Investigation of Four Sets of NMR Spectra for One Racemic Compound of Pseudoresonance Structures

A racemic compound,
(S*)-3-[(1R*,3R*)-3-hydroxy-1,3-dihydroisobenzofuran-1-yl]-2-(naphthalen-1-yl)isoindolin-1-one
(3), was synthesized and found to exhibit four distinct
sets of 1H and 13C NMR signals in CDCl3 solution. The four sets of 1H NMR signals displayed relative
integration ratios of approximately 1:1:0.8:0.8. Subsequent PCC oxidation
of 3 yielded racemic (S*)-2-(naphthalen-1-yl)-3-[(R*)-3-oxo-1,3-dihydroisobenzofuran-1-yl]isoindolin-1-one
(5), which showed simplified NMR behavior with only two
sets of 1H and 13C NMR signals (1:1 ratio) in
CDCl3. Interestingly, compound 5 exhibited
two sets of 1H NMR signals in DMSO-d6 that gradually coalesced into a single set upon variable-temperature
NMR analysis (298–353 K). To further investigate the structural
dynamics, racemate 3 was converted to its corresponding
acetate derivative (8) in CHCl3. Notably,
the acetate 8 displayed only two sets of NMR signals
(near 1:0.9 ratio) in CDCl3, contrasting with the original
four sets (1:1:0.8:0.8) observed for compound 3. This
critical observation eliminated the possibility that hemiacetal isomeric
structures were responsible for the NMR multiplicity in CDCl3. These findings suggest that the two sets of 1H NMR signals
with 0.8:0.8 integration ratios originated from two atropisomers with
near 1:1 ratios.

本研究合成了一种外消旋化合物——(S*)-3-[(1R*,3R*)-3-羟基-1,3-二氢异苯并呋喃-1-基]-2-(1-萘基)异吲哚啉-1-酮（3），该化合物在氘代氯仿（CDCl3）溶液中展现出四组独立的氢核磁共振（1H NMR）与碳核磁共振（13C NMR）信号峰。其四组氢核磁共振信号的相对积分面积比约为1:1:0.8:0.8。随后，以氯铬酸吡啶鎓（Pyridinium Chlorochromate，PCC）对化合物3进行氧化反应，得到外消旋产物(S*)-2-(1-萘基)-3-[(R*)-3-氧代-1,3-二氢异苯并呋喃-1-基]异吲哚啉-1-酮（5）；该产物在氘代氯仿溶液中的核磁共振谱图更为简洁，仅呈现两组氢核磁共振与碳核磁共振信号峰，积分比为1:1。值得注意的是，化合物5在氘代二甲亚砜（DMSO-d6）中展现出两组氢核磁共振信号，经变温核磁共振分析（298~353 K）后，两组信号逐渐合并为单一组峰。为进一步探究该化合物的结构动态学行为，我们在三氯甲烷（CHCl3）中将外消旋体3转化为其对应的乙酸酯衍生物（8）。值得关注的是，乙酸酯衍生物8在氘代氯仿中仅呈现两组核磁共振信号峰，积分比接近1:0.9，这与化合物3最初观测到的四组信号峰（积分比1:1:0.8:0.8）形成鲜明对比。这一关键实验结果排除了氘代氯仿溶液中核磁共振信号多重性源于半缩醛异构体结构的可能性。上述研究结果表明，积分比为0.8:0.8的两组氢核磁共振信号峰，源于两组积分比接近1:1的阻转异构体。