I wrote this post a couple of weeks back, but wasn't happy with how rambling it was. Anyway, it's only getting more out of date, so I'm putting it up now. Someone might learn something.
I’ve always had a soft spot for hypervalent iodine reagents, especially iodine(III). In fact, they were the cornerstone of a methodology project that I worked on last year. You can imagine, then, that the rather usual looking iodosobenzene derivative above, which was published in Org. Lett. a couple of weeks back (DOI: 10.1021/ol301085v), immediately caught my eye. Such compounds tend to be very useful oxidants, and you can check out a few recent applications on the relevant organic-chemistry.com page. Surprisingly, though, this wonderful new reagent wasn’t being touted as an oxidant (although I’m sure it is)… apparently, it’s a great new coupling agent!
You’ll have to read the paper for the specifics, but needless to say good results were obtained for couplings between acids and alcohols, and even the rather more oxidisable amines and acids. Racemisation was low, conditions were mild, and in fact, if your substrate wasn’t too redox active, you might even consider trying out this wonderful sounding reagent. But that’s where things get a little tricky. Of course, you can’t simply just buy this particular magic powder from Aldrich yet, so you’ll have to make it yourself. If you know a little iodine chemistry, you won’t be surprised to hear that you can just make it from the corresponding iodoisophthalic acid by oxidation, and this step has been reported using bleach. Easy. Except you can’t buy the iodide (at least not from any of the common suppliers in the UK). I’m sure you can outsource production of it, but no-one’s going to do that to just to add another line to a table of conditions tried. Better put that iodide into Scifinder!
Perhaps not too surprisingly, it’s made from the corresponding aniline by the very useful Sandmeyer reaction. The aniline itself, though, is still not commercial, although there are a couple of options available for its synthesis. The most recently reported is by the oxidation of acetyl protected toluidine with permanganate, but although that’s a reaction that sometimes doesn’t give total crap, as with many journals whose titles are 60% vowels, I sadly don’t have access to Gaodeng Huexiao Huaxue Xuebao to see what the procedure is. The other option to get the required aniline is via the oxidation of the isatin shown below. Fortunately, it turns out that this actually is commercially available, although for the princely sum of almost £200/10 g. So, unfortunately anyone in the UK wanted to try this new reagent has quite a bit of work to do! At least it’s recyclable.
One thing I did learn from chasing down these references was a new named reaction, the Sandmeyer isatin synthesis. I’d never really given much thought to where isatins actually come from, so let’s quickly look at how you might make the commercial isatin if you had to. Turns out it’s as easy as heating methyl anthranilate with some chloral hydrate and hydroxylamine in sulphuric acid, followed by hydrolysis.
1. Traugott Sandmeyer did particularly well to get two important reactions named after himself, considering he didn’t even have a degree in Chemistry.
2. Interestingly, although chloral hydrate is a controlled substance in the US and Canada, it isn’t in the UK.