Formation of Indazoles Through an Unusual Cyclization Reaction of Hydrazones

Abstract

Abstract Antibacterial resistance has become and increasing problem throughout the world. In 2014 an estimated 480,000 deaths occurred due to complications associated with multi-drug resistant strains of tuberculosis (TB) 1. To combat resistant strains of bacteria, new forms of antibiotics must be utilized. One promising new antibiotic is SAB-P1. SAB-P1 is an effective antibiotic for both resistant and nonresistant strains of TB. However, it has only been biosynthetically produced in small quantities2. In an attempt to couple indole and naphthalene moieties, to produce SAB-P1 like compounds, a Fischer indole synthesis was utilized. This synthesis did not proceed as expected and instead yielded a number a novel indazole compounds. To further investigate the reaction, 1-acetyl-2-naphtol, 2-hydroxy-napthaldehyde, 1-acetyl-2-methoxy napthalene, and N-(1-acetylnaphthalen-2-yl)acetamide were reacted under Fischer indole synthetic conditions with one or more hydrazine derivative. The resultant compounds were then isolated and characterized.