5-Hydroxy-3-Pyridinecarboxamide
[CAS# 101512-21-4]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Pyridine derivative
• Name: 5-Hydroxy-3-Pyridinecarboxamide
• Synonyms: 5-Hydroxynicotinamide; Stock2s-17236
• Molecular Formula: C₆H₆N₂O₂
• Molecular Weight: 138.12
• CAS Registry Number: 101512-21-4
• EC Number: 817-037-0
• SMILES: C1=C(C=NC=C1O)C(=O)N

Properties

• Density: 1.4±0.1 g/cm³, Calc.^*
• Index of Refraction: 1.622, Calc.^*
• Boiling Point: 479.3±30.0 ºC (760 mmHg), Calc.^*
• Flash Point: 243.7±24.6 ºC, 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
Eye irritation	Eye Irrit.	2A	H319
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Specific target organ toxicity - single exposure	STOT SE	3	H335

Discovory and Applicatios

5-Hydroxy-3-pyridinecarboxamide, also known by its systematic name as 5-hydroxynicotinamide, is a derivative of nicotinamide and belongs to the class of hydroxylated pyridines. It has the molecular formula C₆H₆N₂O₂ and is structurally characterized by a hydroxyl group at the 5-position and a carboxamide group at the 3-position of the pyridine ring. This compound is closely related to nicotinamide (niacinamide), a form of vitamin B₃, which plays a crucial role in human metabolism.

The discovery of 5-hydroxy-3-pyridinecarboxamide occurred during broader research into the metabolic and chemical transformation products of nicotinic acid and nicotinamide. Studies in the mid-20th century involving microbial degradation and mammalian metabolism of pyridine compounds identified various hydroxylated nicotinamide derivatives, including 5-hydroxy-3-pyridinecarboxamide, as metabolic intermediates or minor byproducts. These findings were often confirmed using chromatographic and spectroscopic techniques such as ultraviolet absorption spectra and later, nuclear magnetic resonance spectroscopy.

5-Hydroxy-3-pyridinecarboxamide has been isolated and studied in several contexts involving the biotransformation of nicotinamide-related compounds. It has been observed as a metabolite in microbial systems capable of degrading pyridine carboxamides. Such transformations have been reported in soil microorganisms, where pyridine derivatives serve as nitrogen sources under selective growth conditions. The hydroxylation at the 5-position is believed to be enzymatically mediated, often requiring molecular oxygen and cofactors such as flavin-containing enzymes.

In the field of synthetic organic chemistry, 5-hydroxy-3-pyridinecarboxamide has been used as an intermediate in the preparation of more complex heterocyclic compounds. Its functional groups allow for further derivatization, including substitution reactions on the pyridine ring or modifications of the amide moiety. These transformations are relevant in the design of chemical libraries for pharmaceutical screening, particularly in the development of compounds that may exhibit activity as enzyme inhibitors or modulators of biochemical pathways.

Some studies have reported the synthesis of 5-hydroxy-3-pyridinecarboxamide analogues to investigate their potential as precursors in the development of drugs targeting specific pyridine-binding enzymes. While the compound itself is not currently used as an active pharmaceutical ingredient, it has been employed in the study of structure-activity relationships involving pyridine-based molecules.

In analytical chemistry, 5-hydroxy-3-pyridinecarboxamide has occasionally been used as a reference compound for the development of chromatographic methods involving substituted pyridines. Its distinct retention behavior under various chromatographic conditions contributes to method validation and the establishment of compound libraries for environmental or pharmaceutical analysis.

Additionally, the compound has been examined in coordination chemistry. The hydroxyl and amide groups on the pyridine ring can act as ligands in the formation of metal complexes. These properties have been explored in laboratory settings for the synthesis of model compounds that mimic biological metal-binding motifs.

Overall, 5-hydroxy-3-pyridinecarboxamide is a well-characterized pyridine derivative with defined roles in biochemical transformation studies and synthetic chemistry. Its applications remain primarily in research contexts, especially where structural analogues of biologically active pyridine compounds are studied or synthesized for further biological or pharmacological evaluation.

References

2024. Design, synthesis and antitumour activity of pyrimidine derivatives as novel selective EGFR kinase inhibitors. Molecular Diversity.
DOI: 10.1007/s11030-024-11048-8

2020. Magnetically supported ionic liquids: a sustainable catalytic route for organic transformations. Mater. Horiz., 7(12).
DOI: 10.1039/D0MH01088J

2015. Transition metal carboxylate coordination polymers with amide-bridged polypyridine co-ligands: assemblies and properties. CrystEngComm, 17(21).
DOI: 10.1039/C4CE02531H