Synthesis and Confirmation of Azacyclohexanes

Bouchemma, Ahcene (1990) Synthesis and Confirmation of Azacyclohexanes. PhD thesis, University of Glasgow.

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In this thesis, the ring conformations of azacyclohexanes are studied using the 1,3,5-triazacyclohexanes and 3,7-diazabicyclo[3.3.1]nonanes as model structures. A review is presented of the synthesis of mono-, di-, tri- and tetraazcyclohexanes and of studies of their conformations in solution and in the solid state. The synthesis of the 1,3,5-trisubstituted 1,3,5-triazacyclohexanes (106), (107), (108), (110), (111), (112), (113), (114), (115), (116), (118) and (122) has been undertaken by condensation of formalin or paraformaldehyde with the corresponding aryl/alkylamines in an inert solvent, toluene, benzene or ethanol, sometimes with addition of strong base. Compound (117) was formed using the reported reaction of 4-nitroaniline with dimethylsulphoxide in presence of phosphorus pentoxide. Condensation of 2-trifluoromethylaniline with paraformaldehyde and of 4-nitroaniline with formalin gave the N,N'-diaryldiaminomethanes (122) and (123) probably as the result of steric hindrance in the former and decreased nitrogen basicity in the latter. Attempts to prepare the triazacyclohexane (119) by increasing reaction time and temperature gave the 2:1 adduct (122). Condensation of 2-trifluoromethylaniline with DMSO / P2O5 failed to give either (119) or (122). X-ray crystal structure analysis revealed that compounds (106) to (108), (110) to (113), and (114) exist in the solid state as chair conformations in which the nitrogen substituents adopt diaxial-equatorial substituents, whereas, for compounds (115) and (116), the nitrogen substituents are diequatorial-axial. The existence of eight of the ten 1,3,5-triazacyclohexanes studied as the aae conformers is considered to be a manifestation of the rabbit-ear (or generalised anomeric) effect. That the other two 1,3,5-triazacyclohexanes adopt, in the solid state, the aee conformers is most likely the result of crystal packing forces rather than of a major energy difference between the aae and aee conformers. The nitrogen atoms of all ten compounds are pyramidal and the syn-diaxial substituents are displaced apart. The triazacyclohexane (117) as the pyridine solvate adopts a twist-boat conformation with one nitrogen atom planar and the two other nitrogen substituents anti to each other. The diaryldiaminomethane (122) adopts a skewed conformation around the N-CH2 bonds with the trifluoromethyl groups remote from each other. The crystal structure of diaryldiaminomethane (123) was not refined. Compounds (182)-(186) were formed by reaction of the sulphonyl chlorides (RSC2Cl) with diazaadamantanone (144) or the diamine (181). An alternative approach to 3,7-diazabicyclo[3.3.1]nonanes by nucleophilic substitution of tetraiodide (189) by 4-fluoroaniline has led to the monocyclic piperidine (190). In the solid state, 3,7-diazabicyclo [3.3.1]nonanes (182) and (184) were found to adopt a twin-chair conformation with somewhat pyramidal character of the nitrogen atoms. The alternative boat-chair conformation was adopted by (183), and (185) exists in both twin-chair and boat-chair conformations in the solid state. Again, the different conformational preferences are considered to be due to crystal packing forces and not to marked differences in energy between the twin-chair and the boat-chair conformations. The piperidine (190) adopts the chair conformation with N atom pyramidal and with the equatorial orientation on the piperidine ring of all three substituents.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: Organic chemistry
Date of Award: 1990
Depositing User: Enlighten Team
Unique ID: glathesis:1990-78140
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 30 Jan 2020 15:39
Last Modified: 30 Jan 2020 15:39

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