CHIMICA ORGANICA 1 A - L

The course aims to develop a critical and scientific mindset by promoting the rational use of mnemonic skills and the ability to apply theoretical knowledge to problem-solving.

This approach goes beyond the simple “mnemonic repetition” of concepts, aiming at a synthesis between mental operation and practical implementation: from designing an experiment and rational controlling the phases to evaluating the results and practical execution, even in virtual contexts.

 At the end of the course, the student will be able to:

D1 KNOWLEDGE AND UNDERSTANDING ABILITY

• Identify and classify organic molecules based on functional groups and stereochemical characteristics.
• Illustrate the reactions for the formation of carbon-carbon bonds.
• Describe the interconversion reactions of functional groups.
• Design multi-step syntheses of organic molecules.
• Explain the mechanisms of organic reactions, with particular attention to the stereochemistry of the processes.

 D2 Ability to Apply Knowledge and Understanding

•  Give IUPAC names and stereochemistry to multifunctional organic molecules.
• Identify carbon-carbon bond formation and functional group interconversion reactions in an exercise or exam context to design synthetic steps.
• In an exercise or exam context, identify carbon-carbon bond formation and functional group interconversion reactions responsible for changes to the molecular structure.
• Design multi-step syntheses of organic molecules in an exercise or exam context.

 D3 Autonomy of Judgement

•  Predict the chemical-physical properties of an organic molecule based on its structure and functional groups.
• Predict the chemical reactivity of an organic molecule based on its structure and functional groups.

D4 Communication Skills

• Communicate effectively with the teacher and experts in the field using appropriate technical-scientific terminology.
• Discuss competently the synthetic techniques learned during an oral exam.

 D5 Learning Skills

• Learn new information in addition to that provided during the training activity, which is necessary to explain the intermolecular interactions underlying the biological activity of an organic molecule whose chemical structure is known.

The course activities consist of lectures and classroom exercises. Some "case studies" concerning molecules of chemical-pharmaceutical interest will be added to these. The student must actively participate in discussing the topics presented, particularly in the case studies.

If the teaching is taught in mixed mode or remotely, the necessary variations may be introduced concerning what was previously declared to respect the expected program and reported in the syllabus.

Rest assured, the learning assessment can be done online if the conditions require it. We are committed to ensuring that your learning is not disrupted and that you are well informed about any changes in the assessment methods.

Knowledge of basic concepts of Mathematics, Physics, and General Chemistry.

Knowledge of an appropriate study method; the following resources are recommended:

• http://studenti.unimi.it/studentestrategico/metodo/index.htm
• http://helpmetodo.altervista.org/
• https://www.mondadorieducation.it/media/contenuti/statici/didattica/flipped/assets/pdf/04_lavoro_casa.pdf

Obligatory attendance is according to the rules of the teaching regulations of the CdS in CTF, as reported in the following link.

The course is divided into 5 modules, for a total of 8 credits: 7 credits are assigned to lectures, and 1 credit is dedicated to classroom exercises, which will take place during the course.

To facilitate learning, the course program is designed to align with the Degree Course, following the general index of the text "Organic Chemistry" by Bruice and integrating, where necessary, with topics relevant to the Degree Course and insights from the support text "Organic Chemistry" by Clayden. Additional topics will be highlighted in red and found in the support text.

 

MODULE 1. Introduction to the study of organic chemistry

 1. ELEMENTS OF GENERAL CHEMISTRY: ELECTRONIC STRUCTURE AND BOND

Formation of single bonds in organic compounds – Formation of the double bind: the bonds of ethene – Formation of the triple bond: the bonds of ethyne – The bonds of the methyl cation, the methyl radical, and the methyl anion – Hybridization and molecular geometry – Summary: hybridization, bond length, bond strength, and bond angles – Dipolar moments of molecules.

Paragraphs: 1.7–1.10 and 1.14–1.16

 2. Acids and bases: fundamental concepts in organic chemistry

Organic acids and bases – How to predict the outcome of an acid-base reaction – How to determine the position of an equilibrium – Influence of the structure of acid on its pK value – Influence of substituents on the strength of an acid – Introduction to delocalized electrons – Summary of the factors that determine the strength of an acid – Influence of pH on the structure of an organic compound.

Paragraphs: 2.3–2.10; we recommend reading Chapter 8

 3. Introduction to organic compounds: nomenclature, physical properties, and structure

Alkyl groups – Nomenclature of alkanes – Nomenclature of cycloalkanes – Nomenclature of alkyl halides – Nomenclature of ethers – Nomenclature of alcohols – Nomenclature of amines – The structure of alkyl halides, alcohols, ethers, and amines – Non-covalent interactions – Solubility – Rotation around the single carbon-carbon bond – Cycloalkanes and ring tension – Conformers of cyclohexane – Conformers of monosubstituted cyclohexanes – Conformers of disubstituted cyclohexanes – Condensed cyclohexanes – Bicyclic and polycyclic systems and their Nomenclature.

Paragraphs: 3.1–3.16, page 839

 

MODULE 2. Electrophilic, stereochemical addition reactions, and electronic relocation

 4. Isomers: the arrangement of atoms in space

Cis–trans isomers – E,Z nomenclature of the isomers of an alkene – Chirality – An asymmetric center generates chirality in a molecule – Isomers with an asymmetric center – Asymmetric and stereocenter centers – Representation of enantiomers – Naming of enantiomers with the descriptors R,S – Optical activity of chiral compounds – Measurement of specific rotation – Enantiomeric excess – Chiral compounds without stereocenters: Atropisomers – Compounds containing more than one asymmetric center – Stereoisomers of cyclic compounds – Meso compounds – Nomenclature of compounds containing more than one asymmetric center – Nitrogen and phosphorus can be asymmetric centers – Receptors – The separation of enantiomers.

Paragraphs: 4.1–4.18; page 319

 5. Alkenes: structure, nomenclature, and introduction to reactivity • thermodynamics and kinetics

Molecular formulas and degree of unsaturation – Nomenclature of alkenes – Structure of alkenes – Reactivity of organic compounds and functional groups – Reactivity of alkenes • Use of curved arrows – Thermodynamics: how much product is formed? – Increase the amount of product in a reaction – Calculate the values of ∆H – Use the values of ∆H to determine the relative stability of alkenes – Kinetics: how fast are products formed? – Speed of a chemical reaction – Free energy diagram as a function of the reaction coordinate – Catalysis.

Paragraphs: 5.1–5.13; we recommend reading Chapter 12

 6. The reactions of the alkenes • the stereochemistry of additional reactions

Addition of halogenic acid to alkenes – Stability of carbocations – Structure of the transition state – Regioselectivity of electrophilic addition reactions – Addition of water to alkenes – Addition of alcohol to alkenes – Transposition of carbocations – Oxymercuriation–Demercuriation – Addition of borane to alkenes: hydroboration–oxidation – Addition of halogens to alkenes – Addition of a peroxy acid to alkenes (Prilezhaev reaction) – Addition of ozone to alkenes: reductive and oxidative ozonolysis – Regioselective, stereoselective and stereospecific reactions – Stereochemistry of electrophilic addition reactions – Alkenes cyclic – Di–hydroxylation sin – Oxidative cleavage.

Paragraphs: 6.1–6.13; pages 442–444, 906, and 907; we recommend reading Chapter 19

 7. The reactions of the alkynes • introduction to multistage synthesis

Nomenclature of alkynes – Nomenclature of compounds containing more than one functional group – Structure of alkynes – Physical properties of unsaturated hydrocarbons – Reactivity of alkynes – Addition of halogen and halogen acids to alkynes – Addition of water to alkynes – Hydroboration–oxidation of alkynes – Addition of hydrogen to alkynes – Acidity of a hydrogen bonded to an sp carbon – Use of acetylide ions in organic synthesis – Synthetic Strategy I: Introduction to multistage synthesis.

Paragraphs: 7.1–7.12

 8. Electronic relocation and its effect on stability, pK_a, and products of a reaction • aromaticity, electronic effects, and introduction to benzene reactions

Delocalized electrons explain the structure of benzene – Bonds in benzene – Resonance limit and hybrid resonance structures – How to draw resonance limit structures – Predict the stability of resonance limit structures – Resonance energy – Electronic delocalization increases stability – Stability according to the theory of molecular orbitals – Effect of electronic delocalization on pK_a – Electronic effects – Electronic delocalization can influence the product of a reaction – Reactions of dienes – Thermodynamic and kinetic control – Benzene is an aromatic compound – The two criteria for aromaticity – Application of the criteria of aromaticity – Aromaticity according to the theory of molecular orbitals – Aromatic heterocyclic compounds – Reactivity of benzene.

Paragraphs: 8.1–8.13 and 8.16–8.21; we recommend reading Chapter 7

 

MODULE 3. Reactions of replacement and elimination

 9. Reactions of replacement and elimination of the alkyl halides

The S_N2 reaction – Factors influencing S_N2 reactions – The S_N1 reaction – Factors influencing S_N1 reactions – Competition between S_N2 and S_N1 reactions – Elimination reactions of alkyl halides – The E2 reaction – The E1 reaction – Competition between E1 and E2 reactions – Stereoselectivity of E2 and E1 reactions – Elimination by substituted cyclohexanes – Predict the reaction products of an alkyl halide with a nucleophile/base – Benzyl, allyl, vinyl, and aryl halides – Solvent effects – E1cb reaction – Substitution and elimination in organic synthesis – Competition between intermolecular and intramolecular reactions – Synthetic Strategy II: How to deal with the problem.

Paragraphs: 9.1–9.17; pages 399–404, we recommend reading Chapters 15 and 17

 10. Reactions of alcohols, ethers, epoxies, amines, and compounds containing sulfur

Nucleophilic substitution reactions of alcohols: formation of alkyl halides – Lucas’s assay – Other methods used to convert alcohols to alkyl halides – Intramolecular nucleophilic substitution (S_Ni) – Conversion of alcohol to a sulfonic ester – Elimination reaction of alcohols: dehydration – Oxidation of alcohols – Nucleophilic substitution reactions of ethers – Nucleophilic substitution reactions of epoxides – Corona ethers: another example of molecular recognition – Corona ethers can be used to catalyze S_N2 reactions – Oxides of arenes – Benzo[a]pyrene and cancer – Amines do not undergo nucleophilic substitution or elimination reactions – Quaternary ammonium hydroxides undergo elimination reactions – Thiols, sulfides, and sulfonium ions.

Paragraphs: 10.1–10.11 ; https://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/special2.htm#top6

 11. Organometallic compounds of lithium, magnesium, and copper

Organolithium and organomagnesium compounds – Transmetallation – Organocuprates.

Paragraphs: 11.1–11.3; we recommend reading Chapter 9

 12. The radicals

Reactivity of alkanes – Natural gas and oil – Fossil fuels: a problematic energy source – Chlorination and bromination of alkanes – Stability of radicals – Product distribution depends on probability and reactivity – The principle of reactivity–selectivity – Formation of explosive peroxides – Addition of radicals to alkenes – Stereochemistry of radical substitution and addition reactions – Free radical substitution of allyl and benzyl hydrogens – Cyclopropane – Synthetic Strategy III: Examples of multistage synthesis.

Paragraphs: 12.1–12.10

 

MODULE 4. Carbonyl compounds

 15. Reactions of carboxylic acids and carboxylic acid derivatives

Nomenclature of carboxylic acids and carboxylic acid derivatives – Structure of carboxylic acids and carboxylic acid derivatives – Physical properties of carbonyl compounds – How carboxylic acids and carboxylic acid derivatives react – Relative reactivity of carboxylic acids and acid derivatives carboxylic acids – Acyl halide reactions – Ester reactions – Acid-catalyzed hydrolysis and transesterification of esters – Hydrolysis of esters favored by hydroxide ion – Reactions of carboxylic acids – Reactions of amides – Hydrolysis and alcoholysis of amides catalyzed by acids – Hydrolysis promoted by ions hydroxide of amides – Hydrolysis of an imide: Gabriel’s synthesis of primary amines – Nitriles – Anhydrides of carboxylic acids – Dicarboxylic acids – Chemical activation of carboxylic acids – Thioesters.

Paragraphs: 15.1–15.18; we recommend reading Chapter 10

 22. Catalysis in organic reactions

Catalysis in organic reactions – Acid catalysis – Basic catalysis – Nucleophilic catalysis – Catalysis with metal ions – Intramolecular reactions – Intramolecular catalysis.

Paragraphs: 22.1–22.7

 16/23. Reactions of aldehydes and ketones • further reactions of carboxylic acid derivatives

Nomenclature of aldehydes and ketones – Relative reactivity of carbonyl compounds – Reactivity of aldehydes and ketones – Reactions of carbonyl compounds with carbon nucleophiles – Reactions of carbonyl compounds with hydride ion – In-depth analysis of reduction reactions – Chemoselective reactions – Reactions of aldehydes and ketones with nitrogen nucleophiles – Reactions of aldehydes and ketones with oxygen nucleophiles – Protecting groups – Reactions of aldehydes and ketones with sulfur nucleophiles – Reactions of aldehydes and ketones with a peroxy acid – Wittig reaction – Synthetic Strategy IV: Disconnections, synthons, and synthetic equivalents – Nucleophilic addition to a,b–unsaturated aldehydes and ketones – Nucleophilic addition to a,b–unsaturated carboxylic acid derivatives.

Paragraphs: 16.1–16.16; Chapter 23; we recommend reading Chapters 6 and 11

 17. Reactions to carbon a

Hydrogen acidity a – Keto-enol tautomers – Keto-enol interconversion – Carbon halogenation a of aldehydes and ketones – Carbon halogenation a of carboxylic acids – Formation of an enolate ion – Carbon alkylation a – Alkylation and acylation of carbon a via an enamine intermediate – Carbon alkylation b – An aldol addition forms a b-hydroxy aldehyde or a b-hydroxy ketone – Dehydration of an aldol addition product forms aldehydes and a,b-unsaturated ketones – Cross aldol addition – Claisen condensation: formation of b-ketoesters – Other cross condensations – Intramolecular condensation and aldol addition reactions – Robinson ringing – Decarboxylation of b-ketoacids – Malonic synthesis – Acetacetic synthesis – Synthetic Strategy V: Formation of new carbon–carbon bonds.

Paragraphs: 17.1–17.20; we recommend reading Chapters 20, 25 and 26

 

MODULE 5. Aromatic compounds

 18. Reactions of benzene and substituted benzenes

Nomenclature of monosubstituted benzenes – General mechanism of electrophilic aromatic substitution reactions – Halogenation of benzene – Nitration of benzene – Sulfonation of benzene – Friedel-Crafts acylation of benzene – Gatterman-Koch reaction – Friedel-Crafts alkylation of benzene – Alkylation of benzene by acylation–reduction: hydrogenation and Clemmensen and Wolff-Kishner reductions – Use of coupling reactions in benzene alkylation – Chemical transformations of substituents on the benzene ring – Nomenclature of disubstituted and polysubstituted benzenes – Effect of substituents on reactivity – Effect of substituents on orientation – The ortho–para relationship – Further considerations on the effects of substituents – Synthetic Strategy VI: Synthesis of mono and disubstituted benzenes – Synthesis of trisubstituted benzenes – Use of diazonium salts for the synthesis of substituted benzenes – Azobenzenes – Mechanism of the formation of a diazonium ion – Side chain reactions – Synthesis of phenols – Electrophilic aromatic substitution of phenols and phenates – Nucleophilic aromatic substitution – Synthetic Strategy VII: Synthesis of cyclic compounds.

Paragraphs: 18.1–18.8 and 18.10–18.22; page 540, we recommend reading Chapter 21; lecture notes

 19. Amines reactions

Nomenclature – Acid-base properties of amines – Reactivity of amines as bases and as nucleophiles – Synthesis of amines – Hofmann transposition – Curtius transposition – Cope elimination – Mannich synthesis – Heterocyclic amines of biological importance.

Paragraphs: 19.1–19.4, 19.7; pages 620 and 1022, http://organicavirtuale.altervista.org/VirtualText/amine2.html#amin10b

1. Organic Chemistry – P. Y. Bruice – 8ª Ed. Pearson.
2. Organic Chemistry – J. Clayden, N. Greeves, and S. Warren – 2^nd Ed. Oxford University Press.

To pass the course, the student must take a written and possibly an oral test. Access to the oral test requires a minimum of 22 points out of 30 on the written test.

Those who obtain a score equal to or higher than 22 can decide whether to take the oral exam to improve their grade or accept a grade of 21/30. To obtain a grade higher than 21, the oral exam is necessary, which may also result in failure.

The written exam, lasting 90 minutes, consists of 30 multiple-choice questions (with 5 options, of which only one is correct), selected from the Exam Manager online platform and covering the entire course program. Each correct answer is worth one point, while each incorrect answer will be deducted a quarter of a point (−0.25); unanswered questions are worth zero points. The written exam is considered passed with a minimum grade of 18/30. Scores will be rounded to the following whole number starting from 0.5 (rounding does not apply for scores lower than 18). Consult books, notes, or electronic devices are prohibited during the exam.

The oral exam consists of a discussion lasting approximately 20–30 minutes. Its purpose is to verify the student's level of knowledge and understanding of the program's theoretical and methodological contents. Furthermore, the oral exam allows for evaluating the student's ability to communicate using proper language and independently organize the presentation on the same theoretical topics.

The student must explain some topics in detail and conduct retrosynthetic analyses of small molecules using the different approaches presented during the lessons. It will be required to demonstrate an understanding of the general approach to solving a synthetic problem and the ability to design an adequate synthesis considering stereochemistry. The theoretical principles will be discussed, and the ability to apply them rationally to practical problems will be assessed. Furthermore, the student's ability to analyze different synthetic ways to obtain the same product and the degree of critical spirit developed thanks to a solid understanding of the theoretical principles covered in the course will be assessed:

• preparation on the entire program covered;
• ability and clarity of exposition;
• ability to connect and synthesize various topics.

The final grade will be determined based on the scores obtained in the two exam tests. It is essential to clarify that the oral exam should not be considered an opportunity to increase the grade obtained in the written test; on the contrary, in the event of a negative outcome, the overall grade may be reduced to the point of failing the exam.

To pass the exam with the minimum grade, it is necessary to demonstrate sufficient knowledge of the topics covered in all parts of the program. To obtain a score of 30/30 cum laude, however, the student must demonstrate excellent knowledge of all the topics covered during the course and the ability to connect them logically and coherently.

The learning assessment may also be carried out electronically if conditions require it.

An example of structured verification is available at the following link.