การสังเคราะห์พาราเซตามอล (อะซิตามิโนเฟน)

ยาแก้ปวดที่มีการสั่งจ่ายมากที่สุดทั่วโลก

Pharmaceutical & Drug Manufacturing Global Industrial Scale $680 million

ภาพรวม

Paracetamol (acetaminophen) is the most widely used analgesic and antipyretic drug globally, with annual production exceeding 145,000 tons. The industrial synthesis proceeds through reduction of p-nitrophenol to p-aminophenol, followed by acetylation with acetic anhydride. Modern catalytic hydrogenation methods have replaced older iron-acid reduction, improving yields and reducing waste. The drug is formulated into tablets, capsules, liquids, and suppositories for over-the-counter and prescription use.

กระบวนการทางเคมี

p-Nitrophenol is catalytically hydrogenated to p-aminophenol using Pt/C or Pd/C catalyst at moderate pressure. The aminophenol is then acetylated with acetic anhydride in aqueous solution to form paracetamol, which is crystallized and dried.

HOC₆H₄NO₂ + 3H₂ →[Pd/C] HOC₆H₄NH₂ + 2H₂O
HOC₆H₄NH₂ + (CH₃CO)₂O → HOC₆H₄NHCOCH₃ + CH₃COOH

วัตถุดิบ

p-Nitrophenol (C₆H₅NO₃) — Nitration of phenol (Starting material)
Hydrogen gas (H₂) — Steam methane reforming (Reducing agent)
Acetic anhydride ((CH₃CO)₂O) — Ketene process (Acetylating agent)

ผลิตภัณฑ์สำเร็จรูป

Paracetamol (C₈H₉NO₂) — Analgesic and antipyretic (USP grade, >99% purity)

Environmental Impact

The catalytic hydrogenation route is significantly cleaner than the older iron-acid reduction, which generated large quantities of iron oxide sludge. Acetic acid byproduct is recovered and recycled. The process has moderate environmental impact with controlled wastewater treatment.

ข้อควรพิจารณาด้านความปลอดภัย

⚠ p-Nitrophenol is toxic and environmentally persistent
⚠ Hydrogen gas is flammable and explosive
⚠ Platinum group metal catalysts require careful handling and recovery
⚠ Paracetamol dust is a potential inhalation hazard

นวัตกรรมล่าสุด

A new one-pot synthesis from hydroquinone using enzymatic amidation has been developed, eliminating the need for nitrophenol intermediates.
Continuous flow hydrogenation reactors improve safety and throughput.