Would the phosgene give selective halogenation of the right parts of the sugar? I’m a little torn here in that way of doing the synthesis anyway. Yes, phosgene is handy (I do a couple syntheses using a phosgene solution myself) and easily available in very large quantities but the toxicity would make me think twice about using it, especially on such a large scale. Could you use diphosgene or triphosgene and get the same results?
Ah, found the synthesis, or as much as you can get easily pulling info from patents. (I hate using patent literature for research.) Looks like the chlorine sources are trichlorotoluene and thionyl chloride.
Given that, I wish they’d come out with a version that’s sweeter. Maybe double-sweet or something. Then I wouldn’t have to use 50 packets in a mug of coffee (okay, really about 4 or 5).
Eating powdered sodium will kill you*, but if you chemically alter it with chlorine, it becomes salt, which you need to live. Take any molecule, alter it by even a single atom, and you can get a new molecule with completely different properties. You can’t tell much with the properties of the two combined materials by themselves, it’s the properties of the final product that matter.
*At least, it will catch fire in your mouth, esophagus and stomach, and turn into Lye, which I can’t imagine being a good thing.
Without divulging more than is allowable, yes phosgene works. Purely hypothetically of course, if you were a fine chemicals manufacturer that specialized in phosgene derivatives and generated phosgene on site in such a manner that made it dirt cheap and you had excess capacitiy because you were no longer making Z-asp for another artificial sweetener you might be very interested in making Splenda. Furthermore, phosgene’s convenience in synthesis coupled with its toxicity for handling on any scale might be your bread and butter and the only thing that keeps you running in an ultra competitive chemicals market, so you probably wouldn’t bother much with di or triphosgene.
I see. I’m still impressed that it can be done with such selectivity (I have to assume you’re using some sort of catalyst or something that makes it work that well.) Just a professional curiosity on my part–don’t say anything that could get you in trouble.
Thats tritylchloride not trichlorotoluene. I have never seen that used as a chloride source. Or is it a chlorine radical source since the trityl radical is so stable. It seems as if in the next step they are making the acetates to protect some of the hydroxyls. What is confusing is that in the next step it seems as if they are removing them with tosic acid. I can only think they might be making some sort of acetal there. I’ll try to find that paper to figure out more.
Just for my edification, how much household chlorine (in drops, please) to a gallon of suspected water? (You know, just in case they pop the bomb tomorrow!)
You are quite right, I misread the structure. Sorry about that. Even if it was being used as a chlorine radical source, wouldn’t there need to be some kind of initiator?
If I’ve got some downtime today, I’ll take a look in the literature as well. At least, if it’s described in the patent literature, the references will be open.
It’s not as simple as sugar + phosgene = sucralose. (step 3: Profit!)
The sugar does get over chlorinated (not completely). Using phosgene, some of the hydroxyls (but not all) are converted to chloroformates which are then decomposed to chlorides. After that, my info is fuzzy but there is an acylation and hydrolysis to rid the remaining surplus chlorines. Apologies for the lack of detail, not attributed so much to secrecy as the fact that while this work was going on I was busy working on Valacyclovir. (and now am in a totally different line of happy molecules)
Unfortunately my school does not subscribe to Faming Zhuanli Shenging Gongkai Shuomingshu, 1800194, 12 Jul 2006
From what I can figure out based on my SciFinder search
The first step protects the non-ring carbons with a trityl group (I knew it couldn’t be a chloride source.)
The second steps (including the tosic acid step.) puts acetate groups on all the remaining hydroxyls.
The Sodium hydroxide removes the trityl groups.
Somehow the t-butyl amine removes the acetates from the carbons we want chlorinating but ads them to the carbons we don’t. (Mechanism anybody?)
The thionyl chloride of course chlorinates everything we want.
The remaining steps remove the protecting groups.
Grr. Acetylation. Not acylation. Stupid guest inability to edit. Grumble grumble.
Sugar chemistry involves lots of fun protect here, deprotect there, react here, don’t react there, do the hokey pokey turn yourself about tricks. I knew many of them last year for the class I took, and have apparently dumped my brain of everything I knew about the anomeric effect and its kin.
This is reminding me of a stevia sample my mom got at a health food store. This “all natural” plant-based alternative sweetener had a horribly strong chemical taste.
