Synthesis of a nitrile from an amide

[chem_tr]

Hello everyone,

I watched a MS thesis defence examination on chemistry, and one question was asked to the student, "what is the use of thionyl chloride in the reaction which an amide was transformed to a nitrile?" Unfortunately, there is a "fixed" answer, "to remove water from the reaction medium", which is absolutely wrong in my opinion. The student replied this "babble" and the jury approved this one.

However, I am very curious and restless about the real reason of the reaction, and devised a mechanism, would you please look at the mechanism and say if they are wrong or right?

It would be very informative if I tell you the reaction conditions a bit; dry dimethyl formamide was cooled to 0°C and thionyl chloride was added dropwise, by keeping the temperature below 5°C, under nitrogen atmosphere. When the addition was completed, a greenish yellow color was noticed (note: a literature mentions this reaction as dimethyl formamide+thionyl chloride complex). The amide was then added by small portions, again keeping the temperature below 5°C. The slurry formed after all of the amide was added was stirred for four hours at the same temperature, and the temperature was raised to room temperature and the mixture again stirred for twelve hours at ambient temperature. The mixture was poured on cracked ice and washed with water until pH raises to 5.5-6. There was a strong evolution of sulfur dioxide, so almost all of the reaction steps were advised to be performed under an efficient fume hood.

I refuse that the original reaction involves dehydration, and think that evolutions of sulfur dioxide and hydrogen chloride have fooled them about presence of water in the original medium.

Please give me a hand about this one. Movies, are you around?

 

[movies]

I'm not entirely clear on what you think is problematic with the mechanism. The picture you posted looks okay to me (although there are a couple of stylistic things I would draw differently). I think the idea of the "dehydration" is that you lose a total of one oxygen and two hydrogens from the amide. So, although you don't get any water molecules, you lose the equivalent atoms of water.

You could draw a mechanism without thionyl chloride that would convert an amide to a nitrile while losing a water molecule. It obviously doesn't happen that way, probably because the water molecule (or one of the intermediates) would just add back in and go back to the amide. So, you need something like thionyl chloride to "soak up" an equivalent of water somehow.

 

[chem_tr]

Well, I must admit that a really water elimination takes place in the reaction, I have looked up some books and seen that they (and you) are correct. However, I am right about the presence of Me₂⁺=CHCl Cl^-. If there are evolutions of sulfur dioxide and hydrochloric acid, there must be an evolution of water too, which will be "soaked up" by thionyl chloride to form these products.

Thank you for your interest.

Edit: A dehydration step is possible with an intramolecular interaction, so the use of SOCl₂ seems to be enough by itself, but since it is a vaporizable chemical, its dmf complex is far more useful, I think.

 

[movies]

I agree that DMF and thionyl chloride condense to form the so-called Vilsmeier-Haack reagent. I think that the key is that water is not formed as H₂O, although you do lose 2 hydrogens and an oxygen. Since you never have an H₂O molecule, the reverse reaction is not possible.

I'm not entirely sure why thionyl chloride isn't used by itself, perhaps the stability issue you mentioned is the reason.

 

[chem_tr]

The textbook (Jerry March's Advanced Organic Chemistry, 1992) states that thionyl chloride and some alternatives, in which our Vilsmeier-Haack reagent and P₂O₅, etc. are all used for dehydration purposes. However, I think we agree that "real" water does not come up in our case, it may be possible with phosphorus oxides though. Similarly, sole SOCl₂ again does not produce water, it will produce SO₂ and HCl.

Thank you.