Superbases: The Strongest Bases Known

Sodium hydroxide can dissolve grease, hair and aluminium, but to an organic chemist it’s a fairly modest base. Some reactions need a base strong enough to pull a proton off a carbon–hydrogen bond in an ordinary hydrocarbon, something hydroxide can’t come close to doing. For those jobs, chemists use superbases.

Superbases are the mirror image of superacids: substances with an extraordinary appetite for protons. They power some of the most important reactions in organic synthesis, and they have to be handled with just as much care.

What counts as a superbase?

The term is used in two related ways:

1. Loosely, for any base much stronger than hydroxide, typically one able to deprotonate substances with a pKa above about 25–30.
2. In a specific sense (following IUPAC usage), for mixtures of two or more bases that together create a new, more powerful basic species, such as the “Lochmann–Schlosser base” mixture described below.

Either way, the key is the strength of the conjugate acid. A base is strong when its conjugate acid is very weak, and a way to compare bases is the pKa of the conjugate acid (pKaH). The higher it is, the stronger the base. See Kb and pKb.

Base	Conjugate acid	pKaH (approx.)
Hydroxide, OH⁻	H₂O	15.7 (or about 14, depending on convention)
Ethoxide, C₂H₅O⁻	ethanol	16
tert-Butoxide, (CH₃)₃CO⁻	tert-butanol	17–19
Amide, NH₂⁻	ammonia	38
LDA, [(CH₃)₂CH]₂N⁻	diisopropylamine	36
Hydride, H⁻	H₂	about 35
n-Butyl anion (in n-BuLi)	butane	about 50

Exact values depend on the solvent and the method used; these figures are commonly quoted approximations.

Why hydroxide is the limit in water

Just as H₃O⁺ is the strongest acid that can survive in water, OH⁻ is the strongest base that can survive in water. Any stronger base immediately takes a proton from water and becomes its conjugate acid, leaving hydroxide:

NH₂⁻ + H₂O → NH₃ + OH⁻ H⁻ + H₂O → H₂ + OH⁻ C₄H₉⁻ + H₂O → C₄H₁₀ + OH⁻

This is the levelling effect for bases. So superbases must be used in solvents that are even weaker acids than their target, such as ethers (like tetrahydrofuran, THF), hydrocarbons like hexane, or liquid ammonia, and with rigorous exclusion of water and air.

The main families of superbases

Organolithium reagents

n-Butyllithium (n-BuLi), C₄H₉Li, is the workhorse. The carbon–lithium bond is highly polar, so the carbon behaves almost like a carbanion (a negatively charged carbon), one of the strongest bases in practical use. It’s sold as solutions in hexane.

Relatives include sec-butyllithium and tert-butyllithium, which are even more reactive. tert-Butyllithium ignites spontaneously in air (it’s pyrophoric).

Uses:

• removing protons from weakly acidic C–H bonds to make new carbanions
• lithium–halogen exchange, a key way to build complex molecules
• starting polymerisations, including the production of synthetic rubbers

Metal amides

Sodium amide (NaNH₂) and lithium amide are strong bases used, for example, to deprotonate terminal alkynes (R–C≡C–H, pKa about 25) to make acetylide ions, which are then used to form new carbon–carbon bonds.

Lithium diisopropylamide (LDA) is one of the most widely used bases in organic chemistry. Its two bulky isopropyl groups make it strongly basic but a poor nucleophile: it’s too crowded to attack carbon atoms, so it removes protons cleanly without side reactions. It’s the standard reagent for turning ketones and esters into enolates, a crucial step in building carbon skeletons.

Related “hindered” bases include LiHMDS and KHMDS (lithium and potassium hexamethyldisilazide).

Metal hydrides

Sodium hydride (NaH) and potassium hydride (KH) contain the hydride ion, H⁻. They’re used to deprotonate alcohols and other O–H and N–H groups. The by-product, hydrogen gas, bubbles away and drives the reaction forward. NaH is usually sold as a dispersion in mineral oil, which makes it safer to handle.

The Lochmann–Schlosser base (LICKOR)

Mixing n-butyllithium with potassium tert-butoxide creates a “superbase” more reactive than either component alone, often thought to involve an organopotassium species. It can deprotonate even benzene and toluene at useful rates.

Neutral organic superbases

Not all superbases are ionic. Some neutral organic molecules are exceptionally strong bases because their protonated forms are unusually stable:

• Amidines such as DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and guanidines such as TBD. When protonated, the positive charge is spread over two or three nitrogen atoms by resonance. DBU’s conjugate acid has a pKa of about 24 in acetonitrile.
• Proton sponges such as 1,8-bis(dimethylamino)naphthalene. Two nitrogen lone pairs are forced very close together, repelling each other. Protonation relieves the strain by tucking the proton between them.
• Phosphazene bases (Schwesinger bases), such as P4-tBu, are among the strongest neutral bases known. They’re used when metal-free, soluble, very strong bases are needed.

These neutral bases are popular because they dissolve in organic solvents and don’t introduce metal ions.

The record holders

What’s the strongest base ever made? In the gas phase, where there’s no solvent to level anything, chemists have compared proton affinities. The methanide ion (CH₃⁻) and the lithium monoxide anion (LiO⁻) are among the strongest. In 2016, a team led by researchers in Australia reported that the ortho-diethynylbenzene dianion (formed in the gas phase) had the highest proton affinity measured for any base at the time. These species exist only fleetingly and in isolation; they’re about fundamental limits, not practical use.

A worked example: why LDA is chosen

Suppose a chemist wants to turn propanone (acetone, pKa about 19 for its C–H next to the C=O group) completely into its enolate ion. Hydroxide (conjugate acid pKa about 15.7) is too weak: the equilibrium would lie mostly on the side of the ketone, because the enolate is a stronger base than hydroxide. LDA’s conjugate acid, diisopropylamine, has a pKa of about 36. Since the equilibrium favours the weaker acid, deprotonation by LDA goes essentially to completion: roughly 10¹⁷ to one in favour of the enolate. And because LDA is too bulky to attack the carbonyl carbon, it doesn’t cause unwanted side reactions.

Safety

Superbases demand serious precautions:

• Pyrophoric reagents such as tert-butyllithium can ignite on contact with air.
• Hydrides and organolithiums react violently with water, releasing flammable gases (hydrogen, butane).
• They’re corrosive and cause severe burns.
• They’re handled under an inert atmosphere of nitrogen or argon, using dry solvents, syringes and special glassware, by trained chemists only.

Common misconceptions

• “Sodium hydroxide is the strongest base.” It’s the strongest that survives in water; many bases used in synthesis are enormously stronger.
• “Strong bases are always good nucleophiles.” LDA shows the opposite: bulk can make a base strong but non-nucleophilic.
• “Superbases are only ionic.” Neutral organic bases like phosphazenes can be extraordinarily strong.

Key takeaways

• Superbases are much stronger than hydroxide; their conjugate acids have very high pKa values.
• Water levels bases down to OH⁻, so superbases are used in dry, non-aqueous solvents.
• Key families: organolithiums (n-BuLi), metal amides (NaNH₂, LDA), hydrides (NaH), mixed bases (LICKOR) and neutral organic superbases (DBU, proton sponges, phosphazenes).
• They’re essential for making carbanions and enolates in organic synthesis, and they demand strict safety precautions.
• Compare with the everyday end of the scale in the strong bases.