Column: Bench monkey

Dylan Stiles touches on the 299 ways to convert an alcohol to an aldehyde or ketone

It’s pretty easy to oxidise an organic molecule: grab a chemical bottle off the shelf, take the cap off, and within a few days it will start to turn brown. The 20 per cent oxygen-content in the air we breathe is ravishing to organic materials, a fact for which we humans can be thankful. 

But oxidising a compound by letting it sit out on the bench is not very practical to the modern synthetic chemist. So-called autoxidation with air is usually indiscriminate and takes a while. Hence the need for reagents that can get the job done in a controlled manner. 

Alchemists were arguably the first to dabble with oxidation, even if they didn’t know it. These adventurous and often misguided individuals gave us  aqua regia, a voracious liquid named for its ability to dissolve gold.  Aqua regia- a mixture of concentrated nitric and hydrochloric acid - earns high marks for its strength, but it’s not exactly selective (nor is anything else that can devour your jewelry).  

Skip ahead to 2008 and let’s take a look at the current state of oxidation reactions. A simple case is the conversion of an alcohol to an aldehyde or ketone. It’s a fundamental reaction taught to freshmen, and there’s no shortage of methods to do it. My trusty copy of  Comprehensive organic transformations  lists 299, if I’m counting correctly. 

Rather unpleasant 

Some might consider chromium(vi) to be the gold standard in alcohol oxidations. The Jones oxidation was one of the first broadly-useful systems, earning it a special place in the lexicon of named reactions. But the Jones reagent uses chromium trioxide, a rather unpleasant material with a nasty tendency to burst into flames if you rinse off your spatula with methanol. Don’t do that, by the way. 

Chromium oxidations got a lot easier in the 1970s with the introduction of pyridinium chlorochromate (PCC) and pyridinium dichromate (PDC), courtesy of E J Corey. These reagents are nicely shelf-stable, making for chuck-and-stir reactions that are hard to botch. 

The downside of chromium is that Cr(vi) is incredibly toxic. Personal health aside, to properly dispose of chromium waste takes extra work. Every time I reach for the bottle of PCC I hear the voice of Erin Brockovich in my head, scolding me. 

Alcohol oxidations using dimethyl sulfoxide (DMSO) are another cornerstone in synthesis. Although most textbooks mention the wildly-popular Swern reaction, now is as good a time as any to mention that equal credit goes to Moffatt, who first described the basic process. 

Whatever you want to call it, the ’Swern modification of the Moffatt reaction’ does a bang-up job for the synthesis of aldehydes or ketones from alcohols. Although not toxic like chromium, performing this reaction has a different sort of liability. Dimethyl sulfide is produced as a byproduct, and you will incur the wrath of your co-workers when the stench of rotten eggs permeates the air. 

Fast and clean 

No list of oxidants would be complete without the Dess-Martin periodinane (DMP). DMP has a lot going for it: it won’t poison the groundwater and nothing about it smells bad. Reactions are fast and clean, making DMP my personal favourite when screening oxidants. It’s not perfect: there are a some reports that DMP and related compounds are shock sensitive, so you shouldn’t smash the bottle with a hammer. And the molecular weight of DMP is a tad high, so you need to use a hefty amount. 

All these fancy chemicals have the common trait of generating waste that needs to be collected and disposed of. Wouldn’t it be nice to imitate nature by harnessing the oxidising power of O₂ itself? With the concern of climate change in the spotlight, a reaction that produces water as a byproduct seems more attractive than ever. Indeed, developing metal catalysts that use oxygen gas is a major topic of research. 

I’ve only just scratched the surface of oxidation; there are another 290-odd ways to transform an alcohol that have gone unmentioned. That’s quite a lot to choose from. None are perfect, and what’s right for you depends on whether you’re willing to put up with something that’s toxic, stinky, potentially explosive, or quirky in some other way. If that’s not enough, remember that alcohol/ketone interconversion is a two-way street. Just wait for the next installment about reducing agents! (Maybe). 

Dylan Stiles is a PhD student based in California, US