Learning objectives
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 each 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/acidity;
- to be able to apply the acquired knowledge in analysis and solution of simple exercizes of synthesis and retrosynthesis.
Prerequisites
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 Organic Chemistry Basics/Organic Chemistry (for Pharmacy students).
Course unit content
The course mainly describes aromatic heterocycles, in particular five- and six-membered monocyclic and bicyclic systems, focusing on the following aspects: nomenclature, structure, physical-chemical properties, tautomerism, main syntheses and reactivity.
Particular attention will be paid to bioactive compounds and heterocyclic drugs.
Full programme
Definition and classification of heterocyclic compounds. Aromaticity. IUPAC rules for the nomenclature of mono- and polycyclic heteroaromatic compounds.
Pyrrole, pyrrole-containing natural compounds and drugs. Structure of pyrrole and pyridine: comparison; pyrrole-like and pyridine-like nitrogen atoms in nitrogen-containing aromatic heterocycles and their implications in the structure-areactivity relashionship.
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.
Quinolines and isoquinolines: natural compounds and drugs containing these heterocycles. Main syntheses (Combes, Friedlander, Skraup, Bischler-Napieralski, Pictet-Spengler). Reactions with electrophiles and nucleophiles. Halogen exchange.
Pyrilium ion, pyrons, coumarins, chromones, anthocyanins. Natural compounds and drugs. Reactions with nucleophiles.
Indoles. Natural compounds and drugs. Syntheses (Fischer, Reissert). Reactivity. Electrophilic substitutions, alkylations, reactions with alpha,beta-unsaturated compounds.
Diazines (pyrazines, pyrimidines, pyridazines). Introduction on main syntheses. Reactivity. Pyrimidines and purines: structure and tautomerism. RNA- and DNA-based nitrogen-containing bases: structure and tautomerism.
Bibliography
Textbook:
F. BROGGINI, G. ZECCHI, Chimica dei composti eterociclici, Ed. Zanichelli, 2017
Reference books:
1. -J. CLAYDEN, N. GREEVES, S. WARREN, P. WOTHERS, “Organic Chemistry”,
Oxford University Press, Second Edition, 2012, Chapters 29 and 30
2. D. SICA, F. ZOLLO, Chimica dei composti eterociclici farmacologicamente attivi, Ed. Piccin. 2008.
3. J.A. JOULE, K. MILLS, Heterocylic Chemistry, 5th Edition, Wiley-Blackwell Edition.
4. T. GILCHRIST, Heterocyclic Chemistry, Ed. Longman, 1997.
5. D. T. DAVIES, Aromatic Heterocyclic Chemistry, OUP Ed., Oxford Chemistry Primers, 1992.
Additional teaching material for students (loaded on Elly platform):
-slides of the lessons (PDF files);
-possible access to video-recording of the lessons of previous years (via previous agreement with the teacher)
-exercises for each subject matter and their solutions (PDF files).
Teaching methods
According to the regulation of the Italian Government and the University of Parma about the COVID-19 pandemics, the present course is offered via frontal lessons with in-presence 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).
The slides of each lesson are loaded in the Elly platform of the course.
The teacher also performs exercises in the classroom with the help of students to enhance the ability of students to apply knowledge on the synthesis and reactivity of heterocyclic compounds.
At the end of each topic, the teacher loads exercises (on Elly) which are solved by students by themselves to evaluate their knowledge. Thereafter, the teacher furnishes solutions to the problems to give the students an instrument of self-evaluation.
After proper agreement with the teacher, the student may be also provided with video-recording of lessons taken in the past academic year.
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 usually takes 90 minutes and consists of the resolution of 9 or 10 exercises (open questions) concerning the nomenclature, properties, reactivity and synthesis of heterocycles. Each 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 (in this case, the teacher will provide the students with a communication via Elly):
-written examination in the classroom (whenever possible);
-remote written examination via 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, or references are permitted during the examination (a part from some maps previously agreed with the teacher during th course).
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.
Other information
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