Catechol reactivity: Synthesis of dopamine derivatives substituted at the 6-position

ABSTRACT

Dopamine is a ubiquitous neurotransmitter essential in the proper functioning of the human body. In addition to this critical role, the catecholamine core has shown utility as a scaffold for numerous drugs and in other applications, like metal detection and adhesive materials. Substituents at the 6-position of dopamine’s catechol core can modulate its stereoelectronic properties, the acidity of its phenolic hydroxyl groups, and the overall hydrophobicity of the molecule. Herein, we report the synthesis of a series of four novel dopamine analogues substituted at the 6-position of catechol core. The ¹H NMR chemical shift of the aromatic proton meta to the substituent correlated strongly with the Hammett σ_m constant, confirming the electronic properties of substituents.

GRAPHICAL ABSTRACT

KEYWORDS:

• Boron tribromide
• catecholamine
• dopamine
• Hammett constant
• O-demethylation

Acknowledgment

This work was supported by Rhodes College. The authors acknowledge the Baylor University Mass Spectrometry Center for support during this work.