6768-17-8

Upstream product

• 89-98-5 2-chloro-benzaldehyde 
• 105-53-3 diethyl malonate 
• 6768-20-3 diethyl 2-chlorobenzylidene malonate 
• 135822-90-1 o-chloro-N-tosylbenzaldimine 

Downstream Products

• 103857-58-5 3-(2-chlorophenyl)pentanedioic acid 
• 688009-90-7 [4-(2-chloro-phenyl)-2,6-dioxo-piperidin-1-yl]-acetonitrile 

Relevant academic research and scientific papers

Tandem Knoevenagel-Michael addition of aryl sulfonimines with diethyl malonate for synthesis of arylidene dimalonates

(Chemical Equation Presented) A highly efficient, one-flask tandem Knoevenagel-Michael addition reaction of sulfonimines with diethyl malonate in the presence of a catalytic amount of base affords the corresponding arylidene dimalonates in good to excellent yields.

Synthesis, Screening, and Molecular Modeling of New Potent and Selective Antagonists at the α1d Adrenergic Receptor

In the present study, more than 75 compounds structurally related to BMY 7378 have been designed and synthesized. Structural variations of each part of the reference molecule have been introduced, obtaining highly selective ligands for the α1d adrenergic receptor. The molecular determinants for selectivity at this receptor are essentially held by the phenyl substituent in the phenylpiperazine moiety. The integration of an extensive SAR analysis with docking simulations using the rhodopsin-based models of the three α1-AR subtypes and of the 5-HT1A receptor provides significant insights into the characterization of the receptor binding sites as well as into the molecular determinants of ligand selectivity at the α1d-AR and the 5-HT1A receptors. The results of multiple copies simultaneous search (MCSS) on the substituted phenylpiperazines together with those of manual docking of compounds BMY 7378 and 69 into the putative binding sites of the α1a-AR, α1b-AR, α1d-AR, and the 5-HT1A receptors suggest that the phenylpiperazine moiety would dock into a site formed by amino acids in helices 3, 4, 5, 6 and extracellular loop 2 (E2), whereas the spirocyclic ring of the ligand docks into a site formed by amino acids of helices 1, 2, 3, and 7. This docking mode is consistent with the SAR data produced in this work. Furthermore, the binding site of the imide moiety does not allow for the simultaneous involvement of the two carbonyl oxygen atoms in H-bonding interactions, consistent with the SAR data, in particular with the results obtained with the lactam derivative 128. The results of docking simulations also suggest that the second and third extracellular loops may act as selectivity filters for the substituted phenylpiperazines. The most potent and selective compounds for α1d adrenergic receptor, i.e., 69 (Rec 26D/038) and 128 (Rec 26D/073), are characterized by the presence of the 2,5-dichlorophenylpiperazine moiety.

Lewis acidic ionic liquids for the synthesis of electrophilic alkenes via the Knoevenagel condensation

1-Butyl-3-methylimidazolium chloroaluminate, [bmim]Cl·AlCl3, N = 0.67 and 1-butylpyridinium chloroaluminate, [bpy]Cl·AlCl3, N = 0.67 ionic liquids were found to work well as the Lewis acid catalyst and solvent in the Knoevenagel condensations of benzaldehyde and substituted benzaldehydes with diethyl malonate to give benzylidene malonates. The benzylidene malonates subsequently underwent Michael additions with diethyl malonate. The extent of Michael product formed during the reaction was found to vary with the Lewis acidity and the molar proportion of ionic liquid. The influence of Lewis acidity of the ionic liquid on the Knoevenagel and Michael products is demonstrated. In the case of 2-hydroxyarylaldehydes, the reactions led to the formation of 3-ethoxycarbonyl coumarins under ambient conditions.