Coniine - Structural elucidation

Synthesis and structural elucidation

1. CONIINE D. Jim Livingston Asst. Prof. of Chemistry, St. John’s College.

2. Obtained from the plants Conium maculatum (hemlock poison), Sarracenia flava , Aethusa cynapium . Highly toxic disruption of the central nervous system Death occurs by respiratory paralysis OCCURENCE

3. Mol. Formula: C8H17N . RXN I : Reacting with benzoyl chloride, a mono benzoyl derivative is obtained, which on further treatment with phosphorous tribromide gives dihalo compound and benzonitrile . This reaction is characteristic of cyclic 2 amines. (Von-Braun’s 2 nd method) Structural Elucidation

4. Hence, this reaction indicated the presence of secondary nitrogen atom in the ring. RXN : II On reaction with Zinc, it gives conyrine (C8H11N). This on further oxidation with KMNO4 gives pyridine-2-carboxylic acid. Conyrine must be 2- substituted pyridine. (C6H5NO2) There must be an alkyl group having three carbons in the side chain. (2 nd position)

5. Conyrine – pyridine derivative. Coniine –Six hydrogens more than conyrine . piperidine derivative. Comparing M.F. of conyrine C8H11N and pyridine-2-carboxylic acid C6H5NO2 A shortage of 2 carbons and 6 hydrogens . The side chain have the composition C3H7 . Two Possibilities: n - propyl Iso propyl

6. RXN: III Heating with hydroiodic acid at 300 C gives n- octane . RXN: IV Hofmann’s exhaustive degradation gives n-octane . Iso -propyl group iso -octane. Hence, the side group in coniine is n-propyl group .

7. 2-propylpiperidiene Structure

8. used to kill condemned prisoners in ancient Greece Greek philosopher Socrates was executed to death by drinking poison Hemlock. (399BC) Historical Background

9. Ladenberg synthesis 1886 Bergmann synthesis 1932 Synthesis

10. Ladenberg synthesis - 1886 I Step : n- methylpyridiniumiodide to 2-methyl pyridine Ladenberg Rearrangement Mechanism : Hofmann- Martius rearrangement II Step : 2-methylpyridine to 2-propenyl pyridine Knoevenagel type

11. Methylpyridinium iodide was heated at 300 C to obtain 2-methylpyridine. This On treatment with acetaldehyde with Lewis base to give 2-propenyl pyridine. Reduction of the 2-propenyl pyridine yielded coniine . 2-propenyl pyridine coniine III Step : reduction by metal/alcohol to form alkyl compound

12. Bergmann Synthesis - 1932 I Step: 2-methyl pyridine to alkyl lithium compound II step: Nu. Substitution to form 2-propylpyridine III Step: Reduction of pyridine moiety

13. References

14. Homolytic Mechanisms of Aromatic Rearrangements. Part II.* Thermal Rearrangements of I - Alkylpyridinium Salts (The Ladenburg Rearrangement) P . A. Claret and Gareth H. Williams*t Birkbeck College, Malet Street, London W.C. J. Chem. SOC. (C), 1969 http://www.chm.bris.ac.uk/motm/hemlock/synthesis.htm Pyridines and their Benzo Derivatives: (iii) Reactivity of Substituents, B.C. Uff , Comprehensive Heterocyclic Chemistry, 1984