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DOI: 10.1055/s-0036-1591553
Water-Promoted Chlorination of 2-Mercaptobenzothiazoles
Publication History
Received: 10 November 2017
Accepted after revision: 22 February 2018
Publication Date:
09 April 2018 (online)
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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.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0036-1591553.
- Supporting Information
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References
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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.