CN115925658B - Preparation method of 2-aminoethylfuran - Google Patents
Preparation method of 2-aminoethylfuran Download PDFInfo
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- CN115925658B CN115925658B CN202211453727.6A CN202211453727A CN115925658B CN 115925658 B CN115925658 B CN 115925658B CN 202211453727 A CN202211453727 A CN 202211453727A CN 115925658 B CN115925658 B CN 115925658B
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- aminoethylfuran
- furan
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- nitrovinyl
- reducing agent
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- ZQSLNSHMUQXSQJ-UHFFFAOYSA-N 2-(furan-2-yl)ethanamine Chemical compound NCCC1=CC=CO1 ZQSLNSHMUQXSQJ-UHFFFAOYSA-N 0.000 title claims abstract description 52
- 238000002360 preparation method Methods 0.000 title claims abstract description 14
- 238000006243 chemical reaction Methods 0.000 claims abstract description 102
- HYBBIBNJHNGZAN-UHFFFAOYSA-N furfural Chemical compound O=CC1=CC=CO1 HYBBIBNJHNGZAN-UHFFFAOYSA-N 0.000 claims abstract description 52
- WVUICGOYGDHVBH-ONEGZZNKSA-N 2-[(e)-2-nitroethenyl]furan Chemical compound [O-][N+](=O)\C=C\C1=CC=CO1 WVUICGOYGDHVBH-ONEGZZNKSA-N 0.000 claims abstract description 29
- 239000003638 chemical reducing agent Substances 0.000 claims abstract description 14
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000003054 catalyst Substances 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 12
- 239000002994 raw material Substances 0.000 claims abstract description 9
- 239000012279 sodium borohydride Substances 0.000 claims abstract description 9
- 229910000033 sodium borohydride Inorganic materials 0.000 claims abstract description 9
- 239000003513 alkali Substances 0.000 claims abstract description 8
- 238000006555 catalytic reaction Methods 0.000 claims abstract description 8
- 230000009471 action Effects 0.000 claims abstract description 4
- 238000006482 condensation reaction Methods 0.000 claims abstract description 4
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 18
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 14
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
- 238000000034 method Methods 0.000 claims description 12
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 10
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 9
- 230000035484 reaction time Effects 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 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
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims description 3
- 239000011777 magnesium Substances 0.000 claims description 3
- 229910052749 magnesium Inorganic materials 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 229910052700 potassium Inorganic materials 0.000 claims description 3
- 239000011591 potassium Substances 0.000 claims description 3
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 claims description 2
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 2
- 239000011575 calcium Substances 0.000 claims description 2
- 229910052791 calcium Inorganic materials 0.000 claims description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 2
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 2
- 229910052725 zinc Inorganic materials 0.000 claims description 2
- 239000011701 zinc Substances 0.000 claims description 2
- 239000002585 base Substances 0.000 claims 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 8
- 238000001914 filtration Methods 0.000 abstract description 7
- -1 lithium aluminum hydride Chemical compound 0.000 abstract description 6
- 238000009776 industrial production Methods 0.000 abstract description 5
- 239000012280 lithium aluminium hydride Substances 0.000 abstract description 5
- 229910052751 metal Inorganic materials 0.000 abstract description 5
- 239000002184 metal Substances 0.000 abstract description 5
- 150000003839 salts Chemical class 0.000 abstract description 5
- 239000000126 substance Substances 0.000 abstract description 5
- 239000002841 Lewis acid Substances 0.000 abstract description 4
- 239000002253 acid Substances 0.000 abstract description 4
- 239000002131 composite material Substances 0.000 abstract description 4
- 239000000383 hazardous chemical Substances 0.000 abstract description 4
- 150000007517 lewis acids Chemical class 0.000 abstract description 4
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 abstract description 4
- 229910052987 metal hydride Inorganic materials 0.000 abstract description 3
- 150000004681 metal hydrides Chemical class 0.000 abstract description 3
- 238000003756 stirring Methods 0.000 description 26
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 20
- 239000007789 gas Substances 0.000 description 12
- 239000008399 tap water Substances 0.000 description 12
- 235000020679 tap water Nutrition 0.000 description 12
- 238000004809 thin layer chromatography Methods 0.000 description 12
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- 230000008034 disappearance Effects 0.000 description 7
- 238000012544 monitoring process Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- 239000000243 solution Substances 0.000 description 6
- 239000000203 mixture Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 239000012295 chemical reaction liquid Substances 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 238000000605 extraction Methods 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 239000005457 ice water Substances 0.000 description 4
- 239000007788 liquid Substances 0.000 description 4
- 238000001819 mass spectrum Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000010907 mechanical stirring Methods 0.000 description 4
- 239000011259 mixed solution Substances 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 238000010606 normalization Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000010791 quenching Methods 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- 208000007536 Thrombosis Diseases 0.000 description 3
- 239000003814 drug Substances 0.000 description 3
- USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 2
- 239000005695 Ammonium acetate Substances 0.000 description 2
- 229910010082 LiAlH Inorganic materials 0.000 description 2
- 229940043376 ammonium acetate Drugs 0.000 description 2
- 235000019257 ammonium acetate Nutrition 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 230000002401 inhibitory effect Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 208000010110 spontaneous platelet aggregation Diseases 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- IPASVEYYTNTJTM-AATRIKPKSA-N 3-[(e)-2-nitroethenyl]-1h-indole Chemical compound C1=CC=C2C(/C=C/[N+](=O)[O-])=CNC2=C1 IPASVEYYTNTJTM-AATRIKPKSA-N 0.000 description 1
- 208000024172 Cardiovascular disease Diseases 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 210000001772 blood platelet Anatomy 0.000 description 1
- 150000004696 coordination complex Chemical class 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 230000003467 diminishing effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 230000002526 effect on cardiovascular system Effects 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- APJYDQYYACXCRM-UHFFFAOYSA-N tryptamine Chemical compound C1=CC=C2C(CCN)=CNC2=C1 APJYDQYYACXCRM-UHFFFAOYSA-N 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
- Y02P20/584—Recycling of catalysts
Landscapes
- Furan Compounds (AREA)
Abstract
The invention discloses a preparation method of 2-aminoethylfuran, which comprises the following operation steps: s1: taking furfural and nitromethane as raw materials, and performing condensation reaction under the action of alkali to generate 2- (2-nitrovinyl) furan; s2: 2- (2-nitrovinyl) furan is reduced in a solvent by a reducing agent under the catalysis of a catalyst to prepare the 2-aminoethylfuran. The raw material substances involved in each step are easy to obtain, the reaction conditions involved in each step are mild, and the whole operation is simple and easy to implement; in the step S2, the 2-aminoethylfuran is prepared by adopting a metal hydride/protonic acid composite reduction-catalysis mode, so that the use of hazardous chemicals such as lithium aluminum hydride, palladium carbon and the like is avoided, the operation safety coefficient is high, and the economical practicability is high; compared with a sodium borohydride/Lewis acid system, no metal salt is generated, the post-treatment is simple, and the problems of difficult filtration and the like are avoided; the water content of the reaction system is not high, and the industrial production is easy to carry out.
Description
Technical Field
The invention relates to the technical field of organic synthesis, in particular to a preparation method of 2-aminoethyl furan.
Background
Cardiovascular and cerebrovascular thrombotic diseases are common diseases with high incidence rate at present, and seriously endanger human health. Because the platelet aggregation inhibiting drugs play an important role in treating thrombotic diseases, the platelet aggregation inhibiting drugs are always hot spots of research and will also become a medical trend.
2-amino ethyl furan is a medical intermediate, and is mainly used for synthesizing more than ten new medicine precondition raw materials for treating cardiovascular diseases related to blood platelet and thrombus, diminishing inflammation, easing pain and the like. The current reports on 2-aminoethylfuran are mainly the following two: (1) Condensing furfural and nitromethane under the condition of sodium hydroxide or ammonium acetate/acetic acid to obtain 2- (2-nitroethyleneRadical) furan, then KBH 4 With BF 3 Reducing diborane generated by the diethyl ether solution to generate a target product; (2) In the organic solvent, a reducing agent LiAlH is used 4 Reducing 2- (2-nitrovinyl) furan to prepare the target product. In these methods, the yield of 2- (2-nitrovinyl) furan produced by the ammonium acetate/acetic acid system is low; reducing agent KBH 4 With BF 3 Diethyl ether solution and LiAlH 4 The price is high, resulting in higher production cost; in addition, liAlH 4 Is easy to explode when meeting water, has high risk coefficient and is not suitable for large-scale industrialized production. The 3- (2-nitrovinyl) indole is reported to be dissolved in a solvent and reduced by a metal complex hydride-metal salt/Lewis acid system to obtain the 3- (2-aminoethyl) indole, but solid metal salt is generated in the post-treatment of the method, the post-treatment is difficult, and the requirement on the moisture content of a reaction system is high.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provide a preparation method of 2-aminoethylfuran, wherein raw material substances involved in each step are easy to obtain, reaction conditions involved in each step are mild, and the whole operation is simple and easy to implement; in the step S2, the 2-aminoethylfuran is prepared by adopting a metal hydride/protonic acid composite reduction-catalysis mode, so that the use of hazardous chemicals such as lithium aluminum hydride, palladium carbon and the like is avoided, the operation safety coefficient is high, and the economical practicability is high; compared with a sodium borohydride/Lewis acid system, no metal salt is generated, the post-treatment is simple, and the problems of difficult filtration and the like are avoided; the water content of the reaction system is not high, and the industrial production is easy to carry out; the prepared 2-amino ethyl furan has higher yield and purity, and is verified by pilot test, thereby being suitable for industrial production.
In order to achieve the above purpose, the technical scheme of the invention is to design a preparation method of 2-aminoethylfuran, which comprises the following operation steps:
s1: taking furfural and nitromethane as raw materials, and performing condensation reaction under the action of alkali to generate 2- (2-nitrovinyl) furan;
s2: 2- (2-nitrovinyl) furan is reduced in a solvent by a reducing agent under the catalysis of a catalyst to prepare the 2-aminoethylfuran.
In the preferred technical scheme, in the step S1, the alkali is one of sodium carbonate, sodium hydroxide, potassium carbonate, lithium hydroxide and potassium hydroxide, and the molar feed ratio of furfural, nitromethane and alkali is 1: 1-2: 1 to 2.5.
In a further preferred technical scheme, in the step S1, the alkali is sodium hydroxide, and the molar feed ratio of furfural, nitromethane and alkali is 1:1:1.1.
in the preferred technical scheme, in the step S2, the reducing agent is one of potassium borohydride, sodium borohydride, zinc borohydride, magnesium borohydride and calcium borohydride, the catalyst is one of trifluoroacetic acid, acetic acid, sulfuric acid and methanesulfonic acid, and the molar feed ratio of the 2- (2-nitrovinyl) furan, the reducing agent and the catalyst is 1:2 to 6:0.1 to 1, wherein the solvent is one of methanol, ethanol, isopropanol and tetrahydrofuran, and the mass feed ratio of the 2- (2-nitrovinyl) furan to the solvent is 1:5 to 15.
In a further preferred technical scheme, in the step S2, the reducing agent is sodium borohydride, the catalyst is trifluoroacetic acid, and the molar feed ratio of the 2- (2-nitrovinyl) furan, the reducing agent and the catalyst is 1:5:0.1, wherein the solvent is tetrahydrofuran, and the mass feed ratio of the 2- (2-nitrovinyl) furan to the solvent is 1:10.
In the preferred technical scheme, in the step S1, the reaction temperature is-10 ℃ and the reaction time is 1-5 h.
In a further preferable technical scheme, in the step S1, the reaction temperature is-5 ℃ and the reaction time is 2 hours.
In the preferred technical scheme, in the step S2, the reaction temperature is 10-30 ℃ and the reaction time is 1-5 h.
In a further preferable embodiment, in the step S2, the reaction temperature is 20 to 25℃and the reaction time is 4 hours.
The preferable technical scheme also comprises the following step S3: rectifying and purifying the 2-aminoethyl furan prepared in the step S2 to obtain a pure 2-aminoethyl furan product
The invention has the advantages and beneficial effects that:
1. according to the preparation method of the 2-aminoethylfuran, raw material substances involved in each step are easy to obtain, reaction conditions involved in each step are mild, and the whole operation is simple and easy to implement; in the step S2, the 2-aminoethylfuran is prepared by adopting a metal hydride/protonic acid composite reduction-catalysis mode, so that the use of hazardous chemicals such as lithium aluminum hydride, palladium carbon and the like is avoided, the operation safety coefficient is high, and the economical practicability is high.
2. Compared with a sodium borohydride/Lewis acid system, the preparation method of the 2-aminoethylfuran has the advantages that no metal salt is generated, the post-treatment is simple, and the problems of difficult filtration and the like are avoided; the water content of the reaction system is not high, and the industrial production is easy to carry out.
3. The preparation method of the 2-aminoethyl furan has the advantages that the yield and the purity of the prepared 2-aminoethyl furan are high, and the pilot test proves that the preparation method is suitable for industrial production.
Drawings
FIG. 1 is a flow chart of a process for preparing 2-aminoethylfuran of the present invention;
FIG. 2 (a) is a gas chromatogram of 2-aminoethylfuran prepared in example 1;
fig. 2 (b) is analysis data corresponding to the gas chromatogram in fig. 2 (a):
FIG. 3 (a) is a gas chromatogram of 2-aminoethylfuran prepared in example 2;
fig. 3 (b) is analysis data corresponding to the gas chromatogram in fig. 3 (a);
FIG. 4 (a) is a gas chromatogram of 2-aminoethylfuran prepared in example 3;
fig. 4 (b) is analysis data corresponding to the gas chromatogram in fig. 4 (a);
FIG. 5 (a) is a gas chromatogram of 2-aminoethylfuran prepared in example 4;
fig. 5 (b) shows analysis data corresponding to the gas chromatogram in fig. 5 (a).
Detailed Description
The following describes the embodiments of the present invention further with reference to the drawings and examples. The following examples are only for more clearly illustrating the technical aspects of the present invention, and are not intended to limit the scope of the present invention.
Example 1
The method for preparing 2-amino ethyl furan has the synthetic reaction route shown in the attached figure 1, and comprises the following operation steps:
step S1: 150.0g of tap water is added into a dry and clean reaction bottle 1# and cooled to 0-5 ℃, 22.9g (0.57 mol) of sodium hydroxide is added into the reaction bottle, and the mixture is stirred and dissolved and cooled to room temperature for standby; introducing nitrogen into a dry and clean reaction bottle 2# and sequentially adding 50.0g (0.52 mol) of furfural and 100ml of methanol (79 g), cooling to 0 ℃, adding 31.8g (0.52 mol) of nitromethane, controlling the temperature to be-5-5 ℃, dropwise adding a sodium hydroxide aqueous solution prepared in the reaction bottle 1# into the reaction bottle 2# and keeping the temperature of-5-5 ℃ for reaction for 1-2 hours after the dropwise addition is finished, and monitoring the reaction progress by Thin Layer Chromatography (TLC), wherein the disappearance of the furfural is taken as a reaction end point, and the reaction is finished; sequentially adding 150.0g of tap water and 150ml of concentrated hydrochloric acid into a dry and clean reaction bottle 3# and stirring to reduce the temperature to-5-5 ℃; dropwise adding the reaction liquid in the reaction bottle 2# into the reaction bottle 3# and controlling the temperature to be lower than 5 ℃; after the dripping is finished, the temperature is kept at-5 ℃ to 5 ℃ and the mixture is stirred and reacts for 0.5 to 1 hour, and the mixed solution of the reaction products is filtered, washed with tap water, filtered cake and pumped out; transferring the filter cake into a reaction bottle 4# and adding 150ml of methanol, and stirring at room temperature for 1-2h; cooling to 0deg.C, stirring for 0.5-1 hr, filtering, and draining; vacuum drying at 40 ℃ for 4-6h to obtain 59.8g of 2- (2-nitrovinyl) furan, molar yield: 82.6% (calculated as furfural) was used directly in the next reaction without further purification treatment.
Steps S2 and S3: 59.8g (0.43 mol) of 2- (2-nitrovinyl) furan, 598g of tetrahydrofuran and 4.9g (0.043 mol) of trifluoroacetic acid obtained in the above step S1 were successively introduced into a reaction flask 5# equipped with a mechanical stirring device; cooling to 20 ℃ through ice water bath under stirring, keeping the temperature constant, and adding 81.3g (2.15 mol) of sodium borohydride in batches; after the material is fed, the temperature is kept between 20 ℃ and 25 ℃ for stirring reaction, TLC monitors the progress of the reaction, and the 2- (2-nitro group is usedVinyl) furan disappeared as the reaction endpoint; after the reaction is finished, cooling the reaction solution to 0-5 ℃ through an ice salt bath, adding 400g of water to quench the reaction, stirring for 1h, and recovering tetrahydrofuran under reduced pressure; after completion of the recovery, methylene chloride was added for extraction (3 times each of 180 g), the organic layers were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove methylene chloride (recyclable), and then distilled under reduced pressure with an oil pump to obtain 39.4g (0.35 mol) (total molar yield in two steps: 68.2% in terms of furfural) of 2-aminoethylfuran as a colorless oily liquid, the gas chromatogram of which was shown in FIG. 2 (a), as shown in FIG. 2 (b): the purity was calculated by peak area normalization: 99.36%; the mass spectrum data are as follows: ESI-MS (m/z): 112[ M+H ]] + Consistent with theoretical molecular weight data for 2-aminoethylfuran; the nuclear magnetic data are as follows: 1 HNMR(CDCl3,300MHz),δ(ppm)2.75(t,J＝6.5,2H)，2.98(t,J＝6.5,2H)，6.08(t,J＝3.1,1H)，6.29(dd,J＝2.5,4.6,1H)，7.33(d,J＝1.7,1H)。
example 2
The method for preparing 2-amino ethyl furan has the synthetic reaction route shown in the attached figure 1, and comprises the following operation steps:
step S1: 150.0g of tap water is added into a dry and clean reaction bottle 1# and cooled to 0-5 ℃, 29.2g (0.52 mol) of potassium hydroxide is added into the reaction bottle, stirred and dissolved, and cooled to room temperature for standby; introducing nitrogen into a dry and clean reaction bottle 2# and sequentially adding 50.0g (0.52 mol) of furfural and 100ml of methanol (79 g), cooling to 0 ℃, adding 47.6g (0.78 mol) of nitromethane, controlling the temperature to be-5-5 ℃, dropwise adding a potassium hydroxide aqueous solution prepared in the reaction bottle 1# into the reaction bottle 2# and keeping the temperature of-5-5 ℃ for reaction for 1-2 hours after the dropwise addition is finished, and monitoring the reaction progress by Thin Layer Chromatography (TLC), wherein the disappearance of the furfural is taken as a reaction end point, and the reaction is finished; sequentially adding 150.0g of tap water and 150ml of concentrated hydrochloric acid into a dry and clean reaction bottle 3# and stirring to reduce the temperature to-5-5 ℃; dropwise adding the reaction liquid in the reaction bottle 2# into the reaction bottle 3# and controlling the temperature to be lower than 5 ℃; after the dripping is finished, the temperature is kept at-5 ℃ to 5 ℃ and the mixture is stirred and reacts for 0.5 to 1 hour, and the mixed solution of the reaction products is filtered, washed with tap water, filtered cake and pumped out; transferring the filter cake into a reaction bottle 4# and adding 150ml of methanol, and stirring at room temperature for 1-2h; cooling to 0deg.C, stirring for 0.5-1 hr, filtering, and draining; vacuum drying at 40 ℃ for 4-6h to obtain 60.6g of 2- (2-nitrovinyl) furan, molar yield: 83.7% (calculated as furfural) can be used directly in the next reaction without further purification treatment.
Steps S2 and S3: 60.6g (0.44 mol) of 2- (2-nitrovinyl) furan, 303g of tetrahydrofuran and 10.5g (0.174 mol) of acetic acid obtained in the above step S1 were successively introduced into a reaction flask 5# equipped with a mechanical stirring device; cooling to 20 ℃ through ice water bath under stirring, keeping the temperature constant, and adding 75.6g (2.0 mol) of sodium borohydride in batches; after the material feeding is finished, preserving heat for 20-25 ℃ and stirring for reaction, monitoring the reaction progress by TLC, and taking the disappearance of 2- (2-nitrovinyl) furan as a reaction end point; after the reaction is finished, cooling the reaction solution to 0-5 ℃ through an ice salt bath, adding 250g of water to quench the reaction, stirring for 1h, and recovering tetrahydrofuran under reduced pressure; after the completion of the recovery, methylene chloride was added to conduct extraction (180 g each time for 3 times), the organic layers were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove methylene chloride (recyclable), and then distilled under reduced pressure with an oil pump to obtain 38.6g (0.35 mol) (total molar yield in two steps: 66.8% in terms of furfural) of 2-aminoethylfuran as a colorless oily liquid, the gas chromatogram of which was shown in FIG. 3 (a), as shown in FIG. 3 (b): the purity was calculated by peak area normalization: 99.47%; the mass spectrum data and the nuclear magnetic data are consistent with the nuclear magnetic data of the target product prepared in the example 1.
Example 3
The method for preparing 2-amino ethyl furan has the synthetic reaction route shown in the attached figure 1, and comprises the following operation steps:
step S1: adding 225.0g of tap water into a dry and clean reaction bottle 1# and cooling to 0-5 ℃, adding 46.7g (1.95 mol) of lithium hydroxide, stirring and dissolving, and cooling to room temperature for standby; introducing nitrogen into a dry and clean reaction bottle 2# and sequentially adding 75.0g (0.78 mol) of furfural and 150ml of methanol (118.5 g), cooling to 0 ℃, adding 95.3g (1.56 mol) of nitromethane, controlling the temperature to be-5-5 ℃, dropwise adding a lithium hydroxide aqueous solution prepared in the reaction bottle 1# into the reaction bottle 2# and keeping the temperature of-5-5 ℃ for reaction for 1-2 hours after the dropwise adding is finished, and monitoring the reaction progress by Thin Layer Chromatography (TLC), wherein the disappearance of the furfural is taken as a reaction end point, and the reaction is finished; sequentially adding 225.0g of tap water and 450ml of concentrated hydrochloric acid into a dry and clean reaction bottle 3# and stirring to reduce the temperature to-5-5 ℃; dropwise adding the reaction liquid in the reaction bottle 2# into the reaction bottle 3# and controlling the temperature to be lower than 5 ℃; after the dripping is finished, the temperature is kept at-5 ℃ to 5 ℃ and the mixture is stirred and reacts for 0.5 to 1 hour, and the mixed solution of the reaction products is filtered, washed with tap water, filtered cake and pumped out; transferring the filter cake into a reaction bottle 4# and adding 150ml of methanol, and stirring at room temperature for 1-2h; cooling to 0deg.C, stirring for 0.5-1 hr, filtering, and draining; vacuum drying at 40 ℃ for 4-6h to obtain 90.5g of 2- (2-nitrovinyl) furan, molar yield: 83.3% (calculated as furfural) was used directly in the next reaction without further purification treatment.
Steps S2 and S3: 90.5g (0.65 mol) of 2- (2-nitrovinyl) furan obtained in the above step S1, 1357.5g (1718 mL) of methanol and 63.7g (0.65 mol) of sulfuric acid were successively introduced into a reaction flask 5# equipped with a mechanical stirring device; cooling to 20 ℃ through ice water bath under stirring, keeping the temperature constant, and adding 210.2g (3.9 mol) of potassium borohydride in batches; after the material feeding is finished, preserving heat for 20-25 ℃ and stirring for reaction, monitoring the reaction progress by TLC, and taking the disappearance of 2- (2-nitrovinyl) furan as a reaction end point; after the reaction is finished, cooling the reaction solution to 0-5 ℃ through an ice salt bath, adding 1000g of water to quench the reaction, stirring for 1h, and recovering tetrahydrofuran under reduced pressure; after completion of the recovery, methylene chloride was added to conduct extraction (3 times each of 300 g), the organic layers were combined, dried over anhydrous sodium sulfate, and methylene chloride was distilled off under reduced pressure (recyclable), and then, by distillation under reduced pressure with an oil pump, 56.8g (0.51 mol) (total molar yield in both steps: 65.5% in terms of furfural) of 2-aminoethylfuran was obtained as a colorless oily liquid, the gas chromatogram of which was shown in FIG. 4 (a), as shown in FIG. 4 (b): the purity was calculated by peak area normalization: 99.73%; the mass spectrum data and the nuclear magnetic data are consistent with the nuclear magnetic data of the target product prepared in the example 1.
Example 4
The method for preparing 2-amino ethyl furan has the synthetic reaction route shown in the attached figure 1, and comprises the following operation steps:
step S1: adding 225.0g of tap water into a dry and clean reaction bottle 1# and cooling to 0-5 ℃, adding 34.4g (0.86 mol) of potassium hydroxide, stirring and dissolving, and cooling to room temperature for standby; introducing nitrogen into a dry and clean reaction bottle 2# and sequentially adding 75g (0.78 mol) of furfural and 150ml of methanol (118.5 g), cooling to 0 ℃, adding 47.6g (0.78 mol) of nitromethane, controlling the temperature to be-5-5 ℃, dropwise adding a potassium hydroxide aqueous solution prepared in the reaction bottle 1# into the reaction bottle 2#, keeping the temperature of-5-5 ℃ for reaction for 1-2 hours after the dropwise addition is finished, and monitoring the reaction progress by Thin Layer Chromatography (TLC), wherein the disappearance of the furfural is taken as a reaction end point, and the reaction is finished; sequentially adding 225.0g of tap water and 225ml of concentrated hydrochloric acid into a dry and clean reaction bottle 3# and stirring to reduce the temperature to-5-5 ℃; dropwise adding the reaction liquid in the reaction bottle 2# into the reaction bottle 3# and controlling the temperature to be lower than 5 ℃; after the dripping is finished, the temperature is kept at-5 ℃ to 5 ℃ and the mixture is stirred and reacts for 0.5 to 1 hour, and the mixed solution of the reaction products is filtered, washed with tap water, filtered cake and pumped out; transferring the filter cake into a reaction bottle 4# and adding 225ml of methanol, and stirring for 1-2h at room temperature; cooling to 0deg.C, stirring for 0.5-1 hr, filtering, and draining; vacuum drying at 40 ℃ for 4-6h to obtain 90.3g of 2- (2-nitrovinyl) furan with molar yield: 83.1% (calculated as furfural) was used directly in the next reaction without further purification treatment.
Steps S2 and S3: 90.3g (0.65 mol) of 2- (2-nitrovinyl) furan, 903g of ethanol and 6.25g (0.065 mol) of methanesulfonic acid obtained in the above step S1 were successively introduced into a reaction flask 5# equipped with a mechanical stirring device; cooling to 20 ℃ through ice water bath under stirring, keeping the temperature constant, and adding 140.2g (2.6 mol) of magnesium borohydride in batches; after the material feeding is finished, preserving heat for 20-25 ℃ and stirring for reaction, monitoring the reaction progress by TLC, and taking the disappearance of 2- (2-nitrovinyl) furan as a reaction end point; after the reaction is finished, cooling the reaction solution to 0-5 ℃ through an ice salt bath, adding 700g of water to quench the reaction, stirring for 1h, and recovering tetrahydrofuran under reduced pressure; after completion of the recovery, methylene chloride was added for extraction (3 times each of 180 g), the organic layers were combined, dried over anhydrous sodium sulfate, and distilled under reduced pressure to remove methylene chloride (recyclable), followed by distillation under reduced pressure with an oil pump to obtain 58.1g (0.52 mol) (total molar yield in two steps: 66.98% in terms of furfural) of 2-aminoethylfuran as a colorless oily liquid, the gas chromatogram of which was shown in FIG. 5 (a), as shown in FIG. 5 (b): the purity was calculated by peak area normalization: 98.26%; the mass spectrum data and the nuclear magnetic data are consistent with the nuclear magnetic data of the target product prepared in the example 1.
Examples 1 to 4 adopt the preparation method of the 2-aminoethylfuran, which takes furfural and nitromethane as raw materials, and performs condensation reaction under the action of alkali to generate an intermediate product 2- (2-nitrovinyl) furan; 2- (2-nitrovinyl) furan is reduced by a reducing agent under the catalysis of a catalyst to prepare 2-aminoethyl furan, wherein the molar yield of the 2-aminoethyl furan is more than 65 percent (calculated by furfural), and the purity of the 2-aminoethyl furan is more than 98.0 percent; meanwhile, the use of dangerous substances such as lithium aluminum hydride is avoided, and the harm to operators and the environment is reduced.
According to the preparation method of the 2-aminoethylfuran, raw material substances involved in each step are easy to obtain, reaction conditions involved in each step are mild, and the whole operation is simple and easy to implement; in the step S2, the 2-aminoethylfuran is prepared by adopting a metal complex hydride/protonic acid composite reduction-catalysis mode, so that the use of hazardous chemicals such as lithium aluminum hydride, palladium carbon and the like is avoided, the operation safety coefficient is high, the economical practicability is high, and the purpose of the invention is realized.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that it will be apparent to those skilled in the art that several modifications and variations can be made without departing from the technical principle of the present invention, and these modifications and variations should also be regarded as the scope of the invention.
Claims (9)
1. The preparation method of the 2-aminoethylfuran is characterized by comprising the following operation steps:
s1: taking furfural and nitromethane as raw materials, and performing condensation reaction under the action of alkali to generate 2- (2-nitrovinyl) furan;
s2: 2- (2-nitrovinyl) furan is reduced in a solvent by a reducing agent under the catalysis of a catalyst to prepare 2-aminoethylfuran;
in the step S2, the reducing agent is one of potassium borohydride, sodium borohydride, zinc borohydride, magnesium borohydride and calcium borohydride, the catalyst is one of trifluoroacetic acid, acetic acid, sulfuric acid and methanesulfonic acid, and the molar feed ratio of the 2- (2-nitrovinyl) furan to the reducing agent to the catalyst is 1:2 to 6:0.1 to 1, wherein the solvent is one of methanol, ethanol, isopropanol and tetrahydrofuran, and the mass feed ratio of the 2- (2-nitrovinyl) furan to the solvent is 1:5 to 15.
2. The method for preparing 2-aminoethylfuran according to claim 1, wherein in step S1, the base is one of sodium carbonate, sodium hydroxide, potassium carbonate, lithium hydroxide and potassium hydroxide, and the molar ratio of furfural, nitromethane and base is 1: 1-2: 1 to 2.5.
3. The process for preparing 2-aminoethylfuran according to claim 2, wherein in step S1, the base is sodium hydroxide, and the molar ratio of furfural, nitromethane and base is 1:1:1.1.
4. the process for preparing 2-aminoethylfuran according to claim 1, wherein in step S2, sodium borohydride is used as the reducing agent, trifluoroacetic acid is used as the catalyst, and the molar ratio of 2- (2-nitrovinyl) furan, reducing agent and catalyst is 1:5:0.1, wherein the solvent is tetrahydrofuran, and the mass feed ratio of the 2- (2-nitrovinyl) furan to the solvent is 1:10.
5. The process for producing 2-aminoethylfuran according to claim 1, wherein in step S1, the reaction temperature is from-10 to 10℃and the reaction time is from 1 to 5 hours.
6. The process for producing 2-aminoethylfuran according to claim 5, wherein in step S1, the reaction temperature is from-5 to 5℃and the reaction time is 2 hours.
7. The process for producing 2-aminoethylfuran according to claim 1, wherein in step S2, the reaction temperature is 10 to 30℃and the reaction time is 1 to 5 hours.
8. The process for producing 2-aminoethylfuran according to claim 7, wherein in step S2, the reaction temperature is 20 to 25℃and the reaction time is 4 hours.
9. The process for the preparation of 2-aminoethylfuran according to any one of claims 1 to 8, further comprising the step S3 of: and (3) rectifying and purifying the 2-aminoethyl furan prepared in the step (S2) to obtain a pure 2-aminoethyl furan product.
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