Catalytic Synthesis of Benzothiazole and Benzoxazole Derivatives

The catalytic synthesis of benzothiazole and benzoxazole derivatives has emerged as a cornerstone of modern heterocyclic chemistry, driven by the widespread application of these scaffolds in medicinal, agrochemical and materials science. Benzothiazoles and benzoxazoles are typically constructed by cyclocondensation of 2-aminothiophenols or 2-aminophenols with carbonyl partners, a process greatly enhanced by catalysts that promote C–N, C–O and C–S bond formations under mild conditions. Recent advances have focused on earth-abundant metal catalysis—particularly iron and copper systems—alongside organocatalysts such as ionic liquids and deep eutectic solvents. These strategies deliver high regioselectivity, operational simplicity and reduced environmental footprint, enabling one-pot protocols, microwave-assisted reactions and hypervalent-iodine-mediated transformations. As a result, a versatile array of 2-substituted and 2-aryl derivatives can now be accessed in good to excellent yields, with tailored functionalisation for drug discovery and optoelectronic applications.

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Catalytic Synthesis of Benzothiazole and Benzoxazole Derivatives publication trend

The graph below shows the total number of articles in catalytic synthesis of benzothiazole and benzoxazole derivatives across all publications each year (not limited to Nature Index journals).

Technical terms

Catalysis: Acceleration of a chemical reaction by a substance that remains chemically unchanged upon completion of the reaction.

Heterocycle: A ring structure containing at least one atom other than carbon, such as nitrogen, oxygen or sulfur.

Benzothiazole: A bicyclic aromatic heterocycle formed by fusion of a benzene ring with a thiazole ring, known for diverse biological activities.

Benzoxazole: A bicyclic heterocycle composed of a benzene ring fused to an oxazole ring, valued for its electron-rich and photophysical properties.

Deep eutectic solvent (DES): A eutectic mixture of hydrogen-bond donors and acceptors that exhibits a melting point lower than its individual components and can act as a recyclable reaction medium.

Hypervalent iodine reagent: An iodine compound in which iodine exhibits an oxidation state greater than +1, employed to mediate oxidative cyclisations and functional-group transformations.

References

1. Iron‐Catalyzed Regioselective Synthesis of 2‐Arylbenzoxazoles and 2‐Arylbenzothiazoles via Alternative Reaction Pathways. European Journal of Organic Chemistry (2020).
2. Rapid and Simple Microwave-Assisted Synthesis of Benzoxazoles Catalyzed by [CholineCl][Oxalic Acid]. Catalysts (2022).
3. A Novel PIFA/KOH Promoted Approach to Synthesize C2-arylacylated Benzothiazoles as Potential Drug Scaffolds. Molecules (2022).
4. Pioneering Synthetic Strategies of 2-Substituted Benzothiazoles Using 2-Aminothiophenol. Chemistry (2024).