Methyl chloroacetate
[CAS# 96-34-4]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Carboxylic esters and their derivatives
• Name: Methyl chloroacetate
• Synonyms: Chloroacetic acid methyl ester
• Molecular Formula: C₃H₅ClO₂
• Molecular Weight: 108.52
• CAS Registry Number: 96-34-4
• EC Number: 202-501-1
• SMILES: COC(=O)CCl

Properties

• Density: 1.238 g/mL
• Melting point: -33 ºC
• Boiling point: 130-132 ºC
• Refractive index: 1.421-1.423
• Flash point: 47 ºC
• Water solubility: 28 g/L (20 ºC)

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS06;GHS07;GHS09 DangerGHS02
• Hazard Statements: H226-H301-H310+H330-H310-H315-H317-H318-H330-H331-H335-H400
• Precautionary Statements: P210-P233-P240-P241-P242-P243-P260-P261-P262-P264-P264+P265-P270-P271-P272-P273-P280-P284-P301+P316-P302+P352-P303+P361+P353-P304+P340-P305+P354+P338-P316-P317-P319-P320-P321-P330-P332+P317-P333+P317-P361+P364-P362+P364-P370+P378-P391-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	3	H301
Serious eye damage	Eye Dam.	1	H318
Flammable liquids	Flam. Liq.	3	H226
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin sensitization	Skin Sens.	1	H317
Acute toxicity	Acute Tox.	2	H310
Acute toxicity	Acute Tox.	2	H330
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Acute toxicity	Acute Tox.	3	H331

• Transport Information: UN 2295

Discovory and Applicatios

Methyl chloroacetate is an organic compound with the molecular formula C₃H₅ClO₂. It is the methyl ester of chloroacetic acid and appears as a colorless to slightly yellow liquid with a sharp, pungent odor. It belongs to the class of haloalkyl esters and contains both an ester functional group and a reactive chloromethyl group, making it a valuable intermediate in organic synthesis.

The compound was first synthesized in the 19th century as part of the broader exploration of esters and halogenated organic compounds. Its preparation involves the esterification of chloroacetic acid with methanol in the presence of an acid catalyst, typically sulfuric acid. The reaction yields methyl chloroacetate and water, which can be separated by distillation. Industrially, this process is optimized for high yield and purity, and the compound is manufactured on a large scale due to its wide range of applications.

Methyl chloroacetate is used extensively as a building block in the chemical industry. Its chloromethyl group is a reactive site for nucleophilic substitution reactions, allowing the introduction of various functional groups to synthesize a wide variety of chemical products. It serves as an intermediate in the production of pharmaceuticals, agrochemicals, dyes, and other fine chemicals.

In pharmaceutical synthesis, methyl chloroacetate is used to construct molecules that require a masked carboxylic acid group, which can later be hydrolyzed to yield free acid functionality. The compound is also employed in the synthesis of amino acid derivatives, particularly through alkylation reactions with amines. Additionally, it plays a role in the production of heterocyclic compounds and peptide analogs.

In the agrochemical industry, methyl chloroacetate is a precursor to herbicides, insecticides, and fungicides. For example, it is involved in the synthesis of active ingredients containing carboxymethyl or substituted ester moieties. Its reactivity with thiols, amines, and other nucleophiles makes it suitable for forming thioglycolate and glycolamide derivatives, which are important in crop protection formulations.

Beyond pharmaceutical and agrochemical uses, methyl chloroacetate finds application in polymer chemistry. It can be used to introduce ester groups into polymer backbones or side chains, modifying the physical and chemical properties of the resulting materials. The compound has also been studied for use in crosslinking agents and in the preparation of resins and adhesives.

In the laboratory, methyl chloroacetate serves as a reagent for introducing the methyl ester of chloroacetic acid into various molecular frameworks. It is utilized in synthesis protocols requiring esterification, alkylation, and acylation steps. Its relatively simple structure and availability make it a convenient reagent for organic chemists.

Despite its utility, methyl chloroacetate is considered hazardous and must be handled with caution. It is toxic by inhalation, ingestion, and skin absorption. Exposure can lead to respiratory irritation, skin burns, and central nervous system effects. The compound is also flammable and poses a risk of fire or explosion if improperly stored. Proper protective equipment, including gloves, goggles, and adequate ventilation, is required when working with methyl chloroacetate.

Its environmental impact is a subject of regulation. Spillage or improper disposal can lead to contamination of water sources, as it is moderately soluble in water and can hydrolyze to release chloroacetic acid, which is also toxic. Regulations in various countries restrict its use and disposal to minimize potential harm to health and the environment.

In summary, methyl chloroacetate is a versatile and reactive organic compound widely employed as a chemical intermediate in the synthesis of pharmaceuticals, agrochemicals, and industrial materials. Its dual functionality as a halide and an ester enables diverse transformations in organic synthesis. However, due to its toxicity and environmental hazards, careful handling and regulatory compliance are essential in its use and manufacturing.

References

1963. Free-radical addition of chloroacetic acid and of methyl chloroacetate to a-olefins. Bulletin of the Academy of Sciences of the USSR, Division of chemical science.
DOI: 10.1007/bf00846406

2023. Synthesis, Chemical Properties, and Application of 2-Substituted Thiazolo[3,2-a]pyrimidine Derivatives. Russian Journal of Organic Chemistry.
DOI: 10.1134/s1070428023030016

2021. From Monoterpene Alcohols via S-Alkylation or S-Acylation. Science of Synthesis.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-142-00190