(Hons) Part – III Paper: VII – Organic Chemistry (Gr

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1 Department of Chemistry, Anugrah Memorial College, Gaya B. Sc. Chemistry (Hons) Part – III Paper: VII – Organic Chemistry (Gr. – B) Unit II: Heterocyclic Compounds Topic – Pyrrole Lecture: #2 By: Dr. Rajesh Ranjan Pandey (Assistant Professor) PYRROLE (Continuation) Lecture - 2 Contents: Preparations (in continuation: 5 - 10) 2 Preparations (in continuation): 5. From Succinimide: Pyrrole is obtained by the distillation of succinimide over zinc dust. 6. From alkynes: Pyrrole can be prepared by passing a mixture of acetylene and ammonia over red hot tube. Pyrroles can also be prepared by silver-catalyzed cyclization of alkynes with isonitriles, where R2 is an electron-withdrawing group, and R1 is an alkane, aryl group, or ester. The reaction is proposed to proceed via a silver acetylide intermediate. This method is analogous to the azide–alkyne click chemistry used to form azoles. 3 7. Van Leusen reaction: The Van Leusen reaction can be used to form pyrroles, by reaction of tosylmethyl isocyanide (TosMIC) with an enone in the presence of base, in a Michael addition. A 5-endo cyclization then forms the 5-membered ring, which reacts to eliminate the tosyl group. The last step is tautomerization to the pyrrole. 8. Barton–Zard synthesis: The Barton–Zard synthesis proceeds in a manner similar to the Van Leusen synthesis. An isocyanoacetate reacts with a nitroalkene in a 1,4-addition, followed by 5-endo-dig cyclization, elimination of the nitro group, and tautomerisation. Mechanism: 4 9. Hantzsch pyrrole synthesis: The Hantzsch pyrrole synthesis is the reaction of β-ketoesters with ammonia (or primary amines) and α-haloketones to give substituted pyrroles. Mechanism: 5 10. Piloty–Robinson pyrrole synthesis: In the Piloty–Robinson pyrrole synthesis, two equivalents of an aldehyde and hydrazine react to form a pyrrole with substituents at the 3 and 4 positions. The aldehyde reacts with the diamine to an intermediate di-imine (R–C=N−N=C– R). In the second step, a [3,3]-sigmatropic rearrangement takes place between. Addition of hydrochloric acid leads to ring closure and loss of ammonia to form the pyrrole. In one modification, propionaldehyde is treated first with hydrazine and then with benzoyl chloride at high temperatures and assisted by microwave irradiation. (To be continued…) .

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