CN108059616B - Synthesis method of 3, 4-dihydropyrimidine-2 (1H) -thioketone - Google Patents
Synthesis method of 3, 4-dihydropyrimidine-2 (1H) -thioketone Download PDFInfo
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- 238000001308 synthesis method Methods 0.000 title claims description 8
- 239000003054 catalyst Substances 0.000 claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 22
- UMGDCJDMYOKAJW-UHFFFAOYSA-N thiourea Chemical compound NC(N)=S UMGDCJDMYOKAJW-UHFFFAOYSA-N 0.000 claims abstract description 18
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 11
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 claims abstract description 9
- 238000003756 stirring Methods 0.000 claims abstract description 9
- 150000003934 aromatic aldehydes Chemical class 0.000 claims abstract description 8
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 238000007867 post-reaction treatment Methods 0.000 claims abstract description 5
- 239000000758 substrate Substances 0.000 claims abstract description 3
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 15
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzenecarboxaldehyde Natural products O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 claims description 11
- 239000001763 2-hydroxyethyl(trimethyl)azanium Substances 0.000 claims description 9
- 235000019743 Choline chloride Nutrition 0.000 claims description 9
- SGMZJAMFUVOLNK-UHFFFAOYSA-M choline chloride Chemical compound [Cl-].C[N+](C)(C)CCO SGMZJAMFUVOLNK-UHFFFAOYSA-M 0.000 claims description 9
- 229960003178 choline chloride Drugs 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 6
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 claims description 6
- 238000002360 preparation method Methods 0.000 claims description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 6
- XYIBRDXRRQCHLP-UHFFFAOYSA-N ethyl acetoacetate Chemical compound CCOC(=O)CC(C)=O XYIBRDXRRQCHLP-UHFFFAOYSA-N 0.000 claims description 5
- 238000002156 mixing Methods 0.000 claims description 5
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical group COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 claims description 4
- -1 acetoacetate ester Chemical class 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 2
- QMFBVGUFEGVPNG-UHFFFAOYSA-N ethyl 6-methyl-4-phenyl-2-sulfanylidene-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical group CCOC(=O)C1=C(C)NC(=S)NC1C1=CC=CC=C1 QMFBVGUFEGVPNG-UHFFFAOYSA-N 0.000 claims description 2
- 230000005496 eutectics Effects 0.000 claims description 2
- 239000000706 filtrate Substances 0.000 claims description 2
- BITNETQOCMZGKF-UHFFFAOYSA-N methyl 6-methyl-4-phenyl-2-sulfanylidene-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical group COC(=O)C1=C(C)NC(=S)NC1C1=CC=CC=C1 BITNETQOCMZGKF-UHFFFAOYSA-N 0.000 claims description 2
- HUMNYLRZRPPJDN-KWCOIAHCSA-N benzaldehyde Chemical group O=[11CH]C1=CC=CC=C1 HUMNYLRZRPPJDN-KWCOIAHCSA-N 0.000 claims 1
- 238000001704 evaporation Methods 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 12
- 239000003960 organic solvent Substances 0.000 abstract description 5
- 230000003197 catalytic effect Effects 0.000 abstract description 3
- 238000010189 synthetic method Methods 0.000 abstract description 3
- 238000005761 Biginelli synthesis reaction Methods 0.000 description 6
- MBOCEPWYDNXEKN-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidine-2-thione Chemical compound S=C1NCC=CN1 MBOCEPWYDNXEKN-UHFFFAOYSA-N 0.000 description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 5
- 238000006555 catalytic reaction Methods 0.000 description 4
- 238000002474 experimental method Methods 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000011084 recovery Methods 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- JKNHZOAONLKYQL-UHFFFAOYSA-K tribromoindigane Chemical compound Br[In](Br)Br JKNHZOAONLKYQL-UHFFFAOYSA-K 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- QGKGASXQTBQINX-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidin-2-one Chemical class O=C1NCC=CN1 QGKGASXQTBQINX-UHFFFAOYSA-N 0.000 description 1
- 108090000312 Calcium Channels Proteins 0.000 description 1
- 102000003922 Calcium Channels Human genes 0.000 description 1
- 229910002492 Ce(NO3)3·6H2O Inorganic materials 0.000 description 1
- 229910004039 HBF4 Inorganic materials 0.000 description 1
- 239000002841 Lewis acid Substances 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 241001061127 Thione Species 0.000 description 1
- 229910007932 ZrCl4 Inorganic materials 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003377 acid catalyst Substances 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000259 anti-tumor effect Effects 0.000 description 1
- 230000002155 anti-virotic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001735 carboxylic acids Chemical class 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000003181 co-melting Methods 0.000 description 1
- 238000002485 combustion reaction Methods 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- SBTSVTLGWRLWOD-UHFFFAOYSA-L copper(ii) triflate Chemical compound [Cu+2].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F SBTSVTLGWRLWOD-UHFFFAOYSA-L 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- URMNHHAUVFEMIG-UHFFFAOYSA-N ethyl 6-methyl-2-oxo-4-phenyl-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C)NC(=O)NC1C1=CC=CC=C1 URMNHHAUVFEMIG-UHFFFAOYSA-N 0.000 description 1
- 239000000374 eutectic mixture Substances 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 0.000 description 1
- 230000002779 inactivation Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 150000007517 lewis acids Chemical class 0.000 description 1
- 239000002069 magnetite nanoparticle Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- SOQBVABWOPYFQZ-UHFFFAOYSA-N oxygen(2-);titanium(4+) Chemical compound [O-2].[O-2].[Ti+4] SOQBVABWOPYFQZ-UHFFFAOYSA-N 0.000 description 1
- 150000004714 phosphonium salts Chemical group 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 238000001556 precipitation Methods 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- IIACRCGMVDHOTQ-UHFFFAOYSA-N sulfamic acid Chemical compound NS(O)(=O)=O IIACRCGMVDHOTQ-UHFFFAOYSA-N 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- DUNKXUFBGCUVQW-UHFFFAOYSA-J zirconium tetrachloride Chemical compound Cl[Zr](Cl)(Cl)Cl DUNKXUFBGCUVQW-UHFFFAOYSA-J 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/20—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D239/22—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms directly attached to ring carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Plural Heterocyclic Compounds (AREA)
- Catalysts (AREA)
Abstract
The invention relates to a synthetic method of 3, 4-dihydropyrimidine-2 (1H) -thioketone. The method specifically comprises the following steps: taking aromatic aldehyde, acetoacetate and thiourea as substrates, DES as a catalyst, and stirring to react at 60-75 ℃ for 30-45min under the condition of no solvent; the molar ratio of the aromatic aldehyde to the acetoacetate to the thiourea to the DES is 1: 1: 1.5: 0.3. the invention uses the DES which is cheap and easy to obtain as the catalyst, does not need to add other solvents in the reaction process, can effectively reduce the use of other organic solvents and corrosive catalysts, has mild reaction conditions, can be recycled, and has simple process, high catalytic activity and high yield; the post-reaction treatment is simple and convenient, and the method is green and environment-friendly, and is a cheap, safe and environment-friendly synthetic method of the 3, 4-dihydropyrimidine-2 (1H) -thioketone compound.
Description
Technical Field
The invention relates to a method for preparing 3, 4-dihydropyrimidine-2 (1H) -thione through catalysis, in particular to a method for preparing 3, 4-dihydropyrimidine-2 (1H) -thione through Bininelli reaction catalysis by utilizing a deep eutectic solvent.
Background
The 3, 4-dihydropyrimidine-2 (1H) - (sulfur) ketone compound is an important medical intermediate, can be used as a calcium channel agent, an antiallergic agent, a pressure-reducing agent, an antagonist and the like, and also has biological activities of antivirus, antitumor, antibiosis, antiphlogosis and the like[1]。
In 1893, Italian chemists first reported that DHPM was synthesized by a three-component "one-pot" process using aromatic aldehyde, ethyl acetoacetate, and urea under the catalysis of concentrated hydrochloric acid, and the synthesis method is called Biginelli reaction[2]. Although simple and convenient, the method has the defects of long reaction time, low yield and the like. The current choice of catalyst is a key problem limiting the Biginelli reaction, the traditional catalysts are generally protonic acids or Lewis acids, such as HBF4、H3PW12O40、NH2SO3H、InBr3、ZrCl4、Cu(OTf)2、Fe(OTs)3·6H2O、Ce(NO3)3·6H2O and the like[3]. However, the catalyst has some inevitable disadvantages, such as the use of volatile organic solvent for reaction, complicated post-treatment, no recovery, serious environmental pollution, etc.
In recent years, highly efficient and clean heterogeneous catalysts such as PS-PEG-SO have been used3H[4]Amine functionalized nano titanium dioxide[5]Metal complexes[6]And the like. However, the catalyst has the problems of long reaction time, complex catalyst preparation process, easy inactivation of the catalyst and the like, and industrial production is difficult to realize. Sulfonic acid compounds can also be used as catalysts to catalyze Biginelli reactions, such as p-toluenesulfonic acid[7]Sulfonic acid functionalized magnetite nanoparticles[8]However, the sulfonic acid catalyzed reaction needs to be carried out in an organic solvent, the sulfonic acid cannot be recovered, and the preparation process of the supported sulfonic acid is complex, so that the application of the sulfonic acid catalyzed Biginelli reaction is greatly limited.
With the development of society, people are more eager to pursue the quality of life of green and environment protection, green chemistry is more and more emphasized, and the search for a green catalyst is vital and is always emphasized widely by world scientists.
Disclosure of Invention
The invention aims to develop a novel environment-friendly reaction system for preparing 3, 4-dihydropyrimidine-2 (1H) -thione, the reaction system does not need to use a solvent, DES (ChCl/2PTSA) is used as a catalyst, the use of a volatile organic solvent and a traditional catalyst harmful to the environment is avoided, and a safe, cheap and green preparation method is invented. The system has the advantages of wide application range, simple operation, low price, safety, higher yield and environmental friendliness.
The method takes aromatic aldehyde, acetoacetate and thiourea as substrates, DES (ChCl/2PTSA) as a catalyst, and the 3, 4-dihydropyrimidine-2 (1H) -thione is synthesized by Biginelli reaction under the condition of no solvent and stirring reaction at 60-75 ℃ for 30-45 min. The reaction formula is as follows:
the DES is a deep co-melting solvent prepared from p-toluenesulfonic acid (PTSA) and choline chloride (ChCl), and the catalyst can be reused, is green and environment-friendly, and basically keeps the catalytic effect unchanged after four times of recovery. The preparation method of the DES comprises the following steps: mixing the components in a molar ratio of 1: 2, adding the choline chloride and the p-toluenesulfonic acid into a round-bottom flask for mixing, and stirring the mixture for 4 hours at the temperature of 80 ℃ to obtain a transparent liquid, namely the DES catalyst.
The aromatic aldehyde is preferably benzaldehyde.
The acetoacetate ester is methyl acetoacetate or ethyl acetoacetate.
More specifically, the synthesis method of the 3, 4-dihydropyrimidine-2 (1H) -thione comprises the following steps:
0.3 equivalent of DES was added to the reaction vessel, then 1 equivalent of benzaldehyde, 1 equivalent of acetoacetate and 1.5 equivalents of thiourea were added, and the reaction was stopped after stirring at 70 ℃ for 40 min.
The synthesis method has simple and convenient post-reaction treatment, during post-reaction treatment, a water product is directly added for precipitation, a target product can be obtained after recrystallization, water is evaporated from filtrate, and the catalyst DES can be recovered after drying.
DES is a eutectic mixture of hydrogen bond acceptors (e.g., quaternary ammonium salts, quaternary phosphonium salts, etc.) and hydrogen bond donors (e.g., amides, carboxylic acids, polyols, etc.) in a stoichiometric ratio. DES has the advantages of low price, simple preparation, difficult volatilization, difficult combustion, easy storage, recyclable use and the like.
Compared with the traditional process for preparing 3, 4-dihydropyrimidine-2 (1H) -thioketone, the method has the following advantages: the DES which is cheap and easy to obtain is used as a catalyst, other solvents are not required to be added in the reaction process, the use of other organic solvents and corrosive catalysts can be effectively reduced, the reaction condition is mild, the DES can be recycled, the process is simple, the catalytic activity is high, and the yield is high; the post-reaction treatment is simple and convenient, and the method is green and environment-friendly, and is a cheap, safe and environment-friendly synthetic method of the 3, 4-dihydropyrimidine-2 (1H) -thioketone compound.
Detailed Description
The invention is described in more detail below with reference to specific examples, without limiting the scope of the invention. Unless otherwise specified, the experimental methods adopted by the invention are all conventional methods, and experimental equipment, materials, reagents and the like used in the experimental method can be obtained from commercial sources.
In the following examples, the catalyst DES is preferably prepared by the following method:
50mmol (6.98g) choline chloride (ChCl) and 100mmol (19.02g) p-toluenesulphonic acid (PTSA) were added to a 250ml round bottom flask and the mixture was stirred at 80 ℃ for 4h to give a clear liquid, the DES catalyst.
Example 1
The reaction equation is as follows:
the experimental method comprises the following steps: 0.6mmol of the catalyst DES, 2mmol of benzaldehyde, 2mmol of methyl acetoacetate and 3mmol of thiourea were added into a 25mL round-bottomed flask, and the reaction was stopped after stirring at 70 ℃ for 40 min. After the reaction is finished, cooling to room temperature, adding an ice-water mixture to fully separate out a product, performing suction filtration, and washing for 3 times by using distilled water to obtain a crude product. Recrystallizing with ethanol-water solution to obtain 4-phenyl-5-methoxycarbonyl-6-methyl-3, 4-dihydropyrimidine-2 (1H) -thione with the yield of 80%.
Example 2
The reaction equation is as follows:
the experimental method comprises the following steps: 0.6mmol of the catalyst DES, 2mmol of benzaldehyde, 2mmol of ethyl acetoacetate and 3mmol of thiourea were added to a 25mL round-bottomed flask and the reaction was stopped after stirring at 70 ℃ for 40 min. After the reaction is finished, cooling to room temperature, adding an ice-water mixture to fully separate out a product, performing suction filtration, and washing for 3 times by using distilled water to obtain a crude product. Recrystallizing with ethanol-water solution to obtain 4-phenyl-5-ethoxycarbonyl-6-methyl-3, 4-dihydropyrimidine-2 (1H) -thione with the yield of 80%.
Reference documents:
[1]C.O.Kappe,W.M.F.Fabian,M.A.Semones,Conformational analysis of 4-aryl-dihydropyrimidine calcium channel modulators.A comparison of ab initio,semiempirical and X-ray crystallographic studies[J].Tetrahedron,1997,53,2803-2816.
[2]P.Biginelli,Synthesis of4-aryl-3,4-dihydropyrimidin-2(1H)-ones[J].Gazz.Chim.Ital.,1893,23,360-416.
[3]S.S.Panda,P.Khanna,L.Khanna,Biginelli Reaction:A Green Perspective[J].Curr.Org.Chem.,2012,16,507-520.
[4]Z.J.Quan,Y.X.Da,Z.Zhang,X.C.Wang,PS-PEG-SO3H as an efficientcatalyst for 3,4-dihydropyrimidones via Biginelli reaction[J].Catal.Comm.,2009,10,1146-1148.
[5]E.Tabrizian,A.Amoozadeh,T.Shamsi,A novel class ofheterogeneouscatalysts based on toluene diisocyanate:the first amine-functionalized nano-titanium dioxide as a mild and highly recyclable solid nanocatalyst for theBiginelli reaction[J].Reac.
Kinet.Mech.Cat.,2016,119,245-258.
[6]J.H.Wang,E.Zhang,G.M.Tang,et al.Novel bipyridinyl oxadiazole-basedmetal coordination complexes:High efficient and green synthesis of 3,4-dihydropyrimidin-2(1H)-ones through the Biginelli reactions[J].J.Solid StateChem.,2016,241,86-98.
[7]T.S.Jin,S.L.Zhang,T.S.Li,p-toluenesulfonic acid-catalyzedefficient synthesis of dihydropyrimidines:improved high yielding protocol forthe Biginelli reaction[J],Synthetic Commun.,2002,32,1847-1851.
[8]D.Azarifar,Y.Abbasi,O.Badalkhani,Sulfonic acid-functionalizedtitanomagnetite nanoparticles as recyclable heterogeneous acid catalyst forone-pot solvent-free synthesis of 3,4-dihydropyrimidin-2(1H)-ones/thiones[J].J.Iran.Chem.Soc.,2016,13,2029-2038.
the above description is only for the purpose of creating a preferred embodiment of the present invention, but the scope of the present invention is not limited thereto, and any person skilled in the art can substitute or change the technical solution and the inventive concept of the present invention within the technical scope of the present invention.
Claims (3)
- The synthesis method of the 3, 4-dihydropyrimidine-2 (1H) -thioketone compound is characterized in that aromatic aldehyde, acetoacetate and thiourea are used as substrates, DES is used as a catalyst, and the mixture is stirred and reacted for 30-45min at the temperature of 60-75 ℃ to obtain a product; the molar ratio of the aromatic aldehyde to the acetoacetate to the thiourea to the DES is 1: 1: 1.5: 0.3; the aromatic aldehyde is benzaldehyde; the acetoacetate ester is methyl acetoacetate or ethyl acetoacetate; when the acetoacetate is methyl acetoacetate, the product is 4-phenyl-5-methoxycarbonyl-6-methyl-3, 4-dihydropyrimidine-2 (1H) -thione; when the acetoacetate is ethyl acetoacetate, the product is 4-phenyl-5-ethoxycarbonyl-6-methyl-3, 4-dihydropyrimidine-2 (1H) -thione;DES is prepared by mixing choline chloride and p-toluenesulfonic acid according to a molar ratio of 1: 2, preparing a deep eutectic solvent;the preparation method of the DES comprises the following steps: mixing the components in a molar ratio of 1: 2, adding the choline chloride and the p-toluenesulfonic acid into a round-bottom flask for mixing, and stirring the mixture for 4 hours at the temperature of 80 ℃ to obtain a transparent liquid, namely the DES catalyst.
- 2. The synthesis method according to claim 1, wherein the reaction temperature is 70 ℃, and the stirring reaction is carried out for 40 min.
- 3. The synthesis method according to claim 1, comprising the following steps: adding 0.3 equivalent of DES into a reaction vessel, then adding 1 equivalent of benzaldehyde, 1 equivalent of acetoacetate and 1.5 equivalent of thiourea, stirring and reacting at 70 ℃ for 40min, stopping the reaction, adding water to separate out a product during post-reaction treatment, recrystallizing to obtain a target product, evaporating water from the filtrate, and drying to recover the catalyst DES.
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104045541A (en) * | 2014-06-18 | 2014-09-17 | 大连大学 | Method for synthesizing aromatic ketone compound |
| CN106632073A (en) * | 2016-12-19 | 2017-05-10 | 盐城师范学院 | Synthesis method of 3,4-dihydropyrimidin-2-ketone compounds catalyzed by ionic liquid at room temperature |
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Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104045541A (en) * | 2014-06-18 | 2014-09-17 | 大连大学 | Method for synthesizing aromatic ketone compound |
| CN106632073A (en) * | 2016-12-19 | 2017-05-10 | 盐城师范学院 | Synthesis method of 3,4-dihydropyrimidin-2-ketone compounds catalyzed by ionic liquid at room temperature |
Non-Patent Citations (3)
| Title |
|---|
| Basicity and stability of urea deep eutectic mixtures;S.P.Simeonov等;《RSC Advances》;20160105;第6卷(第7期);第5485-5490页 * |
| One-Pot Synthesis of 3,4-Dihydro-2(H)-Pyrimidinones Catalyzed by Reusable Acidic Choline-Based Ionic Liquids;Anlian Zhu等;《Catalysis Letters》;20130226;第143卷(第5期);全文，尤其是第465页左栏第4段、第467页表4 * |
| 深共融溶剂在有机合成中的应用;王爱玲，等;《化学进展》;20141231;第26卷(第5期);第748-795页 * |
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