Solid state structural relation and binary melting phase diagram of (S-) and racemic 2-(2-nitro-1-phenylethyl)-1,3-diphenyl-propane-1,3-dione

In this work, anchoring of cinchona derivatives to trifunctional cores (hub approach) was demonstrated to obtain size-enlarged organocatalysts. By modifying the cinchona skeleton in different positions, we prepared four C3-symmetric size-enlarged cinchona derivatives (hub-cinchonas), which were tested as organocatalysts and their catalytic activities were compared with the parent cinchona (hydroquinine) catalyst. We showed that in the hydroxyalkylation reaction of indole, hydroquinine provides good enantioselectivities (up to 73% ee), while the four new size-enlarged derivatives resulted in significantly lower values (up to 29% ee) in this reaction. Anchoring cinchonas to trifunctional cores was found to facilitate nanofiltration-supported catalyst recovery using the PolarClean alternative solvent. The C3-symmetric size-enlarged organocatalysts were completely rejected by all the applied membranes, whereas the separation of hydroquinine was found to be insufficient when using organic solvent nanofiltration. Furthermore, the asymmetric catalysis was successfully demonstrated in the case of the Michael reaction of 1,3-diketones and trans-β-nitrostyrene using Hub3-cinchona (up to 96% ee) as a result of the positive effect of the C3-symmetric structure using a bulkier substrate. This equates to an increased selectivity of the catalyst in comparison to hydroquinine in the latter Michael reaction.

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“…Retention time for (R)-18: 19.2 min, for (S)-18: 26.1 min. Spectroscopic data are fully consistent with those reported in the literature[61].…”

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confidence: 89%

Synthesis of C3-Symmetric Cinchona-Based Organocatalysts and Their Applications in Asymmetric Michael and Friedel–Crafts Reactions

et al. 2021

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“…Based on these experimentally measured values, a theoretical equilibrium phase diagram of melting phenomena in the racemic – enantiomeric system of amlodipine can be created based on the assumed validity of simplified Schröder‐van Laar equation combined with — because of 1:1 racemate — Prigogine–Defay–Mauser equation (Figure 12). 48,49 …”

Section: Resultsmentioning

confidence: 99%

“…Based on these experimentally measured values, a theoretical equilibrium phase diagram of melting phenomena in the racemicenantiomeric system of amlodipine can be created based on the assumed validity of simplified Schröder-van Laar equation combined with because of 1:1 racemate -Prigogine-Defay-Mauser equation (Figure 12). 48,49 The melting point of racemic amlodipine is approximately 34 C higher than that of enantiomeric ones, what means a large thermodynamic driving force of formation reaction toward racemic amlodipine and reflects high thermal stability of the latter one, as well.…”

Section: Calculation Of the Equilibrium Melting Phase Diagram In The ...mentioning

confidence: 99%

Enantiomeric separation of racemic amlodipine by sequential fractional crystallization through formation of diastereomeric salt solvates and co‐crystals of solvate‐like compounds with specific structure — A tandem resolution

et al. 2021

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A new resolution method of racemic amlodipine has been developed. The racemic compound is reacted in a suitable solvent with 0.25-mol equivalent of (R,R)-tartaric acid. After the decomposition of the diastereomeric salt, the remaining racemic fraction is precipitated with half-equivalent of fumaric acid, and the pure amlodipine enantiomer is obtained. A quarter equivalent of the same resolving agent, (R,R)-tartaric acid has been also added to the mother liquor to obtain the other enantiomer. The advantage of this method is that both of the enantiomers of amlodipine could be obtained with high enantiomeric excess with the same resolving agent. The racemic excess can also be isolated and re-resolved. Achiral reagents (urea and thiourea) have been added to the resolving agent. These neutral additives are incorporated as co-crystals in the structure of the diastereomeric salts. The used solvate-former solvents and achiral additives are structurally similar, and their presence can enable the fractional separation of the diastereomers. In addition, the racemate, the enantiomers, and some intermediate salts with high diastereomeric excess obtained in the resolution process of amlodipine have been also subjected to thermal (DSC, TG/DTA-EGA-MS, and -FTIR), analytical (FTIR spectroscopic), and structural (XRD) comparisons, which indicate that the key-intermediate crystalline diastereomeric salts-as solvates and co-crystals-inherit a kind of structural similarity from their related additives-solvents (DMF, DMAA, and DMSO) or (thio)ureas, respectively.

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The squaramide-catalyzed asymmetric Michael/cyclization tandem reaction for the synthesis of chiral trifluoromethylated hydroxyimino tetrahydrobenzofuranones

et al. 2016

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An enantioselective synthesis of trifluoromethylated hydroxyimino tetrahydrobenzofuranones has been developed. 1,3-Dicarbonyl carbocyclic compounds react with β-CF3-β-disubstituted nitroalkenes in the presence of a chiral squaramide catalyst, providing efficient access to diverse hydroxyimino tetrahydrobenzofuranones featuring a trifluoromethyl group at the C3-position of an all-carbon quaternary stereocenter with good yields (up to 81%) and enantioselectivities (up to 89% ee).

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Solid state structural relation and binary melting phase diagram of (S-) and racemic 2-(2-nitro-1-phenylethyl)-1,3-diphenyl-propane-1,3-dione

Cited by 5 publications

References 13 publications

Synthesis of C3-Symmetric Cinchona-Based Organocatalysts and Their Applications in Asymmetric Michael and Friedel–Crafts Reactions

Synthesis of C3-Symmetric Cinchona-Based Organocatalysts and Their Applications in Asymmetric Michael and Friedel–Crafts Reactions

Enantiomeric separation of racemic amlodipine by sequential fractional crystallization through formation of diastereomeric salt solvates and co‐crystals of solvate‐like compounds with specific structure — A tandem resolution

The squaramide-catalyzed asymmetric Michael/cyclization tandem reaction for the synthesis of chiral trifluoromethylated hydroxyimino tetrahydrobenzofuranones

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