Syntheses based on anabasine. Preparation and transformations of N-oxides

Abstract

The oxidation of N acetyl and N benzoylanabasine with the tert butyl hydroperoxide (TBHP)-МoCl 5 system or МCРBA proceeds selectively at the nitrogen atom of the pyridine ring. The oxidation of N methylanabasine under similar conditions gives a mixture of stereo isomeric N oxides at the piperidine nitrogen atom, their ratio depending on the reagent used. The oxidation of anabasine by TBHP-МoCl 5 or МCРBA is accompanied by dehydrogenation and results in anabaseine N oxide. The reactions of anabasine and anabaseine pyridine N oxides with acetic anhydride were investigated. The substituted 1H 3 pyridin 2 ones were prepared. 2 pyridone, N acetylpiperidyl 2 pyridone, anabasein 3 one.Anabasine, 3 (2 piperidyl)pyridine (1), is the princi pal alkaloid of the Anabasis aphylla L. plant. 1 Anabasine hydrochloride is used as a means for giving up smoking; 2 the mechanism of its action includes binding to nicotine sensitive receptors. The anabasine base exhibits clear cut physiological activity. The action of this alkaloid is due to affection of the H cholinoreactive structures of various parts of the nervous system and violation of the mem brane permeability of cells, which results in a faulty course of redox processes in the organism. 3 Anabasine is an initial base in the synthesis of revers ible and irreversible choline esterase inhibitors, 4 in par ticular, phosphamide, 5 carbamide derivatives, 6 and a number of pharmacologically valuable compounds ob tained by reactions at the piperidine ring nitrogen atom. 7,8 Anabasine derivatives containing bulky acyl and alkyl sub stituents at the piperidine ring nitrogen atom exert an antinicotinic action, 9 and its hydrogenated derivatives ex hibit analgesic activities. 10 Thus, targeted synthetic transformations of anabasine may produce effective analogues with other types of physi ological activities.This paper describes a study of the oxidation of ana basine (1) and its N acetyl (2), N benzoyl (3) and N methyl (4) derivatives on treatment with tert butyl hydroperoxide (TBHP) and МCРBA and some transfor mations of the N oxides thus formed. Results and DiscussionPreviously, 11 we demonstrated that anabasine oxida tion with hydrogen peroxide in acetic acid is accompa nied by cleavage of the piperidine ring. No N oxidation of anabasine or its derivatives 2-4 by other reagents has yet been carried out. We found that refluxing of anabasine (1) in the presence of the TBHP-MoCl 5 system in benzene with water removal gives crystalline anabaseine N oxide (5) in 54% yield (Scheme 1). Thus, the hydroperoxide serves as a dehydrogenating agent. The oxidation of N acetyl (2) or N benzoylanabasine (3) under the ac tion of TBHP-MoCl 5 affords individual N acetyl and N benzoylanabasine pyridine N oxides 6 and 7 in 79 and 89% yields, respectively. It should be emphasized that previously, this reagent has been successfully used for N oxidation of diverse pyridine derivatives. 12-14 The use of VO(acac) 2 as the catalyst proved inefficient. The at tempted N oxidation of anabasine derivatives 2 and ...

Oxidation of C–H bonds to CO bonds by O2 only or N-oxides and DMSO: synthesis of Δ1-bipyrrolinones and pyrrolino[3,2-b]pyrrolinones from 2,6-diazasemibullvalenes

“…Moreover, without the aid of Lewis acids, NSBV 1a could also be highly efficiently oxidized by DMSO at 90 1C. Both the methylene and the carbonyl carbon of 8a showed their respective singlets at d = 44.88 and 200.43 ppm in the 13 C NMR spectrum in CDCl 3 , while the methylene CH 2 also clearly showed two doublets at d = 2.89 and 3.00 ppm in the 1 H NMR spectrum.…”

“…Both the 1 H and 13 C NMR spectra of 2a clearly showed its symmetrical structure. The imine and the carbonyl carbons of 2a showed the respective singlets at d = 177.72 and 197.98 ppm in the 13 C NMR spectrum in CDCl 3 . 1,5-Bridged NSBVs 1 bearing different alkyl or aryl substituents could also be applied in this oxidation reaction, affording their corresponding D 1 -bipyrrolinones 2a-h in good to excellent isolated yields.…”

“…As far as we know, few synthetic methods of dihydropyridone derivatives were reported. 13 Although insertion of carbene 12 into a C-C bond of three or four-membered cyclic ketones has been reported, insertion of 12 into the C-C bond of less-strained fivemembered carbocycles is rarely known and suffered from low yields. 12 Thus, our results showed that the fused-ring skeleton of D 1 -bipyrrolinones has higher reactivity.…”