[Marcos]

Hello, my name is Mark and I've been refreshing my organic chemistry knowledge lately and after reading about carboxylic acids derivatives and their reactions i stumbled upon something that got my attention. So basically the most reactive species of carboxylic acid derivatives are obviously their acyl halides. So lets focus on the most common one - The chloride. There are plenty of ways to form them from which the most common are reactions with thionyl chloride (SOCl₂), phosphorus(III) chloride (PCl₃), phosphorus(V) chloride (PCl₅) or little bit more exotic oxalyl chloride (C₂O₂Cl₂). The reaction with SOCl₂ is quite simple reaction in which SO₂ and HCl are evolved as side products. In the reaction with PCl₅, the POCl₃ and HCl are evolved, and in the reaction with PCl₃ only H₃PO₄ is evolved. The oxalyl chloride reaction is also catalyzed by addition of little bit of DMF that forms imidolyl chloride intermediate products like in the Vilsmeier–Haack reaction reaction with POCl₃. But in some of the articles that i've read i saw that POCl₃ can be also used as a chlorinating agent in carboxylic acid conversion to acyl chlorides. From what i know, POCl₃ is used mainly in alcohol dehydratation reactions and generally in the E2 elimination reactions, not to mention that it is also a side product of using PCl₅, but in those paperworks, to be exact:

Christian A. G. N. Montalbetti* and Virginie Falque Amide bond formation and peptide coupling Tetrahedron report number 740
ROGER ADAMS,O. KAMM, C. S. MARVEL Organic Chemical Reagents UNIVERSITY OF ILLINOIS Vol. XVI June 23, 1919 No. 43

POCl₃ is mentioned as a chlorinating agent. There is really no other paperworks that i could find that mention POCl₃ as a chlorinating agent.
So my wonder is what is the mechanism of the reaction and when would it be favoured over the common ones.
Moreover in this paperwork from 1919 there is a quite interesting result. The synthesis of acetyl chloride was carried by refluxing sodium acetate with POCl₃
The most interesting thing is that in the article there is mentioned that

The acetyl chloride which is thus obtained, is
very much superior to the acetyl chloride formed by the action of
phosphorus trichloride upon acetic acid.

and also

The acetyl chloride as it is formed is so pure that by using a
fractionating column on the original reaction mixture flask, pure
acetyl chloride may be distilled directly and no redistillation is
required.

I couldnt find any reaction mechanism for the reaction of chlorinatin carboxylic acids with POCl₃ so i made one myself (analogue to the SOCl₂ method):



Is this a valid mechanism ? If not then what is the real mechanism ? Is it similiar to the imidolyl chloride intermediate formation ? As it was mentioned in the Amide bond formation and peptide coupling paperwork, so maybe it forms intermediate product with amines and acyl chloride forms only in the presence of amines ?



Greetings

[wildfyr]

Heres how much I appreciate your clearly written and also informative question: I waded through German papers from the 60s .

I found another paper (http://onlinelibrary.wiley.com/doi/10.1002/prac.19610120504/full). It is cited 12 times. I didnt go through them, but I bet several other papers use POCl3 as a chlorinating agent. A quick scifinder search also found several examples of POCl3 to make acyl chlorides with under ordinary conditions. They did not include amines or DMF. Your image didnt work (maybe post to imgur, whatever s13 is is blocked), so I can't comment directly on your proposed mechanism. I would guess that yes, it is analogous to the thionyl chloride mechanism. Those two compounds are closely electronically related.

Also FYI, virtually all of these types of chlorinations are catalyzed by DMF, not just oxalyl chloride. Oxalyl chloride is just the most likely to need the extra kick because it is the weakest chlorination agent. POCl3 is probably the next weakest. I would hazard that it also forms H3PO4 as its byproduct. I do not have a good guess why it was superior to POCl3 for that particular reaction, but in a survey of chlorination agents, each substrate will probably somewhat prefer different ones. My agent of preference is thionyl chloride due its easy handling and measuring as a RT liquid, its easily removable byproducts, and the excess can be removed from reactions directly by distillation, making workup very simple. It also drives itself to completion very well as the SO2 bubbles out, making it basically irreversible.

[rolnor]

I would lika to add that the mixed anhydride from carboxylic acids and trifluormethanesulphonic acid are more reactive than the acyliodides, they can smoothly acylate benzene even without Lewis acid catalysis.

[wildfyr]

Rolnor, could you provide a reference, that is something new to me! Googling got me too much extraneous stuff to sort through

[rolnor]

Its in Marchs Adv. Org. Chem Fifth Ed. page 712. I have never tried this myself, I guess you make these from silvertriflate and acylchlorides perhaps.

[rolnor]

Sorry, I think it should be page 713.