2,5-Hexanedione Property

Melting point:

-6--5 °C (lit.)

Boiling point:

191 °C (lit.)

Density 

0.973 g/mL at 25 °C (lit.)

vapor pressure 

0.43 mm Hg ( 20 °C)

refractive index 

n20/D 1.425(lit.)

Flash point:

174 °F

storage temp. 

Store below +30°C.

solubility 

alcohol: miscible; Miscible with water, ethylalcohol and ether,ess. oils and perfume materials.

form 

Liquid

color 

Clear yellow to brown

Odor

Pleasant, sweet-ethereal odor.

PH

6.1 (10g/l, H2O, 20℃)

explosive limit

1.5%(V)

Water Solubility 

miscible

Merck 

14,71

BRN 

506525

Stability:

Stable. Incompatible with strong bases, strong reducing agents, strong oxidizing agents. Flammable.

InChIKey

OJVAMHKKJGICOG-UHFFFAOYSA-N

LogP

-0.270

CAS DataBase Reference

110-13-4(CAS DataBase Reference)

NIST Chemistry Reference

CH3COCH2CH2COCH3(110-13-4)

EPA Substance Registry System

2,5-Hexanedione (110-13-4)

Safety

Hazard Codes 

Xn,Xi

Risk Statements 

36/38-48/20/21/22-36/37/38

Safety Statements 

23-26-36/37-37/39

WGK Germany 

2

RTECS 

MO3150000

F 

8

Autoignition Temperature

400 °C

TSCA 

Yes

HS Code 

29141990

Toxicity

LD50 orally in rats: 2.7 g/kg (Smyth, Carpenter)

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H373May cause damage to organs through prolonged or repeated exposure

Precautionary statements

P202Do not handle until all safety precautions have been read and understood.

P260Do not breathe dust/fume/gas/mist/vapours/spray.

P301+P312IF SWALLOWED: call a POISON CENTER or doctor/physician IF you feel unwell.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P308+P313IF exposed or concerned: Get medical advice/attention.

2,5-Hexanedione Chemical Properties,Usage,Production

Synthesis

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

Mechanism of Toxicity

Identification of 2,5-hexanedione as the major neurotoxic metabolite of n-hexane proceeded rapidly after its discovery as a urinary metabolite. 2,5-Hexanedione has been found to produce a polyneuropathy indistinguishable from n-hexane. 2,5-Hexanedione is many times more potent than n-hexane, the parent compound, in causing neurotoxicity in experimental animals. 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.

Description

2, 5-hexadione (2,5HD) is a flammable, transparent colorless to amber water-soluble liquid that is a multifunctional platform chemical, a major metabolite of n-hexane, and a key intermediate for the production of high energy density aviation fuels from biomass resources. It has a sweet aromatic smell and neurotoxic effects. It can be used as a high energy density fuel additive of platform chemicals, and can induce ovarian granulosa cell cycle arrest to establish ovarian injury model. It can also be used for biological monitoring of 2, 5-hexanedione exposure to n-hexane^[1-2].

Chemical Properties

colourless to pale yellow liquid

Uses

2,5-Hexanedione is used as a reagent in the preparation of trans-2,5-dimethylpyrrolidine. It is also used in the synthesis of 2,5-dimethylpyrroles. Further, it plays an important role as a reagent used for the protection of amino groups in amino sugars and nucleosides. In addition to this, it is used in the preparation of five-membered heterocycles like indane-type and benzannulated systems. It is also employed as a precursor in Diels-alder cycloaddition reactions.

Uses

It was used as reference standard for the determination of 2,5HD in human urine using gas chromatography-electron capture detection and gas chromatography-mass selective detection.

Uses

It is the metabolite implicated in n-hexane neurotoxicity.

Application

2,5-Hexanedione is a neurotoxic metabolite of n-hexanes and methyl n-butyl ketone. It is also used as the starting material for diels-alder cycloaddition reactions, such as a reactions with amines to form 2,5-dimethylpyrroles.

Preparation

20 g of diethyl 2,3-diacetylbutanedioate are mechanically shaken for several days with 250 ml (excess) of 5% aqueous sodium hydroxide, and until no diethyl 2,3-diacetylbutanedioate separates on acidification of a sample with dilute hydrochloric acid. The solution is then saturated with potassium carbonate and extracted with ether, the extract is washed with brine to remove alcohol, dried over calcium chloride, and distilled, the fraction 192-198° C being retained. You can get 2,5-Hexanedione with a yield of 70%. Colourless liquid; agreeable odour; miscible with water, alcohol and ether; m.p. 9° C; b.p. 194° C; d=0.973 g/ml at 20° C.

Definition

ChEBI: A diketone that is hexane substituted by oxo groups at positions 2 and 5. It is a toxic metabolite of hexane and of 2-hexanone

Synthesis Reference(s)

Canadian Journal of Chemistry, 59, p. 945, 1981 DOI: 10.1139/v81-137
Journal of the American Chemical Society, 105, p. 7200, 1983 DOI: 10.1021/ja00362a047
Tetrahedron Letters, 15, p. 4149, 1974

General Description

Clear colorless to amber liquid with a sweet aromatic odor.

Air & Water Reactions

Highly flammable. Water soluble.

Reactivity Profile

Acetonylacetone is incompatible with oxidizing agents. Acetonylacetone is also incompatible with strong bases and strong reducing agents.

Fire Hazard

Acetonylacetone is combustible.

Purification Methods

Purify it by dissolving in Et2O, stiring with K2CO3 (a quarter of the weight of dione), filtering, drying over anhydrous Na2SO4 (not CaCl2), filtering again, evaporating the filtrate and distilling it in a vacuum. It is then redistilled through a 30cm Vigreux column (p 11, oil bath temperature 150o). It is miscible with H2O and EtOH. The dioxime has m 137o (plates from *C6H6), the mono-oxime has b 130o/11mm, and the 2,4-dinitrophenylhydrazone has m 210-212o (red needles from EtOH). It forms complexes with many metals. [Werner et al. Chem Ber 22 2100 1989, for enol content see Gero J Org Chem 19 1960 1954, Beilstein 1 IV 3688.]

References

[1] KAIXUAN ZHOU, Xin L, Chenggong Sun. Directed glycerol conversion to 2,5-hexanedione and more advanced poly-oxygenates as platform chemicals and high energy–density fuel additives[J]. Chemical Engineering Journal, 2022, 430: Article 132981. DOI:10.1016/j.cej.2021.132981.
[2] XUEMING XU. The Wnt/β-catenin pathway is involved in 2,5-hexanedione-induced ovarian granulosa cell cycle arrest[J]. Ecotoxicology and Environmental Safety, 2023, 268: Article 115720. DOI:10.1016/j.ecoenv.2023.115720.