Phenylhydrazine-4-Sulfonamide in Celecoxib API Manufacturing
- Phenylhydrazine-4-sulfonamide (4-Hydrazinobenzenesulfonamide) is the key hydrazine coupling partner in the regioselective pyrazole ring formation of Celecoxib.
- High industrial purity (>99%) and strict control of regioisomeric impurities are essential for GMP-compliant Celecoxib synthesis with yields exceeding 85%.
- NINGBO INNO PHARMCHEM CO.,LTD. supplies bulk quantities of 4-Hydrazinobenzenesulfonamide with full COA, optimized for water-based condensation processes.
In the industrial synthesis of Celecoxib—a selective COX-2 inhibitor used globally for osteoarthritis and rheumatoid arthritis—the structural precision of intermediates directly dictates final API quality. Among these, Phenylhydrazine-4-sulfonamide, more precisely known as 4-Hydrazinobenzenesulfonamide (CAS 4392-54-5), serves as the indispensable arylhydrazine building block that enables the formation of the 1,5-diarylpyrazole core. This compound, also referenced as p-Hydrazinobenzenesulfonamide or 4-(sulfamyl)phenylhydrazine, undergoes a condensation reaction with 1-(4-methylphenyl)-4,4,4-trifluorobutane-1,3-dione to construct the pharmacologically active scaffold of Celecoxib.
Role in Regioselective Pyrazole Ring Formation
The efficacy of Celecoxib hinges on the exclusive formation of the 1,5-regioisomer over the undesired 1,4-analog, which lacks therapeutic activity and complicates purification. The use of high-purity 4-Hydrazinobenzenesulfonamide under controlled acidic aqueous conditions—typically with HCl at pH < 7 and temperatures near reflux (98–100°C)—ensures >97% regioselectivity toward the desired Celecoxib structure. Impurities such as residual solvents, inorganic salts, or oxidized hydrazine species can catalyze side reactions or promote regioisomer formation, underscoring the necessity for stringent quality control.
When sourcing high-purity 4-Hydrazinobenzenesulfonamide, buyers should verify compliance with ICH Q3 guidelines and confirm analytical validation via HPLC methods capable of resolving structurally similar impurities. NINGBO INNO PHARMCHEM CO.,LTD. provides this intermediate with typical assay purity ≥99.0% (HPLC, area normalization), moisture ≤0.5% (KF), and residual chloride within pharmacopeial limits.
Integration into Commercial GMP Synthesis Routes
Modern Celecoxib manufacturing favors one-pot or telescoped processes that avoid isolating sensitive intermediates. In such workflows, 4-AMINOSULFONYLPHENYLHYDRAZINE is often introduced directly into the reaction mixture containing the trifluoromethyl diketone precursor. Water is the preferred solvent due to its ability to suppress byproduct formation while maintaining adequate solubility of the hydrochloride salt form of the hydrazine intermediate.
Post-condensation, crude Celecoxib is precipitated by adding a mixed solvent system—commonly methanol:toluene (5:95 v/v)—followed by carbon treatment and crystallization to yield Form III Celecoxib with ≥99.8% purity and regioisomer content <0.1%. The efficiency of this step is highly dependent on the initial quality of the 4-Hydrazinobenzenesulfonamide; even minor deviations in sulfonamide group integrity or hydrazine oxidation state can reduce isolated yields by 5–10%.
Industrial Handling, Stability, and Regulatory Compliance
As a hydrazine derivative, 4-HYDRAZINO-BENZENSULFONAMIDE requires careful handling due to its potential reactivity and sensitivity to oxidation. It is typically supplied as a stable white to off-white crystalline powder, stored under nitrogen at 2–8°C, with recommended shelf life of 24 months when sealed. Industrial users must implement inert atmosphere transfers and avoid contact with strong oxidizers or metal catalysts.
For global pharmaceutical manufacturers, documentation is as critical as chemical quality. NINGBO INNO PHARMCHEM CO.,LTD. delivers comprehensive regulatory support, including Certificate of Analysis (COA), Safety Data Sheet (SDS), and Drug Master File (DMF) access where applicable. Their production facilities adhere to ISO 9001 and cGMP standards, ensuring batch-to-batch consistency required for commercial API campaigns.
Typical Specifications for Bulk Supply
| Parameter | Specification | Test Method |
|---|---|---|
| Chemical Name | 4-Hydrazinobenzenesulfonamide | IUPAC |
| CAS Number | 4392-54-5 | - |
| Assay (Purity) | ≥99.0% | HPLC (Area Normalization) |
| Appearance | White to off-white crystalline powder | Visual |
| Water Content | ≤0.5% | Karl Fischer |
| Residual Solvents | Complies with ICH Q3C | GC |
| Heavy Metals | ≤10 ppm | AAS/ICP-MS |
With over a decade of expertise in complex heterocyclic intermediates, NINGBO INNO PHARMCHEM CO.,LTD. stands as a premier global manufacturer of high-purity 4-sulfonamidophenylhydrazine derivatives. Their vertically integrated synthesis route ensures cost-effective bulk pricing without compromising on the stringent quality demands of modern Celecoxib API production. For scale-up projects requiring multi-hundred-kilogram to metric-ton quantities, their technical team offers process optimization support to maximize yield and minimize impurity carryover in your manufacturing workflow.