Medical Chemistry Seminar 2024 PDF

Week 8 Seminar 1 Medical Chemistry Seminar 2024 Aromatic Compounds Department of Medical Chemistry UD Faculty of Medicine What is the concept of aromaticity, and what conditions must a compound meet to be co...

Week 8 Seminar 1 Medical Chemistry Seminar 2024 Aromatic Compounds Department of Medical Chemistry UD Faculty of Medicine What is the concept of aromaticity, and what conditions must a compound meet to be considered aromatic? 1.Is cyclic. 2.Is planar. 3.Has a conjugated π-electron system (Each atom in the ring must have an unhybridized p orbital (sp2). 4.Follows Hückel’s Rule: It must have 4n+2 π-electrons, where n is a non- negative integer. How are aromatic compounds classified? Simple aromatic hydrocarbons: Compounds like benzene (C₆H₆) that contain only carbon and hydrogen. Heteroaromatic compounds: Aromatic rings that include atoms other than carbon, such as nitrogen, oxygen, or sulfur (e.g., pyridine, furan). Polycyclic aromatic hydrocarbons (PAHs): Compounds with multiple fused aromatic rings (e.g., naphthalene, anthracene). What is the structure of benzene, and how does it differ from alkenes? Benzene (C₆H₆) has a planar, hexagonal ring structure Each C atom is sp2 hybridized. The bond angle is 120º bonds are delocalized, meaning that the electrons are shared equally across the entire ring this delocalization gives benzene its unique stability. In contrast, alkenes have localized double bonds and no delocalization. Why is benzene more stable than expected? Benzene is more stable because of resonance; the π-electrons are delocalized over the entire ring, which lowers the overall energy of the molecule. This is referred to as resonance stabilization. Determine whether the following compounds are aromatic or not. cyclopentadiene benzene cyclooctatetraene not aromatic aromatic not aromatic naphthalene phenanthrene aromatic aromatic What are heteroaromatic compounds, and why are they important? Heteroaromatic compounds are aromatic rings that contain atoms other than carbon, such as nitrogen, oxygen, or sulfur. These heteroatoms contribute lone pairs of electrons to the π-system, helping to maintain aromaticity. They are essential in biological molecules (e.g., in DNA bases like adenine and guanine) and are widely used in pharmaceuticals. Can you give examples of common heteroaromatic compounds? Pyridine Furan Thiophene Pyrrole How do the nitrogen atoms in pyridine and pyrrole contribute to the aromaticity of the ring? Pyridine: Pyrrole: How do we name simple aromatic compounds like benzene and its derivatives? Benzene is the simplest aromatic hydrocarbon. When substituents are attached, the compound is named based on the substituent followed by “benzene”. CH3 NH2 methylbenzene aminobenzene hydroxybenzene toluene aniline phenol What is the difference between ortho-, meta-, and para- positions in disubstituted benzene rings? The terms ortho, meta, and para describe the relative positions of two substituents on a benzene ring: Ortho (o-): Substituents on adjacent carbons (positions 1 and 2). Meta (m-): Substituents separated by one carbon (positions 1 and 3). Para (p-): Substituents on opposite sides of the ring (positions 1 and 4). R R R R R R ortho or 1,2- meta or 1,3- para or 1,4- Give the structures. Name the followings. What are the two structural isomers of a monosubstituted naphthalene? a a 8 1 b 7 2 b 6 3 b 5 4 b a a OH OH a-naphthol b-naphthol 1-hydroxynaphthalene 2-hydroxynaphthalene  Naming aromatic compounds Structure Name Cl NO2 1,3-dichloro-2-nitrobenzene Cl CH3 1-methylnaphthalene or a -methylnaphthalene CH3 2-methylnaphthalene or b -methylnaphthalene What is the difference between phenyl and benzyl group ? CH2 phenyl benzyl Name the followings... 4 4 3 3N 4 3 5 2 5.. 2 2.. 5.. N N O.. 1 H H1 1 pyrrole imidazole furan 4 4.. 4 3 3 5 3N 5 5 2 2 6 2 6.. N.. N.. S.. 1 1 1 pyridine pyrimidine thiophene Name the following compounds. Identify the types of fused rings present in each structure. 4 6 5 3 1N 5 N7 4 6.. 2 2.. 8 7 N N N H 3 H 1 9 indole purine benzene + pyrrole pyrimidine + imidazole 5 4 5 4 6 3 6 3 7 1 2 7 N2 8 N 8 1 quinoline isoquinoline benzene + pyridine benzene + pyridine  What type of reactions does benzene typically undergo? H X + X - Y +H-Y SUBSTITUTION aromatic aromatic GENERAL REACTION MECHANISM: SE The aromatic structure is preserved in the reactions! Provide examples of common reactions. 1, Nitration (introduction of nitro group, – NO2 ) H NO2 + HNO3 H2SO4 +H-O-H nitric acid nitrobenzene 2, Sulfonation (production of sulfonic acid) H SO3H + H2SO4 +H-O-H sulfuric acid benzenesulfonic acid 3, Chlorination (introduction of chlorine) H Cl FeCl3 + Cl2 + H - Cl chlorine chlorobenzene Explain how different substituents on a benzene ring affect the rate of electrophilic substitution. Nitration of benzene and its monosubstituted derivatives yields various reaction rates. Explain how various substituents on a benzene ring influence the position of incoming groups during electrophilic substitution. Classify common substituents as either activators or deactivators, and explain how they determine the position (ortho, meta, or para) of subsequent substitutions. -CH3 activating; o/p director deactivating; m director -NO2 -COOH deactivating; m director -Br deactivating; o/p director activating; o/p director -OH -CN deactivating; m director -NH2 activating; o/p director Write the chemical reaction for: 1. Bromination of benzene Br FeBr3 + Br2 + HBr 2. Chlorination of phenol OH OH Cl + HCl + Cl2 OH + HCl Cl 3. Nitration of benzene NO2 + HNO3 H2SO4 + H2O 4. Chlorination of toluene H3C + HCl H3C Cl + Cl2 H3C + HCl Cl 5. Sulfonation of nitrobenzene NO2 NO2 SO3H + H2SO4 + H2O 6. Methylation of phenol HO + HI OH CH3 + CH3- I HO + HI H3C 7. Oxidation of toluene H O HO O CH3 HO - CH2 C C Write the balanced chemical equations for the following reactions: 1, Nitration of benzene 2, Chlorination of nitrobenzene 3, Methylation of chlorobenzene Compare the rate of the reactions! NO2 1, + HNO3 H2SO4 + H2O NO2 NO2 2, FeCl3 + Cl2 + HCl Cl Cl Cl 3, + CH3I AlCl3 + HI CH3 Cl + HI V1 > V3 > V2 H3C  MCQ 1. What is the empirical formula of toluene? A. C7H8 B. C7H7 C. C8H10 D. C8H8 E. C10H8 A 2. What is the formula of the benzyl radical? A. B. CH2 C. D. E. B 3. What is the name of the following compound? A. o-cresol CH3 B. catechol CH3 C. o-xylene D. m-cresol E. p-xylene C 4. What is the mechanism of the reaction? H Cl FeCl3 + Cl2 + H - Cl A. Nucleophilic substitution B. Nucleophilic addition C. Electrophilic elimination D. Electrophilic substitution E. Radical addition D 5. What is the main product of the nitration of toluene? A. m-nitrotoluene B. o- and m-nitrotoluene C. m- and p-nitrotoluene D. o- and p-nitrotoluene E. o-, m,- and p-nitrotoluene D 6. Which compound gives the fastest electrophilic substitution reaction? A. toluene B. benzene C. nitrobenzene D. benzenesulfonic acid E. benzoic acid A 7. Which compound gives the slowest electrophilic substitution reaction? A. toluene B. benzene C. nitrobenzene D. aniline E. phenol C 8. What is the name of the compound? 4 3 A. pyrrole B. pyridine 5 2 C. imidazole.. N D. pyrimidine H 1 E. pyrrolidine A 9. Select the formula of purine. A B C D E 4 5 4 6 5 4 4 5 5 3 6 3 1N 5 N7 3 N 6 3N 6 6.. 2 7 1 2 2 4.. 8 N N 7 N2 2 7 7 H 8 N N N 1 3 H 8 1 N 9 1 8 C