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

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.