For chemists and quality control professionals, a thorough understanding of chemical synthesis, purification, and analytical techniques is crucial. This article delves into 6-Hydroxy-5-nitronicotinic acid (CAS: 6635-31-0), a vital intermediate, exploring its common synthesis pathways, purification methodologies, and the analytical techniques used for its characterization. This information is invaluable for R&D scientists and procurement managers aiming to ensure product quality and process efficiency.

Synthesis of 6-Hydroxy-5-nitronicotinic Acid

The primary synthetic route for 6-Hydroxy-5-nitronicotinic acid involves the nitration of 6-hydroxynicotinic acid. This electrophilic aromatic substitution reaction typically employs a mixed acid system, commonly concentrated sulfuric acid and fuming nitric acid. Critical to the success of this reaction is precise temperature control, usually maintained between 50-65°C, to ensure optimal yield and minimize the formation of byproducts. Reaction times can vary from several hours to over 18 hours, depending on the specific conditions and scale.

The process generates the nitronium ion (NO₂⁺) as the active electrophile, which attacks the activated pyridine ring. The hydroxyl group on the 6-hydroxynicotinic acid acts as an activating and directing group, guiding the nitro group to the desired position. Yields can range significantly, from around 29% in some documented procedures to over 99% under optimized conditions, underscoring the importance of precise parameter control. Manufacturers often employ advanced techniques, potentially including continuous flow reactors, to enhance safety, efficiency, and yield on an industrial scale.

Purification Strategies for High Purity

Achieving the required purity for 6-Hydroxy-5-nitronicotinic acid, typically specified at ≥98.0%, involves meticulous purification steps. Crystallization is the most common method. The crude product is often dissolved in hot water or organic solvents like methanol, followed by controlled cooling to induce precipitation. pH adjustment is also critical; maintaining acidic conditions (pH 1-3) helps precipitate the compound and remove basic impurities. For enhanced purity, recrystallization, sometimes in conjunction with activated carbon treatment to remove colored impurities, is employed. Chromatographic techniques, such as High-Performance Liquid Chromatography (HPLC) with reversed-phase columns (e.g., C18), are also utilized, particularly for analytical purposes or small-scale preparative purification, employing mobile phases typically consisting of water/acetonitrile or water/methanol mixtures with acidic modifiers.

Analytical Characterization Techniques

Confirming the identity and purity of 6-Hydroxy-5-nitronicotinic acid relies on a suite of analytical techniques:

  • Nuclear Magnetic Resonance (NMR) Spectroscopy: ¹H NMR reveals characteristic aromatic proton signals, typically doublets in the δ 8.4-8.9 ppm range, confirming the substitution pattern on the pyridine ring. ¹³C NMR provides information on the carbon skeleton.
  • Infrared (IR) Spectroscopy: Key functional groups are identified by characteristic absorption bands: a strong carbonyl stretch for the carboxylic acid group (~1700 cm⁻¹), and distinct symmetric and asymmetric stretches for the nitro group (~1520 and ~1350 cm⁻¹). The hydroxyl group also exhibits a broad O-H stretch.
  • Mass Spectrometry (MS): High-resolution MS confirms the molecular formula by providing the exact mass of the protonated molecule ([M+H]⁺) at approximately m/z 185.0194. Fragmentation patterns can further elucidate the structure.
  • Melting Point Determination: A sharp melting point within the specified range (269-271°C) indicates good purity.

Procurement and Quality Assurance

For R&D scientists and procurement managers, sourcing 6-Hydroxy-5-nitronicotinic acid requires attention to supplier reliability and product specifications. Purchasing from established manufacturers and suppliers, particularly those based in China, can provide access to competitive pricing and consistent quality. Always request a Certificate of Analysis (CoA) detailing purity, spectral data, and physical properties. Understanding the synthesis and analytical methods used by your supplier helps ensure that you are obtaining a product fit for your intended application, whether it's for pharmaceutical intermediate use or agrochemical research. Discussing purchase options and bulk availability with manufacturers like NINGBO INNO PHARMCHEM CO.,LTD. is crucial for establishing a stable supply chain.

Conclusion

A solid understanding of the synthesis, purification, and analytical characterization of 6-Hydroxy-5-nitronicotinic acid is essential for professionals in the chemical and life sciences industries. By leveraging this knowledge, researchers and procurement specialists can effectively select and utilize this vital intermediate, ensuring the quality and success of their synthesis projects and product development initiatives.