Venting Design for Di-tert-butyl Peroxide Runaway Reaction Based on Accelerating Rate Calorimeter Test

Wei, Tongtong; Jiang, Huiling

doi:10.1016/s1004-9541(11)60239-5

Cited by 13 publications

(4 citation statements)

References 8 publications

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“…In contrast to the MMC and DSC, which are used for initial screening, the ARC is more sensitive to exothermic activity with the ability to detect sample self-heat rates as low as 0.02 °C/min. Adiabatic calorimetry also more accurately mimics conditions found in a pilot plant or manufacturing plant scale, which exhibits limited heat transfer due to the increasing volume to surface area ratio, especially in the case of a thermal runaway. − …”

Section: Resultsmentioning

confidence: 99%

Integrating Process Development and Safety Analysis for Scale-Up of a Diborane-Generating Reduction Reaction

Armstrong

Behre

Turnbull

et al. 2023

Org. Process Res. Dev.

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Our company has developed a robust and scalable process to synthesize an amino alcohol tosylate salt, a penultimate intermediate in the synthesis of nemtabrutinib. A key reaction in this synthetic sequence is a reductive acetal ring opening using boron trifluoride diethyl etherate as a Lewis acid and triethylsilane as the reducing agent. Detailed mechanistic inquisition revealed that in the presence of sulfolane, boron trifluoride is reduced by triethylsilane to generate diborane as the active reductant. Diborane poses many process safety hazards; it is highly reactive, flammable, and acutely toxic. The reaction headspace was studied using infrared spectroscopy and gas chromatography, while the reaction stream was studied using heat flow and adiabatic calorimetry to ensure safe scale-up of the process. Process understanding demonstrated that containing diborane within the reactor was essential to control key impurities. Extensive development efforts were directed to design a process that could safely sequester the hazardous gas. Herein, we describe the process safety analysis, the optimization, and the scale-up of the reduction reaction and the isolation, producing two batches of the amino alcohol tosylate salt with high purity at a pilot scale.

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Section: Resultsmentioning

confidence: 99%

Integrating Process Development and Safety Analysis for Scale-Up of a Diborane-Generating Reduction Reaction

Armstrong

Behre

Turnbull

et al. 2023

Org. Process Res. Dev.

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“…In addition, during high self-heat rate reactions, because of the “thermal lag” of the ARC instrument, two unique features have been observed in our lab and in the literature. The first is a pressure “step-up” before the peak self-heat rate is reached, , or an “offset” of the peak temperatures between the self-heat rate and the pressure rate. , This discrepancy is repeatable in ARC analyses where the maximum self-heat rate is greater than 50 °C/min (e.g., autocatalytic samples) but disappears for the same tested sample when the maximum self-heat rate is decreased to below 10 °C/min simply by reducing the sample mass. The other feature noted in samples with high self-heat rates is a curving effect on the self-heat rate (on a log scale) versus temperature (on a 1/K scale) profile toward the low-temperature side, whereas this profile remains linear for the low self-heat rate range.…”

Section: Introductionmentioning

confidence: 99%

“…Both of these unique features bring challenges in fitting the kinetic parameters of decomposition reactions from ARC results, especially when additional testing is not feasible. Reliable and accurate kinetic modeling is important since it is often used to simulate different scenarios for process safety evaluation or even used for sizing of relief venting. , As an example, vent sizing based on such an ARC result that yields inaccurate kinetic parameters might either put property in danger by undersizing the vent or waste money by oversizing the vent.…”

Section: Introductionmentioning

confidence: 99%

“…Reliable and accurate kinetic modeling is important since it is often used to simulate different scenarios for process safety evaluation 15 or even used for sizing of relief venting. 8,16 As an example, vent sizing based on such an ARC result that yields inaccurate kinetic parameters might either put property in danger by undersizing the vent or waste money by oversizing the vent.…”

Section: Introductionmentioning

confidence: 99%

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Heat Loss in Accelerating Rate Calorimetry Analysis and Thermal Lag for High Self-Heat Rates

Sheng

Valco

Tucker

2020

Org. Process Res. Dev.

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Accelerating rate calorimetry (ARC) is a common tool used in thermal stability evaluation of hazardous materials to provide self-heat rate and pressure data that are used to model the kinetics of a reaction and even calculate relief vent sizing. The ARC accomplishes a conservative approach by maintaining adiabatic conditions. However, an issue with ARC instrument heating occurs when a reaction with a high self-heat rate is analyzed that results in nonadiabatic conditions and a "thermal lag". Testing was conducted to determine the self-heat rate threshold for the ARC instrument and to better understand telltale features that occur during analysis of samples with high self-heat rates. The results indicate that while the oven cannot maintain adiabatic conditions, the convective heat loss from the sample container to the ARC oven does not have a significant effect on either the measured self-heat rate or the calculated overall heat of reaction. However, the conductive heat loss from the sample container to the connection fitting does, causing the total heat measured in ARC analysis to be lower by 16% for an adiabatic ARC test, 33% for a nonadiabatic ARC test, and ∼20% for a typical ARC test in comparison with DSC measurements. A corrected phi estimation is proposed with a correction factor to take into consideration the conductive heat loss to address this issue. In addition, the thermal lag caused by the ARC temperature measurement does create a significant difference between the measured peak pressure rate and peak self-heat rate occurrences. Analysis of the results showed that a simple linear correction can be applied to high self-heat rate results for liquid samples, while the pressure rate is still increasing, to correct for these peak rate differences. The pressure rate after correction matches the self-heat rate and better agrees with the prediction from kinetic modeling. Such corrections can be applied to solid samples, where there is an additional thermal lag due to resistance to heat transfer in the solid sample itself. Accounting for the thermal lag in reactions with high self-heat rates is important when modeling of the data is used for kinetic parameters and especially for relief vent sizing.

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A new criterion to identify safe operating conditions for isoperibolic homogeneous semi-batch reactions

Bai

Lin

Guo

et al. 2017

Chemical Engineering Journal

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Venting Design for Di-tert-butyl Peroxide Runaway Reaction Based on Accelerating Rate Calorimeter Test

Cited by 13 publications

References 8 publications

Integrating Process Development and Safety Analysis for Scale-Up of a Diborane-Generating Reduction Reaction

Integrating Process Development and Safety Analysis for Scale-Up of a Diborane-Generating Reduction Reaction

Heat Loss in Accelerating Rate Calorimetry Analysis and Thermal Lag for High Self-Heat Rates

A new criterion to identify safe operating conditions for isoperibolic homogeneous semi-batch reactions

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