1H NMR spectroscopy in the study of the three-dimensional structure of 7-alkoxyalkyl-3-thia-7-azabicyclo-[3.3.1]nonan-9-ones and some of their derivatives

Abstract

H NMR spectroscopy was used to establish that 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]nonan-9-onesand their decarbonylated derivatives in deuterochloroform solution exist in the double chair conformation. The predominantly formed secondary alcohols isomers have preferred double chair conformation with the hydroxyl group equatorial relative to the plane of the piperidine ring. On the other hand, the epimeric alcohols have predominant boat-chair conformation; the piperidine ring takes the boat form due to intramolecular hydrogen bonding between the unshared electron pair of the nitrogen atom and hydroxyl group proton.Keywords: 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]non-9-one and its derivatives, conformational analysis, 1 H NMR spectra.The study of the three-dimensional structure of bicyclic compounds containing important biogenic elements such as oxygen, nitrogen, and sulfur holds interest not only in regard to the search for new physiologically active compounds but also for the development of conformational analysis and stereochemistry. We have described the synthesis of a series of 7-alkoxyalkyl-3-thia-7-azabicyclo[3.3.1]non-9-ones, their deoxygenated derivatives, and derived secondary alcohols [1]. In the present work, we have determined the three-dimensional structure of these compounds using high resolution 1 H NMR spectroscopy. We studied ketones 1-5 with various substituents at the nitrogen atom, their reduced analogs 6-10, and secondary alcohols 11-14. The chemical shifts and coupling constants for the individual stereoisomers isolated from alcohols 11 and 12 were used to interpret the rather complex spectra of alcohols 13 and 14, each of which is a mixture of two isomers that could not be separated.Bicyclo[3.3.1]nonanes and their 3,7-dihetero analogs exist in solution as one of four forms: double chair (cc), chair-boat (cb), boat-chair (bc), and double boat (bb) or as a mixture in conformational equilibrium [2]. The predominant configuration is determined not only by the overall electronic and steric factors within these __________________________________________________________________________________________

Synthesis, Structure, and Biological Activity of Novel Bispidine Derivatives

“…The interest of chemists in the study of heteroanalogs of bicyclo [3.3.1] nonane is due to the unique properties of these compounds, which makes them valuable from a theoretical and practical point of view [1][2][3][4][5][6][7][8][9][10]. It is also known that methylenecyclopropane residue is a valuable structural unit of bioactive compounds, particularly, opiate antagonists [11,12].…”

“…It is also known that methylenecyclopropane residue is a valuable structural unit of bioactive compounds, particularly, opiate antagonists [11,12]. 1-(3-Isopropoxypropyl-and 3-ethoxypropyl-)-4-oxopiperidine (1,2) as starting substrates was used to obtain the target bispidines (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14) according to Fig. 1.…”

“…Monitoring of the progress of the reaction was carried out by TLC on alumina. The structure of bispidinone derivatives (3)(4)(5)(6)(7)(8)(9)(10) was determined by nuclear magnetic resonance (NMR) and infrared (IR) spectroscopies.…”

“…2.1 g (42% of theory) of 3-cyclopropanmethyl-7-(3-ethoxypropyl)-3,7diazabicyclo[3.3.1]nonane(6) was obtained in the form of a light yellow oil with R f =0.34 (Al 2 O 3 , benzene:isopropanol = 7:1).Found, %: C 72.32, Н 11.12, N 10.65. C 16 H 30 N 2 O.…”

Unusual Conformational Behavior of 3,7-Dihetera(N,N-;N,O-;N,S-) Bicyclo[3.3.1]Nonan-9-Ols Via Nmr Analysis

“…Spatial structures of a few selected bicyclic compounds containing heteroatoms as sulfur, oxygen, and nitrogen have only been partially examined by spectroscopic methods. [4][5][6][7][8][9][10] Certain peculiarities of conformational behavior of 3,7-dihetera(N,N-; N,O; N,S-)bicyclo-[3.3.1]nonane-9-ols in CDCl 3 solutions have been revealed in the present work via 1 H NMR analysis. To illustrate, the proton spectra were obtained and evaluated for 3,7-di- (3-…”