Volhard–Erdmann cyclization

Volhard–Erdmann cyclization is a chemical reaction that involves the cyclization of thiocarboxylic acids or their derivatives to form thiazoles. This reaction is named after the German chemists Jacob Volhard and Hugo Erdmann who first described the process in the late 19th and early 20th centuries, respectively. The Volhard–Erdmann cyclization is an important reaction in the field of organic chemistry, particularly in the synthesis of heterocyclic compounds, which are a core part of many pharmaceuticals, agrochemicals, and materials.

Reaction Mechanism

The Volhard–Erdmann cyclization typically begins with the conversion of a thiocarboxylic acid (or its derivative) into a thiocarbonyl chloride, which then reacts with an α-amino ketone. The reaction proceeds through the formation of an intermediate that undergoes intramolecular cyclization to produce a thiazole ring. The overall process is facilitated by the presence of a base, which helps in deprotonation steps, and a halogenating agent, which aids in the formation of the thiocarbonyl chloride.

Applications

Thiazoles, the products of the Volhard–Erdmann cyclization, are significant in medicinal chemistry due to their presence in a variety of biologically active molecules. These heterocyclic compounds exhibit a wide range of pharmacological properties, including antibacterial, antifungal, and anti-inflammatory activities. Consequently, the Volhard–Erdmann cyclization has been employed in the synthesis of numerous pharmaceuticals and research compounds.

Variations

Over the years, several variations of the Volhard–Erdmann cyclization have been developed to improve the efficiency, selectivity, and scope of the reaction. These modifications often involve the use of different catalysts, solvents, or starting materials. For instance, the use of microwave irradiation has been shown to significantly reduce reaction times and improve yields.

See Also

• Thiazole
• Cyclization
• Organic synthesis
• Heterocyclic compound
• Medicinal chemistry