ECO-FRIENDLY ORGANIC SYNTHESIS AND LABORATORY

The course falls among the training activities of the Master's degree program in Chemistry and Sustainable Technologies, which are dedicated to the deepening of the subjects related to the concept of eco-compatible chemistry. The specific training objective of the course is to provide knowledge by which students deal with a complex chemical problem such as the study and analysis of procedures of organic synthesis with low environmental impact. To this purpose, modern methodological tools using indicators such as atom economy, e-factor, mass index, etc., are introduced to quantify the efficiency or environmental performance of a chemical process in relation to the principles of Green Chemistry. By examining some model processes and model transformations on a laboratory and industrial scale, the course aims at offering students both the general concepts for the implementation of eco-compatible synthesis, and the ability to develop a certain critical capacity in the application of notions of green chemistry to the use of reaction conditions including reagents, solvents and catalysts, and reaction modes. These aspects are integrated into the laboratory section of the course which is articulated through the implementation of some organic transformations with low environmental impact and their analysis by using the aforementioned indicators. Some homeworks are also required by which students (groups of 2-3 units) choose and analyze scientific articles and reviews in the context of journals specialized in the field of green / sustainable chemistry.

1. Knowledge and understanding
i) The student is asked to know the principles of Green Chemistry and some of the most modern synthetic solutions for the implementation of several types of organic reactions with reagents, solvents and catalysts with reduced environmental impact.
ii) The student is asked to know the tools and metrics that allow to quantify the efficiency and environmental performance of a chemical process in relation to the principles of Green Chemistry.
2. Ability to apply knowledge and understanding
i) The student must know how to use the concepts learned during the course, to logically examine the characteristics of environmental impact of an organic synthesis; in particular, he/she has to learn how to propose a coherent analysis of environmental efficiency and performance of a procedure by evaluating the experimental procedure through the application of metrics such as atom economy, e-factor, mass index, reaction mass efficiency, etc. and the related graphic analysis of the process.
ii) The student must know how to formulate original ideas and conclusions on the impact of a synthetic process in terms of benefits and inconveniences/aspects that can be improved from an economic and environmental standpoint. The laboratory session and the homework, as described in the training objectives, contribute to the development of this knowledge.
iii) The student must be able to identify the tools to deal with a complex problem such as the design of an organic synthesis with new reagents / products / solvents and less waste production, respecting human health and protecting the environment.
3. Judgment capacity.
i) the student is asked to know how to evaluate comparatively the effectiveness and environmental performance of different synthetic strategies in terms of choice of reaction conditions, and of chemical-physical and toxicological properties of the chemical compounds involved (reagents, catalysts, solvents, and products).
ii) the student is asked to develop a certain critical capacity on the characteristics of an organic synthesis and its impact on human health and the environment
4. Communication skills
i) the student is asked to know how to use the concepts and principles of Green Chemistry with multiple objectives, such as: a) the discussion and the critical evaluation of eco-compatible solutions for a synthetic process in a context of specialists of the sector; ii) the dissemination of the green chemistry knowledge by making non-expert interlocutors and public opinion aware of the development of an innovative synthesis chemistry in harmony with the environment, welfare and ethical needs of the modern society. The widespread use of the English language during lessons and homework development contributes to the development of these skills; iii) the interaction with the teacher and the classmates during both the lectures and the laboratory sessions, formulating coherent questions and arguing about the complex requirements of sustainability and environmental compatibility in organic synthesis.
5. Learning ability
i) the student is asked to know how to identify and apply independently the salient aspects of the concepts expressed in class;
ii) the student is asked to know how to autonomously enrich one's own training by acquiring new specialized knowledge from the scientific and technical literature in the topics covered during the course

The student must have a solid knowledge of the structure, properties and reactivity of organic compounds. It is therefore highly recommended that he/she has achieved the educational objectives of the course of Organic Chemistry 3 and laboratory, although it is not necessary that he/she has passed the related exam.

In accordance to the training objectives and expected learning outcomes described in the relevant sections, the contents of the course can be divided as follows:
Classroom lectures
- Introduction.
General description of the program, mode of examination, and bibliography.
Definition of Green Chemistry
Description of major green metrics such as atom economy, e-factor, mass index, reaction mass efficiency, stoichiometric factor, mass recovery parameter, and use of such metrics to quantify the efficacy and environmental performance of an organic synthesis
- Carboxylation and alkylation processes with reduced environmental impact.
Comparison between phosgene and green reagents such as dialkyl carbonates, in particular dimethyl carbonate (DMC). Analysis, benefits and metrics of model reactions for the green synthesis of carbamates and polycarbonates. Analysis of green industrial productions of polycarbonates (the melt process, and Asahi-Kasei)
Dialkyl carbonates as alkylating agents of methylene active compounds, phenols and amines. Analysis of the reaction mechanism and the process selectivity in relation to the type of catalysts involved and the reaction methods used.
- Eco-compatible solvents.
Water as a solvent for Diels-Alder cycle reactions. Introduction to the hydrophobic effect and its interpretation on an entropy basis.
Water as a reaction medium for laboratory-scale "on water" synthesis, liquid-liquid phase transfer catalysed processes.
Introductory notes on the use of water on industrial productions with both organometallic catalysis (the Ruhr-Chemie/Rhone-Poulenc process) and aquo-complexes (Wacker process).
Ionic liquids (ILs) as innovative solvents. Synthesis of ILs by conventional and halide-free alkylation of pyridines and imidazoles, and by the carbene method. Main properties of ILs (density, viscosity and polarity). The use of ILs in multi-phase catalysis and the description of the BASIL process as an model for the application of ILs on an industrial scale.
Laboratory session
6 experiments, conducted by groups of 2-3 students, will be carried out:
- Synthesis of adipic acid by oxidation of cyclohexene with hydrogen peroxide under liquid-liquid phase transfer catalysis conditions
- Synthesis of an ionic liquid by direct alkylation of methylimidazole with an alkyl halide
- Synthesis of ethyladipate under multi-phase catalysis conditions mediated by an in-situ generated ionic liquid
- O-methylation of phenol with dimethyl carbonate under base catalysis conditions
- Synthesis of an alkyl methyl carbonate by transesterification of dimethyl carbonate with a glycol ether
- N-Methylation of an amine with a methyl alkyl carbonate, catalyzed by zeolites
The reaction products will be characterized by spectroscopic techniques typical of organic chemistry (NMR and GC / MS).
Student must prepare a brief report describing the results of each experience. The report should include a graphical analysis of the reaction performed according to the model of the radial polygons.
Homework
- After having selected a paper of organic synthesis from the current literature, the student must analyze it through the application of process indicators (green metrics) and the graphical analysis of the synthesis.
- Comparative analysis of C-, O-, and N-methylation procedures with dimethyl carbonate by means of reaction metrics and graphical analysis.
- The student must analyze a modern literature review reporting on the problem of solvents. He/she must then report personal comment/conclusions on the content of the review.

For the study of the theory and for the laboratory experiences
Green Chemistry: Designing Chemistry for the Environment, P. Anastas, T. Williamson, Eds., ACS Symposium Series No. 626, 1996; Ch. 7, pp. 81-91.
• Green Chemistry, Theory and Practice, P. T. Anastas, J. C. Warner Eds., Oxford University Press 1998
• Green Chemistry, Frontiers in Benign Chemical Synthesis and Processes, P. T. Anastas, T. C. Williamson, Oxford University Press, 1998
• Introduction to Green Chemistry, A. S. Matlack, Marcel Dekker, Inc., 2001
• Green Chemistry An Introductory Text, M. Lancaster, Royal Society of Chemistry, 2002.
• Chemistry in Alternative Reaction Media, Wiley, D.J. Adams, P. J. Dyson, S. J. Taverner, Chichester (UK), 2004.
• Sato, K.; Aoki, M.; Noyori, R. Science, 1998, 281, 1646-1647; Reed, S. M.; Hutchinson, J. E. J. Chem. Edu. 2000, 77, 1627-1629.
• Riisager, Bosmann in Experiments in Green and Sustainable Chemistry Eds. Roesky and Kennepohl, Wiley-VCH 2009, 108-113,
• Dupont, J.; Consorti, C. S.; Suarez, P. A. Z.; de Souza, R. F. Org. Synth. 2002, 79, 236-240.
• Selva, M.; Perosa, A. Green Chem. 2008, 10, 457-464
• BASIL “home-made” Adipoil cloruro/etanolo/metil-imidazolo: http://www.basionics.com/
• A. Perosa, M. Selva, P. Tundo, F. Zordan, Synlett 2000, 272-274; M. Selva, P. Tundo, A. Perosa J. Org. Chem. 2002, 67, 9238-9247; M. Selva, P. Tundo, T. Foccardi, J. Org. Chem. 2005, 70, 2476-2485
• Review Articles
Class notes, lecture handouts
Recipes for laboratory experiences and format of the laboratory report.

The evaluation of learning/comprehension of both the theoretical and practical content of the course takes place through an oral test. Before being admitted to the oral test, the student must have received a positive evaluation of both the reports required for the laboratory session, and the homework. According to the timetable planned by the University, the student is invited to contact the teacher to set a date for the oral exam.
The exam consists of a series of open questions aimed at verifying the knowledge acquired by the student on the subjects of the program of the entire course (see contents section). Occasionally, the student is asked to clarify on the content of laboratory reports and the homework. The oral exam lasts from 45 to 60 minutes depending on the clarity and consistency of the answers to the asked questions. The vocabulary and the use of scientific symbology in chemistry will be also evaluated. During the exam, the use of books, notes and electronic media is not permitted.
The final score of the exam is preponderantly assessed (80%) based on the outcome of the oral test. A further evaluation comes from the laboratory reports and homework which may contribute either in positive or negative, to the final score.

The theoretical part of the course is organized through classroom lectures on the subjects reported in the content section. While, during the laboratory part of the course, the teacher offers a brief introduction before conducting the experiments, and he invites students to open discussions on the content of experimental procedures, laboratory techniques, reaction outcomes, results of products characterization. Both the didactic material discussed during the classroom lessons and the recipes for laboratory experiences, can be downloaded from the "moodle" platform of the University.

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This subject deals with topics related to the macro-area "Climate change and energy" and contributes to the achievement of one or more goals of U. N. Agenda for Sustainable Development