Piperazinium Chloride
[CAS# 7542-23-6]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Piperazine
• Name: Piperazinium Chloride
• Synonyms: Piperazine hydrochloride
• Molecular Formula: C₄H₁₁ClN₂
• Molecular Weight: 122.60
• CAS Registry Number: 7542-23-6
• EC Number: 231-422-5
• SMILES: C1CNCCN1.Cl

Properties

• Melting point: 150 - 160 ºC (Expl.)

Safety Data

• Hazard Symbols: GHS08 Danger
• Hazard Statements: H315-H317-H319-H334-H361fd-H412
• Precautionary Statements: P203-P233-P260-P261-P264-P264+P265-P271-P272-P273-P280-P284-P302+P352-P304+P340-P305+P351+P338-P318-P321-P332+P317-P333+P317-P337+P317-P342+P316-P362+P364-P403-P405-P501

Discovory and Applicatios

Piperazinium chloride (C₄H₁₂N₂Cl₂) is the dihydrochloride salt of piperazine, a six-membered heterocyclic diamine. It is formed when piperazine reacts with hydrochloric acid, resulting in a crystalline ionic compound consisting of the doubly protonated piperazinium cation and chloride anions. The salt form is preferred in laboratory and pharmaceutical contexts because it is more stable, less volatile, and easier to handle than the free base.

The origin of piperazine chemistry can be traced back to the late 19th century, when this simple diamine ring was first synthesized and studied as a structural analog of piperidine. Over time, the formation of its salts, including piperazinium chloride, became a key part of chemical and pharmaceutical research, enabling stable storage and controlled use of this otherwise reactive amine. The chloride salt is one of the most commonly prepared derivatives, along with piperazinium dihydrochloride and other hydrohalide forms.

Structurally, piperazinium chloride features protonated nitrogen atoms within the ring, making it a dicationic species that pairs with two chloride anions. The resulting crystalline structure is stabilized through hydrogen bonding and ionic interactions, allowing the salt to form well-defined crystals. These features make it of interest to crystallographers and solid-state chemists, who use such salts to investigate packing arrangements, hydrogen bond networks, and counterion effects on stability.

Piperazinium chloride has been used in laboratory research as a convenient and solid-state source of piperazine. In organic synthesis, the salt can be neutralized to release the free amine, which then participates in reactions leading to a wide range of derivatives, including pharmacologically active compounds. Because piperazine serves as a scaffold for many therapeutic agents, its salts are often used as intermediates in medicinal chemistry programs.

Pharmacologically, salts of piperazine, particularly citrate and phosphate salts, gained importance in the mid-20th century as anthelmintic drugs for the treatment of roundworm and pinworm infections. Piperazinium chloride itself was not a widely used therapeutic, but it provided a convenient alternative salt form for laboratory formulations and early pharmacological experiments. The choice of chloride as the counterion offers advantages of high solubility and ease of preparation, though other salts were favored in clinical settings due to optimized pharmacokinetics and tolerability.

In addition to pharmaceutical applications, piperazinium chloride has been used as a model system in the study of acid–base interactions and proton transfer chemistry. Its well-defined ionic structure makes it suitable for exploring the physicochemical properties of small-molecule salts, including solubility, hygroscopicity, and thermal behavior. These studies contribute to a broader understanding of salt formation, which is a critical step in drug development, where selecting the appropriate counterion can significantly influence a drug candidate’s performance.

The compound also has relevance in material science research, where amine salts are examined for their roles in templating, crystal engineering, and ionic interactions. In this regard, piperazinium chloride serves as a simple and accessible model for studying the influence of protonation on ring-containing organic molecules.

In summary, piperazinium chloride is a stable crystalline salt of piperazine formed through neutralization with hydrochloric acid. While not widely used in direct therapeutic applications, it has value as a laboratory reagent, a precursor for synthesis, and a model compound for research into the chemistry of amine salts. Its stability, solubility, and crystallinity make it useful in both academic and applied chemical investigations.

References

2021. Potential of 1-(1-napthylmethyl)-piperazine, an efflux pump inhibitor against cadmium-induced multidrug resistance in Salmonella enterica serovar Typhi as an adjunct to antibiotics. Brazilian journal of microbiology.
DOI: 10.1007/s42770-021-00492-5

2021. Recent advances in the synthesis of piperazine based ligands and metal complexes and their applications. Dalton transactions (Cambridge, England : 2003).
DOI: 10.1039/d0dt03569f

2021. Piperazine, a Key Substructure for Antidepressants: Its Role in Developments and Structure-Activity Relationships. ChemMedChem.
DOI: 10.1002/cmdc.202100045