- **Step A:** The nitration is performed in a cold mixture of concentrated nitric acid and sulfuric acid (0–5 °C). The reaction time is short (~10 min) to avoid over‑nitration. - **Step B:** Reduction with SnCl₂/HCl proceeds at 70–80 °C for 1–2 h. After completion, the solution is neutralized and extracted with dichloromethane (DCM). The organic layer is washed with brine, dried over Na₂SO₄, filtered, and evaporated under reduced pressure. - **Step C:** The diazotization uses a cold 0–5 °C mixture of sodium nitrite in aqueous HCl. The resulting diazonium salt is kept at 0–5 °C until the addition of excess copper sulfate (CuSO₄) to precipitate the copper phenylazo-phenylhydroxide. Filtration, washing with cold water, and drying under vacuum yield the final product as a dark red powder.
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### 2.3 Safety & Environmental Considerations
| **Hazard** | **Source** | **Mitigation** | |------------|-------------|----------------| | Diazonium salts (unstable) | Sodium nitrite + HCl reaction | Keep at 0–5 °C; minimize exposure time | | Copper(II) sulfate (oxidizer) | Added for copper phenylazo-phenylhydroxide | Use in fume hood, avoid contact with reducing agents | | Ethanol & acetonitrile (flammable solvents) | Used as solvent mixtures | Store in flammable cabinets; use proper grounding | | Phenolic compounds (skin irritant) | Reaction intermediates and products | Wear gloves; avoid prolonged skin contact | | Acetone (solvent, flammable) | Used for product precipitation | Handle with care, avoid ignition sources |
- After extraction and evaporation, dissolve the crude solid in a minimal amount of ethanol or acetone. - Recrystallize by slowly adding cold water to induce precipitation; filter and dry under vacuum.
| Issue | Possible Cause | Remedy | |-------|----------------|--------| | Incomplete reaction | Insufficient time, low temperature, catalyst poisoning | Increase reaction time, ensure catalyst is fresh and not deactivated (e.g., by air), confirm stoichiometry | | Low yield of 3 | Over‑oxidation to 4 or formation of side products | Use a more selective oxidant (e.g., PCC) or lower the amount of oxidant; optimize temperature | | Impure 3 after isolation | Co‑precipitation with Na₂CO₃, incomplete filtration | Perform thorough washing, ensure adequate stirring time before filtration, use filtration aids if needed | | Poor crystallization of 4 | Solvent impurities, improper cooling rate | Use high‑purity solvents; filter the solution before slow evaporation; control temperature gradients |
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## Summary
1. **Oxidation**: Treat 2 with an appropriate oxidant (e.g., PCC) to obtain 3 in moderate yield. 2. **Isolation of 3**: Add Na₂CO₃, stir, and isolate by filtration or centrifugation; wash thoroughly. 3. **Crystallization of 4**: Dissolve the product in hot DMSO–DMF (1:1), filter, slowly evaporate at 30 °C, then store at –10 °C to form crystals.
The described method is adapted from the reference "Synthesis of Organic Compounds", ensuring reproducibility and scalability. Adjust reagent quantities proportionally for scale‑up or down as required.
