无外加催化剂条件下芳香醛与活性亚甲基化合物的缩合反应和迈克尔加成反应

在DMF溶剂中，不外加催化剂使芳香醛(1)与2,2-二甲基-1,3-二氧六环-4,6-二酮(2)发生缩合反应生成2,2-二甲基-5-芳亚甲基-1,3-二氧六环-4,6-二酮(3a～f)。在同样条件下，芳香醛与5,5-二甲基-1,3-环己二酮(4)则发生缩合和迈克尔加成反应生成2,2'-芳亚甲基双(3-羟基5,5-二甲基-2-环己烯-1-酮)(5a～h)。用单晶X-射线分析法确定了产物5b的晶体结构。     

比卡鲁胺的合成

以2-甲基丙烯酸甲醋为起始原料，经氧化、与4-氟苯硫酚缩合、水解成α-羟基酸(Ⅳ)、Ⅳ再与2-三氟甲基-4-氨基苯腈在亚硫酰氯作用下缩合、最后经间氯过氧化苯甲酸氧化而合成比卡鲁胺。总收率为11．2％。     

西维来司钠的合成

以对羟基苯磺酸钠为原料,经2,2-二甲基丙酰氯缩合、与氯化亚砜反应而成4-(2,2-二甲基丙酰氧基)苯磺酰氯,再经与2-氨基苯甲酸缩合、与甘氨酸苄酯成酰胺、加氢脱去保护基团,最后与氢氧化钠成盐而合成了西维来司钠。     

无溶剂、无催化剂条件下5-[(3-吲哚基)-芳甲基]-2,2-二甲基-l,3-二氧六环-4,6-二酮的合成

在无溶剂和催化剂条件下，由芳香醛、吲哚、丙二酸亚异丙酯的三组分缩合反 应，制备了5．[(3-吲哚基)-芳甲基]-2，2-二甲基-1，3-二氧六环-4，6-二酮，产 率为70％～85％，产物结构经～1H NMR，IR确证．     

室温离子液体催化“一锅法”合成3, 4-二氢嘧啶-2-酮

利用室温离子液体作催化剂，芳香醛、尿素和乙酰乙酯或乙酰丙酮三组分缩合制备3,4-二氢嘧啶-2-酮衍生物，反应条件温和，反应时间短，且不需另加有机溶剂，考察了不同取代基对芳香醛、尿素和乙酰乙酸乙酯或乙酰丙酮三组分缩合反应的影响。还考察了不同的室温离子液体的催化性能，发现1-丁基-3-甲基咪唑六氟磷酸盐较1-丁基-3-甲基咪唑四氟硼酸盐的催化效果略好。     

5-羟基嘧啶——Ⅴ.1,3-二甲氧基乙酰丙酮与胍和硫脲的缩合

1,3-二甲氧基乙酰丙酮(1)与胍在中性条件下以低产率(28%)缩合生成5-甲氧基-2-氨基-6-甲氧甲基-4-甲基嘧啶(3),而不与硫脲缩合。在与S-甲基异硫脲的反应中,1降解为甲氧基丙酮和甲氧基乙酸,从而生成甲氧基丙酮缩-S-甲基异硫脲甲氧基乙酸盐(4)和S-甲基异硫脲甲氧基乙酸盐(5)。由此可见,1对碱非常敏感,而对酸有一定的稳定性。     

新型苯并咪唑取代的丙烯腈衍生物的催化合成

从邻苯二胺出发,合成了2-腈甲基苯并咪唑,对2-腈甲基苯并咪唑与醛的Knoevenagel缩合反应催化剂进行了优选,研究表明,吗啡啉/乙酸是催化2-腈甲基苯并咪唑与芳香醛Knoevenagel缩合反应的良好催化剂;在吗啡啉/乙酸催化下,合成了新型的双苯并咪唑丙烯腈衍生物和3-吲哚-2-苯并咪唑丙烯腈衍生物;将2-腈甲基苯并咪唑经过碱性水解,酯化,得到苯并咪唑乙酸乙酯,后者经过次序Knoevenagel缩合/分子内酯交换高产率地得到了新型的苯并咪唑取代的香豆素衍生物。     

Revaprazan的合成

氟苯胺在浓硫酸的作用下与单氰胺缩合制得对氟苯胍碳酸盐(6);6再与2-甲基乙酰乙酸乙酯缩合得到嘧啶环化物(7);7经氯化后再与1-甲基-1,2,3,4-四氢异喹啉缩合合成了Revaprazan,总收率42%.     

无外加催化剂条件下芳香醛与活性亚甲基化合物的缩合反应和迈克尔加成反应

在DMF溶剂中,不外加催化剂使芳香醛(1)与2,2-二甲基-1,3-二氧六环-4,6-二酮(2)发生缩合反应生成2,2-二甲基-5-芳亚甲基-1,3-二氧六环-4,6-二酮(3a～f)。在同样条件下,芳香醛与5,5-二甲基-1,3-环己二酮(4)则发生缩合和迈克尔加成反应生成2,2’-芳亚甲基双(3-羟基-5,5-二甲基-2-环己烯-1-酮)(5a～h)。用单晶X-射线分析法确定了产物5b的晶体结构。     

1-甲基-3-三氟甲基-1H-吡唑-4-甲酸的合成

通过Knoevenagel缩合反应、用甲基肼闭环、再用碱进行酯的水解,得到目标产物1-甲基-3-三氟甲基-4-吡唑甲酸。以三氟乙酰乙酸乙酯为原料,对比原甲酸三乙酯和N,N-二甲基甲酰胺二甲基缩醛与之反应所得中间体对后续反应的优劣。     

Application of Microwave irradiation Techniques for the Knoevenagel Condensation

The reaction rate of Knoevenagel condensation can be dramatically enhanced by irradiating the reaction mixture containing an aldehyde, diethyl malonate, P₂O₅, piperidine, and chlorobenzene with a commercial microwave oven. Six Knoevenagel condensation products were synthesized within 5–15 min in good yields.     

碱性离子液体[bmim]OH在Knoevenagel反应和Perkin反应中的应用

以碱性离子液体[bmim]OH作为催化剂, 在无溶剂条件下, 催化Knoevenagel反应和Perkin反应两类缩合反应. 实验结果表明, 该离子液体对Knoevenagel反应具有很高的催化活性, 一系列的芳香醛和活泼亚甲基化合物在室温条件下10～30 min内顺利完成反应, 以85%～95%的高产率生成取代烯烃产物. 离子液体经简单处理后能多次循环使用. 此外, 初步探讨了该碱性离子液体在Perkin反应中的应用.     

离子液体[2-aemim]im催化Knoevenagel反应和异噁唑酮合成

以碱性离子液体1-(2-氨基乙基)-3-甲基咪唑咪唑盐([2-aemim]im)作为催化剂,催化Knoevenagel反应和4-芳亚甲基异噁唑-5(4H)-酮衍生物的合成。实验结果表明:在无溶剂条件下,该离子液体对Knoevenagel反应具有很高的催化活性,一系列芳香醛和活泼亚甲基化合物的反应在室温条件下2 min内顺利完成,均以90%以上的高产率生成取代烯烃产物.将该碱性离子液体用于催化乙酰乙酸乙酯或苯甲酰乙酸乙酯、盐酸羟胺和芳香醛三组分一锅法缩合制备4-芳亚甲基异噁唑-5(4H)-酮衍生物,具有反应时间较短、产率较高和后处理简单的特点。离子液体经简单处理后能多次循环使用。     

ReBr(CO)_5-Catalyzed Knoevenagel Condensation

Knoevenagel condensations are especially important reactions for the synthesis of alkene compounds having electron-withdrawing groups such as COR,CN,COOR,NO2 etc. Recently, transition metal hydride ruthenium1, hydride and polyhydride rhenium2, and polyhydride iridium complexes have been found to be the efficient catalysts for Knoevenagle condensation. However the mentioned-above transition metal hydride complexes are not easily prepared. In addition, all of them are oxygen and H2O-sensit…     

Practical and Green Protocol for the Synthesis of Substituted 4H‐Chromenes Using Room Temperature Ionic Liquid Choline Chloride–Urea

An efficient and convenient synthesis of substituted 4H‐chromenes is described using room temperature ionic liquid (RTIL) choline chloride–urea in one pot under solvent free conditions. Three‐component Knoevenagel condensation of an aromatic aldehyde, with an active methylene compound, and a cyclohexane dione is reported. This new approach has advantage of excellent yields (82–96%), clean reaction, and short reaction time (15–30 min) at room temperature.     

Microwave-assisted Knoevenagel condensation in aqueous over triazine-based microporous network

A high nitrogen-containing triazine-based microporous polymeric (TMP) network was used as an efficient metal-free catalyst for Knoevenagel condensation of ethylcyanoacetate with aromatic aldehydes. The reactions were performed in water as an environmentally benign medium, under microwave irradiation within a short reaction time of 10 min. The conversions of substituted aromatic aldehydes and selectivities for Knoevenagel products were found to be in the ranges of 44–99 and 65–99 %, respectively. The electron-withdrawing substituent showed higher conversion and selectivity as compared to electron-donating substituents. The TMP network can be readily recovered and reused up to three runs without loss in catalytic activity and selectivity.     

Synthesis of fused uracils: pyrano[2,3-d]pyrimidines and 1,4-bis(pyrano[2,3-d]pyrimidinyl)benzenes by domino Knoevenagel/Diels-Alder reactions

Abstract  

Knoevenagel condensation of barbituric acids with aromatic aldehydes containing one or two formyl groups was carried out. 5-Arylidenebarbituric acids underwent smooth hetero-Diels-Alder (HDA) reactions with enol ethers to afford cis and trans diastereoisomers of pyrano[2,3-d]pyrimidine-2,4-diones and 5,5′-(1,4-phenylene)bis[2H-pyrano[2,3-d]pyrimidine-2,4(3H)-dione] derivatives in excellent yields (75–88 %). Syntheses were realized by Knoevenagel condensation and HDA reaction in four different reaction conditions: Knoevenagel condensation in water and Diels-Alder reaction in methylene chloride solution, Knoevenagel condensation in water and Diels-Alder reaction without solvent, three-component one-pot reaction in methylene chloride solution, or three-component one-pot reaction in water. All reactions were carried out without catalyst at room temperature. The reactions of malononitrile with Knoevenagel condensation products of barbituric acids and heteroaromatic aldehydes or terephthalaldehyde were examined and did not provide corresponding pyranopyrimidines.     

富氮多孔有机聚合物催化制备α⁃氰基肉桂酸乙酯

α-氰基肉桂酸乙酯作为含多种官能团的缺电子烯烃, 是一种极具应用价值的有机合成反应底物, 主要通过催化Knoevenagel缩合反应获得. 本文以多聚甲醛和三聚氰胺为前驱体, 采用溶剂热法制备富氮多孔有机聚合物mPMF, 经K₂CO₃处理得到K₂CO₃-mPMF-X(X=1, 10, 50). 考察了mPMF在苯甲醛和氰乙酸乙酯Knoevenagel缩合反应中的催化性能, 通过mPMF与K₂CO₃-mPMF-X催化活性的比较, 探讨了碱性强弱对Knoevenagel缩合反应的影响, 并对催化反应机理进行了探索. 结果表明, 催化剂中丰富的氮物种为反应提供了碱性环境和大量的碱性活性位点, 催化剂碱性强弱的控制是催化合成α-氰基肉桂酸乙酯的关键因素. mPMF在甲醇溶剂中于60 ℃反应3 h后, 苯甲醛转化率为97%, 目标产物选择性在99.9%以上.     

A Simple,Efficient and Green Procedure for Knoevenagel Condensation in Water or under Solvent‐free Conditions

1,4‐Diazabicyclo[2.2.2]octane was used as an efficient catalyst in the Knoevenagel condensation reaction of various kinds of aromatic/aliphatic/heterocyclic/αβ‐unsaturated aldehydes and ketones with active methylene compounds. This is a convenient and rapid method for Knoevenagel condensation, which affords the corresponding substituted electrophilic alkenes in excellent yields. The reaction condition is mild and the method is operationally simple. The products, only E‐isomers were detected, did not need to be purified. The use of water as the reaction medium makes the process environmentally benign. The catalysts can be recycled six times without activity loss.     

Mn-MOF@Pi composite: synthesis,characterisation and an efficient catalyst for the Knoevenagel condensation reaction

We have synthesised new Mn-MOF@Pi composite by encapsulation of piperidine in desolvated Mn-MOF and investigated its catalytic performance in Knoevenagel condensation reaction. The newly developed composite is compatible with various aromatic aldehydes and converting them to the desired Knoevenagel condensation products in good yields and selectivity. Furthermore, composite Mn-MOF@Pi is reusable and shows good catalytic activity than native MOF.