2-Chloronicotinic acid (CAS 2942-59-8, C6H4ClNO2, MW 157.55) is a chlorinated pyridine carboxylic acid widely used as a building block in pharmaceutical and agrochemical synthesis. Its two functional handles – the carboxylic acid and the 2-chloro substituent – make it a versatile intermediate for APIs, neonicotinoid insecticides and heterocyclic scaffolds. This guide covers its chemistry, production routes, specifications, applications and buying considerations.
1. What Is 2-Chloronicotinic Acid?
2-Chloronicotinic acid is the 2-chloro derivative of nicotinic acid (niacin, pyridine-3-carboxylic acid). The chlorine at the 2-position activates the ring for nucleophilic substitution and cross-coupling, while the 3-carboxyl group provides a second synthetic handle. This makes it a key intermediate for building substituted pyridines, quinolines and fused heterocycles in pharmaceutical and agrochemical programmes.
2. Physical and Chemical Properties
| Property | Value |
|---|---|
| Molecular formula | C6H4ClNO2 |
| Molecular weight | 157.55 g/mol |
| Appearance | White crystalline powder |
| Melting range | >177 °C (decomposes) |
| Solubility | Soluble in aqueous NaOH (clear solution); limited water solubility as free acid |
| pKa | Carboxylic acid, weakly acidic |
3. Production Routes
Commercial 2-chloronicotinic acid is produced mainly by two routes:
- Chlorination of nicotinic acid: nicotinic acid is treated with a chlorinating agent (thionyl chloride, phosphorus oxychloride, or catalytic oxidative chlorination) followed by hydrolysis, giving the 2-chloro isomer with careful control of the 6-chloro by-product.
- Oxidation of chloromethylpyridines: 2-chloro-3-methylpyridine (or the chlorinated methylpyridine precursor) is oxidized to the carboxylic acid with nitric acid or a metal-catalysed oxidation.
Process control focuses on isomer selectivity (minimising 6-chloronicotinic acid), colour, and impurity profile (dimer and related substances), since pharmaceutical-grade material requires HPLC assay ≥99.5%.
4. Specifications
| Parameter | Value |
|---|---|
| Appearance | White crystalline powder |
| Assay (HPLC) | 99.5% min |
| 6-Chloronicotinic acid | 0.10% max |
| 2-CNA dimer | 0.10% max |
| Correlated each other impurity | 0.10% max |
| Sulphate | 0.10% max |
| Loss on drying | 0.30% max |
| Residue on ignition | 0.20% max |
| Melting range | >177 °C (decomposes) |
| Solution clarity | Clear (0.5 mol/L aqueous NaOH) |
For pharmaceutical intermediate use, request a COA showing HPLC purity, each impurity limit, loss on drying and residue on ignition per batch.
5. Applications Overview
- Pharmaceutical intermediates – building block for pyridine-containing APIs, heterocyclic drugs and fine chemicals.
- Agrochemical intermediates – chloronicotinic acid fragments for neonicotinoid insecticide chemistry.
- Ligands and specialty organics – substituted pyridine carboxylic acids for catalysts, dyes and electronic materials.
6. Application Details
6.1 Pharmaceutical synthesis
The 2-chloro group is a leaving group for SNAr substitution with amines, alkoxides and thiols, enabling rapid library synthesis around the pyridine core. The carboxyl group is esterified or amidated to build amide/ester drug fragments. Typical transformations include Suzuki coupling at C2 after conversion to the boronate, and amidation to pyridine carboxamides.
6.2 Agrochemical chemistry
Chloronicotinic acid derivatives are central to neonicotinoid-type chemistry; 2-chloronicotinic acid serves as a regioisomeric building block for chloropyridine insecticides and their acid chlorides.
6.3 Custom derivatisation
Because the molecule offers two orthogonal handles, custom synthesis of 2-chloro-pyridin-3-yl amides, esters, and 2-substituted nicotinates is straightforward at kilogram to hundred-kilogram scale.
7. Industry Landscape
Major producers of chloronicotinic acid and chloropyridine chemistry are located mainly in China (specialised fine-chemical and agrochemical intermediate plants). Buyers should compare isomer purity, impurity profile and batch consistency; for pharmaceutical use, supplier GMP/ISO status and change control matter.
8. Buying Guide
- Specify assay ≥99.5% (HPLC) and each impurity limit from the table above.
- Require COA per batch with measured values and test methods.
- Packaging: 25 kg fibre drums or bags with PE liner; smaller custom packs for trials.
- Storage: sealed, cool and dry; keep away from moisture and strong bases/oxidizers.
9. Safety and Handling
- Irritant to eyes, skin and respiratory tract; use gloves, goggles and ventilation.
- Avoid dust generation; keep away from strong oxidizers and bases.
- Dispose per local regulations; request MSDS from the supplier.
10. FAQ
Is 2-chloronicotinic acid the same as 6-chloronicotinic acid?
No – they are regioisomers. 2-Chloronicotinic acid has the chlorine at C2; 6-chloronicotinic acid at C6. Their reactivity and uses differ, and each is a separate specification item.
What is 2-chloronicotinic acid used for?
Mainly as a pharmaceutical and agrochemical intermediate for substituted pyridine compounds and heterocyclic APIs.
Can you supply custom derivatives?
Yes – custom esters, amides and 2-substituted nicotinates can be made to specification; contact us with your target structure.
11. References and Further Reading
- PubChem entry for 2-chloronicotinic acid (CID via PubChem REST API).
- Supplier COA and MSDS for the specific grade quoted.
This article is published for industrial and technical reference by PolyblueChem. Verify all values against the supplier’s COA and applicable standards before specification.
PolyblueChem supplies 2-chloronicotinic acid (CAS 2942-59-8) with COA and MSDS. Contact us for specifications and quotations.