Sciencemadness Discussion Board

Synthesis of Davis Reagent - Questions

chempyre235 - 27-2-2025 at 11:15

I was doing some research the other day, and I came across information about Davis reagents. Apparently, they are capable of oxidizing amines to hydroxyl amines, without further oxidation. Furthermore, the Davis reagents can be re-oxidized with NaOCl, with yields up to 90%.

After seeing the general structure of this compound, I thought of a possible inexpensive synthesis. My confidence in the viability of the synthesis was strengthened when I saw the article on the same compound. Here is the idea for synthesis:

  1. Condensation of benzaldehyde with ammonia to benzlyimide;
  2. reaction of benzylimide with tosyl chloride (followed by treatment with base to remove the chloride);
  3. oxidation to form the oxazidirine

So, my questions are these: (1) How is benzylimide synthesized; (2) Can Davis reagents oxidize ammonium salt in solution to hydroxyl ammonium salt; (3) Can Ca(OCl)2 substitute for NaOCl; (4) Can a milder oxidant be used to generate Davis' reagent in situ?

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[Edited on 2/27/2025 by chempyre235]

Elemental Phosphorus - 27-2-2025 at 21:47

Quote: Originally posted by chempyre235  
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So, my questions are these: (1) How is benzylimide synthesized; (2) Can Davis reagents oxidize ammonium salt in solution to hydroxyl ammonium salt; (3) Can Ca(OCl)2 substitute for NaOCl; (4) Can a milder oxidant be used to generate Davis' reagent in situ?


I can't answer all of these questions (nor can anyone without doing the experiments).

However, I would suggest this: Schiff base formation is much less efficient on ammonia than using primary amines. Although I did not look on SciFinder, I didn't readily see a reference, although surely it's possible to synthesize benzylimine, probably using a Dean-Stark would be necessary to remove water and push the equilibrium. However, the reference I found to making the Davis reagent uses benzenesulfonamide. So basically a change in step order - react the ammonia with benzenesulfonyl chloride (or tosyl chloride, but the methyl group may be a problem as it is easy to oxidize) to make benzenesulfonamide, then react that with benzaldehyde to make the N-benzylidenebenzenesulfonamide. OrgSyn has a procedure:

https://orgsyn.org/demo.aspx?prep=cv8p0546

As for the other questions, it's highly likely that Ca(OCl)2 can work, although there may be technical issues, if the pH is maintained, the Na or Ca should be spectator ions. However, I would imagine that not may 'milder' oxidants would function. It seems like every other variant of this reaction uses a compound with an O-O bond, and NaOCl is very powerful in its own right. A weaker oxidant would probably be unlikely to work, and other powerful oxidants like permanganate would probably cause side reactions. But there is no way to actually know without trying!


vertexrocketry - 28-2-2025 at 00:19

so that means it can convert ammonia to hydroxylamine?

Niklas - 28-2-2025 at 02:33

Quote: Originally posted by chempyre235  

So, my questions are these: (1) How is benzylimide synthesized; (2) Can Davis reagents oxidize ammonium salt in solution to hydroxyl ammonium salt; (3) Can Ca(OCl)2 substitute for NaOCl; (4) Can a milder oxidant be used to generate Davis' reagent in situ?


(1) That question has been answered, but it’s best to proceed via p-toluenesulfonamide and condense it with benzaldehyde by a Davis-Ellmann type reaction anyway.
(2) Depends on the counterion we are talking about, ammonium compounds in general aren’t nucleophilic and won’t directly react, but as far as it isn’t the salt of a strong acid there will generally be enough free amine present in the equilibrium for the reaction to still proceed at a reasonable rate.
(3) I would expect the calcium salt to work as well, while the sodium salt probably does has a stronger Lewis acid action on the imine, as you already have a sulfonyl group pulling electron density I doubt it would make a striking difference though.
(4) It isn’t really about the strength of the oxidant but rather about this very particular situation of having an nucleophilic oxygen with a leaving group attached. So besides hypochlorite peracids would be the obvious option. Chlorite should maybe work as well, I guess you could call that milder if you want.

Dr.Bob - 1-3-2025 at 17:34

You may find p-TsNH2 easier to find than the chloride as well, skipping a step. The tosyl sulfonamide is available and will react with the benzaldehyde under the right conditions to make the imine. Might work with CsCO3 or CuSO4 (anhydrous) or mol sieves to drive the reaction. I have made some similar thigns, but been a while, so I would have to look some to find it.

Lionel Spanner - 9-3-2025 at 16:48

Quote: Originally posted by vertexrocketry  
so that means it can convert ammonia to hydroxylamine?

You can do that pretty easily without using Davis reagent. Just convert it to monochloramine (keeping the pH around 8), carefully displace the chloride with hydroxide, and isolate the hydroxylamine by heating it with formaldehyde to form formaldoxime, extracting the formaldoxime with a suitable solvent, then hydrolysing it back to hydroxylamine with a strong aqueous acid.