Iodine/Copper(I)‐Catalyzed Direct Annulation of N‐Benzimidazolyl Amidines with Aldehydes for the Synthesis of Ortho‐Fused 1,3,5‐Triazines

Abstract

A direct annulation reaction of N-benzimidazolyl amidines with aldehydes has been established and allows the synthesis of ortho-fused 1,3,5-triazine derivatives. The N-benzimidazolyl amidine substrates are readily accessible by the addition of 2-aminobenzimidazoles to the corresponding nitriles. In the presence of molecular iodine and copper iodide, cyclization of benzimidazolyl amidines with various aldehydes in toluene under reflux followed by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) gives the corresponding products. In this reaction, iodine acts more as a Lewis acid catalyst than as an oxidant. This synthetic process is insensitive to air and operationally simple, and provides facile access to a variety of novel 1,3,5-triazino[1,2-a]benzimidazoles and related heterocycles.

Concise Pyrimido[4,5‐d]pyrimidine Synthesis via Direct Annulation of N‐Uracil Amidines with Benzaldehydes Under Transition Metal Free Conditions

“…A plausible reaction mechanism for the formation of pyrimido[4,5‐ d ]pyrimidines ( 3 ) is shown in Scheme . Initially, the aza‐diene 4 is formed in situ from the condensation reaction of N ‐uracil amidine ( 1 a ) with benzaldehyde ( 2 a ) . The intramolecular [4+2] cycloaddition reaction of 4 is followed by [1,5]‐hydrogen shift to form the intermediate 5,6‐dihydropyrimido[4,5‐ d ]pyrimidine 4 a , which on oxidation by molecular oxygen yields the desired product 3 a .…”

“…The requisite amidine substrates can be easily prepared using a Pinner approach, starting from the corresponding nitriles and ammonia, and allowing installation of R at C7 position. Very recently, Chang and co‐workers have utilized CuI/I 2 mixture as catalyst, N,N ‐dimethylglycine as a ligand and DDQ as oxidant for the similar annulation reaction between N ‐benzimidazolyl amidines and aldehydes for the synthesis of ortho ‐fused 1,3,5‐triazines . In this condensation type reaction a stoichiometric oxidant is required.…”

“…Moreover, catalyst‐free synthetic methods, have attracted much attention because of their lower cost, mild conditions, reduced pollution and ease of purification. Therefore, in comparison to the previous methods our approach is operationally simpler, more environment friendly and does not require transition metal catalyst or ligand besides providing facile access to a variety of novel pyrimido[4,5‐ d ]pyrimidines. All these aspects make our approach attractive from sustainability point of view.…”

Bicyclic 5-6 Systems With One Bridgehead (Ring Junction) Nitrogen Atom: Four Extra Heteroatoms 2:2

“…The latter would cyclize in the presence of a catalytic amount of copper (I) and iodine through complex 333 to build dihydrotriazine 334 followed by oxidation with 2,3dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) (Scheme 71). 129…”

DBU mediated one-pot synthesis of triazolo triazines via Dimroth type rearrangement

“…Various synthetic methods have been reported for the C-N bond formation by employing different starting materials [13][14][15] via oxidative cyclisation, 16 high temperature condition [17][18][19] and/ or metal-catalysed reactions. 20 However, the current reported protocols were environmentally unfriendly as they suffered from drawbacks such as, multistep, and tedious procedures, use of carcinogenic solvents, high-temperature, expensive and toxic metal-catalysts, and other hazardous reagents.…”