Photoacid-Catalyzed C–C and C–O Bond Formation and the Synthesis of Triazole - Containing Bis(indolyl)methanes
Date of Award
Chemistry and Biochemistry
Joseph Badillo, PhD
Gregory Wiedman, PhD
Cecilia Marzabadi, PhD
photochemistry, Photoacid Catalysis, Bis(indolyl)methanes (BIMs), Schreiner's thiourea, 6-bromo-2-naphthol, Copper-catalyzed azide-alkyne cycloaddition (CuAAC)
From photosynthesis to transition metal-type photocatalysts, the conversion of light energy into chemical energy is a fundamental process in chemistry. While photochemistry is not new to the world of science, there has been a renewed interest in the field, specifically with the use of photocatalysts. There is a wide variety of compounds that function as photocatalysts, ranging from transitions metal complexes, organic dyes, and photoacids. Photoacids, which have typically been used for polymer synthesis and the pH modulation of biological systems and have recently gained popularity due to their catalytic potential. These compounds offer an efficient, cost-effective way to conduct synthetic processes.
Chapter 1 of this dissertation describes the recent advancements in photoacid photocatalysis. The specific class of photoacids investigated here are PAHs. Catalysts covered in this chapter include transition metal complexes, naphthols, organic dyes and others. The chapter is further categorized based on different classes of reactions.
Chapter 2 describes a thiourea-catalyzed C–C bond-forming reaction. Schreiner’s thiourea [(N,N’-bis[3,5- bis(trifluoromethyl)phenyl]-thiourea] functions as a photoacid to facilitate the double Friedel-Crafts addition of indoles to aldehydes and isatins to form the corresponding triarylmethanes and 3,3’- diarylindolin-2-ones. The mechanism of catalysis was also investigated, it was determined that an in situ acidic species is being generated due to a hydrogen bonding complex forming between the carbonyl reagents and thiourea catalyst.
Chapter 3 describes the use of 6-bromo-2-naphthol as a photoacid catalyst for the formation of C–O bonds. Using 10 mol% photoacid catalyst enables the photo-induced acetalization of aldehydes with a range of alcohols. The chapter also describes methods for determining the ground-state acidity (pKa) and excited- state acidity (pKa*)for 2-naphthol and 6-bromo-2-naphthol. This was the first time that the pKa for 6-bromo- 2-naphthol has been determined in water. It was also observed that 2-naphthol in the presence of a photosensitizer facilitates the acetalization of electron-deficient aldehydes.
Chapter 4 describes both photochemistry in conjunction with click chemistry to synthesize triazoles. First the methodology developed in chapter two is used to synthesize alkyne containing bis(indolyl)methanes (BIMs). Afterwards, these compounds are then converted to their corresponding triazoles using copper- catalyzed azide alkyne cycloaddition (CuAAC) reactions. This chapter also includes preliminary biological results into the inhibitory effects of these compounds on glioblastoma cancer cell lines.
Saway, Jason, "Photoacid-Catalyzed C–C and C–O Bond Formation and the Synthesis of Triazole - Containing Bis(indolyl)methanes" (2023). Seton Hall University Dissertations and Theses (ETDs). 3086.