Reagent Friday: PCC (Pyridinium Chlorochromate)
Last updated: February 21st, 2020 |
Pyridinium Chlorochromate (PCC), A Useful Oxidant For Alcohols In Organic Chemistry
In a blatant plug for the Reagent Guide, each Friday I profile a different reagent that is commonly encountered in Org 1/ Org 2. Version 1.2 just got released, with a host of corrections and a new page index.
What it’s used for: PCC is a milder version of chromic acid. Essentially, what it does is oxidize alcohols one rung up the oxidation ladder, from primary alcohols to aldehydes and from secondary alcohols to ketones. Unlike chromic acid, PCC will not oxidize aldehydes to carboxylic acids.
Similar to or the same as: CrO3 and pyridine (the Collins reagent) will also oxidize primary alcohols to aldehydes.
Oxidation Of Primary Alcohols To Aldehydes With Pyridinium Chlorochromate (PCC) And Oxidation Of Secondary Alcohols To Ketones
Here are two examples of PCC in action. If you add one equivalent of PCC to either of these alcohols, you obtain the oxidized version. The byproducts (featured in grey) are Cr(IV) as well as pyridinium hydrochloride.
One has to be careful with the amount of water present in the reaction. If water is present, it can add to the aldehyde to make the hydrate, which could be further oxidized by a second equivalent of PCC were it present. This is not a concern with ketones, since there is no H directly bonded to C.
Mechanism For The Oxidation Of Primary Alcohols To Aldehydes With Pyridinium Chlorochromate
How does it work? Oxidation reactions of this sort are actually a kind of elimination reaction. We’re going from a carbon-oxygen single bond to a carbon-oxygen double bond. [See: Demystifying Alcohol Oxidations] The elimination reaction can occur because we’re putting a good leaving group on the oxygen, namely the chromium, which will be displaced when the neighboring C-H bond is broken with a base.
The first step is attack of oxygen on the chromium to form the Cr-O bond. Secondly, a proton on the (now positive) OH is transferred to one of the oxygens of the chromium, possibly through the intermediacy of the pyridinium salt. A chloride ion is then displaced, in a reaction reminiscent of a 1,2 elimination reaction, to form what is known as a chromate ester.
The C-O double bond is formed when a base removes the proton on the carbon adjacent to the oxygen. [aside: I’ve drawn the base as Cl(-) although there are certainly other species which could also act as bases here (such as an alcohol). It is also possible for pyridine to be used as the base here, although only very low concentrations of the deprotonated form will be present under these acidic conditions.] The electrons from the C-H bond move to form the C-O bond, and in the process break the O-Cr bond, and Cr(VI) becomes Cr(IV) in the process (drawn here as O=Cr(OH)2 ).
Real life notes: If you end up using PCC in the lab, don’t forget to add molecular sieves or Celite or some other solid to the bottom of the flask, because otherwise you get a nasty brown tar that is a real major pain to clean up. The toxicity and mess associated with chromium (as popularized by this lady) has spurred the development of other alternatives like TPAP, IBX, DMP, and a host of other neat reagents you generally don’t learn about until grad school.
P.S. You can read about the chemistry of PCC and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.
(Advanced) References and Further Reading
- Pyridinium chlorochromate. An efficient reagent for oxidation of primary and secondary alcohols to carbonyl compounds
E.J. Corey, J. William Suggs
Tetrahedron Letters Volume 16, Issue 31, 1975, Pages 2647-2650
The original paper by Nobel Laureate Prof. E. J. Corey on the use of pyridinium chlorochromate as a mild oxidation reagent in organic synthesis.
- The story of the discovery of PCC was rather serendipitous, as explained by Prof. Suggs in this blog post: https://blogs.sciencemag.org/pipeline/archives/2005/10/11/the_old_stuff#comment-2123
- Pyridinium Chlorochromate: A Versatile Oxidant in Organic Synthesis
Piancatelli, A. Scettri, M. D’Auria
Synthesis 1982; 1982 (4): 245-258
Review on the applications of PCC in organic synthesis. Includes a discussion on the mechanism.
- Kinetics and Mechanism of the Oxidation of Alcohols by Pyridinium Chlorochromate
Banerji Kalyan K.
Bull. Chem. Soc. Jpn. 1978, 51 (9), 2732
A nice mechanistic study of PCC oxidation, and includes a probable mechanism of the reaction.
- Stoichiometry of the oxidation of primary alcohols with pyridinium chlorochromate. Evidence for a two-electron change
Herbert C. Brown, C. Gundu Rao, and Surendra U. Kulkarni
The Journal of Organic Chemistry 1979 44 (15), 2809-2810
In this paper, Nobel Laureate H. C. Brown proves that PCC oxidations involve a transfer of 2 electrons from the Cr to the substrate. Therefore, one does not need to use an excess of PCC – 1 equivalent works fine.
- SYNTHESIS OF 1,2:4,5-DI-O-ISOPROPYLIDENE-D-erythro-2,3-HEXODIULO-2,6-PYRANOSE. A HIGHLY ENANTIOSELECTIVE KETONE CATALYST FOR EPOXIDATION
Yong Tu, Michael Frohn, Zhi-Xian Wang, and Yian Shi
Org. Synth. 2003 80, 1
This tested procedure from Organic Syntheses uses PCC to make the chiral ketone catalyst for asymmetric epoxidation, known as ‘Shi epoxidation’ after its creator, Prof. Yian Shi (Colorado State).