Carbonyl deoxygenation — desulfurization
Mozingo reduction (thioketal desulfurization)
How the Mozingo reduction (thioketal desulfurization) works, in 3 steps. Each step shows the structures and the curved arrows that move the electrons.
In short. A 3-step mechanism. Typical reagents: 1,2-Ethanedithiol, BF₃·OEt₂ (or TsOH); then Raney Ni (H-saturated). Conditions: Step 1: CH₂Cl₂, 25 °C; step 2: EtOH, reflux. Bonds formed: C–H ×2 (new CH₂); Ni–S; bonds broken: C=O; two C–S. Stereochemistry: Any carbonyl stereocentre α is untouched; no new stereocentre. Rate and selectivity: Strong Ni–S bond formation drives desulfurization.
At a glance
Step 1: Thioketal formation
A ketone or aldehyde condenses with a dithiol (like 1,2-ethanedithiol) under acid, forming a cyclic dithioketal — the sulfur analog of the acetal-protecting-group chemistry used throughout carbonyl protection strategies.
Step 2: Adsorption on Raney Ni
Raney nickel, a hydrogen-saturated metal surface, adsorbs the dithioketal and cleaves both C–S bonds via a surface-mediated radical/organometallic process, releasing nickel sulfide and generating a carbon-centered species that is immediately quenched by surface-bound hydrogen.
Step 3: C–S cleavage and H delivery
The net result is full deoxygenation to a CH₂ group — a third distinct route to the same overall transformation as Wolff-Kishner and Clemmensen reduction, useful specifically when a substrate is incompatible with either of those two other conditions (strong base or strong acid, respectively).
Abbreviations and terms
- DCM
- Dichloromethane. Common non-polar-ish solvent for reactions that need no nucleophilic or protic solvent.
- EtOH
- Ethanol. Polar protic solvent.
- H2
- Hydrogen gas. Reductant for catalytic hydrogenation.
- BF3
- Boron trifluoride. Lewis acid (usually as the Et₂O complex).
- TsOH
- p-Toluenesulfonic acid. Strong organic acid catalyst, soluble in organic solvents.
- Δ
- Heat. Reaction is run at elevated temperature.
How it compares with related reactions
| Mozingo reduction (thioketal desulfurization) | Clemmensen reduction | Wolff-Kishner reduction | |
|---|---|---|---|
| Reagents | 1,2-Ethanedithiol, BF₃·OEt₂ (or TsOH); then Raney Ni (H-saturated) | Zn(Hg), conc. HCl | N₂H₄; KOH (or t-BuOK) |
| Conditions | Step 1: CH₂Cl₂, 25 °C; step 2: EtOH, reflux | Reflux, heterogeneous (metal surface) | Diethylene glycol, 180–200 °C (Huang-Minlon) |
| Stereochemistry | Any carbonyl stereocentre α is untouched; no new stereocentre | Not stereocontrolled; mechanism debated | Carbanion is protonated; no stereocontrol |
| Rate / selectivity | Strong Ni–S bond formation drives desulfurization | Works best for aryl ketones; avoid acid-sensitive groups | N₂ loss is irreversible; needs base-stable substrate |
Test yourself
Try to answer each question before opening it.
Which reagents and conditions are typical for the Mozingo reduction (thioketal desulfurization)?
1,2-Ethanedithiol, BF₃·OEt₂ (or TsOH); then Raney Ni (H-saturated). Conditions: Step 1: CH₂Cl₂, 25 °C; step 2: EtOH, reflux.
Which bonds are formed and which are broken?
Formed: C–H ×2 (new CH₂); Ni–S. Broken: C=O; two C–S.
What is the stereochemical outcome?
Any carbonyl stereocentre α is untouched; no new stereocentre
What controls the rate or the selectivity?
Strong Ni–S bond formation drives desulfurization
Study guides that help with this reaction
- Carbonyl chemistry: addition, acyl substitution and enolates
- SN1, SN2, E1 or E2? How to decide which mechanism wins
- Nucleophiles, electrophiles and leaving groups: what makes a reaction go