Explosion from aqueous hydrogen peroxide and acetic anhydride

We’ve got a safety letter in today’s issue of C&EN:

WE ARE WRITING to report on an accident that occurred in the chemistry department at Northwestern University on Dec. 3, 2010. Unfortunately, one of our advisees was seriously injured. The accident—a reaction mixture detonation—occurred during an attempt to synthesize 2-(tert-butylsulfonyl)iodosylbenzene, a partially soluble form of iodosylbenzene that is particularly convenient for use as an oxygen source in studies of catalytic chemical oxidations, such as olefin to epoxide reactions. The synthesis had been performed about a dozen times previously at Northwestern without incident.

The synthesis procedure was a modified version of a procedure first described by Dainius Macikenas and coworkers (J. Am. Chem. Soc., DOI: 10.1021/ja991094j), which in turn had been adapted from a tested “Organic Syntheses” preparation (Sharefkin, J. G. and H. Saltzman, in “Organic Syntheses”; H. C. Baumgarten, Ed.; New York: John Wiley & Sons, 1973; Collection Vol. 5, page 660). One modification was the use of a higher H2O2/iodobenzene ratio (25 instead of 2.8) while maintaining a similar H2O2 concentration. Likely more relevant was a second modification: the use of 35% by weight (freshly opened) hydrogen peroxide, rather than the 30 wt % solution indicated in the Macikenas procedure and used previously at Northwestern.

We do not know with any certainty what caused the explosion. However, the procedure entails combining aqueous H2O2 with acetic anhydride to form peracetic acid. The water component of the aqueous H2O2 solution should serve to remove excess acetic anhydride. We speculate that if some acetic anhydride remained after conversion of the majority to peracetic acid (the desired intermediate compound) or acetic acid (side product), the anhydride could have combined with peracetic acid to form diacetyl peroxide. This organic peroxide is known to be a shock-sensitive explosive.

If our reasoning is correct, the amount of diacetyl peroxide that potentially can form is greater in the modified reaction. Presumably, the less water initially present the greater the chance of forming the unstable organic peroxide. For a given amount of H2O2, the number of moles of water present in 35 wt % hydrogen peroxide is about 21% less than the number present in 30 wt % hydrogen peroxide. It is sobering to realize that even with 35 wt % hydrogen peroxide, the combined number of moles of water and hydrogen peroxide likely exceeded the number of moles of acetic anhydride initially present—and yet an explosion occurred. It is unclear what the margin of error is with regard to water and hydrogen peroxide concentration versus acetic anhydride concentration. However, we believe that at least some diacetyl peroxide is formed under all reaction conditions.

We emphasize that the above “explanation” and discussion are speculative. Nevertheless, there is support from the patent literature. (See, for example, U.S. Patent No. 3,079,443, “Production of a Solution of Diacetyl Peroxide in Acetic Anhydride.”) In the patented process the coreactant is aqueous H2O2.

At least until the cause of the explosion can be determined, we strongly encourage researchers to consider using alternative, nonperoxide, routes to 2-(t-butylsulfonyl)iodosylbenzene, iodobenzene diacetate, and related compounds (J. Am. Chem. Soc., DOI: 10.1021/ja1069773). More generally, we recommend that aqueous H2O2 and acetic anhydride never be combined—despite the fact that, until now, this has been a commonly used reagent combination in oxidation chemistry.

Joseph T. Hupp and SonBinh T. Nguyen
Evanston, Ill.

I e-mailed Hupp and Nguyen to see if they wanted to add anything else. Hupp replied that “Safety glasses did successfully protect the advisee’s eyes.”

Author: Jyllian Kemsley

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  1. I really appreciate this letter. It’s nice to see folks spreading the word on dangerous procedures!

  2. Thank you for your discussion. Basic safety is always issue #1.

  3. I have a couple of questions about the procedure:

    1) What was the scale of the reaction? The authors report ratios and percentages (by mass), but what were the absolute volumes or masses used?

    2) What type of container was used as the reaction vessel? Was the reaction mixture open to the atmosphere? Was it an rb flask sealed by a septum? Was it a vial sealed by a screw cap?

  4. Peracids, not just peracetic acid, are all highly reactive chemicals and all work with them must be treated as a high risk task. As such, a specific work procedure (experimental protocol) must be developed, reviewed, and followed. Because the nature of the the work is experimental, specific safeguards must be used.
    Work with the smallest quantities consistent with the objective
    Place the work behind a double layer shield – a portable lab shield behind a fume hood sash
    Wear appropriate PPE – absolutely eye/face protection, and appropriate gloves when handling the reaction vessel. Blue nitrile gloves will not protect your fingers if the flask ruptures.

    We regret that someone was injured at Northwestern (my alma mater) but we must learn from this unexpected event, and work to prevent a recurrence.

    Hupp and Nguyen are to be thanked for their timely reporting of the incident.

  5. @Paul: I sent your comment to Nguyen, who pointed me to a recent paper in Chemical Science (DOI: 10.1039/C0SC00339E).

    From the supporting information, it looks like the initial combination was 35 mL of 35% by weight H2O2 in water added to 165 mL of acetic anhydride in a 500-mL round-bottom flask. There are several more manipulations, though, and it wasn’t until the final product was isolated that the researcher was injured: “Upon concentrating the product in this reaction and drying, enough of the explosive diacetyl peroxide remains behind in the solid product to trigger the explosion that injured the researcher when this person attempted to break up the product with a spatula.”

  6. I can’t access that paper for the moment; the RSC site might be down.

    So…they were working on a ~0.2 kilogram scale? I’m not a hardcore synthetic chemist, but anything dealing with strong oxidants on that scale would make me a little nervous. I am not familiar with the authors’ research, but wonder whether they use enough of this compound to necessitate its preparation in such large quantities.

    I could be wrong, but it seems to me that these types of compounds are relatively stable when wet. Perhaps a better course of action would be to partition the large batch into smaller (plastic) vials while it is still wet, then dry the samples individually.

    Just a thought. And all the best to the wounded chemist.

  7. Oxidations always carry a certain amount of risk. It is difficult to imagine that we should forgo hydrogen peroxide / anhydride reactions, which is the classical way to produce peracids. I would like to know more about the “concentrating and drying” operation. Generally speaking, many peroxides become unstable under anhydrous conditions.

  8. The explosion that occurred in the lab of my collaborator and colleague, Prof. Nguyen, was a consequence of an attempt to synthesize somewhat less than 4 grams of oxidant. A typical experiment, using the smallest accurately measurable amount of one of our oxidation catalysts, consumed 0.5 to 1 g of oxidant.

  9. What was the experience level of the person performing the experiment (presumably the same one as was injured)? PhD candidate?

  10. Thank you to Professors Hupp and Nguyen for warning the chemistry community about the hazard risk associated with the procedure. I hope for a quick recovery for the student involved.

    In thinking about the procedure further, I decided to pull up the supporting information from the Chemical Sciences paper and look at the experimental procedure in question. If the protocol that was followed was as described, then a potential source of the problem may be the order of addition of reagents. The procedure states that hydrogen peroxide was added to acetic anhydride. This way of mixing the two reagents is expected to favor formation of diacetyl peroxide: as the peroxide is added, depending on the rate of addition as well as the rate of acylation, there will be peracetic acid being formed in the presence of an excess of acetic anhydride, especially in the early part of the addition. The OH of peracetic acid formed can then get acetylated by the excess acetic anhydride, giving rise to diacetyl peroxide, which could persist throughout the reaction. Were the acetic anhydride added to the aqueous hydrogen peroxide solution, then the anhydride would encounter an excess of aqueous hydrogen peroxide, so less of the diacetyl peroxide should form. The above reasoning assumes that the acetylation of the hydrogen peroxide and peracetic acid is fast.

  11. Peroxide Explosion Hazard Test

    Re. N-oxidations using 30% H2O2 in Glacial Acetic Acid.

    Potassium Iodode Starch Test Paper turns blue when hydrogen peroxide is present.

    The test does not work when the solvent is acetic acid.
    This means that the presence of the explosive peracetic acid is not detected.

    Peracetic acid explodes spontaneously when concentrated (as we all know) or if heated above 110oC.

    To save your life: Dilute your acetic acid / hydrogen peroxide
    Reacton mixture with water. This shifts the equilibrium to acetic acid and peroxide
    and the KI/starch paper will now turn blue if peracetic acid was present.

    Acetic acid / peroxide mixtures must never be concentrated without diluting with lots of water first. Acetic acid is removed in the azeotrope . Keep adding water and test for H2O2 with the KI/Starch paper.

    Peroxide can be chemically destroyed with Sodium metabisulfite. This reaction can be very violent and very exothermic as I discovered when testing with 5% H2O2 in water.

    When in doubt,
    dilute your acetic acid peroxide mixture
    with lots of water then add sodium sulfite
    (or metabisulfite)
    until a negative is indicated with the
    Potassium Iodode Starch test paper.


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