69080 - Organic Chemistry II

Learning outcomes

At the end of the module, the student knows how to use structure-reactivity correlations to predict the behavior of organic and multifunctional molecules; knows the mechanistic bases of reactivity; is able to offer a short multistage synthesis of a simple organic molecule; knows the structure and properties of the most important classes of natural organic substances.

Course contents

Chapter 0. Review of acidity and basicity and other key notions of organic chemistry. Orbitals and hydrogen atom. Meaning. The molecular orbital method. Huckel's method (outlines). Energy of the orbitals as a function of the substituents, and differences.

Chapter 1. The Mayr scale. Brief introduction to the scale. Definitions of nucleophile, electrophile. Basicity and nucleophilicity. Mayr equation and prediction of organic reactivity. Examples. Classification of nucleophiles and electrophiles. Using the ladder. The (useless) principle of reactivity and selectivity. Chapter 1. pKa and pH scales in different solvents. When a reaction occurs and when it does not. Syncline and periplanar. Definitions. Cyclic compounds and conformations.

Chapter 2. Orbital. Review and clarifications. Molecular orbitals. Huckel's method. The energy scale. Frontier orbitals (HOMO and LUMO). How the energy of the orbitals varies with substitution. Chapter 3. Aromaticity. Definition. Aromatic systems. Huckel's rule. Systems that follow the rule. Systems with 3, 4, 5, 6, 7, 8 and 9 orbitals. Shape and structure of benzene orbitals. Cyclobutadiene. Cyclooctadiene. Nomenclature of aromatic compounds. Electrophilic aromatic substitution and the main reactions (halogenation, nitration, sulfonation, alkylation and acylation). Intermediates, reactivity and mechanism. Retrosynthesis applied to benzene systems. Retrosynthesis and synthesis exercises. Use of diazonium salts and other reactions. Heteroaromatic hexa-atomic, five-atomic and condensed systems. Properties of pyridines. Pyridine reactions. Reactions of furan, thiophene, pyrrole and indole. Notes on other heteroaromatic systems.

Chapter 4 Alkylation of enolates. Kinetic and thermodynamic conditions. pKa. Enolates Z and E. Use of cosolvents. Enamine. Alkylations and enolates. LDA. Mechanism for controlling the geometry of enolates. Michael's reaction Diastereoselective alkylation of enolates. Oxazolidinones. Aldol condensation. Lithium and boron enolates. Enolate formations with Lewis acids. Tin enolates. Boron enolates of ketones. Zinc enolates. Reformatsky. Mukaiyama reaction. Silicon enolates. Coordination of Lewis Acids to Carbonyls. Acyclic transition states. Examples and exercises.

Chapter 5. Advanced Stereochemistry. Symmetry operation. Necessary and sufficient condition for chirality. Other stereogenic elements. Planks and plans. Absolute configuration in stereogenic axes and planes Topological and mechanical chirality (outline). Nodes, links and chiral graphs.

Chapter 6. Protective groups. Examples and applications. Silicon derivatives, THP, ethers, benzyl. Unlocking groups. Groups for amines.

Chapter 7. Oxidations and reductions. Oxidizers that are used very little (Chromium). Modern oxidation methods. Perruthenate, Dess-Martin, TEMPO oxidations, Swern oxidation and variants. Oxidation from aldehydes to acids. Epoxidation Reduction. Hydrides and their different reactivity. Hydrogenation. Ni-Raney. Reductions with metals. Chelated Cram and Felkin-Ahn rule.

Chapter 8. Retrosynthetic analysis. Introduction to retrosynthesis and the main and simple disconnections. Syntones and synthetic strategies. Interconversion of functional groups. Disconnections 1-2, 1-3, 1-4. Unpolong reactivity.

Chapter 8.1 Retrosynthetic analysis. Guide to retrosynthesis and reactivity of functional groups. Exercises in the synthesis of molecules and execution of synthetic plans.

Chapter 9. Chemistry of sulfur, silicon, and phosphorus Sulfur, reactivity and oxidation states. pKa in compounds. Thioacetals, dithianes, sulfonium salts. Ilids. Silicon chemistry. Pedersen Olefination, Allylsilani. Olefinations according to Julia, Julia-Kocienski, Wittig, Still-Gennari

Chapter 10. Cycloadditions. Endo rule. Lewis acids. 1-3 dipoles Pericyclic, electrocyclic and sigmatropic reactions. Woodward-Hoffmann rules

Chapter 11. Radical reactions. Reaction of carbenes. Nitrenes and nitrenoids.

Chapter 12. available (not subject to examination). Organometallic Chemistry (Outline). Metals and oxidation states. The binders. Oxidative addition and reductive elimination. The catalytic cycle. Examples of reactions with transition metals. Electrophilic etching of palladium. Cross coupling and metathesis reaction.

Readings/Bibliography

Course lecture notes provided by the teacher and course slides provided by the teacher.

We recommend the book: Jonathan Clayden, Nick Greeves, Stuart Warren Publisher: Piccin-Nuova Libraria: 2023. Attention. The recommended book is not organized by functional groups, and cannot be used for the Organica I course. Instead it covers ALL the topics of the Organica II course, at the same level, with examples, mechanisms, reactions of all the topics discussed in the course.

Teaching methods

Lessons with power point and overhead projector with comments on transparencies.

Synthesis and retrosynthesis exercises discussed on the blackboard

Assessment methods

To pass the part of Organic Chemistry II relating to the 6 credits (excluding laboratory), the student must pass a WRITTEN exam. A "partial" written exam is introduced which covers the topics of the first semester (Aromatic compounds and Alkylations of enolates). There are 3 partial tests at the end of the first semester.

The partial is structured as follows: PARTIAL Exam Score Organic Chemistry: 2 theory questions (2 x 3 points); 1 mechanism exercise (3 points); 1 exercise (reactions, methodology, transformations 3 points). Total 12 points

Test time: 1 hour

The final written exam is structured as follows

2 theory questions (2 x 3 points);

1 mechanism exercise (3 points);

1 exercise on synthesis methodologies (intermediate, 3 points);

2 reaction exercises, 2 x 3 points);

two exercises on the synthesis of an organic molecule (2 x 6 points). Total 30 points + 6 starting points = 36 Score for Honors 36 points.

The student who took the partial will choose to accept the partial score (up to 12 points) which will be added to the exam score. By choosing to accept the exam score, the student will NOT have to respond to a reaction exercise, and to ONE synthesis exercise.

If you instead opt for the total exam, refusing to add the partial score, you will have to take the entire exam.

The exam time with acceptance of the partial score (and two less exercises) is 1.30 hours Total exam time is 2 hours.

Teaching tools

Possibility of using online sessions to analyze problems with Reaxys

Office hours

See the website of Pier Giorgio Cozzi