Chemistry 301 Q1 September 19, 2017: Agenda Lecture: TLC stains, hi-vac/NMR, continue Med Chem Lab today (1-4 pm) – Rob must leave at 4:30 pm today: 1) flash chromatography likely in some cases (how do you know?); 2) check online target info for arrival of your materials – I believe all amines for “B” are here!; 3) be sure you’re using the online data repository for all lab notebook, etc.!; 4) proposed syntheses back from Rob; 5) new 1 x 5 mL RB and new 1 x 10 mL RB for each group! Next time in lecture: Continue talking med chem Due: schematic update on your progress so far  -- if you need today to work out some more details, that’s fine Homework: keep working on chemistry

TLC TLC stains: What the heck are they? Why are they used? How do you choose the/a good one to use? See Moodle under tips/tricks and today’s entry for nice lists of recipes and corresponding typical functional groups a given stain picks up! (We provide several (KMnO4, PMA, ninhydrin), but we may be able to make additional stains if you need)

TLC Super quick review: Does this ring any bells? Hopefully it doesn’t stir up any nightmares! Downloaded on 9/19/17 from: http://www.napavalley.edu/people/sfawl/Documents/Chem%20240/Alkene%20Oxidations%20using%20KMnO4.pdf

TLC TLC stains: Why do they work? Remember talking about the reactivity of double bonds back in Chem 225? For example, KMnO4 (K+1/Mn+7/O4-8) dip plus heating! Permanganate ion (MnO4-) is deep purple! Reduction of Mn+7 to Mn+4 to give MnO2 gives a red/orange/brown color on the plate where you have a compound with “reactable” double bonds! See umber! Downloaded on 9/19/17 from: http://www.thesynapticleap.org/userfiles/DSC08904a(1).jpg

Hi-Vac Hi-Vac: What do you need to do? Why? How? Ask one of our wonderful TAs to help Another hint: the “CDCl3 trick”. What’s that? How might it apply to a first step “F” reaction involving malononitrile?

Let’s continue talking about some fundamental Med Chem topics!

Solubility/Numerical Representations Examples of molecules with low and high log P values Remember, we try to avoid very hydrophilic and very hydrophobic compounds for oral administration Do these values make sense?

Solubility – Varying N-alkyl substituents to vary pKa We may need to alter the structure of a drug with a pKa outside the range of 6-9. Why? We can add a) extra N-alkyl groups or b) larger N-alkyl groups to increase basicity BUT! What is the potential problem there? What additional “trick” can you see to the right in “PRO 3112”? - High or low pKa tends to lead to greater ionization and more difficulty of absorption of compound through cell walls Amidine is more basic than PRO 3112 as 3112 “wraps up” the basicity without a loss of activity Adding N-R groups increases electron-donating effect to increase basicity but more bulky groups prevents interaction with water