Can $\ce{PCl5}$, phosphorus pentachloride, react with an amide?
I saw a reaction where the corresponding cyanide was formed in this process. What other reagents could do the same?
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1$\begingroup$ Dunno about PCl5, but POCl3 gives a chloroiminium ion (see the Vilsmeier reaction) $\endgroup$– orthocresolJan 7, 2017 at 14:13
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2 Answers
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There's a couple of newer methods, using
- zinc + N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA)
- copper + N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA)
- diethyl chlorophosphate $\ce{(EtO)2POCl}$
- $\ce{PdCl2}$ in $\ce{CH3CN/H2O}$
- $\ce{(COCl)2}$ with DMSO at -78 °C (Swern-type conditions)
Thionyl chloride, $\ce{SOCl2}$ is almost a classic here.
Under these conditions, the side products of the amide dehydration are $\ce{SO2}$ and $\ce{HCl}$.
$\ce{R-CONH2 + SOCl2 -> R-C#N + SO2 ^ + 2 HCl ^}$
On the first view, $\ce{PCl5}$ looks like leave quite a mess. Thinking in the workup, that's probably the last thing I would try.
answered Jan 7, 2017 at 14:09
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$\begingroup$ Thanks a lot sir.!!...btw pcl5 is considered as a dehydrating reagent ,right? $\endgroup$ Jan 7, 2017 at 14:29
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$\begingroup$ Yes, it is. But it can be used to convert carboxylic acids to their chlorides too. $\endgroup$ Jan 7, 2017 at 14:32
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As someone who has done lots of amide dehydrations, there are two methods I'd recommend. The cheapest is thionyl chloride in dry DMF. You need to dry the latter thoroughly by stirring overnight over calcium hydride (this evolves hydrogen, so don't stopper the vessel). Then distil under vacuum. Then suspend your amide in the dry DMF and stir in an ice bath, and drop in the thionyl chloride. Let it stir and room to warm temperature, then pour onto crushed ice. I also used to purify the thionyl chloride first by reflux over triphenyl phosphite and then distilling.
A more expensive method, but just as effective, is to use trifluoroacetic anhydride / pyridine as the agent, and sodium-dry dioxane as the solvent. This is incredibly mild, specific, and leads to a very clean work up and high purity product.
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1$\begingroup$ Welcome to Chemistry SE! We hope you continue to share your expertise, on this site. $\endgroup$ Oct 25, 2019 at 16:18
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$\begingroup$ Thank you! Always nice to have a warm welcome! $\endgroup$ Oct 30, 2019 at 19:22