Isobutyl chloride
[CAS# 513-36-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Halogenated aliphatic hydrocarbon
• Name: Isobutyl chloride
• Synonyms: 1-Chloro-2-methylpropane
• Molecular Formula: C₄H₉Cl
• Molecular Weight: 92.57
• CAS Registry Number: 513-36-0
• EC Number: 208-157-9
• SMILES: CC(C)CCl

Properties

• Density: 0.9±0.1 g/cm³ Calc.^*, 0.883 g/mL (Expl.)
• Melting point: -131 °C (Expl.)
• Boiling point: 69.2±8.0 °C 760 mmHg (Calc.)^*, 68 - 69 °C (Expl.)
• Flash point: 21.1 °C (Calc.)^*, -19 °C (Expl.)
• Solubility: water 28 mg/L (20 °C) (Expl.)
• Index of refraction: 1.393 (Calc.)^*, 1.398 (Expl.)

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

Safety Data

• Hazard Symbols: GHS02 Danger
• Risk Statements: H225
• Safety Statements: P210-P233-P240-P241-P242-P243-P280-P303+P361+P353-P370+P378-P403+P235-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	2	H225

Discovery and Applications

Isobutyl chloride, also known as 2-chloro-1-methylpropane, is a branched primary alkyl halide with the molecular formula C₄H₉Cl. It is a colorless, flammable liquid with a characteristic pungent odor and is primarily used as an intermediate in organic synthesis. Structurally, the chlorine atom is attached to a primary carbon, which is connected to a methyl group and a methylene unit, giving it the branched isobutyl configuration. This structure influences its chemical reactivity, making it more prone to nucleophilic substitution reactions typical of primary alkyl halides.

Isobutyl chloride was first synthesized through the reaction of isobutanol with hydrochloric acid or thionyl chloride. The reaction proceeds via a substitution mechanism where the hydroxyl group is replaced by chlorine, providing a relatively straightforward route to obtain the halide. The synthesis has been refined in industrial processes to optimize yield and minimize side reactions such as elimination, which could produce isobutylene as a byproduct. Its preparation and handling require control of temperature and moisture to ensure safety and purity of the product.

In organic chemistry, isobutyl chloride serves as a versatile building block for a wide variety of chemical transformations. It is commonly employed in nucleophilic substitution reactions, including S_N2 mechanisms, due to the primary nature of the carbon bearing the leaving group. This allows for the efficient formation of ethers, alcohols, amines, and esters when reacted with suitable nucleophiles. Its reactivity makes it a key intermediate in synthesizing more complex molecules, including pharmaceuticals, agrochemicals, and specialty chemicals.

One significant industrial application of isobutyl chloride is in the synthesis of isobutyl esters, which are used in the manufacture of fragrances, flavorings, and plasticizers. The ester derivatives often impart desirable odor or chemical stability characteristics, making isobutyl chloride an important reagent for commercial applications in the chemical and consumer products industries. Additionally, it is utilized in the production of lubricants and surfactants where the branched isobutyl group influences hydrophobicity and molecular interactions.

In pharmaceutical chemistry, isobutyl chloride is employed as an intermediate to introduce isobutyl groups into drug molecules, which can modify lipophilicity, steric properties, and metabolic stability. The introduction of branched alkyl chains can enhance the bioavailability and therapeutic performance of active pharmaceutical ingredients. Similarly, the compound finds use in agrochemical synthesis, where it is transformed into herbicides, pesticides, or other crop protection agents, contributing to specific activity and formulation stability.

Mechanistically, the primary chloride of isobutyl chloride provides a model system for studying S_N2 reactivity and steric effects on substitution reactions. Its behavior under various nucleophilic conditions offers insight into reaction kinetics, the influence of solvents, and the development of efficient synthetic routes. The compound’s volatility and relatively low boiling point also facilitate its use in distillation and other separation techniques in both laboratory and industrial contexts.

Physically, isobutyl chloride is insoluble in water but miscible with most organic solvents such as ethers, alcohols, and hydrocarbons. It is flammable, and exposure precautions are necessary to avoid inhalation, skin, or eye contact. Proper handling, including the use of gloves, eye protection, and adequate ventilation, is essential to minimize health risks. Environmental considerations focus on controlling emissions and preventing contamination of water and soil, as halogenated compounds can pose ecological risks.

The discovery and utilization of isobutyl chloride underscore its importance as a primary branched alkyl halide. Its versatility in nucleophilic substitution reactions, role as a chemical intermediate, and applications in pharmaceuticals, agrochemicals, and specialty chemical industries highlight its continued relevance in modern organic chemistry and industrial processes.

References

2017. Viscosity of 1-chloro-2-methylpropane. Viscosity of Pure Organic Liquids and Binary Liquid Mixtures.
DOI: 10.1007/978-3-662-49218-5_107

2017. Refractive index of 1-chloro-2-methylpropane. Optical Constants.
DOI: 10.1007/978-3-662-49236-9_138

2015. Catalytic Arene C(sp2)—H Alkylation Reactions via C(sp3)—X Bond Cleavage (X = Cl, Br, I). Science of Synthesis.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-217-00116