Les synthèses assistées par un heterocycle

Tout comme un atome d’halogène ou un groupe diazonium, certaines entités hétérocycliques neutres ou chargées peuvent jouer le rôle de groupe partant et donc être considérées comme de précieux auxiliaires de synthèse, pour autant que :
  1. L’hétérocycle de départ soit bon marché et facilement disponible;
  2. Le dérivé hétérocyclique puisse être préparé avec un excellent rendement;
  3. L’auxiliaire hétérocyclique puisse être facilement déplacé;
  4. La molécule cible puisse être isolée avec un excellent rendement et soit difficilement accessible par une autre méthode;
  5. L’auxiliaire hétérocyclique puisse être facilement recyclé.



De nombreux dérivés du benzotriazole et des sels de pyridinium satisfont ces conditions.

Le benzotriazole est un acide faible (pKa ~ 8, comme la penta-2,4-dione); il réagit facilement, entre autres, avec un aldéhyde et une amine dans une réaction à trois composants pour fournir un aminal pour lequel un équilibre avec les formes chargées correspondantes peut être considéré. Une réaction subséquente avec un nucléophile est accompagnée du déplacement de l’anion benzotriazole et conduit, de la sorte, à une amine fortement substituée. Comme démontré par A.R. Katritzky et al., ceci est seulement l’un des nombreux exemples des possibilités offertes par la chimie du benzotriazole.



En 1987, E. Anders and J. Tropsch (Bull. Soc. Chim. Belges, 96, 719 – 720, 1987) ont décrit la première synthèse de chlorures de N-(1-chloroalkyl)pyridinium chlorides à partir de pyridine, d’aldéhydes et de chlorure de thionyle. Nous avons ensuite prouvé que ces sels représentent d’intéressantes formes activées des aldéhydes précurseurs. Soulignons, parmi les multiples exemples que nous avons étudiés, la préparation d’esters de Hantzsch (1,4-dihydropyridines, N-substituées ou non) et la synthèse directe de benzimidazoles, imidazopyridines et périmidines, sans la nécessité d’utiliser un agent oxydant extérieur.


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  • 1,4-Diarylpiperazine and Analogs as Anti-tubercular Agents: Synthesis and Biological Evaluation. D. Forge, D. Cappoen, J. Laurent, D. Stanicki, A. Mayence, T.L. Huang, L. Verschaeve, K. Huygen, J.J. Vanden Eynde. Eur. J. Med. Chem., 49, 95 (2012)
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  • New Methodologies for the Preparation of Drugs and their Metabolites. Application to 1,4-Dihydropyridines structurally related to Calcium Channel Modulators of the Nifedipine™-type. J.J. VANDEN EYNDE, A. MAYENCE. Int. J. Med. Biol. Environm., 28, 89 (2000).
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