Friday Fun: Super-Calcium!

Super-Calcium
Source: Niggemann Group, RWTH Aachen

I like to stroll through journals on quiet mornings, over coffee. After a few months, you start to see trends crop up: The Gold Rush. Carbon-carbon bond cleaving chemistries. Fluorine and boron everywhere.

A new trend almost snuck in under my radar: Calcium catalysis. In the past, a few groups had played around with amino-ene reactions, arylated tertiary alcohols, and made some enantioselective calcium pincer complexes. But I couldn't honestly tell you that I had branded any specific group with the "calcium" label, as opposed to the "palladium" or "organocatalysis" badges worn by many.

Well, the Niggemann group in Aachen, Germany appears to want that distinction. Prof. Meike and her team have released a slew of interesting reactions - Friedel / Crafts, [3+2] cyclizations, cyclopropanations - with more popping up seemingly monthly. But...calcium? The stuff ingrained in our bodies, stapled in the phosphate matrix of our bones and teeth? The stuff I eat in yogurt, milk, and cheese is now a catalyst?

Source: Niggemann Group, RWTH Aachen

Let's dig a bit deeper. To start, Niggemann's group uses a weakly-coordinated calcium complex, calcium (II) bistriflimide. Next, they exchange anions with a quaternary ammonium source, producing the "mixed" catalyst Ca(II) PF6 NTf2, increasing organic solubility. The group claims that this complex exhibits both high selectivity for olefin coordination and stability against air and moisture - both important properties if you're exploring new reactions!

This new catalyst combo, dubbed "Super-Calcium" (with mascot, above), reacts like a wild hybrid of alumnium, gold, and palladium. It activates alcohols as leaving groups (Al). It permits [1,2] hydride shifts (Pd). It's a hard enough Lewis acid to unzip donor-acceptor cyclopropanes, but soft enough to permit hydroarylation (Al / Au). Checking some of the historical calcium-catalysis reactions (above) reveals even more head-scratching reactivity reminiscent of magnesium, titanium, or vanadium.

So, what's really going on here? First, I'd say it's early days: Some deuterium-labeling studies were done on the older reactions, and molecular modeling on this latest batch, but several steps (Vinyl cations? Hydride shifts?) make me wonder exactly how intimately the central calcium atom gets involved. Second, no one yet knows the exact structures of these reagents in solution; look how long it took to figure out LDA!!! Third, Meike's battle cry rings mostly true: reactions exploring the reactivity of early alkali metals (potassium? barium?) remain largely terra incognita.

More reactions will lead to more interest; perhaps a Calcium Craze looms over the horizon? Time will tell.

Happy Friday, Everyone!
-SAO

Please Set Me Straight on Synthetic Yellow Dyes

Dear Ms. Hari and Ms. Leake,

Good evening. Earlier tonight, I read your change.org petition calling for a ban on Yellow #5 (tartrazine) and Yellow #6 (Sunset Yellow) in Kraft Mac & Cheese. I must say that, while not a mac connoisseur myself, I have certainly eaten it once or twice. Furthermore, I agree that all processed food companies should periodically review their popular brands, taking into consideration consumer sentiment, and should make every effort to produce quality goods. 

Since your petition now has well over 230,000 signatories, I assume many in the general public agree with us. But I must know: Where did you source the scientific data for your claims?

Let's start from the top:

"Artificial food dyes...are man-made in a lab with chemicals derived from petroleum (a crude oil product, which also happens to be used in gasoline, diesel fuel, asphalt, and tar)."

Well, I can't disagree with the first part - they're certainly synthetic azo dyes. However, I'd like to discuss your second point, where you equate 'petroleum-derived' to well-known flammable, smelly, or oozy black 'chemicals.' These azo dyes don't really resemble the compounds you've mentioned at all - gasoline and diesel are long saturated chains of carbon atoms, while tar / asphalt are collections of polycyclic aromatic hydrocarbons (PAHs), which might resemble these dyes if you took just the naphthalene portion (right-hand side), deleted the "OH" group, and chained a whole bunch of 'em together.

Yes, azo dyes come from organic chemists (like me!) in a lab somewhere. But, you know what else comes from petroleum? Pharmaceuticals. Plastics. Cosmetics. Synthetic fibers. Coatings. Many of the modern materials you interact with on a daily basis.

"Require a warning label in other countries outside the US."

I believe the US also mandates (Code of Federal Regulations Title 21, section 74.1705) inclusion of tartrazine on labels - I've seen it listed on my mouthwash. (Incidentally, that same CFR page sets exacting limits on impurity content in these dyes)

"Have been banned in countries like Norway and Austria (and are being phased out in the UK)."

Are we just lifting directly from Wikipedia by this point? 

"Yellow 5 and Yellow 6 are contaminated with known carcinogens (a.k.a. an agent directly involved in causing cancer)."

Now here's where things get interesting. Head on over to TOXNET, the National Library of Medicine toxicology database. I've looked up both Yellow 5 (tartrazine) and Yellow 6 (Sunset Yellow), and I can't find any positive studies suggesting carcinogenicity. Ditto both Wikipedia pages, and even my copy of the Merck Index (13th Ed., pp. 9091 and 9157).

What about the potential impurities, you ask? Sunset Yellow can indeed be contaminated with Sudan I (see picture, above), a non-sulfonated version of the compound. Sudan I lists as a Class 3 Carcinogen, which (thanks, ACS!) means "unclassifiable as to carcinogenicity in humans." The European Food Safety Authority (EFSA) actually re-evaluated Yellow 6 in 2009, declaring an acceptable daily intake and noting Sudan I contamination was well below the allowed limit for lead in processed foods.

I won't argue against your claims regarding hyperactivity and allergic reactions; the Hazardous Substances Databank (linked through TOXNET) indicates several studies in which patients do indeed respond poorly to artificial dyes. However, I will note that the responsive patient percentages are often low, and many weren't deemed statistically significant relevant to placebo.

I don't disagree with consumers' rights to petition companies for product changes. But please, check the science, lest you lapse into harmful chemophobia.

Thanks,

See Arr Oh

Update (8:00AM 3/15) - @thefoodbabe contacted me on Twitter with the following: "you are incorrect in your critique of our petition, I've got to go interview live with CNN now - Ciao"

Update 2 (9:00PM 3/15) - CNN posted two responses to the petition.
One leans scientific, the other mostly re-states the bloggers' objectives.