TY - BOOK
T1 - Interrogating Planar Cyclooctatetraenes
T2 - Synthesis and Properties of Hetero[8]circulenes
AU - Hensel, Thomas
PY - 2015
Y1 - 2015
N2 - The present thesis addresses the synthesis, analysis and possible applications of different diazadioxa- and azatioxa[8]circulenes to investigate antiaromaticity of a planar cyclooctatetraene (COT). To achieve this goal, different synthetic strategies were developed, all employing 3,6-dihydroxycarbazoles as precursors. The most promising pathway involved a direct dimerization of benzylated 3,6-dihydroxycarbazole, followed by a debenzylation and substitution of the pyrrole nitrogen, realized in a small amount of steps and with great yields. The substituents introduced through this pathway included ortho and para aniline, pyridine (also methylated), 1-bromopropyl, 1-bromobutyl, allyl, dimethylbutylamine and trimethylbutylammonium moieties. With the dibenzyl circulene formation, a trimeric structured side product was isolated. It consisted of a circulene with a tert-butyl group replaced by a furan bound carbazole, giving the trimer a helical structure. On the basis of the investigations on oxidative dimerizations of 3,6-dihydroxycarbazoles and previous mechanistic studies by Erdman and Högberg on 1,4-benzqoquinone condensations, the mechanisms of the formation of azatrioxa- and diazadioxa-[8]circulenes were established. The antiaromaticity of the formal COT core of the hetero[8]circulenes was interrogated by comparison of the respective 13C-NMR carbon shifts with those of 3,6-dimethoxycarbazole (the starting material), tetrahydroxy intermediate and literature values. No uniform paratropic (antiaromatic) ring-current influence on the chemical shift values was visible. In addition to that, a comparison of bond-lengths derived from single crystal X-ray structure showed slight alternations (1.40-1.43 Å) in the COTs of azatrioxa- and diazadioxa[8]circulenes. All investigated COT cores therefore partially fulfilled the structural criterion of antiaromaticity requiring a strict alternation of bond lengths (Δ ≥ 0.1 Å). ortho Dianiline substituted diazadioxa[8]circulene (forms two atropisomers) was selected as a host to bind ligands for the investigation of the COT core, however the pursued covalent and non-covalent approaches were not successful. In an application oriented research project, water soluble hetero[8]circulenes have been investigated by temperature dependent CD spectroscopy regarding their ability to stabilize DNA G-quadruplexes. The data did not indicate any stabilization of G-quadruplex DNA, but the findings led to a short investigation of the aggregation behavior of diazadioxa[8]circulenes in water.
AB - The present thesis addresses the synthesis, analysis and possible applications of different diazadioxa- and azatioxa[8]circulenes to investigate antiaromaticity of a planar cyclooctatetraene (COT). To achieve this goal, different synthetic strategies were developed, all employing 3,6-dihydroxycarbazoles as precursors. The most promising pathway involved a direct dimerization of benzylated 3,6-dihydroxycarbazole, followed by a debenzylation and substitution of the pyrrole nitrogen, realized in a small amount of steps and with great yields. The substituents introduced through this pathway included ortho and para aniline, pyridine (also methylated), 1-bromopropyl, 1-bromobutyl, allyl, dimethylbutylamine and trimethylbutylammonium moieties. With the dibenzyl circulene formation, a trimeric structured side product was isolated. It consisted of a circulene with a tert-butyl group replaced by a furan bound carbazole, giving the trimer a helical structure. On the basis of the investigations on oxidative dimerizations of 3,6-dihydroxycarbazoles and previous mechanistic studies by Erdman and Högberg on 1,4-benzqoquinone condensations, the mechanisms of the formation of azatrioxa- and diazadioxa-[8]circulenes were established. The antiaromaticity of the formal COT core of the hetero[8]circulenes was interrogated by comparison of the respective 13C-NMR carbon shifts with those of 3,6-dimethoxycarbazole (the starting material), tetrahydroxy intermediate and literature values. No uniform paratropic (antiaromatic) ring-current influence on the chemical shift values was visible. In addition to that, a comparison of bond-lengths derived from single crystal X-ray structure showed slight alternations (1.40-1.43 Å) in the COTs of azatrioxa- and diazadioxa[8]circulenes. All investigated COT cores therefore partially fulfilled the structural criterion of antiaromaticity requiring a strict alternation of bond lengths (Δ ≥ 0.1 Å). ortho Dianiline substituted diazadioxa[8]circulene (forms two atropisomers) was selected as a host to bind ligands for the investigation of the COT core, however the pursued covalent and non-covalent approaches were not successful. In an application oriented research project, water soluble hetero[8]circulenes have been investigated by temperature dependent CD spectroscopy regarding their ability to stabilize DNA G-quadruplexes. The data did not indicate any stabilization of G-quadruplex DNA, but the findings led to a short investigation of the aggregation behavior of diazadioxa[8]circulenes in water.
UR - https://rex.kb.dk/primo-explore/fulldisplay?docid=KGL01009188025&context=L&vid=NUI&search_scope=KGL&tab=default_tab&lang=da_DK
M3 - Ph.D. thesis
BT - Interrogating Planar Cyclooctatetraenes
PB - Department of Chemistry, Faculty of Science, University of Copenhagen
ER -