Greener Nylon Synth? Just Add UV and Ozone!

"Any sufficiently-developed technology is indistinguishable from magic" - Arthur C. Clarke

Looks like we'll soon have a more straightforward way to make stockings, zip-ties, and tire belts. 

Adipic acid, a six-carbon diacid representing one of the "sixes" in Nylon 6-6, apparently takes quite a bit of industrial "elbow grease" to make. The current process, starting from cyclohexane, requires cobalt, manganese, copper, and vanadate salts, high pressures of oxygen gas, and hot nitric acid. Out the other side, its responsible for 5-8% of the nitrous oxide we humans spew into the atmosphere each year.

From Science 2014, Hwang and Sagadevan

Now, researchers Hwang and Sagadevan (National Tsing Hua University, Taiwan) believe they have a better method. Reporting in this week's Science, the two disclose a method that sounds so much simpler: flush a sample of cyclohexane with ozone and UV light, and, presto! Solid adipic acid at the bottom of your reactor. No metal salts, no nitrous oxide, no high pressures or temperatures.

Wow, that looks a lot simpler.

The researchers note that zapping ozone produces both singlet oxygen, ¹O₂, and a single singlet oxygen atom O(¹D). The highly reactive single singlet (say that three times fast!) can easily insert into C-H bonds, and, since it seems to prefer insertion next to an already-oxidized carbon, the diol, diketone, and finally diacid products are formed preferentially.

Applause, please: Look at this beautiful pictorial SI!
Twice, in two days.

Just for fun, Hwang and Sagadevan crack open some larger hydrocarbons, and check the selectivity of alkyl-functionalized rings and aromatics. There are tantalizing possibilities here that I'm sure, given the ease of this reaction setup, most organic chemists will already be trying: how do complex natural products* react under these conditions? If anyone tries it this weekend, please drop me a line.

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*For that matter, I wonder if this pathway is operative in human tissues under physiological conditions? Sunlight does have some 300 nm band, and we certainly come into contact with ozone out in the wide world. Hmm.

Oxidation? Just Add LEDs

Researchers at the University of St. Andrews recently reported an extremely short synthesis of melohenine B, just two steps from a related commercially available alkaloid. The (6-9-6-6) core skeleton of melohenine B, a rare duck for sure, had only just been disclosed in 2009.

Ready for the kicker? The final step requires nothing more than dye, air, and light.

After LAH reduction of commercially available (-)-eburnamonine (a vasodilator), the chemists needed to find a reliable method to blast apart the indole 2,3 pi-bond to bring about the core 9-membered ring. Various "go-to" oxidants such as m-CPBA or sodium periodate gave N-oxide or returned SM. Hitting the compound with a molecular piledriver - ruthenium oxide - produced the product in a stingy 21% yield, along with elimination side products.

Taking a cue from an early photo-oxidation example, and perhaps the ozone-based Witkop indole oxidation, the researchers tried methylene blue-promoted singlet oxygen cleavage. This worked much better than anticipated ("quantitative" yield) and returned a single diastereomer resulting from hemiaminal ring-opening and substrate-controlled closure.

Now I've seen a lot of photochem go by in the past 10 years, most of which requires 1) sunlight, 2) a CFL bulb, or 3) an array of blue LEDs. But this may be the first time I've seen such simple conditions; the reaction requires a single red LED! Check out the protocol, lifted from the SI:

"The substrate (12 mM) in methanolic methylene blue (40 uM) was irradiated by a 627 nm 3 W LED with vigorous stirring under an air atmosphere. The progress of the reaction was monitored by TLC (generally 3-24 hrs)."

That 627 nm light shouldn't surprise anyone, since it's right in the middle of methylene blue's absorbance spectrum. Still, the application of technology usually found in day spas to organic synthesis makes me smile.