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Department of Chemistry, Anugrah Memorial College, Gaya
B. Sc. Chemistry (Hons) Part – III Paper: VII – Organic Chemistry (Gr. – B) Unit II: Heterocyclic Compounds Topic – Pyridine Lecture: #2 By: Dr. Rajesh Ranjan Pandey (Assistant Professor)
PYRIDINE (In Continuation)
Lecture - 2 Contents: Synthesis (#6 - 14)
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Synthesis of Pyridine (In Continuation):
6. From acroline: Pyridine can be prepared by the reaction of acroline (Acrylaldehyde, Prop-2-enal) and ammonia.
7. From β-Picoline: β-picoline on oxidation with potassium dichromate and sulphuric acid gives nicotinic acid, which on decarboxylation with calcium oxide gives pyridine.
8. Chichibabin synthesis: First, acrolein is formed in a Knoevenagel condensation from the acetaldehyde and formaldehyde. The acrolein is then condensed with acetaldehyde and ammonia to give dihydropyridine, which is oxidized with a solid-state catalyst to pyridine. This process is carried out in a gas phase at 400–450 °C.
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9. By Diels-Alder reaction: Pyridine derivatives can be formed in a 4-1 condensation i.e. [4+2] cycloaddition by the reaction of dienes with nitriles.
10. Hantzsch pyridine synthesis: Its typically uses a 2:1:1 mixture of a β-keto acid (often acetoacetate), an aldehyde (often formaldehyde), and ammonia or its salt as the nitrogen donor. First, a double hydrogenated pyridine is obtained, which is then oxidized to the corresponding pyridine derivative.
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Mechanism:
11. By Condensation of 1,5-dicarbonyls with ammonia: Condensation of 2,3-ene-1,5-diones with ammonia gives 1,4-dihydropyridine which followed by oxidation give corresponding pyridine derivative.
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The oxidation step can be avoided by using hydroxylamine instead of ammonia.
12. The Guareschi Synthesis: Pyridines derivatives (3-cyano-2–pyridones) are formed from the interaction between a 1,3-dicarbonyl compound and a cyanoacetamide.
13. Guareschi-Thorpe condensation: 2-Pyridone formation from the condensation of cyanoacetic ester with diketone in the presence of ammonia is known as Guareschi-Thorpe condensation.
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14. Kondrat'eva pyridine synthesis: Oxazole reacts with a dienophile to form pyridine with elimination of water. The reaction is an example of a Diels-Alder reaction.
Mechanism: By Zerong Wang
The oxazole (1) reacts with the dienophile (2) to form the bicycle (3.) Electron rearrangement leads to a simple ring system. With elimination of water, the pyridine derivative (4) is then formed with aromatization.
(To be continued…)