MUST: MicroflUidics for Structure-reactivity relationships aided by Thermodynamics & kinetics

化学物(反应物或产物)的结构与其反应性(动力学和热力学)之间的关系是一个交叉热力学、动力学、有机化学和化学工程的研究领域。该项目将由德国和法国的专家对这一研究领域进行调查。线性自由能关系(LFER)的概念，包括Taft方程，是一个强大的结构-反应性工具，可以解释一系列化学反应中的空间效应、极性效应和共振效应。Taft方程表明，在一系列反应中，反应物的结构(即靠近反应中心的取代基)与其反应性之间存在关系。将其应用于化学反应(如酯化反应)是最先进的，并声称所开发的参数是有效的，与反应条件无关。然而，在一种溶剂中主要使用酯化和水解反应，这在原则上限制了这些关系的一般有效性。因此，将LFER概念推广到大量的溶剂或溶剂混合物，甚至多相反应体系，需要在没有浓度和温度梯度的情况下的本征动力学曲线，以热力学活性表示。重新开发的基于Taft的方法将主要应用于三个涉及木质纤维衍生平台分子的化学反应系统：1)葡萄糖在不同的乙醇溶剂中溶解生成乙酰丙酸酯；2)乙酰丙酸-乙酰丙酸酯的酯化-水解反应；3)乙酰丙酸或乙酰丙酸酯在氢气和固体催化剂作用下加氢生成γ-戊内酯。对于这些体系，我们将改变反应物，即1)和2)不同的醇，以及3)不同的乙酰丙酸酯。系统2)将证明LFER概念在酶催化中的有效性。目标是使用重新开发的方法来研究和预测反应物中的-R取代基效应和溶剂对动力学曲线的影响。微流控技术的使用将允许进行动力学实验，避免运输限制。反应物和产物的活度将根据实验动力学曲线和状态方程EPC-SAFT进行预测。这最终将允许预测反应性质(标准热焓、标准吉布斯能)以及基于本征活性的反应动力学常数。此外，EPC SAFT将被用来预测反应体系所需的相行为(例如，氢气在反应介质中的溶解度)；所有的预测(相行为和反应特性)都将被实验验证。LFER和EPC-SAFT这两种方法的结合将意味着对化学合成设计的新的理解和新的维度。

The relationships between the structure of chemicals (reactants or products) and their reactivity (kinetics and thermodynamics) is a research area that crosslinks thermodynamics, kinetics, organic chemistry and chemical engineering. This project will investigate this research area by German and French specialists. The concept of Linear Free Energy Relationships (LFER), including Taft equation, is a powerful structure-reactivity tool that accounts for steric, polar and resonance effects on a series of chemical reactions. Taft equation shows that there is a relationship between the structure of reactants (i.e., the substituent near to the reaction center) and their reactivities within a reaction series. It is state-of-the art to apply this to chemical reactions (e.g. esterification), and it is claimed that the developed parameters are valid independent of the reaction conditions. However, mainly esterification and hydrolysis reactions were used in one kind of solvent, which in principle limits the general validity of the relationships. Thus, generalizing LFER concepts to vast number of solvents or solvent mixtures and even to multiphase reaction systems requires intrinsic kinetic profiles in the absence of concentration and temperature gradients, expressed in terms of thermodynamic activities. This will be developed in this project.The redeveloped Taft-based method will be mainly applied to three chemical reaction systems that involve lignocellulosic-derived platform molecules: 1) glucose solvolysis to levulinate ester using different alcohol solvents, 2) esterification-hydrolysis of levulinic acid-levulinate ester and 3) hydrogenation of levulinic acid or levulinate ester to gamma-valerolactone by H2 and solid catalyst. For these systems, we will vary the reactants, i.e., different alcohols for 1) and 2), and different levulinate esters for 3). System 2) will prove the validity of the LFER concept to enzyme catalysis. The goal is to use the redeveloped method to study and predict the -R substituent effect in the reactant and the solvent effect on kinetic profiles.Reaching the goal requires different research expertise. The use of microfluidic technologies will allow performing kinetic experiments avoiding transport limitations. Activities of the reactants and products will be predicted based on the experimental kinetic profiles and the equation of state ‘ePC-SAFT’. This will ultimately allow predicting reaction properties (standard enthalpies, standard Gibbs energies) as well as intrinsic activity-based reaction kinetic constants. Furthermore, ePC SAFT will be used to predict the required phase behavior of the reaction systems (e.g. H2 solubility in reaction medium); all predictions (phase behavior and reaction characteristics) will be validated by experiments.The association of both methods –LFER & ePC-SAFT– will mean a significant new understanding and a new dimension in designing chemical syntheses.