Molecule of the Day

This is one that will be familiar to anyone who works in chemistry, but I was a bit surprised to see it the first time I went into a lab.

Certain compounds, called esters, can be prepared from an acid and an alcohol (usually a carboxylic acid). They are ubiquitous in the flavor and fragrance industry (although they’re not quite stable to water over the long-term, and once an ester is hydrolyzed, it liberates its component alcohol and acid, which are often pretty rank).

One classic organic lab is preparing some sweet-smelling esters from otherwise nasty-smelling carboxylic acids and esters (such as, for example, amyl butyrate, prepared from pentanol and butyric acid, the latter of which smells of vomit). So, with all this, I always just thought of small molecule esters as slightly unstable, nice-smelling things you usually encountered in small quantities.

I was surprised to see a giant 4-liter jug of ethyl acetate the first time I worked in an organic synthesis lab. Like most esters, it has a nice smell, although this one isn’t quite as sweet as other esters. Apparently it’s used as a fruit flavoring occasionally, but it finds most of its use as a solvent (non-acetone nail polish remover usually mostly EtOAc, for example).

Ethyl acetate is one of the few bulk esters you’ll encounter – probably because ethanol and acetic acid are so ubiquitous and cheap. The only other I can think of off the top of my head is propylene carbonate. You used to see people use butyrolactone (GBL) a lot – I’m told it’s tops as far as solvents go – but being a precursor to GHB, legitimate use decreased sharply a few years back. Apparently you can still buy it, but I’m sure it’s one of those “watched” chemicals.

Esters – gotta love ‘em.

Comments

  1. #1 MiddleO'Nowhere
    September 21, 2006

    You can still get GBL from Aldrich for $0.03/g. I bought some a while back for a test reaction. It was only after I received the bottle that it clicked that GBL was just a simple reaction away from GHB. I’m guessing my name is now on a list somewhere keeping track of who buys it.

  2. #2 Dennis
    September 21, 2006

    I’m angry, because we ran out of ethyl acetate and have to use acetone to run TLCs and columns. :_(

  3. #3 Dirk
    September 21, 2006

    Is it true (or am I misremembering) that ethyl acetate sold as an industrial solvent contains lead? And that the government mandates sellers add lead so that the buyers will not use the ethyl acetate to make ethanol for consumption and circumvent the liquor tax? A teacher told me that a long time ago.

    Also, didn’t fraternities used to mix ethyl acetate into the party punch? People would drink the punch (no alcohol), but the ethyl acetate would hydrolyze in the stomach and result in drunk partygoers. Maybe that is an urban myth.

  4. #4 MOTD
    September 21, 2006

    Not sure about ethyl acetate in punch, but it’s not particularly water soluble. In fact, one venerable procedure in organic chemistry is liquid-liquid extraction with water and ethyl acetate (concentrating your organic product in the organic phase of EtOAc, while salts, etc. are left behind in the water). In lots of cases, this is convenient, because water sinks in ethyl acetate, so you can wash over and over with water (such extractions are usually done in a pear-shaped bit of glass called a separatory funnel, with a nozzle on the bottom to let out liquids). Not sure how metabolism/hydrolysis goes in vivo.

    I had no idea GBL was available. I heard rumblings of people (in legit academic labs) in the early 2000s preparing it by some bizzare street prep (KMnO4 oxidation of THF, if I remember correctly). Haven’t ever had cause to use it, but if you look at the old literature, I get the impression it used to be fairly ubiquitous. I don’t think you even need to hydrolyze it for it to have the requisite GABAergic activity (i.e., one could just take GBL orally).

  5. #5 Adam
    September 22, 2006

    Fascinating! I saw a huge (like 2 L) jug of acetone at the hardware store today.

    Speaking of ethanol, I have just made wine soap (it looks a lot like chocolate) and am about to go on to Seagram’s Seven Crown whiskey! :-)

    The FDA says GBL can be converted to GHB in vivo.

  6. #6 Adam
    September 22, 2006

    Also, best wikipedia sentence ever: “If ingested undiluted through the oral route, GBL can irritate innards.”

    I wonder if any papers in refereed journals get to use the word “innards.”

  7. #7 Snarfevs
    September 22, 2006

    Let’s not forget Ethyl Acetate’s wonderfully resonance stabilised and similarly pleasant smelling big brother, Diethyl Malonate!

    Ooh ooh do the knoevenagel condensation or the diethyl malonate / urea condensation to barbituric acid – extremely elegant.

  8. #8 KevinC
    September 22, 2006

    Ethyl acetate is the most common posion entomoglogists use in kill jars. Knocks most of them out pretty fast. We use several liters when we hold the entomology class every other summer at the coumunity college I work at.

  9. #9 MiddleO'Nowhere
    September 22, 2006

    Maybe GBL is like pseudoephedrine. If you buy too much in a short amount of time, they come after you. I only bought 25g.

  10. #10 Yttrai
    September 22, 2006

    “Like most esters, it has a nice smell…”

    Bah! Spend more than a few minutes around it. Ethyl acetate is beyond nauseating past the first few dozen times you smell it. I know of few med chemists who can stand the smell of it anymore. Even methylene chloride has a less offensive odor at this point. (Note: I’m not saying it is a less offensive compound!) I will risk the headache and take the extra precautions to work with diethyl ether as an ethyl acetate substitude any day.

  11. #11 MOTD
    September 22, 2006

    Yttrai: Really, that bad? It’s not my favorite smell, but I enjoy the odd whiff (the fact that I rarely run a column, and when I do, it’s in the hood probably has something to do with this). I notice a cloying buttered popcorn note after I’ve smelled it for more than a minute or so. Dichloromethane I barely smell, which always scared me a bit. Same with chloroform, come to think of it. Ether I love for the first few minutes, then I just want to vomit. THF always smelled like ether that went bad to me.

  12. #12 Yttrai
    September 22, 2006

    MOTD:

    Its a saturation thing, i think. When i was young (be nice, pretty please) i found it mildly annoying. Now it is up there with piperidine or pyrrolidine. I can’t use it outside the hood at all. Ether still smells nice to me :D THF isn’t as bad as it was in grad school when i ran the THF still – again, i was oversaturated.

    Keep in mind a lot of these are genetic. I can’t smell methyl indoles (skatol – the stench in poop) or other amines, or sulfur-containing compounds that are not sp3, like thiophenes or thioamides or isothiocyanates, but all of those drive my coworkers insane. I can smell tin, however, as well as tosyl chloride, which many people can’t smell.

    This would be a fun survey or seven to run: what can and can’t you smell, and what smells nice versus what makes you nauseous.

  13. #13 Molecule of the Day
    September 22, 2006

    I can’t believe you can’t smell skatole. Can you smell unsubstituted indole? I think they are the two main odorants in feces (both are present). Does this mean they don’t smell at all to you? Bizzare.

    I have to agree on tosyl chloride. Here, again, I get buttered popcorn…sort of. I don’t know if it’s actually buttery, but it’s sort of thick and sticky, one of those smells that doesn’t go away very fast.

    Piperidine smells like any other low-MW amine to me. I’ve never used pyrrolidine. As for sp2 sulfur, have you ever smelled OCS? (O=C=S) That smells just like saturated sulfur compounds to me.

    More smell weirdness: I love thiols at dilution. I can’t smell acetonitrile at all. I can’t smell DMSO unless I’ve been working with it a lot lately (which I have, now even the room temperature stuff gets me).

    I hope everyone can just agree that acetophenone smells wonderful.

  14. #14 Paul Dietz
    September 26, 2006

    I don’t know if you’d count it (it’s a mixture), but biodiesel (methyl esters of fatty acids) is being produced in industrial quantities as a motor fuel.

    I don’t know what it smells like.