Sunday, October 27, 2019

The Difference Between XtalFluor-M and XtalFluor-E

I was questioning about the difference between these two reagents: XtalFluor-M and XtalFluor-E. I know from the structure, clearly, we can see the difference, but what else?

Then, I found out the history of how these two reagents were invented. Couturier and co-workers in 2009, were capturing the necessity of more stable and safe deoxyfluorinating reagents to cover the weakness of DAST and Deoxo-Fluor. To make it brief, the weakness of DAST and Deoxo-Fluor are liquid, thermally unstable, and unsafe as they generate highly toxic HF. 

Then, if we went back for over three decades, Markovskii et al was the one reported that DAST, dimethylamino, piperidino, and morpholino analogues all react with BF3.Et2O to form dialkylaminodiflurosulfinium tetrafluoroborates 3-6 (see below figure) which is in a salt form (not a liquid). Other researchers were also invented other analogues 7-11 of this reagents. However, the reactivity of this reagent derivatives have not been studied further toward alcohol, even aldehyde, ketone, or carboxylic acid, as well as the termal stability. Therefore, Couturier studied this. 

From their studies, when comparing using derivatives with different fluoride ion acceptors such as BF3, PF5, SeF4, SbF5, and AsF5, they found out that the derivatives with BF3, dialkylaminodifluorosulfinium tetrafluoroborate salts precipitated directly out of solution so from the manufacturing overview, it will make the isolation procedure at ease. Furthermore, they got derivatives 4 and 6 as the reagents with good thermal stability. 

How about the reactivity towards alcohol compound? At first, it was not a success, the reaction with geraniol, ended up with a mixture. They presumed that the problem was from the solvent used. After they studied the mechanistic pathways, and as we knew already that the mechanistic pathway is similar with DAST, they both involve a common dialkylaminodifluorosulfane intermediate, when DAST generated HF, Xtal-Fluor E and M generated tetrafluoroboric acid which the reactions then are a fluoride starved, that's why side reactions occur. 

In order to avoid the side reaction, exogenous fluoride addition is required as a promoter. They found out that the use of Et3N.3HF successfully improved the yield and selectivity. Then, the order of the reaction was a key parameter in this reaction as I already mentioned in this post.

Talking about the difference, here is the difference between these two reagents: thermal stability. Xtal-Fluor-M was found out to have greater thermal stability than XtalFluor-E (regardless of both are having greater stability compared to DAST and Deoxo-Fluor). Thermal stability was measured using DSC (Differential Scanning Calorimetry).

DAST and Deoxo-Fluor showed a decomposition at 155 (released 1641 J/g) and 158 (released 1031 J/g) degree Celcius respectively. While for the case of XtalFluor-E, it showed at 205-degree Celcius (released 1260 J/g). Moreover, XtalFluor-M showed greater stability as it showed at a higher temperature and a lower exothermic heat (243-degree Celcius and releasing only 773 J/g).

Another difference maybe about the price, but I found out, the price in Sigma Aldrich is comparable, not so different in price. 

The last, I think the difference is the scope of the reaction. Couturier and co-workers in 2010 have already studied the scope, but there is not so much difference, both reagent did work well for some substrate, but I believe, in another scope of substrate, a certain substrate may only work with just XtalFluor-E or XtalFluor-M.

In conclusion, about the difference between XtalFluor-M and XtalFluor-E, the most vivid is the thermal stability that XtalFluor-M is having greater stability than XtalFluor-E. Regardless of this difference, both XtalFluor-E and M are a great alternative for a stable, safe, and selective deoxyfluorination.


Beaulieu, F., Beauregard, L., Courchesne, G., Couturier, M., & Heureux, A. L. (2009). Tetrafluoroborate Salts as Stable and Crystalline Deoxofluorinating Reagents, 57(3), 3–6.

Heureux, A. L., Beaulieu, F., Bennett, C., Bill, D. R., Clayton, S., Mirmehrabi, M., … Couturier, M. (2010). Aminodifluorosulfinium Salts : Selective Fluorination Reagents with Enhanced Thermal Stability and Ease of Handling †,‡, 3401–3411.


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