1-boc Piperazine

1-Boc Piperazine: A Critical Intermediate in Medicinal Chemistry and Drug Development

Chemical and Physical Properties

• Chemical Name: 1-(tert-Butoxycarbonyl)piperazine

• Synonyms: Boc-piperazine, tert-butyl piperazine-1-carboxylate

• Molecular Formula: C9H18N2O2

• Molecular Weight: 186.25 g/mol

• CAS Number: 57260-71-6

• Appearance: White to pale yellow crystalline powder

• Boiling Point: Approx. 335°C (decomposes)

• Solubility: Freely soluble in common organic solvents like dichloromethane (DCM), acetonitrile, and methanol

Its structure contains a six-membered piperazine ring substituted with a Boc protecting group on one nitrogen. This feature ensures regioselective reactivity, ideal for stepwise synthesis in both industrial and academic labs.

Synthesis of 1-Boc Piperazine

1-Boc Piperazine is synthesized by reacting piperazine with di-tert-butyl dicarbonate (Boc₂O) under basic conditions (commonly with triethylamine or sodium bicarbonate). This selective reaction introduces the Boc group to one nitrogen atom, leaving the other available for further modification. The Boc group is acid-labile, meaning it can be easily removed with trifluoroacetic acid (TFA) or HCl in dioxane — a common step in deprotection strategies.

Pharmaceutical and Industrial Applications

1. Intermediate for Drug Molecules

Piperazine-based compounds appear in over 20 approved drugs, such as:

• Ciprofloxacin (antibiotic)

• Risperidone (antipsychotic)

• Sildenafil (vasodilator)

• Dasatinib (anticancer)

1-Boc Piperazine serves as a protected precursor, simplifying the synthetic route to such molecules by providing clean, reproducible, and controlled substitution.

2. Lead Optimization & Structure-Activity Relationship (SAR) Studies

Due to its solubility and flexibility, medicinal chemists use 1-Boc Piperazine during lead generation and SAR exploration. It contributes to better:

• Receptor binding affinity

• Lipophilicity tuning

• Solubility improvements

• Metabolic stability

3. Scaffold in Peptidomimetics and Macrocycles

1-Boc Piperazine is widely used in macrocyclic drugs and peptidomimetic design, where its nitrogen atoms and ring flexibility help mimic natural peptides. These features are essential for creating protease inhibitors, antiviral agents, and enzyme blockers.

Advantages of Boc Protection

The Boc group offers:

• Stability during base-sensitive reactions

• Easy deprotection under mild acid

• Increased synthetic selectivity

• Minimized side reactions during multi-step synthesis

Its compatibility with automated synthesis platforms makes it indispensable for combinatorial chemistry libraries.

Storage and Handling

• Shelf-life: Stable under normal conditions if kept dry and away from light

• Storage Temperature: 2°C – 8°C recommended for extended shelf life

• Hazards: May cause irritation; not considered highly toxic

• Precautions: Use gloves, lab coat, and goggles; handle in well-ventilated area

Always refer to the Material Safety Data Sheet (MSDS) for proper handling guidelines.

Packaging and Availability

Offered by chemical suppliers in:

• Research packs: 1g, 5g, 25g, 100g

• Bulk & commercial lots: 1kg, 5kg, 25kg, with custom contract manufacturing available

Documentation: Supplied with COA, MSDS, TDS, and batch analysis reports. Export supported globally with REACH & ISO compliance as required.

Conclusion

1-Boc Piperazine is an indispensable tool for organic and medicinal chemists. Its protected structure, ease of functionalization, and pharmacological relevance make it a go-to intermediate in the development of next-generation therapeutics. Whether you're working in drug discovery, process chemistry, or academic research, this versatile compound supports innovation with efficiency, flexibility, and reproducibility.