4-Aminophenylacetic acid
[CAS# 1197-55-3]

Identification

• Classification: Biochemical >> Amino acids and their derivatives >> Other amino acid derivatives
• Name: 4-Aminophenylacetic acid
• Synonyms: p-Aminophenylacetic acid
• Molecular Formula: C₈H₉NO₂
• Molecular Weight: 151.16
• CAS Registry Number: 1197-55-3
• EC Number: 214-828-7
• SMILES: C1=CC(=CC=C1CC(=O)O)N

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Melting point: 201 °C (Decomposes) (Expl.)
• Boiling point: 344.0±17.0 °C 760 mmHg (Calc.)^*
• Flash point: 161.9±20.9 °C (Calc.)^*
• Index of refraction: 1.615 (Calc.)^*

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

Safety Data

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

Hazard Classification

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

Discovery and Applications

4-Aminophenylacetic acid is an aromatic amino acid derivative with the molecular formula C₈H₉NO₂. It consists of a phenyl ring substituted with an amino group (–NH₂) at the para position (position 4) and a carboxymethyl group (–CH₂COOH) at position 1, giving the compound its name. The structure combines characteristics of both aromatic amines and carboxylic acids, making it a useful intermediate in organic synthesis, pharmaceutical development, and biochemical research.

This compound is one of the isomeric aminophenylacetic acids, with the para-amino derivative being especially valuable due to its symmetrical substitution pattern. It can be synthesized via several classical methods. One approach involves the nitration of phenylacetic acid to form 4-nitrophenylacetic acid, followed by catalytic hydrogenation or chemical reduction of the nitro group to an amino group. Alternatively, it may be prepared by direct amination of halogenated phenylacetic acid derivatives under nucleophilic substitution conditions.

4-Aminophenylacetic acid exhibits both acidic and basic properties, due to the presence of a carboxylic acid and an amino group. It can therefore exist in zwitterionic form under physiological conditions, and this amphoteric nature influences its solubility and reactivity. The compound is generally soluble in polar solvents such as water, methanol, or ethanol, especially in the form of its salts.

In pharmaceutical chemistry, 4-aminophenylacetic acid serves as a building block for the synthesis of various bioactive compounds. It has been used in the preparation of nonsteroidal anti-inflammatory drugs (NSAIDs), antitumor agents, and enzyme inhibitors. Its amino group allows for the formation of amides, ureas, sulfonamides, and Schiff bases, while the carboxylic acid group can undergo esterification, amidation, or salt formation.

One notable application is in the synthesis of drug candidates that target cyclooxygenase (COX) enzymes or other inflammatory mediators. The molecule’s structure allows it to be incorporated into larger frameworks that interact with biological targets through hydrogen bonding and hydrophobic interactions. Derivatives of 4-aminophenylacetic acid have also been studied for potential antibacterial, antifungal, and analgesic properties.

From a synthetic standpoint, 4-aminophenylacetic acid is versatile in multistep organic transformations. The para-amino group can be selectively protected or modified, for example, through acetylation or diazotization, to allow for further functionalization of the aromatic ring. The carboxylic acid moiety can be converted into acid chlorides, esters, or amides, expanding its utility in medicinal and materials chemistry.

In analytical chemistry, characterization of this compound is typically performed using proton nuclear magnetic resonance (²H NMR), carbon-13 NMR (³C NMR), infrared (IR) spectroscopy, and mass spectrometry. The amino and carboxyl groups give rise to characteristic absorption bands in IR spectra, including N–H stretching around 3300–3500 cm⁻¹ and C=O stretching near 1700 cm⁻¹. NMR data provide detailed structural information on aromatic proton splitting patterns and aliphatic side chains.

4-Aminophenylacetic acid is also used in peptide synthesis, particularly when introducing aromatic residues with amino functionalities into peptide backbones. It offers the advantage of incorporating both hydrophobic and hydrogen-bonding interactions into bioactive peptides and peptidomimetics.

In conclusion, 4-aminophenylacetic acid is a synthetically valuable compound with broad utility in organic and pharmaceutical chemistry. Its bifunctional nature and well-defined reactivity make it a key intermediate in the synthesis of therapeutic agents, chemical probes, and specialized polymers.

References

2019. Bioprocess Development for the Synthesis of 4-Aminophenylacetic Acid Using Nitrilase Activity of Whole Cells of Alcaligenes faecalis MTCC 12629. Catalysis Letters, 149(10).
DOI: 10.1007/s10562-019-02762-2

2015. A vibrational spectroscopy study on 3-aminophenylacetic acid by DFT calculations. Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy, 149.
DOI: 10.1016/j.saa.2015.03.094

2019. Metabolic engineering of microorganisms for production of aromatic compounds. Microbial Cell Factories, 18(1).
DOI: 10.1186/s12934-019-1090-4