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What is the best way to do this reaction to form the dichloride as an reactive intermediate when the substituent R is acid sensitive?

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In the literature the reaction is either performed with PCl5, a mixture of POCl3 and PCl5, SOCl2 or Oxalylchloride + TMSBr. This goes for ethyl or isopropyl moieties, I also saw an example for benzyl. I think my best shot would be SOCl2 which is as I know more reactive than oxalylchloride and because it is a liquid, while PCl5 (can't be evaporated so easy) is a solid and my compound may not be stable to TMSBr, because it is suspected to be sensitive to TMS+ cation.

All of these reagents will generate acid when they have contact to trace water. These reactions are all performed under schlenk conditions, still usually I see back reactions to the hydrolysis product. Is the only viable strategy to remove the excess of chlorination agent in vacuo or is there the possibility to perform a quenching step that does not release acid while keeping the dichloride intact?

For example when I use oxalyl chloride, to produce an phosphorus acid chloride, the removal at the rotivap is often not complete. I doubt, that there is the possibility to perform this reaction from the start under basic conditions?

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  • $\begingroup$ Boron trichloride cleaves hindered esters (see pubs.rsc.org/en/content/articlepdf/1971/c2/c29710000667 researchgate.net/publication/… ) so seems a reasonable possibility for this $\endgroup$
    – Waylander
    Commented Jun 15 at 13:04
  • $\begingroup$ I think the best approach is to used thionyl chloride, vac down hard and be rigorous in excluding water. $\endgroup$
    – Waylander
    Commented Jun 15 at 18:11
  • $\begingroup$ I have the reaction running right now, and it seems there is diester forming (control in MeOH). To the chlorination agent I added quite some pyridine which should work as catalyst as well as an acid scavenger in case any moisture is getting into the flask. Exciting $\endgroup$
    – raptorlane
    Commented Jun 20 at 19:26

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I was able to solve the formation problem. The dichloride can be formed reliably even for an acid sensitive R, when an overproportional amount of pyridine is present. On mixing, the pyridine should neutralize all present acid in the SOCl2 and keep the mixture basic, even if small amounts of moisture enter the reaction mixture. If I recall correctly, I used 5 percent of pyridine in thionylchloride and refluxing overnight under nitrogen. However the absolute removal of thionylchloride and pyridine at reaction finish present a challenge. To perform this task I used the rotivap at 60 degrees C. If you ever attempt this, make sure that this is performed in a fume hood. I heard, that the co evaporation with (dried) DCM or toluene can help to remove it more completely and it is maybe a good idea to additionally dry it overnight with temperature under high vacuum.

The next challenge will be the clean and soft transformation of the dichloride in the phosphonic acid.

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