Organic Chemistry Heterocyclic Compounds Lec.6 PDF

Organic Chemistry III Heterocyclic Compounds Pyrrole II | Lec.6 Organic Chemistry | Heterocyclic Compounds Contents : Synthesis of Pyrrole 4 Chemical properties 6 Reactivity in electrophilic substitution 7 Evidences of aromatic character in pyrrole 8 Acidic properties of pyrrole 10 Strong acids effe...

Organic Chemistry III Heterocyclic Compounds Pyrrole II | Lec.6 Organic Chemistry | Heterocyclic Compounds Contents : Synthesis of Pyrrole 4 Chemical properties 6 Reactivity in electrophilic substitution 7 Evidences of aromatic character in pyrrole 8 Acidic properties of pyrrole 10 Strong acids effect on pyrrole 11 Organic Chemistry | Heterocyclic Compounds Contents : Electrophilic substitution reactions 12 Reduction and Oxidation reactions 18 Electrophilic substitution of monosubstituted pyrrole 20 Medicinal uses 22 Furan 24 Aromaticity of Furan 25 Organic Chemistry | Heterocyclic Compounds Synthesis of Pyrrole : 4) From Furan (Commercial method): Furan passing over ammonia in presence of Aluminium oxide catalyst at high temperature 480-490 °C gives Pyrrole. Organic Chemistry | Heterocyclic Compounds 5) From acetylene: By passing a mixture of acetylene and ammonia through a red hot tube. Organic Chemistry | Heterocyclic Compounds Chemical properties : Pyrrole is aromatic and more reactive than benzene. It gives electrophilic substitution reactions such as halogenation, nitration ,etc. It also undergoes diazotization and Reimer-Tiemann reactions, while benzene does not. Organic Chemistry | Heterocyclic Compounds Reactivity in electrophilic substitution : In comparison to benzene, pyrrole is more reactive thus the substitution is easier and milder reagents can be used. The increased reactivity is a result of resonance which pushes the electrons from the N-atom into the ring making the C-atoms of pyrrole ring more electron rich than in case of benzene. In fact pyrrole resembles most reactive benzene derivatives (phenols and amines) Organic Chemistry | Heterocyclic Compounds Evidences of aromatic character in pyrrole : 1. All ring bonds are intermediates between single & double bonds. 2. It tends to react by electrophilic substitution Organic Chemistry | Heterocyclic Compounds 3. Its exceptional lack of basicity and strong acidity as a secondary amine compared to the aliphatic analog (pyrrolidine). This can be explained on the basis of participation of N lone pair in aromatic sextet, thus the dipole moment of pyrrole compared with pyrrolidine. Organic Chemistry | Heterocyclic Compounds Acidic properties of pyrrole : Due to participation of N lone pair in aromaticity, pyrrole has exceptionally strong acidic properties for a secondary amine for instance it can react with strong bases (KOH) or Grignard reagent (RMgX) in inert solvents, and with sodium hydride, to give salt-like compounds which can be used to alkylate or acylate the nitrogen atom as shown below: Organic Chemistry | Heterocyclic Compounds Strong acids effect on pyrrole : Pyrrole is sensitive to strong acids, protonation occurs at carbons not at N. This is due to protonation occurs at C-2 and the resulting protonated molecule will add to another unprotonated pyrrole molecule this continues to give pyrrole trimer. This reaction is considered as electrophilic addition to pyrrole. Organic Chemistry | Heterocyclic Compounds Electrophilic substitution reactions : Pyrrole tends to react by electrophilic substitution due appearance of –ve charge on carbon atoms (2 & 3) due to delocalization as shown in the following resonance structures: Organic Chemistry | Heterocyclic Compounds Electrophilic substitution normally occurs at a carbon atoms instead of at the nitrogen. Also it occurs preferentially at C-2 (the position next to the heteroatom) rather than at C-3 (if position 2- is occupied it occurs at position 3). This is due to attack at C-2 gives more stable intermediate (it is stabilized by three resonance structure) than the intermediate resulted from C-3 attack (it is stabilized by two resonance structure). Organic Chemistry | Heterocyclic Compounds Pyrrole undergoes electrophilic substitution reaction at 2nd position C2 Attack – more stable C3 attack – less stable C2 attack gives more resonance structures than C3 Organic Chemistry | Heterocyclic Compounds Organic Chemistry | Heterocyclic Compounds Organic Chemistry | Heterocyclic Compounds Organic Chemistry | Heterocyclic Compounds Reduction and Oxidation reactions : 1. Reduction 2. Oxidation Organic Chemistry | Heterocyclic Compounds 3. Ring expansion reaction Organic Chemistry | Heterocyclic Compounds Electrophilic substitution of monosubstituted pyrrole: a) Monosubstituted parole with electron withdrawing group Organic Chemistry | Heterocyclic Compounds b) Monosubstituted parole with election donating group Organic Chemistry | Heterocyclic Compounds Medicinal uses : 1. Proline A major amino acid found in cartilage and is important for maintaining youthful skin as well as repair of muscle, connective tissue and skin damage. An essential component of collagen and is important for proper functioning of joints and tendons. 2. Nicotine A stimulant and potent parasympathomimetic (Cholinergic) alkaloid. It is used for smoking cessation to relieve withdrawal symptoms. Organic Chemistry | Heterocyclic Compounds 3. Glycopyrrolate, anticholinergic drug: used in Peptic ulcer. 4. Atorvastatin used in management of high cholesterol and high blood pressure. Organic Chemistry | Heterocyclic Compounds Furan : Properties 1. Aromaticity Organic Chemistry | Heterocyclic Compounds Aromaticity of Furan : Furan have 4C and 1O, all are sp2 hybridized. sp2 hybridization is planar, it makes a planar furan ring structure. Each ring atom also contains unhybridized p orbital that is perpendicular to the plane of σ bonds (plane of ring). Here p orbitals are parallel to each other, so overlapping btwn p orbitals is possible. The total nu of non bonding e- are 6 (4 of four C, 2 from one O) The resonance of 6 e-follows the Hückel's rule. So the furan is aromatic. Note: nu = number