CHIMICA ORGANICA 1 M - Z

The course aims to provide a critical and scientific mentality and rational use of mnemonic abilities, favoring the ability to apply theoretical knowledge to problem-solving.

This means overcoming the limit of mere "mnemonic repetition" of concepts that, in doing so, would be aimed at simple learning. Critical and scientific mentality at the same time constitute a high-level objective; it requires a synthesis between mental operation and actual realization: the first is expressed in the design of an experiment, in the rational-intuitive control of the execution and calculation phases and the evaluation phase of the results; the second is expressed in the actual execution of the experiment, even at the virtual level.

Therefore, at the end of the course, the student must be able to:

D1 KNOWLEDGE AND UNDERSTANDING ABILITY

• Know in-depth the reactivity of new classes of organic compounds and the reaction mechanisms through which they react.

• Illustrate the criteria for carrying out processes with a pronounced chemical, positional, and stereochemical selectivity.

D2 ABILITY TO APPLY KNOWLEDGE AND UNDERSTANDING

• Identify the nature of the synthetic process to which the organic molecules are subjected based on the described reaction conditions.

• Correctly describe the reaction mechanism for the related processes.

• Discuss the nature of the selective processes that these mechanisms involve.

D3 AUTONOMY OF JUDGMENT

• Choose the most suitable reagents with the desired selectivity degree for the required synthetic process.

• Use the most efficient method available to synthesize even multi-functionalized structures.

D4 COMMUNICATION SKILLS

• Communicate, using appropriate technical-scientific terminology, with the teacher and experts in the subject of study.

• Competently discuss, even in the context of an oral examination, the synthetic techniques learned.

D5 LEARNING SKILLS

• Find and learn the information, new compared to those provided during the training activity, necessary to broaden the knowledge on topics more or less correlated with those covered by the course.

• Understand and process the contents of scientific publications containing new research results.

• Use the knowledge acquired to make it easier to understand topics related to organic chemistry delivered in other educational activities.

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 the case studies.

Should teaching be carried out in mixed mode or remotely, it may be necessary to introduce changes concerning previous statements in line with the program planned and outlined in the syllabus.

Learning assessment may also be carried out online, regardless of the conditions.

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

Knowledge of an adequate study method; the following sites and readings 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 consists of 5 modules, corresponding to 8 credits, of which 7 lectures and 1 classroom exercise; these last will be carried out at the end of the fifth module.

To allow the student to follow the topics covered without difficulty and to find them quickly and effectively, a program has been drawn up that follows the general index of the Bruice “Organic Chemistry”, which will be considered as the leading introductory text, integrating it, where appropriate, with some topics deemed relevant to the Degree Course. Additions and insights can be found in the Clayden “Organic Chemistry”, which will be considered a supporting text. The added parts, highlighted in red, refer to the Clayden.

 

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 will have to take a written test and, possibly, an oral test; access to the oral test is achieved by scoring a minimum of 22 points out of 30 on the written test.

Those who obtain a score equal to or higher than 22 have the right to decide whether to take the oral exam, improve their grade, or record the subject with a grade of 21/30. You must take the oral exam to obtain a grade above 21; the latter may jeopardize the promotion.

The written test, lasting 90 minutes, consists of 30 multiple choice questions (5 possible answers, of which only one is correct), found from the Exam Manager online platform, which will cover the entire program. One point will be attributed to each correct answer, while a quarter point will be deducted for each wrong answer (−0.25); the answers not given will be worth zero points. The written test will be passed with a minimum grade of 18/30.

It is not allowed to consult books, notes, or electronic devices during the examination.

The oral exam consists of a discussion, lasting about 20-30 minutes, aimed at ascertaining the level of knowledge and understanding reached by the student on the theoretical and methodological contents indicated in the program. The oral exam will also allow you to verify the student's communication skills with properties of language and autonomous organization of the exposition on the same theoretical topics.

The student will be asked to explain some topics in detail and to carry out the retrosynthetic analysis of small molecules using the different approaches presented during the lessons. The student will have to demonstrate knowledge of the general approach to solving a synthetic problem and be able to design an adequate synthesis considering stereochemical issues. Theoretical principles will be discussed, and the ability of the rational application to practical problems will be evaluated. The student's ability to analyze different synthetic ways to obtain the same product and the critical spirit developed thanks to a robust acquisition of the theoretical principles covered during the course will be evaluated.

The oral exam ends with an evaluation out of thirty to whose numerical formulation the following elements contribute:

    preparation on the entire program carried out;
    ability and clarity of presentation;
    ability to link and synthesize various topics.

The final grade will be established considering the scores achieved on both tests. It is important to underline that the oral test should not be understood as aimed at raising the grade obtained in the written test but, if it is negative, the grade may be lowered to the point of also failing.

Passing the exam with minimum marks requires sufficient knowledge of the topics covered in the various parts of the program. To achieve a score of 30/30 cum laude, the student must demonstrate that he has acquired an excellent knowledge of all the topics covered during the course and that he can connect them logically and coherently.

Learning verification can also be carried out electronically, regardless of the conditions.

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