Naphthalene is a pervasive pharmacophore in organic synthesis due to its unique structure that allows for its use in commodity chemicals (e.g. dyes, resin, coal, tar), agrochemicals, and pharmaceuticals (Figure 1). Naphthalene has two characteristic fused benzene rings that are structurally modified to aid in drug discovery processes by varying the peripheral substituents on the bicycle. Its unique structure and bioactivity allow diverse drug modifications to target numerous pathophysiological conditions. The expansive uses for naphthalene and its derivatives are controlled by the peripheral substituents, meaning that site selectivity for naphthalene formation is important.
Due to naphthalene’s’ importance in organic chemistry, methods of their synthesis are valuable. Previous methods of naphthalene synthesis have shown difficulty forming naphthalene’s with substituent specificity. Benzannulation reaction have been reported previously for naphthalene synthesis which require forcing conditions, complex starting materials, or expensive catalysts.
This work presents a novel method complementary to previous benzannulation reactions using an inexpensive catalyst, non-forcing conditions, with a straightforward synthesis of starting materials. This method, shown in Figure 1, provides a cyclization with high site selectivity at multiple positions on the aromatic bicycle. This work focuses on the synthesis and testing of differently substituted precursors under the optimized reaction conditions showcasing the versatility of this method to form naphthalene’s with multiple substituents. This convenient method rapidly undergoes a cyclization that selectively forms naphthalene’s utilizing iron (III) bromide as a catalyst.

<b>Figure 1.</b> Conditions developed for cyclizing carbonyls to achieve a substituted naphthalene.

Figure 1. Conditions developed for cyclizing carbonyls to achieve a substituted naphthalene.

Cora Kirk

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