Water-Promoted Chlorination of 2-Mercaptobenzothiazoles

Abstract

Substituted benzothiazoles play an important role in medicinal chemistry due to their pharmacological properties. Their 2-substituted derivatives are often prepared from 2-chlorobenzothiazoles, which in turn can be synthesized from the 2-mercapto precursor using sulfuryl chloride. In practice, this seemingly straightforward and widely used reaction can be impeded by poor reproducibility and low reaction yields. In this communication, we report that the simple addition of water to the reaction leads to remarkable improvements in reaction efficiency. We attribute this effect to the formation of acid through partial hydrolysis of sulfuryl chloride. This hypothesis is supported by the observation that improved yields were also obtained in the presence of some anhydrous acidic additives. The simple combination of sulfuryl chloride and water reproducibly provides excellent yields for a range of chlorinated products.

Key words

benzothiazoles - sulfuryl chloride - chlorination - acid-catalyzed - water-promoted

• References

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• 5 The addition of one, two or three equivalents of water led to the same reaction performance. After these initial experiments, we decided to use 2 equivalents of water as standard conditions.
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• 7 When quenching excess reagent from a reaction containing 5 g of mercaptobenzothiazole in 25 g of sulfuryl chloride, 6 liters of gaseous by-products (mainly hydrogen chloride) were released.