3-Chloropropionyl chloride
[CAS 625-36-5]

Identification

• Classification: Chemical reagent >> Organic reagent >> Acid halide
• Name: 3-Chloropropionyl chloride
• Molecular Formula: C₃H₄Cl₂O
• Molecular Weight: 126.97
• CAS Registry Number: 625-36-5
• EC Number: 210-890-4
• SMILES: C(CCl)C(=O)Cl

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*, 1.325 g/mL (Expl.)
• Melting point: -32 °C (Expl.)
• Boiling point: 144.9±13.0 °C 760 mmHg (Calc.)^*, 143 - 145 °C (Expl.)
• Flash point: 61.7 °C (Calc.)^*, 63 °C (Expl.)
• Solubility: water: reacts (Expl.)
• Index of refraction: 1.437 (Calc.)^*, 1.457 (Expl.)

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

Safety Data

• Hazard Symbols: GHS05;GHS06;GHS07 DangerGHS05
• Risk Statements: H290-H302-H314-H318-H330
• Safety Statements: P234-P260-P264-P264+P265-P270-P271-P280-P284-P301+P317-P301+P330+P331-P302+P361+P354-P304+P340-P305+P354+P338-P316-P317-P320-P321-P330-P363-P390-P403+P233-P405-P406-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	1	H330
Skin corrosion	Skin Corr.	1A	H314
Substances or mixtures corrosive to metals	Met. Corr.	1	H290
Serious eye damage	Eye Dam.	1	H318
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	2	H330
Flammable liquids	Flam. Liq.	3	H226
Germ cell mutagenicity	Muta.	2	H341
Skin corrosion	Skin Corr.	1C	H314

Discovery and Applications

3-Chloropropionyl chloride is an acid chloride containing both an acyl chloride functional group and a terminal chlorine substituent. It belongs to the class of halogenated acylating agents and is primarily used as a reactive intermediate in organic synthesis. The compound combines the high reactivity of an acid chloride with the additional functionalization provided by a chloroalkyl group, making it useful for preparing a variety of organic compounds.

Acid chlorides have been important reagents in synthetic organic chemistry since the development of methods for activating carboxylic acids. Their high reactivity toward nucleophiles allows efficient formation of amides, esters, and other carboxylic acid derivatives. Halogen-containing acid chlorides such as 3-chloropropionyl chloride were developed as versatile intermediates because they provide both acylation capability and a halogen site available for further chemical modification.

The molecular structure of 3-chloropropionyl chloride consists of a three-carbon chain containing an acyl chloride group at one end and a chlorine atom attached to the terminal carbon at the other end. The compound can be described as the acid chloride derivative of 3-chloropropionic acid. Its structure contains the functional sequence ClCH₂CH₂COCl.

The acyl chloride group is the most reactive part of the molecule. The carbonyl carbon is strongly electrophilic because the chlorine atom attached to the carbonyl carbon can act as a good leaving group. Nucleophiles such as alcohols, amines, and other reactive compounds can attack the carbonyl carbon, resulting in substitution reactions that replace the chlorine atom with another functional group.

The terminal chloro group provides a second site for chemical transformation. Unlike the acyl chloride chlorine, the carbon-chlorine bond in the alkyl chloride portion is involved in nucleophilic substitution reactions at a saturated carbon atom. Under suitable conditions, nucleophiles can replace this chlorine atom, allowing further functionalization of molecules derived from 3-chloropropionyl chloride.

The combination of two reactive sites gives 3-chloropropionyl chloride particular value in organic synthesis. The acyl chloride group can first react with nucleophiles to introduce a 3-chloropropionyl moiety into a molecule. The remaining chloro group can then undergo additional reactions, enabling the preparation of compounds with more complex structures.

A major application of 3-chloropropionyl chloride is the synthesis of amide and ester derivatives. Reaction with amines produces chloropropionamide compounds, while reaction with alcohols produces chloropropionate esters. These products can serve as intermediates for further synthetic transformations.

The compound has also been used in the preparation of heterocyclic compounds. Molecules containing a 3-chloropropionyl group can undergo intramolecular or intermolecular reactions that lead to the formation of nitrogen- or oxygen-containing ring systems. Such synthetic approaches are widely used in medicinal chemistry and organic synthesis.

In pharmaceutical and agrochemical research, halogenated acyl chlorides are valuable because they allow controlled introduction of functional groups into complex molecules. The chloroalkyl portion can provide a handle for additional modification, while the acyl chloride functionality enables efficient attachment to amine or alcohol-containing structures.

The chemical behavior of 3-chloropropionyl chloride is dominated by its electrophilic nature and sensitivity to nucleophilic attack. Because acid chlorides readily react with moisture to form the corresponding carboxylic acids, they are typically handled under dry conditions during synthesis.

The physical and chemical properties of the compound arise from the combination of its polar carbonyl chloride group and chlorinated hydrocarbon chain. The molecule has no hydrogen-bond donor groups but contains functional groups capable of strong dipole interactions.

Overall, 3-chloropropionyl chloride is an important halogenated acid chloride used as a synthetic intermediate. Its dual functionality, consisting of a highly reactive acyl chloride group and a modifiable chloroalkyl group, makes it a useful building block for preparing amides, esters, heterocycles, and other functionalized organic compounds in chemical research and industrial synthesis.

References

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URL: https://pharmaceutical-substances.thieme.com/lexicon/KD-19-0154

2026. Lazertinib. Pharmaceutical Substances.
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2025. Synthesis, Properties, and Structure of Ferrocenoylpyrazoles. Russian Journal of Coordination Chemistry.
DOI: 10.1134/s1070328425600809