tert-Butyl chloroacetate
[CAS# 107-59-5]

Identification

• Classification: Chemical reagent >> Organic reagent >> Ester >> Butyl ester compound
• Name: tert-Butyl chloroacetate
• Molecular Formula: C₆H₁₁ClO₂
• Molecular Weight: 150.60
• CAS Registry Number: 107-59-5
• EC Number: 203-506-1
• SMILES: CC(C)(C)OC(=O)CCl

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*, 1.053 g/mL (Expl.)
• Boiling point: 157.5 °C 760 mmHg (Calc.)^*, 177.4 - 178.8 °C (Expl.)
• Flash point: 46.7 °C (Calc.)^*, 47 °C (Expl.)
• Solubility: water: $lessThan$0.1 g/L (20 °C) (Expl.)
• Index of refraction: 1.425 (Calc.)^*, 1.423 (Expl.)

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

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS06;GHS07;GHS09 Danger
• Risk Statements: H226-H302+H312-H302-H312-H314-H315-H317-H319-H331-H400-H410
• Safety Statements: P210-P233-P240-P241-P242-P243-P260-P261-P264-P264+P265-P270-P271-P272-P273-P280-P301+P317-P301+P330+P331-P302+P352-P302+P361+P354-P303+P361+P353-P304+P340-P305+P351+P338-P305+P354+P338-P316-P317-P321-P330-P332+P317-P333+P317-P337+P317-P362+P364-P363-P370+P378-P391-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Flammable liquids	Flam. Liq.	3	H226
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	3	H331
Skin corrosion	Skin Corr.	1B	H314
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Skin sensitization	Skin Sens.	1	H317
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H332

• Transport Information: UN 3272

Discovery and Applications

tert-Butyl chloroacetate is an ester of chloroacetic acid with the molecular formula C₆H₁₁ClO₂. Structurally, it consists of a chloroacetyl group linked to a tert-butyl ester moiety, combining a reactive halogenated methylene group with a bulky, acid-labile protecting group. Under ambient conditions, tert-butyl chloroacetate is typically a colorless liquid with a characteristic ester odor. It is soluble in common organic solvents and exhibits limited solubility in water.

The compound is widely used as a synthetic intermediate in organic chemistry. The presence of the chloro substituent on the methylene carbon activates the molecule toward nucleophilic substitution reactions, allowing displacement of the chloride by a variety of nucleophiles such as amines, thiols, or alkoxides. This reactivity makes tert-butyl chloroacetate a convenient reagent for introducing protected acetic acid units into more complex molecular frameworks.

A key feature of tert-butyl chloroacetate is the tert-butyl ester group, which functions as a protecting group for carboxylic acids. The tert-butyl ester is stable under neutral and basic conditions but can be readily removed under mildly acidic conditions, typically generating isobutene and carbon dioxide as byproducts. This property is particularly valuable in multistep synthesis, where selective protection and deprotection of carboxyl groups is required.

In practice, tert-butyl chloroacetate is commonly employed in the synthesis of amino acid derivatives, peptides, and pharmaceutical intermediates. Alkylation of nitrogen- or sulfur-containing nucleophiles with this reagent introduces a protected carboxymethyl group, which can later be converted into the free acid. This strategy allows chemists to control functional group reactivity and improve overall synthetic efficiency.

The compound can be prepared by esterification of chloroacetic acid with tert-butanol or by reaction of tert-butanol with chloroacetyl chloride under controlled conditions. Its handling requires standard precautions typical for halogenated esters, as the chloroacetyl moiety can be irritating and reactive toward biological nucleophiles.

Overall, tert-butyl chloroacetate is a versatile and widely used reagent in organic synthesis. Its combination of a reactive chloroacetyl group and an acid-labile tert-butyl ester makes it especially valuable for constructing protected carboxylic acid derivatives and for enabling controlled functional group transformations in complex synthetic sequences.

References

2018. Multi-colored electrochromic devices based on mixed mono- and bi-substituted 4,4'-bipyridine derivatives containing an ester group. Journal of Applied Electrochemistry, 48(6).
DOI: 10.1007/s10800-018-1190-6

2015. A One-Pot and Efficient Synthesis of Zoledronic Acid Starting from Tert-butyl Imidazol-1-yl Acetate. Pharmaceutical Chemistry Journal, 49(1).
DOI: 10.1007/s11094-015-1205-0