The conformational diastereomers of 5-substituted-5H-6-chlorodibenzo[a,c]cycloheptene

Abstract

Conformational diastereomers of 5-substituted-5H -6-chlorodibenzo[a,c]cycloheptene 1 are observed at room temperature in solution. Empirical force field and the AM1 semi-empirical quantum mechanics calculations indicate that the conformation of the cycloheptatriene ring in 1 is a boat (B) form. In the B form, the C-5 substituent can be oriented in equatorial (e) and axial (a) directions. The e-a interchange involves inversion of the biphenyl moiety in the range of 14.1-17.7 kcal mol Ϫ1 , determined by 1 H-NMR band shape analysis. The free energy difference between the e-a forms is not reproduced by the AM1 calculations. The e-a equilibrium in derivatives of 1 depend on the solvent polarity: for 1i the e-a ratio in CDCl 3 (28 : 72) changes to (55 : 45) in DMSO-d 6 .The conformational space of the flexible side chains in all mono-substituted compounds except 1k is searched by molecular mechanics and the AM1 semi-empirical method and the relative heats of formation of all rotamers are considered in estimation of the e-a ratio. Many of the rotamers show an internal hydrogen bond calculated by the AM1 method. The diethylamino derivative of 1 (1l) was found just in the e form. The preferred conformation of 1h in the solid state was found by X-ray crystallography of a single crystal to be e with a strong OH ؒ ؒ ؒ N internal hydrogen bond in the side chain. Dissolution of the 1h single crystals at low temperature and recording the 1 H-NMR spectrum at Ϫ60 ЊC show that assignment of the e form as the dominant one at room temperature for 1h is justified.

New Bioactive Prenylflavonoids and Dibenzocycloheptene Derivative from Roots of Dendrolobium lanceolatum

“…The structure of 4 was also confirmed by X-ray analysis (Figure ). A few 5H-dibenzocycloheptene derivatives have been reported as synthesis products. , This is the first dibenzocycloheptene derivative from a natural source.

2 ORTEP diagram of the crystal structure of compound 4 .

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“…A few 5H-dibenzocycloheptene derivatives have been reported as synthesis products. 18,19 This is the first dibenzocycloheptene derivative from a natural source.…”

The stereochemistry of the stable conformational diastereomers in substituted dihydrodibenzo[ef,kl]heptalenes, the doubly bridged biphenyls. Synthesis, structural elucidation and barrier to conformational diastereomerismElectronic supplementary information (ESI) available: Tables I–III comparing X-ray structural data for 2Aendo–exo, 1Aendo–exo and 1Aexo–exo with AM1 calculations. See http://www.rsc.org/suppdata/p2/b1/b109336n/

“…Conversion of 1A endo-endo to 1A exo-exo was followed by 1 H-NMR by following the changes in signal intensities. (19), 273 (21), 245 (17), 244(95), 236 (12), 213 (25), 202 (18), 201 (15), 200 (18), 161 (9), 149(4), 142 (7), 111(3), 100(3), 97 (2)…”

“…[18][19][20] Recently we have found a new, 2,2Ј-bridged biphenyl system in which the diastereomeric conformers are observed by 1 H-NMR spectroscopy in solution at room temperature. 21 The barrier to conformational conversion should be raised by double bridging of the biphenyl moiety at the 2,2Ј and 6,6Ј positions such that the conformational diastereomers would be stable enough to be separated and studied. In the present paper we report on the synthesis, separation, structural elucidation and barrier to diastereomeric conversion in substituted dihydrodibenzo-[ef,kl]heptalenes.…”

The conformational diastereomers of 7-substituted-(8Z)-8-chloro-6,7-dihydro-9-(1,2-dihydro-6-R-naphthalen-4-yl)-2-R-5H-benzo[7]annulene, the question of atropisomerism versus ring inversion

“…It is expected that the difference in the chemical shift of pseudo equatorial and pseudo axial protons to be about 0.4 to 0.7 ppm as reported previously. 5,6 The ratio of the two forms in CDCl 3 and DMSO-d 6 could be derived directly from the 1 H-NMR spectra. The free energy between the two conformers (∆G°) is calculated by using the equilibrium constant taken as the ratio of the major/minor ( Table 6).…”