formation of tetrazoles from ketones

Normally in schmidt reaction of ketones, amides are formed however for some reason here further reaction takes place and a tetrazole is formed. Here is my try for this reaction mechanism, (if my mechanism attempt is wrong please point out the mistakes and the proper mechanism.)

reaction mechanism attempt

relating to the mechanisms I have the following doubts:

  • is this a special case of reaction or are tetrazoles formed with many different ketone reactions? if not, what makes this case special?

  • what are the driving forces in each step? is the aromaticity the main reason?


  • $\begingroup$ One particular question comes to mind. Do lactams react with HN3? You might check the stoichiometry in the Schmidt reaction. $\endgroup$ – user55119 Sep 28 '20 at 19:58
  • $\begingroup$ Stoichiometry is fine I checked. It is reacting with HN3 after all. What about the mechanism I wrote? Does it seem ok? Or do you have a source with actual mechanism $\endgroup$ – napstablook Sep 29 '20 at 1:42
  • 1
    $\begingroup$ Hydrazoic acid, a weak acid, is usually prepared in H2SO4 from sodium azide. The initially formed amide (lactam) forms a nitrilium ion via the enol of the amide that is protonated with loss of water. Whether the addition of hydrazoic acid is stepwise or "electrocyclic" is at issue. Take a look. here: organicreactions.org/index.php/Schmidt_reaction_(2) $\endgroup$ – user55119 Sep 29 '20 at 3:16
  • $\begingroup$ i understand the nitrilium ion formation. but you have presented 2 pathways one is electrocyclic and other is stepwise. i dont seem to get what mechanisms you have implied here. i tried drawing a mech where the N(-) part of hydrazoic acid attacks the nitrilium ion followed by a cyclic rearrangement(after a nucleophilic attack on the N in the cycle by -NH of hydrazoic acid. which one of your mechanisms is that? and what is the other one you think is possible. $\endgroup$ – napstablook Sep 29 '20 at 3:53
  • $\begingroup$ Stepwise means a terminal nitrogen of hydrazoic acid adds to the nitrilium cation then the nitrogen of the ring adds to the other terminus to close the ring. Some double bond migration will likely be necessary. Perhaps someone will speak to the hybridization of N3 in the ring closure. You can see the problem in your third to last structure. BTW, the synthesis of losartan employs trioctyltinazide or tritylazide addition to a nitrile. Probably electrocyclic in this case. patents.google.com/patent/US7915425B2/en $\endgroup$ – user55119 Sep 29 '20 at 12:01

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