Organic Chemistry Heterocyclic Compounds Reactions of Furan & Derivative PDF

Organic Chemistry III Heterocyclic Compounds Reactions of furan & Derivative of pyridine | Lec.10 Reactions of furan & Derivative of pyridine Contents : Reactions of furan 3 Derivative of pyridine 11 Reactions of furan Electrophilic Aromatic substitution Reactions of furan: 1) Nitration Furan is nit...

Organic Chemistry III Heterocyclic Compounds Reactions of furan & Derivative of pyridine | Lec.10 Reactions of furan & Derivative of pyridine Contents : Reactions of furan 3 Derivative of pyridine 11 Reactions of furan Electrophilic Aromatic substitution Reactions of furan: 1) Nitration Furan is nitrated with mild nitrating agent, acetyl nitrate, at low temperature. The reaction proceeds by an addition-elimination mechanism involving an intermediate, 2,5-addition product. In certain cases, the intermediate 2,5- addition product , may be isolated, if a base (pyridine) is not used to eliminate acetic acid. Reactions of furan Note: Electrophilic substitutions in 2,5-disubstituted heterocycles normally occur at the 3-position. Reactions of furan In some cases, specially with furan, electrophilic substitution occurs with the displacement of -substituent (carboxyl, acyl or halogen) Reactions of furan 2) Sulfonation Furan and its simple alkyl - derivatives are decomposed by the usual strong acid reagents, but the pyridine – sulfur - trioxide complex or dioxane can be used, and provides 2-sulfonic or 2,5disulfonic acid depending on the reaction conditions, disubstitution of furan occurring even at room temperature. However, furan substituted with an electron-withdrawing substituent at the position-2 can be sulfonated by oleum with the formation of 5-sulfonic acid derivative. Reactions of furan Reactions of furan 3) Halogenation Furan reacts vigorously with chlorine and bromine at room temperature to give polyhalogenated products, but does not react at all with iodine. The milder conditions are required for the formation of monobromo- and monochloro-furans. Bromination of furan by bromine in dimethylformamide at room temperature – smoothly produce 2 - bromo - or 2,5 - dibromo - furans. Dioxane-dibromide (Br2 + dioxane) at -5°C gives 2-bromofuran. Reactions of furan Note: Bromination of furan substituted with an electron-withdrawing substituent at the position-2 generally provides 5-bromo derivative involving an electrophilic substitution mechanism. Reactions of furan Derivative of pyridine Derivative of pyridine Derivative of pyridine: N-oxide pyridine Pyridine can be oxidized easily to N-oxide pyridine by peracids. Derivative of pyridine On the basis of dipole moment studies, N-oxide pyridine is considered as a resonance hybrid of the following structures. The -ve. charges appear at positions 2, 4 thus active towards E+ s. Derivative of pyridine As appears from the previous canonical forms, there are positive and negative charges at positions 2 and 4 thus N- oxide pyridine is more activated for electrophilic and nucleophilic attack at these positions than pyridine itself. N-oxide pyridines are very important intermediates for preparing pyridine derivatives that are difficult to prepare due to the easiness of removal of oxygen atom by reduction. For instance, nitration of pyridine is very difficult and low yielding reaction and it occurs at position 3, however using N- oxide pyridine will direct the nitration to position 4 and then the oxygen can be easily removed by reduction as shown in the following scheme. Derivative of pyridine Derivative of pyridine Problems: 1. 2-Aminopyridine can be nitrated or sulfonated under much milder conditions than pyridine itself; substitution occurs chiefly at the 5-position. Account for these facts. 2. Because of the difficulty of nitrating pyridine, 3-aminopyridine is most conveniently made via nicotinic acid. Outline the synthesis of 3-aminopyridine from beta-picoline. 3. Predict the relative basicities of amines (RCH2NH2), imines (RCH=NH), and nitriles (RCN). Derivative of pyridine 4. Like any other tertiary amine, pyridine can be converted (by peroxy-benzoic acid) into its N-oxide. In contrast to pyridine itself, pyridine N-oxide readily undergoes nitration, chiefly in the 4-position. How do you account for this reactivity and orientation?