The Half Decent Pharmaceutical Chemistry Blog

Look at these two molecules: obviously they are two xanthines and rather similar too. Still, one is Dyphylline (aka diprophylline) and the other is etofylline and, if you're asked to distinguish them, I'd better not be in a hurry and have good music with you.

The IR spectra, for example, look exactly the same. Annoyingly, even the melting point can't help you very much: both melt between 160°C and 165°C.

And don't fool yourself: yes, go on trying to see a different absorbance (273 v. 270) with the UV spectroscopy...rumour has it that someone is still in the lab hopelessly trying to detect any difference

These molecules are so similar to each other to make the job in hand look impossible.
Unless you fiercely fight the enemy here: water.

Your only option is acetic anhydride (99%). By the way, once again both are soluble in this aprotic solvent, but this is just the beginning.

The mixture boils for 15 minutes at 160°C. Meanwhile, the "magic" happens: both substances are capable of reacting with the anhydride, yielding acetylated derivatives, whose melting points, however, are fortunately different.



The derivative of dyphylline melts between 142 and 148 degrees, while acetyl etofylline needs approximately 120.

But this is just the end of the work. Before you could reach a verdict, the flask has to cool down to room temperature, so that a mixture (20:80) of ether and petroleum could be added.

Then, there is the trickiest part: you place the flask on ice for about 20 minutes. Meanwhile, you regularly stir the solution, increasing the chances of yielding a nice crystalline precipitate of the acetate by rubbing vigorously the inner of the flask every so often.

So you can't go out of the lab to check your inbox...

Finally, the precipitate is purified (through filtration), washed with the same mixture of ether and benzine, recrystallized from alcohol and dryed much as possible (which means this procedure takes 30 minutes, at least).

To sum up, the message here is rather direct: water is the enemy, ether is your best friend.

And you'd better take your MP3 player with you in such a circumstance, because the lab is cold and depressing when everybody has left.