Tailored Solvents for Pollution Source Reduction in Phamaceutical & Fine Chemical Processing

摘要提出开发一种新型溶剂，其溶剂化性能与传统用于制药和精细化学加工的溶剂相似，但由于对环境不利的空气排放或水排放流而损失的可能性最小。将对新溶剂进行全面的鉴定，并评价它们在尽量减少潜在污染、减少溶剂交换次数和特定工艺所需的单元操作方面的作用。经济和环境影响评估将包括溶剂使用的所有方面，包括其合成和由此可能产生的任何废物。这些新溶剂将通过对要取代的溶剂四氢呋喃（THF）进行适当的衍生化来获得，以使其挥发性或水溶性显著降低，从而不易进入环境；活性溶剂部分也将通过附着在柔性聚合物上“固定化”，然后将其溶解在更良性的连续相中。这些新溶剂将作为反应介质在广泛的模型反应系统中进行测试，包括在HIV蛋白酶抑制剂Crixivan的生产中重要的一系列反应，详细的光谱表征以及整体热力学性质将用于根据溶剂改性引入的空间和电子效应来合理化动力学结果。将进行过程系统建模，以量化使用这些溶剂的过程的经济和环境影响，并与传统系统进行比较。将开发一系列新的溶剂，并对其溶剂化、热力学和输运性质进行表征，并使用一系列不同的模型反应测试其作为反应介质的功效。将建立产品回收和溶剂再生的指导方针，并将开发过程系统模型，以优化药物和精细化学合成中的反应/分离顺序。这些新溶剂从合成到加工使用的生命周期分析，包括溶剂再生，将描述它们有用的应用参数。

CTS-9729404 Hatton, T.A. MIT Abstract It is proposed to develop a new class of solvents that have solvation properties similar to those of solvents used conventionally in pharmaceutical and fine chemical processing but for which the potential for loss by environmentally-unfavorable air emissions or in aqueous discharge streams is minimized. A complete characterization of the new solvent is to be undertaken, and their role in minimizing the potential for pollution, and in reducing the number of solvent exchanges and unit operations required for specific processes will be evaluated. The economic and environmental impact assessment will include al aspects of the solvent usage, including its synthesis and any wastes that may be generated thereby. These new solvents will be obtained by suitable derivatization of the solvent tetrahydrofuran (THF) to be replaced to render it significantly less volatile or water soluble, and thus less inclined to enter the environment; the active solvent moiety will also be 'immobilized' by attachment to flexible polymers, which are then dissolved in a more benign continuous phase. These new solvents will be tested as reaction media for a broad range of model reaction systems, including a series of reactions that are important in the production of the HIV protease inhibitor Crixivan Detailed spectroscopic characterization as well as bulk thermodynamic properties will be used to rationalize the kinetics results in terms of steric and electronic effects introduced by the solvent modification. Process systems modeling will be carried out to quantify the economic and environmental impact of processes using these solvents, and compared with conventional systems. A new range of solvents will be developed and characterized in terms of their solvation, thermodynamic and transport properties, and tested for their efficacy as reaction media using a range of different model reactions. Guidelines will be established for product recovery and solvent regeneration, and process systems models will be developed for optimization of reaction/separation sequences in pharmaceutical and fine chemical syntheses. A life cycle analysis of these new solvents from synthesis through to use in processing, including solvent regeneration, will be made to delineate their useful application parameters.