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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: Twitter: Dereklowe

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November 29, 2011

A "Things I Won't Work With" Request

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Posted by Derek

I've been putting together a revised-and-expanded "Things I Won't Work With" collection, which I hope to release first as a Kindle e-book (with other platforms following close behind). Each entry in the series has been revisited, with more useful (or not so useful) information and raised-eyebrow opinions added, and I'm throwing in some bonus chapters that haven't appeared on the blog yet.

But I'd like to expand the list, both for the e-book and for future blog entries. So, what will you not work with? I'd be glad to take suggestions for the unpredictably explosive, alarmingly toxic, overwhelmingly stinky stuff that everyone with any sense avoids on sight. There have to be a lot of them that I've never come across, and I'd be glad to give them the full TIWWW treatment!

Comments (91) + TrackBacks (0) | Category: Blog Housekeeping


1. Anon-Amos on November 29, 2011 9:00 AM writes...

1. dimethyl mercury (reputation precedes it)
2. hexamethyl ditin (hate the smell)
3. HF (gas or freshly condensed) (Why use Meerifield resin anyway?)
4. diphenyl diselenide (hate the smell)
5. HMPA (hate distilling it)
6. NaK (boom boom pow)
7. 3-mercaptopropionic acid (hate the smell)
8. skatole (hate the smell)
9. sodium amalgam (hate sacrificing glassware)
10. hydrogen cyanide (hate the drama, love reading the Org Syn Prep)
11. pyrrole (hate the smell, klutzy labmate once broke a full 100-mL bottle in lab)

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2. Xmas on November 29, 2011 9:06 AM writes...

Oh! Let me know when you're going to release it on B&N. I'll buy it.

I got a bootleg PDF of Ignition, and it was a fun read. I love reading about chemistry that I'd never do.

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3. Anonymous on November 29, 2011 9:22 AM writes...

1,5-pentanediamine (stench)
dialkyl zinc(s) (good fire)
benzyl bromide (I had a grad school labmate drop a 500mL on the floor and had to help it clean up)

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4. eugene on November 29, 2011 9:26 AM writes...

"So, what will you not work with?"

Multi-ring natural products that take a four year PhD with KCN and still won't get you a job. Bam!

But seriously... from the stuff that hasn't been mentioned... maybe PH3? I know other people work with it and I often looked it up since I wanted to use it as a reagent, but the safety precautions and stories of others have always made me choose much longer alternate routes.

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5. OrganicExtract on November 29, 2011 9:27 AM writes...

I used O-(tertbutyldimethylsilyl)hydroxylamine at one point in my graduate work. It smells nasty!

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6. opsomath on November 29, 2011 9:34 AM writes...

ZOMG so excited.

I spent a good bit of my grad school time making p-phenylene bis(diazonium) salts. You need a non-nucleophilic counterion for those, and the old school one is perchlorate. Yes, you heard right, you combine a famously touchy explosive cation with the Grand Old Man of pyrotechnic oxidizer anions. The results are here:

Needless to say, I went with bisulfate for my compounds.

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7. patentgeek on November 29, 2011 9:41 AM writes...

1. Triethyl phosphite (cringing at the cellular level from the memory of the odor)

2. Carbon disulfide /liquid N2 temp. bath (a postdoc I worked with set himself on fire twice in one day with this)

3. Diazomethane in refluxing trifluoroethanol

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8. See Arr Oh on November 29, 2011 9:45 AM writes...

Hey Derek!

Two submissions:
Propargyl dichlorides - I've twice had them explode during distillation

Short-chain nitro-olefins - Only compounds that make me burst into tears with just a slight whiff

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9. Donough on November 29, 2011 10:08 AM writes...

@ Anon-Amos. Dont go to near PV processing then if you dont like gaseous HF.

Also from PV processing (but also other areas like gold mining), I have seen KCN used. The cyanide is a pretty good cleaning agent. However its smell is not detected by everyone. I also have it on good authority that the smell is the last thing to worry about. An ex collegue was taking fresh samples that had not been cleaned properly. His described the sensation of the body shutting down within seconds. Fortunately he was not knocked down.
PS. When moist it emits small amounts of HCN.

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10. Harry on November 29, 2011 10:11 AM writes...

Here are a few of my candidates:

Carbon Diselenide- STENCH!

Isocyanides- Stench


HF, especially anhydrous

2-bromopropionaldehyde- incredibly strong lachrymator

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11. Indy on November 29, 2011 10:31 AM writes...

1) Phenylacetic acid... That thing has a particular smell that sticks with you down the pores!

2) 10 M BuLi... Try it out and you'll see what a beautiful flame you get off the tip of the syringe!

3) Ni(CO)4... My PhD mentor wanted to use it for carbonyl insertion reactions. Sure... Never touched the darned thing and might still be in his lab ever since (20 years ago and going!).

Gee... the things one had to avoid to survive the PhD program! :)

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12. James on November 29, 2011 10:35 AM writes...

Fluorine gas
nickel carbonyl
HMPA (although it's sometimes necessary)
H2S (condensed) is lots of fun

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13. billswift on November 29, 2011 10:40 AM writes...

>You need a non-nucleophilic counterion for those, and the old school one is perchlorate. Yes, you heard right, you combine a famously touchy explosive cation with the Grand Old Man of pyrotechnic oxidizer anions.

Maybe that's the old school way of keeping out/getting rid of the "klutzy labmates" several commenters have mentioned ;-)

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14. rhodium on November 29, 2011 10:41 AM writes...

Unfortunately my list is things I won't work with again.
1. Nickel carbonyl. And yes, it does smell like newly mown hay. Not as well known as its carcinoginicity is its ability to burst into flame in the air if enough of it decomposes to finely divided Ni.
2. Diphenylcyclopropenone. The synthesis goes through the dibromodiphenylacetone. Either that or the final product introduced me to the concepts vesicant and contact dermatitis.
3. Any methytin comounds due to the small and headaches.
4. Not really something I won't work with again, but benzoyl peroxide and aniline gives of, after a variable delay, copious white smoke. A trail of this may be what one sees in old Keystone Kops films.
5. Four liter flasks with THF, benzophenone and pieces of sodium, due to the getting rid of sodium problem. Perhaps you have covered this problem in a different context.
Continuing this list is hard, since I am now wondering how it is I am still alive.

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15. bbooooooya on November 29, 2011 11:17 AM writes...

Phenylethanethiol: foul foul foul, permeates nitrile/vinyl gloves, seeps into skin, never goes away. Awful Awful stuff.

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16. nova1966 on November 29, 2011 11:24 AM writes...

tetramethylenedisulfotetramine (in the kitchen)

castor bean allergen (after sensitization, unless air stops moving)

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17. Clarence gatemouth brown on November 29, 2011 11:26 AM writes...

I have a variety of current and former colleagues/supervisors and bosses that would fit the bill here - unpredictably explosive, alarmingly toxic, overwhelmingly stinky etc. Just say the word.....

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18. sigma147 on November 29, 2011 11:39 AM writes...

I'm surprised no one aside from Harry has mentioned isocyanides. Nasty little beasts, those...

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19. Eric on November 29, 2011 11:51 AM writes...

Silver azide. Used to work with it, now I'm typing this with 7 fingers.

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20. Laura on November 29, 2011 11:55 AM writes...

I still remember thinking that I was going to die a horrible flaming death when smoke billowed out of the bottle of trimethyl aluminum that I opened. Time to recharge the glove box!

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21. skatesailor on November 29, 2011 11:55 AM writes...

Pass up the chance to work with 2-chlorobezalmalononitrile (CS, C10H5Cl2), the riot control agent. Your wrists and neck will burn for hours when a dirty lab coat shares its contaminant with you. I hate to imagine the pain felt by someone sprayed in the eyes, nose, or mouth with CS.

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22. quintus on November 29, 2011 11:59 AM writes...

methyldichlorophosphine MePCl2. Especially upon distillation, if it goes wrong you get a horrendous smell which pervade everything, not to mention the pyrophoric byproducts.
9-BBN is another one trying to prepare it on scale caused a cloud of smoke and what may have been a flame!

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23. myma on November 29, 2011 12:22 PM writes...

the supercalifragiliciousexpeali boom boom
from last week

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24. Acme_Rocket on November 29, 2011 12:27 PM writes...

1,2-ethanedithiol (awful smell)
alpha-bromo-phenylacetonitrile (tear gas/potent lachrymator)

There are many more, but these two stuck out.

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25. Lisa Balbes on November 29, 2011 12:45 PM writes...

Can I put "stupid people on the list? :-)

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26. Anonymous on November 29, 2011 1:47 PM writes...

Trimethyl thallium (There was a guy called Dr. Hub in Prague in 70s who was preparing Me3Tl from Me2Hg as a starting material. He had a runaway spill one night and he fell ill with CNS damage symptoms next morning, and died in horrible spasms few weeks later). Thallium(III) salts in general - they generate organothallium compounds from tyrosine residues in your skin.
Volatile organolead and trimethyltin compounds.

Carbonyl sulfide - COS is a gas that even in trace amounts makes carbon disulfide smell like carbon disulfide. Pretty neurotoxic too.

Ni(CO)4 and FSO3Me. They put quite a few people in hospital ICUs.

Me2AsCN - neoroparalytic warfare agent-like properties. Work with cacodyl cyanide cost Bunsen his right eye (from an explosion) then caused his nearly fatal poisoning. "The vapor from 1 grain (0.0648 g) of cacodyl cyanide in a room produces sudden numbness of the hands and feet, and dizziness and insensibility to the point of unconsciousness. The tongue becomes covered with a black coating. "

Diethyl tellutium, it taints your body and makes you a smelly social outcast for many months after. Or even inorganic tellurium compounds - when absorbed in trace amounts they give you tellurium breath.

Beryllium compounds
Radioisotopes by default.
NCl3, N2O5, Cl2O7, Mn2O7 and BrF5

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27. luysii on November 29, 2011 1:54 PM writes...

Patients with 'multiple chemical sensitivity syndrome'

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28. xyz on November 29, 2011 1:55 PM writes...

methyl iodide (large scale), I would not use.

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29. nucleofuge on November 29, 2011 2:10 PM writes...

Nickel Boride: Requires too much finesse for what you get.

DCC: Better coupling reagents have been developed, plus it tends to form a rock-solid brick in reagent bottles.

DDQ: Generates byproducts with problematic water and organic solubility.

Thiophosphoryl chloride: Burning stink.

DAST: Too smokey.

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30. Hap on November 29, 2011 2:50 PM writes...

Since I don't work in lab, this is sort of arbitrary, but...

Thallium salts, dimethylmercury, et al. - anything with irreversible toxicity is a nonstarter.

1-methyl-4-aryl-1,2,3,6-tetrahydropyridines (MPTP analogs) - see above.

Interhalogen compounds (and their cyanogen and azide analogs), selenium and tellurium compounds - they're not all horrific, but since they vary between icky to nasty to uncontrollable, I don't see enough of a point in them to worry about them.

Nickel tetracarbonyl - I suggested it for an allyl-allyl coupling on a synthesis exam, and if the professor had wanted to end my career, he could have actually bade me to follow my own route.

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31. Hap on November 29, 2011 3:39 PM writes...

I thought it was phosgene that smelled like newly-mown hay. Speaking of which...

Phosgene, dimethyl sulfate, methyl fluorosulfonate, and mustard gas/nitrogen mustards all seem like good choices - the first three particularly because their toxicities are not immediately apparent but are easily fatal.

The diazomethane twins (diazomethane and trimethylsilyldiazomethane) - even if only the unsubstituted one likes to detonate, they're both pretty toxic (as for the first three above).

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32. Hap on November 29, 2011 3:43 PM writes...

Anon26's paper (Milkshake also suggested it a while ago) is a fiesta of TIWWW goodness. Arsenic compounds have lots of good reasons to be on that list, and the paper with that quote gives many of them.

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33. quintus on November 29, 2011 4:04 PM writes...

How about management?

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34. CMCguy on November 29, 2011 4:22 PM writes...

Anything with Radioactivity has always scared me.

OsO4: although have used myself and know is "popular" in many labs not sure all who use treat with proper respect (particularly in regards to disposal)

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35. Bunsen on November 29, 2011 4:27 PM writes...

Yay, more superneurotoxexplosivexotherminoxious compounds to read about! (That adjective can probably be improved upon, but it fits the meter better than hexanitrohexaazaisowurtzitane did. Might make a good intro title or something. Noxious is a bit hard to rhyme, though...)

It looks like diazomethane was already the subject of a How Not to Do It entry, though that could probably be adapted for the book. In fact, I'd bet there are a few other things in that might be useful.

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36. B on November 29, 2011 5:06 PM writes...

Cycloproparene, C7H6 of stinkyness...

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37. metaphysician on November 29, 2011 5:12 PM writes...

*goes to look for a way to read Kindle e-books without a Kindle*

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38. Handles on November 29, 2011 6:43 PM writes...

re: cycloproparenes

I dimly remember seeing Brian Halton give a lecture once, I think he mentioned a bromo-substituted cycloproparene as being the stinkiest thing ever made. I wish I had access to his reviews (e.g. DOI: 10.1021/cr010009z) in case he published any anecdotes.

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39. Martin on November 29, 2011 7:18 PM writes...

trimethyltin hydride. Used the chloride many many times in PhD. Mentioned to boss I wanted to make some of the hydride for alkyne additions and that my initial attempt in fumehood hadn't worked as gas too volatile. He said no in a _very_ clear way (with explanations)

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40. rural on November 29, 2011 7:27 PM writes...

phenylphosphine, that smell will hunt me for the rest of my life.

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41. Chemcat on November 29, 2011 7:42 PM writes...

Isovaleraldehyde -- a stinky bugger, although I read once that almost 40% of people cannot detect its stench. Would you like to see if you're so lucky? ;)

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42. Lu on November 29, 2011 7:50 PM writes...

Iodoacetic acid: volatile and very irritating even in miniscule quantities.

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43. Canageek on November 29, 2011 8:25 PM writes...

No one has mentioned noble gas compounds yet? Some of those are rather energetic. I'm not sure I wouldn't work with them, but I'd sure be doing it on a small scale-- I recall hearing about someone getting hurt working with 50 mg of the stuff.

Lets see, also on my 'handle with oh so much care' list is anything that randomly explodes. I had to read about this gem for a class I took last year:
"Although violent detonations occasionally occurred when BrO3F was brought into contact with CH3CN, the [...] make CH3CN a useful solvent for the synthesis of anions derived from strong oxidative fluorinators." --John F. Lehmann; Gary J. Schrobilgen; J. Am. Chem. Soc.  2005, 127, 9416-9427 10.1021/ja0402607

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44. Susurrus on November 29, 2011 8:44 PM writes...

Allyl mercaptan. It smelled like a skunk even before I opened the can containing the bottle.

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45. Tanith on November 29, 2011 9:36 PM writes...

Hydrofluoric acid - scared the **** out of me when I spilt the stuff

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46. Anonymous BMS Researcher on November 29, 2011 10:45 PM writes...

Google Yale Sabia Virus NEJM for a case report -- free full text -- of a 1994 incident when a researcher was treated with ribavirin after exposure to an exotic virus. I was at Yale when this incident happened -- in a building just across the street.

Fortunately it wasn't Ebola for which there is no treatment. I'd also be reluctant to work with hantavirus or some highly pathogenic flu strains, among others.

A much less dangerous virus -- the 2009 H1N1 flu -- gave two Canadian government inspectors a stern lesson about infection control rules. They were investigating an outbreak at an Alberta pig farm -- I believe the likely vector was a farm worker who had been on vacation in Mexico. Anyway, it was hot and humid among thousands of pigs and the face masks got very unconfortable so they took off their masks. A few days later they had reason to regret having taken those masks off!

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47. Hurin on November 29, 2011 10:47 PM writes...

You've written a fair amount about azides in the past, but tetraazidomethane might deserve special mention.

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48. David Bush on November 30, 2011 3:47 AM writes...

If you might be interested in biological work, look into prion research. Since they're just malformed proteins, they survive most things that you can use to get rid of even the nastiest bugs, like heat and radiation.

Our group was asked to do some sequencing work on one by MS, we politely declined after hearing that one group had to move their instrument into a BSL-3 lab to work with one.

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49. Crystallographer on November 30, 2011 6:32 AM writes...

Tetrahydrothiophene. A bottle had apparently been kept in the lab freezer previously. Several years later, you would get comments from people working at the other end of the lab about thirty seconds after opening the freezer very briefly. The stink of that stuff lingers...

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50. Chemist on November 30, 2011 7:46 AM writes...

The most stinky thing I worked with was where we took the acid chloride of iso-buteric acid and reacted it the 2-thiopyridine to make the thipryridylester.

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51. Anonymous on November 30, 2011 7:57 AM writes...

I'd like to second the nomination of scatole. There is a reason it is named after sh$@t!

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52. Mr. Fixit on November 30, 2011 8:09 AM writes...

As a general rule, I prefer not to work with compounds, such as heavy metals that will silently accumulate in my system, then WHAM kill you (sorta). I am much less concerned about compounds like tBuLi, where there are definitive safety precautions one can take to ensure the ability to walk away from the reaction to live a long and healthy life.

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53. bonedriven on November 30, 2011 8:50 AM writes...

Selenium Dioxide. I was looking into oxidizing a heteroaromatic methyl group to the acid, which called for stoichiometric SeO2 on a several gram scale. It's MSDS is pretty terrifying : Of interest is the LD50 for skin contact: 4mg/kg in rabbits.

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54. OldLabRat on November 30, 2011 8:57 AM writes...

Cyclobutylcarboxylic acid = pure sour milk.
Iodyl sulfate + nitrohalobenzenes = large boom.

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55. Fiona on November 30, 2011 9:02 AM writes...

@David Bush - How on Earth do you move an MS machine? I thought they were pretty fixed. (NB - It's been years since I've seen an actual MS machine, they may have got smaller in the intervening time)

Reagents I thoroughly wish never to use again - ethidium bromide, just say no to intercalating agents.

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56. Anne on November 30, 2011 9:13 AM writes...

There are some dreadful stories about smallpox post-eradication. The Russians did biowarfare work on it, and some got loose. Worse, the work (that is, they blew up 400 g of the agent) was isolated on Vozrozhdeniya Island in the Aral Sea - which is mostly gone now, so the island isn't an island any more. There was a case, too, where a British researcher, Janet Parker, caught it at work. She died, and the head of the lab committed suicide as a sort of apology.

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57. DannoH on November 30, 2011 9:56 AM writes...

Any of the hydrolyzed chemical warfare agents with a sulfur in the parent compound (HD and VX)? Those two little beauties are why I cant smell garlic, onion, or skunk anymore...

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58. Ethan C on November 30, 2011 11:58 AM writes...

Old picric acid/metal picrates. As a graduate student TA, I was told to mix up Beaujard's etchant solution for an undergraduate steel metallography lab The absolutely ancient picric ac