Hi,
I'm currently working on the synthesis of some 4,5-disubstituted acridine derivatives with different aminomethylene groups. The starting material is 4,5-bis(bromomethyl)acridine that is reacted with a secondary amine and K2CO3 in MeCN or CHCl3.
The reactions themselves work reasonably well. After workup (filtration and removal of the solvent) an NMR of the crude product usually shows complete consumption of the 4,5-bis(bromomethyl)acridine but often some unidentifiable side products are present. As I want to do fluorescence studies with the final products they have to be absolutely free of impurities. However I have great trouble with the purification.
I tried silica gel columns in most cases but the yields were terrible and separation was bad despite the TLC looking ok. Wet loading usually is not possible because of the limited solubility of my substances and dry loading doesn't work so well (the compounds seem to stick to the silica afterwards). I tried dry loading on celite (washed with acid and DI H2O) and it seems to help. Nonetheless separation is bad.
I also tried some columns with basic alumina but they didn't go much better. We only have TLC plates with neutral alumina and I think the separation results I get on those aren't really comparable to the basic alumina columns.
Is it possible to modify the TLC plates beforehand to make them more similar to the column material? Perhaps by treatment with NEt3?
Also neither my coworkers nor me have much experience with alumina compared to silica. How do you estimate the amount of alumina needed for a certain separation? Can I use the same rules of thumb as for silica (rf of the product ~0.3, diameter of the column depends on the amount of crude product, the stationary phase is packed ~15 cm high, flow rate of 5 cm/minute)?
Any help would be greatly appreciated!