Lab tricks for organic chemistry researchers (chomatography edition)

A wide-bore needle is great for dipping TLC capillaries into airfree reactions. Try at 15 or 16 Ga. needle for commercial tubes (18 Ga. works if you order thin capillaries or pull your own, e.g., from Pasteur pipettes).
Handy flash chromatography tricks
- This is based on a post from Phil Baran’s excellent blog. For small reactions (50–150 mg), 160 mm test tubes are convenient, disposable columns for flash chromatography. They are also highly useful for ion exchange chromatography, etc. Simply use a Bunsen burner and forceps to make a hole in the bottom, jam a cotton wad in, add a thin layer of sand, and pour in your silica gel/stationary phase (leaving plenty of room for mobile phase at the top). Apply pressure with a standard 14/20 gas adapter.
- Pipette columns are highly convenient for purifying 10–40 mg of material, as noted by Alison Frontier’s excellent “Not Voodoo” page about it. I have a few practical tips to add for running these columns (see picture):
  - 1/2 dram glass vials are convenient for collecting fractions, and can easily be organized in a Simport Scientific “UniRack Jr.” rack (Fisher 22-038-542, Simport S50025Y). The pipette can be left standing in these vials and positive pressure applied as needed via Tygon tubing.
  - To “pause” the column, plug the top with a small septum (a 5 mm ID x 11 mm OD/ 8-9 mm OD tubing VWR sleeve stopper is shown here, VWR cat. no. 89097-534). After the stopper pushes out a few drops of mobile phase, flow will stop if you’ve sealed the headspace properly.
  - Set the R_fto 0.2, or set it to 0.3 and then either 1) cut the %EtOAc in half, or 2) switch EtOAc to Et₂O (which has half of the eluting strength).
- For purifying polar compounds, there is no reason to shy away from highly polar mobile phases. There’s a common myth going around that silica gel dissolves in mobile phases containing a high percentage of methanol. Newsflash(chromatography) — this has been disproved time and time again ([1] [2]). I routinely use the following mobile phases and have never had a problem:
  - Amino acids with less polar side chains: 50:50 dichloromethane:methanol
  - Gangliosides: 60:35:8 chloroform:methanol:water
  - I have even filtered an aqueous solution of an amino acid over silica gel. For that, I did use a syringe filter to remove particles.
  - For TLC, there are no limits! 3:1:1 n-butanol:water:acetic acid, for example, is great for amino acids. It is quite viscous and runs slowly, however, and would be poorly suited for flash chromatography.
- For sensitive compounds (e.g., electrophiles), consider using specialty deactivated silica gel (post forthcoming).
- Reference: the original flash chromatography paper is only < 3 pg. and worth a read. Read for free at https://tinyurl.com/uzlcl6z.