Analysis of the Production Process for 3-Methyl-6-Nitro-1H-Indazole

Alias: 3-Methyl-6-nitro-1H-indazole

CAS No: 6494-19-5

Molecular Formula: C8H7N3O2

Molecular Weight: 177.16

Physical State: Solid powder

Melting Point: 187-188°C

Boiling Point: 384.9±22.0 °C (Predicted)

Density: 1.437

Applications: Used as an organic intermediate and pharmaceutical intermediate.

3-Methyl-6-nitro-1H-indazole is an important chemical intermediate widely used in the pharmaceutical, pesticide, and materials science fields. Its core structure is an indazole ring, with a methyl group introduced at the 3-position and a nitro group at the 6-position. The production process of this compound directly determines its product quality, yield, and cost. This article will analyze the production process of 3-methyl-6-nitro-1H-indazolefrom the aspects of raw material selection, reaction conditions, and process optimization.

1. Overview of the Production Process

The production of 3-methyl-6-nitro-1H-indazole is mainly achieved through two steps:

Construction of the Indazole Ring: Synthesize 3-methylindazole from o-aminotoluene through a cyclization reaction.

Nitration Reaction: Introduce a nitro group at the 6-position of the indazole ring through a nitration reaction using nitric acid or mixed acid.

2. Production Process Steps

2.1 Construction of the Indazole Ring

Using o-aminotoluene as the starting material, the indazole skeleton is generated through a cyclization reaction. Common cyclization methods include the following steps:

Raw Material Preparation: React o-aminotoluene with an acidic catalyst (such as sulfonyl chloride or phosphorus trichloride) under high-temperature conditions.

Cyclization Reaction: Heat at high temperatures to generate the indazole structure, and purify the product through distillation or recrystallization.

Chemical Reaction Formula:

o-Aminotoluene → 3-Methylindazole

2.2 Nitration Reaction

Nitration is a crucial step in the production of 3-methyl-6-nitro-1H-indazole from 3-methylindazole. This process is usually carried out in a mixed acid system (nitric acid and sulfuric acid), with the following specific steps:

Dissolution and Reaction: Dissolve 3-methylindazole in concentrated sulfuric acid and slowly add nitric acid solution dropwise at low temperatures.

Temperature Control: The reaction temperature needs to be controlled at 0-10°C to avoid the generation of by-products.

Post-treatment: Through neutralization of the reaction solution, extraction, and recrystallization, a target product with high purity is finally obtained.

Chemical Reaction Formula:

3-Methylindazole + HNO₃/H₂SO₄ → 3-Methyl-6-nitro-1H-indazole

3. Process Optimization and Challenges

3.1 Improving Yield

Optimizing the addition speed of nitric acid: Slowly adding nitric acid can avoid excessively high local reactivity and reduce the generation of by-products.

Selecting appropriate catalysts: Using efficient catalysts (such as sulfonyl chloride) in the cyclization reaction can improve the yield.

3.2 Enhancing Product Purity

Controlling reaction temperature: The nitration reaction needs to be carried out at low temperatures to avoid impurities caused by side reactions.

Optimizing post-treatment: Increasing the number of extractions or using column chromatography techniques can further improve product purity.

3.3 Greening the Process

Waste acid treatment: The waste acid generated during the nitration process needs to be neutralized or reused through waste acid recovery devices to reduce environmental pollution.

Alternative reagents: Researching more environmentally friendly nitration reagents (such as ammonium nitrate) can reduce by-product emissions.

4. Production Equipment Requirements

Due to the involvement of strong acids and highly corrosive substances at high temperatures in the nitration reaction, the production equipment needs to meet the following requirements:

Corrosion-resistant materials: The reaction kettle should be made of stainless steel or enamel to avoid acid corrosion.

Temperature control system: Precise temperature control devices can ensure the stability of the reaction.

Waste gas treatment devices: Equipped with an off-gas absorption tower (such as a NaOH solution tower) to treat harmful gases generated during the nitration reaction.

5. Applications and Market Prospects

As an important intermediate, 3-methyl-6-nitro-1H-indazole has a wide range of applications in the following fields:

Pharmaceutical intermediates: Used in the synthesis of antibacterial and anti-tumor drugs.

Agricultural chemicals: An important raw material for insecticides and plant growth regulators.

Materials science: Has potential in the development of fluorescent materials and electrochemical materials.

With the development of the fine chemicals industry, the demand for 3-methyl-6-nitro-1H-indazole will continue to grow, and the optimization of its production process and the improvement of large-scale production capacity are of great significance.

The core of the production process for 3-methyl-6-nitro-1H-indazole lies in the efficient control of cyclization and nitration reactions. By optimizing reaction conditions, improving equipment, and applying green processes, the yield and product purity can be significantly improved, while reducing production costs and environmental impacts. In the future, this compound will have broad market prospects in the pharmaceutical, agricultural chemical, and materials science fields.