One-pot synthesis of (1

Area of Science:

• Organic Chemistry
• Supramolecular Chemistry
• Medicinal Chemistry

Background:

• Aza-crown ethers are versatile macrocyclic compounds with diverse applications.
• Michael addition reactions are fundamental in organic synthesis for C-C bond formation.
• Understanding molecular conformation and hydrogen bonding is crucial for predicting chemical and biological properties.

Purpose of the Study:

• To synthesize and characterize a novel aza-crown ether derivative.
• To investigate the molecular structure, conformation, and crystal packing of the synthesized compound.
• To predict potential biological activities using computational methods.

Main Methods:

• Michael reaction between an aza-crown ether and dimethyl acetylenedicarboxylate.
• Ammonia addition to the reaction mixture.
• Single crystal X-ray diffraction for structural analysis.
• Computational prediction of biological activities using the PASS program.

Main Results:

• Synthesis of compound C30H34N2O9 (4) through a multi-step reaction.
• Determination of the molecular conformation, including bowl-shaped aza-14-crown-4-ether ring and boat-like tetrahydro-pyridine ring.
• Identification of intramolecular hydrogen bonds (N-H⋯O, C-H⋯O) stabilizing the conformation.
• Observation of racemic crystallization with molecules forming chains via N-H⋯O hydrogen bonds.
• Predicted biological activities: 72% anti-allergic, 67% anti-asthmatic, 65% membrane permeability inhibitor.

Conclusions:

• The synthesized aza-crown ether derivative exhibits unique conformational features stabilized by intramolecular hydrogen bonds.
• The compound crystallizes as a racemate with specific intermolecular interactions in the solid state.
• Computational predictions suggest promising therapeutic potential as an anti-allergic, anti-asthmatic agent, and membrane permeability inhibitor.