Ateneo - UPO

The course aims to supplement the knowledge of organic chemistry, the acquisition of which began during the first year of the bachelor's degree, by examining classes of reactions, organic compounds and synthetic strategies that were not covered in the first core course, or by supplementing classes of reactions already introduced. Green Chemistry will be introduced with a description of the main indicators (green metrics: atom economy, e-factor, mass index, reaction mass efficiency, stoichiometric factor, mass recovery parameter) of effectiveness and environmental performance of an organic synthesis. Alternative reaction media and biphasic systems, produced from renewable natural sources. Circular bioeconomy. LABORATORY MODULE: To provide the student with initial experience in the context of low-impact reactions, including the main indicators (green metrics: atom economy, e-factor, mass index, reaction mass efficiency, stoichiometric factor, mass recovery parameter) of effectiveness and environmental performance of an organic synthesis.

1) J. Clayden, N. Greeves, S. Warren, “ChemicaOrganica”; PICCIN (ISBN 978-88-299-3233-7). 2) P W.H. Brown, C.S. Foote, Organic Chemistry, Edises (ISBN 9788836231355); 3) Green Chemistry and Catalysis. I. Arends, R. Sheldon, U. Hanefeld, 2007 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim ISBN: 978-3-527-30715-9. Exercise books: 1) T.W. Solomons et al, “La chimica organica attraverso gli esercizi” Zanichelli 2) M.V. D'Auria, “Guida ragionata allo svolgimento di esercizi di chimica organica” Loghia. 3) G. Broggini, C. Loro, G. Palmisano. "Chimica Organica: 800 esercizi con soluzione" Zanichelli. Course slides will be made available on DiR. LABORATORY MODULE: Module slides.

MODULE: SUBSTANCES AND METHODS FOR LOW ENVIRONMENTAL IMPACT ORGANIC CHEMISTRY: This course integrates with the FUNDAMENTALS OF ORGANIC CHEMISTRY AND LABORATORY course, examining classes of reactions, organic compounds, and synthetic strategies not previously covered. 1. Students will acquire knowledge of the fundamental principles of organic synthesis and the ability to develop simple synthetic sequences of polyfunctional organic compounds and apply the principles of modern synthetic strategies: disconnection approaches, carbon-carbon bond formation, and an introduction to the protection/deprotection of functional groups. 2. They will also acquire the ability to understand and critically discuss reaction mechanisms and the methodologies used. 3. Finally, the specific educational objective of the course is to provide at least basic knowledge that will enable students to address complex chemical problems, such as the study and analysis of low-impact organic synthesis procedures. This knowledge will be achieved through modern methodological tools that, using indicators such as atom economy, e-factor, mass index, etc., allow for the quantification of the efficiency or environmental performance of a chemical process in relation to the principles of Green Chemistry. Students will therefore demonstrate learning ability and the ability to draw independent conclusions, as well as communication skills: students must be able to present the results of a scientific article focused on green chemistry, selected independently using available databases, and present it appropriately using the correct terminology.
Basic knowledge for determining the structure of an organic compound (which will not be assessed) will also be provided, with application in the laboratory module. LABORATORY MODULE: Understanding and comprehension skills: knowledge of the basic reactions of synthetic organic chemistry and the theoretical and practical principles of operating in an organic chemistry laboratory. Ability to apply knowledge and understanding: ability to carefully fill out the laboratory notebook; acquisition of essential laboratory skills.

The student should have a solid knowledge of the structure, properties, and reactivity of the organic compounds. It is therefore highly recommended that the student has achieved the training objectives of the course of Fundamentals of Organic Chemistry and Laboratory.

The theoretical part is organized in lectures on the topics indicated in the content section. Particular attention will be paid to providing students with the skills necessary to apply the knowledge provided during the course, also through joint exercises.
A mock exam is planned to be held in the classroom to better engage students. The laboratory part includes both a brief introduction by the lecturer to each laboratory experience and a lecturer/student discussion during the material execution of the experiments, in order to deepen the content of the experimental procedures, the laboratory techniques adopted, and the results/methods of analysis of the products. Lecture materials projected in the classroom during lectures and introduction to the laboratory will be present and downloadable on the University's DIR platform.

Students with physical disabilities, Learning Disabilities or Special Education Needs can request specific services and tools via the Staff Sviluppo e Coordinamento Carriere e Servizi alle Studentesse e agli Studenti, consulting the University webpage: https://www.uniupo.it/en/services/services-students-physical-or-learning-disabilities. Students with disabilities, learning disabilities or special education needs, once they have contacted the University Staff, can refer to the tutor in charge of the course to define the examination modalities, concerning academic aspects.

The oral exam will consist of two parts: 1. A requirement for the synthesis of a multifunctional molecule, followed by a discussion of synthetic and mechanistic aspects, with particular emphasis on the ability to establish logical connections between different topics. A passing grade will be achieved by demonstrating the ability to use fundamental concepts of organic chemistry (acidity and basicity, kinetics and thermodynamics, resonance, orbitals and their energies), correctly write reaction mechanisms, be able to use the key reactions illustrated during the course to address the problem,
and correctly set up a retrosynthetic analysis. 2. A critical analysis of a literature article relevant to the program, possibly including the application of process indicators (green metrics), as well as a written report for the laboratory part. Quantifying the different parts in the composition of the overall evaluation, the first part will weigh 70%, the article analysis 20% and the laboratory evaluation 10%.

Introduction to the course. General definition of Green Chemistry. Description of the main indicators (green metrics: atom economy, e-factor, mass index, reaction mass efficiency, stoichiometric factor, mass recovery parameter) of environmental effectiveness and performance of organic synthesis. PROTECTIVE GROUPS: Introduction to the use of protective groups in organic synthesis. Protective groups for the main functional groups: introduction and removal. Orthogonality of protective groups. Molecular orbitals applied to the reactivity of organic molecules. HOMO and LUMO. Chemoselectivity in reduction and oxidation reactions. Use of borane, DIBAL; hydrogenolysis reaction; reductions with dissolved metal; Birch reduction. Swern oxidation. Oxidation with TEMPO. ENOLS, ENOLATES, CONJUGATE ADDITIONS AND CONDENSATIONS Enols and enolates. Enolates of carbonyl compounds and carboxylic acid derivatives. E1cB elimination. Enolate ion reactivity and alpha-halogenation. Nature of the base and regioselectivity in the formation of enolate ions. Enol ethers and silyl enol ethers. Alkylation of enolates. Alkylation of aldehydes using enamines and azaenolates. Alkylation of beta-dicarbonyl compounds and decarboxylation. Kinetic and thermodynamic control in the formation and alkylation of enolates. Alpha-beta unsaturated compounds: Michael addition and direct addition. Factors influencing the Michael reaction. Hard and soft nucleophiles. Conjugated substitution reaction. Introduction to copper organometallics. Michael acceptors and Michael donors. Enolates from dicarbonyl compounds as donors. Enols, enamines, silyl enol ethers and nitro compounds as Michael donors. Darzens and Henry reactions. Cross aldol condensation: use of enolic equivalents (lithium enolates, silyl enol ethers, aza-enolates). Mannich, Knoevenagel, and Reformatski reactions. Intramolecular aldol reactions and Robinson annulation. Direct and cross Claisen condensation. Non-enolizable reactive esters. Dieckmann condensation. PHOSPHORUS AND SULPHUR REAGENTS Wittig reaction. Phosphonium ylides. Stereoselectivity. Use of phosphonium ylides or alkylphosphonates as enolic equivalents in condensation reactions. Sulphonium and sulfoxonium ylides. E/Z stereoselectivity. Sulphur and its compounds (structure and reactivity). Stabilisation of carbanions. Thioacetals. Dithians and their use as acyl anion equivalents. Hydrolysis and desulphurisation of dithians. PERICYCLIC REACTIONS Diels-Alder reaction. Dienes and dienophiles. Stereochemistry of Diels-Alder reactions. Endo rule. Kinetic and thermodynamic products of the Diels-Alder reaction. Approach with molecular orbitals. Influence of solvent and catalysis with Lewis acids. Intramolecular reactions. Regioselectivity in Diels-Alder reactions. Electrocyclic reactions: [2+2] cycloadditions by thermal and photochemical means. 1,3-dipolar cycloadditions. Sigmatropic reactions: Claisen rearrangement. CARBENES Diazomethane. Carbenes: structure, preparation and reactivity. Synthesis of cyclopropanes. Simmons Smith reaction. Insertion of carbenes into C-H bonds. Alkenes metathesis reaction. Ring closing metathesis. Catalysts and examples. ORGANOMETALLIC REAGENTS AND CROSS-COUPLING REACTIONS Introduction to organometallic chemistry. Synthesis of organometallic reagents by oxidative addition, transmetallation and metal-halogen exchange. Oxidative addition. Reductive elimination. Ligand insertion/migration. Beta elimination. Lithium, magnesium and copper, Palladium, reactivity and complexes of Pd(0) and Pd(II). In situ reduction of Pd(II) to Pd(0). Heck reaction. Catalytic cycle. Regioselectivity and stereochemistry of Heck reactions. Cross-coupling reactions. Generic catalytic cycle. Suzuki reaction. Catalytic cycle and boron activation. Examples for the formation of biaryls, dienes and arylalkynes. Overview of Stille and Negishi reactions. Sonogashira reaction. AROMATIC COMPOUNDS Diazonio salts and their reactivity, formylation reactions, hints to reactivity of phenols and aromatic amines, aromatic nucleophilic substitution reactions. INTRODUCTION TO RETROSYNTHESIS A brief history of synthetic organic chemistry, including contributions from different genders. Retrosynthetic approach. Definitions and examples of synthons and reagents. Retrosynthetic analysis of aromatic derivatives using electrophilic and nucleophilic substitutions. Retrosynthetic analysis with examples. Alternative reaction media and biphasic systems. Choice of solvents, unconventional reaction media, biphasic reaction systems, fluorinated biphasic systems, oxidation and reduction reactions in unconventional media. Products from renewable natural sources. Circular bioeconomy. Carbohydrates and their fermentation products, lactic acid, indigo, riboflavin, chemical and chemoenzymatic transformations of carbohydrates into fine chemicals and building blocks, oils and fats, biodiesel, biodegradable polymers from natural sources. Introduction to NMR spectroscopy. LABORATORY MODULE: introduction to safety, indicators of effectiveness and environmental performance. Introduction to laboratory experiments. 1. Grignard-type reaction in water 2. Biodiesel synthesis 3. Solvent-free aldol condensation 4. Glycerol carbonate synthesis 5. Friedel-Crafts reaction with graphite 6. Epoxidation with dimethyldioxirane prepared in situ. The reactions will be analysed using the parameters introduced in the theoretical lessons.

ORGANIC CHEMISTRY MODULE II: Knowledge and Ability to Understand: 1)to know in depth the structure-reactivity relationships in polyfunctional organic compounds 2) to know the principles that guide organic reactions and enable interpretation of their mechanisms. Ability to apply knowledge and understanding: 1) to know how to describe reaction mechanisms in polyfunctional organic molecules 2) to know how to classify organic transformations on the basis of interactions between different functional groups present in an organic molecule 3) to know how to describe the design of a simple synthetic sequence. Autonomy of judgment: 1) to propose synthetic strategies; 2) to be able to deal easily with a simple retrosynthetic analysis. Communication skills: be able to clearly describe the use of the various concepts learned in the course in appropriate scientific language. LEARNING SKILLS: 1) Demonstrate ability to find, understand, apply and present new information with emphasis on aspects related to green chemistry. LABORATORY MODULE: 1. Knowledge and understanding skills: a. knowledge and understanding of basic reactions in synthetic organic chemistry b. knowledge of the theoretical and practical principles of operating in an organic chemistry laboratory. 2. Ability to apply knowledge and understanding: the student will be expected not only to demonstrate theoretical knowledge of the above topics, but also, and more importantly, to be able to apply them to laboratory practice. Thus, it is expected that the student will know how to operate properly in an organic chemistry laboratory, at least in terms of fundamental manual dexterity. Also required is the ability to duly complete the laboratory notebook.