CN108129399A - 4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1h)-酮的合成方法 - Google Patents
4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1h)-酮的合成方法 Download PDFInfo
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- HUMNYLRZRPPJDN-KWCOIAHCSA-N benzaldehyde Chemical group O=[11CH]C1=CC=CC=C1 HUMNYLRZRPPJDN-KWCOIAHCSA-N 0.000 claims 1
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- 125000003118 aryl group Chemical group 0.000 abstract 1
- 150000002576 ketones Chemical class 0.000 abstract 1
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 abstract 1
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- JKNHZOAONLKYQL-UHFFFAOYSA-K tribromoindigane Chemical compound Br[In](Br)Br JKNHZOAONLKYQL-UHFFFAOYSA-K 0.000 description 2
- ZYMCBJWUWHHVRX-UHFFFAOYSA-N (4-nitrophenyl)-phenylmethanone Chemical class C1=CC([N+](=O)[O-])=CC=C1C(=O)C1=CC=CC=C1 ZYMCBJWUWHHVRX-UHFFFAOYSA-N 0.000 description 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 description 1
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- 239000007848 Bronsted acid Substances 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
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- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical compound OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 description 1
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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
Abstract
本发明涉及一种4‑芳基‑5‑甲氧羰基‑6‑甲基‑3,4‑二氢嘧啶‑2(1H)‑酮的合成方法。该方法具体为:以芳香醛、乙酰乙酸甲酯和尿素为底物,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、乙酰乙酸甲酯、尿素和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、环保的合成方法。
Description
技术领域
本发明涉及一种催化制备4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-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4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮类化合物的方法。
背景技术
3,4-二氢嘧啶-2(1H)-酮(DHPM)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]。
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。
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。
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。
发明内容
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4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-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。
本发明以芳香醛、乙酰乙酸甲酯和尿素为底物,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4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮。反应通式如下:
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。
所述的芳香醛优选为苯甲醛、4-甲氧基苯甲醛、4-溴苯甲醛或4-硝基苯甲醛。
更为具体地,3,4-二氢嘧啶-2(1H)-硫酮的合成方法为:
将0.3当量的DES加入到反应容器中,然后加入1当量的芳香醛,1当量的乙酰乙酸甲酯和1.5当量的尿素,在70℃下,搅拌反应40min后停止反应。
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,抽滤得粗产品,重结晶后可获得目标产物。
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。
本发明与传统制备4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-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、环保的合成方法。
具体实施方式
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。
下述实施例中,催化剂DES优选下述方法制备:
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。
实施例1
反应方程式:
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的尿素加入到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)-酮,产率90%。
实施例2
反应方程式:
实验方法:将0.6mmol的催化剂DES,2mmol的4-甲氧基苯甲醛,2mmol的乙酰乙酸甲酯和3mmol的尿素加入到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-(4-甲氧基苯基)-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮,产率88%。
实施例3
反应方程式:
实验方法:将0.6mmol的催化剂DES(ChCl/2PTS),2mmol的4-溴苯甲醛,2mmol的乙酰乙酸甲酯和3mmol的尿素加入到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-(4-溴苯基)-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮,产率90%。
实施例4
反应方程式:
实验方法:将0.6mmol的催化剂DES(ChCl/2PTSA),2mmol的4-硝基苯甲醛,2mmol的乙酰乙酸甲酯和3mmol的尿素加入到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-(4-硝基苯基)-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮,产率88%。
参考文献:
[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 of3,4-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.
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。
Claims (6)
1.4-芳基-5-甲氧羰基-6-甲基-3,4-二氢嘧啶-2(1H)-酮的合成方法,其特征在于,以芳香醛、乙酰乙酸甲酯和尿素为底物,DES为催化剂,于60-75℃搅拌反应30-45min;
所述芳香醛、乙酰乙酸甲酯、尿素和DES的摩尔比为1:1:1.5:0.3。
2.根据权利要求1所述的合成方法,其特征在于,DES是由氯化胆碱与对甲基苯磺酸按照摩尔比1:2制备的深共融溶剂。
3.根据权利要求2所述的合成方法,其特征在于,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。
4.根据权利要求1所述的合成方法,其特征在于,反应温度70℃,搅拌反应40min。
5.根据权利要求1所述的合成方法,其特征在于,具体步骤为:将0.3当量的DES加入到反应容器中,然后加入1当量的芳香醛,1当量的乙酰乙酸甲酯和1.5当量的尿素,在70℃下,搅拌反应40min后停止反应,反应后处理时,直接加水产物析出,抽滤得粗产品,重结晶后可获得目标产物。
6.根据权利要求1所述的合成方法,其特征在于,所述的芳香醛为苯甲醛、4-甲氧基苯甲醛、4-溴苯甲醛或4-硝基苯甲醛。
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Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110128413A (zh) * | 2019-06-10 | 2019-08-16 | 陕西科技大学 | 5-乙酰基-4-(n-取代咔唑基)-6-甲基-3,4-二氢嘧啶-2-酮及制备方法 |
CN111100085A (zh) * | 2019-12-31 | 2020-05-05 | 东华理工大学 | 一种3-芳基-2H-苯并[β][1,4]苯并恶嗪-2-酮化合物的制备方法 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104045541A (zh) * | 2014-06-18 | 2014-09-17 | 大连大学 | 芳香酮类化合物的合成方法 |
CN106632073A (zh) * | 2016-12-19 | 2017-05-10 | 盐城师范学院 | 离子液体常温催化3,4‑二氢嘧啶‑2‑酮类化合物的合成方法 |
-
2018
- 2018-02-13 CN CN201810150053.XA patent/CN108129399B/zh active Active
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN104045541A (zh) * | 2014-06-18 | 2014-09-17 | 大连大学 | 芳香酮类化合物的合成方法 |
CN106632073A (zh) * | 2016-12-19 | 2017-05-10 | 盐城师范学院 | 离子液体常温催化3,4‑二氢嘧啶‑2‑酮类化合物的合成方法 |
Non-Patent Citations (4)
Title |
---|
ANLIAN ZHU等: "One-Pot Synthesis of 3,4-Dihydro-2(H)-Pyrimidinones Catalyzed by Reusable Acidic Choline-Based Ionic Liquids", 《CATALYSIS LETTERS》 * |
S.P.SIMEONOV等: "Basicity and stability of urea deep eutectic mixtures", 《RSC ADVANCES》 * |
李进军,等: "《绿色化学导论》", 31 August 2015, 武汉大学出版社 * |
王爱玲,等: "深共融溶剂在有机合成中的应用", 《化学进展》 * |
Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110128413A (zh) * | 2019-06-10 | 2019-08-16 | 陕西科技大学 | 5-乙酰基-4-(n-取代咔唑基)-6-甲基-3,4-二氢嘧啶-2-酮及制备方法 |
CN111100085A (zh) * | 2019-12-31 | 2020-05-05 | 东华理工大学 | 一种3-芳基-2H-苯并[β][1,4]苯并恶嗪-2-酮化合物的制备方法 |
CN111100085B (zh) * | 2019-12-31 | 2023-07-28 | 东华理工大学 | 一种3-芳基-2H-苯并[β][1,4]苯并恶嗪-2-酮化合物的制备方法 |
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