Industrial Purity Specifications for 5-Chloro-2-Fluoro-3-Methylpyridine
- CAS Registry: 375368-84-6 ensures precise identification for regulatory compliance and procurement.
- Assay Standards: Industrial grades typically require ≥98.0% to ≥99.0% purity verified by GC/HPLC.
- Supply Chain: Bulk procurement relies on verified manufacturing processes and stable logistics for hazardous chemicals.
In the realm of advanced organic synthesis, fluorinated pyridine derivatives represent a critical class of building blocks. Specifically, 5-Chloro-2-Fluoro-3-Methylpyridine (CAS: 375368-84-6) has emerged as a vital intermediate for pharmaceutical and agrochemical development. The molecular formula C6H5ClFN and a molecular weight of 145.56 g/mol define its structural integrity, but for process chemists and procurement officers, the defining metric is industrial purity. Achieving consistent assay levels above 98% is not merely a specification; it is a requirement for downstream reaction yield optimization and impurity profile control.
At NINGBO INNO PHARMCHEM CO.,LTD., we understand that the reliability of a synthesis campaign depends on the quality of the starting materials. This technical overview details the physical properties, analytical verification methods, and commercial considerations necessary for sourcing this compound at an industrial scale.
Physicochemical Properties and Specification Limits
Accurate characterization is the foundation of quality control. When evaluating batch data, procurement teams must verify that the physical constants align with theoretical predictions. Deviations in boiling point or density often indicate the presence of solvent residues or regioisomeric impurities. The following table outlines the standard specification parameters expected for high-grade material.
| Property | Specification / Value |
|---|---|
| CAS Number | 375368-84-6 |
| IUPAC Name | 5-chloro-2-fluoro-3-methylpyridine |
| Molecular Formula | C6H5ClFN |
| Molecular Weight | 145.56 g/mol |
| Appearance | Crystalline powder to faint yellow liquid |
| Boiling Point | 189.4 ± 35.0 °C (Predicted) |
| Density | 1.264 ± 0.06 g/cm³ |
| Storage Temperature | 2-8°C (Under inert atmosphere) |
| Purity (Assay) | ≥ 98.0% (GC Area Normalization) |
It is crucial to note that storage conditions significantly impact stability. Due to the reactivity of the halogenated pyridine ring, material should be stored between 2-8°C to prevent degradation or polymerization over extended periods. Proper handling ensures that the Pyridine 5-chloro-2-fluoro-3-methyl- structure remains intact until it is introduced into the reaction vessel.
Analytical Verification and COA Compliance
For GMP-aligned production, the Certificate of Analysis (COA) is the primary document verifying quality. A robust COA should not only list the final assay percentage but also detail the specific analytical methods used. Gas Chromatography (GC) and High-Performance Liquid Chromatography (HPLC) are the standard methods for quantifying the main peak and identifying impurities.
Key impurities to monitor include regioisomers such as 3-chloro-2-fluoro-5-methylpyridine or unreacted starting materials from the halogenation steps. A purity level of 95% may be acceptable for early-stage research, but commercial-scale manufacturing typically demands ≥98.0% to minimize purification burdens downstream. The presence of heavy metals or residual solvents must also be quantified according to ICH Q3 guidelines. When reviewing documentation, buyers should ensure that the testing laboratory is accredited and that the batch number on the COA matches the physical labeling.
Optimization of the Manufacturing Process
The scalability of this intermediate relies heavily on the efficiency of the synthesis route. Industrial production typically involves selective halogenation of methylpyridine precursors. The challenge lies in controlling the regioselectivity to ensure the fluorine and chlorine atoms occupy the 2 and 5 positions respectively, without generating excessive isomeric byproducts.
Advanced manufacturing process controls utilize precise temperature regulation and catalyst selection to maximize yield while suppressing side reactions. At NINGBO INNO PHARMCHEM CO.,LTD., continuous improvement in reactor design allows for better heat dissipation during exothermic halogenation steps, resulting in higher consistency across large batches. This technical capability is essential for maintaining supply continuity for clients producing anti-infective agents or specialized agrochemicals.
Commercial Considerations and Bulk Procurement
Pricing for fluorinated pyridines fluctuates based on raw material costs, particularly fluorinating agents, and energy consumption during synthesis. While small-scale packaging (grams) commands a premium due to handling and packaging costs, bulk procurement (kilograms to tons) offers significant economic advantages. The bulk price is generally determined by the required purity grade and the complexity of the logistics involved in shipping hazardous chemicals.
Supply chain reliability is paramount. When evaluating potential partners, it is advisable to assess their production capacity and regulatory compliance history. When sourcing high-purity global manufacturer capabilities ensure consistent batch-to-batch reproducibility and adherence to international safety standards. This reduces the risk of production delays caused by quality failures or customs hold-ups.
Safety and Regulatory Handling
Safety data indicates that this compound carries specific hazards that must be managed during transport and handling. The GHS classification typically includes a Warning signal with hazard statements H315 (Causes skin irritation), H319 (Causes serious eye irritation), and H335 (May cause respiratory irritation).
Appropriate personal protective equipment (PPE), including chemical-resistant gloves and eye protection, is mandatory. Precautionary statements such as P261 (Avoid breathing dust/fume/gas/mist/vapours/spray) and P305+P351+P338 (IF IN EYES: Rinse cautiously with water for several minutes) should be strictly followed. The HS Code 2933399990 is commonly used for customs declaration, but exporters must verify local regulations regarding halogenated organic compounds.
Conclusion
5-Chloro-2-Fluoro-3-Methylpyridine is a high-value intermediate requiring stringent quality control. From verifying the industrial purity via GC analysis to ensuring the manufacturing process meets safety standards, every step impacts the success of the final drug substance or agrochemical product. By prioritizing verified suppliers who provide comprehensive COA documentation and stable bulk supply, organizations can mitigate risk and optimize their synthesis campaigns.