CN115925656B - Method for industrially synthesizing 5-HMF and derivatives thereof - Google Patents
Method for industrially synthesizing 5-HMF and derivatives thereof Download PDFInfo
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- alkali
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- NOEGNKMFWQHSLB-UHFFFAOYSA-N 5-hydroxymethylfurfural Chemical compound OCC1=CC=C(C=O)O1 NOEGNKMFWQHSLB-UHFFFAOYSA-N 0.000 title claims abstract description 79
- 238000000034 method Methods 0.000 title claims abstract description 38
- 230000002194 synthesizing effect Effects 0.000 title claims abstract description 23
- 239000002904 solvent Substances 0.000 claims abstract description 49
- 150000001875 compounds Chemical class 0.000 claims abstract description 32
- 239000003513 alkali Substances 0.000 claims abstract description 16
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 16
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 16
- 238000010438 heat treatment Methods 0.000 claims abstract description 15
- 238000005917 acylation reaction Methods 0.000 claims abstract description 13
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 87
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 37
- 238000006243 chemical reaction Methods 0.000 claims description 32
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 29
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 27
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 20
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- 239000002585 base Substances 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 15
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 14
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 12
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 10
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 10
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 7
- 235000011181 potassium carbonates Nutrition 0.000 claims description 7
- 239000001632 sodium acetate Substances 0.000 claims description 7
- 235000017281 sodium acetate Nutrition 0.000 claims description 7
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 claims description 6
- UOCLXMDMGBRAIB-UHFFFAOYSA-N 1,1,1-trichloroethane Chemical compound CC(Cl)(Cl)Cl UOCLXMDMGBRAIB-UHFFFAOYSA-N 0.000 claims description 5
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 claims description 5
- 239000011736 potassium bicarbonate Substances 0.000 claims description 4
- 229910000028 potassium bicarbonate Inorganic materials 0.000 claims description 4
- 235000015497 potassium bicarbonate Nutrition 0.000 claims description 4
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 claims description 4
- 235000011118 potassium hydroxide Nutrition 0.000 claims description 4
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 4
- 235000017550 sodium carbonate Nutrition 0.000 claims description 4
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 3
- 239000012346 acetyl chloride Substances 0.000 claims description 3
- 150000008065 acid anhydrides Chemical class 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
- 238000000926 separation method Methods 0.000 abstract description 12
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 abstract description 8
- 239000008103 glucose Substances 0.000 abstract description 7
- 230000008569 process Effects 0.000 abstract description 5
- 239000002994 raw material Substances 0.000 abstract description 5
- 238000001308 synthesis method Methods 0.000 abstract description 4
- 230000002411 adverse Effects 0.000 abstract description 2
- 230000007613 environmental effect Effects 0.000 abstract description 2
- 239000002360 explosive Substances 0.000 abstract description 2
- 238000004519 manufacturing process Methods 0.000 abstract description 2
- 238000000746 purification Methods 0.000 abstract description 2
- 238000011084 recovery Methods 0.000 abstract description 2
- 231100000331 toxic Toxicity 0.000 abstract description 2
- 230000002588 toxic effect Effects 0.000 abstract description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- 239000007787 solid Substances 0.000 description 25
- 238000002360 preparation method Methods 0.000 description 23
- 239000012074 organic phase Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 16
- GSNUFIFRDBKVIE-UHFFFAOYSA-N 2,5-dimethylfuran Chemical compound CC1=CC=C(C)O1 GSNUFIFRDBKVIE-UHFFFAOYSA-N 0.000 description 14
- 238000009835 boiling Methods 0.000 description 13
- 239000003208 petroleum Substances 0.000 description 13
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 description 12
- 238000004090 dissolution Methods 0.000 description 11
- 238000004821 distillation Methods 0.000 description 11
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 11
- 239000000203 mixture Substances 0.000 description 11
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
- 238000011160 research Methods 0.000 description 10
- 239000000243 solution Substances 0.000 description 10
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 9
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 8
- 239000012044 organic layer Substances 0.000 description 8
- 239000003960 organic solvent Substances 0.000 description 8
- 239000000047 product Substances 0.000 description 8
- 239000002608 ionic liquid Substances 0.000 description 7
- 150000001720 carbohydrates Chemical class 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- 239000012043 crude product Substances 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 239000006227 byproduct Substances 0.000 description 4
- 239000003054 catalyst Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 229930091371 Fructose Natural products 0.000 description 3
- RFSUNEUAIZKAJO-ARQDHWQXSA-N Fructose Chemical compound OC[C@H]1O[C@](O)(CO)[C@@H](O)[C@@H]1O RFSUNEUAIZKAJO-ARQDHWQXSA-N 0.000 description 3
- 230000018044 dehydration Effects 0.000 description 3
- 238000006297 dehydration reaction Methods 0.000 description 3
- 229960002737 fructose Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 230000004048 modification Effects 0.000 description 3
- 238000012986 modification Methods 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
- QAVITTVTXPZTSE-UHFFFAOYSA-N (5-formylfuran-2-yl)methyl acetate Chemical compound CC(=O)OCC1=CC=C(C=O)O1 QAVITTVTXPZTSE-UHFFFAOYSA-N 0.000 description 2
- NOGFHTGYPKWWRX-UHFFFAOYSA-N 2,2,6,6-tetramethyloxan-4-one Chemical compound CC1(C)CC(=O)CC(C)(C)O1 NOGFHTGYPKWWRX-UHFFFAOYSA-N 0.000 description 2
- JOOXCMJARBKPKM-UHFFFAOYSA-N 4-oxopentanoic acid Chemical compound CC(=O)CCC(O)=O JOOXCMJARBKPKM-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 239000005715 Fructose Substances 0.000 description 2
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 2
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 238000010924 continuous production Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 239000000178 monomer Substances 0.000 description 2
- 238000007086 side reaction Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- PXJJKVNIMAZHCB-UHFFFAOYSA-N 2,5-diformylfuran Chemical compound O=CC1=CC=C(C=O)O1 PXJJKVNIMAZHCB-UHFFFAOYSA-N 0.000 description 1
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 239000002028 Biomass Substances 0.000 description 1
- 229960000583 acetic acid Drugs 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001263 acyl chlorides Chemical class 0.000 description 1
- 239000003125 aqueous solvent Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000003197 catalytic effect Effects 0.000 description 1
- 238000006555 catalytic reaction Methods 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000012467 final product Substances 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 239000000446 fuel Substances 0.000 description 1
- 239000012362 glacial acetic acid Substances 0.000 description 1
- XXMIOPMDWAUFGU-UHFFFAOYSA-N hexane-1,6-diol Chemical compound OCCCCCCO XXMIOPMDWAUFGU-UHFFFAOYSA-N 0.000 description 1
- 239000002815 homogeneous catalyst Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 229940040102 levulinic acid Drugs 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- -1 methyl alpha-glucoside Chemical class 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000003541 multi-stage reaction Methods 0.000 description 1
- 150000003214 pyranose derivatives Chemical group 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000008929 regeneration Effects 0.000 description 1
- 238000011069 regeneration method Methods 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011973 solid acid Substances 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
Classifications
-
- 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
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Abstract
The invention belongs to the technical field of industrialized synthesis of 5-HMF, and particularly relates to a method for industrialized synthesis of 5-HMF and derivatives thereof. The compound I is dissolved in a solvent, and the 5-HMF can be prepared under the conditions of alkali and heating; the 5-HMF derivative is prepared by carrying out hydrolysis reaction on the compound I, then carrying out acylation reaction, and finally preparing the 5-HMF derivative under the conditions of alkali and heating. The synthesis method of the invention combines the existing methods for synthesizing the compound I, and the like, can realize the synthesis of the 5-HMF and the derivatives thereof by taking glucose as a raw material, has the synthesis cost far lower than the price of the 5-HMF sold in the market, does not need additional separation and purification in the synthesis process, and has no environmental and safety problems of adverse production such as extremely toxic, explosive, difficult recovery and the like of the used reagent, so the invention provides a new process route for synthesizing the 5-HMF and the derivatives thereof, and has huge industrial economic value.
Description
Technical Field
The invention belongs to the technical field of industrialized synthesis of 5-HMF, and particularly relates to a method for industrialized synthesis of 5-HMF and derivatives thereof.
Background
Along with the daily exhaustion of traditional petroleum resources, how to obtain alternative fuel resources and novel chemical raw materials from substances on a large scale is the key point of the research at present. Cellulose is used as renewable biological source with huge quantity, low price, easy availability, little pollution and the like in the world, and D-glucose monomer can be obtained with the yield of more than 90 percent through large-scale strong acid hydrolysis. Therefore, how to convert the monomer serving as a starting material into some basic chemical raw materials has important research significance. According to the research of the literature, the research is mainly focused on the direct catalysis method for directly preparing 5-hydroxymethylfural (5-hydroxymethylfural, 5-HMF, CAS: 67-47-0) from glucose, and other high-added-value chemicals such as 2, 5-diformylfuran, 2, 5-dimethylfuran, 1, 6-hexanediol and the like are further prepared on the basis.
How to efficiently prepare and obtain 5-HMF from glucose is always an important point of research and development of biomass energy, so far, many thousands of research papers on the aspect of the preparation are not needed, but many application difficulties still exist when the preparation can be really and effectively used for industrial production, and the price of high-purity compounds is still high. According to the comprehensive prior research literature, the direct catalytic conversion of glucose into 5-HMF is characterized in that 2-hydroxyl is oxidized and carbonylated to form 3-deoxyglucurolactone (4084-27-9), then the 3-deoxyglucurolactone is condensed and cyclized to obtain a furan ring structure, and finally the furan ring structure is dehydrated at high temperature to form the target product. Although yields reported in the literature are not low, once these methods are applied to actual commercial continuous production, the large number of unpredictable by-products from side reactions lead to rapid failure of the carefully prepared catalyst types, and the large-scale continuous production is not possible, further affecting the regeneration of the catalyst. Meanwhile, due to the characteristics of low melting point, high boiling point, good compatibility and the like of the 5-HMF, the separation of the 5-HMF and byproducts is difficult to realize by conventional separation means such as crystallization, distillation, extraction and the like.
The reason why 5-HMF is difficult to be industrially produced will be described below with specific reference to different synthetic methods:
(1) Synthesis of 5-HMF from fruit sugar in aqueous System
Since saccharides such as fructose have high solubility in water and are poorly soluble in most organic solvents, in the first place, HMF has been synthesized by dehydration of saccharides using water as a solvent. Water is an excellent solvent for the saccharides and thus high raw material concentrations can be used. However, the strong polarity of water molecules and the strong interaction of hydrogen bonds make many solid acid catalysts unstable in water, resulting in loss of acid sites on the catalyst. Therefore, homogeneous catalysts are generally used in water systems, and the problems of difficult recycling exist at the same time. In addition, under acidic conditions, HMF is susceptible to rehydration reactions, producing levulinic acid and formic acid as byproducts, resulting in reduced HMF yields.
(2) Synthesis of 5-HMF from high boiling organic solvent
High boiling point organic solvents having a strong polarity such as dimethyl sulfoxide (DMSO, tb 189 ℃) and N, N-dimethylformamide (DMF, tb 153 ℃) are strongly soluble in saccharides and thus are increasingly used as solvents for dehydration of saccharides.
A great deal of current research uses high boiling point organic solvents, and the HMF selectivity and yield obtained tend to be much higher than aqueous solvents, with DMSO being the best. However, high boiling solvents also have significant drawbacks in that they are compatible with water and many common organic solvents, making separation of the product by extraction difficult; the high boiling point results in high energy consumption of the product by distillation under reduced pressure, and difficult removal of the solvent. The use of high boiling solvents for large scale production of HMF still depends on the resolution of these problems.
(3) Synthesis of 5-HMF from low boiling organic solvent
Compared with the high-boiling point solvent, the low-boiling point solvent has advantages in separation of the product, the product solution can be distilled at a lower temperature under reduced pressure to remove the solvent, and low-energy separation of the product and the solvent is realized, so that more attention is paid. Due to the separation advantage, low boiling solvents should be preferred in HMF synthesis. However, there are relatively few studies on HMF synthesis in low boiling solvent systems, and further improvements in HMF selectivity and yield are desired.
(4) Synthesis of 5-HMF by two-phase System
The two-phase system consists of water and an organic solvent which is difficult to dissolve in water, the generated HMF can be continuously extracted from the water phase into the organic phase, and the generation rate of the HMF is improved, and meanwhile, the occurrence of rehydration side reaction of the HMF is restrained. Methyl isobutyl ketone (MIBK)/water is the most reported two-phase system. Because of the high solubility of HMF in water, the extraction efficiency of HMF by organic solvents is low, making it difficult to increase the overall HMF yield, and two-phase systems still require more intensive research.
(5) Synthesis of 5-HMF from ionic liquids
The Ionic Liquids (ILs) are widely used for reaction and separation as green solvents due to the characteristics of strong structural/performance designability, low volatility and the like. In recent years, a plurality of reports of ionic liquids for synthesizing an HMF system by dehydrating saccharides have appeared. At present, dehydration of fructose in ionic liquids has been reported to yield HMF of greater than 90%. However, similar to high boiling solvents, the ionic liquid cannot be removed by conventional distillation under reduced pressure, and an extractant such as diethyl ether is required to separate HMF from the ionic liquid. However, this method requires a large amount of circulating solvent and the extraction time is long, and the extracted HMF still has a problem of secondary separation from the extractant.
The development of novel processes for the preparation of 5-HMF remains an important point of research. Based on the previous research of the applicant, one of the derivatives which is easy to prepare from glucose, namely methyl 2, 3-O-sulfonyl-alpha-D-glucopyranoside, can be used for efficiently preparing 5-HMF, and provides good methodological support for converting glucose into 5-HMF.
Disclosure of Invention
The invention aims to overcome the defects of the prior art and provides a method for industrially synthesizing 5-HMF and derivatives thereof.
The aim of the invention is realized by the following technical scheme: a method for industrially synthesizing 5-HMF, comprising the following steps:
dissolving a compound I in a solvent, and preparing the 5-HMF under the conditions of alkali and heating;
wherein the structural formula of the compound I is as follows:
the solvent comprises H 2 One or more of O, DMF, DMSO, trichloroethane, toluene, 1, 4-dioxane;
the alkali comprises one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, sodium acetate, potassium hydroxide, triethylamine and pyridine;
the heating temperature is 80-150 ℃.
Further, the mass ratio of the compound I to the solvent is in the range of 1:5-1:40;
and/or the molar ratio of the compound I to the alkali is in the range of 1:1-1:10.
Further, the method comprises the following steps:
s1, carrying out hydrolysis reaction on a compound I to generate a compound II;
s2, the step ofThe compound II is subjected to an acylation reaction to generate a compound III; wherein R is 1 And R is 2 Are respectively one of hydrogen atoms, acetyl groups or benzoyl groups;
s3, dissolving the compound III in a solvent, and preparing the 5-HMF derivative under the conditions of alkali and heating;
the solvent comprises one or more of DMF, DMSO, trichloroethane and water;
the alkali comprises one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, sodium acetate, potassium hydroxide, triethylamine and pyridine;
the heating temperature is 60-150 ℃.
Further, in step S1, the hydrolysis reaction method includes: selecting alcohol or water as solvent, adjusting pH to 1-7 or heating to 0-150deg.C;
and/or in the step S1, the mass ratio of the compound I to the hydrolysis reaction solvent is in the range of 1:5-1:50.
Further, in step S1, the alcohol is methanol or ethanol.
Further, in step S2, the method of the acylation reaction is as follows: an acid anhydride method or an acid chloride method.
Further, in step S2, the reagent for the acylation reaction is an acyl chloride or an acid anhydride, preferably one of acetyl chloride, benzoyl chloride, acetic anhydride, and benzoyl chloride.
Further, in step S2, the solvent for the acylation reaction includes one or more of N, N-dimethylformamide, tetrahydrofuran, ethyl acetate, and dichloromethane;
and/or, in step S2, the base used in the acylation reaction includes one or more of pyridine, triethylamine, and sodium bicarbonate;
and/or in the step S2, the molar ratio of the compound II to the acylating agent, the solvent and the alkali in the acylating reaction is 1:1-3:1-3;
and/or in the step S2, the mass ratio of the compound II to the solvent in the acylation reaction is 1:5-1:50.
Further, in the step S3, the mass ratio of the compound III to the solvent is in the range of 1:5-1:50;
and/or the molar ratio of the compound III to the alkali is in the range of 1:1-1:5.
The invention also provides an application of the method for industrially synthesizing 5-HMF in synthesizing 5-HMF and an application of the method for industrially synthesizing 5-HMF derivatives in synthesizing 5-HMF derivatives.
The beneficial effects of the invention are as follows: the synthesis method of the 5-HMF and the derivative thereof provided by the invention has the characteristics of low cost, low byproducts, easy separation of products and the like.
The synthesis method of 5-HMF and its derivatives provided by the invention can be carried out by taking glucose as a starting material, obtaining methyl alpha-glucoside in almost equal proportion in reference (Synth. Commun. 2001,31, (9), 1277-1284), obtaining 4, 6-O-ethylene-alpha-D-glucopyranose in 90% yield in reference (J. Org. Chem. 1999,64, (1), 144-152), obtaining starting compound I in 55% yield according to the subject group patent (CN 114671849A, a method for opening a pyranose ring, a product and application thereof), finally recovering and reusing all non-reacted solvents in 80% proportion according to the method embodiment of the subject patent, wherein the raw material is only 42 yuan/kg, which is far lower than 6500 yuan/kg of commercial price, and the industrial economic value is huge.
The synthesis method of the 5-HMF and the derivatives thereof provided by the invention is carried out in a multi-step reaction mode, but the yield of each step is relatively high, when the compound I is obtained, experiments prove that no additional separation and purification are needed, all reagents used in the process have no environmental and safety problems of adverse production such as extremely toxic, explosive, difficult recovery and the like, and the final product can be obtained in a rectification mode, so that the invention provides a new process route for synthesizing the 5-HMF and the derivatives thereof, and accords with the characteristics of the existing green industrialization.
Detailed Description
The technical scheme of the present invention is described in further detail below, but the scope of the present invention is not limited to the following.
EXAMPLE 1 preparation of methyl 2, 3-O-Cyclosulfonyl-alpha-D-glucopyranoside (Compound II)
Compound I (15 g,0.0506 mol) was weighed into a round bottom flask (150 mL), followed by addition into a solvent of methanol (75 mL), followed by dropwise addition of 10 drops of 98% by mass of concentrated sulfuric acid, stirring at room temperature (15-25 ℃) for 3h, judging whether the reaction was complete (pure ethyl acetate as developing agent) by TLC, diluting with 300mL of ethyl acetate, washing the combined organic layers with 100mL of saturated brine, drying over anhydrous sodium sulfate, filtering, distilling under reduced pressure to give about 12.2g of a white solid in 94% yield. 1 H NMR(600MHz,DMSO-d6):δ5.75(s,2H,OH),5.24(d,J＝1.8Hz,1H),4.93-4.97(m,2H),3.95-3.99(m,1H),3.69(dd,J＝12.0,1.2Hz,1H),3.59(dd,J＝12.0,5.4Hz,1H),3.44-3.46(m,1H),3.41(s,3H). 13 C NMR(150MHz,CDCl 3 ):δ94.61,86.19,81.43,75.24,67.22,59.89,55.41.
EXAMPLE 2 preparation of methyl 2, 3-O-Cyclosulfonyl-alpha-D-glucopyranoside (Compound II)
Example 2 differs from example 1 in that no 98% concentrated sulfuric acid was added and the heating was directly carried out at a temperature of 30℃or higher, resulting in a white solid of about 12.3g and a yield of 94.5%.
Example 3-4 preparation of methyl 2, 3-O-Cyclosulfonyl-alpha-D-glucopyranoside (Compound II)
Examples 3-4 differ from example 1 in the difference in solvents, i.e., equal amounts of ethanol and water were used to replace methanol, respectively, example 3 resulted in about 12.3g of white solid with 94.8% yield, and example 4 resulted in about 12.2g of white solid with 94.0% yield.
EXAMPLE 5 methyl 2, 3-O-Cyclosulfonyl-6-O-acetyl-alpha-D-glucopyranoside (Compound III, R 1 Is Ac, R 2 Preparation of H)
Compound I (10.0 g,0.0390 mol) was weighed into a round bottom flask in stoichiometric proportionsTo the mixture thus obtained was added 60mL of glacial acetic acid, and after complete dissolution, 5 drops of concentrated sulfuric acid were added dropwise, and the mixture was stirred at room temperature for 6 hours, and it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=7:3 as developing agent), 150mL of ethyl acetate was added to dilute the mixture, and the organic phase was washed with water (100 ml×2) and the aqueous phases were combined. The aqueous phase was back-extracted with 50mL of ethyl acetate, the organic phases were combined, the organic phase was washed with 100mL of saturated brine, and separated to give an organic phase, which was dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to give about 10.7g of a white crude product in 91.92% yield. 1 H NMR(600MHz,CDCl 3 )δ5.12(d,J＝3.1Hz,1H),5.09(t,J＝10.0Hz,1H),4.59–4.49(m,2H),4.26(dd,J＝12.5,2.2Hz,1H),3.99(t,J＝9.5Hz,1H),3.80(ddd,J＝9.5,3.9,2.2Hz,1H),3.68(s,1H),3.52(s,3H),2.14(s,3H). 13 C NMR(151MHz,CDCl 3 )δ172.09,95.41,83.49,80.13,77.37,77.16,76.95,71.86,68.18,62.15,56.35,20.93.
EXAMPLE 6 methyl 2, 3-O-Cyclosulfonyl-4, 6-acetoxy-alpha-D-glucopyranoside (Compound III, R 1 Is Ac, R 2 Ac)
Compound II (10.0 g,0.0390 mol) was weighed into a round bottom flask (250 mL) in stoichiometric ratio, after which about 60mL of methylene chloride and 6.6mL of pyridine were added for complete dissolution, then 7.7mL of acetic anhydride was added, the reaction was stirred at 35 ℃ for 3 hours, it was judged by TLC whether the reaction was complete, 150mL of ethyl acetate was added to the completely reacted mixture, the organic phase was washed with water (50 ml×2) and the pH was adjusted to weak acidity by adding a small amount of hydrochloric acid, and the aqueous phase was combined. The aqueous phase was back-extracted with 50mL of ethyl acetate, the organic phases were combined, the organic layer was washed with 100mL of saturated brine, and separated to give an organic phase, which was dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to give 12.5g of a white amorphous solid in 94% yield. 1 H NMR(600MHz,CDCl 3 ):δ5.40(d,J＝10.2Hz,1H),5.17(m,2H),4.68(dd,J＝10.2,3.0Hz,1H),4.28(dd,J＝12.6,4.8Hz,1H),4.18(dd,J＝12.6,2.4Hz,1H),3.99-3.97(m,2H),3.69-3.66(m,1H),3.54(s,3H),2.13(s,3H),2.11(s,3H). 13 C NMR(150MHz,CDCl 3 ):δ170.47,168.77,96.08,80.99,79.85,69.31,67.08,61.21,56.33,20.66,20.49.
Examples 7-9 methyl 2, 3-O-Cyclosulfonyl-4, 6-acetoxy-alpha-D-glucopyranoside (Compounds III, R) 1 Is Ac, R 2 Ac)
Example 7 differs from example 6 in the solvents, base, DMF as the solution used in example 7 and triethylamine as the base, and yielded 12.4g of a white amorphous solid in 93.5% yield.
Example 8 and example 6 differ in the solvent, base, the solution used in example 8 was THF and the base was sodium bicarbonate, resulting in a white amorphous solid 12.3g, 92.8% yield.
Example 9 and example 6 differ in the solvents, acylating agent, DCM, the solution used in example 9, acetyl chloride, and finally a white amorphous solid 12.6g was obtained in 94.5% yield.
EXAMPLE 10 methyl 2, 3-O-Cyclosulfonyl-6-O-benzoyl-alpha-D-glucopyranoside (Compound III, R 1 Bz, R 2 Preparation of H)
Compound II (10.0 g,0.0390 mol) was weighed into a round bottom flask (250 mL), followed by addition of 60mL of dichloromethane, followed by quantitative addition of 4.0mL of pyridine, stirring under ice bath for 5min, mixing well, then adding 5.8mL of benzoyl chloride, stirring for 4h, judging whether the reaction was complete (petroleum ether: ethyl acetate=7:3 as developing agent) by TLC, adding 200mL of ethyl acetate to dilute the completely reacted mixture, washing the separated organic phase with water (50 ml×2), adjusting pH to be weak acid by adding a small amount of hydrochloric acid, and combining the aqueous phases. The aqueous phase was back-extracted with 50mL of ethyl acetate, the organic phases were combined, the organic layer was washed with 100mL of saturated brine, and separated to give an organic phase, which was dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to give 12.8g of a white amorphous solid in 91% yield. 1 H NMR(600MHz,CDCl 3 )δ8.10–7.94(m,2H),7.61(t,J＝7.4Hz,1H),7.46(t,J＝7.6Hz,2H),5.23–5.06(m,2H),4.89–4.77(m,1H),4.55(dd,J＝10.4,3.1Hz,1H),4.06(t,J＝9.5Hz,1H),3.95–3.88(m,1H),3.53(s,3H). 13 C NMR(150MHz,CDCl 3 )δ167.54,133.92,133.77,130.13,129.97,129.08,128.76,128.62,95.33,83.59,80.22,72.07,68.27,62.65,56.29.
Examples 11-13 methyl 2, 3-O-Cyclosulfonyl-6-O-benzoyl-alpha-D-glucopyranoside (Compounds III, R 1 Bz, R 2 Preparation of H)
Example 11 differs from example 10 in the solvents, base, DMF as the solution used in example 11 and triethylamine as the base, and yielded 12.9g of a white amorphous solid in 91.5% yield.
Example 12 differs from example 10 in the solvents, base, THF as the solution used in example 12 and sodium bicarbonate as the base, resulting in a white amorphous solid 12.9g, 92.0% yield.
Example 13 differs from example 10 in that the solvent, the acylating agent, DCM, was used as the solution in example 13 and benzoic anhydride, yielding 12.7g of a white amorphous solid in 90.5% yield.
EXAMPLE 14 methyl 2, 3-O-Cyclosulfonyl-4, 6-O-dibenzoyl-alpha-D-glucopyranoside (Compound III, R) 1 Bz, R 2 Bz) preparation
Compound II (10.0 g,0.0390 mol) was weighed into a round bottom flask (250 mL), then about 60mL of methylene chloride was added, after complete dissolution, then 9.5mL of benzoyl chloride (or benzoic anhydride of corresponding proportion) was added, the reaction was stirred at room temperature for 4h, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=7:3 as developing agent), 100mL of ethyl acetate was added to the completely reacted mixture for dilution, the organic phase was washed with water (50 ml×2) for separation, a small amount of hydrochloric acid was added to adjust pH to weak acidity, and the aqueous phase was combined. The aqueous phase was back-extracted with 50mL of ethyl acetate, the organic phases were combined, the organic phase was washed with 100mL of saturated brine, and separated to give an organic phase, which was dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to give 17g of a white amorphous solid in 94% yield.
1 H NMR(600MHz,CDCl 3 )δ8.02(ddd,J＝17.4,8.3,1.4Hz,4H),7.65–7.53(m,2H),7.50–7.39(m,5H),5.78(t,J＝9.7Hz,1H),5.36(t,J＝10.1Hz,1H),5.21(d,J＝3.1Hz,1H),4.76(dd,J＝10.3,3.1Hz,1H),4.64(dd,J＝12.4,2.8Hz,1H),4.43(dd,J＝12.3,4.8Hz,1H),4.29(ddd,J＝9.7,4.8,2.8Hz,1H),3.58(s,3H). 13 C NMR(151MHz,CDCl 3 )δ166.09,164.57,134.20,133.52,130.16,129.80,129.41,128.78,128.63,128.26,95.24,81.15,80.07,69.64,68.25,62.19,56.52.
Examples 15-17 methyl 2, 3-O-Cyclosulfonyl-4, 6-O-dibenzoyl-alpha-D-glucopyranoside (Compounds III, R) 1 Bz, R 2 Bz) preparation
Example 15 differs from example 14 in that ethyl acetate was used instead of chloroform and 7.8ml of pyridine was added, resulting in 16.3g of a white amorphous solid with a yield of 90%.
Example 16 differs from example 14 in that DMF was used instead of chloroform and 7.8ml of triethylamine was added, resulting in 16.8g of a white amorphous solid with 93% yield.
Example 17 differs from example 14 in that THF was used instead of chloroform and 7.8ml of sodium bicarbonate was added to give 17g of a white amorphous solid in 94% yield.
Example 18 from Compound III, R 1 Is Ac, R 2 Preparation of 5-acetoxymethylfurfural for Ac
Compound III (8.0 g,0.0235 mol) was weighed into a round-bottomed flask (250 mL), DMF was added to the flask to be about 40mL, after complete dissolution, 4.0g of sodium bicarbonate was then added to the flask to be quantitative, the reaction was heated and stirred at 95 to 150 ℃ for 1 to 10 hours, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=7:3 as developing agent), 100mL of ethyl acetate was added to the completely reacted mixture to dilute the organic phase, and the organic phase was washed with 100mL of saturated brine, separated to obtain an organic phase, dried over anhydrous sodium sulfate, filtered, distilled under reduced pressure to obtain 3.6g of colorless oily liquid, yield 91%. 1 H NMR(600MHz,CDCl 3 )δ10.08(s,1H),7.44(t,J＝1.6Hz,1H),6.77(t,J＝1.5Hz,1H),5.34(d,J＝1.3Hz,2H),2.11(d,J＝1.2Hz,3H). 13 C NMR(150MHz,CDCl 3 )δ184.83,170.38,156.61,144.08,125.32,108.69,56.11,20.78.
Example 19 from Compound III, R 1 Is Ac, R 2 Preparation of 5-acetoxymethylfurfural for Ac
Example 19 differs from example 18 in the solvents and the base, the solution used in example 19 being DMSO and the base being potassium hydroxide, and the final yield being 3.6g as colourless oil, 90.5%.
Example 20 preparation of the Compound III, R 1 Bz, R 2 Preparation of 5-benzoyloxymethyl furfural for Bz
Compound III (10.0 g,0.0215 mol) was weighed into a round-bottomed flask (250 mL), DMF was added to the flask to be about 50mL, after complete dissolution, 3.6g of sodium bicarbonate was then added quantitatively, the reaction was heated and stirred at 80 to 150 ℃ for 1 to 10 hours, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=7:3 as developing agent), 100mL of ethyl acetate was added to the completely reacted mixture to dilute the organic layer, and the organic layer was washed with 100mL of saturated brine, separated to obtain an organic phase, dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain about 4.5g of a pale yellow solid crude product with a yield of 91%. 1 H NMR(600MHz,CDCl 3 )δ9.65(s,1H),8.10–8.02(m,2H),7.58(tt,J＝7.4,1.4Hz,1H),7.44(t,J＝7.8Hz,2H),7.23(d,J＝3.6Hz,1H),6.67(d,J＝3.6Hz,1H),5.38(s,2H). 13 C NMR(150MHz,CDCl 3 )δ177.99,166.07,155.66,153.03,133.58,129.97,129.41,128.62,121.84,112.90,58.37.
Example 21 from Compound III, R 1 Bz, R 2 Preparation of 5-benzoyloxymethyl furfural for Bz
Example 21 differs from example 20 in the solvents and the base, the solution used in example 21 being chloroform and the base being potassium carbonate, and the crude product being obtained as a pale yellow solid in a yield of about 4.5g and 91%.
Example 22 from Compound III, R 1 Bz, R 2 Preparation of 5-benzoyloxymethyl furfural as H
Compound III (5.0 g,0.0139 mol) was weighed into a round-bottomed flask (250 mL), then about 50mL of DMF was added, after complete dissolution, then 2.33g of sodium bicarbonate was quantitatively added, the reaction was heated and stirred for 1 to 10 hours at 80 to 150 ℃, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=7:3 as developing agent), 100mL of ethyl acetate was added to the completely reacted mixture, the organic layer was washed with 100mL of saturated brine, separated to obtain an organic phase, dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain about 2.8g of a pale yellow solid crude product, yield 87.6%.
Example 23 from Compound III, R 1 Bz, R 2 Preparation of 5-benzoyloxymethyl furfural as H
Example 23 differs from example 22 in the solvents and the bases, the solution used in example 23 being chloroform and the base being potassium carbonate, and the crude product being obtained as a pale yellow solid in a yield of about 2.8g, 88%.
Example 24 from Compound III, R 1 Is Ac, R 2 For H, preparing 5-acetoxymethyl furfural
Compound III (10.0 g,0.0335 mol) was weighed into a round-bottomed flask (250 mL), DMF was added to the flask to be about 50mL, after complete dissolution, 5.63g of sodium bicarbonate was then added to the flask to be quantitative, the mixture was heated and stirred at 80 to 150 ℃ for 1 to 10 hours, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=7:3 as developing agent), 100mL of ethyl acetate was added to the completely reacted mixture to dilute the organic layer, and the organic layer was washed with 100mL of saturated brine, separated to obtain an organic phase, dried over anhydrous sodium sulfate, filtered, and distilled under reduced pressure to obtain about 5.1g of colorless oily liquid in 90% yield.
Example 25 from Compound III, R 1 Is Ac, R 2 For H, preparing 5-acetoxymethyl furfural
Example 25 differs from example 24 in that the solvent, base, used in example 23 is water and the base is potassium carbonate, resulting in a colourless oily liquid with a yield of about 5.0g, 88%.
EXAMPLE 26 preparation of 5-HMF from Compound I
Weighing compound I (10 g,0.0338 mmol) according to stoichiometric ratio, adding into round bottom flask (250 mL), adding DMF about 50mL, dissolving thoroughly, adding 5.70g sodium bicarbonate quantitatively, heating and stirring at 80-150deg.C for 1-10h, judging whether the reaction is complete (petroleum ether: ethyl acetate=1:1 as developing agent) by TLC, adding appropriate amount of hydrochloric acid to adjust pH to neutrality after the reaction is complete, filtering, and depressurizingDistillation and final rectification gave 3.80g of pale yellow solid with 89% yield. 1 H NMR(600MHz,CDCl 3 )δ9.59(s,1H),7.22(d,J＝3.5Hz,1H),6.52(d,J＝3.6Hz,1H),4.72(s,2H). 13 C NMR(150MHz,CDCl 3 )δ177.81,160.63,152.54,110.13,57.81.
EXAMPLE 27 preparation of 5-HMF from Compound I
Compound I (10 g,0.0338 mmol) was weighed into a round bottom flask (250 mL), then about 50mL of DMF was added, after complete dissolution, then 5.54g of sodium acetate was quantitatively added, the reaction was heated and stirred for 1-10h at 80-150 ℃, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=1:1 as developing agent), after the reaction was complete, an appropriate amount of hydrochloric acid was added to adjust the pH to neutral, filtration, distillation under reduced pressure, final distillation gave 3.90g of pale yellow solid in 91.6% yield.
EXAMPLE 28 preparation of 5-HMF from Compound I
Compound I (10 g,0.0338 mmol) was weighed into a round bottom flask (250 mL), followed by addition of about 50mL of trichloroethane, after complete dissolution, followed by quantitative addition of 5.54g of sodium acetate, heating and stirring at 80-150 ℃ for 1-10h, judging whether the reaction was complete (petroleum ether: ethyl acetate=1:1 as developing agent) by TLC, after completion of the reaction, adding an appropriate amount of hydrochloric acid to adjust pH to neutral, filtering, distillation under reduced pressure, final distillation to give 3.50g of pale yellow solid with 82.2% yield.
EXAMPLE 29 preparation of 5-HMF from Compound I
Compound I (10 g,0.0338 mmol) was weighed into a round bottom flask (250 mL), then about 50mL of DMSO was added, after complete dissolution, then 5.54g of sodium acetate was quantitatively added, the reaction was heated and stirred for 1-10h at 80-150 ℃, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=1:1 as developing agent), after the reaction was complete, an appropriate amount of hydrochloric acid was added to adjust the pH to neutral, filtration, distillation under reduced pressure, final distillation gave 3.50g of pale yellow solid, yield 82.2%.
EXAMPLE 30 preparation of 5-HMF from Compound I
Compound I (10 g,0.0338 mmol) was weighed into a round bottom flask (250 mL), then about 50mL of DMSO was added, after complete dissolution, then 5.54g of sodium bicarbonate was quantitatively added, the reaction was heated and stirred for 1-10h at 80-150 ℃, it was judged by TLC whether the reaction was complete (petroleum ether: ethyl acetate=1:1 as developing agent), after the reaction was complete, an appropriate amount of hydrochloric acid was added to adjust the pH to neutral, filtration, distillation under reduced pressure, and final distillation gave 3.50g of pale yellow solid with 82.2% yield.
The foregoing is merely a preferred embodiment of the invention, and it is to be understood that the invention is not limited to the form disclosed herein but is not to be construed as excluding other embodiments, but is capable of numerous other combinations, modifications and environments and is capable of modifications within the scope of the inventive concept, either as taught or as a matter of routine skill or knowledge in the relevant art. And that modifications and variations which do not depart from the spirit and scope of the invention are intended to be within the scope of the appended claims.
Claims (10)
1. A method for industrially synthesizing 5-HMF, comprising the steps of:
dissolving a compound I in a solvent, and preparing the 5-HMF under the conditions of alkali and heating;
wherein the structural formula of the compound I is as follows:
the solvent comprises H 2 One or more of O, DMF, DMSO, trichloroethane, toluene, 1, 4-dioxane;
the alkali comprises one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, sodium acetate, potassium hydroxide, triethylamine and pyridine;
the heating temperature is 80-150 ℃.
2. The method for industrially synthesizing 5-HMF according to claim 1, wherein the mass ratio of the compound I to the solvent is in the range of 1:5 to 1:40;
and/or the molar ratio of the compound I to the alkali is in the range of 1:1-1:10.
3. A method for industrially synthesizing a 5-HMF derivative, comprising the steps of:
s1, carrying out hydrolysis reaction on a compound I to generate a compound II;
s2, carrying out an acylation reaction on the compound II to generate a compound III; wherein R is 1 And R is 2 Are respectively one of hydrogen atoms, acetyl groups or benzoyl groups;
s3, dissolving the compound III in a solvent, and preparing the 5-HMF derivative under the conditions of alkali and heating;
the solvent comprises one or more of DMF, DMSO, trichloroethane and water;
the alkali comprises one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, potassium bicarbonate, sodium hydroxide, sodium acetate, potassium hydroxide, triethylamine and pyridine;
the heating temperature is 60-150 ℃.
4. A method for the industrial synthesis of 5-HMF derivatives according to claim 3, characterized in that in step S1, the hydrolysis reaction is carried out by: selecting alcohol or water as solvent, adjusting pH to 1-7 or heating to 0-150deg.C;
and/or in the step S1, the mass ratio of the compound I to the hydrolysis reaction solvent is in the range of 1:5-1:50.
5. The method for industrially synthesizing a 5-HMF derivative according to claim 4, wherein in step S1, the alcohol is methanol or ethanol.
6. A method for the industrial synthesis of 5-HMF derivatives according to claim 3, characterized in that in step S2, the method for the acylation reaction is: an acid anhydride method or an acid chloride method.
7. The method for industrially synthesizing a 5-HMF derivative according to claim 6, wherein in the step S2, the reagent for the acylation reaction is one of acetyl chloride, benzoyl chloride, acetic anhydride, and benzoyl chloride.
8. The method for industrially synthesizing a 5-HMF derivative according to claim 6, wherein in the step S2, the solvent for the acylation reaction includes one or more of N, N-dimethylformamide, tetrahydrofuran, ethyl acetate, and methylene chloride;
and/or, in step S2, the base used in the acylation reaction includes one or more of pyridine, triethylamine, and sodium bicarbonate;
and/or in the step S2, the molar ratio of the compound II to the acylating agent, the solvent and the alkali in the acylating reaction is 1:1-3:1-3;
and/or in the step S2, the mass ratio of the compound II to the solvent in the acylation reaction is 1:5-1:50.
9. A method of industrially synthesizing a 5-HMF derivative according to claim 3, wherein in step S3, the mass ratio of the compound III to the solvent is in the range of 1:5 to 1:50;
and/or the molar ratio of the compound III to the alkali is in the range of 1:1-1:5.
10. Use of a method of industrially synthesizing 5-HMF according to claim 1 or 2 for synthesizing 5-HMF and of a method of industrially synthesizing 5-HMF derivative according to any one of claims 3 to 9 for synthesizing 5-HMF derivative.
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