CHEMISTRY OF HETEROCYCLIC COMPOUNDS
Learning outcomes of the course unit
At the end of the course the student is able:
- to know the IUPAC nomenclature of aromatic heterocyclic compounds and to apply the IUPAC rules to unknown compounds;
- to know the structural features of the main aromatic heterocycles;
- to know the synthesis of the aromatic heterocycles explained in the course;
- to know the reactivity of the heterocycles tackled during the course and, for every class of compounds, to understand the regioselectivity issue of the different reactions;
- to be able to analyze the chemical behavior of the heterocycles in the presence of given reactants;
- to know the acid-base behavior and the tautomeric equilibria (when present) of the heterocycles tackled during the course, and to be able to order different heterocycles based on scales of reactivity and basicity;
- to be able to apply the acquired knowledge in analysis and solution of simple exercizes of synthesis and retrosynthesis.
It is necessary to have knowledge of organic chemistry. To access the final examination the student must have passed the Organic Chemistry I exam (for CFT students) or Chemistry (for students in Pharmacy).
Course contents summary
The course mainly describes aromatic heterocycles, in particular five- and six-membered monocyclic and bicyclic systems, focusing on the following aspects: nomenclature, struture, physical-chemical properties, tautomerism, main syntheses and reactivity.
Particular attention will be paid to bioactive compounds and heterocyclic drugs.
Definition and classification of heterocyclic compounds. Baldwin rules. Aromaticity. IUPAC rules for the nomenclature of mono- and polycyclic heteroaromatic compounds. Pyrrole, pyrrole-containing natural compounds and drugs. Pyrrole syntheses: Paal-Knorr, Knorr, Hantzsch. Acidity. Reactivity: nitration, sulfonation, formylation, Mannich reaction, metalation.
Furans and thiophenes. Syntheses (Paal-Knorr, Feist-Benary, Hinsberg, Gewal). Reactivity: nitration, bromination, metalation, acylation, Mannich reaction, Diels-Alder cycloaddition.
Imidazoles, oxazoles and thiazoles. Natural compounds and drugs. Acid/base properties. Tautomerism. Reactivity: nitration, sulfonation, bromination, alkylation, acylation, reactions with bases, metalation, SNAr.
Pyrazoles, isoxazoles, isothiazoles. Natural compounds and drugs. Main syntheses. Acidity. Reactivity, SEAr, metalation.
Five-membered heterocycles containing 3-to-5 heteroatoms. Syntheses. Properties, isosterism.
Pyridine. Natural compounds and drugs. Properties, basicity. Reactivity with electrophiles and nucleophiles. Metal-halogen exchange. Metalation. Pyridones. Pyridine-N-oxide.
Pyrilium ion, pyrons, coumarins, chromones. Natural compounds and drugs. Reactions with nucleophiles.
Indoles. Natural compounds and drugs. Syntheses (Fisher, Bishler, Leimgruber-Batcho). Reactivity. Electrophilic substitutions, alkylations, reactions with alpha,beta-unsaturated compounds.
Diazines (pyrazines, pyrimidines, pyridazines). Syntheses. Reactivity. Purines (syntheses). RNA- and DNA-based nitrogen-containing bases.
F. BROGGINI, G. ZECCHI, Chimica dei composti eterociclici, Ed. Zanichelli, 2017
1. D. SICA, F. ZOLLO, Chimica dei composti eterociclici farmacologicamente attivi, Ed. Piccin. 2008.
2. J.A. JOULE, K. MILLS, Heterocylic Chemistry, 5th Edition, Wiley-Blackwell Edition.
3. T. GILCHRIST, Heterocyclic Chemistry, Ed. Longman, 1997.
4. D. T. DAVIES, Aromatic Heterocyclic Chemistry, OUP Ed., Oxford Chemistry Primers, 1992.
Additional teaching material for students:
-slides (Pdf files) of the lesson;
-exercises (Pdf files) for each subject matter and their solutions.
According to the regulation of the Italian Government and the University of Parma about the COVID-19 pandemics, the present course is realized with frontal lessons with mixed in-presence and at-distance modality. In particular, the teacher takes lessons in the classroom with the help of PC (Powerpoint slides) and board (either graphic table connected to the PC or blackboard); simultaneous connection of the PC to the Teams platform in streaming modality ensures connection with students not present in the classroom.
Each lesson is registered and loaded in the Elly portal of the course, together with the slides.
The teacher also performs exercises in the classroom with the help of students (with simultaneous connection via Teams-streaming) to enhance the ability of students to apply the knowledge on the synthesis and reactivity of heterocyclic compounds.
At the end of each topic, the teacher loads exercises (on Elly portal) which are solved by students in autonomy to prove their knowledge. Thereafter, the teacher furnished solutions to the problems to give the students an instrument of self-evaluation.
Assessment methods and criteria
Learning outcomes are checked by a written examination. The written examination aims at verifying whether the student has acquired the knowledge and developed the skill in applying this knowledge in the analysis and resolution of exercises. The examination takes 90 minutes and consists in the resolution of 9/10 exercises (open questions) concerning the nomenclature, properties, reactivity and synthesis of heterocycles. Every exercise corresponds to a numeric value, which is reported. The student is qualified (idoneo) when the exam is judged equal or superior to 18/30.
In case the COVID-related sanitary emergence continues, the written examination will proceed as follows:
-written examination in the classroom (whenever possible);
-remote written examination on the Teams platform (see the guidelines at the address: http://selma.unipr.it/). The teacher will give the students detailed instructions on the modality to access the examination (link, ID loading, honour declaration loading). No texts, notes nor references are permitted during the examination; possible compensatory material will be allowed to students with DSA or BES, which will be agreed upon with the teacher at least one week before the examination.