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Reactivity and Synthetic Applications of 4,5-Dicyanopyridazine: An Overview†
Laboratorio di Progettazione, Sintesi e Studio di Eterocicli Biologicamente Attivi (HeteroBioLab), Dipartimento di Chimica, Università di Firenze, Polo Scientifico e Tecnologico, Via della Lastruccia 3/13, I-50019 Sesto Fiorentino, Italy
† Dedicated to Prof. Rodolfo Nesi on the occasion of his 70th anniversary.
* Author to whom correspondence should be addressed.
Received: 28 December 2009; in revised form: 12 February 2010 / Accepted: 5 March 2010 / Published: 12 March 2010
Abstract: Despite the poor reputation of electron-deficient pyridazines in intermolecular Hetero Diels-Alder (HDA) reactions, 4,5-dicyanopyridazine (DCP) showed a surprising reactivity as a heterocyclic azadiene in inverse electron-demand HDA processes with different dienophiles. The use of alkenes, alkynes and enamines as 2p electron counterparts afforded dicyanocyclohexa-1,3-dienes and substituted phthalonitriles, respectively, while the use of suitable bis-dienophiles provides a general strategy for the one-pot synthesis of polycyclic carbo- and hetero-cage systemsthrough pericyclic three-step homodomino processes. HDA reactions with heterocyclic dienophiles allowed direct benzoannelation: in particular, pyrrole and indole derivatives were converted to dicyano-indoles and -carbazoles. In addition an unprecedented reactivity of DCP as a very reactive heterocyclic electrophile at the C-4 carbon was also evidenced: by changing the experimental conditions, cyanopyrrolyl- and cyanoindolyl-pyridazines were obtained through reactions of pyrrole and indole systems as carbon nucleophiles in formal SNAr2 processes where a CN group of DCP acts as leaving group. Thus, careful control of the reaction conditions allows exploitation of both pathways for the synthesis of different classes of heterocyclic derivatives.
Keywords: pyridazine derivatives; Hetero Diels-Alder reactions; nucleophilic aromatic substitutions; cage compounds; phthalonitriles
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Alfini, R.; Cecchi, M.; Giomi, D. Reactivity and Synthetic Applications of 4,5-Dicyanopyridazine: An Overview. Molecules 2010, 15, 1722-1745.
Alfini R, Cecchi M, Giomi D. Reactivity and Synthetic Applications of 4,5-Dicyanopyridazine: An Overview. Molecules. 2010; 15(3):1722-1745.
Alfini, Renzo; Cecchi, Marco; Giomi, Donatella. 2010. "Reactivity and Synthetic Applications of 4,5-Dicyanopyridazine: An Overview." Molecules 15, no. 3: 1722-1745.