Access to Pyridyl-Substituted 1,3,5-Triazines from 4H-Pyrido[1,3]oxazin-4-ones via a Cyclocondensation Process

Abstract

Pyridyl-substituted 1,3,5-triazines were synthesized in good to excellent yields via an unprecedented one-step cyclocondensation of 4H-pyrido[1,3]oxazin-4-ones with amidines at room temperature or under microwave irradiations. The broad applicability was demonstrated by 33 examples with a variety of amidines and three different 4H-pyrido[1,3]oxazin-4-one chemical series. In addition, a one-pot process from 4H-pyrido[1,3]oxazin-4-one precursors (imide sodium salts) was developed and led to the desired triazines compounds, thus allowing a one-step economy in their global synthetic preparation. This approach provides rapid access to pyridyl (or pyridone)-substituted 1,3,5-triazines with high potential in various fields of application.

Chemoselective Access to π‐Conjugated Heterocycles by Stille and Sonogashira Reactions on 2‐Substituted 4H‐Pyrido[e][1,3]oxazin‐4‐ones

“…Unfortunately, none of these structures provided acceptable data to be used as fluorescent dyes. Consequently, to expand the utility of the cross‐coupling of pyridooxazinones and to develop an easy way to access push–pull systems with fluorescent properties, according to our recent published procedure,[8b] we converted 3f and 4c into 2‐hydroxy‐1‐pyridyl‐substituted 1,2,4‐triazoles 6 and 7 , respectively, which are aza analogues of reported 1,2,4‐triazoles possessing electroluminescence properties (Scheme ) . The UV/Vis absorption and fluorescence spectra were recorded and showed promising fluorescence data in DMSO with a large Stokes shift ( λ ex = 370 nm, λ em = 493 nm for triazole 6 ; λ ex = 270 nm, λ em = 515 nm for triazole 7 ).…”

“…In the meantime, we recently reported the first synthesis of 2‐substituted‐4 H ‐pyrido[ e ][1,3]oxazin‐4‐ones 1 , which were identified in 2009 from a calculation study within a list of hundreds of virtually generated heteroaromatic bicyclic ring systems as a new and original chemical series with potential medicinal interest . We also reported full studies on the preparation of halogen‐containing 4 H ‐pyrido[ e ][1,3]oxazin‐4‐ones and their transformations into original hydroxypyridinyl‐substituted 1,2,4‐oxadiazoles, 1,2,4‐triazoles, and 1,3,5‐triazines (Scheme ) . The synthesis of π‐conjugated molecules containing these new classes of compounds may represent an attractive way to develop new fluorescent dyes for bioanalysis and materials science.…”

Oxidative Functionalization of Styrenes: Synthesis of 1,3,5‐triazines from Styrenes via Tandem Cyclization with Amidines

“…However, the former method requires CuI as a catalyst in the presence of pyridine/triethylamine base and the latter methods have been carried out by employing costly Ru‐phosphine complex or Cu(OAc) 2 as a catalyst. [14, 15] Subsequently, there was another report on the synthesis of 1,3,5‐triazines using 4 H ‐pyrido[1,3]oxazin‐4‐ones with amidines . But, this method involves an additional step for the preparation of 4 H ‐pyrido[1,3]oxazin‐4‐ones, thereby decreasing the atom economy and increasing the cost of process (Scheme ).…”

Preparation of Halogen‐Containing 4H‐Pyrido[e][1,3]oxazin‐4‐ones and Their Transformation into 2‐Hydroxypyridinyl‐Substituted 1,2,4‐Oxadiazoles and 1,2,4‐Triazoles

“…We faced the synthetic challenge represented by these new scaffolds, and developed the first synthesis of the 4H-pyrido[e] [1,3]oxazin-4-ones, which used an unprecedented intramolecular O-arylation, and proceeded in good to excellent yields. [11] We also demonstrated the transformation of the pyridooxazinone ring into various hydroxypyridyl-substituted 1,3,5-triazines, [12] and into only one example (R = Ph) of a hydroxypyridyl-substituted 1,2,4-oxadiazole or 1,2,4-triazole in 78 % yield (Scheme 1). [11] Since an halogen substituent is certainly one of the most useful groups for structural modifications, we wish to report here a complete study on the synthesis of halogen-containing 4H-pyrido[e] [1,3]oxazin-4-ones.…”