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All halogen derivatives (except fluorine) of succinimide exist and are used in various chemical processes. What makes N-fluorosuccinimde difficult to prepare? Still chemists have not been able to figure out the preparation of N-fluorosuccinimde and don't even bother to synthesize it since electrophilic/radical fluorination is accomplished by N-fluoro-o-benzenedisulfonimide (NFOBS), N-fluorobenzenesulfonimide (NFSI), and Selectfluor. Moreover, even if NFS is successfully synthesized, can it be used as a fluorinating agent in electrophilic/radical fluorination?

According to Wikipedia, NBS is made by reacting sodium hydroxide and bromine in an ice-water solution of succinimide. The NBS product precipitates and is collected by filtration. I am assuming that NCS and NIS are made in the similar fashion (using appropriate halogens). But, why NFS has still not been made through a similar way (using fluorine)? Is the reaction condition unsuitable for fluorine or is there any other reason?

I was reading a forum discussing the scope of NFS as a fluorinating agent. It says:

Does anyone know why is N-fluorosuccinimide (201281-58-5) such uncommon reagent for fluorination? I checked some major suppliers and none of them sells it.

In my knowledge, N-Halogenesuccinimide are obtained by reacting of Succinimide with the halogen itself. This is valid for Chlorine, Bromine, and Iodine. Fluorine is too reactive. For the fluorine derivative, iodinesuccinimide is treated with silver fluoride to exchange the halogen.

The other option is to treat N-Hydroxysuccinimide with Thionyl fluoride or Phosphorous trifluoride.

Is this true? I couldn't find any source confirming the above synthesis and I am skeptical about the preparation process. Can NFS be made through the above process?

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Maybe NFS doesn't work well? Bear in mind that bonds from a second-period element to fluorine are generally stronger and less labile than the corresponding bonds to heavier halogens. If that's true, getting fluorine off a nitrogen-fluorine bond requires more work than, say, getting bromine off a nitrogen-bromine bond.

In https://en.m.wikipedia.org/wiki/Electrophilic_fluorination#Mechanism_and_stereochemistry several common fluorinating reagents are given, these being the compounds mentioned by the OP. The listed compounds all withdraw electrons from the nitrogen-fluorine bond more strongly than the carbonyl groups would in NFS (they use sulfonyl groups or a cationic function), so it seems this attribute is necessary to get the fluorination to go.

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    $\begingroup$ Nice. Also, I'd posit that since fluorine is the most electronegative halide, getting a compound $\ce{X-F}$ to act as a source of $\ce{F+}$ is harder than getting a compound $\ce{X-I}$ to act as a source of $\ce{I+}$. Hence, again, a more electron-withdrawing $\ce{X}$ moiety is needed. $\endgroup$ – orthocresol Apr 8 '17 at 13:08
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The synthesis of NBS and NIS involve adding succinimide, the relevant halogen and NaOH (and AgNO3 in the case of NIS) in water. Fluorine reacts very violently with both oxygen and water forming HOF and FOOF, both highly toxic and explosive compounds. Water is thus an incompatible solvent for running fluorinations, you need a polar aprotic solvent such as MeCN. Secondly, in the presence of base, fluorine could undergo alpha-fluorinations to the carbonyl depending on the pKa of the C-3 and C-4 hydrogens.

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  • $\begingroup$ You can get NFS from a heavier halogen counterpart plus silver fluoride. But that does not actually mean it will work as a fluorinating agent, which I suspect is the real problem. $\endgroup$ – Oscar Lanzi May 23 '17 at 21:43
  • $\begingroup$ NFS has a very similar N-F bond strength in MeCN to N-fluoroquinuclidinium (also a pain), so might work. But I think it's just much more difficult to make then NFOBS/ NFSI which do just as good a job. $\endgroup$ – Alexander Hampton May 25 '17 at 12:18

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