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

Conformational diastereomers of 5-substituted-5H-6-chlorodibenzo[a,c]cycloh eptene 1 are observed at room temperature in solution. Empirical force fiel d and the AM1 semi-empirical quantum mechanics calculations indicate that t he conformation of the cycloheptatriene ring in 1 is a boat (B) form. In th e 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 moiet y in the range of 14.1-17.7 kcal mol(-1), determined by H-1-NMR band shape analysis. The free energy difference between the e-a forms is not reproduce d by the AM1 calculations. The e-a equilibrium in derivatives of 1 depend o n the solvent polarity:for 1i the e-a ratio in CDCl3 (28:72) changes to (55 :45) in DMSO-d(6).The conformational space of the flexible side chains in a ll mono-substituted compounds except 1k is searched by molecular mechanics and the AM1 semi-empirical method and the relative heats of formation of al l rotamers are considered in estimation of the e-a ratio. Many of the rotam ers show an internal hydrogen bond calculated by the AM1 method. The diethy lamino derivative of 1 (1l) was found just in the e form. The preferred con formation 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 inthe side chain. Dissolution of the 1h single crystals at low temperature and r ecording the H-1-NMR spectrum at -60 degreesC show that assignment of the e form as the dominant one at room temperature for 1h is justified.