Fast Equilibrium in N-(Ethoxycarbonyl)-r-2,c-7-diphenylhexahydro-1,4-diazepin-5-ones in Flattened Boat Conformations

Abstract

The preferred conformations of three N-ethoxycarbonyl derivatives of r-2,c-7-diphenylhexahydro-1,4-diazepin-5-ones 9-11 have been studied using NMR spectral techniques. The N(1),N(4)-bis(ethoxycarbonyl)-r-2,c-7-diphenylhexahydro-1,4-diazepin-5-ones 9 and 10 were found to prefer flattened boat conformations with fast equilibrium between two N-CO rotamers while 4-(ethoxycarbonyl)-t-3-isopropyl-r-2,c-7-diphenylhexahydro-1,4-diazepin-5-one (11) was found to prefer a chair conformation with the N-COOEt group locked in one rotameric state. Dynamic (1)H NMR studies have been carried out on the N(1),N(4)-bis(ethoxycarbonyl) derivatives 9 and 10, and the barriers for the N-CO rotation were found to be 49.9 and 58.0 kJ mol(-1), respectively. These barriers are much lower than those observed for N-nitroso- and N-formyl-r-2,c-7-diphenylhexahydro-1,4-diazepin-5-ones (90.0 and 84.4 kJ mol(-1), respectively), indicating a fast equilibrium in 9 and 10 at room temperature.

A Twist on Facial Selectivity of Hydride Reductions of Cyclic Ketones: Twist-Boat Conformers in Cyclohexanone, Piperidone, and Tropinone Reactions

“…Previous studies on cis-2,6-disubstituted N -acylpiperidones have indicated that the chair conformation with equatorial 2- and 6-substituents is unstable. 9g , 15 The resulting A 1,3 -strain between the 2,6-diequatorial and the N-substituents disfavors such a conformation, and instead these substituents exist in an axial (or pseudoaxial) orientation in conformation 6 ch . Indeed, our calculations show that the energy penalty for placing these two groups equatorial is 6.1 kcal mol –1 relative to 6 ch (see Supporting Information ).…”

Synthesis, characterization and stereochemistry of N-acyl-r-2,c-4-bis(4-methoxyphenyl)-3-azabicyclo[3.3.1]nonanes

“…The conformational http://dx.doi.org/10.1016/j.molstruc.2015.03.052 0022-2860/Ó 2015 Elsevier B.V. All rights reserved. equilibria in N-nitroso and N-acyl-3-azabicyclo[3.3.1]nonanes have also been studied [11][12][13][14][15][16]. In all these compounds, A 1,3 -strain [17] plays a major role in deciding the preferred conformation.…”

Molecular structures and conformations of three 3-azabicyclononanes

“…The azabicyclononanes derived from primary amines and aldehydes are found to be potential antitumour agents (Jeyaraman & Avila, 1981). In order to throw some more light on these antitumour agents, a series of aza bicyclic ring compounds have been synthesized (Jeyaraman & Ponnuswamy, 1997) and studied by using crystallographic methods. The crystal and molecular structures of 7-tert-butyl-N-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonane (MTABN), N-acetyl-2,4-diphenyl-3aza-bicyclo[3.3.1]nonane (AABN) and N-methyl-2,4bis(2-methylphenyl)-3-azabicyclo[3.3.1]nonan-9-ol (MH-ABN) are reported herein.…”