Z–E Isomerism of 5‐cyclohexylmethylenehydantoins

Abstract

Singapore 5-Cyclohexylmethylenehydantoin and its 1-and 3-methyl derivatives were studied as the aliphatic analogues of the 5benzylidenehydantoins to examine the effects of replacing a benzene by a cyclohexane ring on Z-E isomerism. The relative stabilities of the Zand E-isomers were compared by estimating the free energy differences from thermal equilibration experiments and the heats of formation by AM1 calculation. I n the Z-isomers, the possible existence of weakly attractive interaction between the C(4) = 0 and C(6b-H groups, which form parts of a stereochemically favourable, conjugated a,B-unsaturated system, is suggested as a contributory factor to the observed configurational preference. Assignment of configurations was based mainly on N M R and is supported by IR and UV spectra. N M R spectra also revealed the conformation of the cyclohexane ring and the cyclohexyl proton signals were assigned by double resonance and by high-field N M R in two solvents where solubility allows.

The structure of hydantoins in solution and in the solid state

“…The relative proton chemical shift of the vinyl proton H-6 also proved most diagnostic of the E/Z configuration of the 5-cyclohexyl-methylene-hydantoins 7-10 (Scheme 5) [26]; for 7 and 8, as expected, the Z isomer was found to be preferred, while for 9 and 10 the reverse was observed, both in agreement with the results obtained for 1-6 (Table II). The preferred conformation of the cyclohexane chair with respect to the exo-methylene-hydantoin moiety was additionally estimated both from detailed proton NMR studies and AM I quantum chemical calculations [26].…”

“…Tan et al [9,[25][26][27][28][29][30][31], Ivin et al [32], Korohoda [33], and Kleinpeter et al [15] studied the E/Z isomerism of 5-arylmethylene- [15,[29][30][31], 2-(hydantoin-3-yl)-crotonate [34], 5-pyridylmethylenc- [27], 5-cyclohexylmethylcn- [26], and 5-thienyl(5-furyl)methylenehydantoins [25] (Scheme 2). In order to assign in solution the tH chemical shifts of the vinyl proton, N(1)--H and the ortho-phenyl protons were employed [28]: the anisotropy effect of the 4-carbonyl group deshields the vinyl proton H-6 in the Z isomer; for the same reason, the ortho-phcnyl protons of the E isomer are more deshielded than the corresponding ones in the Z isomer.…”

“…Orthosubstituents at the benzene ring increase this twist up to 46 ~ [15,29]. The E/Z isomerism of the pyridyl (Scheme 4), thienyl, furyl, and crotonyl analogues was assigned by employing the same proton chemical shifts [26,28,34] and the NH stretching vibrations [27]; in addition, the Z isomers of the hydantoins with 2-or 3-pyridyl rings prefer an s-cis conformation (due to intramolecular hydrogen bonding), whereas the E isomers prefer an s-trans conformation (Scheme 4 for 2-pyridyl analogues) due to repulsion between the lone pairs on the pyridyl nitrogen and on the C-4 carbonyl oxygen [28].…”

“…The preferred conformation of the cyclohexane chair with respect to the exo-methylene-hydantoin moiety was additionally estimated both from detailed proton NMR studies and AM I quantum chemical calculations [26].…”

Salt contribution to the flexibility of single‐stranded nucleic acid of finite length

“…24 The PB theory is a mean-field theory that ignores ion-ion correlations, which can be important for multivalent ions, e.g., Mg 21 . [32][33][34] The DH theory, characterized by a screened Coulomb potential between charged particles, is the linearized analytical form of PB equation, and thus applicable to the case of relatively weak electrostatic field and monovalent ion solution. Recently, to account for the effects of ion correlation and ion-binding fluctuation, a tightly bound ion (TBI) model was developed.…”