Organic Chemistry - Heterocyclic Compounds - Ring Reactions PDF

Organic Chemistry Heterocyclic Compounds Heterocyclic Ring Reactions | Lec.16 Heterocyclic Ring Reactions Contents : Resemblance With Phenol 3 Reaction of pyrrole with aldehydes and ketones 9 Reactivity Comparison with Benzene 18 Heterocyclic Ring Reactions Resemblance With Phenol: 1- Riemer Tiemann...

Organic Chemistry Heterocyclic Compounds Heterocyclic Ring Reactions | Lec.16 Heterocyclic Ring Reactions Contents : Resemblance With Phenol 3 Reaction of pyrrole with aldehydes and ketones 9 Reactivity Comparison with Benzene 18 Heterocyclic Ring Reactions Resemblance With Phenol: 1- Riemer Tiemann Reaction On reaction with CHCl3 and strong alkali Pyrrole is giving two type of reactions. The first one is the formylation at position 2 and other one is formation of 3-chloro pyridine. Heterocyclic Ring Reactions Heterocyclic Ring Reactions In both the cases carbine is generated; second one is carbine insertion reaction. Heterocyclic Ring Reactions 2- Kolbe Schmitt Reaction Resemblance with amines, hoffmann martiu Rearrangement Heterocyclic Ring Reactions Heterocyclic Ring Reactions Mechanism Reaction of pyrrole with aldehydes and ketones Heterocyclic Ring Reactions Reaction of pyrrole with aldehydes and ketones: Aldehydes and ketones condense with unsubstituted pyrrole at apposition in acidic medium to give dipyrryl methane. The condensation may continue to give tetramer (4 pyrrole rings connected by methine bridge). The tetramers are known as porphyrinogens, they are stable, planar structures that can accommodate a wide range of metal ions. Heterocyclic Ring Reactions Heterocyclic Ring Reactions The order of reactivity in five-membered heterocycles is : Pyrrole > Furan > Thiophene > Benzene (for comparison). The order of aromaticity is Benzene > Thiophene > Furan > Pyrrole Heterocyclic Ring Reactions The greater reactivity of pyrrole towards electrophiles is attributed to the greater electron releasing ability of trivalent nitrogen (when linked by three bonds) making ring carbon atoms electron rich and to the greater stabilization of transition states involving positive charge on the tetravalent nitrogen atom Heterocyclic Ring Reactions Furan is also reactive (although less than pyrrole) towards electrophiles (preferably at C-2) and the reason is the same as for pyrrole. Since oxygen is more electronegative than nitrogen and withdraws electrons from the ring carbon atoms, the positive charge is less readily accommodated by oxygen atom than by nitrogen atom. The transition state with oxygen atom positively charged resulting from the electrophilic attack on furan is, therefore, less stable than that of pyrrole. Thus, furan is less reactive towards electrophiles than pyrrole as phenol is less reactive than aniline. Heterocyclic Ring Reactions Heterocyclic Ring Reactions Thiophene is less reactive than even furan towards electrophiles. The sulfur atom is less electronegative than the oxygen atom and therefore withdraws electrons less readily from the ring carbon atoms. Moreover, +M effect of sulfur (mesomeric electron release from sulfur) is smaller than that of oxygen because of not effective overlapping of differently sized p-orbitals of carbon and sulfur than in carbon and oxygen. Heterocyclic Ring Reactions The relative reactivity of thiophene and furan can be shown by the following reaction in which nitration with mild nitrating agent occurs only in furan nucleus at C-2. Reactivity Comparison with Benzene Heterocyclic Ring Reactions Reactivity Comparison with Benzene: The electrophilic substitution in thiophene is much easier than in benzene. Benzene is much less reactive than the five-membered heterocycles towards electrophiles. The reactivity depends on: 1. The stabilisation energy. 2. The stability of transition state. Heterocyclic Ring Reactions The lower reactivity of benzene towards electrophiles is attributed partly to the greater resonance stabilisation energy of benzene. The higher energy of the transition state of benzene than the structurally related transition states of five-membered heterocycles is also responsible for the lower reactivity of benzene. The stability order of the transition states has been observed to be as follows Heterocyclic Ring Reactions Furan is not very aromatic therefore if there is a possibility of forming stable bonds such as C-0 bonds by addition, this may be preferred to substitution i.e. tendency to give addition products rather than substitution products increases as aromaticity decreases. The order of aromaticity is Benzene > Thiophene > Furan > Pyrrole Heterocyclic Ring Reactions In comparison to benzene the order of reactivity in electrophilic substitution is as follows: Pyrrole > Furan > Thiophene > Benzene The 2 & 5 (α) positions are more reactive than 3 & 4 (β) Positions as in pyrrole the intermediate results from electrophilic attack at C2 can be stabillized by three resonance structure while the intermediate results from the attack C3 is only satbilized by two resonance structures. Thus the former is more preferred. Heterocyclic Ring Reactions Friedel-Crafts Alkylation: Furan does not undergo Friedel-Crafts alkylation. The catalysts required in Friedel-Crafts alkylation affect polymerization because of the acid sensitivity of furan. The alkylation is affected by alkenes at the position-2 in the presence of mild catalysts (phosphoric acid or boron trifluoride) Heterocyclic Ring Reactions Heterocyclic Ring Reactions Note: Furans substituted with electron-withdrawing substituents at the position-2 undergo Friedel-Crafts alkylation at room temperature providing a mixture of alkylfurans.