Question

I have a situation in which I want to hydrolyze a phosphonic acid halide under basic conditions. In my specific case, the halide is a fluorine substituent. Other halides like chlorine and bromine are known to hydrolyze quite quickly under aqueous conditions. Until now fluorine abstraction was not possible, even under strongly basic conditions. An additional substituent on the phosphorous is an oxido moiety which carries a negative charge. I am wondering about two things: Is there the possibility to increase the leaving capacity of fluorine by electron-donating groups in close proximity (bond to the same atom)? When the oxido moiety is replaced by an alkyl group R- or Alkoxygroup RO-, the molecule loses a negative charge, which might stabilize the fluorine and inhibits the hydrolyzation. What are the underlying principles that might explain the problems of hydrolyzation when an oxido moiety is present? Are there other strategies to make hydrolyzation an energetically more favored process?

Answer 1

Increased fluorine leaving capacity can be influenced by electron-donating groups, and the hydrolyzation of phosphonic acid halides can be affected by substituents such as an oxido moiety, alkyl, or alkoxy groups. Strategies to enhance hydrolysis include adjusting the substrate's structure and using an activating group.

Step-by-step explanation:

To address the hydrolysis of a phosphonic acid halide under basic conditions, particularly with a fluorine substituent, the ability of the fluorine to act as a leaving group is generally poor because of its strong bond to the central phosphorus atom.

Electron-donating groups can potentially increase the leaving capacity of fluorine by destabilizing the bond through electron donation, making the fluorine more likely to leave.

However, this is not as straightforward as it might be with other halogens like chlorine and bromine, especially under aqueous and basic conditions.The presence of an oxido moiety (O-) and its replacement with an alkyl (R-) or alkoxy (RO-) group can indeed influence the hydrolyzation process.

The negative charge of the oxido moiety increases the electron density of the phosphorous center which can make fluorine a poorer leaving group. However, when replaced with a neutral alkyl or alkoxy group, this interruption of charge distribution can potentially make the fluorine a better leaving group.

Hydrolysis is often driven by the stability of the leaving group; for fluorine abstraction to occur efficiently, strategies such as the use of a suitable base, altering the substrate structure, or using an activating group might be employed. This can make the process of hydrolyzation energetically more favored.