Understanding the nucleophilic character and stability of the carbanions and alkoxides of 1-(9-anthryl)ethanol and derivatives.

The nucleophilic character and stability of the carbanions vs. alkoxides derived from 2,2,2-trifluoro-1-(9-anthryl)ethanol and 1-(9-anthryl)ethanol containing X electron-releasing and X electron-acceptor substituents attached to C-10, have been studied at the B3LYP/6-31+G(d,p) level of theory. Results analyzed in terms of the absolute gas-phase acidity, Fukui function, the local hard and soft acids and bases principle, and the molecular electrostatic potential, show that the central ring of the 9-anthryl group confers an ambident nucleophilic character and stabilizes the conjugated carbanion by electron-acceptor delocalization.

Influence of fluorine atoms and aromatic rings on the acidity of ethanol.

Absolute gas-phase acidities Delta(acid)G(0)(OH) and Delta(acid)G(0)(CH) were calculated at the B3LYP and MP2 levels using six different standard basis sets for the OH and CH heterolytic bond cleavage of ethanol and twelve derivatives of the type CH(3-n)F(n)CHX(r)OH, where n ranges from zero to three and represents the number of fluorine atoms and r represents hydrogen and the type of aromatic ring, namely: X(0) = hydrogen, X(1) = phenyl, X(2) = 1-naphthyl, and X(3) = 9-anthryl. The similarity between calculated and experimental Delta(acid)G(0)(OH) values for ethanol (1a), 2-fluoroethanol (1b), 2,2-difluoroethanol (1c), 2,2,2-trifluoroethanol (1d), and 1-phenylethanol (2a) was used to validate the right theoretical method for this study. Substituent partial contributions to hydroxyl-, methylene-, and methine-hydrogen acidities were evaluated by linear combination. Good parameter fittings of the primary and secondary alcohols were obtained and interpreted as additive contribution of the substituent effects. The nonlinear contributions were identified. Calculations prove that fluoroalcohols exhibit C-H acidity, which is usually lower than O-H acidity. In principle, the inversion of this acidity order is possible by the introduction of a large aromatic ring instead to increase the number of fluorine atoms.

Synthesis, NMR and crystallographic studies of 2-substituted dihydroquinazolinones derived from (S)-phenylethylamine.

2,3-Dihydro-3-[(S)-1-phenethyl]quinazolinone and some new 2-substituted derivatives bearing isopropyl, o-nitrophenyl and p-nitrophenyl groups were prepared in 40-90% yield by amidation of isatoic anhydride with (S)-phenylethylamine, followed by condensation with triethyl orthoformate, isopropylaldehyde, o-nitro- and p-nitro-benzaldehyde, respectively. The two 2-subtituted dihydroquinazolinones obtained either by using isopropylaldehyde, o-nitro- or p-nitrobenzaldehyde, were separated and purified before their NMR spectra in CDCl3 solutions were recorded. The detection of the low energy conformation of O=C-N-phenethyl segment in solution allowed the correlation of the NMR data with the configuration of newly stereogenic carbon C-2; thus, one diastereomer was labeled SS while the other was RS. Configurations determined by the NMR method were corroborated by X-ray diffraction analysis. X-ray structures of each diastereomeric series showed characteristic conformational types: a propeller-like for the SS and a hairpin for the RS series. Interatomic distances of the hairpin conformation suggest the existence of intramolecular face-to-face interactions between two aromatic rings.

Determination of enantiomeric composition of (-)-(R)-2-tert-butyltetrahydroimidazolidin-4-one by polarimetry, 1H NMR, and chiral SFC.

Partial resolution of rac-2-tert-butyltetrahydroimidazolidin-4-one was carried out by recrystallization of diastereomeric salts. The enantiomeric composition of enriched samples was estimated by polarimetry, (1)H NMR, and chiral SFC. Enantiomeric composition estimated by polarimetry or by (1)H NMR was directly proportional to that estimated by chiral SFC. The occurrence of solute self-association in chloroform was detected through measurements of optical and specific rotation at variable concentration of (-)-(R)-2-tert-butyltetrahydroimidazolidin-4-one. Our data suggest that solute self-association in chloroform might be independent of enantiomeric composition.

Synthesis and NMR configurational analysis of 1,3-imidazolidin-4-ones derived from (-)-(S)-phenylethylamine.

The preparation and NMR study in the solution state of (-)-(S)-1-acetyl-3-(phenylethyl)-1,3-imidazolidin-4-one, (-)-(2R,1'S)- and (+)-(2S,1'S)-1-acetyl-2-tert-butyl-3-(phenylethyl)-1,3-imidazolidin-4-one, and (-)-(2S,1'S)- and (+)-(2R,1'S)-1-carboethoxy-2-tert-butyl-3-(phenylethyl)-1,3-imidazolidin-4-one are described. The orientations of acetyl, carboethoxy, and phenethyl groups attached to nitrogen atoms N-1 and N-2 were deduced from the proton and (13)C chemical shifts. The typical orientation of phenethyl group, which has the hydrogen H-6 syn and close to the oxygen of carbonyl C-4, was observed in (-)-(S)-1-acetyl-3-(phenylethyl)-1,3-imidazolidin-4-one but not in the other four compounds; nevertheless, interpretation of chemical shifts based on the ring current effects correlated with the true configuration of the new stereogenic center at C-2. Four of these imidazolidinones were analyzed by X-ray diffraction to corroborate the configuration determined by NMR. The structures determined by X-ray diffraction revealed the existence of intramolecular hydrogen bonds capable to control the conformation of the phenethyl and acyl groups in the solution state.