Decomposition and Isomerization of 1,2-Benzisoxazole:  Single-Pulse Shock-Tube Experiments, Quantum Chemical and Transition-State Theory Calculations

Abstract

Isomerization and decomposition of 1,2-benzisoxazole were studied behind reflected shock waves in a pressurized driver, single-pulse shock tube. It isomerizes to o-hydroxybenzonitrile, and no fragmentation is observed up to a temperature where the isomerization is almost complete (approximately 1040 K at 2 ms reaction time). The isomerization experiments in this investigation covered the temperature range 900-1040 K. The lack of fragmentation is in complete contrast to the thermal behavior of isoxazole, where no isomerization was observed and the main decomposition products over the same temperature range were carbon monoxide and acetonitrile. In a series of experiments covering the temperature range 1190-1350 K, a plethora of fragmentation products appear in the post shock samples of 1,2-benzisoxazole. The product distribution is exactly the same regardless of whether the starting material is 1,2-benzisoxazole or o-hydroxybenzonitrile, indicating that over this temperature range the 1,2-benzisoxazole has completely isomerized to o-hydroxybenzonitrile prior to fragmentation. Two potential energy surfaces that lead to the isomerization were evaluated by quantum chemical calculations. One surface with one intermediate and two transition states has a high barrier and does not contribute to the process. The second surface is more complex. It has three intermediates and four transition states, but it has a lower overall barrier and yields the isomerization product o-hydroxybenzonitrile at a much higher rate. The unimolecular isomerization rate constants kinfinity at a number of temperatures in the range of 900-1040 K were calculated from the potential energy surface using transition-state theory and then expressed in an Arrhenius form. The value obtained is kfirst=4.15x10(14) exp(-51.7x10(3)/RT) s-1, where R is expressed in units of cal/(K mol). The calculated value is somewhat higher than the one obtained from the experimental results. When it is expressed in terms of energy difference it corresponds of ca. 2 kcal/mol.

Isobaric metabolite interferences and the requirement for close examination of raw data in addition to stringent chromatographic separations in liquid chromatography/tandem mass spectrometric analysis of drugs in biological matrix

“…It was also found that IIA and the unidentified component in plasma showed the same exact mass (data not shown), suggesting that the interference component was derived from IIA , possibly by isomerization. All structure moieties are not likely to undergo isomerization except for the isoxazole ring whose ring‐opening isomerization has previously been documented in the literature 12. Additionally, all product ions of the interference component were consistent with the postulated ring‐opened metabolite (Scheme ).…”

On the Photochemistry of 1,2‐Benzisoxazole: Capture of Elusive Spiro‐2H‐azirine and Ketenimine Intermediates

“…For instance, the base-catalyzed isomerization of 1,2-benzisoxazoles to 2-cyanophenols proceeds through N-O bond ring-opening reaction triggered by deprotonation of the carbon atom adjacent to the nitrogen. [1,[7][8][9][10][11][12][13][14][15] Scheme 1. [5,6] Thermal and photochemical transformations of 1,2-benzisoxazoles are also known to take place as a result of N-O bond cleavage (Scheme 1).…”

“…[3,4] Named as the Kemp elimination, this reaction can be promoted by biocatalysis and has been used as an important model to rational enzyme design. [7,10] Previously, combining experimental and theoretical investigations on the parent isoxazole, we established that open-shell singlet vinylnitrenes (1A′′-VN) are key reactive intermediates respective PES of the parent isoxazole. [1,[7][8][9][10][11][12][13][14][15] Scheme 1.…”

Kinetics of the thermal decomposition of tetramethylsilane behind the reflected shock waves between 1058 and 1194 K

“…To overcome the effects like real gas and boundary layer effects, chemists have developed the chemical thermometry method [32][33][34][35] to get the accurate reflected shock temperatures. In kinetics, as the accuracy in measuring the temperature is very important, the chemical thermometric method was used in our investigations.…”