Methyl chlorodifluoroacetate
[CAS# 1514-87-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Ester >> Methyl ester compound
• Name: Methyl chlorodifluoroacetate
• Synonyms: Methyl 2-chloro-2,2-difluoroacetate
• Molecular Formula: C₃H₃ClF₂O₂
• Molecular Weight: 144.50
• CAS Registry Number: 1514-87-0
• EC Number: 216-154-9
• SMILES: COC(=O)C(F)(F)Cl

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*, 1.371 g/mL (Expl.)
• Index of Refraction: 1.359, Calc.^*, 1.349 (Expl.)
• Boiling Point: 80.0 °C (760 mmHg), Calc.^*, 79-81 °C (Expl.)
• Flash Point: 19.4 °C, Calc.^*, 19 °C (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS05 Danger
• Risk Statements: H225-H314
• Safety Statements: P210-P233-P240-P241-P242-P243-P260-P264-P280-P301+P330+P331-P302+P361+P354-P303+P361+P353-P304+P340-P305+P354+P338-P316-P321-P363-P370+P378-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	2	H225
Skin corrosion	Skin Corr.	1B	H314
Serious eye damage	Eye Dam.	1	H318
Specific target organ toxicity - single exposure	STOT SE	3	H335

• Transport Information: UN 2924

Discovery and Applications

Methyl chlorodifluoroacetate (C₃H₃ClF₂O₂) is a fluorinated organic compound that serves as a key intermediate in the synthesis of various fluorinated materials. It is structurally characterized by the presence of a chlorodifluoromethyl (-CF₂Cl) group attached to an ester functional group, which influences its reactivity and physicochemical properties.

The synthesis of methyl chlorodifluoroacetate has been documented in the literature, typically involving the reaction of chlorodifluoroacetic acid or its derivatives with methanol in the presence of an acid catalyst. Alternatively, fluorination strategies employing chlorodifluoromethylation reagents allow for its formation under controlled conditions. The resulting ester is a stable compound with a reactive halogenated center, making it useful for further transformations.

Methyl chlorodifluoroacetate finds applications as a precursor in the production of fluorinated pharmaceuticals, agrochemicals, and specialty materials. The presence of the -CF₂Cl group enhances the metabolic stability and lipophilicity of derived compounds, properties that are often desirable in drug discovery and pesticide development. This compound is also utilized in fluorinated polymer synthesis, where its reactivity enables the incorporation of halogenated moieties into high-performance materials.

In organic synthesis, methyl chlorodifluoroacetate serves as an electrophilic reagent for introducing the chlorodifluoromethyl functionality into complex molecules. The ester group allows for hydrolysis, transesterification, and nucleophilic substitution reactions, expanding its synthetic utility. Additionally, the halogenated carbon center can undergo further functionalization through metal-catalyzed coupling reactions, providing access to structurally diverse fluorinated compounds.

The handling and storage of methyl chlorodifluoroacetate require appropriate safety precautions due to its potential reactivity and volatility. It should be kept in a sealed container under dry and inert conditions to prevent hydrolysis and decomposition. Exposure to this compound may pose health risks, necessitating the use of personal protective equipment and proper ventilation when working with it in laboratory and industrial settings.

The continued demand for fluorinated compounds in pharmaceuticals, agrochemicals, and material sciences ensures the relevance of methyl chlorodifluoroacetate as a valuable synthetic intermediate. Its well-established role in chemical transformations highlights its importance in the development of advanced fluorinated molecules.

References

2019. Expanding the 18F-Radiochemical Space: Synthesis and Applications of 1,1-18F-Difluorinated Alkenes. Synlett, 30(10).
DOI: 10.1055/s-0037-1611764

2014. Electron driven processes in chlorodifluoroacetic acid methyl ester. The European Physical Journal D, 68(7).
DOI: 10.1140/epjd/e2014-50089-3

2013. A theoretical investigation on the kinetics and reactivity of the gas-phase reactions of ethyl chlorodifluoroacetate with OH radical and Cl atom at 298 K. Structural Chemistry, 24(6).
DOI: 10.1007/s11224-013-0312-3