OVERVIEW

The module aims at developing the fundamental notions of organic chemistry apprehended in Organic Chemistry 1, Laboratory of Organic Chemistry and Organic Chemistry 2, by the introduction of new subjects or deepening some arguments previously treated in a preliminary way. The module aims at improving the understanding of reaction mechanisms and in making the student able to design a synthesis.

AIMS AND CONTENT

LEARNING OUTCOMES

The student will deepen various aspects of organic chemistry not covered in the previous teachings (in particular the formation reactions of C-C bonds, transpositions, the synthesis of cyclic compounds and the chemistry of aromatic compounds), and will be guided to achieve a good understanding retrosynthetic strategies, to design simple syntheses of aliphatic and aromatic derivatives, to interpret the reaction mechanisms and the experimental methodologies to corroborate them.

AIMS AND LEARNING OUTCOMES

The student will deepen various aspects of organic cgemistry not yet treated in previous modules (in particular C-C bond forming reactions) and will be guided to reach a good capacity to understand retrosynthetic strategies, design simple syntheses of aliphatica and aromatic compounds, to interpret reaction mechanisms and the strategies used to corroborate them.

PREREQUISITES

For an optimal fruition of the course, the knowledge of the basic notions of  Organic Chemistry 1 and 2 and of the Laboratory of Organic Chemistry is essential.

TEACHING METHODS

The module includes mainly frontal lessons, with the prevalent use of slides. However, a set of retrosynthesis exercises will be provided and the students may access a recording of the described solutions of these exercises by the teacher. All lessons and exercise solutions will be in italian.

The module corresponds to 6 credits. The student is expected to spend 48 hours for attending the lessons, about 22 hours to do autonomously the retrosynthesis excercises (also listening to the recordings), and 80 hours for studying the subject of the module.

SYLLABUS/CONTENT

1. C-C and C=C bond formation (11 hours)
   • Homoaldol reaction and homocrotonic condensation under acid or basic catalysis
   • Cross aldol reactions.
   • Allyl derivatives as synthetic equivalents of aldehydes
   • Claisen, Dieckmann, Darzens reactions
   • Active methylene compounds. malonic and acetoacetic synthesis.
   • Knoevenagel reaction.
   • Modern oxidation and reduction  methods for oxygen-containing functional groups.
   • Reactions of α,β-unsaturated systems: kinetic and thermodynamic control. Addition of organometal compounds (Cu, Ce) and selective reductions.
   • Michael reactions with active methylene compounds.
   • Robinson annulation.
   • Use of enamines.
   • Nitroaldol reaction. Trasformations of nitro group.
   • Wittig and Horner-Wadsworth-Emmons reactions.
   • Cross-coupling reactions (hints).
2. Chemistry of aromatic and heteroaromatic compounds (8 hours)
   • Polycyclic aromatic hydrocarbons. Naming.
   • Naphthalene: properties and reactions.
   • Anthracene and phenanthrene
   • Review of main electrophilic and nucleophilic substitutions.
   • Formylation and carboxylation reaction.
   • Nucleophilic aromatic substitutions: mechanism and synthetic potential.
   • Benzylic oxidations.
   • Strategies for synthesis of aromatic compunds. Removable and orienting groups.
   • Hints on Hantzsch-Widmann nomenclature of heterocyclic compounds..
3. Synthesis design: aliphatic compounds (7 hours)
   • General concepts: linear, convergent synthesis. Total synthesis and semi-synthesis. Retrosynthetic approach. 
   • Synthetic equivalence.
   • Synthesis of C-X bonds.
   • Synthesis of amines
   • Retrosynthesis of C-C bonds (1 functional group).
     • Alcohols
     • Ketones.
     • Carboxylic derivatives
   • Retrosynthesis of C-C bonds (2 functional groups). Logical and illogical disconnections
   • Logical disconnections: synthesis of 1,3 and 1,5 derivatives
   • Synthesis of 1,3 and 1,5 derivatives:
     • Use of alpha-halocarbonyl compounds: alpha-halogenation under acid and basic conditions
     • Use of cyanide
     • Synthesis of 1,2-diols and epoxides. Pinacol reaction. Corey-Chaikovski reaction.
   • Synthesis design exercises
4. Protecting groups (5 hours)
   • Protection of amines. Peptide synthesis.
   • Protection of alcohols.
   • Protection of carbonyl compounds.
5. Synthesis of cyclic compounds (6 hours)
   • General issues of cyclization reactions
   • Examples of synthesis of 5-membered rings
   • Examples of synthesis of 6-membered rings
   • Hints on synthesis of 3- and 4-membered rings
   • Hints to olefin metatesis
   • Diels-Alder reaction.
   • 1,3-dipolar cycloadditions
6. Rearrangements (3 hours)
   • Carbocation rearrangement with 1,2 hydride shif
   • Pinacol rearrangement (also in tandem with Corey-Chaikovski reaction)
   • Wagner-Meerwein rearrangement
   • Baeyer-Villiger reaction
   • Curtius rearrangement
   • Wolff rearrangement
   • Sigmatropic rearrangements: Cope and Claisen reactions
7. Diversity oriented synthesis (3 hours)
   • General concepts
   • Multicomponent reactions
8. Reaction mechanisms (5 hours)
   • Non kinetical methods for delucidating a mechanism.
   • Kinetical methods for delucidating a mechanism.

RECOMMENDED READING/BIBLIOGRAPHY

The slides of the lessons will be available in pdf format on Aulaweb.

For the review / deepening of basic organic chemistry topics, the latest editions of the same texts recommended for the courses of Organic Chemistry I and II can be used; in particular:

-- Brown, Foote, Iverson, Anslyn - Organic Chemistry - EdiSES

-- Bruice - Organic Chemistry - EdiSES

-- Clayden, Greeves, Warren . Chimica Organica, seconda edizione - Piccin

-- Stuart Warren, Paul Wyatt - Organic synthesis - The Disconnection Approach, 2nd Edition - J. Wiley & Sons (2008).

The first three books are available also in english or in other languages.

TEACHERS AND EXAM BOARD

LESSONS

LESSONS START

From September 30, 2024

Class schedule

The timetable for this course is available here: Portale EasyAcademy

EXAMS

EXAM DESCRIPTION

The exam will be written and then oral.

The written exam lasts 120 minutes, that are increased by 30% for students with SLD* or 50% for students with disabilities.* The written exam will have two parts

1. specific questions that will generate an overall mark. According to the mark obtained the students will be admitted or not to the oral. The mark will also influence the final mark.
2. A retrosynthesis problem..

The latter will not provide a mark. However, the exercise will be discussed during the oral exam. Obviously, if the student does not propose a suitable synthess, this will have an outcome on the oral evauation.

The oral exam will follow the written one, typically on the same very day.

If the student fails the oral exam or gives up, he/she will repeat the written exam in a later date.

The oral exam is an interview in front of the commission (of at least 2 persons). The student will necessarily use the blackboard and be able to draw chemical equations, formulas, and reaction mechanisms.

Important: there will be 7 possibility per year to give the exam. Further dates may be decided, but, if the student has formally attended the module in year 20xx/20xx+1, he/she will be allowed to take part to these additional exams only until the end of febrauary of 20xx+2.

* Students who have valid certification of physical or learning disabilities on file with the University and who wish to discuss possible accommodations or other circumstances regarding lectures, coursework and exams, should speak both with the instructor and with Professor Sergio Di Domizio (sergio.didomizio@unige.it), the Department’s disability liaison.

ASSESSMENT METHODS

During the interview, it is intended to ascertain, through the initial discussion of topics developed in the frontal lectures, the degree of understanding reached by the student as well as his reasoning ability in making connections between different parts of the program and in dealing with case studies related to those expressly treated in the program.

Exam schedule