Thermally unstable tosyloximes

David H. Brown Ripin
David J. Am Ende
Neil P. Weston
Pfizer Global R&D
Groton, Conn.

Chemical & Engineering News ( 01 July 2001) Vol. 79, No. 40, p. 8.

We would like to call attention to a thermally unstable class of tosyloximes that are intermediates in a preparation described in Organic Syntheses [64, 19 (1985)]. This procedure is commonly used to produce -aminoketopyridines and the corresponding acetals via Neber rearrangement of the tosyloximes.

In preparing to scale this procedure, we investigated the energies of decomposition of these intermediates using differential scanning calorimetry analysis. We found that the 2-, 3-, and 4-substituted pyridines all decomposed with a large output of energy (995–1,400 J per g, about one-quarter of the energy released by TNT) with rapid onset at temperatures of 83–92 ºC. Similar findings were published by the Merck process research group, who noted that the 3-substituted pyridine also demonstrated low-level shock sensitivity [Tetrahedron Lett. 40, 6739 (1999)].

We also have anecdotal evidence that a sample of the 2-substituted pyridine detonated on drying in a drying pistol. The oxime precursors to the tosylates also decompose with significant energies (900–1,200 J per g), but at much higher onset temperatures (200–218 ºC). The corresponding tosyloxime derived from acetophenone decomposes with significantly lower energy (356 J per g), but with a low onset temperature of 42 ºC. We recommend using extreme caution when handling these materials.

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