1-Chlorohexane
[CAS# 544-10-5]

Identification

• Classification: Chemical reagent >> Organic reagent >> Halogenated aliphatic hydrocarbon
• Name: 1-Chlorohexane
• Synonyms: Hexyl chloride
• Molecular Formula: C₆H₁₃Cl
• Molecular Weight: 120.62
• CAS Registry Number: 544-10-5
• EC Number: 208-859-5
• SMILES: CCCCCCCl

Properties

• Density: 0.9±0.1 g/cm³ Calc.^*, 0.879 g/mL (Expl.)
• Melting point: -94 °C (Expl.)
• Boiling point: 133.9±3.0 °C 760 mmHg (Calc.)^*, 133 - 134 °C (Expl.)
• Flash point: 26.7 °C (Calc.)^*, 27 °C (Expl.)
• Index of refraction: 1.414 (Calc.)^*, 1.419 (Expl.)

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS02 Warning
• Risk Statements: H226-H412
• Safety Statements: P210-P233-P240-P241-P242-P243-P273-P280-P303+P361+P353-P370+P378-P403+P235-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	3	H226
Chronic hazardous to the aquatic environment	Aquatic Chronic	3	H412
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319

• Transport Information: UN 1993

Discovery and Applications

1-Chlorohexane, also known as n-hexyl chloride, is a straight-chain primary alkyl halide with the molecular formula C₆H₁₃Cl. It appears as a colorless, flammable liquid with a characteristic odor and is primarily used as an intermediate in organic synthesis. Structurally, the chlorine atom is bonded to the terminal carbon of a six-carbon linear chain, giving the compound the typical reactivity of primary alkyl halides, favoring nucleophilic substitution reactions while being relatively resistant to elimination under mild conditions.

The synthesis of 1-chlorohexane generally involves the reaction of n-hexanol with hydrogen chloride, thionyl chloride, or phosphorus trichloride. In this substitution reaction, the hydroxyl group is replaced by a chlorine atom, producing the desired primary alkyl halide. Industrial preparations often emphasize controlling temperature, reaction time, and solvent to minimize byproducts such as hexene isomers, which can form through dehydration under acidic conditions. Proper handling is essential because 1-chlorohexane is flammable and can cause irritation upon skin or eye contact.

In organic synthesis, 1-chlorohexane serves as a versatile building block. It undergoes nucleophilic substitution reactions (S_N2) efficiently due to the accessibility of the primary carbon. Reactions with alcohols, amines, thiols, and cyanides allow the formation of hexyl ethers, amines, thioethers, and nitriles, respectively. These transformations are valuable for producing intermediates in the synthesis of pharmaceuticals, agrochemicals, and specialty chemicals. The ability to introduce a hexyl group makes it particularly useful for modifying the lipophilicity and chemical properties of target molecules.

Industrial applications of 1-chlorohexane include its use in the manufacture of surfactants, plasticizers, lubricants, and other chemical intermediates. For example, alkylation reactions with phenols or amines can produce compounds that alter surface activity, viscosity, or hydrophobicity in coatings, detergents, and cosmetic formulations. Its role in the preparation of higher molecular weight molecules highlights its importance as a precursor in processes requiring linear hexyl chains.

In the pharmaceutical sector, 1-chlorohexane is used to introduce hexyl moieties into bioactive compounds, which can influence drug solubility, membrane permeability, and metabolic stability. In agrochemical synthesis, it is used as an intermediate in the production of herbicides, insecticides, and fungicides, enhancing the chemical specificity and performance of active ingredients.

Mechanistic studies involving 1-chlorohexane provide insight into S_N2 reaction kinetics and the effects of linear primary halides on nucleophilic substitution. Its simple structure allows chemists to explore reaction conditions, solvent effects, and nucleophile strength, aiding in the optimization of laboratory and industrial synthetic routes. The compound’s moderate boiling point also facilitates purification by distillation.

Physically, 1-chlorohexane is slightly soluble in water but readily miscible with organic solvents such as ethers, alcohols, and hydrocarbons. Due to its flammability, proper precautions including storage in well-ventilated areas and the use of personal protective equipment are necessary. Environmental precautions focus on preventing its release into soil and water, as halogenated hydrocarbons can have adverse environmental effects.

The discovery and application of 1-chlorohexane underscore its value as a primary straight-chain alkyl halide. Its chemical reactivity, versatility in synthesis, and broad use in pharmaceuticals, agrochemicals, and industrial products make it a significant reagent in modern chemical processes.

References

2020. Using a Microchannel Reactor to Optimize the Production of 1-Alkyl-3-Methylimidazolium Chlorides. Catalysis in Industry, 12(3).
DOI: 10.1134/s2070050420030071

2022. Negative-mode ion mobility spectrometry—comparison of ion-molecule reactions and electron capture processes. Analytical and Bioanalytical Chemistry, 414(6).
DOI: 10.1007/s00216-022-04019-1

2020. Extrication of the Microbial Interactions of Activated Sludge Used in the Textile Effluent Treatment of Anaerobic Reactor Through Metagenomic Profiling. Current Microbiology, 77(8).
DOI: 10.1007/s00284-020-02020-4