About this product:
CAS Number : 57260-71-6
Molecular weight : 186.25
Molecular formula : C9H18N2O2
Linear formula : NH (CH2CH2)2 NCOOC (CH3)3
Synonym(s) : Tert-Butyl piperazine-1-carboxylate
1-BOC-PIPERAZINE; BOC-PIPERAZINE, PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER,
1-N-BOC-PIPERAZINE, 1-(TERT-BUTOXYCARBONYL), N-(TERT-BUTYLOXYCARBONYL)-PIPERAZINE;PIBOC,
BOC-PAZ; N-Boc Piperizene,
Physical properties:
Appearance : Off- White to Slight Yellow Coloured Solid
Purity : >98% (GC)
Melting point : 43°C – 47°C
Storage temperature : Keep in dark place Room temperature
Moisture content : NMT 0.50%
Solubility : Soluble in MDC and Methanol
Density : 1.030 ± 0.06 g/cm3
Description : 1-Boc-Piperazine (CAS 57260-71-6), Is a chemical compound used as a building block in organic synthesis, particularly in the production of pharmaceuticals. It functions as a protected form of piperazine, a cyclic diamine, allowing selective reactions at one of the nitrogen atoms. This protective group (Boc) can be readily removed under specific conditions.
Research involving this compound spans several key domains:
1-Boc-piperazine is a versatile intermediate used in the synthesis of pharmaceuticals, including antipsychotics, anti-allergics, and antibacterial drugs. It is also a crucial building block for creating other chemicals, such as (m-phenoxy)phenyl substituted piperazine derivatives, indazole DNA gyrase inhibitors, and components in lipopolymer synthesis. Its primary role is in organic and medicinal chemistry for creating more complex molecules through reactions like N-arylation and Buchwald-Hartwig coupling.
Applications in pharmaceutical synthesis
- Arylpiperazine derivatives: Used to create compounds with dual receptor binding affinities (D2 and 5-HT1A) for potential psychiatric treatments.
- Antitussive, anti-allergic, and antipsychotic drugs: A key raw material in the production of various drugs in these categories.
- Antiparasitic drugs: Although piperazine itself is used to treat parasitic infections, 1-Boc-piperazine is a key intermediate for creating modified versions.
Applications in chemical synthesis
- (m-phenoxy)phenyl substituted piperazine derivatives: Used to prepare a series of these specific derivatives.
- Indazole DNA gyrase inhibitors: A key component in the synthesis of these inhibitors, which are used to combat DNA gyrase.
- α,β-poly(2-oxazoline) lipopolymers: Functions as a terminating agent during the synthesis of these complex polymers via living cationic ring opening polymerization.
- Coupling reactions: Participates in coupling reactions, such as Buchwald-Hartwig coupling, with aryl halides to form carbon-nitrogen bonds.
General use
- Building block: Serves as a fundamental building block in modern chemical synthesis due to its protected amine function.
- Medicinal chemistry: Its wide range of uses makes it an important chemical for designing a variety of therapeutic agents.
Synthesis of Biologically Active Compounds: This compound is a crucial intermediate in the synthesis of a variety of biologically active molecules. This includes piperazinyl amides and derivatives with dual receptor affinities, such as those targeting D2 and 5-HT1A receptors. It is also used in the synthesis of indazole DNA gyrase inhibitors and in the preparation of (m-phenoxy)phenyl substituted piperazine derivatives. Its application extends to the synthesis of compounds with potential anticancer activity.
Development of Novel Synthetic Methodologies: this compound is frequently employed as a substrate in the development and application of new synthetic reactions. This includes Buchwald-Hartwig coupling reactions with aryl halides, allowing for the formation of carbon-nitrogen bonds. It has also been utilized in copper-catalyzed cross-coupling reactions with aryl iodides. Recent advancements in C-H functionalization of piperazines have also involved N-Boc protected piperazine derivatives.
Material Science Applications: Beyond medicinal chemistry, this compound plays a role in the preparation of materials such as alpha,beta-poly(2-oxazoline) lipopolymers through living cationic ring opening polymerization.
Amidation Reactions
Amidation reactions involving 1-Boc-piperazine are crucial for incorporating the piperazine core into amide-containing structures. These reactions typically involve the coupling of the secondary amine of this compound with a carboxylic acid or a carboxylic acid derivative.
Synthesis of Piperazinyl Amides (e.g., with Glycyrrhetinic Acid Derivatives)
This compound has been utilized in the synthesis of piperazinyl amides of 18β-glycyrrhetinic acid, a triterpene with various biological activities. One reported procedure involves the amidation of this compound with 3-acetyl-18β-glycyrrhetinic acid. This reaction can be carried out under specific conditions to yield the desired piperazinyl amide intermediate. Another approach involves the amidation of 18β-glycyrrhetinic acid first, followed by esterification with acetic anhydride . The resulting Boc-protected piperazinyl amide can then undergo N-Boc deprotection to yield the final piperazinyl amide product. The reaction between 18β-glycyrrhetinic acid and this compound has shown temperature dependence.
An example of conditions used for the amidation of 18β-glycyrrhetinic acid with this compound involves using EDCl, triethylamine, and HOBt in acetonitrile under reflux for 24 hours.
Solvent-Free Amidation Protocols
While some amidation reactions involving this compound may utilize solvents, research has explored solvent-free protocols for the synthesis of piperazinyl amides. For instance, a method for preparing 3-acetyl-18β-glycyrrhetinic acid involves the reaction of 18β-glycyrrhetinic acid with acetic anhydride without any solvent at 130 °C, which is then used in an amidation step with this compound. Another study mentioned a solvent-free N-Boc protection catalyzed by iodine to prepare this compound itself in 80% yield. However, under certain solvent-free conditions utilizing water as a solvent for the direct amidation of esters, N-Boc piperazine was reported to be completely inactive towards phenyl esters.
Carbon-Nitrogen (C-N) Coupling Reactions
C-N coupling reactions, particularly Buchwald-Hartwig and copper-mediated cross-couplings, are significant for forming bonds between the nitrogen atom of this compound and carbon atoms of aryl or heteroaryl halides, allowing for the synthesis of substituted arylpiperazines.
Buchwald-Hartwig Coupling with Aryl Halides
This compound is a known substrate for Buchwald-Hartwig coupling reactions with aryl halides. This reaction is a powerful tool for synthesizing arylpiperazine derivatives, which are valuable intermediates in the synthesis of various pharmaceutical compounds. Buchwald-Hartwig amination typically involves palladium catalysts and suitable ligands. The coupling of mono-N-substituted piperazine rings, such as N-Boc piperazine, with aryl halides is a common transformation in drug discovery.
Copper-Mediated Cross-Coupling Reactions
Copper-catalyzed cross-coupling reactions provide an alternative method for the N-arylation of this compound with aryl iodides. A convenient and practical strategy involves the cross-coupling of N-Boc protected piperazines with aryl iodides in the presence of a catalytic system such as CuBr/rac-BINOL and K3PO4 as a base. This method has been applied in the synthesis of key intermediates for pharmaceutical compounds like trazodone. Excited-state copper-catalyzed reactions have also been explored, demonstrating compatibility with piperazine derivatives in annulation reactions.
Research into Cannabinoid Receptor Modulators
Research into cannabinoid receptor modulators, particularly those targeting the CB1 receptor, has also involved the use of Boc-protected piperazine derivatives. Compounds acting as antagonists or inverse agonists of peripheral CB1 receptors are being investigated for potential therapeutic applications in conditions such as obesity, liver disease, metabolic syndrome, and dyslipidemias . The synthesis of certain functionalized 6-piperazin-1-yl-purines, which act as CB1 inverse agonists, has utilized Boc-piperazine as a reactant in a nucleophilic reaction with a chlorinated purine intermediate . This step, followed by acid-mediated deprotection of the Boc group, yields the piperazine core necessary for the final compounds
