This document describes the chemical structure and synthesis of coniine. Coniine is a highly toxic piperidine alkaloid obtained from hemlock plants. The document outlines reactions that determined coniine has the molecular formula C8H17N and is a 2-propylpiperidine. It also describes three historical syntheses of coniine: the Ladenburg synthesis from 1886, the Bergmann synthesis from 1932, and a more recent nucleophilic substitution synthesis. Coniine was famously used to execute the Greek philosopher Socrates in 399 BC and is still used in some countries to carry out capital punishment.

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

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 20 amines. (Von-
Braun’s 2nd method)

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. (2nd 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 3000C 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

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

9.  Ladenberg synthesis
 1886
 Bergmann synthesis
 1932

10. 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 3000C 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. I Step: 2-methyl pyridine to alkyl lithium compound
II step: Nu. Substitution to form
2-propylpyridine
III Step: Reduction of pyridine moiety

15.  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.h
tm
 Pyridines and their Benzo Derivatives: (iii)
Reactivity of Substituents, B.C. Uff,
Comprehensive Heterocyclic Chemistry, 1984