4-Chlorobutyryl chloride
[CAS# 4635-59-0]

Identification

• Classification: Chemical reagent >> Organic reagent >> Acid halide
• Name: 4-Chlorobutyryl chloride
• Synonyms: 4-CBC; 4-Chlorobutanoic acid chloride; 4-Chlorobutyroyl Chloride; 4-Chlorobutyric acid chloride
• Molecular Formula: C₄H₆Cl₂O
• Molecular Weight: 141.00
• CAS Registry Number: 4635-59-0
• EC Number: 225-059-1
• SMILES: C(CC(=O)Cl)CCl

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*, 1.257 g/mL (Expl.)
• Melting point: -49 °C (Expl.)
• Boiling point: 174.3±13.0 °C 760 mmHg (Calc.)^*, 173 - 174 °C (Expl.)
• Flash point: 70.2±20.2 °C (Calc.)^*, 85 °C (Expl.)
• Index of refraction: 1.442 (Calc.)^*, 1.461 (Expl.)

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 Danger
• Risk Statements: H290-H302-H314-H330
• Safety Statements: P234-P260-P264-P270-P271-P280-P284-P301+P317-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P320-P321-P330-P363-P390-P403+P233-P405-P406-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	2	H330
Acute toxicity	Acute Tox.	4	H302
Skin corrosion	Skin Corr.	1A	H314
Serious eye damage	Eye Dam.	1	H318
Skin corrosion	Skin Corr.	1B	H314
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301

Discovery and Applications

4-Chlorobutyryl chloride is an acyl chloride with the molecular formula C₄H₆Cl₂O. Structurally, it consists of a four-carbon straight chain with a chlorine atom on the terminal carbon (position 4) and an acyl chloride functional group (–COCl) on the first carbon. This bifunctional structure gives it both electrophilic reactivity at the carbonyl carbon and potential for substitution reactions at the terminal chlorinated position.

The compound is a clear to light yellow liquid at room temperature with a pungent, irritating odor. It is moisture-sensitive and reacts readily with water, alcohols, and amines to form corresponding carboxylic acid derivatives, releasing hydrogen chloride (HCl) gas in the process. This reactivity makes it useful in a variety of chemical syntheses.

4-Chlorobutyryl chloride is mainly employed as an intermediate in the synthesis of pharmaceuticals, agrochemicals, and fine chemicals. It is frequently used to introduce a 4-chlorobutyryl group into amines, alcohols, or aromatic rings via acylation reactions. This step is often followed by nucleophilic substitution at the terminal chlorine, enabling the attachment of further functional groups such as thiols, amines, or alkoxides. As such, it is a valuable building block in multistep synthetic pathways.

In medicinal chemistry, 4-chlorobutyryl chloride has been used to prepare amide derivatives or prodrugs containing the 4-chlorobutanoyl moiety. These derivatives can serve as enzyme inhibitors, receptor ligands, or modulators of biological activity, depending on the nature of the rest of the molecule. It has also been incorporated into the design of linkers in drug–polymer conjugates or bioconjugation strategies.

In polymer and materials chemistry, this reagent has been utilized to functionalize polymers or monomers, adding a reactive acyl group that can be further modified. The 4-chlorobutyryl group is useful in tailoring polymer solubility, crosslinking capability, or adhesion to surfaces.

Due to its corrosive nature and the evolution of HCl upon reaction, 4-chlorobutyryl chloride must be handled with care. It should be used in a well-ventilated fume hood with appropriate personal protective equipment, including gloves and eye protection. Containers should be tightly sealed and kept dry to prevent hydrolysis. Upon contact with moisture, it may fume and produce irritating or corrosive vapors.

In summary, 4-chlorobutyryl chloride is a reactive acylating agent widely used in organic synthesis to introduce functional groups and build complex molecular architectures. Its dual reactivity as an acyl chloride and alkyl chloride makes it versatile in chemical transformations, particularly in pharmaceutical and materials research.

References

2021. Improved Method for the Total Synthesis of Azaperone and Investigation of Its Electrochemical Behavior in Aqueous Solution. Chemical Research in Chinese Universities, 37(3).
DOI: 10.1007/s40242-021-1061-2

2015. Synthesis, biological evaluation and molecular docking studies of thiazole-based pyrrolidinones and isoindolinediones as anticonvulsant agents. Medicinal Chemistry Research, 24(4).
DOI: 10.1007/s00044-015-1371-3

2014. Synthesis and antiprotozoal activities of new 3-azabicyclo[3.2.2]nonanes. Archives of Pharmacal Research, 37(11).
DOI: 10.1007/s12272-014-0523-1