2-(4-Hy-droxy-phen-yl)acetamide.

Area of Science:

• Crystallography
• Organic Chemistry
• Computational Chemistry

Background:

• The title molecule, C8H9NO2, is an isomer of acetaminophen (N-(4-hydroxyphenyl)acetamide).
• Understanding the conformational preferences and intermolecular interactions of such isomers is crucial in crystal engineering and drug design.

Purpose of the Study:

• To determine the solid-state structure of the C8H9NO2 isomer.
• To investigate the orientation of the acetamide group relative to the phenyl ring.
• To analyze the hydrogen bonding network and compare the experimental structure with theoretical predictions.

Main Methods:

• Single-crystal X-ray diffraction analysis was performed to elucidate the molecular and crystal structure.
• Density Functional Theory (DFT) calculations were employed for *in vacuo* geometry optimization.
• A survey of existing crystal structures of related 4-substituted 2-phenyl-acetamide derivatives was conducted.

Main Results:

• The acetamide group plane is nearly perpendicular (dihedral angle of 89.95°) to the phenyl ring plane, with the -NH2 group directed outward.
• This observed orientation contrasts with the *in vacuo* DFT optimized geometry, where the -NH2 group is directed inward.
• The extended crystal structure features N-H⋯O hydrogen bonds organizing molecules into stacks along the [100] direction, with additional inter-stack hydrogen bonding.

Conclusions:

• The solid-state structure exhibits a distinct acetamide group orientation compared to theoretical predictions.
• Intermolecular hydrogen bonding plays a significant role in dictating the crystal packing and molecular arrangement.
• The study highlights the variability in acetamide group orientation in 4-substituted 2-phenyl-acetamide derivatives, influenced by crystal packing forces.