Neue cyclische Ester der Malonsäure und deren Kondensationsprodukte mit Aldehyden

The reaction of malonylchloride with ethylene glycol or dithioglycol at low temperatures and high dilution leads to cyclic condensation products of 2∶2 composition, of which the first one reacts with aldehydes to give alkenes (Knoevenagel condensation). On the other hand, malonyl chloride and pinacol react under the same conditions to give a linear oligomeric condensation product. The Knoevenagel condensation products are electrically neutral organic Lewis acids (pK′ _L -values: 8.3₅ and 7.8₅). Mass-spectra, NMR-, UV- and IR-spectra were employed for structural determinations.     

Knoevenagel condensation of aldehydes with active methylene compounds catalyzed by MgC2O4/SiO2 under microwave irradiation and solvent-free conditions

MgC₂O₄/SiO₂ catalyzes the efficient Knoevenagel condensation of aldehydes with active methylene compounds in solvent-free conditions under microwave irradiation to give alkenes derivatives in excellent yields. MgC₂O₄/SiO₂ can be reusable for Knoevenagel condensation. However, ketones have been found to be unsatisfactory in the reaction under the same conditions.     

Hydrotalcite catalysis in ionic liquid medium: a recyclable reaction system for heterogeneous Knoevenagel and nitroaldol condensation

Knoevenagel condensation proceeds efficiently in recyclable [bmim]PF₆ and [bmim]BF₄ without any catalyst, and hydrotalcites in ionic liquid serve as a safe and recyclable reaction system for both Knoevenagel as well as nitroaldol condensations.     

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.     

Titanium isopropoxide/pyridine mediated Knoevenagel reactions

We report a Ti(OiPr)₄/pyridine-mediated Knoevenagel reaction between aromatic ketones and cyanoacetamides to provide Knoevenagel olefin products in good to excellent yields. Almost in all cases studied, a single geometrical isomer was formed and isolated under the Ti(OiPr)₄/pyridine condensation conditions. This methodology was also demonstrated to be highly effective between some other Knoevenagel active methylene compounds and aromatic ketones.     

A simple strategy to prepare graphene oxide modified by ammonia gas catalysts for Knoevenagel condensation

A facile and simple strategy to prepare ammonia gas-modified graphene oxide (GO) catalysts was successfully established by gas–solid acid–base reaction at room temperature. The catalytic performances of ammonia gas-modified GO samples were examined in Knoevenagel condensation. The samples were characterized by X-ray diffraction, Fourier transform infra-red spectroscopy, X-ray photoelectron spectroscopy, atomic force microscope, NH₃ temperature-programmed desorption and elemental analysis. The results indicated that the excellent performances of the ammonia gas-modified GO samples in Knoevenagel condensation should be ascribed to the formation of ammonium ions (NH₄ ⁺) by the reaction between ammonia gas and the carboxyl groups located on the edge of the GO.     

Fe3O4–cysteamine hydrochloride magnetic nanoparticles: New,efficient and recoverable nanocatalyst for Knoevenagel condensation reaction

Fe₃O₄ magnetic nanoparticles (MNPs) were obtained using a reduction–precipitation method. These MNPs were modified with cysteamine hydrochloride. This catalyst was characterized using a number of physicochemical measurements. The Fe₃O₄–cysteamine MNPs, as an efficient and heterogeneous catalyst, were successfully used for Knoevenagel condensation under mild conditions. The activity of this nanomagnetic catalyst in the Knoevenagel condensation of aromatic aldehydes and malononitrile is described. Easy preparation of the catalyst, easy work‐up procedure, excellent yields and short reaction times are some of the advantages.     

Alum catalyzed simple and efficient synthesis of 5-arylidene-2,4-thiazolidinedione in aqueous media

Abstract

Alum (KAl(SO₄)₂·12H₂O) is an inexpensive, efficient, and non-toxic catalyst used for the synthesis of 5-arylidine-2,4-thiazolidinediones by the Knoevenagel condensation of aromatic aldehydes with 2,4-thiazolidinedione in aqueous media at 90°C. This method affords the 5-arylidine-2,4-thiazolidinediones in short reaction times, high yields, and green aspects by avoiding toxic catalysts and hazardous solvents.     

On the reactions of aroylacetonitriles with acetoacetates

2,7-Diaryl-3-cyano-4-methylpyrano[4,3-b]pyridin-5-ones were synthesized by Ni(acac)₂-catalyzed condensation of aroylacetonitriles with acetoacetates. The competitive Knoevenagel reaction gave 6-aryl-5-cyano-4-methylpyran-2-ones as by-products. A preparative method for the synthesis of the latter compounds in the presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a catalyst was proposed.     

Preparation, characterization and catalyst application of ternary interpenetrating networks of poly 4-methyl vinyl pyridinium hydroxide-SiO2-Al2O3

In this work, Al₂O₃ was mixed with SiO₂ and poly 4-vinylpyridine by the sol-gel method in order to make a composite which is used as a heterogeneous basic catalyst for Knoevenagel condensation reaction. The physical and chemical properties of the composite catalyst were investigated by XRD, FT-IR, TG, BET and SEM techniques. The catalytic performance of each material was determined for the Knoevenagel condensation reaction between carbonyl compound and malononitrile. The reactions were performed in solvent-free conditions and the product was obtained in high yield and purity after a simple work-up. The effects of the amount of catalyst, amount of monomer for the synthesis of composite and recyclability of the heterogeneous composite were investigated. The composite catalyst used for this synthetically useful transformation showed considerable level of reusability besides very good activity.     

Magnetic nanoparticle supported amine: An efficient and environmental benign catalyst for versatile Knoevenagel condensation under ultrasound irradiation

Amine functionalized silica coated Fe₃O₄ nanoparticles (SiO₂@MNP-A) were successfully prepared as a novel heterogeneous amine. The catalyst was characterized by XRD, FT-IR, TEM, magnetic measurement, elemental analysis and was found to be a magnetically separable and highly active catalyst for ambient Knoevenagel condensation of aromatic aldehydes and α-aromatic (heteroaromatic or polyaromatic)-substituted methylene compounds in water under ultrasonic irradiation to afford the corresponding products in good to excellent yields. Very interestingly, SiO₂@MNP-A successfully catalyze the reaction of the non-cyano substituted compound with benzaldehyde to achieve a key intermediate for the preparation of Atorvastatin calcium in green and atom-economic manner. In addition, the catalyst SiO₂@MNP-A can be reused for 8 times without any obvious loss of its activity. The role of ultrasonication in the Knoevenagel condensation was also discussed with the assistance of UV–vis spectrometry.     

One-pot synthesis of substituted indolo[1,2-a]quinolines under transition-metal-free conditions

A simple and efficient one-pot synthesis of substituted indolo[1,2-a]quinolines under transition-metal-free conditions has been developed. When 2-fluorobenzaldehyde was treated with substituted 2-methylindoles in the presence of Cs₂CO₃, the desired products were typically obtained in good to excellent yields. This reaction sequence involves a nucleophilic aromatic substitution and a Knoevenagel condensation reaction. Our mechanistic investigation revealed that both reactions could proceed as an intermolecular reaction in the first step.     

Iron(III) chloride-catalyzed convenient one-pot synthesis of β-acetamido carbonyl compounds

A one-pot multi-component reaction of aldehydes, enolizable ketones or 1,3-dicarbonyls, acetonitrile/benzonitrile, and acetyl chloride is described for the preparation of β-acetamido carbonyl compounds using FeCl₃·6H₂O as a mild, inexpensive, and highly efficient catalyst. The effect of substrate as well as substituent for multi-component reaction versus Knoevenagel condensation is also illustrated. The key features of this methodology are operational simplicity, mild reaction conditions, and good yields.     

A Novel Thermal Knoevenacel Condensation via A Thermal Michael Reaction

In connection with the total synthesis of natural products by retro-mass spectral approach,^1–3 the thermal reaction between 6,7-dimethoxy-3-isochromanone 1 and benzalmalononitrile 3 was studied. The Knoevenagel condensation product⁴ was obtained over and above the expected Diels-Alder adduct. The scope, limitation and mechanism of the aforesaid unusual thermal Knoevenagel condensation through a thermal Michael reaction is described.     

Fe3O4‐Methylene diphenyl diisocyanate‐guanidine (Fe3O4–4,4′‐MDI‐Gn): A novel superparamagnetic powerful basic and recyclable nanocatalyst as an efficient heterogeneous catalyst for the Knoevenagel condensation and tandem Knoevenagel‐Michael‐cyclocondensation reactions

In this paper, guanidine groups (Gn) supported on modified magnetic nanoparticles (Fe₃O₄–4,4′‐MDI) were synthesized for the first time. The catalyst synthesized was characterized by various techniques such as SEM (Scanning Electron Microscopy), TEM (Transmission electron microscopy), XRD ( X‐ray Diffraction ), TGA (Thermogravimetric ananlysis), EDS ( Energy‐dispersive X‐ray spectroscopy ) and VSM (vibrating sample magnetometer). The catalyst activity of modified MNPs–MDI‐Gn, as powerful basic nanocatalyst, was probed through the Knoevenagel and Tandem Knoevenagel–Michael‐cyclocondensation reactions. Conversion was high under optimal conditions, and reaction time was remarkably shortened. This nanocatalyst could simply be separated and recovered from the reaction mixture by simple magnetic decantation and reused many times without significant loss of its catalytic activity. Also, the nanocatalyst could be recycled for at least seven (Knoevenagel condensation) and six (Knoevenagel and Tandem Knoevenagel–Michael‐cyclocondensation) additional cycles after they were separated by magnetic decantation and, washed with ethanol, air‐dried, and immediately reused.     

Chemoselective synthesis of xanthenes and tetraketones in a choline chloride-based deep eutectic solvent

A chemoselective synthesis of tetraketone and xanthene derivatives, by means of tandem Knoevenagel condensation and Michael addition in choline chloride-based deep eutectic solvents (DESs), is presented. The reaction of readily available aldehydes and active methylene compounds in malonic acid- and ZnCl₂-based DES gives various xanthenes derivatives with good to excellent yields under mild reaction conditions. On the other hand, tetraketones were synthesized in almost quantitative yields by simple condensation of an aldehyde and active methylene compounds in milder deep eutectic solvents of urea and SnCl₂. In addition, the reaction of other types of choline chloride-based DES leads to a mixture of tetraketone and xanthene.     

A cascade formation of N-pyridylacrylamides from pyrido[1,2-a]pyrimidine diones and chromene aldehydes

Various N-(pyridin-2-yl)acrylamides bearing 4H-chromene fragment were synthesized via the condensation of 4H-chromene-3-carbaldehydes and their fused analogues with 2H-pyrido[1,2-a]pyrimidine-2,4(3H)-diones employing NH₄OAc/AcOH system. Possible mechanism of this hetero- domino reaction involves the consecutive Knoevenagel condensation, oxa-6v-electrocyclization, aza-6v-electrocyclic ring-opening, nucleophilic addition, retro-Alder-ene reaction and oxa-6v-electrocyclic ring-disclosure.     

酸碱双功能MgO/HMCM-22催化剂上Knoevenagel缩合反应

采用浸渍法制备了一系列MgO改性催化剂MgO/HMCM-22, 利用X射线衍射、N₂物理吸附-脱附、扫描电镜、傅里叶变换红外光谱、NH₃及CO₂程序升温脱附等技术对所制催化剂进行了表征. 结果表明, MgO改性后MCM-22分子筛仍保持原有的结构; 随着MgO负载量的增加, 催化剂的碱强度和碱含量显著增加, 而强酸含量明显减少, 弱酸酸位有所增加. 以Knoevenagel缩合为探针反应, 考察了所制催化剂的性能. 在优化的反应条件下, MgO/HMCM-22上苯甲醛转化率高达92.6%. 催化剂 MgO/HMCM-22和MgO/NaMCM-22的催化性能明显优于HMCM-22和MgO. 酸中心和碱中心均对该缩合反应起着重要的促进作用. MgO/HMCM-22对Knoevenagel缩合反应显示出较高的催化活性, 体现出明显的酸碱协同催化作用.     

An eco-compatible multicomponent strategy for the synthesis of new 2-amino-6-(1H-indol-3-yl)-4-arylpyridine-3,5-dicarbonitriles in aqueous micellar medium promoted by thiamine-hydrochloride

A thiamine hydrochloride (VB₁) accelerated, one-pot synthesis of 2-amino-6-(1H-indol-3-yl)-4-arylpyridine-3,5-dicarbonitriles was achieved via four-component reaction of 3-cyanoacetyl indole, aromatic aldehydes, ammonium acetate, and malononitrile in aqueous micellar conditions by a Knoevenagel condensation reaction followed by Michael-addition, which upon cyclization and dehydration yielded the corresponding product in excellent proportion.     

Simple,Efficient, and Green Method for Synthesis of Trisubstituted Electrophilic Alkenes Using Lipase as a Biocatalyst

A simple and efficient Knoevenagel condensation method for the synthesis of trisubstituted electrophilic alkenes was developed using lipase as a biocatalyst. Knoevenagel condensation was performed using the conventional method and using lipases (Aspergillus oryzae or Rhizopus oryzae) as biocatalysts, and reaction time, reaction temperature, yield, and recyclability were compared. Using a lipase as a biocatalyst eliminated the need for bases such as piperidine and pyridine. A wide range of aromatic aldehydes and ketones readily undergo condensation with active methylene compounds. The workup procedure is also very simple, and yields of the reactions are in the range of 75% to 95%. Both the biocatalysts were effectively recycled four times with no major decrease in the yield of product. The remarkable catalytic activity and reusability of lipase widens its applicability in Knoevenagel condensation with good to excellent yields for synthesis of trisubstituted electrophilic alkenes.