Neuvonen K, Fülöp F, Neuvonen H, Koch A, Kleinpeter E, Pihlaja K
Department of Chemistry, University of Turku, FIN-20014 Turku, Finland.
J Org Chem. 2001 Jun 15;66(12):4132-40. doi: 10.1021/jo001114w.
Substituent effects on the stabilities of the ring and chain forms in a tautomeric equilibrium of five series of 2-phenyloxazolidines or -perhydro-1,3-oxazines possessing nine different substitutions at the phenyl moiety have been studied with the aid of 13C NMR spectroscopy and PM3 charge density and energy calculations. Reaction energies of the isodesmic reactions, obtained from the calculated energies of formation, show that electron-donating substituents stabilize both the chain and ring tautomers but the effect is stronger on the stability of the chain form than on that of the ring form. The 13C chemical shift changes induced by the phenyl substituents (SCS) were analyzed by several different single and dual substituent parameter approaches. The best correlations were obtained by equation SCS = rhoFsigmaF + rhoRsigmaR. In all cases the rhoF values and in most cases also the rhoR values were negative at both the C=N and C-2 carbons, indicating a reverse behavior of the electron density. This concept could be verified by the charge density calculations. The 13C chemical shifts of the C=N and C-2 carbons show a normal dependence on the charge density (q(tot)), but the charge density shows a reverse dependence on substitution. Correlation analysis of the 13C chemical shifts, solvent effect (CDCl3 vs DMSO-d6) on the NMR behavior as well as the effect of substituents on the electron densities and on the stabilities of the ring and chain tautomers show that the substituent dependence of the relative stability of the ring and chain tautomers in equilibrium is governed by several different electronic effects. At least intramolecular hydrogen bonding between the imine nitrogen and the hydroxyl group as well as polarization of the C=N bond seem to contribute in the chain form. Stereoelectronic and electrostatic effects are possible to explain the increase in stability of the ring form by electron-donating substituents.
借助13C核磁共振光谱、PM3电荷密度和能量计算，研究了在苯基部分具有九种不同取代基的五系列2-苯基恶唑烷或-全氢-1,3-恶嗪的互变异构平衡中，取代基对环式和链式结构稳定性的影响。从计算得到的生成能量得出的等键反应的反应能量表明，给电子取代基使链式和环式互变异构体都稳定，但对链式结构稳定性的影响比对环式结构稳定性的影响更强。通过几种不同的单取代和双取代参数方法分析了苯基取代基引起的13C化学位移变化（SCS）。通过方程SCS = rhoFsigmaF + rhoRsigmaR得到了最佳相关性。在所有情况下，C=N和C-2碳处的rhoF值以及在大多数情况下的rhoR值均为负，表明电子密度的反向行为。这一概念可以通过电荷密度计算得到验证。C=N和C-2碳的13C化学位移显示出对电荷密度（q(tot)）的正常依赖性，但电荷密度显示出对取代的反向依赖性。对13C化学位移、NMR行为的溶剂效应（CDCl3与DMSO-d6）以及取代基对电子密度和环式与链式互变异构体稳定性的影响进行的相关性分析表明，平衡中环式和链式互变异构体相对稳定性的取代基依赖性受几种不同的电子效应支配。至少亚胺氮与羟基之间的分子内氢键以及C=N键的极化似乎对链式结构有贡献。立体电子效应和静电效应可能解释了给电子取代基使环式结构稳定性增加的原因。
