OVERVIEW

The course builds upon and provides an in-depth study of the concepts covered in the Organic Chemistry I course. The topics covered enable you to gain a more comprehensive understanding of the fundamental concepts of organic chemistry. Furthermore, they are chosen mainly to prepare for subsequent courses, such as Biochemistry and Pharmaceutical Chemistry.

AIMS AND CONTENT

LEARNING OUTCOMES

In-depth study of the reactivity of organic molecules through the study of difunctional compounds. Expansion of carbon-carbon bond formation reactions with particular attention to the construction of cyclic systems. Introduction to natural and heterocyclic organic substances.

AIMS AND LEARNING OUTCOMES

The Organic Chemistry II course aims to provide more advanced concepts of the subject, compared to those learned in the previous Organic Chemistry I course. At the end of the lessons, the student will have acquired theoretical knowledge of the structure and reactivity of bifunctional compounds, polycyclic aromatic compounds, and heterocyclic compounds (both aromatic and non-aromatic). He/she will also have explored the fundamental strategies for forming carbon-carbon bonds. This knowledge is fundamental for future studies in the fields of biochemical and pharmaceutical chemistry.
Specifically, the student will be able to:
• know the main classes of synthetic and natural organic compounds;
• apply the fundamental rules of the IUPAC nomenclature, with an introduction to the heterocycle compounds;
• apply basic stereochemical knowledge also to more complex systems;
• think critically to apply the reactions studied to simple synthetic sequences for the production of required molecules, arguing the choices.

PREREQUISITES

Basic knowledge of the main topics of organic chemistry I.

TEACHING METHODS

The course comprises three two-hour weekly lectures, during which students are taught all the key concepts related to the organic chemistry teaching program. Teaching materials to support the lessons (presentations, exercises, and in-depth articles) are provided to students through the AulaWeb platform. Fundamental texts are recommended for studying theory and for completing the exercises. However, part of the lesson is conducted on the blackboard, utilising digital media and molecular models to educate students in the two- and three-dimensional design of molecules and in the execution of chemical reactions with their respective mechanisms. To face dynamic frontal lessons, students must actively participate by answering questions and completing exercises individually or in groups. Quizzes and exercises will be available on the AulaWeb platform to keep the study updated, which allows a profitable accompaniment of the lessons throughout the teaching period of organic chemistry.

Activities are planned to promote the ability to peer-review and self-evaluate papers, fostering the development of the ability to learn to learn (at a basic level). The production of multimedia products is encouraged to develop functional alphabetic skills that enable students to seek and process information, present, communicate, and argue theories and practical concepts in both oral and written forms (basic level).

Tips on how to study:

1) keep the study of the weekly topics updated, never let them accumulate;

2) study the material in small teaching units and make sure you understand each new section before moving on to the next;

3) solve all the problems of the chapter;

4) write during the study in a theory and exercise notebook;

5) learn by teaching and explaining (study better in a group);

6) use molecular models during the study.

Any Student with documented Specific Learning Disorders (SLD), or with any special needs, shall reach out to the Lecturer(s) and to the dedicated SLD Representative in the Department ( Prof. Luca Raiteri, Luca.Raiteri@unige.it ) before class begins, in order to liaise and arrange the specific learning methods and ensure proper achievement of the learning aims and outcomes. VERY IMPORTANT: any request for compensatory tools and adaptations in the exam MUST be done within 10 working days before the date of the exam according to the instructions that can be found at https://unige.it/disabilita-dsa/comunicazioni

SYLLABUS/CONTENT

1. ANALYSIS OF THE ORGANIC CHEMISTRY OF FUNCTIONAL AND BIFUNCTIONAL COMPOUNDS (30 hours)

1.1 Conformations of cycloalkanes and bicycloalkanes. Nomenclature and properties of bridged bicyclic systems. Structures of bicyclic (cis- and trans-decalin) and polycyclic molecules. Molecular orbital (TOM) and frontier orbital (HOMO and LUMO) theory. Energy diagrams of OA and OM for the molecules of H2O, BH3; ethene, ethyne, butadiene, and hexatriene. UV-Visible absorption of the electromagnetic spectrum of ethene, butadiene, hexatriene, and formaldehyde.

1.2 Electrophilic additions to conjugated dienes. Kinetic and thermodynamic control of the addition products (1,2- and 1,4-) to butadiene. Introduction to pericyclic reactions (cycloadditions, electrocyclic reactions, and sigmatropic arrangements) and common characteristics of pericyclic reactions. Thermodynamic considerations of Diels-Alder reactions. Description of Diels-Alder cycloaddition reactions according to the TOM (Frontier Orbitals: HOMO of the diene and LUMO of the dienophile). Introduction to the regioselective and stereochemical aspects of the Diels-Alder reaction.

1.3 Origin of axial chirality in allenes, biaryls, and binaphthalenes. Symmetry planes, symmetry axes, and rotor-reflection axes. Atropoisomerism. Assignment of the absolute R/S configuration for compounds with axial chirality. Palladium chemistry. Suzuki reaction in the synthesis of biaryls and dienes.

1.4 Polycyclic aromatic systems. Nomenclature and properties. Electrophilic substitution in naphthalene. New allotropes of carbon: fullerenes, graphene, and carbon nanotubes.

1.5 Nomenclature of common dicarboxylic acids and acidity of dicarboxylic acids; Carboxylic acid derivatives of biological importance. Synthesis of succinic anhydride and hydrolysis (acid and base) of succinic anhydride. Synthesis of succinic acids by the Diels-Alder reaction. Gabriel synthesis: formation of primary amines with phthalimide.

1.6 Keto-enol equilibrium (tautomerism) via acid and base catalysis. Aldol addition of aldehydes and ketones. Crossed aldol addition. Aldol addition of nonenolizable aldehydes. Alpha-halogenation to a carbonyl/elimination (enals/enones). Alpha-halogenation to a carboxylic acid (Hell-Vohardt-Zelinsky reaction)/elimination (enoic acids);

1.7 Enolates of dicarbonyl compounds and respective synthetic equivalents of acetoacetic ester and malonic ester. Synthesis of acetoacetic acid ester for the formation of 4-ketoesters, 1,4-diketones, 1,3-diketones, mono- and dialkylated ketones.

1.8 Preparation of derivatives with an oxygen function and unsaturation (α,β-unsaturated carbonyl compounds):

A) Knoevenagel reaction (enoic acids/enoates);

B) Wittig reactions (alkenes, enals, enones, CIS enoates);

C) Horner-Wadsworth-Emmons reaction (TRANS enoates);

D) Aldol and crossed aldol condensation (enals/enones);

E) Intramolecular aldol condensation (cyclic enals/enones).

F) Robinson annulation: conjugate Michel addition + intramolecular aldol condensation.

1.9 Nucleophilic addition reactions to α,β-unsaturated carbonyls: 1,2-addition (direct to the carbonyl) and 1,4-addition (conjugate addition). Conjugate addition to α,β-unsaturated carbonyl compounds by mild nucleophiles: enolates, enamines, Gilmann cuprates, and the Michael reaction.

1.10 Mechanism of enamine formation and synthetic equivalence of enamines. Stork reaction: alkylation, acylation, and Michael addition.

1.11 1,3-oxygenated compounds. Crossed aldol condensations with enolate preformation. Synthesis of acetoacetic ester and estermalonic ester. Diacetoxyiodobenzene and Swern oxidations. Solutions to problems encountered in aldol reactions. Diastereoselectivity of aldol reactions (syn-aldol and anti-aldol). Six-membered transition state for the aldol reaction proposed by Zimmerman-Traxler (Zimmerman-Traxler transition state). α-Alkylation via azaenolate. Claisen condensations (synthesis of β-ketoesters and β-diketones) and Dieckmann condensations. Biological aldol and Claisen reactions.

1.12 Logical and Illogical Disconnections. Synthesis of 1,2-Oxygenated Compounds. Formation of cyclic acetals or methods that do not involve the formation of C-C bonds: osmylation and epoxide opening. Preparation of 1,2-diols involving the formation of C-C bonds: pinacol reaction and Corey-Chaikovsky reaction. Use of dithianes as synthetic equivalents of an acyl anion (formyl anion). Cyanide as a synthetic equivalent of an acylanion. Hydrolysis of cyanohydrin to an α-hydroxyacid. Synthesis of α-hydroxyaldehyde by reduction of trimethylsilyl ether cyanide in the presence of DIBALH. Strecker reaction for the formation of an α-amino acid. Benzoin condensation. Variation of the Stetter reaction for the formation of 1,4-dicarbonyl systems in the presence of a thiazolium salt. Stetter reaction for the synthesis of 1,4-oxygenated compounds (4-ketoester).

1.13 Passerini reactions (multicomponent). Protection of carbonyl groups with formation of cyclic acetals. Cyclic hemiacetals: 4-hydroxyaldehydes (γ-hydroxyaldehydes) and 5-hydroxyaldehydes (δ-hydroxyaldehydes). Protection of alcohols with DHP.

2. HETEROCYCLIC COMPOUNDS (18 hours)

Classification and nomenclature of heterocyclic compounds. Electron-rich aromatic heterocycles: general characteristics, synthesis, and reactivity of pyrrole, furan, and thiophene. Electron-poor aromatic heterocycles: general characteristics, synthesis, and reactivity of pyridine, quinoline, isoquinoline, and pyrimidine. Aromatic pentaatomic heterocycles with two heteroatoms: general characteristics and synthesis and reactivity of imidazole, oxazole, isoxazole.

RECOMMENDED READING/BIBLIOGRAPHY

Students are strongly encouraged to attend lectures and in-class exercises. Teaching materials are available on Aulaweb.

The following textbooks may be useful:

• Chimica Organica di P. Y. Bruice, EdiSES
• Chimica Organica di W. H. Brown, B. L. Iverson, E. V. Anslyn, C. S. Foote, EdiSES
• Chimica dei Composti Eterociclici di D. Sica, F. Zollo - EdiSES (l'ultima edizione)
• Chimica degli Eterocicli di G. Broggini, G. Zecchi – vol. 1 LaScientifica
• Chimica Organica di P. C. Vollhardt e N. E. Schore, Zanichelli
• Chimica Organica AA. VV. a cura di B. Botta Edi-Ermes
• Chimica Organica di M. Loudon, EdiSES
• Chimica Organica di J. McMurry, Piccin

TEACHERS AND EXAM BOARD

LESSONS

LESSONS START

Lectures will begin as indicated in the academic calendar. Updates will also be posted on Aulaweb.

Class Schedule: The timetable for this course is available via the Portale EasyAcademy, or the MyUniGe app.

Class schedule

The timetable for this course is available here: Portale EasyAcademy

EXAMS

EXAM DESCRIPTION

Written and oral. In the written test, within three hours, the student is required to identify reagents and products for a single or multi-stage organic synthesis, propose a reaction mechanism, assign the stereochemistry, and provide the correct nomenclature of reagents and products. The subsequent oral test typically begins with a discussion of the written test, followed by the exposition of theoretical concepts in organic chemistry, and includes exercises on the board.

During the course, an additional (optional) individual or group activity will be required to produce a video (maximum 10-12 minutes) on a topic covered in the classroom. Through the evaluation of the video, the transversal skills (communicative, functional, and social) of the student or the work group will be determined. The videos will be peer-evaluated through an evaluation rubric that will allow them to delve deeper into topics covered by other students.

ASSESSMENT METHODS

The written exam will include theoretical questions and organic chemistry exercises, to be completed within a three-hour time frame. The oral exam requires the student to be able to answer theoretical questions and solve exercises, through which it will be possible to evaluate the knowledge of the content, quality, and organisation of the presentation. The control tools provided in the teaching and examination methods, which accompany the teaching-learning process, aim to assess the students' levels of knowledge, skills, and competencies.

FURTHER INFORMATION

As the course aims to develop specific skills, and classroom exercises are essential to this goal, attendance is strongly recommended.