nosyl

Nosyl, short for p-nitrobenzenesulfonyl, is a sulfonyl protecting group used to mask amine functionalities in organic synthesis. It is introduced by reacting a primary or secondary amine with nosyl chloride (p-nitrobenzenesulfonyl chloride) to form the corresponding nosyl sulfonamide.

The Nos group is valued for its chemical stability under a range of reaction conditions and its orthogonality to other common protecting groups, such as Fmoc or Boc. This property makes it useful in multi-step sequences where selective deprotection is required.

Deprotection of the nosyl group typically proceeds via nucleophilic attack on the sulfonamide bond. Common methods employ thiolate reagents (for example, thiophenol) under basic conditions, or other specialized conditions that cleave the sulfonamide to regenerate the free amine and yield a nitrobenzenesulfonate byproduct. The exact conditions can vary depending on the substrate and the desired scale.

Nosyl protection is widely used in peptide synthesis and medicinal chemistry to shield amines during reactions that might otherwise affect them. It is considered orthogonal to several other protecting groups, allowing selective removal without disturbing other functionalities in complex molecules. The Ns/Nos terminology also appears in literature as a shorthand for this protecting group.

Safety and handling: Nosyl chloride is a reactive, irritant reagent and should be handled with appropriate protective equipment and procedures. Proper disposal of nitroaromatic byproducts is recommended in accordance with applicable regulations.