One-Pot Synthesis of 1,3,5-Triazine Derivatives via Controlled Cross-Cyclotrimerization of Nitriles: A Mechanism Approach

• Published in: Journal of organic chemistry 2014-08, Vol.79 (15), p.7012-7024
• Main Authors: Herrera, Antonio, Riaño, Alberto, Moreno, Ramón, Caso, Bárbara, Pardo, Zulay D, Fernández, Israel, Sáez, Elena, Molero, Dolores, Sánchez-Vázquez, Angel, Martínez-Alvarez, Roberto
• Format: Article
• Language: English
• ISSN: 0022-3263; 1520-6904
• DOI: 10.1021/jo501144v

The reaction of equimolecular amounts of a nitrile and triflic anhydride or triflic acid at low temperature produces an intermediate nitrilium salt that subsequently reacts with 2 equiv of a different nitrile at higher temperature to form 2,4-disusbstituted-6-substituted 1,3,5-triazines in moderate to good yields. This synthetic procedure has also been applied to the preparation of a 1,3,5-triazine having three different substituents. The results are explained in terms of a mechanism based on the relative stability of the intermediate nitrilium salts that are formed through a reversible pathway. The formation of a substituted isoquinoline using benzyl cyanide as the second nitrile supports the postulated mechanism as well as the structure of derivatives of the proposed intermediate when the reaction is carried out in the presence of different nucleophiles other than nitriles. Theoretical calculations and the monitoring of the reaction using 1H and 13C NMR spectroscopy are in agreement with the proposed mechanism pathway.