Experimental Design and Optimization: Application to a Grignard Reaction

Abstract

This project is conducted by students during the second semester of their second year in our educational institution. This project constitutes an initiation into research and allows a broadening of knowledge, a development in autonomy, organization, team work, and initiative. It helps prepare the student-engineer for an internship in industry. The experiment is done in student pairs over 5 weeks (three, eight-hour days per week). We introduce experimental design to undergraduate students because such methodology is increasingly important in modern industrial research. The well-prepared chemist will need to apply these concepts easily. Other pedagogical goals include increasing experience in synthetic techniques, scientific rigor to obtain reproducibility in the yield, and using quantitative analysis methods. This project investigates optimizing the synthesis of benzyl-1-cyclopentan-1-ol using experimental design. It is carried out in three steps: first the factors that can have a potential influence on the reaction are screened; second, a factorial design is used to study the interactions between the factors; and finally, response surface methodology is used to optimize the yield.

DoE (Design of Experiments) Assisted Allylic Hydroxylation of Enones Catalysed by a Copper–Aluminium Mixed Oxide

“…This statistic tool is commonly used in analytical chemistry or chemical engineering, but it is rarely used in synthetic organic chemistry. [11][12][13][14][15] The design of experiments approach, in contrast to the classical OVAT method (changing one variable at a time), allows us to study a system by changing many variables at the same time. A matrix delimited by low and high levels of each variable involved in the reaction is defined.…”

“…Cyperone itself (12; Table 6, Entry 6) proceeded quantitatively, providing 6α-hydroxycyperone derivative 13 in synthetically useful yields. Table 6, Entry 7 shows the oxidation of a more complex ketone such as testosterone (14). The inertness of this substrate is well known, and a low yield (20 %) of the product was isolated, although in the absence of Cu-Al Ox, only starting material was recovered.…”

Chemometrically Assisted Optimization of Pregabalin Fluorescent Derivatization Reaction with a Novel Xanthone Analogue and Validation of the Method for the Determination of Pregabalin in Bulk via a Plate Reader

“…Although DoE has been widely used in analytical chemistry, its utility in synthetic chemistry remains largely unknown, especially in the academic field [ 36 ]. A few previous studies report significant applications of DoE in synthetic chemistry, leading to improved yields of high purity products in the shortest time and with minimum amounts of reagents [ 37 , 38 , 39 ].…”

Process Development of the Weiss–Cook Reaction for the Preparation of cis-1,5-Dimethylbicyclo[3.3.0]octane-3,7-dione in the Undergraduate Organic Laboratory

“…Often, these reactions are carried out in the undergraduate organic chemistry laboratory to help solifidy and support the concepts learned in lecture. Classical transformations such as Wittig, Grignard, and Diels–Alder reactions have been successfully carried out and incorporated in the second-year organic chemistry curriculum. Performing these reactions in the laboratory allows for extensive investigation of new laboratory techniques, proposed reaction mechanisms, and structure elucidations.…”