Organic Synthesis

Code

Course teacher

Associate teachers

Status of the course

Course objectives

Acquisition of advanced knowledge of modern organic synthesis that involves studying practical laboratory techniques that are used in the synthesis of organic compounds.

Course enrolment requirements and entry competences required for the course

Organic chemistry

Learning outcomes expected at the level of the course (4 to 10 learning outcomes)

After completing the course, the student will become familiarized with the major concepts of organic analysis, which includes:
- developing strategy and planning the organic synthesis
- writing the mechanisms in organic synthesis
- analysis of examples of synthesis from published papers in order to sharpen student’s reasoning ability and critical thinking
- conclusion of the synthesis by using the retrosynthetic analysis
- mastering new laboratory procedures used in organic synthesis
- application of acquired knowledge in research projects.

Course content broken down in detail by weekly class schedule (syllabus)

 Lectures and seminars (L+S):
1. Introduction. Target molecule. The carbon skeleton and functional groups. The main concepts in organic synthesis (mechanistic and retrosynthetic approach). Yields. Selectivity. (2 + 0)
2. Mechanistic approach. Writing mechanisms. Lewis structures, Lewis acids (LA), and bases (LB), LA / LB reactions. Resonance. Carbocation chemistry. Rearrangement. Problems. (3 + 1)
3. Electrophilic reactions to unsaturated carbon-carbon bonds, and aromatic compounds. LA / LB reaction of alcohols, alkenes, alkynes, and epoxides. LA / LB reactions that involving aromatic rings (electrophilic aromatic substitution reactions; Friedel-Crafts reaction and acylation reaction). Problems. (3 + 1)
4. Overview of the main nucleophilic substitution at saturated carbon. Formation of anions (the nucleophiles). Nucleophilic substitution (SN1, SN2). The stereochemistry and conformation of the synthesis. Elimination reaction (thermal and anti sin elimination reaction). Problems. (2 + 2)
5. Chemical reactivity and ring strain. Nucleophilic opening of the epoxide, episulphide and aziridine ring. The reaction with the nucleophile 3-membered species (and selinene halonium ions) and 3- and 4-membered cyclic esters (lactones) and cyclic amides (lactams). Problems. (2 + 1)
6. Nucleophilic addition reaction of aldehydes and ketones. Aldol condensation reaction. Michael addition reactions. The reaction of aldehydes or ketones with Wittig reagent. Problems. (2 + 2)
I. Partial exam (written, 2 hours)
7. Reaction of primary amines with aldehydes and ketones: (imine, Schiff base). Reactions of secondary amines with aldehydes and ketones: (enamines). Problems. (2 + 2)
8. Nucleophilic acyl substitution reactions. Problems. (2 + 1)
9. Retrosynthetic analysis. Fundamental concepts. Sinton and half-reactions. (3 + 0)
10. Strategy and planning. Convergent and linear synthesis of the target molecule. The aim of retrosynthetic analysis: the greatest simplification. Using the symmetry of the target molecule. The introduction of reactive functional groups in the final step of the synthesis. The introduction of functional groups to facilitate the formation of chemical bonds. Problems. (2 + 1)
11. Chemoselectivity and protecting groups. Protection of the carbonyl group to form a cyclic acetal. Protecting the alcohol group. Protection of the amine. Omitting the use of protecting groups. Reaction of one from two identical functional groups. Problems. (3 + 2)
12. Strategy of retrosynthetic analysis. Chemical transform - the guiding principle in retrosynthetic analysis. Diels-Alder cycloaddition as a target chemically transform. The strategy based on identifying the potential reactants, Building blocks and structural subunits (substructures). Topological strategy. Problems. (2 + 1)
13. Stereochemistry and conformation of the synthesis. Stereoselective synthesis and preparation of the optically pure compounds. The syntheses with isotopes of carbon and hydrogen. Examples of the synthesis of complex organic compounds. Problems. (2 + 1)
II. Partial exam (written, 1 hour 30 min)
III. Partial exam (oral, 30 min)
 Laboratory exercises (E)
1. Grignard reactions: Synthesis of phenyl acetic acid. (6)
2. Condensation reaction: Perkin synthesis: Synthesis of cinnamic acid. (6)
3. Addition reaction of carbonyl compounds: Claisen Schmidt condensation: Synthesis of dibenzylacetone. (6)
Multi-step synthesis: Benzoin - benzil - benzilic acid - phenytoin.
4. Synthesis of benzoin (condensation reaction) (6)
5. Synthesis of benzil (oxidation) (6)
6. Synthesis of benzilic acid (Molecular rearrangement - Benzilic rearrangement) (6)
7. Synthesis of phenytoin (Molecular rearrangement – Pinacol rearrangement) (6)
8. Cycloaddition reaction (Diels-Alder reaction): endo - exo selectivity. (6)
9. Beckmann rearrangement: Synthesis of ε-caprolactam. (6)
10. Confirmation of the compounds obtained by the synthesis. Determination of the UV and IR spectrum. (6)

Format of instruction:

Student responsibilities

Students are required to attend classes (lectures, seminars, exercises) and actively participate in the learning process. This will be recorded and evaluated in making the final grade.

Optional literature (at the time of submission of study programme proposal)

P. Wyatt, S. Warren, Organic synthesis: Strategy and control, John Wiley & Sons Ltd., England, 2007.
E. J.Corey, X. M. Cheng, The Logic of Chemical Synthesis, John Wiley & Sons, New York 1989.
Stanley H. Pine, Organska kemija, Školska knjiga, Zagreb, 1994.
E. Pretsch, P. Buhlmann, C. Affolter, Structure Determination of Organic Compounds, Springer, 2000;

Quality assurance methods that ensure the acquisition of exit competences

Quality assurance will be performed at three levels:
(1) University Level;
(2) Faculty Level by Quality Control Committee;
(3) Lecturer’s Level.

Other (as the proposer wishes to add)