Ethyl 5-hydroxynicotinate
[CAS# 59288-38-9]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Hydroxypyridine
• Name: Ethyl 5-hydroxynicotinate
• Synonyms: 5-Hydroxy-3-Pyridinecarboxylic Acid Ethyl Ester
• Molecular Formula: C₈H₉NO₃
• Molecular Weight: 167.16
• CAS Registry Number: 59288-38-9
• SMILES: CCOC(=O)C1=CC(=CN=C1)O

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.542, Calc.^*
• Boiling Point: 375.4±22.0 ºC (760 mmHg), Calc.^*
• Flash Point: 180.8±22.3 ºC, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

Ethyl 5-hydroxynicotinate is an organic compound that belongs to the class of substituted nicotinic acid esters. It consists of a nicotinic acid (pyridine-3-carboxylic acid) core substituted at the 5-position with a hydroxyl group and at the carboxylic acid moiety with an ethyl ester functional group. The molecular formula of the compound is C₈H₉NO₃, and it possesses a pyridine ring that is commonly found in many bioactive molecules and pharmaceutical agents.

The synthesis of ethyl 5-hydroxynicotinate has been described in the chemical literature as part of efforts to modify the pyridine scaffold for various applications. One typical route involves the esterification of 5-hydroxynicotinic acid using ethanol in the presence of acid catalysts or under reflux conditions. This transformation allows for the protection of the carboxylic acid group as an ester, which is a commonly used strategy in synthetic organic chemistry to facilitate further functional group modifications.

Ethyl 5-hydroxynicotinate has been used as an intermediate in the synthesis of more complex heterocyclic compounds and pharmacologically active molecules. Its hydroxyl-substituted aromatic ring allows for additional chemical reactions, such as etherification, acylation, or coupling reactions. The presence of the pyridine nitrogen also makes it amenable to coordination with transition metals, which can be useful in the design of metal complexes for catalytic or medicinal purposes.

In medicinal chemistry, ethyl 5-hydroxynicotinate and related compounds have been studied for their potential roles as anti-inflammatory, antimicrobial, or enzyme inhibitory agents. While the compound itself is not a marketed pharmaceutical, its derivatives and structurally similar analogs have appeared in screening programs and research studies targeting biological receptors and enzymes. The ester functionality also permits hydrolysis under physiological or enzymatic conditions, releasing the corresponding carboxylic acid, which may influence bioavailability and pharmacokinetic properties.

Analytically, ethyl 5-hydroxynicotinate is characterized using standard spectroscopic methods, including nuclear magnetic resonance (NMR), infrared (IR) spectroscopy, and mass spectrometry (MS). Its structure is confirmed by the presence of characteristic signals corresponding to the ethyl ester group, the hydroxyl group on the aromatic ring, and the heterocyclic pyridine nucleus. The compound is typically obtained as a solid and stored under standard laboratory conditions.

In chemical research, this compound is often used as a starting material in the synthesis of fused heterocyclic systems, such as quinolines and pyrido[2,3-d]pyrimidines. The hydroxyl group at the 5-position serves as a nucleophilic site, which allows for the construction of more complex frameworks through condensation or cyclization reactions. These types of heterocycles are of interest due to their presence in a wide range of biologically active molecules.

Ethyl 5-hydroxynicotinate is available from chemical suppliers in research-grade purity and is commonly used in academic and industrial research laboratories. It is handled with standard safety precautions appropriate for small organic molecules, including the use of personal protective equipment and proper ventilation. It is typically stable under ambient conditions and soluble in common organic solvents such as ethanol, methanol, and dichloromethane.

Overall, ethyl 5-hydroxynicotinate is a well-characterized and synthetically accessible compound used in the development of heterocyclic chemistry and pharmaceutical intermediates. Its structural features offer versatility for further derivatization, and it continues to serve as a valuable tool in organic synthesis and drug discovery research.

References

2022. First synthesis of an ABCE ring substructure of daphnicyclidin A. Org. Biomol. Chem., 20(32).
DOI: 10.1039/D2OB01137G

2021. A highly efficient solution and solid state ESIPT fluorophore and its OLED application. New J. Chem., 45(6).
DOI: 10.1039/D0NJ05537A

1989. Synthesis and pharmacological activity of amino acid derivatives of nicotinic acid. Pharmaceutical Chemistry Journal, 23(12).
DOI: 10.1007/bf00764700