4-(4-Chlorobutyl)morpholine HCl: Properties & Lab Uses

4-(4-Chlorobutyl)morpholine hydrochloride is a chloroalkyl-morpholine building block widely employed as a synthetic intermediate in organic and medicinal chemistry for the introduction of the morpholinylbutyl pharmacophore into target molecules.

Chemical Name

4-(4-Chlorobutyl)morpholine hydrochloride

Aladdin SKU

C471801

Functional Groups

Tertiary amine (morpholine ring), alkyl chloride, hydrochloride salt

Primary Application

Synthetic intermediate for N-alkylation and nucleophilic substitution reactions

Physical Form

Solid (hydrochloride salt form)

Storage Recommendation

Store in a cool, dry, well-ventilated area away from moisture and incompatible materials

Chemical Identity and Structure

4-(4-Chlorobutyl)morpholine hydrochloride consists of a morpholine ring nitrogen linked via a four-carbon chain to a terminal chloride, presented as the protonated hydrochloride salt. The morpholine moiety contributes a cyclic tertiary amine and an ether oxygen, imparting moderate polarity and water solubility to the salt form. The terminal alkyl chloride serves as an electrophilic handle for downstream functionalization.

The compound is catalogued under Aladdin SKU C471801 and is cross-referenced with Sigma-Aldrich catalogue number 728446. Researchers should confirm the CAS registry number against the certificate of analysis provided with each lot to ensure reagent identity prior to use.

Physicochemical Properties and Handling

As a hydrochloride salt, 4-(4-Chlorobutyl)morpholine hydrochloride is typically encountered as a white to off-white crystalline solid. The salt form improves stability and ease of weighing compared with the free base. It is expected to be hygroscopic to some degree; therefore, containers should be resealed promptly after use and stored in a desiccated environment.

The compound contains an alkyl chloride, which is a reactive electrophile. Standard laboratory precautions apply: use appropriate personal protective equipment (gloves, safety glasses, lab coat), work in a well-ventilated fume hood, and avoid contact with strong bases or nucleophiles outside of intended reaction conditions. Dispose of waste in accordance with local regulations for halogenated organic compounds.

Synthetic Applications in Organic and Medicinal Chemistry

The principal utility of 4-(4-Chlorobutyl)morpholine hydrochloride lies in its bifunctional architecture: the electrophilic chloroalkyl terminus enables nucleophilic substitution (S_N2) reactions with amines, thiols, alcohols, and carbon nucleophiles, while the morpholine ring provides a pharmacophore frequently encountered in approved drugs and drug candidates. The four-carbon tether offers optimal chain length for many receptor-binding applications compared with shorter or longer homologues.

Typical transformations include N-alkylation of secondary amines and heterocycles, O-alkylation of phenols, and C-alkylation of active methylene compounds. After free-basing the hydrochloride (e.g., with aqueous base or solid K₂CO₃), the liberated tertiary amine can also act as a mild nucleophile or ligand in metal-catalyzed processes. Researchers involved in library synthesis, lead optimization, and structure–activity relationship studies may find this reagent valuable for appending a solubility-enhancing morpholinylbutyl group to a scaffold of interest.

Quality, Purity, and Specification Considerations

When sourcing 4-(4-Chlorobutyl)morpholine hydrochloride, researchers should request a certificate of analysis (CoA) specifying purity (typically assessed by HPLC or titration), water content (Karl Fischer), residual solvents, and appearance. For sensitive synthetic routes, higher-purity lots reduce the risk of side reactions caused by morpholine free base, related alkyl chloride homologues, or hydrolysis products (the corresponding alcohol).

Aladdin Scientific's C471801 is aligned with the specification standards of the corresponding Sigma-Aldrich reference (728446). Laboratory managers are advised to document lot numbers in experimental records to facilitate reproducibility and traceability. For GMP or regulated research environments, confirm whether a GMP-grade or additional documentation package is required prior to ordering.

Frequently asked questions

What is the recommended solvent for dissolving 4-(4-Chlorobutyl)morpholine hydrochloride?

The hydrochloride salt is generally soluble in polar protic solvents such as water, methanol, and ethanol, as well as in polar aprotic solvents like DMSO and DMF. Solubility in dichloromethane may be limited for the salt form; free-basing with dilute aqueous base before extraction into organic solvent is a common approach when anhydrous conditions are required.

How should 4-(4-Chlorobutyl)morpholine hydrochloride be stored to maintain stability?

Store the compound in a tightly sealed container in a cool, dry, and well-ventilated area, away from moisture, heat, and incompatible reagents such as strong oxidizers and strong bases. Because the salt may be hygroscopic, the use of a desiccant is advisable. Under appropriate conditions, the material is expected to be stable for an extended period; always refer to the CoA and SDS for lot-specific guidance.

How does 4-(4-Chlorobutyl)morpholine hydrochloride differ from shorter-chain analogues such as 4-(2-Chloroethyl)morpholine hydrochloride?

The four-carbon butyl chain provides greater conformational flexibility and a longer linker relative to two-carbon (ethyl) or three-carbon (propyl) analogues, which can influence binding affinity, membrane permeability, and pharmacokinetic properties of the resulting products. The longer chain also reduces the tendency toward intramolecular cyclization that can occur with shorter chains, improving reaction selectivity in some N-alkylation protocols.

Is this compound suitable for use as a direct pharmacological agent or only as a synthetic intermediate?

4-(4-Chlorobutyl)morpholine hydrochloride is primarily employed as a synthetic building block rather than a pharmacologically active agent in its own right. Its value lies in transferring the morpholinylbutyl group onto a target scaffold. Researchers interested in pharmacological testing should consult the literature for the specific target molecule synthesized using this intermediate.

References

1. Sigma-Aldrich (Merck KGaA). 4-(4-Chlorobutyl)morpholine hydrochloride, catalogue number 728446. Product information page.
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley-Interscience: New York, 1992. (General reference for SN2 alkylation reactions and morpholine chemistry.)
3. Aladdin Scientific. 4-(4-Chlorobutyl)morpholine hydrochloride, SKU C471801. Certificate of Analysis and Safety Data Sheet (consult current lot documentation).

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