Hexane-2,5-dione

Hexane-2,5-dione

Names
Other names 1,2-diacetylethane 'α','β'-diacetylethane acetonyl acetone diacetonyl 2,5-dioxohexane 2,5-diketohexane 2,5-hexanedione
Identifiers
CAS Number	110-13-4
3D model (Jmol)	Interactive image
ChEBI	CHEBI:85104
ChemSpider	7744
ECHA InfoCard	100.003.400
PubChem	8035
RTECS number	MO3150000
InChI InChI=1S/C6H10O2/c1-5(7)3-4-6(2)8/h3-4H2,1-2H3 Key: OJVAMHKKJGICOG-UHFFFAOYSA-N InChI=1/C6H10O2/c1-5(7)3-4-6(2)8/h3-4H2,1-2H3 Key: OJVAMHKKJGICOG-UHFFFAOYAH
SMILES O=C(C)CCC(=O)C
Properties
Chemical formula	C6H10O2
Molar mass	114.1438 g mol^−1
Appearance	colorless liquid
Density	0.973 g cm^−3, liquid
Melting point	−5.5 °C (22.1 °F; 267.6 K)
Boiling point	191.4 °C (376.5 °F; 464.5 K)
Solubility in water	≥ 10 g/100 mL (22 °C)
Structure
Molecular shape	trigonal planar at carbonyl tetrahedral elsewhere
Hazards
Flash point	78 °C (172 °F; 351 K)
Related compounds
Related diketones	acetylacetone
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Infobox references

2,5-Hexanedione (Acetonylacetone) is an aliphatic diketone. In human, 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 problems of vision.^[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

It appears that the neurotoxicity of 2,5-hexanedione resides in its γ-diketone structure since 2,3-, 2,4-hexanedione and 2,6-heptanedione are not neurotoxic, while 2,5-heptanedione and 3,6-octanedione and other γ-diketones are neurotoxic.^[2] In fact, higher α-diketones, like 2,3-pentanedione and 2,3-hexanedione, are found in small amounts in various foods. They are used as aroma components in alcohol-free beverages and in baked goods.^[3]

2,5-Hexanedione reacts with critical lysine residues in axonal proteins by Schiff base formation followed by cyclization to give pyrroles. Oxidation of the pyrrole residues then causes cross-linking between two n-hexane-modified proteins. The resulting denaturation of proteins perturbs axonal transport and function and causes damage to nerve cells.^[4]

Synthesis

A Process for preparing 2,5-hexanedione has been described:^[5][6]

Uses

Acetonylacetone has a few uses, for example, in the synthesis of Isocarboxazid^[7] and Rolgamidine.^[8]

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. Stephen R Clough; Leyna Mulholland (2005), "Hexane", Encyclopedia of Toxicology, 2 (2nd ed.), Elsevier, pp. 522–525
3. Hardo Siegel; Manfred Eggersdorfer (2007), "Ketones", Ullmann's Encyclopedia of Industrial Chemistry (7th ed.), Wiley, p. 16
4. Wolfgang Dekant; Spiridon Vamvakas (2007), "Toxicology", Ullmann's Encyclopedia of Industrial Chemistry (7th ed.), Wiley, p. 23
5. U.S. Patent 3,819,714
6. http://www.prepchem.com/synthesis-of-2-5-hexanedione/ Primary: Systematic organic chemistry, by W. M. Cumming, 194, 1937.
7. U.S. Patent 2,908,688
8. U.S. Patent 4,140,793