66173 - Organic Chemistry with Laboratory M

Learning outcomes

At the end of the course the student will be able to design retrosynthetic pathways, using catalytic coupling reactions for the formation of new C-C bonds as well as C-heteroatom bond. The studetnwill be able to plan asymmetric syntheses of organic compounds of medium complexity. The course will focus on the application of the principal techniques used for the structural identification and analysis of organic molecules The course will apply basic knowledge on spectroscopic methods such as Nuclear Magnetic resonance and Mass Spectroscopy to the solution of the structures of organic molecules.. The main part of the course will be carried out with exercitations on experimental data, and by exercitations on the spectrometers.

Course contents

INSTITUTIONAL PART

Background knowledge: the background knowledge in organic chemistry expected from a student entering this course is that of a student who has completed an Eurobachelor(R) certified degree in Chemistry and visible here

1. Determination of the reaction mechaninsm of organic reactions
1. Thermodynamics and kinetic considerations
2. Substituent effect
3. Basic concepts:
1. Thermodynamic and kinetic control
2. Hammond's postulate
3. Principles of Curtin-Hammett
4. Eyring's equation
4. Isotope effect
5. Other useful techniques for the determination of the reaction mechanism
1. Crossed experiments
2. Trapping of intermediates
3. Isotopical marking
   
   
2. Organic reactions mediated by transition metals
1. Palladium in organic synthesis
2. Reactions of organopalladium with:
1. Alkenes: Heck reaction
2. Aryl boronic acids: Suzuki-Miyaura reaction
3. Terminal alkynes cuprates: Sonogashira reaction
4. Aryl stannanes (Stille); organo-zinc (Negishi); organo-silicon (Hiyama)
3. Carbon-heteroatom coupling: Buchwald-Hartwig amination
4. Olefine metathesis
   
   
3. Concerted reactions
1. Diels-Alder reaction: dienes e dienophiles
2. The frontier orbital description of cycloaddition: Woodward-Hoffmann rules
3. Stereochemistry of the Diels-Alder reaction: the “endo” rule
4. Catalysis of the Diels-Alder reaction. Effect of water as the solvent.
5. Thermal and photochamical [2+2]-cycloadditions.
6. 1,3-dipolar cycloadditions
7. Sigmatropic rearrangements and elettrocyclic reactions
8. Rearrangements
1. Neighbouring group effect. Stereochemical considerations. Migratory aptitude
2. Wagner-Meerwein; Pinacolic; Baeyer-Villiger; Beckmann
   
   
4. Asymmetric synthesis
1. Stereochemistry of dynamic processes
2. Prochirality
3. Enantiomeric excess and optical purity
4. Thermodynamic description of asymmetric reactions
5. Methods for the obtainment of enantiomerically enriched substances:
1. Classical resolutions
2. Dynamic resolutions of the first and the second kind
3. Synthesis from the chiral pool
4. Stoichiometric methods with chiral auxiliaries
5. Asymmetric catalysis
1. Metallocatalysis
2. Organocatalysis and asymmetric chiral phase transfer catalysis

 

LABORATORY

The course will focus on the application of the principal techniques used for the structural identification and analysis of organic molecules The course will apply basic knowledge on spectroscopic methods such as Nuclear Magnetic resonance and Mass Spectroscopy to the solution of the structures of organic molecules.. The main part of the course will be carried out with exercitations on experimental data, and by exercitations on the spectrometers.

1. NMR Spectroscopy
1. Nuclear spin and resonance
2. NMR spectromers and FT technique.
3. Spin relaxation theory
4. Acquisition parameters, spectral width and RF pulses
5. 1H spectra: chimica shift, cpupling constants and integration
6. 13C spectra and DEPT techniques for the signal assignment
7. NOE spectra
8. exercitations
   
   
2. Mass Spectroscopy
1. Ionization techniques: electron impact, electron spray, MALDI
2. Ion analyzers: magnetic secton, quadrupolem ionic trap, TOF and FT-ICR
3. Fragmentation mechanism
4. Fragmentation analysis for the structural assignment of simple molecules
5. Practical exercitations on experimental mass spectra
   
   
3. Analysis of optically active compounds
1. Enantioselective HPLC
2. Optical purity by NMR spectroscpy
3. Optical purity by optical methods: polarimetry, circular dichroism
4. Use of X-ray diffraction for the absolute configuration.
   
   
4. Laboratory activities
1. Two multi-step syntheses related to the theoretical contents will be held by students in the chemical laboratory

Readings/Bibliography

Lectures' handouts available via web at AlmaDL

Clayden, Greeves, Warren & Wothers "Organic Chemistry - 2nd Ed." - OUP 2012
Laboratory

1. D.H.Williams, I.Fleming; 'Spectroscopic Methods in Organic Chemistry' 5° ed. Inglese; McGraw-Hill Book Company. ISBN 0-07-709147-7
2. R.M.Silverstein, F.X.Webster, D.J.Kiemle, "Spectrometric identification of Organic Compounds", 7° ed,; Wiley International Edition. ISBN 0-471-42913-9

Teaching methods

PowerPoint presentations Exercises

Assessment methods

The assessment of learning is done through a practical test based on the experiences carried out in the laboratory, and through a written test which is held during one of the six exam dates defined by the teachers during the academic year.

The practical test allows to obtain a score between 0 and 3, and consists of: i) the identification of the structure of an unknown molecule synthesized in the laboratory on the basis of NMR and mass spectroscopic data, to be made during laboratory experiments (from 0 to 1 point); ii) reports on experiments performed in the laboratory, whose evaluation will determine the understanding of conducted experiments, the ability to write a short scientific report, and processing, interpretation and presentation of data collected during the experiences (0 to 2 points).

Only students who attended the experimental activities of the laboratories will be admitted to the final written test. The delivery of the reports shall be made in any case before the spring examination session.

The written test will be held during exam sessions and it consists of two exercises: (1) an exercise in structural assignment with a score between 0 and 8 points and (2) 1-2 exercises on the of theoretical part of the course with a score between 0 and 20 points. The time available for the test is 3 hours. The exercise of structural assignment involves the use of experimental data of NMR / mass spectroscopy data for the determination of the structure of an unknown organic compound. The exercise on the theory aims to assess the level of learning of the concepts in class and the student's ability to apply them to the understanding and resolution of real problems taken from the scientific literature. The final written test is open-book and it is allowed to consult books, handouts and notes. It is not allowed to use internet connectable devices (tablets, smartphones, etc.).

The final grade is obtained by adding the scores obtained in the practice test rating (0-3 points) and that obtained in the final written test exam (0-28 points). Scores above 30 are equivalent to 30 cum laude. When not passing the exam, the student must repeat the final written exam in full in a subsequent appeal, while holding valid practice test score laboratory.

Teaching tools

PDF presentations available via web, through AlmaDL - the University delivery system of teaching materials

LABORATORY
The teacher will use Powerpoint Presentations (available to the students at the beginning of the lessons) for the theoretic part, and printed spectra for the exercitations. The course will proceed with theoretical concepts, followed by examples and exercise

Office hours

See the website of Paolo Righi

See the website of Andrea Mazzanti

See the website of Luca Bernardi