Scalable Process for the Production of a Highly Energetic Bromoacetylene Building Block

Quantum mechanical (QM) applications to predict heat of reaction (ΔH r ) and thermal stability of strained aminocarbocylic salts, diazo compounds, and nitroalkanes for early phase thermal hazard risk assessment is presented. We provide examples on the use of explicit solvation to predict accurate ΔH r . Based on the QM calculations, the criticality class of a coppercatalyzed C−N coupling reaction is determined according to Stoessel's reaction criticality class and the predictions are consistent with RC1 calorimetric experiment. We emphasize that to predict accurate ΔH r , it is important to consider the roles of reagents and solvents in QM calculations rather than simply considering the bond formation and bond breaking steps involved with reactants and products. Further, the use of predicted ΔH r for salt formation is applied to predict the thermal stability of bromoacetylene azetidine compounds to establish structure−stability relationship which would be useful to identify stable salt intermediates for safe reaction design. A strong correlation between ΔH r and the left limit of the DSC onset temperature (T init , °C) of the of exothermic peak is identified (T init = −2.85 ΔH r − 99.5). We propose that this model can be used as a prediction tool for novel azetidine salts to provide an estimate of thermal stability before synthesis. In this paper, for the first time we report molecular electrostatic potential (MESP) descriptor for the prediction of T init of diazo compounds. The deepest MESP minimum (V min ) on the diazo group is considered as a probe to quantify the variation in structural effects. A strong correlation between V min and T init is found which would provide a new way of interpreting the thermal stability of novel diazo molecules just based on chemical structure. Further, the applicability of V min is verified on another set of compounds (nitroalkanes) and a good correlation is obtained. The structure− stability relationships that involves V min can be a useful QM descriptor for thermal stability prediction of a variety of molecules.

show abstract

“… a Taken from ref . b As 1c and 1d are dicarboxylic acid salts, Δ H r is calculated per mole of free base. …”

Section: Resultsmentioning

confidence: 99%

Quantum Mechanical Methods for Thermal Hazard Risk Assessment in Early Phase Pharmaceutical Development

Sayyed

Kolis

Xia

2022

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…The focus of this exercise is to do a literature search for potential hazards involving the compounds being used and to identify functional groups known to potentially exhibit exothermic decomposition, as reagents and intermediates with one or more of these high-energy functional groups indicate a potential for thermal hazard. Our literature search found two instances where there was a warning that drying propargyl alcohol and other acetylenic compounds with alkalines could lead to an explosion, which was a concern. , There were also several references which highlighted the extremely energetic and explosive nature of acetylenic compounds . In addition, the terminal alkyne of propargyl alcohol is considered a high-energy functional group .…”

Section: Results and Discussionmentioning

confidence: 99%

Thermal Hazards of Using Propargyl Alcohol with Strong Bases

Brown

Allian

Chen

2021

Org. Process Res. Dev.

View full text Add to dashboard Cite

Thermal hazard screening of a reaction mixture that involves the use of propargyl alcohol as the reactant/solvent along with potassium hydroxide as catalyst resulted in catastrophic thermal decomposition that ruptured an accelerating rate calorimeter (ARC) test cell. Due to this critical hazard, scale-up of the chemistry was not advisible. In order to enable scale-up, further investigations into solvent and base combinations were carried out. New optimum conditions enabled the synthesis of the desired product in a safe manner. The main purpose of this manuscript is to alert the scientific community to the thermal hazards of this compound.

show abstract

“…To evaluate the thermal hazard of the catalytic oxidation of cyclohexene with hydrogen peroxide, we combined probability ( TMR ad ) and consequence (Δ T ad,r ) measurements at different phases by using the risk matrix presented in Table 8. The critical temperatures of the Stoessel criticality diagram are listed in Table 9 38 . Because the reaction system was open, MTT was mainly selected based on the boiling point of the solvent.…”

Section: Resultsmentioning

confidence: 99%

Thermal hazard and reaction mechanism of the preparation of adipic acid through the oxidation with hydrogen peroxide

Jiang

et al. 2020

AIChE Journal

View full text Add to dashboard Cite

In this study, various calorimetric and analytical techniques were used to evaluate the thermodynamics of the preparation of adipic acid through the oxidation with hydrogen peroxide. The reaction exotherm was combined with the reaction mechanism. Differential scanning calorimetry revealed that the hydrogen peroxide was relatively stable when Na2WO4.2H2O and H2SO4 were used as cocatalysts. Reaction calorimetry, in situ Fourier transform infrared spectroscopy and gas chromatography/mass spectrometry (GC/MS) results indicated a possible macroscopic reaction pathway at 73 and 90°C stage. Furthermore, the results obtained through adiabatic calorimeter (Phi‐TEC II) and GC/MS indicated the possibility of catastrophic accidents if control of the target reaction was lost. The criticality classes of this reaction were of Grade 5. The results of this study can be further used to improve the inherent safety of its operating measures, as a result, this reaction process can be scaled up.

show abstract

Scalable Process for the Production of a Highly Energetic Bromoacetylene Building Block

Cited by 8 publications

References 24 publications

Quantum Mechanical Methods for Thermal Hazard Risk Assessment in Early Phase Pharmaceutical Development

Quantum Mechanical Methods for Thermal Hazard Risk Assessment in Early Phase Pharmaceutical Development

Thermal Hazards of Using Propargyl Alcohol with Strong Bases

Thermal hazard and reaction mechanism of the preparation of adipic acid through the oxidation with hydrogen peroxide

Contact Info

Product

Resources

About