Hexane-2,5-dione explained

Hexane-2,5-dione should not be confused with Acetylacetone.

2,5-Hexanedione (Acetonylacetone) is an aliphatic diketone. It is a colorless liquid. In humans, it is a toxic metabolite of hexane and of 2-hexanone.

Symptoms of poisoning

The chronic toxicity of hexane is attributed to hexane-2,5-dione. The symptoms are tingling and cramps in the arms and legs, followed by general muscular weakness. In severe cases, atrophy of the skeletal muscles is observed, along with a loss of coordination and vision problems.[1]

Similar symptoms are observed in animal models. They are associated with a degeneration of the peripheral nervous system (and eventually the central nervous system), starting with the distal portions of the longer and wider nerve axons.

Mechanism of action

2,5-Hexanedione reacts with lysine residues in axonal proteins by Schiff base formation followed by cyclization to give pyrroles. Oxidation of the pyrrole residues then causes cross-linking and denaturation of proteins, which perturbs axonal transport and function and causes damage to nerve cells.

Synthesis

2,5-Hexanedione has been prepared in several ways.[2] A common method involves hydrolysis of 2,5-dimethylfuran, a glucose derived heterocycle.[3]

Uses

Acetonylacetone can be used in the synthesis of isocarboxazid, rolgamidine, and mopidralazine. Treatment with P4S10 gives 2,5-dimethylthiophene.

Notes and References

  1. Couri D, Milks M. "Toxicity and metabolism of the neurotoxic hexacarbons n-hexane, 2-hexanone, and 2,5-hexanedione" Annu. Rev. Pharmacol. Toxicol. 1982;22:145-66.
  2. http://www.prepchem.com/synthesis-of-2-5-hexanedione/ Primary: Systematic organic chemistry, by W. M. Cumming, 194, 1937.
  3. 10.15227/orgsyn.016.0025. 2,5-Dimethylpyrrole. D. M. . Young. C. F. H.. Allen. Organic Syntheses. 16. 25. 1936.