NaHMDS

Sodium hexamethyldisilazide (NaHMDS) is a strong, non-nucleophilic base used in organic synthesis to deprotonate substrates and generate carbanions or enolates. It is the sodium salt of hexamethyldisilazide (HMDS), with the formula Na+[HN(SiMe3)2]−. In typical use, NaHMDS functions as a bulky base that can abstract protons from relatively acidic C–H bonds without promoting extensive nucleophilic side reactions.

NaHMDS is commonly sold as a solution in inert solvents such as THF or toluene, often in the range of about 0.5–1.0 M, though solid forms are also available. It is moisture- and air-sensitive and is normally handled under inert atmosphere. The conjugate acid HMDS has a pK_a in the mid-20s in common organic solvents, reflecting the strong basicity of the anion. The reagent is highly soluble in many polar aprotic solvents and is used under cryogenic to ambient temperatures depending on the substrate.

In practice, NaHMDS is employed to deprotonate ketones, esters, nitriles, and other weakly acidic substrates to form enolates or carbanions, which can then undergo alkylation, acylation, or various carbon–carbon bond-forming reactions. It is valued for being bulky and relatively non-nucleophilic, reducing the likelihood of unwanted S_N2 or acyl transfer side reactions. Comparatively, it is milder and more selective for certain deprotonations than NaH, and it is often used as an alternative to LDA or KHMDS in sensitive transformations. Safety considerations include handling under inert conditions and avoiding exposure to moisture or air, as hydrolysis yields HMDS and inorganic bases.