Exploring Phthalimide as the Acid Component in the Passerini Reaction
Jingyao Li, Qiang Zheng, Alexander Dömling*
*Czech Advanced Technology and Research Institute, Palackı University in Olomouc, 779 00 Olomouc,
Czech Republic, Email: alexander.domling
upol.cz
J. Li, Q. Zheng, A. Dömling, Org. Lett., 2024, 26, 829-833.
DOI: 10.1021/acs.orglett.3c03962
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Abstract
Phthalimide moieties can react in the Passerini reaction as acid componentd. The phthalimide moiety stands out as a favorable building block due to its oxidative stability, heat-stable characteristics, and resistance to solvents. Incorporating NH-based acid components in multicomponent reactions addresses the ongoing need for the development of innovative molecular scaffolds.
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cleavage of phthalimides
General procedure for the synthesis of alcohols:
A 5 mL microwave vial equipped with a magnetic stirring bar was charged with aldehyde (1.0 mmol, 1.0 equiv), phthalimide or its derivative (1.0 mmol, 1.0 equiv) and isocyanide (1.0 mmol, 1.0 equiv) in 2mL DCM at room temperature. The vial was sealed with a cap containing a septum and subjected to metal block heating at 80 °C till completion of reaction (reaction monitored by TLC). The solvent was removed under reduced pressure and residue was purified by silica gel flash chromatography using EtOAc-hexane as eluent on to afford the titled product.
General procedure for the synthesis of 3a:
A 5 mL microwave vial equipped with a magnetic stirring bar was charged with an aldehyde (1.0 mmol, 1.0 equiv), phthalimide or its derivative (1.0 mmol, 1.0 equiv) and isocyanide (1.0 mmol, 1.0 equiv) in 2mL DCM at room temperature. The vial was sealed with a cap containing a septum and subjected to metal block heating at 80 °C till completion of reaction (reaction monitored by TLC). The reaction was cooled to room temperature. 2mL THF and NH2NH2·H2O (65μL, 1.05 mmol, 1.05 equiv) were added to the reaction, sequentially. After 1 h, the reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by silica gel flash chromatography using DCM-MeOH as eluent on to afford the titled product.
General procedure for the synthesis of 4a:
A 5 ml microwave vial equipped with a magnetic stir bar was added with product 1d (195mg, 0.5 mmol, 1.0 equiv) and hydrazine hydrate (62 μL, 1.0 mmol, 2.0 equiv) in 2ml DCM/THF(1:1), the mixture was stirred under room temperature for 2 h and then 0.25mL 4 N HCl in dioxane (2.0 equiv) was added to the mixture. The mixture was extracted with EtOAc and then purified by silica gel flash chromatography using EtOAc-hexane as eluent to afford the product 4a.
Key Words
ID: J54-Y2024
