The conformational behaviour of 4,4a,5,6,7,8-hexahydropyrido[1,2-d] [1,3,4]oxadiazine derivatives studied by NMR spectroscopy and molecular mechanics

Ari Rosling, Matti Hotokka, Karel D. Klika, F. Fülöp, Reijo Sillanpää, Jorma Mattinen

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The diastereomers (1'R*,2R*)- and (1'S*,2R*)-1-amino-2-(1'-hydroxypiperidinebenzyl) and 1-amino-2-(1-hydroxy-1,1-diphenylmethyl) piperidine have been synthesized and transformed into the corresponding 4,4a,5,6,7,8-hexahydropyrido[1,2d][1,3,4]oxadiazines. Similarly to the unsubstituted parent compound 2-phenylhexahydropyrido[1,2d][1,3,4]oxadiazine, both the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines were found to be predominantly in the trans-annellated conformation. This was concluded from low temperature NMR measurements, the chemical shift differences of the methylene protons adjacent to the bridged nitrogen, or the ΔH° values derived from ab initio calculations. In 2,4,4-triphenylhexahydropyrido[1,2-d][1,3,4]oxadiazine the conformational preference was switched to a slight predominance of the cis N-in conformation (53%). The conformational preference in the solid state for the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines was the same as in solution. The 15N chemical shifts of the bridgehead nitrogens were found to correlate to some extent with the conformational preference, while no correlation was observed between the geminal coupling constant of the methylene protons adjacent to the bridgehead and the adopted ring annellation.

Original languageEnglish
Pages (from-to)213-221
Number of pages9
JournalActa Chemica Scandinavica
Volume53
Issue number3
Publication statusPublished - Mar 1999

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Molecular mechanics
Chemical shift
Nuclear magnetic resonance spectroscopy
Conformations
Protons
Nitrogen
Derivatives
Nuclear magnetic resonance
Hydrogen
Temperature
piperidine

ASJC Scopus subject areas

  • Chemical Engineering(all)

Cite this

The conformational behaviour of 4,4a,5,6,7,8-hexahydropyrido[1,2-d] [1,3,4]oxadiazine derivatives studied by NMR spectroscopy and molecular mechanics. / Rosling, Ari; Hotokka, Matti; Klika, Karel D.; Fülöp, F.; Sillanpää, Reijo; Mattinen, Jorma.

In: Acta Chemica Scandinavica, Vol. 53, No. 3, 03.1999, p. 213-221.

Research output: Contribution to journalArticle

Rosling, Ari ; Hotokka, Matti ; Klika, Karel D. ; Fülöp, F. ; Sillanpää, Reijo ; Mattinen, Jorma. / The conformational behaviour of 4,4a,5,6,7,8-hexahydropyrido[1,2-d] [1,3,4]oxadiazine derivatives studied by NMR spectroscopy and molecular mechanics. In: Acta Chemica Scandinavica. 1999 ; Vol. 53, No. 3. pp. 213-221.
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abstract = "The diastereomers (1'R*,2R*)- and (1'S*,2R*)-1-amino-2-(1'-hydroxypiperidinebenzyl) and 1-amino-2-(1-hydroxy-1,1-diphenylmethyl) piperidine have been synthesized and transformed into the corresponding 4,4a,5,6,7,8-hexahydropyrido[1,2d][1,3,4]oxadiazines. Similarly to the unsubstituted parent compound 2-phenylhexahydropyrido[1,2d][1,3,4]oxadiazine, both the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines were found to be predominantly in the trans-annellated conformation. This was concluded from low temperature NMR measurements, the chemical shift differences of the methylene protons adjacent to the bridged nitrogen, or the ΔH° values derived from ab initio calculations. In 2,4,4-triphenylhexahydropyrido[1,2-d][1,3,4]oxadiazine the conformational preference was switched to a slight predominance of the cis N-in conformation (53{\%}). The conformational preference in the solid state for the (4R*,4aR*)- and the (4S*,4aR*)-2,4-diphenylhexahydropyrido[1,2-d][1,3,4]oxadiazines was the same as in solution. The 15N chemical shifts of the bridgehead nitrogens were found to correlate to some extent with the conformational preference, while no correlation was observed between the geminal coupling constant of the methylene protons adjacent to the bridgehead and the adopted ring annellation.",
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