Enol ethers derived from 2-bromomalonaldehyde are useful intermediates for the preparation of functionalized imidazolecarboxaldehydes. Recent work in our group required that bromomalonaldehyde be converted to an enol ether on a large scale and be used in a campaign to generate a late-stage intermediate in the synthesis of an investigational active pharmaceutical ingredient (API). 2-Bromomalonaldehyde was converted into several enol ethers and each was evaluated with respect to its suitability for long-term storage and the temperature at which thermal decomposition was initiated. Although the highest onset temperature was measured with the ethyl enol ether (178 °C), the cyclohexyl enol ether was discovered to be an isolable solid (mp 66.5 °C). Other enol ethers examined in our hands could not be isolated as solids and storage as stock solutions did not offer the long-term stability required to support our campaign. A process safety hazards analysis revealed that the most potential for a hazardous event to occur was during the solvent exchange from processing solvent to isolation solvent. The total energy released during decomposition at this point would have exceeded the emergency vent relief capacity of the reactor set. The final concentration of reagent in solvent was adjusted so that the remaining solvent would function as a heat sink and diluent should decomposition occur, ensuring that the process did not exceed available vent relief capacity. The chemistry detailed in this communication was scaled up and produced a total of 1.1 MT of 2-bromo-3-(cyclohexyloxy)acrylaldehyde in four batches. Batch sizes ranged from 200 − 330 kg and the average yield was 80%.

中文翻译：

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2-溴-3-（环己氧基）丙烯醛：溴苯甲醛的可分离的烯醇醚，适用于咪唑甲醛的制备†

衍生自2-溴丙二醛的烯醇醚是用于制备官能化的咪唑甲醛的有用中间体。我们小组最近的工作要求将溴代丙二醛大规模地转化为烯醇醚，并用于合成研究活性药物成分（API）的后期中间体生产活动。将2-溴丙二醛转化为几种烯醇醚，并分别评估其对于长期储存的适用性以及引发热分解的温度。尽管使用乙烯醇醚（178°C）测量了最高起始温度，但发现环己基烯醇醚是可分离的固体（mp 66.5°C）。我们手中检测到的其他烯醇醚不能作为固体和储存品分离，因为储备溶液不能提供支持我们战役所需的长期稳定性。过程安全危害分析表明，最有可能发生危险事件的过程是在溶剂从加工溶剂转换为分离溶剂的过程中。此时在分解过程中释放的总能量将超过反应堆机组的紧急通风口泄压能力。调节溶剂中试剂的最终浓度，以使剩余的溶剂起散热器的作用，并在发生分解时稀释剂，以确保该过程不超过可用的泄压口容量。此通讯中详细介绍的化学反应按比例放大，总共得到1。分四批1 MT 2-溴-3-（环己氧基）丙烯醛。批量大小在200至330千克之间，平均产量为80％。