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 1. Review of Important Organic Reactions. Acidity and basicity and other key concepts in organic chemistry. Using pKa for the thermodynamics of a reaction. pKa and pH scales in different solvents. When a reaction occurs and when it does not. Reactivity predictions. Carboxylic acids and their derivatives. Reactivity scale. Nucleophilic acyl substitution reaction. Effect of substituents. Reactions of carboxylic acids. Preparation of esters and chlorides. Hydrolysis. Transesterifications. Thiolesters and biological chemistry. Amides and nitriles. Solvents in organic chemistry. Overview. The Mayr scale. A brief introduction to the scale. Definitions of nucleophile and electrophile. Basicity and nucleophilicity. The Mayr equation and predictions of organic reactivity. Examples. Classification of nucleophiles and electrophiles. Use of the scale. The (useless) principle of reactivity and selectivity.

Chapter 2. Carbanions. Alkynes, Grignards, and Lithium Derivatives (Review) In this chapter, we will review and delve deeper into the concept of enolates. Enolates. Classical enolate reactions. Enol formations. pKa of carbonyls. Halogenation. Aldol condensation. Reactions of esters, thiolesters, and amides. Reactions of nitriles and nitro compounds. The Michael reaction. Kinetic and thermodynamic enolization. Cis- and trans-enolates. Use of bases to control enolization. Enolates of aldehydes. Enamines. Azaenolates. Enolizations of amides. Alkylation of enolates. Kinetic and thermodynamic conditions. pKa. Z- and E-enolates. Use of cosolvents. Enamines. Alkylations and enolates. LDA. Mechanism for controlling the geometry of enolates. Diastereoselective reactions with enolates. Chiral auxiliaries and their use. Aldols with lithium and other metal enolates. Cyclic transition states. Z enolates yield syn, E enolates anti. Boron enolates. Enolization. Examples. Diastereoselective alkylation of enolates. Oxazolidinones. Aldol condensation. Lithium and boron enolates. Zinc enolates: the Reformatsky Reaction. Silylene ethers and silylketene acetals. Preparation and use: the Mukaiyama reaction. Mechanism and transition states. Complexes of Lewis acids with carbonyls.

Chapter 3. Advanced stereochemistry. Symmetry operation. Necessary and sufficient conditions for chirality. Other stereogenic elements. Axes and planes. Atropoisomers. Allenes and biphenyl systems. CIP rules for assigning absolute configuration. Examples of other atropoisomeric systems. Stereogenic planes and compounds with stereogenic planes. Absolute configuration of incomposite planes with stereogenic planes. Topological and mechanical chirality (notes). Nodes, links, and chiral graphs.

Chapter 4. Protecting Groups. Use of Protecting Groups in Organic Synthesis. Examples and Applications. Silicon Derivatives, THP, Ethers, and Benzyl. Group Unblocking. Protecting Groups for Carbonyls. Groups for Amines.

Chapter 5. Oxidations and Reductions. Modern Oxidants: Perruthenate, Dess-Martin, TEMPO oxidations, Swern oxidation, and variations. Oxidation of Aldehydes to Acids. Epoxidation-Reduction. Hydrides and Their Different Reactivities. Hydrogenation. Ni-Raney. Reductions with Metals. Chelate Cram Rule and Felkin-Ahn Rule.

Chapter 6. Complementary Aromatic Reactivity. Fluorination, Formylation, and Side Chain Modification. Diazonium Salts and Their Uses. Overview of the Use and Reactivity of Heteroaromatic Systems. Retrosynthetic Analysis. Introduction to Retrosynthesis and the Main and Simple Disconnections. Syntons and synthetic strategies. Interconversion of functional groups. Disconnections 1-2, 1-3, and 1-4. Unpolymerized reactivity. Retrosynthetic analysis exercises. Guide to retrosynthesis and the reactivity of functional groups. Exercises in the synthesis of molecules and synthetic plans.

Chapter 7. Chemistry of sulfur, silicon, and phosphorus. Sulfur, reactivity and oxidation states. Sulfoxides and their reactivity. Optically active sulfoxides. pKa in compounds. Thioacetals, dithianes, sulfonium salts. Ylides. Silicon chemistry. Pedersen olefination. Allylsilanes. Phosphorus chemistry. Overview of the origins of phosphorus compounds. Phosphonium salts and ylides. Julia, Julia-Kocienski, Wittig, and Still-Gennari olefinations.

Chapter 8. Orbitals. Review and clarifications. Molecular orbitals. The Huckel method. The energy scale. Frontier orbitals (HOMO and LUMO). How orbital energies vary with substitution. Cycloadditions. The Endo rule. Lewis acids. 1-3 dipolar reactions. Pericyclic, electrocyclic, and sigmatropic reactions. Woodward-Hoffmann rules.

Chapter 9. Radical reactions. Definition of transient and persistent radicals. Examples of radicals. Geometry and stabilization of radicals. Nucleophilic and electrophilic radicals. Ketyl. Radical reactions. Generation of radicals by photochemical and electrochemical methods (notes). Diazomethane. Generation of carbenes. Carbene structure and reactivity. Cyclopropanation reaction. Reaction of carbenes. Heterocyclic carbenes. Nitrenes and nitrenoids.

 

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 6-credit Organic Chemistry II component (excluding laboratory), students must pass a WRITTEN exam. A "partial" written exam is introduced that covers the topics of the first semester (Aromatic Compounds and Enolate Alkylations). Three partial exams are scheduled at the end of the first semester. The partial exam is structured as follows: Organic Chemistry PARTIAL Exam Scoring: 2 theory questions (2 x 2.5 points); 1 mechanism exercise (2.5 points); 1 exercise (reactions, methodology, transformations; 2.5 points). Total: 10 points. Exam duration: 1 hour. The final written exam is structured as follows: 2 questions (2 x 3 points); 1 mechanism exercise (3 points); 1 synthesis methodology exercise (intermediates; 3 points); 2 reaction exercises (2 x 3 points); two synthesis exercises (2 x 6 points). Total: 30 points + 3 starting points = 33 points. Score for Honors (32–35 points). Students who took the partial exam may choose to accept the partial exam score (up to 10 points), which will be added to the final exam score. By choosing to accept the partial exam score, the student is exempt from answering one reaction exercise and one synthesis exercise. If, instead, the student opts for the full exam—declining to add the partial exam score—they must complete the entire exam. The duration of the exam with the accepted partial score (and two fewer exercises) is 1 hour and 30 minutes. The duration of the full exam is 2 hours. The final score for the Organic Chemistry II course is calculated as the average of the scores from the "Organic Chemistry Laboratory" exam (69081) and the "Organic Chemistry" exam (69080). The following method is used to calculate the average: 30 (for scores of 30–31) 32 (for scores of 32–35) Once the average is calculated, the assessment for scores > 30 will be as follows: 30-31 => rating 30 > or = 32 => rating 30L

 Students with learning disabilities (LD) or temporary or permanent disabilities: please contact the relevant University office promptly (https://site.unibo.it/studenti-con-disabilita-e-dsa/it). They will be responsible for suggesting any adjustments to the students concerned. However, these must be submitted to the instructor for approval 15 days in advance, who will evaluate their suitability, also taking into account the course's learning objectives.

The use of AI is prohibited during assessments. Any use constitutes a violation of academic integrity.

Teaching tools

Possibility of using online sessions to analyze problems with Reaxys

Office hours

See the website of Pier Giorgio Cozzi