Is the neutral Knoevenagel reaction initiated by the carbanion formation?

The title reactions were studied by means of the density functional theory calculations. A base promoted reaction (called here ‘B’) was traced in a model composed of benzaldehyde, malononitrile, and (H₂O)₁₁. A neutral model (‘N’) of Ph‐CHO, H₂C(CN)₂ and (H₂O)₁₂ was also examined in line with a reported clean reaction. It was found that the ion pair of HC(CN) and H₃O⁺ is generated at the first step for N. For B, there are five elementary processes, and for N, four ones were obtained. By RB3LY/6‐311 + G** SCRF = PCM//RB3LYP/6‐31(+)G* energy calculations, the rate determining steps for both B and N reactions are the second proton removal, TS5(B) and TS3(N), respectively. In both B and N, the neutral species Ph(HO)HC‐CH(CN)₂ is the key intermediate. Copyright © 2010 John Wiley & Sons, Ltd.     

Synthesis and Esterification of 3‐Ferrocenyl Acrylic Acid in Ionic Liquid

3‐Ferrocenyl acrylic acid, synthesized from ferrocenecarboxaldehyde and propandioic acid in water‐insoluble ionic liquid (1‐butyl‐3‐methylimidazolium hexafluorophosphate, [BMIM]PF₆) at 85 °C in high yield, was transformed to a series of 3‐ferrocenyl acrylate of alcohols and phenols in water‐soluble ionic liquid (1,3‐dimethylimidazolium dimethylphosphate, [DMIM]Me₂PO₄) at room temperature in the presence of dicyclohexylcarbodiimide (DCC) and 4‐dimethylaminopyridine (DMAP).     

An efficient regioselective synthesis of functionalized biphenyls via sequential reactions of aromatic aldehydes and β-keto esters or ketones

Knoevenagel/Michael/Aldol reactions of aromatic aldehydes and β-keto esters/ketones in a sequential manner yielded intermediate cyclohexanones in good yields. The latter, on oxidative aromatization with iodine, afforded functionalized biphenyls with at least one phenolic hydroxyl in moderate to good yields.     

An efficient one-pot multicomponent approach to 5-amino-7-aryl-8-nitrothiazolo[3,2-a]pyridines

A series of thiazolo[3,2-a]pyridines have been prepared using a multicomponent reaction between aromatic aldehydes, 2-nitromethylenethiazolidine and nitriles containing an active methylene group (malononitrile, ethyl 2-cyanoacetate and 2-phenylsulfonylacetonitrile) in the presence of Et₃N under mild conditions with high yields. One of the compounds shows promising anticancer activity across a range of cancer cell lines.     

A flow chemistry route to 2-phenyl-3-(1H-pyrrol-2-yl)propan-1-amines

The Knoevenagel condensation of pyrrole-2-carboxaldehyde (1) with a range of substituted benzyl nitriles (2a-e) afforded rapid access to a family of α,β-unsaturated nitriles (3a-e) in good yields (67-78%). Flow hydrogenation (ThalesNano H-cube™) at 60 °C, 50 bar H₂ pressure, 1.0 mL/min through a 10% Pd-C catalyst selectively, and quantitatively, hydrogenated the olefin double bond (4a-e). Use of a Raney Nickel catalyst at 70 °C, 70 bar H₂ pressure and flow rates of 0.5-1.0 mL/min afforded quantitative conversion into the corresponding saturated amines with the reduction of both the olefin and nitrile bonds (5a-e). The versatility of this approach was further exemplified by reaction of 5a and 5c with norcantharidin to afford acid amide norcantharidin analogues 7 and 8 as novel protein phosphatase 1 and 2A inhibitors.     

Synthesis and Crystal Structure of 10-（3,4-Dichlorophenymethylidyne）-9,10-dihydrofluorene

A novel compound of 10-(3,4-dichlorophenymethylidyne)-9,10-dihydrofluorene (C20H12Cl2, Mr = 323.20) was synthesized via Knoevenagel reaction under microwave irradiation (500 w) within short reaction time (8 min), giving a high yield of product (87%). Its structure was determined by IR, 1H NMR, MS, elemental analysis and X-ray diffraction. The crystal of the new compound is of monoclinic system, space group P21/c with a = 12.8781(13), b = 16.5067(16), c = 7.4656(7), β = 103.567(2)o, V = 1542.7(3)3, Z = 4, Dc = 1.392 g/cm3, μ = 0.413 mm-1, F(000) = 664, R = 0.0569 and wR = 0.1342 for 3355 observed reflections with I > 2σ(I). The crystal structure involves a conjugated system which shows an olefin structure.     

A new tricyclic triketone from tandem condensation reactions

Perhydrophenanthrene-1,5,10-trione (6) was isolated from the reaction of methyl 3-(carboxymethyl)cyclohexanone and cyclohexenone in a tandem Michael-Claisen reaction. NMR and X-ray analysis confirmed the structure of the product.