I had this lovely discussion with a coworker the other day. She's a nice post doc in a group made almost entirely of post docs like myself, but I really didn't expect work like this from someone who finished grad school.
She comes up to me with a reaction scheme from our boss' current project and asks me about a step in it; a nice McKlusky N-demethylation. Well 2 steps, really. [Shameless plug: if you need or want a name reaction book get this one. It's from my friend Bert, it's almost 3000 pages long, it's a searchable pdf, and it's only $40.] Anyway I could tell by the way she was asking she wasn't interested in generalities, I guessed, correctly, she had tried it and it worked poorly.
She asks a few questions about it, and it was obvious she didn't know how the reaction worked. Not that you need to know how everything works, but if it is an important reaction it won't kill you to spend a few minutes to figure out what the hell is going on. I guess I'd call this mistake #1.
She said she had found a good prep, I didn't ask what her definition of 'good' was, but that it involved carrying on the intermediate crude to the second step. She did this, which is fine, but she didn't take an NMR along the way to see if the demethylation/carbamate formation had worked. Mistake #2.
So at this point it's obvious it didn't go well, and she tells me there is no demethylation and the starting material is all gone. I'm trying to remember her structure and thinking of things that could go wrong. In my poor recollection of her target I can see one really obvious problem with the reaction as a choice which she totally missed due to her lack of understanding of the reaction mechanism. I'm telling her how it works and asking if she talked to the boss about the reaction. She hadn't. Mistake #3.
I know many people wouldn't talk to their boss about day to day stuff, and I know I would have not liked to talk to my old PI about any routine stuff unless I felt like getting raked over the coals about various and sundry horseshit, but our boss here is very different. He is an exceptionally cool guy, and the only thing he like more than doing chemistry is talking about chemistry. And maybe drinking wine. His reaction scheme was the source of the idea in the first place, lots of our targets share route details like the mid to late stage McKlusky, and he has lots and lots of experience with both her class of compounds AND the McKlusky/von Braun type demethylations. Who wouldn't spend the less than 5 min asking him if he thought it would work, especially if he could say "we tried that on a really similar substrate and it did/didn't work"?
I next asked her what she thought the product was, just to see if my suspicions about the side reaction were correct, and she told me she didn't really know. She had just looked for the N-methyl, saw it, and realized she was boned. I tried to get her to talk to the boss and she didn't want to until she did more reactions, which is a little silly, but whatever. She asked me about the next set of conditions she was going to try, and I tried to come up with some helpful ideas but she said she didn't have enough material to do too many trials. I figured she must be near the end of her route if she was doing the demethylation, so I wasn't to surprised, but the reason she didn't have the material was because she bombed all her material through the step! She put 500 mg of advanced material into a reaction she had never done, and didn't understand! That's only mistake #4, but the rest sort of don't matter in comparison. Really it's mistake #1 and the rest should all be pushed back into the background. I mean, shit, 500 fucking mg! Damn! There were times I would have done many evil things to get 500 mg of advanced materials, and would hoard and covet every single milligram. Fucking hell!
It was all I could do to not look shocked, cough, and splutter. She was already painfully aware of how much that little trip to the hood had cost her in terms of time and effort, and I didn't really feel like she wanted any "you should have ..." crap.
She still doesn't want to talk to the boss, and managed to find a mg or two to try another set of conditions today that she checked after the first rxn this time (the N-Me is gone this time if anyone is interested), but she is still going to have to go back a ways to come up with some material.
I guess we all have bad days, and I expect she won't fuck up quite this badly for a while. I sure know I won't do anything like that. Sometimes it's nice to be other peoples sounding board (aka emotional tampon) to be reminded of how bad shit can go if you aren't paying enough attention, not to mention the fact that it's always nice to NOT be the one dropping the ball.