First Synthesis of 2-Heteroarylazulenes by the Electrophilic Substitution of Azulene with Triflate of N-Containing Heterocycles

An efficient synthesis of 2-heteroarylazulene derivatives was established via electrophilic substitution. The reaction of 6-dimethylamino-1,3-di(methylthio)azulene (1a) with the triflate of N-containing heteroarenes proceeded in the presence of excess heteroarenes to afford the corresponding 2-dihydroheteroarylazulene derivatives 3−7. The 2-dihydroheteroarylazulene derivatives were readily converted into the desired 2-heteroarylazulene derivatives 8−11 by the treatment with KOH in alcohols in excellent yields, except for 4 and 5. Electrophilic substitution reactions are a very important and general methodology for the functionalization of aromatic compounds. In azulene derivatives, there are numerous reports for the electrophilic substitution reactions at the 1and 3-positions of the azulene ring. However, there are few reports on the functionalization of azulene derivatives at the 2-position utilizing electrophilic substitution reactions, because 2-position of azulene is inert site toward the electrophile. In 1962, Hafner and co-workers reported that 1,3-dialkyl-substituted azulene derivatives undergo the Vilsmeier formylation reaction using DMF and POCl3 to give corresponding 2-formylazulenes, but only with very low selectivity compared to ipso-substitution at the 1-position and electrophilic substitution at the 5-position. HETEROCYCLES, Vol. 85, No. 1, 2012 35