66179 - Industrial Organic Chemistry M

Course Unit Page

SDGs

This teaching activity contributes to the achievement of the Sustainable Development Goals of the UN 2030 Agenda.

Responsible consumption and production

Academic Year 2018/2019

Learning outcomes

The student will know the production methodologies of organic compounds, with particular regards to the production methodologies of high added value compounds such as pharmaceutical compounds, fragrances and food additives, agrochemicals. He/she will also be able to devise simple industrially viable organic synthesis taking into considerations economic considerations and their ecofriendliness 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.

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

Vessels and Mixing. Batch vs. Continuous Processing. Use of Continuous Flow Reactors to Scale Up Processes.

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. Cleaning Procedures and Waste Disposal Procedures. Documentation: Efficient Process Transfer

Analysis of a case study : the industrial synthesis of sildenafil citrate. Tutorials on various case studies from literature articles

Readings/Bibliography

Neal G. Anderson "Practical Process Research & Development" - Academic Press, 2012
Lectures' handouts available thorugh Alma Digital Library - AlmaDL

Teaching methods

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

Assessment methods

The assessment of learning is through the only final exam which is supported at one of the six defined by the teacher during the academic year during exam sessions arranged by the program. The final examination confirms the acquisition of the knowledge and skills expected by conducting a written test with a duration of 2.5 hours that are allowed to consult texts, handouts and notes. A week before the exam date, an article about literature, which will be tested, is made available to students via the web. The written test consists of two parts: 1) a series of questions (5-10, 1-2 maximum score points in question) multiple choice on understanding the item in relation to the issues addressed during the course, 2) cost analysis a synthetic sequence reported in the article, according to the mode explained in class (maximum score 15-21 points). The final grade is the sum of the scores obtained in the two parts of the written examination.

Teaching tools

Powerpoint slides

Office hours

See the website of Letizia Sambri