[Haribo]

Hi all,

I performed some experiments for the coupling of nucleotides. My building block doesn't dissolve in 100% ACN, I've used 25% DCM in ACN for one experiment and 25% THF for the other experiment. The reaction whereby DCM was used resulted in an efficient coupling, and THF did not result in a efficient coupling. I'm not able to explain why the coupling reaction succeed when DCM is used and not with THF as a solvent. Both solvents are polar aprotic solvents.

[phth]

Yes, both solvents are polar aprotic, they are different as you noted by observation, so it's a bad habit to classify them as the same.  The measuring sticks of the solvent are the dielectric constant and the dipole moment of the solvent.  Here is a good list.  http://depts.washington.edu/eooptic/linkfiles/dielectric_chart%5B1%5D.pdf
The result you got worked better in a solvent with a higher dielectric constant and a lower dipole moment.  Can you think of a reason why this would be?

[Haribo]

Yes, both solvents are polar aprotic, they are different as you noted by observation, so it's a bad habit to classify them as the same.  The measuring sticks of the solvent are the dielectric constant and the dipole moment of the solvent.  Here is a good list.  http://depts.washington.edu/eooptic/linkfiles/dielectric_chart%5B1%5D.pdf
The result you got worked better in a solvent with a higher dielectric constant and a lower dipole moment.  Can you think of a reason why this would be?

During the coupling there is formed a protonated amine, this protonated amine normally acts as a good leaving group. Could it be that since THF has a higher dipole moment it can act a little bit more like a protic solvent? so for instance the lone pairs of the oxygen of THF which is very exposed, are coordinating towards the protonated amine and therefore balancing the positive charge and blocking it from leaving?

[phth]

Is the product neutrally charged?