Intramolecular Cyclization with Oxocarbenium Ion. Synthesis of 1-Azabicyclo[3.3.1]nonene and [3.2.1]octene Derivatives

Sólyom, Sándor; Ábrahám, Gizella; Szöllõsy, Márta; Pallagi, István; Csuzdi, Emese; Vitalis, B.; Horvath, K.; Horvath, Edit; Hársing, László G.; Kajtár, Judit

doi:10.3987/com-94-6975

Cited by 7 publications

(2 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The compound was synthesized in the frame of extended research work (21,22,68) with azabicyclic compounds, originally aimed at finding muscarinic ligands. The synthesis of the compound is summarized in Fig.…”

Section: Chemistrymentioning

confidence: 99%

See 1 more Smart Citation

The Pharmacology of GYKI‐46 903, a New Cognition Enhancer

Vitalis¹,

Bakonyi²,

Csillik-Perczel³

et al. 1995

CNS Drug Reviews

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Chemistrymentioning

confidence: 99%

“…The absolute configuration of (+)-7 was determined on the corresponding ketone by CD spectroscopy (68). The correct stereochemistry of GYKI-46 903 is indicated in the name and the formula.…”

Section: Chemistrymentioning

confidence: 99%

The Pharmacology of GYKI‐46 903, a New Cognition Enhancer

Vitalis¹,

Bakonyi²,

Csillik-Perczel³

et al. 1995

CNS Drug Reviews

Self Cite

View full text Add to dashboard Cite

show abstract

ChemInform Abstract: Intramolecular Cyclization with the Oxocarbenium Ion. Synthesis of 1‐ Azabicyclo(3.3.1)nonene and (3.2.1)octene Derivatives.

Sólyom¹,

Ábrahám²,

Szoellosy³

et al. 1995

ChemInform

View full text Add to dashboard Cite

show abstract

Synthesis of 1‐azabicyclo[3.3.1]nonadienes by intramolecular cyclization of 1‐(3‐oxo‐2‐phenylbutyl)tetrahydropyridines

Sólyom¹,

Pallagi²,

Ábrahám³

et al. 1995

Liebigs Ann./Recl.

View full text Add to dashboard Cite

Intramolecular cyclization reactions were performed with 1-(3-0~0-2-phenylbutyl)-1,2,5,6-tetrahydropyridine derivatives 6a-h in sulfuric acid to give 3,6-diphenyl-substituted 1-azabicyclo(3.3. llnonadienes 9. The intermediate carbinols 7a-f and 8b, c could be isolated. Carrying out the reaction in methanesulfonic acid stereoselectivity was found in the formation of carbinols with preferential production of derivatives 7 . Some of the compounds 9 show remarkable dopamine uptake inhibition.As a part of our research program on new memory-enhancing agents various substituted 1-azabicyclic derivatives were synthesized by intramolecular electrophilic cyclization between differently generated oxocarbenium and a conjugated C=C bond, because several 1-azabicyclic systems are known to show affinity to either the m~scarinic[~l of 5HT3 receptorL5I. Later, among the different types of compounds synthesized other activities were found as well. Thus, e. g. some 4,6-diaryl-substituted 1 -azabicyclo-[3.3.l]nona-3,6-dienes (e. g. 2 in Scheme 1) show remarkable antifungal and antibacterial effects[*]. Cationic cyclization between a benzylic cation and a conjugated C=C bond afforded another type Scheme 2 Y 4% 4% 8b.e 6a-h 7a-f ~~ of diaryl-substituted 1-azabicyclononenes where one of the aryl groups is in 3-position to the bridgehead nitrogen atomr61. Scheme 1 1 (R=H,Me, n=l) 2 (R=H. Me, n=1) 5 (X=H, CI) 3 (R=H, n=O) (R=H. n=O)From different structure-activity considerations we expected from this substitution pattern, involved in an azabicyclic ring system, dopamine uptake inhibitory potential. Therefore the synthesis of diaryl-substituted I-azabicyclo[3.3. llnonadines 9 (Scheme 2) was aimed at.Our previous work suggested that rac-N-(3-oxo-3-phenylpropyl or -phenacyl)-substituted tetrahydropyridine derivatives of type 1 or 3 (X = H, halogen, methyl, methoxy, nitro; Y = H, m-or phalogen, methyl) can be cyclized with strong mineral acids in a modified Prins reaction to give azabicyclic derivatives 2 or 4 re-~pectively[~.~.'] (Scheme 1). We assume that the protonated carbonyl group provides an oxocarbenium ion, which is responsible for the electrophilic attack on the conjugated double bond. We also con-clude that the oxocarbenium ion, stabilized by the adjacent phenyl group, is required for a successful ring closure, because no cyclization could be observed with ketone S'].Nevertheless, the success with the Prins-type cyclizations of 1 and 3 prompted us to try the same reaction with ketones 6 to obtain the desired 3,6-diphenyl-substituted 1-azabicyclo[3.3. llnona-3,6-dienes 9 (Scheme 2). When compounds 1 were treated with about 80% sulfuric acid the expected azabicyclic dienes 9 were formed in moderate yield. As a consequence of the reaction conditions, additional sulfonation occurred on the dialkoxy-substituted 3-phenyl group in derivatives 9g, h. According to the 'H-NMR spectra of the latter compounds the site of the sulfonation is the less hindered ortho-phenyl position and the compounds exist in solution as 1 : 1 mixture of two rot...

show abstract

Intramolecular Cyclization with Oxocarbenium Ion. Synthesis of 1-Azabicyclo[3.3.1]nonene and [3.2.1]octene Derivatives

Cited by 7 publications

References 0 publications

The Pharmacology of GYKI‐46 903, a New Cognition Enhancer

The Pharmacology of GYKI‐46 903, a New Cognition Enhancer

ChemInform Abstract: Intramolecular Cyclization with the Oxocarbenium Ion. Synthesis of 1‐ Azabicyclo(3.3.1)nonene and (3.2.1)octene Derivatives.

Synthesis of 1‐azabicyclo[3.3.1]nonadienes by intramolecular cyclization of 1‐(3‐oxo‐2‐phenylbutyl)tetrahydropyridines

Contact Info

Product

Resources

About