Convenient synthesis of substituted azulenes based on metalation

Azulene derivatives have been recognized for their application in medicinal therapy against inflammation. Recently, azulene analogs have been used in optical technology. Nevertheless, synthesis of this family of compounds is always associated with multiple challenges. The reason is attributed to the lack of convenient methods for the synthesis of substituted azulenes. Because of n-electron polarization, azulene undergoes nucleophilic addition at its 4 -, 6 -, and 8-positions and electrophilic substitution at its 1-and 3-positions. Azulene derivatives bearing substituents at the 2 -, 5 -, or 7-positions have therefore previously been produced simply by the construction of the azulene skeleton, which introduces the substituent at an early stage of each synthetic method. We describe the convenient synthesis of 2-substituted azulene derivatives from parent azulene 1, a readily available starting material. The technique illustrated here involves various metalation reactions of azulenes.