2-Chloro-N-methoxy-N-methylacetamide: Properties & Lab Use

2-Chloro-N-methoxy-N-methylacetamide is a chloroacetyl-functionalized Weinreb amide serving as a versatile bifunctional electrophilic reagent in organic synthesis, enabling selective acylation and subsequent nucleophilic transformations.

CAS Number

Not specified in source material — see product page for confirmed CAS

SKU / Product Code

C124448

Functional Groups

Chloroacetyl (alpha-chloro ketone equivalent) and Weinreb amide (N-methoxy-N-methyl amide)

Primary Reactivity

Electrophilic at the alpha-carbon (alkylation via chloride displacement) and at the carbonyl carbon (acylation with organometallic reagents)

Storage Conditions

Store cool and dry, away from moisture and incompatible nucleophiles; consult SDS for full guidance

Purity Grade

Research-grade; consult product specification sheet for confirmed purity value

Chemical Identity and Structure

2-Chloro-N-methoxy-N-methylacetamide (Aladdin SKU: C124448) is an organic compound that combines two distinct reactive motifs within a single molecule: a chloroacetyl group and a Weinreb amide moiety. The Weinreb amide portion — defined by the N-methoxy-N-methyl substitution pattern — is well-established in synthetic organic chemistry for its ability to react with organolithium and Grignard reagents to furnish ketones or aldehydes in a controlled manner, resisting over-addition by chelating the metal through the methoxy oxygen.

The alpha-chloro substituent introduces a second electrophilic handle, rendering the compound bifunctional. This combination enables sequential or orthogonal reactivity: the chloride can be displaced by a variety of nucleophiles (amines, thiols, enolates) under mild conditions, while the Weinreb amide carbonyl can be engaged by organometallic nucleophiles in a subsequent or independent step. The molecular framework is compact, making the reagent convenient to handle and incorporate into multi-step synthetic routes.

Applications in Organic Synthesis

The dual electrophilic character of 2-Chloro-N-methoxy-N-methylacetamide makes it particularly attractive in target-oriented synthesis and the preparation of pharmaceutical intermediates. Key application areas include:

• Ketone synthesis via Weinreb amide chemistry: Treatment with organolithium or Grignard reagents selectively converts the amide to a ketone without proceeding to the tertiary alcohol. This controlled reactivity is advantageous when preparing alpha-chloromethyl ketones or related structures that serve as warheads in covalent inhibitor design.
• Alkylation reactions: The activated chloromethyl group undergoes nucleophilic substitution (S_N2) with nitrogen, oxygen, sulfur, and carbon nucleophiles, allowing the introduction of diverse functional groups in a single step.
• Building-block diversification: The compound can act as a linker-building block in combinatorial and medicinal chemistry workflows, providing a handle for further elaboration at both reactive sites.
• Heterocycle synthesis: Bifunctional alpha-haloamide reagents are well-documented precursors for the construction of nitrogen- and sulfur-containing heterocycles through condensation or cyclization reactions with bifunctional nucleophiles.

Researchers should consult primary literature and validate reaction conditions in their specific substrate context before large-scale use.

Safe Handling and Storage

As with all alpha-haloamide reagents, 2-Chloro-N-methoxy-N-methylacetamide should be treated as a potentially reactive lachrymator and skin/eye irritant. The following general precautions apply (always defer to the product-specific Safety Data Sheet, SDS, for authoritative guidance):

• Personal Protective Equipment (PPE): Wear chemically resistant gloves (nitrile recommended), safety goggles, and a laboratory coat. Work in a well-ventilated fume hood.
• Storage: Store in a tightly sealed container under cool, dry conditions, protected from light and moisture. Keep away from strong bases, strong nucleophiles, and reducing agents that could trigger uncontrolled reactions.
• Waste disposal: Dispose of in accordance with local, national, and institutional regulations for halogenated organic waste.
• Incompatibilities: Avoid contact with water (potential hydrolysis), strong oxidizers, and reactive nucleophilic solvents.

Users should review the current SDS before first use and ensure that institutional chemical safety protocols are followed at all times.

Ordering and Availability

2-Chloro-N-methoxy-N-methylacetamide is available from Aladdin Scientific under SKU C124448. Researchers and procurement teams can request detailed specifications — including confirmed purity, lot-specific certificates of analysis, and available pack sizes — directly through the Aladdin Scientific product page or by contacting the sales team.

When placing an order, please have the SKU and your institutional purchase order details ready. Aladdin Scientific's reagents are supplied for research use only. Contact customer support for information on bulk quantities, custom packaging, or expedited shipping options.

Frequently asked questions

What makes 2-Chloro-N-methoxy-N-methylacetamide useful as a synthetic building block?

The compound is bifunctional, containing both a reactive alpha-chloro leaving group and a Weinreb amide carbonyl. This allows chemists to perform two orthogonal transformations — nucleophilic substitution at the carbon bearing chlorine and controlled acylation via the amide — either sequentially or independently, providing significant flexibility in multi-step synthesis.

How does the Weinreb amide group prevent over-addition by organometallic reagents?

The N-methoxy group coordinates to the metal of the organolithium or Grignard reagent after the first addition, forming a stable chelated tetrahedral intermediate. This chelate complex is stable under the reaction conditions and releases the ketone product only upon aqueous workup, effectively suppressing the second addition that would otherwise yield a tertiary alcohol.

What safety precautions should I take when handling this compound in the laboratory?

Always work in a well-ventilated fume hood and wear appropriate PPE including nitrile gloves, safety goggles, and a lab coat. Store the compound sealed, cool, and dry, away from moisture and strong nucleophiles. Consult the product-specific SDS from Aladdin Scientific for full hazard information and disposal guidance before use.

Can 2-Chloro-N-methoxy-N-methylacetamide be used to synthesize heterocycles?

Yes, alpha-haloamide reagents of this class are established precursors for heterocycle synthesis. Reaction with bifunctional nucleophiles such as aminothiols or diaminocompounds can lead to ring closure, affording nitrogen- or sulfur-containing heterocyclic products. Specific conditions should be validated against primary literature for each target heterocycle.

References

1. Nahm, S.; Weinreb, S. M. N-Methoxy-N-methylamides as effective acylating agents. Tetrahedron Letters, 1981, 22(39), 3815–3818. doi:10.1016/S0040-4039(01)91316-4
2. Sibi, M. P. Chemistry of N-methoxy-N-methylamides (Weinreb amides). Organic Preparations and Procedures International, 1993, 25(1), 15–40.
3. Aladdin Scientific. Product page: 2-Chloro-N-methoxy-N-methylacetamide, SKU C124448. Aladdin Scientific Corporation.

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