CN108059616B - Synthetic method of 3,4-dihydropyrimidine-2(1H)-thione - Google Patents
Synthetic method of 3,4-dihydropyrimidine-2(1H)-thione Download PDFInfo
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- MBOCEPWYDNXEKN-UHFFFAOYSA-N 3,4-dihydro-1h-pyrimidine-2-thione Chemical compound S=C1NCC=CN1 MBOCEPWYDNXEKN-UHFFFAOYSA-N 0.000 title claims abstract description 8
- 238000010189 synthetic method Methods 0.000 title claims description 6
- 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 16
- WDJHALXBUFZDSR-UHFFFAOYSA-M acetoacetate Chemical compound CC(=O)CC([O-])=O WDJHALXBUFZDSR-UHFFFAOYSA-M 0.000 claims abstract description 11
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Natural products NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims abstract description 10
- 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 6
- 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 16
- 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
- 238000002360 preparation method Methods 0.000 claims description 9
- 239000000047 product Substances 0.000 claims description 9
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 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
- 239000000203 mixture Substances 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
- 238000001953 recrystallisation Methods 0.000 claims description 4
- 230000005496 eutectics Effects 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 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
- 239000000706 filtrate Substances 0.000 claims description 2
- 238000002156 mixing Methods 0.000 claims description 2
- HUMNYLRZRPPJDN-KWCOIAHCSA-N benzaldehyde Chemical group O=[11CH]C1=CC=CC=C1 HUMNYLRZRPPJDN-KWCOIAHCSA-N 0.000 claims 1
- BACVXBIMPCMUAE-UHFFFAOYSA-N benzaldehyde thiourea Chemical compound NC(N)=S.O=CC1=CC=CC=C1 BACVXBIMPCMUAE-UHFFFAOYSA-N 0.000 claims 1
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 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
- 230000002194 synthesizing effect Effects 0.000 abstract 2
- 238000005761 Biginelli synthesis reaction Methods 0.000 description 5
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- -1 3,4-dihydropyrimidine-2(1H)-(thione) ketones Chemical class 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 239000012153 distilled water Substances 0.000 description 2
- 230000007613 environmental effect Effects 0.000 description 2
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- KLRHPHDUDFIRKB-UHFFFAOYSA-M indium(i) bromide Chemical compound [Br-].[In+] KLRHPHDUDFIRKB-UHFFFAOYSA-M 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000000967 suction filtration Methods 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- OKGNMRKOGWTADH-UHFFFAOYSA-N 1,4-dihydropyrimidine Chemical compound C1C=CNC=N1 OKGNMRKOGWTADH-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
- 239000002841 Lewis acid Substances 0.000 description 1
- 206010028980 Neoplasm Diseases 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical group [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 229910007926 ZrCl Inorganic materials 0.000 description 1
- 239000000370 acceptor Substances 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000006937 anti-inflammatory bioactivity Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 239000002220 antihypertensive agent Substances 0.000 description 1
- 229940030600 antihypertensive agent Drugs 0.000 description 1
- 230000015572 biosynthetic process 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
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 230000009849 deactivation Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000000374 eutectic mixture Substances 0.000 description 1
- 239000002638 heterogeneous catalyst Substances 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
- BITNETQOCMZGKF-UHFFFAOYSA-N methyl 6-methyl-4-phenyl-2-sulfanylidene-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound COC(=O)C1=C(C)NC(=S)NC1C1=CC=CC=C1 BITNETQOCMZGKF-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 239000012450 pharmaceutical intermediate Substances 0.000 description 1
- 229920005862 polyol Polymers 0.000 description 1
- 150000003077 polyols Chemical class 0.000 description 1
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N titanium dioxide Inorganic materials O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 1
- 230000001173 tumoral effect Effects 0.000 description 1
Classifications
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- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
- Catalysts (AREA)
Abstract
本发明涉及一种3,4‑二氢嘧啶‑2(1H)‑硫酮的合成方法。该方法具体为：以芳香醛、乙酰乙酸酯和硫脲为底物，DES为催化剂，无溶剂条件下，于60‑75℃搅拌反应30‑45min；所述芳香醛、乙酰乙酸酯、硫脲和DES的摩尔比为1：1：1.5：0.3。本发明以价廉易得的DES做催化剂，反应过程中不需要加入其它溶剂，可以有效减少其他有机溶剂和腐蚀性催化剂的使用，反应条件温和，可重复利用，工艺简单，催化活性高，产率高；反应后处理简单方便，绿色环保，是一种价廉、安全、环保的3,4‑二氢嘧啶‑2(1H)‑硫酮类化合物的合成方法。The invention relates to a method for synthesizing 3,4-dihydropyrimidine-2(1H)-thione. The method is specifically as follows: using aromatic aldehyde, acetoacetate and thiourea as substrates, DES as a catalyst, and under solvent-free conditions, stirring and reacting at 60-75 DEG C for 30-45min; the aromatic aldehyde, acetoacetate, The molar ratio of thiourea and DES was 1:1:1.5:0.3. The invention uses cheap and easy-to-obtain DES as a 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 reused, simple process, high catalytic activity, and yields high yields. The reaction rate is high; the post-reaction treatment is simple and convenient, environmentally friendly, and is a cheap, safe and environmentally friendly method for synthesizing 3,4-dihydropyrimidine-2(1H)-thione compounds.
Description
技术领域technical field
本发明涉及一种催化制备3,4-二氢嘧啶-2(1H)-硫酮的方法，更具体地说，涉及一种利用深共融溶剂通过Bininelli反应催化制备3,4-二氢嘧啶-2(1H)-硫酮的方法。The invention relates to a method for catalyzing the preparation of 3,4-dihydropyrimidine-2(1H)-thione, more particularly, to a method for catalyzing the preparation of 3,4-dihydropyrimidine through Bininelli reaction using deep eutectic solvent - Method for 2(1H)-thione.
背景技术Background technique
3,4-二氢嘧啶-2(1H)-(硫)酮类化合物是重要的医药中间体，可以作为钙通道剂、抗过敏剂、降压剂、拮抗剂等，还具有抗病毒、抗肿瘤、抗菌和消炎等生物活性[1]。3,4-dihydropyrimidine-2(1H)-(thione) ketones are important pharmaceutical intermediates, which can be used as calcium channel agents, antiallergic agents, antihypertensive agents, antagonists, etc. Tumor, antibacterial and anti-inflammatory biological activities [1] .
1893年，意大利化学家首次报道在浓盐酸催化下，利用芳香醛、乙酰乙酸乙酯和尿素三组分“一锅煮法”合成DHPM，这一合成法被称为Biginelli反应[2]。该方法虽然简单方便，但存在反应时间长、产率低等缺点。目前催化剂的选择是制约Biginelli反应的关键问题，传统的催化剂一般为质子酸或路易斯酸，例如HBF4、H3PW12O40、NH2SO3H、InBr3、ZrCl4、Cu(OTf)2、Fe(OTs)3·6H2O、Ce(NO3)3·6H2O等[3]。然而这类催化剂具有一些不可避免的缺点，如反应需要使用易挥发有机溶剂、后处理复杂、无法回收，对环境造成严重污染等。In 1893, Italian chemists first reported the synthesis of DHPM under the catalysis of concentrated hydrochloric acid, using aromatic aldehyde, ethyl acetoacetate and urea three-component "one-pot method" to synthesize DHPM, which is called the Biginelli reaction [2] . Although this method is simple and convenient, it has disadvantages such as long reaction time and low yield. At present, the choice of catalyst is the key problem that restricts the Biginelli reaction. Traditional catalysts are generally protonic acid or Lewis acid, such as HBF 4 , H 3 PW 12 O 40 , NH 2 SO 3 H, InBr 3 , ZrCl 4 , Cu(OTf) 2. Fe(OTs) 3 ·6H 2 O, Ce(NO 3 ) 3 ·6H 2 O, etc. [3] . However, this type of catalyst has some unavoidable disadvantages, such as the need to use volatile organic solvents for the reaction, complicated post-treatment, inability to recover, and serious pollution to the environment.
近年来，人们开始利用高效清洁的多相催化剂如PS-PEG-SO3H[4]，胺功能化的纳米二氧化钛[5]，金属配合物[6]等。但上述催化剂面临反应时间长、催化剂制备工艺复杂、催化剂易失活等问题，很难实现工业化生产。磺酸类化合物也可作为催化剂催化Biginelli反应，如对甲基苯磺酸[7]，磺酸功能化的磁铁矿纳米粒子[8]等，但磺酸催化的反应需在有机溶剂中进行，磺酸不可回收，而复载磺酸的制备过程又较复杂，极大限制了磺酸催化Biginelli反应的应用。In recent years, people have begun to utilize efficient and clean heterogeneous catalysts such as PS-PEG-SO 3 H [4] , amine-functionalized nano-titania [5] , and metal complexes [6] . However, the above-mentioned catalysts face problems such as long reaction time, complex catalyst preparation process, and easy deactivation of the catalysts, and it is difficult to realize industrial production. Sulfonic acid compounds can also be used as catalysts to catalyze the Biginelli reaction, such as p-toluenesulfonic acid [7] , sulfonic acid-functionalized magnetite nanoparticles [8] , etc., but 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 multiplexed sulfonic acid is complicated, which greatly limits the application of the sulfonic acid catalyzed by the Biginelli reaction.
随着社会的发展，人们更渴望追求绿色环保的生活品质，绿色化学受到了越来越多的重视，寻找一种绿色催化剂是至关重要的，一直倍受到世界科学家的广泛重视。With the development of society, people are more eager to pursue a green and environmentally friendly quality of life. Green chemistry has received more and more attention. It is very important to find a green catalyst, which has always been widely valued by scientists around the world.
发明内容SUMMARY OF THE INVENTION
本发明的目的是发展一种新型环境友好的反应体系用于制备3,4-二氢嘧啶-2(1H)-硫酮，该反应体系无需使用溶剂，以DES(ChCl/2PTSA)为催化剂，避免了使用易挥发性有机溶剂，对环境有害的传统催化剂，发明了一种安全、价廉、绿色的制备方法。该体系适用范围广、操作简单、廉价安全、产率较高、对环境友好。The purpose of the present invention is to develop a novel environment-friendly reaction system for the preparation of 3,4-dihydropyrimidine-2(1H)-thione, which does not require a solvent, uses DES (ChCl/2PTSA) as a catalyst, A safe, cheap and green preparation method is invented by avoiding the use of volatile organic solvents and traditional catalysts that are harmful to the environment. The system has wide application range, simple operation, low cost and safety, high yield and environmental friendliness.
本发明以芳香醛、乙酰乙酸酯和硫脲为底物，DES(ChCl/2PTSA)为催化剂，在无溶剂条件下，于60-75℃搅拌反应30-45min，通过Biginelli反应来合成3,4-二氢嘧啶-2(1H)-硫酮。反应通式如下：In the present invention, aromatic aldehyde, acetoacetate and thiourea are used as substrates, DES (ChCl/2PTSA) is used as catalyst, and under solvent-free conditions, the reaction is stirred at 60-75 DEG C for 30-45min, and 3 is synthesized by Biginelli reaction. 4-Dihydropyrimidine-2(1H)-thione. The general reaction formula is as follows:
其中，DES为对甲基苯磺酸(PTSA)与氯化胆碱(ChCl)制备的深共融溶剂，且该催化剂可重复使用，绿色环保，在回收四次后催化效果基本保持不变。DES的制备方法为：将摩尔比1：2的氯化胆碱和对甲基苯磺酸加入到圆底烧瓶中混合，将混合物在80℃条件下搅拌4h，得透明液体，即为DES催化剂。Among them, DES is a deep eutectic solvent prepared by p-toluenesulfonic acid (PTSA) and choline chloride (ChCl), and the catalyst is reusable, green and environmentally friendly, and the catalytic effect basically remains unchanged after four times of recovery. The preparation method of DES is as follows: adding choline chloride and p-toluenesulfonic acid in a molar ratio of 1:2 into a round-bottomed flask and mixing, and stirring the mixture at 80° C. for 4 hours to obtain a transparent liquid, which is the DES catalyst .
所述的芳香醛优选为苯甲醛。The aromatic aldehyde is preferably benzaldehyde.
所述的乙酰乙酸酯为乙酰乙酸甲酯或乙酰乙酸乙酯。Described acetoacetate is methyl acetoacetate or ethyl acetoacetate.
更为具体地，3,4-二氢嘧啶-2(1H)-硫酮的合成方法为：More specifically, the synthetic method of 3,4-dihydropyrimidine-2(1H)-thione is:
将0.3当量的DES加入到反应容器中，然后加入1当量的苯甲醛，1当量的乙酰乙酸酯和1.5当量的硫脲，在70℃下，搅拌反应40min后停止反应。0.3 equivalent of DES was added to the reaction vessel, then 1 equivalent of benzaldehyde, 1 equivalent of acetoacetate and 1.5 equivalent of thiourea were added, and the reaction was stopped after stirring for 40 min at 70 °C.
该合成方法，反应后处理简单方便，反应后处理时，直接加水产物析出，重结晶后可获得目标产物，滤液蒸出水，干燥，即可回收催化剂DES。In the synthesis method, the post-reaction treatment is simple and convenient. During the post-reaction treatment, water is directly added to separate out the product, and the target product can be obtained after recrystallization. The filtrate is distilled to remove water and dried to recover the catalyst DES.
DES是由一定化学计量比的氢键接受体(如季铵盐，季磷盐等)和氢键给体(如酰胺，羧酸和多元醇等化合物)组合而成的低共熔混合物。DES具有价格低、制备简单、不易挥发、不易燃、易储存、可回收循环使用等诸多优点。DES is a eutectic mixture composed of a certain stoichiometric ratio of hydrogen bond acceptors (such as quaternary ammonium salts, quaternary phosphorus salts, etc.) and hydrogen bond donors (such as compounds such as amides, carboxylic acids and polyols). DES has many advantages, such as low price, simple preparation, non-volatile, non-flammable, easy to store, and recyclable.
本发明与传统制备3,4-二氢嘧啶-2(1H)-硫酮工艺相比，有如下优点：以价廉易得的DES做催化剂，反应过程中不需要加入其它溶剂，可以有效减少其他有机溶剂和腐蚀性催化剂的使用，反应条件温和，可重复利用，工艺简单，催化活性高，产率高；反应后处理简单方便，绿色环保，是一种价廉、安全、环保的3,4-二氢嘧啶-2(1H)-硫酮类化合物的合成方法。Compared with the traditional process for preparing 3,4-dihydropyrimidine-2(1H)-thione, the present invention has the following advantages: using cheap and easily available DES as a catalyst, no other solvent needs to be added in the reaction process, and can effectively reduce The use of other organic solvents and corrosive catalysts, mild reaction conditions, reusable, simple process, high catalytic activity, high yield; simple and convenient post-reaction treatment, green and environmental protection, is a cheap, safe and environmentally friendly 3, Synthetic method of 4-dihydropyrimidine-2(1H)-thione compounds.
具体实施方式Detailed ways
下面通过具体实施例详述本发明，但不限制本发明的保护范围。如无特殊说明，本发明所采用的实验方法均为常规方法，所用实验器材、材料、试剂等均可从商业途径获得。The present invention is described in detail below through specific embodiments, but the protection scope of the present invention is not limited. Unless otherwise specified, the experimental methods used in the present invention are all conventional methods, and the experimental equipment, materials, reagents, etc. used can be obtained from commercial sources.
下述实施例中，催化剂DES优选下述方法制备：In the following examples, the catalyst DES is preferably prepared by the following method:
将50mmol(6.98g)氯化胆碱(ChCl)和100mmol(19.02g)对甲基苯磺酸(PTSA)加入到250ml的圆底烧瓶中，将混合物在80℃条件下搅拌4h，得一种透明液体，即DES催化剂。50mmol (6.98g) of choline chloride (ChCl) and 100mmol (19.02g) of p-toluenesulfonic acid (PTSA) were added to a 250ml round-bottomed flask, and the mixture was stirred at 80°C for 4h to obtain a Transparent liquid, namely DES catalyst.
实施例1Example 1
反应方程式：Reaction equation:
实验方法：将0.6mmol的催化剂DES，2mmol的苯甲醛，2mmol的乙酰乙酸甲酯和3mmol的硫脲加入到25mL的圆底烧瓶中，在70℃下，搅拌反应40min后停止反应。反应结束后，冷却至室温，加入冰水混合物使产物充分析出，抽滤，经蒸馏水洗涤3次即可得到粗产品。用乙醇-水溶液重结晶即可得到4-苯基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-硫酮，产率80％。Experimental method: 0.6 mmol of catalyst DES, 2 mmol of benzaldehyde, 2 mmol of methyl acetoacetate and 3 mmol of thiourea were added to a 25 mL round-bottomed flask, and the reaction was stopped after stirring for 40 min at 70 °C. After the reaction is completed, it is cooled to room temperature, and an ice-water mixture is added to fully separate out the product, suction filtration, and washing with distilled water 3 times to obtain a crude product. 4-phenyl-5-methoxycarbonyl-6-methyl-3,4-dihydropyrimidine-2(1H)-thione was obtained by recrystallization from ethanol-water solution in 80% yield.
实施例2Example 2
反应方程式：Reaction equation:
实验方法：将0.6mmol的催化剂DES，2mmol的苯甲醛，2mmol的乙酰乙酸乙酯和3mmol的硫脲加入到25mL的圆底烧瓶中，在70℃下，搅拌反应40min后停止反应。反应结束后，冷却至室温，加入冰水混合物使产物充分析出，抽滤，经蒸馏水洗涤3次即可得到粗产品。用乙醇-水溶液重结晶即可得到4-苯基-5-乙氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-硫酮，产率80％。Experimental method: 0.6 mmol of catalyst DES, 2 mmol of benzaldehyde, 2 mmol of ethyl acetoacetate and 3 mmol of thiourea were added to a 25 mL round-bottomed flask, and the reaction was stopped after stirring for 40 min at 70 °C. After the reaction is completed, it is cooled to room temperature, and an ice-water mixture is added to fully separate out the product, suction filtration, and washing with distilled water 3 times to obtain a crude product. 4-phenyl-5-ethoxycarbonyl-6-methyl-3,4-dihydropyrimidine-2(1H)-thione was obtained by recrystallization from ethanol-water solution in 80% yield.
参考文献：references:
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以上所述，仅为本发明创造较佳的具体实施方式，但本发明创造的保护范围并不局限于此，任何熟悉本技术领域的技术人员在本发明创造披露的技术范围内，根据本发明创造的技术方案及其发明构思加以等同替换或改变，都应涵盖在本发明创造的保护范围之内。The above is only a preferred embodiment of the present invention, but the protection scope of the present invention is not limited to this. The equivalent replacement or modification of the created technical solution and its inventive concept shall be included within the protection scope of the present invention.
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