Pyridinium Chlorochromate (PCC) Corey-Suggs Reagent

Pyridinium chlorochromate is a reddish orange solid reagent used to oxidize primary alcohols to aldehydes and secondary alcohols to ketones. Pyridinium chlorochromate, or PCC, will not fully oxidize a primary alcohol to the carboxylic acid as does the Jones reagent. A disadvantage to using PCC is its toxicity. PCC was developed by Elias James Corey and William Suggs in 1975.  Pyridinium dichromate has the advantage of being less acidic than its class of oxidizing agents.

Preparation:

First chlorochromic acid is prepared by the dissolution of chromium trioxide in 6M aq. hydrochloric acid. Addition of pyridine gives pyridinium chlorochromate as orange crystals.

The properties of PCC can be compared with those of PDC: it is not particularly hygroscopic, is stable, commercial available and can be stored. PCC is soluble in many organic solvents, and especially dichloromethane at room temperature has been used in most cases, whereas DMF promotes the over-oxidation of primary alcohols into carboxylic acids.

PCC is more acidic than PDC, but acid-labile compounds can be oxidized in the presence of sodium acetate or other buffers such as carbonates. Another drawback is the formation of viscous materials that complicate product isolation. Addition of Celite, powdered molecular sieves or magnesium sulfate to PCC oxidation reaction mixtures can simplify the work-up, because the reduced chromium salts and other reagent-derived byproducts are deposited onto these solids, which can then be readily removed by filtration.

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. 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.

Attention: Chromium (VI) compounds are toxic and must be handled with care as it is a known carcinogen. Other methods for oxidizing alcohols using less toxic reagents have been introduced and are more preferred by green chemists:

• DMSO-based oxidations (Swern oxidation, Moffatt oxidation)
• hypervalent iodine based oxidation (such as the Dess-Martin periodinane)

Procedures:

A 500-mL, round-bottomed flask equipped with a 4.5-cm, egg-shaped Teflon-coated magnetic stir bar is charged with 130 mL of CH₂Cl₂, the alcohol (10.4 g, 40.0 mmol), and 15 g of freshly powdered 3 Å molecular sieves. Pyridinium chlorochromate (21.5 g, 100 mmol) is added portionwise over 10 min and the resulting mixture is stirred at room temperature for 15 hr. Ether (200 mL) is added slowly with vigorous stirring and the solution is filtered under vacuum through a pad of 35 g of Celite. The solids remaining in the reaction flask are transferred to the Celite pad by scraping with a spatula and washing with three 50-mL portions of ether. The resulting cloudy brown filtrate is concentrated by rotary evaporation at room temperature to give a brown solid. To this solid is added 25 mL of 1:1 ether:hexane and the solids are scraped with a spatula. The mixture is then poured onto 60 g of Whatman 60 Å (230-400 mesh) silica gel packed in a 4-cm diameter chromatography column and the liquid is adsorbed onto the silica gel by gravity. The material remaining in the flask is further washed with 1:1 ether:hexane and transferred onto the silica gel; this process is repeated until all the material has been loaded onto the silica gel. The ketone is eluted using 500 mL of 1:1 ether:hexane and the eluent is concentrated by rotary evaporation to afford the crude ketone as a white solid. This material is dissolved in 40-45 mL of boiling hexane. Upon cooling the solution to room temperature, the ketone begins to crystallize. The flask is then cooled to −25°C for 2 hr. The resulting solids are collected by filtration, washed with three 25-mL portions of cold (−25°C) hexane, and dried to afford 8.84-9.08 g, (86-88%) of the ketone as a white solid.

------------------------------------------------------------------------------------

A flame-dried, 250-mL, three-necked, round-bottomed flask is equipped with a magnetic stir bar, rubber septum, glass stopper, and an argon inlet. The flask is charged with pyridinium chlorochromate (16.4 g, 76 mmol) and 75 mL of dichloromethane. A solution of crude (6R)-(+)-1,6-dimethylcyclohex-2-en-1-ol (4.79 g, 38 mmol) prepared as described above in 25 mL of dichloromethane  is transferred into the reaction mixture via cannula over 5 min, and the resulting mixture is stirred at ambient temperature for 3 hr. The reaction mixture is then diluted with 120 mL of diethyl ether, the solution is decanted, and the remaining black resinous polymer is thoroughly washed with three 50-mL portions of diethyl ether. The combined dark brown/black ether solution is washed successively with two 100-mL portions of 5% aqueous sodium hydroxide solution, 100 mL of 5% aqueous hydrochloric acid, and two 50-mL portions of saturated aqueous NaHCO3 solution, dried over anhydrous magnesium sulfate, filtered, and concentrated by rotary evaporation at room temperature (50 mmHg) to give 4.42 g of the crude product as a yellow oil. Purification by column chromatography  yields 3.71-3.85 g (79-82% overall from 1) of (R)-(+)-3,4-dimethylcyclohex-2-en-1-one (3) as a colorless oil.

Tips:

In practice the chromium byproduct deposits with pyridine as a sticky black tar, which can complicate matters. Addition of an inert adsorbent such as crushed molecular sieves or silica gel allows the sticky byproduct to adsorb to the surface, and makes workup much easier.