Z) -4-pentanone-2-enal into disodium hydrogen phosphate solution for reaction, extracting, drying and concentrating the obtained reaction liquid to obtain a crude product, and carrying out column chromatography on the crude product to obtain 4-hydroxycyclopent-2-enone.
In step S1, the organic solvent is methanol or ethanol; the oxidant is selected from any one of N-bromosuccinimide, N-chlorosuccinimide, dibromohydantoin or trichloroisocyanuric acid.
In step S1, the acid-binding agent is selected from any one of sodium carbonate, sodium bicarbonate or potassium carbonate, and the dosage of the acid-binding agent is 2-5 equivalents of 2-methyl furan.
Further, in step S1, the temperature of the reaction is 0 ℃.
Further, in step S1, the molar ratio of the oxidizing agent to 2-methylfuran is (1 to 3): 1.
further, in step S2, the reaction temperature is 0℃to 50℃and more preferably 0 ℃.
Further, in step S2, the molar ratio of the acetic acid to 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran is (0.1 to 1): 1, more preferably 0.2:1.
further, in the step S3, the molar ratio of the disodium hydrogen phosphate to the 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran is (1 to 2): 1.
further, in step S3, the reaction temperature is 0 to 60 ℃, more preferably 50 ℃, and at this temperature, the reaction rate is fast and byproducts are few.
The reaction route of the invention is as follows:
the invention has the beneficial effects that:
the invention provides a novel method for synthesizing 4-hydroxycyclopent-2-enone, which is prepared by taking 2-methylfuran as an initiator and sequentially carrying out oxidation, hydrolysis, cyclization and other reactions. Compared with the existing synthesis method of 4-hydroxycyclopent-2-enone, the method has the advantages of low-cost and easily obtained raw materials, mild reaction conditions, simple operation, easy purification of products, high total yield and easy realization of industrial production.
Drawings
FIG. 1 is a diagram of the product 4-hydroxycyclopent-2-enone synthesized in example 1 1 H-NMR spectrum.
Detailed Description
The technical solutions of the present invention will be clearly and completely described below with reference to the accompanying drawings and specific embodiments, and it is apparent that the described embodiments are only some embodiments of the present invention, not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
A method for synthesizing 4-hydroxycyclopent-2-enone comprises the following steps:
s1, adding 200 ml of absolute ethyl alcohol, 10 g of 2-methylfuran and 51.7 g of sodium carbonate into a 500 ml round bottom flask, uniformly mixing, adding 22 g of oxidant N-bromosuccinimide at 0 ℃, reacting at 0 ℃, carrying out thin layer tracking reaction (developing agent: ethyl acetate: petroleum ether=10:1), adding 200 ml of saturated saline after the reaction is finished, extracting 3 times with 300 ml of dichloromethane, drying, and concentrating to obtain 20 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran;
s2, adding 200 ml of deionized water and 20 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into a 500 ml round bottom flask, adding 1.5 ml of acetic acid at 0 ℃, and reacting for 1h at 0 ℃ to obtain (Z) -4-pentanone-2-enal;
s3, (Z) -4-pentanone-2-enal is added into 68 ml of 1.7M disodium hydrogen phosphate solution for reaction at 50 ℃, the reaction is completed by thin layer tracking (developing agent: ethyl acetate: petroleum ether=1:1), the reaction is completed, the ethyl acetate is extracted for 5 times by 1000 ml, and the product of 9.3 g (78%) of 4-hydroxycyclopent-2-enone is obtained by drying, concentrating and column chromatography.
FIG. 1 is a diagram of the product 4-hydroxycyclopent-2-enone synthesized in example 1 1 H-NMR spectrum, nuclear magnetism (CDCl) of 4-hydroxycyclopent-2-enone 3 ) The data are as follows: 1 HNMR(CDCl 3 ，400MHz)：7.54(d，1H)，6.15(d，1H)，4.99(m，1H)，3.05(brs，1H)，2.70(dd，1H)，2.21(dd，1H)。
example 2
A method for synthesizing 4-hydroxycyclopent-2-enone comprises the following steps:
s1, adding 200 ml of absolute ethyl alcohol, 10 g of 2-methylfuran and 51.7 g of sodium carbonate into a 500 ml round bottom flask, uniformly mixing, adding 16.2 g of oxidant N-chlorosuccinimide at 0 ℃, reacting at 0 ℃, carrying out thin layer tracking reaction (developing agent: ethyl acetate: petroleum ether=10:1), adding 200 ml of saturated saline after the reaction is finished, extracting 3 times with 300 ml of dichloromethane, drying, and concentrating to obtain 15.6 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran;
s2, adding 200 ml of deionized water and 15.6 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into a 500 ml round bottom flask, adding 1 ml of acetic acid at 0 ℃, and reacting for 1h at 0 ℃ to obtain (Z) -4-pentanone-2-enal;
s3, (Z) -4-pentanone-2-enal is added into 53 ml of 1.7M disodium hydrogen phosphate solution for reaction at 50 ℃, the reaction is completed by thin layer tracking (developing agent: ethyl acetate: petroleum ether=1:1), the reaction is completed, the ethyl acetate is extracted for 5 times by 1000 ml, and the product of 7.2 g (60%) of 4-hydroxycyclopent-2-enone is obtained by drying, concentrating and column chromatography.
The nuclear magnetic data of the product synthesized in example 2, 4-hydroxycyclopent-2-enone, is consistent with the nuclear magnetic data of the product synthesized in example 1.
Example 3
A method for synthesizing 4-hydroxycyclopent-2-enone comprises the following steps:
s1, adding 200 ml of absolute ethyl alcohol, 10 g of 2-methylfuran and 51.7 g of sodium carbonate into a 500 ml round bottom flask, uniformly mixing, adding 35 g of oxidant dibromohydantoin at 0 ℃, reacting at 0 ℃, carrying out thin-layer tracking reaction (developing agent: ethyl acetate: petroleum ether=10:1), adding 200 ml of saturated saline solution after the reaction is finished, extracting 3 times with 300 ml of dichloromethane, drying, and concentrating to obtain 16 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran;
s2, adding 200 ml of deionized water and 16 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into a 500 ml round bottom flask, adding 1.1 ml of acetic acid at 0 ℃, and reacting for 1h at 0 ℃ to obtain (Z) -4-pentanone-2-enal;
s3, (Z) -4-pentanone-2-enal is added into 55 ml of 1.7M disodium hydrogen phosphate solution for reaction at 50 ℃, the reaction is completed by thin layer tracking (developing agent: ethyl acetate: petroleum ether=1:1), the reaction is completed, the ethyl acetate is extracted for 5 times by 1000 ml, and the product of 7.4 g (62%) of 4-hydroxycyclopent-2-enone is obtained by drying, concentrating and column chromatography.
The nuclear magnetic data of the product synthesized in example 3, 4-hydroxycyclopent-2-enone, is consistent with the nuclear magnetic data of the product synthesized in example 1.
Example 4
A method for synthesizing 4-hydroxycyclopent-2-enone comprises the following steps:
s1, adding 200 ml of absolute ethyl alcohol, 10 g of 2-methyl furan and 51.7 g of sodium carbonate into a 500 ml round bottom flask, uniformly mixing, adding 28.2 g of oxidizer trichloroisocyanuric acid at 0 ℃, reacting at 0 ℃, carrying out thin layer tracking reaction (developing agent: ethyl acetate: petroleum ether=10:1), adding 200 ml of saturated saline after the reaction is finished, extracting 3 times with 300 ml of dichloromethane, drying, and concentrating to obtain 14.1 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran;
s2, adding 200 ml of deionized water and 14.1 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into a 500 ml round bottom flask, adding 1 ml of acetic acid at 0 ℃, and reacting for 1h at 0 ℃ to obtain (Z) -4-pentanone-2-enal;
s3, (Z) -4-pentanone-2-enal is added into 48 ml of 1.7M disodium hydrogen phosphate solution for reaction at 50 ℃, the reaction is completed by thin layer tracking (developing agent: ethyl acetate: petroleum ether=1:1), the reaction is completed, the ethyl acetate is extracted for 5 times by 1000 ml, and the product of 4-hydroxycyclopent-2-enone 6.6 g (55%) is obtained by drying, concentrating and column chromatography.
The nuclear magnetic data of the product synthesized in example 4, 4-hydroxycyclopent-2-enone, is consistent with the nuclear magnetic data of the product synthesized in example 1.
Example 5
A method for synthesizing 4-hydroxycyclopent-2-enone comprises the following steps:
s1, adding 2000 ml of absolute ethyl alcohol, 100 g of 2-methylfuran and 517 g of sodium carbonate into a 5000 ml round-bottom flask, uniformly mixing, adding 217 g of oxidant N-bromosuccinimide at 0 ℃, reacting at 0 ℃, finishing the thin layer tracking reaction (developing agent: ethyl acetate: petroleum ether=10:1), adding 1000 ml of saturated saline solution, extracting with 3000 ml of dichloromethane for 5 times, drying, and concentrating to obtain 200 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran;
s2, adding 2000 ml of deionized water and 200 g of 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into a 5000 ml round bottom flask, adding 15 ml of acetic acid at 0 ℃, and reacting for 2 hours at 0 ℃ to obtain (Z) -4-pentanone-2-enal;
s3, (Z) -4-pentanone-2-enal is added into 680 ml of 1.7M disodium hydrogen phosphate solution for reaction at 50 ℃, the reaction is completed by thin layer tracking (developing agent: ethyl acetate: petroleum ether=1:1), the reaction is completed, the mixture is extracted for 8 times by 3000 ml of ethyl acetate, and 89 g (75%) of 4-hydroxycyclopent-2-enone is obtained by drying, concentrating and column chromatography.
The nuclear magnetic data of the product synthesized in example 5, 4-hydroxycyclopent-2-enone, is consistent with the nuclear magnetic data of the product synthesized in example 1.
Although embodiments of the present invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the invention, the scope of which is defined in the appended claims and their equivalents.
Claims (10)
1. The synthesis method of the 4-hydroxycyclopent-2-enone is characterized by comprising the following steps:
s1, adding 2-methylfuran and an acid binding agent into an organic solvent, uniformly mixing, adding an oxidant, and reacting at a temperature of minus 30 ℃ to 0 ℃ to obtain 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran;
s2, adding 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran into deionized water, and adding acetic acid to react to obtain (Z) -4-pentanone-2-enal;
s3, adding (Z) -4-pentanone-2-enal into disodium hydrogen phosphate solution for reaction, extracting, drying and concentrating the obtained reaction liquid to obtain a crude product, and carrying out column chromatography on the crude product to obtain 4-hydroxycyclopent-2-enone;
in the step S1, the organic solvent is methanol or ethanol, and the oxidant is any one selected from N-bromosuccinimide, N-chlorosuccinimide, dibromohydantoin and trichloroisocyanuric acid.
2. The method for synthesizing 4-hydroxycyclopent-2-enone according to claim 1, wherein in step S1, the acid binding agent is selected from any one of sodium carbonate, sodium bicarbonate or potassium carbonate.
3. The method for synthesizing 4-hydroxycyclopent-2-enone according to claim 1, wherein the temperature of the reaction in step S1 is 0 ℃.
4. The method for synthesizing 4-hydroxycyclopent-2-enone according to claim 1, wherein in step S1, the oxidizing agent is N-bromosuccinimide.
5. The method for synthesizing 4-hydroxycyclopent-2-enone according to claim 1, wherein in step S1, the molar ratio of the oxidizing agent to 2-methylfuran is (1-3): 1.
6. the method for synthesizing 4-hydroxycyclopent-2-enone according to claim 1, wherein in step S2, the reaction temperature is 0-50 ℃.
7. The method for synthesizing 4-hydroxycyclopent-2-enone according to claim 1, wherein in step S2, the molar ratio of acetic acid to 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran is (0.1-1): 1.
8. the method for synthesizing 4-hydroxycyclopent-2-enone according to claim 1, wherein in step S3, the molar ratio of disodium hydrogen phosphate to 2, 5-diethoxy-2-methyl-2, 5-dihydrofuran is (1-2): 1.
9. the method for synthesizing 4-hydroxycyclopent-2-enone according to any one of claims 1 to 8, wherein the reaction temperature in step S3 is 0 to 60 ℃.
10. The method for synthesizing 4-hydroxycyclopent-2-enone according to claim 9, wherein the temperature of the reaction in step S3 is 50deg.C.
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