Hi,
So I have a bit of a problem. I am trying to make benzyl alcohol from bromo benzene using Lithium-halogen exchange followed by treatment with paraformaldehyde (Simplifying the structure of my tarting material here but there is not much more complexity to the molecule I am actually working with than what I am stating here).
Starting with bromo benzene dissolved in anhydrous diethyl ether at -78C I added 1.5eq of n-BuLi. After stirring for 30minuts at -78 I add my electrophile,dried paraformaldehyde in great excess (5eq). I stir the reaction for another 2hrs at -78 and slowly bring it up to 0C which I stir at for 1hr and then stop the reaction. This whole time I keep the reaction under nitrogen. I do a water work-up and get a brilliant 0% of product. The reaction does not work. This whole time I am observing the reaction and can actually visually see the paraformaldehyde solids (White solid - Bought from Sigma) just stirring in solution (Et2O). Now I tried this reaction today with formaldehyde (%50Wt H20 - Sigma aldrich) and I do see minor product formation but I mainly just destroy the Lithium specie.
After doing some research I realize that my current methodology which involves adding dry paraformaldehyde without trying to break it via heat is not ideal. Any suggestions? How does one properly carry out such a reaction?
Any advice would be highly appreciated.
Have a look at the following;
Anionic, in Situ Generation of Formaldehyde: A Very Useful and Versatile Tool in Synthesis
Geoffrey Deguest, Laurent Bischoff,* Corinne Fruit, and Francis Marsais
Laboratoire de Chimie Organique Fine et Hétérocyclique, CNRS UMR 6014, IRCOF-INSA Rouen, B.P. 08, 76131 Mont-Saint-Aignan, France
Org. Lett., 2007, 9 (6), pp 1165–1167
DOI: 10.1021/ol070145b