3
$\begingroup$

What is the mechanism of halogenation of carbonyl compounds using molybdenum hexafluoride? How does it work?

Here's a reaction I came across:

halogenation of carbonyl compounds using molybdenum hexafluoride

Can we use it for all carbonyl compounds? Are there any limitations to the method?

$\endgroup$
  • $\begingroup$ What makes you think this particular fluorinating agent was so thoroughly researched? $\endgroup$ – Mithoron Aug 18 '18 at 18:33
  • 2
    $\begingroup$ Never seen this used, the standard reagents are DAST or Deoxfluor $\endgroup$ – Waylander Aug 18 '18 at 18:48
4
$\begingroup$

Molybdenum(VI) fluoride can be used as a fluorinating agent though not as popular as the selective DAST and Deoxyfluor as @Waylander noted. Molybdenum(VI) fluoride fall under the category of electrophilic fluorinating agent where it acts as a Lewis acid. The reaction is run in an inert solvent like $\ce{CH2Cl2}$ and a catalyst like boron trifluoride is used. The following is the reaction procedure taken from an e-book$\ce{^{[1]}}$. Also yield of various gem-difluorocarbonyl compounds from corresponding carbonyl compounds are listed:

A solution of $\ce{MoF6}$ (102g, 0.49g) in anhydrous $\ce{CH2Cl2}$(500mL) is cooled at 20-30 C. While passing a gentle flow of $\ce{BF3}$ through the solution, the carbonyl compound(0.5g) is added in small portion. The mixture is stirred while warming upto rt. Anhyd. $\ce{NaF}$ and silica gel were added. After filtration, the solvent is distilled in vacuo. The residue is distilled/purified by chromatography.

Further, it is written that:

In general, the yields are not that high due to the sensitivity of the reaction towards electronic and steric factors. Yield increase with the elctronic withdrawing group of the substituent of the substrate and decrease with the steric hindrance of the carbonyl group. $\ce{MoF6}$ attacks ether, amino, hydroxy, carboxy as well as $\ce{C=C}$ bonds. Ester, amide, cyano, nitro are inert towards the reagent. Halo substituent are not exchanged for fluorine.

The general reaction is given by$\ce{^{[2]}}$:

enter image description here

If a cyclic compound is used then R1 and R2 will be fused together.

If fluorination is proceeded at high temperature then catalyst is not needed. Aromatic carboxylic acids are converted into into gem-trifluoro derivatives without any catalyst. Also, Aryl trifluoromethyl derivatives can also be obtained under less drastic conditions by fluorination of aromatic acid chlorides.

Now, the same reaction can be achieved by using DAST or Deoxylfluor and they are the more popular fluorinating reagent than $\ce{MoF6}$. Their reaction mechanism has been studied extensively. The mechanism is more or less similar than the mechanism achieved by $\ce{MoF6}$. The following is an explanation of the mechanism$\ce{^{[3]}}$(emphasis mine):

The electronic effect of the substituent exerted a significant influence on the reactivities of benzophenones. The presence of an electron-withdrawing group is believed to facilitate the nucleophilic attack of the fluoride anion to the carbonyl group, causing more facile cleavage of the carbon–oxygen double bond. Among the benzophenone substrates examined, 4-nitrobenzophenone exhibited the highest reactivity and the corresponding gem-difluorinated product was obtained in 91% yield[...]

Notes and References

  1. Houben-Weyl Methods of Organic Chemistry Vol. E 10b/1, 4th Edition Supplement: "Organo-Fluorine Compounds - Synthesis of Fluorinated Compounds I, Transformations of Fluorinated Compounds" by Bernd Baasner and Georg Thieme Verlag, 14-May-2014 (link)
  2. http://reag.paperplane.io/00002051.htm#2
  3. Ying Chang, Amit Tewari, Avi-Izak Adi, Chul sung Bae "Direct nucleophilic fluorination of carbonyl groups of benzophenones and benzils with Deoxofluor" Volume 64, Issue 42, 13 October 2008, Pages 9837-9842 DOI: https://doi.org/10.1016/j.tet.2008.08.009
  4. https://www.alfa.com/media/docs/FluorinatingAgents.pdf

  5. Direct carbonyl group attack can be avoided and α-fluorination of ketones can be achieved by using highly selective fluorinating agent, NFSI. α-fluorination of cyclohexanone has been observed.

    enter image description here

    Enantioselective Organocatalytic α-Fluorination of Cyclic Ketones Piotr Kwiatkowski, Teresa D. Beeson, Jay C. Conrad, and David W. C. MacMillan Journal of the American Chemical Society 2011 133 (6), 1738-1741 DOI: 10.1021/ja111163u

$\endgroup$

Your Answer

By clicking “Post Your Answer”, you agree to our terms of service, privacy policy and cookie policy

Not the answer you're looking for? Browse other questions tagged or ask your own question.