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Small scale:

I attempted the oxidation of an aryl amine (2-amino-6-bromonaphtalene) to the nitroarene using hydrogen peroxide (ArNH2, H2O2, MeCN (15 mL as solvent). After trying it on small scale (0.1 mmol), I figured out I needed much more hydrogen peroxide than in the reference paper to observe my product. Nothing special was observed during the reaction, even after using more than 10 equ of hydrogen peroxide.

Larger scale:

I eventually repeated the reaction on a 4 mmol scale using 80 mmol of hydrogen peroxide (20 equ.). After 5 min of stirring at room temperature, the reaction bubbled up. The use of a very large flask and being lucky allowed me to stop the stirring and contain the reaction. Even after stopping the magnetic stir bar, the reaction continued to foam for another 2 or 3 minutes.

After pouring into cold water followed by a very short silica plug using ethyl acetate I obtained the pure product (confirmed by NMR) but with only 15% yield. The TLC from the reaction before purification showed two spots. One that corresponded to my product, and one that would not come off the baseline (hence it could be multiple) even in pure DCM.

Mechanism

A possible mechanism pf the oxidation reaction is shown here:

Plausible mechanism of the reaction extracted from the article cited

Possible explanation

To make things easier, I only considered the formation of 3.

To explain this I proceeded to do a thermodynamic cycle and ended up finding that to go from the starting material to (3), around 900 KJ/mol was released. ( enthalpy energies found here )

Total broken bonds: 2OH + 2xC≡N + C=N + O-O + N-O + C-N + N-H Bonds made: 2CO + 3*NH + O=O + N=O + C=N + N-O + C-N

deltaH= - (2CO + 2NH + O=O + N=O) + (2OH + 2xC≡N + C=N + O-O) = - (2358 + 2391 +(495-146) + 405) + ( 2463 +2*(891-615-293) + (615-293) + 146) ) = - 892 kj/mol

This number is on the same order of magnitude as combustion reactions for methane (-890 kj/mol). Based on the reaction mechanism, only 4 mmol should react (theoretically), hence producing 3600 kj.

Using Q = m * Cp * dT with Cp = 2.09 J/g·°C for acetonitrile and rearranging leads to an increase in temperature (15 mL of MeCN) of 135 degrees celsius, above the decomposition temperature for hydrogen peroxide. This thus may explain the decomposition I am observing.

This reasoning suggests that the stochiometric addition of hydrogen peroxide to this reaction will produce enough heat to drastically increase the temperature of the flask, hence decomposing any excess hydrogen peroxide.

Regarding the very low yield of my reaction, I am quite confused on what could be happening to my starting material to produce something so much more polar than the nitro arene. Following the mechanism, it would feel natural to suggest an over-nitration.

Questions

Is my reasoning above correct to explain why I am observing the decomposition of hydrogen peroxide?

Since we do not always have access to the mechanisms, are there ways to predict a reaction to be very exothermic to manipulate safely?

Any advice or suggestions on what could be happening to my starting material for it to be totally consumed into extremely polar products? Could the decomposition of hydrogen peroxide affect the starting material?

Notes: My starting material is quite stable under ambient conditions. Regarding the TLC mentioned at the start, I am aware that DCM is not that polar, so I am planning to use methanol:dcm if I redo the reaction. Nevertheless, going from a bromo naphtalene to a product that does not elute in pure dcm seems rather unusual. My product elutes to 0.5 rf in 50% DCM:Hex.

My apologies for such a long description. I do hope this may be useful to inexperienced chemists if manipulating hydrogen peroxide.

Ref:

Scheme:

Capperucci, A.; Tanini, D. Synthesis of Nitroarenes by Oxidation of Aryl Amines. Chemistry 2022, 4, 77-97. https://doi.org/10.3390/chemistry4010007

Errika Voutyritsa, Alexis Theodorou, Maroula G. Kokotou and Christoforos G. Kokotos. Organocatalytic oxidation of substituted anilinesto azoxybenzenes and nitro compounds:mechanistic studies excluding the involvement of a dioxirane intermediate. GreenChem., 2017,19,1291. DOI: 10.1039/c6gc03174a

Original reaction

Gupta, S., Ansari, A., & Sashidhara, K. v. (2019). Base promoted peroxide systems for the efficient synthesis of nitroarenes and benzamides. Tetrahedron Letters, 60(39), 151076. https://doi.org/10.1016/J.TETLET.2019.151076

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  • $\begingroup$ H2O2 is no good unless you use some catalyst. It doesn't need much of a reason to decompose. $\endgroup$
    – Mithoron
    Mar 28 at 15:52
  • $\begingroup$ Bit of Ag and $\ce{H2O2}$ and your project could really take off! youtube.com/watch?v=iNUppNTT9RI $\endgroup$ Mar 28 at 18:20

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