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Digging Chemdraw.

  Folks, we're about to reach the highest Dan of Chemdraw, the mastery of which enables you to make molecules without even lifting your ass from the chair. Yeah, dream on.

  Last time I was talking about some basics, and also hotkeys, which are absolutely crucial to productivity in any computer work. Quoting myself, "what ChemDraw really lacks is the hotkeys for switching between different drawing tools" — now I refute this statement. Find a file called CS Chemdraw HotKeys.txt under ChemDraw Items folder. On XP it's hiding somewhere in the Application Data dumpster, I hope you can find in on a Mac (yeah, I'm a PC, whatever). You can manually edit the hotkeys in there. Here's how I have it set up:

1 TOOL_MARQUEE
! TOOL_LASSO
2 TOOL_SOLIDBOND
@ TOOL_ACYCLICCHAIN
3 TOOL_TEXT
4 TOOL_ARROW
$ TOOL_CYCLOBUTANE
5 TOOL_CYCLOPENTANE
% TOOL_CYCLOPROPANE
6 TOOL_CYCLOHEXANE
^ TOOL_BENZENE
  It's a little funny that these settings sit in a separate .txt file, but this is what we get when we don't provide much needed feedback to the developers. I'm going to write them. Some of them (arrows, brackets) actually don't work.

  Finally, I present you... the "making" of the notorious aspidophytine. *exasperated gasp* However, let us not be overly cynical, for The Man actually gave us ChemDraw. I learned it from the preface to "The Logic of Chemical Synthesis". Moreover, in all his publications EJ actually abides by his original style used in the book, which quite different from what's commonly used. You can read about a recent synthesis of aspidophytine here at TotSyn.com. And, seriously, Angewandte, you waved the haplophytine flag like a year ago already, and it's still "almost published" in the VIP papers. Haplophytine is the bigger cousin of aspidophytine, which might have killed many more Japanese grad students. We just don't know about it, because they go straight to heaven North Korea.

  Note how my cursor doesn't even leave the screen to reach for different drawing tools. Note the use of Rotate and Join tools. This was the fifth try, I believe. This is at native speed, try beating my 71 seconds!



  Recorded with the outrageously awesome and free CamStudio. Drawn at 200% magnification. Drawing settings used:
Fixed Length: 0.525 cm
Bold Width: 0.07 cm
Line Width: 0.035 cm
Margin Width: 0.07 cm
Hash Spacing: 0.084 cm
Font: Calibri, size 9
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Hail yeah!

  Rejoice, my friends, for the ACS removed the stupid first page that annoys readers from all its publications. I like to think that it was a result of visiting the ACS Publications booth at the meeting in Salt Lake City. In the other news: Alfa Aesar is working on redesigning their labels to make them more informative.
  I have to admit though that the meeting wasn't quite to my expectations.
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Rise. And shine.

  One of the reason why human is human is that he has his place in the world. But the desire to do chemistry is a manifest of his willingness to rise above it. If only he knew how many eyes is he exposing himself to, he'd never, ever do it. If only he saw a tiny fraction of those staring at him, he'd die of fear.


Actually, it is originally about hallucinogenic drugs.

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Saturday Night Distillation.

  As one of those spoiled by flash chromatography (and solvent columns), I realized that I forgot when was the last time I distilled anything. After that insane month preceding the ACS meeting, I decided that my homecoming to the hood should commence from distilling furfurylamine, which I use quite a lot as a starting material. No matter what I do, this 250 mL bottle with orange liquid would never end, so I helped it. Not a desperate call for purification in this case, it usually works fine, giving 90+% yields, but it seemed like in a couple of cases the amides wouldn't crystallize because of this colored crap that dragged on from the amine — requiring a column to make it solid.

  I spent a good hour looking for the distillation equipment. I looked everywhere. The only possible apparatus good for about 150 mL was finally assembled, consisting exclusively of the parts occuring only once. It appears that nobody distills things on this scale in our lab. 1–2 L setups and Kugelrohr were much easier to find. I used house vacuum, since the subject boils a little bit too high at about 145 °C at 1 atm. It came out pale-yellow. I used a capillary to bleed in air and was lazy to set it up under nitrogen. But... I took NMR of my fractions. As far as I could tell, all of them contained satisfactorily pure furfurylamine. The brown residue was enriched in some crap, and most of the water came out in the first one. The latter was evidenced by a very broad peak (~0.15 ppm @ half-height) centered at 1.49, as opposed to moderately broad (~0.07) at 1.42 in the main fraction (all in chloroform, stored over calcined, powdered pot carb). And I'm definitely not the winner in "The most original and appropriate choice of an internal standard" nomination. For the absence of mesitylene, 2,4,6-collidine seemed like a good replacement. It is not. Yay long-range coupling.

  It seems like the main justification of these efforts is going to be the augmented aesthetic appeal of pale-yellow over bright-orange.

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Murphy's #1 in industry.

  In particular, the unexpected appearance in early 1998 of a more thermodynamically stable form (Form II) of ritonavir (Norvir, Abbott Laboratories, protease inhibitor for the treatment of HIV), with different dissolution properties compared to those of the earlier commercial Form I. Form II is <50% as soluble as Form I, resulting in the observed poor dissolution behavior and eventual withdrawal of the capsule from the market. This incident had serious implications for the marketed product and the patients receiving the drug. The project was suspended until a modified procedure was found. Renitidin, sertraline, and frentizole are some important examples of pharmaceuticals that exhibit polymorphism.
  This is from this OPRD ASAP; they were dealing with a similar issue. They have ultimately performed some 3600 recrystallization before they found the right one.
  Reminds me how easy my life is and how badly I suck at recrystallizations.