Description

Technical Parameters

Introduction

raws

product-1400-1400

Products Description

#### 1. Overview of Phenacetin

Phenacetin is a classic antipyretic analgesic, with a chemical name of p-Acetophenetidine, a molecular formula of C₁₀H₁₃NO₂, a molecular weight of 179.22 g/mol, and a CAS number of 62-44-2. Since its synthesis in the late 19th century, it has been widely used to treat fever and pain, but it has been banned in many countries because of the risk of nephrotoxicity and carcinogenicity caused by long-term use. Despite this, it still has important value in chemical synthesis, laboratory research and specific industrial fields.

#### 2. Main classification of phenacetin APIs

According to the purity, use and production process, phenacetin APIs can be divided into the following categories:

##### **1. Pharmaceutical Grade Phenacetin**

- **Definition and Standard**

Meet the pharmacopoeia standards (such as USP, EP), purity ≥ 99.5%, impurity content strictly controlled below 0.1%, and must pass microbial limits, heavy metal residues and other tests.

- **Advantages**

- High purity ensures the stability of pharmacological effects;

- Comply with international pharmaceutical production standards (GMP);

- Once used as the core ingredient of compound preparations (such as APC tablets: aspirin, phenacetin, caffeine).

- **Application limitations**

Due to kidney damage and carcinogenicity, it has been gradually withdrawn from the market since the 1970s, and currently only a few countries allow limited use.

##### **2. Industrial Grade Phenacetin**

- **Definition and Characteristics**

Purity 90%-95%, containing a small amount of unreacted intermediates (such as p-nitrophenyl ethyl ether), mainly used as chemical intermediates or synthesis of other compounds.

- **Advantages**

- Low production cost, suitable for large-scale industrial synthesis;

- Used as a precursor to prepare dyes, pesticides and polymer materials.

- **Typical Applications**

- Synthesis of p-aminophenol (PAP), used in the dye industry;

- Preparation of rubber antioxidants;

- Production of photosensitive material precursors.

##### **3. Research Grade Phenacetin**

- **Definition and Standard**

Purity ≥ 99.9%, exclusively for laboratory use, requires analysis and verification by HPLC, NMR, etc., to meet trace analysis needs.

- **Advantages**

- Ultra-high purity reduces experimental interference;

- Used for pharmacological model construction (such as analgesic mechanism research);

- Used as a standard for mass spectrometry or chromatography analysis.

- **Research fields**

- Metabolic pathway research (the main metabolite is acetaminophen);

- Toxicological evaluation (analysis of nephrotoxicity mechanisms);

- Historical drug elimination case teaching.

##### **4. Custom Synthesis of Phenacetin (Custom Synthesis)**

- **Features**

Adjust the synthesis path according to customer needs (such as isotope labeling, structural modification), and flexibly customize the purity and specifications.

- **Application scenarios**

- ¹³C or ²H labeled phenacetin for metabolic tracking;

- Development of derivatives to reduce toxicity (such as methylation modification);

- Special crystal form research (improving solubility or stability)

#### 3. Synthesis process and technological progress of phenacetin

1. **Traditional synthesis method**

Using p-nitrochlorobenzene as raw material, it is prepared by three steps of ethoxylation, reduction and acetylation. The process is mature but the yield is low (about 65%) and there are many by-products.

2. **Green chemistry improvement**

- Use ionic liquid catalyst to improve ethoxylation efficiency;

- Microwave-assisted synthesis shortens reaction time;

- Bioenzymatic reduction reduces heavy metal pollution.

3. **Process comparison**

|------------|--------|--------|---------|

| Traditional method | 65% | Low | Low |

#### 4. Physical and chemical properties and quality control

- **Physical properties**

White crystalline powder, melting point 134-136°C, slightly soluble in water (0.1 g/100 mL), easily soluble in ethanol and chloroform.

- **Chemical stability**

It is easily hydrolyzed in strong acid and alkali to generate p-aminophenyl ether and acetic acid, and needs to be sealed and stored away from light.

- **Key quality control indicators**

- Related substances (HPLC method to detect impurities);

- Residual solvents (such as ethanol, ethyl acetate);

- Crystal consistency (X-ray diffraction analysis).

#### 5. Market status and regulatory environment

- **Global regulation**

- The EU, the United States, and China have banned medicinal use;

- Some Asian countries still allow veterinary use or limited use.

- **Supply chain analysis**

- Major producing countries: China and India (accounting for 80% of global production capacity);

- Price fluctuations: industrial grade is about $50-80/kg, and research grade is as high as $2000/kg.

- **Alternative trend**

Paracetamol and ibuprofen completely replace its medicinal status.

#### 6. Future prospects

- **Recycling technology**

Extract phenacetin from discarded drugs for industrial use to reduce resource waste.

- **Toxicity mechanism research**

Explore its carcinogenicity through gene editing technology to provide new ideas for safe application.

- **Development of new derivatives**

Design low-toxic and high-activity analogs to expand its new application in the field of analgesia.

#### Conclusion

Although phenacetin API has withdrawn from the mainstream pharmaceutical market, it is still irreplaceable in the field of chemical synthesis and scientific research. With the advancement of green synthesis technology and in-depth analysis of toxicity mechanisms, it may be reborn in specific fields in the future.