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

Abstract

-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 1-and 3-positions of the azulene ring. Thus, functionalization for 2-position of azulene by electrophilic reaction is remained as a subject of azulene chemistry.In recent years, there has been intense interest in transition-metal-catalyzed carbon-carbon and carbon-heteroatom bond formation in aromatic compounds.

Azulene, Reactivity, and Scientific Interest Inversely Proportional to Ring Size; Part 1: The Five-Membered Ring

“…In the following, the behavior of compound 12.1, which undergoes a S E Az reaction at position 2, is analyzed (Scheme 12) [34]. The suitable structure of this compound with two protecting groups at positions 1 and 3 and with a strong electron donor, dimethylamino, at azulene position 6 allows the electrophilic attack at position 2.…”

Synthesis of Azulene Derivatives from 2H-Cyclohepta[b]furan-2-ones as Starting Materials: Their Reactivity and Properties

“…The introduction of aryl moiety to the 2-position of azulene ring is mostly achieved by the cross-coupling reactions using the corresponding haloazulenes as starting materials because of the low reactivity of electrophiles to these sites [ 75 , 76 , 77 , 78 ]. There is only one example of the electrophilic substitution reaction by heterocyclic compound at the 2-position of the azulene ring, but in this case, a strong electron-donating group such as dimethylamino group at the 6-position and protection at the 1,3-positions of the azulene ring are both essential [ 79 , 80 ]. Recently, the reaction of 2 H -cyclohepta[ b ]furan-2-ones 13c , 13g , 17 , and 26 with silyl enol ethers substituted by various aryl groups have been reported as a new synthetic method for 2-arylazulenes 169 – 172 ( Scheme 41 ) [ 81 ].…”

Development of Heterocycle-Substituted and Fused Azulenes in the Last Decade (2010–2020)

“…The synthesis of 2-heteroarylazulenes via electrophilic substitution reaction was first described in 2012. The reaction of 6-dimethylamino-1,3-bis(methylthio)azulene ( 23 ) with pyridine in the presence of Tf 2 O, followed by treatment with KOH, gives 2-(4-pyridyl)azulene 24 ( Scheme 9 ) [ 25 ]. In a similar reaction, it is possible to employ quinoline, acridine, and 1,10-phenanthroline to furnish the corresponding 2-heteroarylazulene derivatives.…”