Synthesis of 10-Ethyl Flavin: A Multistep Synthesis Organic Chemistry Laboratory Experiment for Upper-Division Undergraduate Students

Abstract

A multistep synthesis of 10-ethyl flavin was developed as an organic chemistry laboratory experiment for upper-division undergraduate students. Students synthesize 10-ethyl flavin as a bright yellow solid via a five-step sequence. The experiment introduces students to various hands-on experimental organic synthetic techniques, such as column chromatography, thin layer chromatography (TLC), extraction techniques, and characterizing intermediates and final products by IR and NMR spectroscopy. It also provides an opportunity for students to review important topics such as nucleophilic substitution reactions, hydrolysis of amides, condensation reactions, and reduction of aromatic nitro groups to amines.

Structure and Reactivity of Alloxan Monohydrate in the Liquid Phase

“…Many important organic synthetic reactions utilizing alloxan as a reagent are typically performed in acid, such as flavin synthesis, for example. 28 This is likely due to the fact that alloxan has been shown to rapidly break down to the five-membered isomer alloxanic acid in aqueous solutions with pH values greater than ∼3 2,29 (see Supporting Note 1 for an explanation of this effect within our recrystallization experiments). In addition, acidic protonation of one of the gem-diol alcohol moieties followed by loss of water is thought to produce the active hydronium ionic species susceptible to nucleophilic attack in these types of syntheses.…”

“…We further confirmed this protic chemical reactivity by testing another protic solvent, acetic acid. Many important organic synthetic reactions utilizing alloxan as a reagent are typically performed in acid, such as flavin synthesis, for example . This is likely due to the fact that alloxan has been shown to rapidly break down to the five-membered isomer alloxanic acid in aqueous solutions with pH values greater than ∼3 , (see Supporting Note 1 for an explanation of this effect within our recrystallization experiments).…”

A Visual Organic Chemistry Reaction: The Synthesis of 4-Amino-3-nitrobenzoic Acid Methyl Ester via Fischer Esterification

“…The amount of water present in the reaction mixture affects the equilibrium position and thus impacts the final yield of the product. Recent research on ester synthesis for undergraduate laboratories focuses on more transferable skills, including isolation of the final product and characterizing using 1 H NMR and IR spectroscopy, gas chromatography, and thin-layer chromatography (TLC). − This paper proposes the methylation reaction of 4-amino-3-nitrobenzoic acid for use in a typical 2–3 h laboratory class. The reaction mixture is purified using a liquid–liquid extraction protocol that involves a salt-forming reaction.…”

Four Step Total Synthesis of an H3 Receptor Antagonist Using Only Tools Found in a Typical Teaching Laboratory

“…While a number of papers describing laboratory experiments involving multistep organic syntheses have been published in recent years, − these have universally formed part of an undergraduate course. To our knowledge, this is the first report describing a multistep organic synthesis completed solely by high school students, demonstrating the value and educational benefits of collaboration between schools and universities.…”