Synthesis of 3-(Alkylamino)-, 3-(Alkoxy)-, 3-(Aryloxy)-, 3-(Alkylthio)-, and 3-(Arylthio)-1,2,4-triazines by Using a Unified Route with 3-(Methylsulfonyl)-1,2,4-triazine

In our attempts to synthesize 3‐(alkylthio)‐ and 3‐(alkoxy)‐1,2,4‐triazines without substituents at the 5‐ or 6‐position, the synthesis of their anticipated precursor 3‐(methylsulfonyl)‐1,2,4 triazine was also optimized. The reactivity of 3‐(methylsulfonyl)‐1,2,4‐triazine towards alkyl and aryl thiols, primary and secondary alkylamines, phenols, and alcohols was explored, and the reactions were optimized to maximize the isolation of the corresponding 3‐substituted 1,2,4‐triazine. Good yields were obtained for the products of the reactions with all of the aforementioned nucleophiles, with the exception of alcohols, by using alkali metal carbonates. Higher yields of 3‐(alkoxy)‐1,2,4‐triazines were obtained by using the appropriate magnesium alkoxide as the nucleophile. The studies herein focus on our efforts to optimize the synthesis of 3‐(methylsulfonyl)‐1,2,4‐triazine and also determine the reaction conditions that use this heterocycle in SNAr reactions with a variety of sulfur‐, oxygen‐, and nitrogen‐containing nucleophiles.