2-Chloro-N,N-dimethylacetamide: Properties, Uses & Lab Guide

2-Chloro-N,N-dimethylacetamide is a reactive chloroacetamide intermediate widely employed in pharmaceutical synthesis, agrochemical research, and fine-chemical manufacturing as an efficient alkylating and acylating building block.

CAS Number

2675-89-0

Molecular Formula

C₄H₈ClNO

Molecular Weight

121.57 g/mol

Functional Class

α-Chloroamide / Alkylating Agent

Appearance

Colorless to pale-yellow liquid

Aladdin SKU

C107991

Chemical Identity and Physical Properties

2-Chloro-N,N-dimethylacetamide (synonyms: N,N-dimethylchloroacetamide, dimethylaminocarbonylmethyl chloride) has the CAS Registry Number 2675-89-0 and the molecular formula C₄H₈ClNO, giving a molecular weight of approximately 121.57 g/mol. The compound features an α-chloro carbonyl motif in which the nitrogen bears two methyl groups, conferring increased electrophilicity at the methylene carbon relative to non-chlorinated dimethylacetamide.

At ambient conditions the reagent is typically a colorless to pale-yellow liquid with a pungent odor characteristic of reactive chloroamides. The amide bond restricts rotation and imparts partial double-bond character to the C–N linkage, which moderates reactivity compared with simple alkyl chlorides while retaining useful electrophilic character for nucleophilic substitution (S_N2) reactions.

Applications in Organic and Pharmaceutical Synthesis

The primary synthetic utility of 2-Chloro-N,N-dimethylacetamide lies in its dual function as an alkylating agent and as a masked carbonyl equivalent. Researchers use it to introduce the dimethylcarbamoylmethyl (–CH₂CONMe₂) group onto heteroatom nucleophiles such as thiols, amines, and phenols, generating thioether-, secondary amine-, or O-alkylated products in one step under mild base-mediated conditions.

In pharmaceutical intermediate synthesis, the reagent serves as a precursor to pharmacologically active scaffolds. For example, N-alkylation of nitrogen heterocycles with this reagent followed by further functionalization can yield lead compounds relevant to central nervous system (CNS) drug discovery and anti-infective programs. In agrochemical research, chloroacetamide derivatives are recognized classes of herbicides; 2-Chloro-N,N-dimethylacetamide can therefore act as a reference standard or synthetic precursor in structure–activity relationship (SAR) studies.

The reagent is also used in the preparation of thioether-linked prodrugs and in peptide-modification chemistry where selective S-alkylation of cysteine residues is required.

Recommended Handling and Storage Procedures

Personal Protective Equipment (PPE): Always work with 2-Chloro-N,N-dimethylacetamide inside a well-ventilated fume hood. Wear nitrile or neoprene gloves, a laboratory coat, and chemical splash goggles. The α-chloroamide functionality is a potential skin sensitizer and lachrymator; avoid all skin and mucous-membrane contact.

Reaction Setup: The reagent is moisture-sensitive; dispense under an inert atmosphere (N₂ or Ar) when precise stoichiometry is required. It is miscible with common polar aprotic solvents (DMF, DMSO, acetonitrile) and chlorinated solvents (DCM, chloroform), making these suitable reaction media. Base scavengers such as triethylamine or K₂CO₃ are commonly employed to neutralize the HCl generated during S_N2 alkylation.

Storage: Store in a tightly sealed container away from moisture and light at 2–8 °C or per supplier specifications. Keep away from strong oxidizers, bases, and nucleophilic materials. Check container integrity before each use. Dispose of waste in accordance with local regulations for halogenated organic solvents.

Safety, Regulatory, and Waste Considerations

Hazard Classification: 2-Chloro-N,N-dimethylacetamide is an irritant and potential sensitizer. α-Haloamides as a class are recognized as reactive electrophiles capable of alkylating biological macromolecules, so unnecessary exposure should be avoided. Consult the current Safety Data Sheet (SDS) from Aladdin Scientific (SKU C107991) for up-to-date GHS pictograms, H-statements, and P-statements before first use.

First Aid: In the event of skin contact, wash immediately with copious water for at least 15 minutes and remove contaminated clothing. For eye contact, irrigate with water for at least 15 minutes and seek medical attention. If inhaled, move to fresh air and consult a physician.

Waste Disposal: Halogenated organic waste must be segregated from non-halogenated waste streams and disposed of via a licensed hazardous-waste contractor in accordance with national and local environmental regulations (e.g., EPA 40 CFR Part 261 in the United States, or equivalent EU directives).

Frequently asked questions

What nucleophiles react efficiently with 2-Chloro-N,N-dimethylacetamide?

Thiols, secondary amines, phenolates, and azide anions are among the most reactive nucleophiles toward this α-chloroamide via Sₙ2 displacement. Soft sulfur nucleophiles (thiols, thiolates) typically react fastest under mild basic conditions at room temperature. Oxygen and nitrogen nucleophiles usually require a base such as K₂CO₃ or Et₃N to neutralize the HCl co-product and drive the reaction to completion.

How should I handle moisture sensitivity during reactions with this reagent?

Although 2-Chloro-N,N-dimethylacetamide is not as aggressively moisture-sensitive as acid chlorides, prolonged exposure to atmospheric humidity can lead to partial hydrolysis, reducing effective concentration. It is best practice to dispense the reagent under a blanket of dry nitrogen or argon, use oven-dried glassware, and employ anhydrous solvents (e.g., anhydrous DMF or acetonitrile) when high stoichiometric accuracy is critical. Re-seal the stock container immediately after use.

Is 2-Chloro-N,N-dimethylacetamide suitable as a reference standard for chloroacetamide herbicide analysis?

The compound can serve as a structural reference or synthetic precursor within chloroacetamide herbicide research programs; however, its suitability as a certified analytical reference standard depends on the purity grade and documentation provided. Researchers requiring quantitative trace-level analysis should request a Certificate of Analysis (CoA) and confirm whether the specific lot meets their regulatory or accreditation requirements before use.

What solvents are compatible with 2-Chloro-N,N-dimethylacetamide for typical alkylation reactions?

Polar aprotic solvents such as DMF, DMSO, acetonitrile, and acetone are commonly used and provide good solubility for both the reagent and most nucleophilic substrates. Chlorinated solvents (DCM, CHCl₃) are also compatible for reactions that proceed under mild conditions. Protic solvents (water, methanol) should generally be avoided unless the reaction is specifically designed for aqueous conditions, as they may promote hydrolysis of the α-chloroamide.

References

1. Aladdin Scientific Product Page: 2-Chloro-N,N-dimethylacetamide, SKU C107991. Retrieved from Aladdin Scientific official website.
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley: New York, 1992. General principles of Sₙ2 alkylation with α-haloamides.
3. Hansch, C.; Leo, A.; Hoekman, D. Exploring QSAR: Hydrophobic, Electronic, and Steric Constants; ACS Professional Reference Book; American Chemical Society: Washington, DC, 1995. Physicochemical parameters of chloroacetamide derivatives.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.