things I've learned recently

I've had a run of less than optimal luck recently when it comes to health issues. Everything is fine now, but I think I've learned (or re-learned in some cases) some useful things.

Flu:
If you're feeling a bit under the weather and don't know if you should go to work or not, here's a clue, don't. You're just going to cough on your hand, use a doorknob, and get someone like me sick who will curse you for being such an asshole.

It's a good idea to have things on hand in the pantry for times of sickness. I forgot this cardinal rule and was totally out of Gatorade or any of its generic knockoffs, and was subsequently too sick to go out and get some. Rehydration is of the utmost importance when you're pissing out your ass every 15 minutes, and the human body is quite bad at absorbing pure water. By accessing the sodium channels in the GI tract, water is absorbed much more readily.

Canned chicken broth is like a magic fucking bullet, and has an extended shelf life. After a few days of not being able to hold anything down, including water, a warm cup of this poultry flavored brine is the most sublime dinner treat ever. And, of course, the salt helps to rehydrate.

Rabies:
Rabies is a deadly disease, everyone knows this, but by the time you show symptoms you're fucked. If you actually show symptoms of having rabies the chances of dying are greater than 99.99%. If you take the vaccine prior to that the chances of survival are very good.

The modern vaccine is no where near as bad as old vaccine with the multitude of injections in the abdomen, however it is much more expensive at ~$1500. These days only five shots are needed: immunoglobin, and four rabies vaccine shots over two weeks (days 1, 3, 7, and 14). All are intramuscular (IM), and the the immunoglobin, the "first shot" is 6 x 2 mL vials for someone ~195 lbs. As a reference a typical vaccine booster shot is in the neighborhood of 1 mL in the arm. This shot is actually 3 or 4 big-ass, deep tissue shots (e.g. thigh or buttocks).

If you get bitten by a dog take the time right then to find out if the dog has had its shots. Don't assume that just because it's a healthy looking poodle-like dog in one of the richest neighborhoods in the US that everything is fine, and he/she must be healthy.

There are several ways to test for rabies in humans, but no individual test is sufficient by itself. One of the tests involves spinal fluid. I'll let your imagination run wild with that one.

If for some reason you get bitten and are stupid enough not to get the necessary information right then, and need to go back and find the dog more than two weeks later do it regardless of how unlikely the possibility of success seems. The kindness of strangers can be truly surprising sometimes.

If a dog were to have rabies such that its saliva were infectious the life expectancy for the animal is less than five days. Quarantine guidlines for animals is ten days, just to be sure. Therefore just getting to see the furry bastard walking around two weeks later is sufficient to clear a bite victim of being used as a pin cushion.

nice simple method

Saw this today in the JOC ASAPs.


I'm a fan of any new method, or method improvement that is simple, efficient, straightforward, and useful. While I haven't ever made a sulfonamide that wasn't a protecting group, they are handy for other things, and pop up in drugs as well. These guys got the reaction to work with one set of conditions on electron rich and poor aromatic thiols, a few aliphatic as well, and it appears to be selective and mild as well.

In fact the only things I can negatively comment on at all are that I would have liked to see more aliphatic examples, and acetonitrile is an expensive solvent. However, I bet that within the next year or so people will be buying cars in stupid numbers again, and acetonitrile will come back down in price.

Edit: I somehow gave the wrong journal title, but the right link. Thanks to Dr. Miller for pointing it out.

great idea

Yesterday our lab and another had the privilege to go have lunch with Philip S. Portoghese and see him give a seminar later. During lunch we were talking about journals and the state of the business of journals, he's been the editor of J. Med. Chem. for 37 years, and ACS's new headache inducing paper journal format where they have two pages of material per page of paper came up. I mentioned that it felt like I was reading a girlie magazine whenever I turned it sideways to flip through the issue, and someone else in attendance remarked that we should have a centerfold with a reaction or compound of the month. What an awesome idea! People would be vying for the cover with pretty pictures, but others would be competing to get the centerfold with great science! Truly an idea who's time has come!

edit:
I said something stupid, and would like to clarify. You usually get the cover by publishing good work, but the cover itself is something pretty that is related to the work, and usually not the work itself.

The centerfold could be pure, unadulterated, awesome science.

Somebody Explain

Am I missing something?



This is a really expensive and complicated way to do a sophomore organic reaction. Instead of making the silyl enol ether and treating it with stoichiometric CAN and 2,6-di-tBuPy (both expensive and used in large excess 2 eq and 4 eq respectively), why not just deprotonate with LDA and add an allyl halide?

Can anyone think of a reason to do this reaction (aside from somehow publishing it in Org Lett)?

ignorance is bliss

Our secretary is a true sweetheart, but is also rather fond of drama, especially if it is totally unnecessary. A recent example includes someone attributing her name to a work order incorrectly. This would usually involve a simple "that wasn't me" phone call or email to rectify, but for her she planned out an involved strategy of who needs to be contacted and provisions for difficulty with backup plans. In reality the order actually has nothing to do with her at all, excepting the bookkeeping error, and she could simply ignore the problem and it would go away.

Typically when I talk to her, like after a morning greeting, I'm prepared for some sort of soliloquy on her crushing life events. I try to remain stoic throughout. She's a sweetie, so I don't want to shut her down, but I also don't want to add fuel to the fire. Typically I give her some noncommittal remarks, and, if I actually have any knowledge of the area, some help.

Today she was extra excited and proceeded to tell me a story about a man who had some rare condition and had kept a gorilla in his basement and fought with it for several years until it had actually killed him, even tearing off his arm at one point. I, politely, called bullshit, and recommended she check it on snopes.com. She continued like she hadn't heard anything so I nodded, repeated myself, she continued, I spelled snopes.com for her, and then left. A little while later she said she had found the article and tried to give it to me, so I chatted with her, but didn't take the article and left.

Eventually I had a minute and was curious so I actually looked it up using some nice generic, but defining terms, and it popped right up as hit number one. As it turns out it's an onion article, and her lack of understanding was so goddamned hilarious I couldn't decide whether to tell her or not. In the end I told her. There was no practical way to follow the progress of the story as she told it to other people, so the entertainment value was pretty much used up, and it was time for some modicum of damage control.

wow

It's hard to say if this is completely and utterly awesome, or just another interesting blip on the radar that may someday make it into textbooks.

JACS ASAP, DOI: 10.1021/ja9061097

I had and organic prof. years ago who referred to fullerenes as full of shit arenes, due to all the press they had garnered with little real applications found. They still have produced relatively little, especially when compared to sibling compounds such as carbon nanotubes, but every now and then something really neat like this comes out.


Also I learned a new word today, that I wish I hadn't: Suicidality.

practicality

This went to ASAP a little while ago. The method is interesting, and apparently successful, but the thing I liked most about it was one of the footnotes.


It's a bit unfortunate that a good method needs to be supported for not being catalytic, or any other little darling of the day, but it's nice to see it done once in a while.

It seems like most people who use buzzwords, especially in the title of the article, really do the buzzword in question a disservice, and it has little to do with the method besides poor advertising.

fun weekend

Esther came to town for a visit this last weekend, and we got to do some fun stuff. In addition to the fun stuff we ran into some interesting and odd things too, two of which I thought I would share.

On Saturday we thought we would go to Old Town Alexandria and check out the Torpedo Factory. We'd never been and heard it was neat, if the chance arises to go there, I recommend it. that place was pretty damn cool.

On the way out of town to go there we knew it was going to be a long day, so we stopped off at the CVS to get some water bottles to take. And the expected customers for a Saturday morning were milling around the store. Only one thing stood out, and I wouldn't have noticed it at all if I hadn't happened to look over at just the right time. There was a little old lady browsing in an aisle who looked for all the world like any middle America grandmother except for one thing. She had no nose. Where her nose had once, presumably, been was a flat spot covered by a triangular band-aid. For just a moment I involuntarily thought of Vincent D'Onofrio's character Pooh-Bear from the Salton Sea, and subsequently of his pet/torture device badger Captain Stubing. Rather an odd juxtaposition for a nameless granny.

I couldn't find a pic of him without the bad prosthesis, sorry

The other encounter happened when we went to a movie one night. We saw District 9, and pretty early on I had to go to the bathroom, and I felt it would be best to get it out of the way before all the crazy action really started in earnest. It just so happened that there was a unisex singlr bathroom right outside our theater that was open. As I approached it, I could see through the slightly open door that someone had already vomited in there. I peeked my head in to see how bad it was, to determine if I could still use it, or would need to look for another. I was shocked to see that not only had someone basically turned their entire alimentary canal inside out, but they had placed the bulk of the detritus as far from the toilet and trash can as possible while still residing in the same room.



In addition to the grotesque landscape was a not unpleasant odor of blueberries or raspberries. So I was able to use the bathroom in relative comfort, even in that state. I went back after the movie to snap these pics and the odor had persisted.

sweet, sweet buzzwords

I saw this beauty this morning while having my morning tea, and it just cements in my mind how badly people want to latch onto popular, and often useless, nomenclature. Perhaps the best example of worthless jargon that is used frequently is "chemoselective" which appears to have no proper definition, and adds nothing to the chemist's lexicon that wasn't already available, but a close second these days seems to be "organocatalytic".

David MacMillan appears to be a great chemist, and an ok guy, but the real fame in his chosen area seems to be based largely on sales tactics. His classic contributions to the area are merely improvements on existing methods. Is that bad? Of course not, but now everyone else wants in on the game.

I think it's a bit odd to call most of these things "organo" catalized reactions anyway, because the active centers typically are nitrogen. Anchimeric assistance is often provided by oxygen or other nitrogens, and the hydrocarbon organic portion is typically scaffolding, as in many inorganocatalized reactions.

In today's example the authors most likely wanted to add some pizazz to their paper with needless, and inappropriate, jargon. It's too bad, really, because the method is actually quite nice, and doesn't need the added tripe. While the title proudly claims the method is organocatalytic, the graphical abstract has a nice large fluorine cation, and no carbon to be seen.


The fact that it says salts in the title should be a giveaway, but it never hurts to look on a bit further. The first depiction of the catalyst is given in scheme 2, where we see it's N-fluoropyridinium
triflate. That's like calling a reduction with tetrabutylammonium borohydride organostoichiometric.


Some very quick math shows that the hydrocarbon portion of the salt is only 31.2% of the mass of the compound, and that the inorganic active fluorine is just below that at 30.8%. To really beat this dead horse lets look at a heavily skewed example of a common inorganic catalyst, tetrakis(triphenylphosphine)palladium. This common catalyst and catalyst precursor has more than 10 times the hydrocarbon mass per mole and the portion of the catalyst that is hydrocarbon is over 80%, that's even better than the carbon rich MacMillan catalyst (5S)-(−)-2,2,3-trimethyl-5-benzyl-4-imidazolidinone monohydrochloride at 69% hydrocarbon.

Suffice to say I wish people's chemistry would stand on its own two feet but it seems everyone knows that massaging the system works better, and if someone else has laid the groundwork why not capitalize on it.

lab accidents

I'm pretty lucky in that I have very few of them, and they tend to be minor. Oddly, however, the worst lab accidents have always been doing mundane things. The things that can really go awry are usually surrounded by a lot of care and multiple layers of safety and protection, so if things go wrong it's not too bad. Messy, but not damaging.

The few accidents I have had that involved personal injury typically come from things I really didn't expect, and therefore I wasn't watching like the paranoid neurotic I typically am. Quite a while ago I was doing a liquid liquid extraction and, since I wear glasses anyway, I wasn't wearing safety glasses. A lone drop flew off the drip tip of the funnel and arced perfectly over my glasses into my eye. I don't remember what was exactly in the funnel at the time, but it was probably the usual mix of aqueous mineral acid and product mixture in organic solvent. I do remember that it was so stunningly painful that it took specific effort on my part to maintain my grip on the funnel, and keep my hands and arms from involuntarily relaxing and dropping it.

My eye picked up a slight yellow tint for the rest of the day, and shortly thereafter I grew some small bumps on my lower eyelid in a cluster. I don't know if they came from that incident or not, but they were an almost daily reminder of it for about 10 years until they grew out and fell off earlier this year.

In grad school, on two separate occasions, I was putting the cap on an NMR tube, and the tube broke directly between the two sets of fingers holding the tube and cap respectively. Both times I accidentally pushed the shards into either hand. The first time it was about 2 am, and I wanted to get one last NMR in before I left. I was bleeding so bad from one of the cuts I couldn't really do anything but hold a paper towel on it, and there was no one left in the lab, or on my floor that I could find. I had to sit there like an idiot until it stopped bleeding sufficiently that I could tape it shut with label tape. We were, of course, out of band aids. When I got home much later, after cleaning up the mess I had made, I changed the tape out for a bandage. It was interesting/gross to see that I had cut a question mark shaped hole as the tube attempted to get a core sample, and it was a challenge to remove the tape off without the flap peeling up and separating from the fat and collagen layers. I now throw out severely chipped and cracked NMR tubes, and put the caps on very very carefully.

Earlier this week I was getting ready to go home for the night, and was shutting everything down at my hood and bench. I kneeled, turned off my pump, and raised the trap out of the dry ice/acetone filled dewar. The dewar tipped over and poured its contents down the front of my shin and into my shoe. I was happy to see it hadn't broken and sent glass flying while deafening me, while at the same time I was stomping and shaking my shoe to remove the acetone from around my ankle. Oddly, and thankfully, there was little damage. My sock did soak up quite a bit in the front and freeze, unfortunately. An immediate survey showed the damage was minor, I finished shutting down and split. When I got home, I figured I would photograph it for fun. I have a great series of a fluid filled, swollen, and highly colored ankle healing from hitting my shin a few years ago, you just never know when this stuff will come in handy.

I apologize for the shitty pictures. Apparently my recently replaced phone had a protective film covering the INSIDE of the lens cover that I was unaware of until today.

The night of the "incident"

the hair was already gone,
too many cheap ski boots took care of that in my youth

As you can't really see, the affected area is reddened and swollen pretty evenly. There is already a bit of ridging where the elastic of the sock was. It felt a lot like a reasonably bad sunburn.

Several days later:

Most of the swelling and redness are gone except in the most burned part. Doesn't hurt anymore except for when direct pressure is applied. Usually on accident, and is quite a surprise.

Today:

Look at how clear that is when you remove that little piece of fucking plastic! The color is somewhat unpleasant looking, but it feels fine, and is healing well.

Interestingly, a few days ago the same thing happened, and without any surprise or real thought my knee shot forward to catch the dewar and balance it until I had a hand free to right it. I think perhaps it's time to reevaluate my pump trap system.

Back to lab today for the first time in almost a week, in many ways I love ACS meetings, in many ways my liver hates them.



A few weeks ago an acquaintance was in town for a night as he passed through, so Liam and I took him out to Adams Morgan for some drinks. While we were there he got flyered, and spent some time trying to pass it off on someone else for fun, while we made fun of him. Eventually I had a look at the flyer, which was covered in scantily clad chicks, so I kept it for later inspection. It's been sitting on my desk at home ever since, and periodically I pick it up and and check it out. This amazing little card never seems to disappoint and has revealed something new to me on almost every occasion.

hubba, hubba

Of course I grabbed it cause it's covered in scantily clad hot chicks, but the nature of the chicks is pretty intriguing, as well. All are black, all have pretty significant booty, and pretty much all are facing away from the camera or otherwise presenting their assets. "Birthday Sex Bash", "U Turn Me Out Sex Bash" ... wow! Now that's advertising!

Notice the completely naked girl in the forefront of the first side? That's not a pole wedged betwixt her cheeks, it's a sword.

A later assessment revealed some more details of interest, in nice small letters "No Athletic Wear" and "This is a Nigga Free Zone". Holy shit that's a bold statement.

Somehow, inexplicably, I missed what might be the best part. I was googling the names of the companies involved to see if there was any info about this place. Where was it? Is it a club, or a warehouse party-type set up? Were there police reports? I found an article describing this very flyer, which pointed out something very important I had missed. While on the front it says "Gentleman Only 25 years and Up", on the back it says "Ladies Night No Dudes Allowed 21 Years and Up". They are apparently trying to tap into a market of both chicks and dudes that want exactly the same thing in their smut! Absolutely amazing!

If that place was anywhere near here I think I would live there!

then profit!

Today's Org. Lett. ASAPs had this gem.


Things like this piss me off a bit but mostly confuse me. At first blush everything seems fine, they even clarify that the mechanism is proposed. Step one is a straightforward sequence of additions which is (probably) inaccurately described as a Diels-Alder, but the second step is pretty interesting. It includes the addition of a nucleophile to a tertiary carbinol under basic conditions. I can think of a couple of reasonable mechanisms that lead to the drawn product, but they aren't immediately obvious. In fact the one I like best doesn't even use that particular intermediate. In any case it seems to me to be a significant intellectual leap to the final product, and the authors a) don't actually know what's going on, b) think that it's the direct displacement of the carbinol, or c) know what is going on, but can't be bothered to describe it, even though they wrote the scheme in the first place.

None of those options is particularly satisfying, and these types of half baked situations always remind me of the South Park episode with the underpants gnomes and their business plan.

CRC

In today's JACS ASAP is a review of the 90th edition of the CRC Handbook. This thing has been around for so long that it never occurred to me that I didn't know what CRC stood for, until my octagenarian coworker asked to borrow my "rubber book". When he saw my confusion, he explained that the rubber book was a reference put out by the Chemical Rubber Company.

This huge tome may be the best know of all science reference books. I was actually really surprised to see a review of it. To me it seems that if you like reference information in book form, it's fairly obvious you need this book. I mean it's been out for 95 years, how could you not know about it?

As a side note, they seem pretty good about adding things to it, and seldomremoving old info. Sometimes the internet isn't the best place to find old information, but if it's chemistry and physics it's in the CRC handbook. They even take out errors from older versions. A collegue wanted to remove some water via an azeotrope that he found in the CRC. I thought it sounded like it wouldn't work (azeotropes tend to form between polar and nonpolar liquids, not polar and polar - good bit of minutiae to know), and after a little looking we found out it was a mistake that was removed from later versions.

big brass balls

I read a neat paper today in JACS. These guys used a laser to induce crystallization in a gel as a super sweet way to control crystal nucleation. As an example of their laser-jock prowess they exhibited Figure 1:

Laser? I hardly knows her!

In an odd way I love it when people do things like this. It's like they're saying "Our shit is so awesome we can dick around and pull off things only dreamt of a few decades ago as an exercise in fun and games", but in a much less insulting way.

more errors

Jim should like this one. In today's JACS ASAPs someone has a four component reaction, and published this graphical abstract on the website:

nice colors

I looked at it for a second not knowing what was wrong, but that something was up. Then I noticed that they have the same nitrile containing amide twice with different colors and slightly different drawing conventions. I assume that they used the colors for clarity of functional group positioning in the product, and that the difference in nitrile representation is simply a typo. However they may just be trying to make themselves look good, and indicate more strongly that the two components that are the same component are in fact two components. As everyone knows the greater the number of components in your multi-component reaction, the larger your chemistry phallus appears to be.

traveling

I spent this last week helping my Hot Baby move to California. Aside form the usual bits of car trouble and bad weather, it went very well.

The first part was spent in Austin packing, preparing and saying goodbye to people. I miss Austin a lot, but seeing things like the Cathedral of Junk, which I was unaware of when I lived there, make me miss it even more. Here's a grainy video I took of one small part of the Cathedral.

not bad for a vid from a phone, really

The drive to the bay area was long and, mostly, uneventful with some beautiful views once we were out of west Texas. Once we made it to the East bay, the usual housing issues were resolved, and there was even some time for sightseeing. We even had a chance to go out with Hillary and Dave for dinner and drinks one night.

As it turns out, all the bad things you hear about Oakland are entirely true. just look at the size of the rats in out hotel bathroom!

the dark one is longer than the toilet bowl when layed out

Feynman Lectures

I just found out about this really cool series of lectures at Cornell by Richard Feynman on physics. I have only watched the first lecture, but he does better than anyone I have ever seen at describing in a simple and interesting way the process of scientific discovery. Highly recommended.

There are seven lectures included on various topics. Click here to watch.

Allyl Amines - A Long Standing Problem

According to a recent journal article I read, allyl amines are among the most useful of synthetic intermediates. I happen to agree. If only there were a convenient and cost-effective way to make these compounds. Let me think. OK. Amines are good nucleophiles. And allyl halides are great electrophiles. Maybe if I mixed those together, I could get my precious allyl amine.

No. You idiot. That is way too complicated. There is a MUCH easier way. Just mix this "simple" gold catalyst with your amine and an allene at 100 degrees for 12 hours. And BAM! you got an allyl amine.



But wait you ask. What about other allenes than the one in the abstract picture above. Don't worry, they tried those too.


Finally, an easy way to make N-allyl morpholine! Check out the awesome E/Z selectivity with unsymmetrical allenes! Allenes as starting materials, what a great idea! They are so easy to make, especially these low molecular weight ones!

The world was waiting for a solution to this long standing problem in organic chemistry. Thank you for this. Nobel! Nobel!

Tip of the hat to Dr. B. Mike O'Keefe for pointing out this gem.

highly Michael

I'm having my lunch and reading and the very first article I see is this:


I'm sure many of you saw this before me, but damn. That's a pretty big fuck up, in my book.

Edit:

Moments later I saw that the very next paper has a botch in its graphical abstract.


The chemistry isn't earth shattering, but I was so confused by the graphical abstract, that I read it to see what the hell was going on. In a way their mistake got me to read a paper I would have otherwise blown by.

It's like Org. Lett. has taken the week off from editing for the holidays.

gram scale

It took me a few months longer than I would have liked, but I finally got there. Here are two large (if I do say so myself) bottles of >99% ee enantiomers of my branching point compound. There should be more than 100 g of each, and there is a bit more coming through the resolution still. This is the culmination of seven steps and one resolution.

take that, Baran

It took a hell of a lot longer to get here than I had planned, but now I should be able to make dozens of targets and their enantiomers without ever having to repeat any of those steps again.

gross, but funny

I've had an ingrown hair along my jawline for a long time now. I don't get ingrown hairs too often, and usually when I do it comes out with some fussing/scratching/picking. This little bastard had resisted all my weak attempts to free it, and just festered. It was also in a place that was difficult for me to see, so it was hard to see what could be done about it.

Early last week I had finally had enough and decided to actually take care of it, and to even try to do it the proper way to provide the best results. I scratched the dead skin off the top of it, then put a concerted effort into not touching it for several days except to clean it. I shaved carefully around that area, and let it rest a day. I waited until right after a hot shower, and then took a clean pin and gingerly poked at it. Immediately a small loop of hair popped out! I put the pin in the loop and popped the end out, and that little fucker was ~1/8" long. I left it, and figured I would leave it a day, shave then, and hopefully the issue would be resolved.

Two or three hours later it was still a bit sore, and similarly irritating. I went to the bathroom, and gave it a small pull, and a lot more hair came out! The whole thing came out and wasn't attached at the root anymore. In the end it was more like 1/2" than the originally exposed 1/8". It was such an odd feeling and sight that I snapped a pic.

frodus

Seminal spazzcore band Frodus, who broke up before I had the pleasure of listening to them, have regrouped almost 10 years later and are playing once again! On Saturday they played the Black Cat, and I went, all bright eyed and bushy tailed, excited to see them.

I showed up early enough to see the end of the first, and all of the second acts. The first act immediately made me think of the "space rock" stage at fun fun fun fest lat year, and I was left wondering what they were doing playing this show. My buddy said it sounded like they had tried really hard to write one good song, and then played it over and over again. We grabbed some beers and sat in the back and waited for the next act.

The next act was much the same, stylistically. If you go to a punk show, and see the guitarist of any of the bands "rocking out" by gently rotating his body back and forth while he nods, also gently, something is wrong. They sounded like they had grown up listening to Don Cabellero, and really, really wanted to be that good, but it was too hard so they added some lyrics and hoped no one would notice.

At this point I was getting nervous. I didn't own any Frodus records, could I have heard the only good songs and the rest sounded like these other guys? Had I made a grave error in judgement? I was actually jumpy as they were tuning up and taking the stage.

They came out and started off like a bomb exploding and I could feel waves of relief come crashing down on me. The first 3 songs were like one long crescendo building to an insane sonic peak. I tried to get some pics, but there was just too much movement for the camera in my phone to capture it.

you wouldn't even know it was Frodus if it weren't for the base drum

It was almost like it was planned to have oddly misplaced music as the intro, it made the aural assault of the headline seem that much more significant.

Another thing they did, which I REALLY thought was great was to eschew the "encore". Encores are total bullshit, and I think I've only ever seen one real one. Even that one was pretty expected.

At the end of the set, Frodus stopped, the singer said it was time for a period of reflection, cause encores are stupid, and they brought out chairs and sat there for a minute in silence. They then got up, played more, thanked everyone, then the show was over.

If you have the chance to see Frodus, do it.

another great scheme

Once again I'm at my desk trying to plow through ISI's weekly barrage of information, and I happened on this beauty:

Ann. N.Y. Acad. Sci. 2009, 1163, 330-339

Obviously not the worst one, but still has some nice features. Again we see the complete disposal of the typical left to right, top to bottom method of layout most people in the western world are familiar with. Who doesn't like to needlessly read charted information the goes up?

The first little loopy section has 3 different sizes of arrowheads, when one or two would have sufficed, and later in the scheme there are another two different styles of arrowheads used for no reason.

There is text above the arrows, below the arrows, and even some partially upside down text.

Perhaps the best part is that there are no structures for just over half the compounds. That always clarifies a scheme. I'm sure everyone reading the paper know what 1,2-dihydroreticulinium and salutaridine look like, but not tyrosine or morphine.

I suppose the strange part is that the structures are drawn pretty well, for an author that can't keep the font size and capitalization consistent.

edit:

I almost immediately found this one after posting:

Russ. Chem. Bull., Int.Ed. 2008, 57, 6, 1277-1284

All the lines around the piperidines are supposed to be hydrogens. I assume they used the cyclohexane drawing tool in ChemDraw and just left all the lines. For some reason they took them out in some of the other drawings that weren't in table form, and in at least one case used a drawing with all the extra lines, and actually put an H on the one they were specifically talking about without madifying ant of the rest. It's like some sort of odd selective vision on the author's part.

xmas trip

I kept forgetting to post this, but better late than never.

This last holiday season my girlfriend and I went to visit my parents for a few days. My girlfriend and I live in different states, and see each other only once every two or three months. The though it's weird to have sex under my parents roof was a little disconcerting, but desperate times call for desperate measures.

On the flight there, my lady and I were discussing how we were going to pull this off with a minimum of fuss. We figured condoms were the way to go, so my mom wouldn't have to launder DNA impregnated sheets, and I grabbed a flight sickness bag so we could use it as our own personal trash bag for a later, surreptitious, disposal.

Everything went as planned, and I ended up packing the little goodie bag and bringing it back home with me. After I had landed and was commuting back, it occurred to me that I had inadvertently left a nice trap for the TSA. There wasn't a note in my bag indicating it had been searched, which actually surprised me a bit. In addition to packing the latex balloons of genetic material, I had a bunch of tools I had purchased on the trip as well.

Here is a series of me unpacking what I had flown back with.

bag full of dirty laundry

xmas socks and underwear from mom

there's some more interesting things

and the goods

In retrospect, I think it would have taken some actual effort to come up with a better trap for the TSA. Too bad they didn't fall for it.

resolution step 2

I recrystallized the material from the resolution, and the ee went up to 98.9%. Perhaps I didn't use a sufficient volume of solvent or enough wash. In any case it will be easy to recrystallize again to get the ee up enough.

I took the mother liquor from the bulk resolution, which was heavily enriched in the diasteromer salt, and free based it. The opsque, dark brown, mixture was treated with D-tartaric acid, and crashed out to give the much more enriched salt. Interestingly, when the boiling solution of base was added to the boiling solution of acid, in similar concentration to the racemic case, the salt started to come out of solution even before I was done mixing the two. The already highly enriched enantiomer gave almost optically pure material (96.8% ee) that had only a hint of color. In a typical resolution of this compound from racemic I expect to get >75% ee, so this was a pleasant surprise.



I didn't add a pic of the mother liquor because it was on the rotovap when I took this, and I expect everyone is familiar with what a flask full of tar being stripped looks like.

I recrystallized the D-tartrate salt to get the ee up, and it took nearly twice the volume of solvent it would have if it were 75% ee, presumably due to the significantly higher optical purity.

resolution

I was taking the products from the distillation and resolving them via their tartrate salts, and decided that was inefficient to do individually on a reaction by reaction basis. I saved up the products from all the remaining reactions I had, and started the resolution on a large scale today. On the left is all the product from the distillations of material in 7 volumes of solvent, and on the right is an equivalent of acid in about 7 volumes as well.



They are heated to boiling and then combined (adding the amine to the acid), and, when it works well, the salt starts to crystallize out immediately.



After cooling it is filtered and washed. One of the wonderful things about a good chiral resolution that is not often mentioned is that in addition to increasing diastereo purity, it increases chemical purity as well.


The product should be > 99.5% ee after one recrystallization, and I can take the dark mother liquor, free base the salt, and crystallize it with D-tartaric acid to get it with >99.5% ee.

art?

I was distilling some material yesterday. At the end there was a small amount of tar left that was free flowing at the distillation temperature, and the last volatile material was coming over a drop at a time. I shut off the heat to the oil bath and left, and when I came back sometime later I was greeted with this.


At first it reminded me of Eddie VanHalen's guitar, Frankenstein:


But now I think it looks more like a Jackson Pollock knock-off.

nice set up

I'm pushing a bunch of material through a known reaction that, before my boss and I improved it, sucked. It worked very well on small scale and the yield and quality of the product dropped off precipitously as it was scaled up. Now the reaction can be performed on most any scale and yields of purified product are typically 90% or above.

Now there is only one small problem, the solvent for the reaction is triglyme. I run the reaction quite concentrated, but I still have hundreds of milliliters of solvent to deal with that has 50-100 g of crude product in it. Extraction on this scale is doable, but vacuum distillation is not only easier and faster in this case, it leads to significantly more pure product.

Herein lies the issue, triglyme is a bitch to distill. It has a relatively high boiling point, typically 80-100 centigrade with the vacuum my pump generates, and is prone to bumping. By prone to bumping I mean that the shit bumps almost continuously when contaminated with a product mixture, and treated in the fashion I usually treat short path distillations.

The first time I ran this reaction at 50 g scale in 500 mL of triglyme, I distilled a significant portion of the solvent off starting with the 1 L flask the reaction took place in, rinsed into a 250 mL flask, and removed the remaining solvent, rinsed into a 100 mL flask and distilled the product. There was some bumping over of the product, but not too much, and the reaction-purification sequence took all day. All in all not too bad for a 50 g reaction, but I still needed to put a few hundred more grams through it in the coming days.

I remembered a set up my boss had mentioned to me in another context once that he used for distillation of a heat sensitive compound. Many people are aware of the falling film distillation apparatus, and they are available from places like Aldrich for the low low price of $800 for the lovely 24/40 model.

an easily broken paper weight that cost almost as much as an ounce of gold

When my boss needed to do some sensitive distillation a long time ago, he made up an exceedingly useful contraption to effect very similar conditions using common lab glassware. My target compounds are plenty stable to heat, but I thought the apparatus would be usefull to deal with the bumping issue. Here is my practice run with the apparatus.

sweetness!

It's a 3-neck 250 mL rbf fitted with a stopper, a pressure equalizing addition funnel, and a short path. Notice that the addition funnel has a glass stopcock, teflon stopcocks do not work well at all for vacuum applications. The oil bath is heated to ~150 centigrade and the mixture is added to the hot flask a little at a time. It distills rapidly, and there is never a significant amount at any one time so the bumping is inconsequential, additionally I spin the shit out of it (1,000-1,200 rpm) which helps quite a bit. This pic is a practice run, and contains the solvent from the 50 g reaction containing a trace of product, hence the slight color. I was able to distill off 500 mL water white solvent leaving the crude product in 30-40 minutes this way.

When I ran the reaction on 100 g scale I was able to distill off all the solvent, and then distill the product in less than half the time the first 50 g reaction distillation took.

Waste Disposal

Let say that hypothetically you are a member of an organic research group at a well regarded department. What would you do with this form?

Yeah, I know it's complicated. Sure you are here to get a PhD in organic chemistry, but that doesn't mean that you can fill out one of these crazy hard waste disposal forms. Good thing that we keep these forms conveniently stored in a folder with easy to follow instructions.


Where can I find instructions to dispose of wastes of space?