Intramolecular hydrogen bonds in 1,4-dihydropyridine derivatives

Area of Science:

• Organic Chemistry
• Spectroscopy
• Computational Chemistry

Background:

• 1,4-Dihydropyridine (1,4-DHP) derivatives are important in medicinal chemistry.
• Understanding their structural properties, including hydrogen bonding, is crucial for their applications.

Purpose of the Study:

• To synthesize and characterize novel 1,4-DHP derivatives.
• To investigate the presence and nature of intramolecular hydrogen bonds (NH⋯O=C and CH⋯O=C) within these derivatives.
• To elucidate the impact of these hydrogen bonds on molecular structure and spectroscopy.

Main Methods:

• Synthesis of 1,4-DHP derivatives.
• Characterization using Nuclear Magnetic Resonance (NMR) spectroscopy (¹H, ¹³C, ¹⁵N).
• Variable temperature ¹H NMR experiments.
• Secondary proton/deuterium ¹³C isotope shift analysis.
• Quantum-chemical calculations.

Main Results:

• Successful synthesis and characterization of 1,4-DHP derivatives.
• Establishment of intramolecular NH⋯O=C and CH⋯O=C hydrogen bonds.
• NMR data (downfield NH proton shift, upfield ¹⁵N shift) and infrared spectroscopy (higher NH stretching wavenumber) indicate N-H bond shortening.
• Increased ¹J(¹⁵N,¹H) coupling constants further support N-H bond strengthening/shortening.

Conclusions:

• Intramolecular hydrogen bonds are confirmed in the synthesized 1,4-DHP derivatives.
• These hydrogen bonds significantly influence the electronic and structural properties, particularly the N-H bond length.
• The combined spectroscopic and computational evidence provides a comprehensive understanding of hydrogen bonding in 1,4-DHP systems.