Reagent Friday: Zinc Amalgam (Zn-Hg)
Last updated: January 29th, 2020 |
Zinc Amalgam (Zn-Hg)
What it’s used for: For our purposes, zinc amalgam (Zn-Hg) has one important use: in the Clemmensen reduction of ketones to alkanes.
Similar to: The reagent has essentially the same effect as the Wolff-Kishner reaction, although it is done under acidic conditions.
Zinc amalgam (Zn-Hg) is most commonly used in the Clemmensen reduction, which takes ketones adjacent to aromatic rings down to the alkane. This can be useful in, say, after the Friedel-Crafts acylation when you want to obtain a straight chain alkane that would otherwise rearrange.
Note that the Clemmensen isn’t as effective on ketones that aren’t adjacent to aromatic systems, a sign that the reaction is probably proceeding through a carbocation or other electron-deficient intermediate that is stabilized through resonance with the aromatic ring.
How it works:
Amalgams are alloys of mercury and other metals. They are among the oldest of reducing agents, but their precise mode of action remains somewhat mysterious. I remember reading at some point that their mode of action is not unlike that of an electrochemical cell. In the Clemmensen, addition of acid protonates the ketone, and electrons from the Zn(Hg) are delivered to the carbon; the new hydrogens come from the acid, while the oxygen is eventually expelled as water.
Real life tips: Although I’ve never prepared zinc amalgam, for a good time, try making sodium amalgam through dropping liquid Hg into a beaker of molten Na in mineral oil. Watch that you don’t get splattered. Shulgin uses aluminum amalgam as the reductant of choice for taking ketones and aldehydes to alcohols. In PIKHAL I recall him describing the preparation of aluminum amalgam through cutting conventional aluminum foil into small squares and adding a solution of mercuric chloride in water.
P.S. You can read about the chemistry of Zn(Hg) and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF. The Reagents App is also available for iPhone, click on the icon below!
(Advanced) References And Notes
- γ-PHENYLBUTYRIC ACID
L. Martin Org. Synth. 1935, 15, 64
A reliable, tested procedure for a simple Clemmensen Reduction that demonstrates how this reaction can be used to reduce a ketone in the presence of a carboxylic acid.
- Elrik Clemmensen: Reduktion von Ketonen und Alahyden su den entspcechenden Kohlenwaaserstoflbn unter Anwendung von amalgamiertem Zink und Salesaure.
Clemmensen, E. Chem. Ber. 1913 46 (2), 1837-1843
The original paper by Clemmensen on the reduction of aldehydes and ketones with Zn metal in acid. Note that even though this was submitted to a German journal and written in German, Clemmensen was working at Parke-Davis, in the U.S.Two reviews on the Clemmensen Reduction:
- THE CLEMMENSEN REDUCTION
Martin, E. L. React. 1942, 1, 155
- CLEMMENSEN REDUCTION OF KETONES IN ANHYDROUS ORGANIC SOLVENTS
Vedejs, E. React. 1975, 22, 401
- Stereoselective total synthesis of (–)-pumiliotoxin C by an aqueous intramolecular acylnitroso Diels–Alder approach
Masaichi Naruse, Sakae Aoyagi and Chihiro Kibayashi
Chem. Soc., Perkin Trans. 1, 1996, 1113-1124
Clemmensen reductions can be used in total synthesis due to the mild conditions – in this case 34 to 35 is a Clemmensen reduction that selectively reduces a ketone in the presence of an amide.