Synthesis of a Stereochemically Defined 1,2-Diazetine N,N‘-Dioxide and a Study of Its Thermal Decomposition

Abstract

Diazetine dioxide 1a has been synthesized in a single step via oxidation of meso-2,3-diphenyl-1,2-ethanediamine with dimethyldioxirane, albeit in low yield (7%). Thermal decomposition of 1a afforded predominantly either trans-stilbene or diphenyl glyoxime depending on solvent, temperature, and the presence of an amine catalyst. Reaction in chloroform at 69 degrees C favored elimination of NO and formation of trans-stilbene. The stereospecific formation of trans-stilbene suggests a mechanism of decomposition in which C-N bond cleavage leads to a diradical intermediate stabilized by the phenyl group. Bond rotation followed by cleavage of the second C-N bond accounts for the trans-stilbene. At 25 degrees C in chloroform, while trans-stilbene was still the major product, some diphenyl glyoxime was also observed (4% yield). However, 1a as a solution in chloroform in the presence of Et3N, or 1a as a solution in DMSO-d6, afforded predominantly diphenyl glyoxime. These results are interpreted in terms of two closely competing reactions subject to the effects of entropic contributions.

Thermal Decomposition of meso- and d,l-3,4-Diethyl-3,4-dimethyldiazetine N,N‘-Dioxide

“…Clean, first-order kinetics were observed. The rate determined ( k = [1.2 ± 0.2] × 10 -4 s -1 ) was consistent with the rate determined by NMR spectroscopy in DMSO- d 6 ( k = [8.9 ± 0.1] × 10 -5 s -1 ) . Compounds 1c ( k = [2.2 ± 0.1] × 10 -4 s -1 ) and 1d ( k = [1.7 ± 0.2] × 10 -4 s -1 ) exhibited marginally higher rates of decomposition, possibly attributable to the slightly greater steric interactions of the larger ethyl groups on these compounds relative to the four methyl groups of 1b (the cis -oriented ethyl groups of 1c affording the greatest steric interactions and therefore the highest reaction rate).…”

“…We recently reported the thermal decomposition of cis -1,2-diphenyl-3,4-diazetine N , N ‘-dioxide ( 1a , Figure ) . This compound decomposed at a rate much greater than that of alkyl-substituted diazetine dioxides (e.g., 1,1,2,2-tetramethyldiazetine dioxide, 1b ), and the product distribution was found to be solvent dependent.…”

“…1,2-Diazetine N , N ‘-dioxides (diazetine dioxides), 1 in Figure , are a class of strained four-membered ring azo dioxide heterocycles . They have been used as highly effective low-energy triplet quenchers in photochemical reactions, and have recently been investigated for their pharmaceutical potential as vasorelaxants and antiaggregants. , Their biological activity can be attributed to the liberation of 2 equiv of nitric oxide (NO) upon thermal decomposition (Figure ).…”

“…1,2-Diazetine N , N ‘-dioxides (diazetine dioxides), 1 in Figure , are a class of strained four-membered ring azo dioxide heterocycles . They have been used as highly effective low-energy triplet quenchers in photochemical reactions, and have recently been investigated for their pharmaceutical potential as vasorelaxants and antiaggregants. , Their biological activity can be attributed to the liberation of 2 equiv of nitric oxide (NO) upon thermal decomposition (Figure ). However, the mechanism of decomposition is still in question. ,, To realize the full potential of diazetine dioxides as therapeutic agents it is imperative to have a clear understanding of their preferred mode of thermal decomposition.…”

“…We recently reported the kinetics of decomposition of compound 1b as determined by 1 H NMR spectroscopy . We desired to compare the rate of decomposition of compounds 1c , d with that of 1b , but 1 H NMR spectroscopy was not nearly as appealing a method because of the greater complexity of the NMR spectra of 1c , d (and, hence, expected overlap of signals).…”