Heteroarylamination and Heteroarylsulfidation of 2-Chloro-1-azaazulenes

Heteroarylamination and heteroarylsulfidation of 2-chloro-1-azaazulenes (1) were investigated. Palladium catalyzed coupling of 2-amino-1-azaazulenes (2) with 1 underwent to give bis(1-azaazulen-2-yl)amine derivatives in good yields, but the reaction of 2-mercapto-1-azaazulenes (4) with 1 did not give good results in the same conditions. The reaction of 4 with 1 under basic conditions gave bis(1-azaazulen-2-yl) sulfide derivatives in good yields. Heteroarylamino-substitution was proceeded on the reaction of 4-amino-3-mercapto-4H-1,2,4-triazoles (6) with 1 in BuOH under reflux, whereas heteroarylsulfido-substitution was proceeded on the reaction of 6 with 1 in the presence of NaH in dioxane. The chemistry of azaazulenes is of interest for their physiological properties as well as physical and chemical properties. Aryl amines have a potential functionality in pharmaceutical drug candidates, therefore Pd-catalyzed amination of aryl halides has attracted attention. Recently, we reported that heteroarylaminatition of ethyl 2-chloro-1-azaazulene-3-carboxylate proceeded well by Pd-catalyzed amination. In the extension of the chemistry, we examined the reaction of 2-chloro-1-azaazulenes with 2-amino-1-azaazulenes, mercapto-1-azaazulenes, and 4-amino-3-mercapto-4H-1,2,4-triazoles. Treatment of 2-chloro-1-azaazulene (1a) with 2-amino-1-azaazulene (2a) in the presence of Pd2(dba)3, Xantphos, and Cs2CO3 in dioxane under reflux for 4 h gave bis(1-azaazulen-2-yl)amine (3aa) in 39% yield. The H NMR spectrum of 3aa was symmetrical and the C NMR spectrum showed 9 signals; this showed that heteroarylamination occurred at amino group at C-2, and not at N-1 of 1-azaazulene nuclei. Similar treatment of 1b, 1c, and 1d with 2a and 2b gave 3ba (70%), 3ca (63%), and 3db (43%), respectively. Although the yields were slightly low as the case, the usefulness of Pd-catalyzed heteroarylamination was certified for the synthesis of bis(1-azaazulen-2-yl)amine derivatives.