[Regioselectivity in the dehydrogenation of substituted ethylenediamines as nicotine models].
The direction of dehydrogenation with Hg(II)-EDTA of 2-substituted pyrrolidines and piperidines is examined at the model substances 1-4 featuring a N-(2-amino-2-phenylethyl) substituent, which is able to capture an iminium intermediate. Compounds 1-4 represent mixtures of diastereomers; the separation of 2-phenylpyrrolidine derivative 1 into the racemic diastereomers 1A and 1B is achieved. The oxidation of 1 results in a double dehydrogenation to give the pyrrolizidine amidine 5, which, depending on the work-up conditions is partially hydrolyzed to pyrrolidone 6. The dehydrogenation of the 2-phenylpiperidine compound 2 yields as sole product nearly quantitatively the cyclic amidine 10, which shows no hydrolysis due a minor strain compared to 5. Thus, in both reactions the primary intermediate is the less substituted iminium ion in 5- and 6-position, respectively. On the contrary, the Hg(II)-EDTA treatment of the 2-methylpyrrolidine 3 leads to an electron withdrawal with a different regioselectivity and gives predominantly rise to the angular methylaminal 14. To a minor amount, the azapyrrolizidine 12 is received from the 5-iminium precursor 11. In the oxidation of the 2-methylpiperidine 4, an essentially similar regioselectivity is observed. Besides the angular methylindolizidine 15 as main product, the indolizidine aminal resulting from the less substituted iminium intermediate is due to a favourable steric situation further oxidized to the cyclic amidine 16. The diastereomeric mixtures of the anellated imidazolines 5, 10 and 16 were transfered by boiling with Pd/C in toluene or with activated MnO2 in chloroform to the racemic imidazoles 19-21 in good yields.
Möhrle
H
H
Institut für Pharmazeutische und Medizinische Chemie, Heinrich-Heine-Universittät, Düsseldorf, Germany. h.moehrle@uni-duesseldorf.de
Berlitz
J
J
D000578:Amidines / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry*; D006865:Hydrogenation; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D009538:Nicotine / Q000737:chemistry*; D013237:Stereoisomerism
D000578:Amidines; D000588:Amines; D005029:Ethylenediamines; D009538:Nicotine