Long before high-throughput screening sped up drug discovery, chemists relied on methodical trial-and-error work. 1-Acetyl-4-(4-Hydroxyphenyl)Piperazine reflects the spirit of these early scientific endeavors. The compound’s backstory reaches into the roots of medicinal chemistry, when researchers experimented with piperazine derivatives to harness their central nervous system effects and tap their potential as intermediates for active pharmaceuticals. Interest in piperazine scaffolds grew in the late 1900s, as their flexibility and reactivity allowed medicinal chemists to construct diverse bioactive molecules. Its structure, marked by an acetyl group on the nitrogen and a hydroxyphenyl moiety, became a foundation in drug structure-activity relationship studies. This opened doors for exploring modifications that altered physiochemical properties and bioactivity.
1-Acetyl-4-(4-Hydroxyphenyl)Piperazine often appears as a white or off-white powder. It strikes a balance between water solubility and lipophilicity, which has fueled its use as a synthetic intermediate in research. Manufacturers distribute it for research, formulation development, and as a test substrate in analytical method validation. Its accessible functionality on both the piperazine ring and the aromatic system makes it a handy piece for academic and industrial labs. Its multiples points of reactivity offer chemists avenues for novel drug design as well as materials science work.
With a molecular formula of C12H16N2O2, 1-Acetyl-4-(4-Hydroxyphenyl)Piperazine presents a moderate molecular weight of about 220 grams per mole. The solid melts in the range of 109-112°C. In water, it displays low to moderate solubility, and it tends to dissolve much more readily in polar aprotic solvents such as DMSO. The compound features a neutral or slightly acidic phenolic group, which affects both its solubility and its behavior in organic reactions. Ultraviolet light detects this compound efficiently because the aromatic ring absorbs in the relevant regions. In routine storage under cool, dry conditions, the powder remains stable for extended periods, with little tendency toward degradation.
Producers offer this compound at a reported purity exceeding 98%. Analytical labs certify each lot through several techniques, including proton NMR and HPLC. Some distributors follow industry standards for container labeling, using globally harmonized system icons and hazard rankings. The labels highlight possible irritation and recommend basic precautions for handling, such as wearing gloves and eye protection. Trace impurities, if noted at all, fall below 1% and rarely impact research outcomes.
Synthesis commonly starts from 4-hydroxyaniline, which undergoes alkylation with a piperazine derivative, often via a nucleophilic substitution reaction. An acetylation step usually follows, using acetic anhydride under mild conditions and in the presence of a base such as sodium acetate or pyridine. The resulting product is purified by recrystallization from water-ethanol mixtures. Operators may rely on vacuum drying to ensure removal of solvents, leaving a dry, stable product for downstream use. Some laboratories choose alternative one-pot approaches to simplify and streamline the process, anchoring on operational simplicity and avoiding hazardous reagents.
This compound's core offers chemists a set of reliable modification sites. The phenolic group undergoes etherification and esterification, often to tune hydrophobicity or to attach targeting moieties for biological assays. The acetyl functionality can be removed or exchanged for other acyl groups, providing routes to structurally diverse analogues without altering the core piperazine system. Electrophilic aromatic substitution on the phenyl ring, such as halogenation or nitration, brings further diversity for structure-activity studies. The piperazine ring itself supports N-dealkylation or N-oxidation, giving rise to metabolites that researchers track in drug metabolism studies. These synthetic handles make the molecule attractive for both single compound synthesis and as a feedstock for combinatorial libraries.
Across the chemical and pharmaceutical industries, this molecule might travel under several names. Some catalogs list it as N-Acetyl-4-(4-Hydroxyphenyl)piperazine. The shorthand abbreviation 4-HO-APP is common in some research communities. Chemical supply houses occasionally use the systematic name 1-Acetyl-4-(p-hydroxyphenyl)piperazine in line with IUPAC conventions. Other synonyms, like N-[4-(4-Hydroxyphenyl)piperazin-1-yl]acetamide, may appear in patent or regulatory filings. Keeping track of these synonyms helps navigate the maze of literature and purchase orders.
Working with nitrogen-containing aromatics always deserves respect for safety protocols. This compound, though less hazardous than some aromatic amines, can still introduce risks. Inhalation or skin contact might trigger irritation in sensitive individuals. Good laboratory protocols call for use of gloves, protective eyewear, and adequate ventilation, especially if handling gram-scale quantities. Any accidental release onto work surfaces or skin should prompt prompt washing with soap and water. Waste material—whether solid residue or rinse—should go into chemical waste streams, not general trash or drains. Most labs find that careful adherence to written SOPs and regular safety reviews prevent accidents, even with novel compounds.
Researchers often turn to 1-Acetyl-4-(4-Hydroxyphenyl)Piperazine as a versatile intermediate. Its piperazine motif attracts attention in drug discovery, since many CNS-active agents share this backbone. Scientists use it as a template when designing serotonin receptor ligands or when probing the binding characteristics of enzyme inhibitors. Analysts in chemical testing labs also depend on it as a test probe to calibrate instruments for complex drug sample work. In materials research, the phenol group’s reactivity opens up possibilities for linking to polymers or surfaces, an application relevant in sensor development and analytical chemistry.
The R&D community has watched this compound with keen interest, driven by the realization that piperazine derivatives act as privileged structures in medicinal chemistry. Lab teams employ it as a chemical handle when building libraries for screening campaigns, targeting conditions ranging from psychiatric disorders to metabolic disease. Structural modifications around the hydroxyphenyl segment inspire new approaches to selectivity and metabolic stability. Published studies, especially in the past decade, reflect a surge in structural analogues aimed at hitting newer targets, including receptor subtypes and protein interaction interfaces. Each new variant helps pin down which atomic tweaks drive therapeutic outcomes or liabilities, so the compound’s popularity rarely wanes.
Toxicological screenings shed light on the limits and potential of molecules like 1-Acetyl-4-(4-Hydroxyphenyl)Piperazine. Preclinical data, often published as part of broader piperazine class exploration, point to mild to moderate toxicity at higher exposures in cell and animal models. Investigators flag the potential for liver enzyme interactions, a hallmark issue with aromatic amines and piperazine ring structures. The phenolic group, though generally seen as benign, can bioactivate in some metabolic contexts, which leads scientists to track oxidative byproducts closely. Regulatory bodies advise focusing on dose ranges, exposure frequencies, and possible cumulative effects—steps that mirror standard industry practice. The body of evidence gathered so far supports the view that cautious, well-controlled lab practice keeps risks well managed.
Continued advances in molecular biology, drug design, and analytical chemistry keep driving up the profile of specialty intermediates like 1-Acetyl-4-(4-Hydroxyphenyl)Piperazine. With every fresh insight into receptor function or enzyme selectivity, the need for sturdy, modifiable scaffolds grows. Many startups and university labs have begun exploring these modified piperazines not only as drug leads, but also as biosensor elements and chemical tags. Software-driven molecule screening and AI-predicted binding dynamics could soon unlock new roles for these compounds in both healthcare and high-tech manufacturing. As investment pours in to back early-stage research, piperazine-based intermediates stand poised to deliver innovation faster and help address everything from therapeutic gaps to diagnostics challenges.
