3.7- Diazabicyclo nonane conformation

The 3,7-diazabicyclo[3.3.1]nonanes (bispidines) are among the most thoroughly investigated hetero analogs of bicyclo[3.3.1]nonane (1,2). Conformational studies of 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (147) in solution by the dipole moment method, and by H- and 13C-NMR spectroscopy (107,108), have shown a preference for the chair-chair conformation. Semiempirical calculations (EH, CNDO/2) (109) and analysis of the photoelectron spectrum of 147 in combination with three sets of other MO calculations (MINDO/3, MNDO, and ab initio at the STO-3G level) lead to the conclusion that, in the gas phase, 147 exists in the chair-chair conformation (108). 

A flattened CC conformation has been assigned for the 3,7-diazabicyclo[3.3.1]nonan-9-ones 156-159 in (CD3)2SO and in CDC13 on the basis of H-and 13C-NMR, IR, and Raman spectral data (111,114). H-and 13C-NMR studies of compounds 156 and 160-162 in CDC13 solution have confirmed for 156 and shown for 160-162 a flattened chair-chair conformation with the N-substituents in the equatorial position. Additionally, an increase in distortion of the A-alkylpiperidine ring was observed as the size of the JV-substituent was increased (115). 

X-ray studies of a series of 1,5-diphenyl /V,/V -disubstituted derivatives of 3,7-diazabicyclo[3.3.1]nonan-9-one have shown that their conformation depends on whether the lone-pair electron density is delocalized away from the... 

For the unsubstituted diazabicyclo[3.3.1]nonane carbohydrate backbone there are three stable strain energy minimized conformations cc, cb, and bb (see Chart 9). While aU three conformations are free from angular strain, each is to some extent destabilized by nonbonded interactions. 

By H-NMR spectroscopy and dipole measurements, the 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonane (dimethylbispidine) 88 was shown to adopt a cc conformation with flattened wings (108). This was later confirmed by C-NMR spectroscopy and semiempirical molecular orbital (MO) calculations (EH, CNDO/2 the double-chair form was found to be more stable than the cb isomer by --83.8kJmoP and the bb form is even more destablized (133). This preference for cc is not due to solvent or packing effects since 88 has the same conformational preference in the gas phase, as shown by a computational study, which involved a scan of the potential energy surface (PES) and the calculated... 

CDCI3, CCI4, and CS2 only a small amount of free OH groups related to the cc conformer could be detected. However, the spectra in ( 03)280 indicated, that in more polar solvents there is a competitive solute-solvent interaction, which leads to a switch from the cb to the cc form. X-ray data of 3,7-dimethyl-3,7-diazabicyclo[3.3.1]nonan-9-ol 2H20 EtOH have shown that both nitrogen atoms take part in hydrogen bonds, either with water or ethanol, and the molecule adopts a cc conformation. With IR spectroscopy of a water-free crystal, the cb conformation was assigned to the same molecule, and this is stabilized by an intramolecular N H—O bond (136). 

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