N-(4-Aminophenyl)-N,4-dimethyl-1-piperazineacetamide
[CAS# 262368-30-9]

Identification

• Classification: Organic raw materials >> Amino compound >> Amide compound
• Name: N-(4-Aminophenyl)-N,4-dimethyl-1-piperazineacetamide
• Molecular Formula: C₁₄H₂₂N₄O
• Molecular Weight: 262.35
• CAS Registry Number: 262368-30-9
• EC Number: 939-634-6
• SMILES: CN1CCN(CC1)CC(=O)N(C)C2=CC=C(C=C2)N

Properties

• Density: 1.2±0.1 g/cm³ Calc.^*
• Boiling point: 434.8±40.0 ºC 760 mmHg (Calc.)^*
• Flash point: 216.7±27.3 ºC (Calc.)^*
• Index of refraction: 1.598 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Specific target organ toxicity - single exposure	STOT SE	3	H335
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H332
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2	H319

Discovory and Applicatios

N-(4-Aminophenyl)-N,4-dimethyl-1-piperazineacetamide is a substituted acetamide featuring a piperazine ring and a para‑substituted aniline moiety. Its molecular formula is C₁₃H₂₁N₃O, and it has a molecular weight of approximately 231.33 g/mol. The molecule contains a piperazine ring substituted at the nitrogen with a methyl group and connected via an acetamide linker to a 4-aminophenyl group, while the other nitrogen of the piperazine bears a methyl group. This structure combines a flexible nitrogen-containing heterocycle with an aromatic amine and an amide, conferring both hydrophilic and lipophilic properties.

The synthesis of N-(4-aminophenyl)-N,4-dimethyl-1-piperazineacetamide typically begins with acylation of N,4-dimethylpiperazine using chloroacetyl chloride or a similar activated acyl derivative. The resulting N-acylated piperazine is then reacted with 4-aminophenylamine to form the amide linkage through nucleophilic substitution or direct coupling, often facilitated by a base or activating agent. Protective groups can be employed to shield reactive amines during the synthesis to ensure selectivity and prevent polymerization or side reactions. The final compound is usually purified by recrystallization or chromatography to obtain a homogeneous solid.

Chemically, the acetamide group provides a site for hydrogen bonding, contributing to solubility in polar solvents and potential interactions with biological targets. The piperazine ring is a tertiary diamine, with the nitrogen atoms able to act as hydrogen-bond acceptors or be protonated under acidic conditions. The para-aminophenyl group introduces an additional nucleophilic site that can participate in derivatization or act as a hydrogen-bond donor, influencing the electronic and steric environment of the molecule.

The compound is generally a solid at room temperature and exhibits moderate solubility in polar organic solvents such as ethanol, methanol, and dimethylformamide. Its stability is adequate under ambient conditions, but care should be taken to avoid prolonged exposure to strong acids or bases that could hydrolyze the amide or protonate the piperazine ring. The combination of rigid aromatic and flexible heterocyclic portions allows the molecule to adopt conformations that can be relevant for interactions with proteins or other molecular targets.

In practical applications, N-(4-aminophenyl)-N,4-dimethyl-1-piperazineacetamide is primarily used as a building block in medicinal chemistry and pharmaceutical research. The piperazine ring is a common motif in biologically active molecules, and its substitution pattern allows for tuning of lipophilicity, solubility, and hydrogen-bonding characteristics. The amide linkage and para-aminophenyl group provide additional handles for functionalization or conjugation, enabling the generation of derivatives for drug discovery, receptor binding studies, or other chemical biology applications.

Overall, the combination of a substituted piperazine, an aromatic amine, and an acetamide functionality makes N-(4-aminophenyl)-N,4-dimethyl-1-piperazineacetamide a versatile intermediate in synthetic and medicinal chemistry. Its structural features allow controlled functionalization, predictable reactivity, and suitability for incorporation into larger molecular frameworks, supporting the development of compounds with defined chemical and biological properties.

References

2021. Eschenmoser Sulfide Contraction in the Synthesis of Kinase Inhibitors. Synfacts.
DOI: 10.1055/s-0040-1720208

2015. Nintedanib. Pharmaceutical Substances.
URL: KD-14-0113