00153 - Industrial Organic Chemistry

Learning outcomes

At the end of the course, the student will be acquainted with the scale up of organic reactions. The student will know the main technologies enabling the efficient production of highly added value compounds, such as pharmaceuticals, fragrances and food additives, agrochemicals. He/she will also be able to devise simple industrially viable organic syntheses taking into consideration their environmental impact and sustainability.

Course contents

Pre-requisites: expertise in advanced organic chemistry, in particular synthesis and reactivity of the main functional groups, aromatic compounds and their reactivity and metal-mediated organic reactions. Recommended course: Chimica Organica con Laboratorio M

Approaches to Process Development. The Importance of Simple Scale-up Operations; The Importance of Teamwork; Operations That Can and Cannot Be Used On Scale; Safety Considerations; Define the Time Available for Process Optimization. Green chemistry. Green Metrics.

Route Selection. Expedient Routes. Cost-Effective Routes

Reagent Selection. Reagents for Scale-up. Safety and Toxicity Considerations. Cost of Reagents. Families of Reagents Useful for Scale-up

Solvent Selection. Solvent Characteristics. Physical Characteristics of Solvents. Inappropriate and Useful Solvents for Scale-up. Solvent Impurities. Applications of Solvents

Running the Reaction. Determining Reaction Safety. Assessing Safe Operating Conditions for the Laboratory. Selecting the Reaction Scale. Choose Equivalents of Reagents, Starting Materials, and Solvents. Inert Conditions. Charge Starting Materials and Solvents. Reaction Temperature. Duration and Temperature of an Addition. Sequence of Additions. Adjust Stirring. Monitor the Reaction Conditions.

In-Process Controls. The Importance of IPC for Processes Filed with regulatory agencies. Choosing the Appropriate IPC. Generating Reproducible IPCs.

Optimizing the Reaction by Minimizing Impurities. Steps to Optimizing Reactions. Optimizing Reaction Temperature; Optimizing Number of Reagent Equivalents; Optimizing Addition of Reagents; Optimizing Use of Solvents and Cosolvents; Optimizing Reaction Concentration; Changing Reagents and Intermediates; Optimizing Catalysts and Ligands; Optimizing Stirring; Importance of Extending Reaction Times. Identifying Impurities. Statistical Design of Experiments. Robotics and Automated Process Optimization.

Work-up. Aspects of Work-up: Quench; Extraction; Activating Carbon Treatment; Filtration; Concentrating Solutions and Solvent Displacement; Deionization and Removing Metals; Destruction of Process Streams; Derivatization.

Purifying the Product. Column Chromatography. Crystallization. Classification of Solids: Morphic States. Salt Selection. Washing and Drying Solid Products. Purification by Reslurrying.

Preparing for and Implementing the Scale-up Run. Anticipating Scale-up Problems. Scale-up Considerations: Goals of Scale-up. Safety Considerations. Critical Processing Steps. Equipment Limitations. Rugged IPC for the Scale-up Operation. Contingency Plans for Incomplete and Runaway Reactions. Effects of Extended and Interrupted Processing. Qualify Components. Process Tolerances for Scale-up. Documentation: Efficient Process Transfer

Analysis of case studies. Tutorials on various case studies from literature articles.

Readings/Bibliography

Neal G. Anderson "Practical Process Research & Development" - Academic Press, 2012

Lecture handouts available via the virtuale platform.

Teaching methods

The course consists of lectures accompanied by exercises on the application of the presented concepts.

Process chemists from industry will be invited.

Assessment methods

The assessment of learning is through a final exam. At least six exam sessions will be defnied during the academic year. The final examination inspects the acquisition of the knowledge and skills expected by conducting a written test.

Students are allowed to consult texts, handouts and notes during the exam.

The exam will be based on an article from the literature, describing the development of a large scale synthesis. Several closed-ended questions are followed by one or more questions on the mechanism of the reactions under study. Part of the exam will deal with the calculation of costs, and of the metrics typically used to assess the environmental impact and the efficiency of a synthetic process.

Teaching tools

Powerpoint presentations.

Excercises at the blackboard.

Quizzes and problems via Virtuale platform.

Office hours

See the website of Luca Bernardi