Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095, USA.
Chemistry. 2022 Jan 10;28(2):e202103135. doi: 10.1002/chem.202103135. Epub 2021 Dec 4.
The 4-anilino-6,7-ethylenedioxy-5-fluoroquinazoline scaffold is presented as a novel model system for the characterization of the weak NH⋅⋅⋅F hydrogen bonding (HB) interaction. In this scaffold, the aniline NH proton is forced into close proximity with the nearby fluorine (d ∼2.0 Å, ∠∼138°), and a through-space interaction is observed by NMR spectroscopy with couplings ( J ) of 19±1 Hz. A combination of experimental (NMR spectroscopy and X-ray crystallography) and theoretical methods (DFT calculations) were used for the characterization of this weak interaction. In particular, the effects of conformational rigidity and steric compression on coupling were investigated. This scaffold was used for the direct comparison of fluoride with methoxy as HB acceptors, and the susceptibility of the NH⋅⋅⋅F interaction to changes in electron distribution and resonance was probed by preparing a series of molecules with different electron-donating or -withdrawing groups in the positions para to the NH and F. The results support the idea that fluorine can act as a weak HB acceptor, and the HB strength can be modulated through additive and linear electronic substituent effects.
4-苯胺基-6,7-亚乙基二氧基-5-氟喹唑啉结构被提出作为一种新型模型体系，用于研究弱 NH⋯⋯F 氢键（HB）相互作用的特性。在这个支架中，苯胺 NH 质子被迫与附近的氟原子非常接近（d ∼2.0 Å，∠∼138°），通过 NMR 光谱观察到通过空间相互作用，耦合（ J ）为 19±1 Hz。实验（NMR 光谱和 X 射线晶体学）和理论方法（DFT 计算）的组合用于研究这种弱相互作用的特性。特别是，研究了构象刚性和空间位阻对耦合的影响。该支架用于直接比较氟化物和甲氧基作为 HB 受体，并通过制备一系列在 NH 和 F 对位具有不同供电子或吸电子基团的分子，研究了 NH⋯⋯F 相互作用对电子分布和共振变化的敏感性。结果支持了氟原子可以作为弱 HB 受体的观点，并且可以通过加和线性电子取代基效应来调节 HB 的强度。
