Troubleshooting TBAF Trihydrate Production

[milindgar]

Dear Sir,

We have been manufacturing tetrabutylammonium fluoride (TBAF) 1M solution in THF (tetrahydrofuran). Our quality is very good and has been accepted by few MN pharma companies.

We have also been able to produce TBAF, 3H20 (TBAF trihydrate) with +99% purity and other specs such as water content is also well within the range. The only problem we are facing is we have not been able to get the solid material or at least semi-solid or chunk type. The compound is reported as solid having purity 97-99% and mp 58-63 deg C. Our product remains as thick viscous light yellowish brown liquid. Even after cooling to 0 deg C, it does not solidify.

We did literature survey and one of the papers says-Sometimes the product did not solidify after completing the reaction. In that case one can prepare its solution in water with conc. of 13 to 14% (~0.5 M), cool to 5 deg C, The white solids obtained are reported as a clathrate of TBAF, 38.5 H2O. The solids are then filtered, washed with cold water and air-dried. This compound has mp of 30 deg C. The water of crystallization can be removed under vacuum at < 50 deg C.

We feel this is good for lab scale preparation but may not be good for commercial production such as 500 to 1000 Kg.

How could we get solid TBAF, 3H2O? Could somebody guide us?

Milind Garkhedkar.

 

[Zefram]

Dear Milind Garkhedkar,

Thank you for bringing this issue to our attention. We understand the importance of obtaining solid TBAF, 3H2O for your commercial production. We have some suggestions that may help you achieve this goal.

Firstly, we recommend investigating the reaction conditions and parameters used in the literature method you mentioned. It is possible that slight modifications to the reaction conditions, such as temperature, concentration, or reaction time, could help in obtaining the desired solid product.

Additionally, we suggest exploring different solvents for the reaction. While THF is commonly used for TBAF preparation, other solvents such as acetonitrile or methanol may also be suitable and could potentially aid in obtaining solid TBAF, 3H2O.

Another approach to consider is using a different drying method. Instead of air-drying, you could try using a desiccator or a vacuum oven to remove the water of crystallization. This may help in obtaining a solid product at a lower temperature.

Furthermore, it may be helpful to consult with other scientists or experts in the field who have experience with TBAF preparation. They may be able to provide more specific advice and guidance based on their own experiences.

We hope these suggestions will be helpful in your pursuit to obtain solid TBAF, 3H2O. Please feel free to reach out to us with any further questions or concerns.