59832-47-2

Upstream product

• 89-98-5 2-chloro-benzaldehyde 
• 108-59-8 malonic acid dimethyl ester 

Downstream Products

• 1393729-48-0 dimethyl 2-(2-chlorophenyl)cyclopropane-1,1-dicarboxylate 
• 1030919-37-9 dimethyl 2-((Z)-2-benzylidene-1-(2-chlorophenyl)-3-oxobutyl)propanedioate 

Relevant academic research and scientific papers

TiCl4 promoted formal [3 + 3] cycloaddition of cyclopropane 1,1-diesters with azides: Synthesis of highly functionalized triazinines and azetidines

A TiCl4 promoted formal [3 + 3] cycloaddition of cyclopropane 1,1-diesters with azides has been developed for the synthesis of highly functionalized triazinines. Both stoichiometric and substoichiometric versions of this reaction were accomplished dependent on the choice of solvent. It is noteworthy that the corresponding products could be easily converted to biologically important azetidines by simple thermolysis.

Synthesis of Substituted β-Styrylmalonates by Sequential Isomerization of 2-Arylcyclopropane-1,1-dicarboxylates and (2-Arylethylidene)malonates

A method has been developed for the synthesis of substituted β-styrylmalonates by conversion of 2-arylcyclopropane-1,1-dicarboxylates (ACDCs) in the presence of gallium trichloride into the corresponding- 1,2-zwitterionic intermediates or (2-arylethyl-idene)malonates, followed by treatment with pyridine at room temperature leading to an isomerization of the emerging double bond. This method allows one to expand these reactions to include ACDCs with acceptor substituents at the aromatic ring.

Intermolecular Reductive Couplings of Arylidene Malonates via Lewis Acid/Photoredox Cooperative Catalysis

A cooperative Lewis acid/photocatalytic reduction of arylidene malonates yields a versatile radical anion species. This intermediate preferentially undergoes intermolecular radical-radical coupling reactions, and not the conjugate addition-dimerization reactivity typically observed in the single-electron reduction of conjugate acceptors. Reported here is the development of this open-shell species in intermolecular radical-radical cross couplings, radical dimerizations, and transfer hydrogenations. This reactivity underscores the enabling modularity of cooperative catalysis and demonstrates the utility of stabilized enoate-derived radical anions in intermolecular bond forming reactions.

Cascade One-Pot Synthesis of Indanone-Fused Cyclopentanes from the Reaction of Donor-Acceptor Cyclopropanes and Enynals via a Sequential Hydrolysis/Knoevenagel Condensation/[3+2] Cycloaddition

A cascade reaction of donor-acceptor cyclopropanes with enynals to construct indanone-fused cyclopentanes via a sequential hydrolysis/Knoevenagel condensation/[3+2] cycloaddition is reported. The desired indanone-fused cyclopentanes were obtained in good yields. This method features mild reaction conditions and broad substrate scope, which render it very appealing to chemists for the synthesis of complex molecules containing an indanone-fused cyclopentane moiety. Moreover, the products could be further converted into compounds with different functional groups through the well-known transformations. (Figure presented.).

Indium(III)-catalyzed knoevenagel condensation of aldehydes and activated methylenes using acetic anhydride as a promoter

The combination of a catalytic amount of InCl3 and acetic anhydride remarkably promotes the Knoevenagel condensation of a variety of aldehydes and activated methylene compounds. This catalytic system accommodates aromatic aldehydes containing a variety of electron-donating and -withdrawing groups, heteroaromatic aldehydes, conjugate aldehydes, and aliphatic aldehydes. Central to successfully driving the condensation series is the formation of a geminal diacetate intermediate, which was generated in situ from an aldehyde and an acid anhydride with the assistance of an indium catalyst.

A new type of donor-acceptor cyclopropane reactivity: The generation of formal 1,2- and 1,4-dipoles

A new type of donor-acceptor cyclopropane reactivity has been discovered. On treatment with anhydrous GaCl3, they react as sources of even-numbered 1,2- and 1,4-dipoles instead of the classical odd-numbered 1,3-dipoles due to migration of positive charge from the benzyl center. This type of reactivity has been demonstrated for new reactions, namely, cyclodimerizations of donor-acceptor cyclopropanes that occur as [2+2]-, [3+2]-, [4+2]-, [5+2]-, [4+3]-, and [5+4]-annulations. The [4+2]-annulation of 2-arylcyclopropane-1,1-dicarboxylates to give polysubstituted 2-aryltetralins has been developed in a preparative version that provides exceedingly high regio- and diastereoselectivity and high yields. The strategy for selective hetero-combination of donor-acceptor cyclopropanes was also been developed. The mechanisms of the discovered reactions involving the formation of a comparatively stable 1,2-ylide intermediate have been studied. Old ring, new reactivity: A new type of donor-acceptor cyclopropane reactivity has been discovered. On treatment with anhydrous GaCl3, they react as sources of even-numbered 1,2- and 1,4-dipoles instead of the classical odd-numbered 1,3-dipoles owing to the migration of positive charge from the benzyl center.

Selection, synthesis, and anti-inflammatory evaluation of the arylidene malonate derivatives as TLR4 signaling inhibitors

Inhibition of TLR4 signaling is an important therapeutic strategy for intervention in the etiology of several pro-inflammatory diseases. There has been intensive research in recent years aiming to explore this strategy, and identify small molecule inhibitors of the TLR4 pathway. However, the recent failure of a number of advanced drug candidates targeting TLR4 signaling (e.g., TAK242 and Eritoran) prompted us to continue the search for novel chemical scaffolds to inhibit this critical inflammatory response pathway. Here we report the identification of a group of new TLR4 signaling inhibitors through a cell-based screening. A series of arylidene malonate analogs were synthesized and assayed in murine macrophages for their inhibitory activity against LPS-induced nitric oxide (NO) production. The lead compound 1 (NCI126224) was found to suppress LPS-induced production of nuclear factor-kappaB (NF-κB), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and nitric oxide (NO) in the nanomolar-low micromolar range. Taken together, this study demonstrates that 1 is a promising potential therapeutic candidate for various inflammatory diseases.