Conformation and crystal structures of 1-aminocyclohexaneacetic acid (β3,3Ac6c) in N-protected derivatives

Abstract

N-Protected derivatives of 1-aminocyclohexaneacetic acid (β3,3-Ac6c), namely Valeroyl-β3,3-Ac6c-OH [2-(1-pentanamidocyclohexyl)acetic acid, C13H23NO3], (I), Fmoc-β3,3-Ac6c-OH [2-(1-{[(9H-fluoren-9-yloxy)carbonyl]amino}cyclohexyl)acetic acid, C23H25NO4], (II), and Pyr-β3,3-Ac6c-OH {2-[1-(pyrazine-2-amido)cyclohexyl]acetic acid, C13H17N3O3}, (III), were synthesized and their conformational properties were determined by X-ray diffraction analysis. The backbone torsion angles (ϕ, θ) for β3,3-Ac6c-OH are restricted to gauche conformations in all the derivatives, with a chair conformation of the cyclohexane ring. In the crystal structure of (I), the packing of molecules shows both carboxylic acid R22(8) O—H...O and centrosymmetric R22(14) N—H...O hydrogen-bonding interactions, giving rise to chains along the c-axis direction. In (II), centrosymmetric carboxylic acid R22(8) O—H...O dimers are extended through N—H...O hydrogen bonds and together with inter-ring π–π interactions between Fmoc groups [ring centroid distance = 3.786 (2) Å], generate a layered structure lying parallel to (010). In the case of compound (III), carboxylic acid O—H...Npyrazine hydrogen bonds give rise to zigzag ribbon structures extending along the c-axis direction.

Keywords

• crystal structure
• disubstituted-β-amino acids
• π–π interaction
• hydrogen bonds
• conformation