Production Process of Tetramethylethylenediamine (TMEDA)

English Name: N,N,N′,N′-Tetramethylethylenediamine (TMEDA)

CAS No.: 110-18-9

Chromatographic Purity: ≥99.0%

Molecular Weight: 116.2

Flash Point: 50 °F

Physical Form: Liquid

Refractive Index: n20/D 1.4179 (lit.)

Density: 0.775 g/mL at 20 °C (lit.)

Applications: Pharmaceutical intermediate

N,N,N′,N′-Tetramethylethylenediamine (TMEDA) is a colorless transparent liquid with a slight ammonia odor. It is miscible with water and most organic solvents such as ethanol. TMEDA is an important organic intermediate widely used as a biochemical reagent, epoxy resin curing agent, and intermediate for the synthesis of quaternary ammonium compounds.

1. Industrial Synthesis Routes of TMEDA

Currently, TMEDA  production mainly adopts a two-step process:

Step 1: Condensation of Acetaldehyde with Ethylenediamine to Form an Intermediate

Reaction principle: Acetaldehyde (CH₃CHO) reacts with ethylenediamine (NH₂CH₂CH₂NH₂) under controlled conditions to form a dimethyl-substituted ethylenediamine intermediate (often referred to as acetaldehyde amine).

Reaction equation:

(Note: Specific balanced chemical equation can be added as per detailed process.)

Process conditions:

• Molar ratio (Acetaldehyde : Ethylenediamine) = 2:1

• Reaction temperature: 100–150 °C

• Reaction time: 3–6 hours

• Controls: Stirring, temperature control, slow addition of reactants

Post-processing:

• Removal of water and impurities → Distillation → Obtain acetaldehyde amine intermediate with purity ≥99%.

• Step 2: Methylation of the Intermediate with a Methylating Agent to Produce TMEDA

• Reaction principle: The acetaldehyde amine intermediate undergoes N-methylation with a methylating agent, commonly methyl iodide (CH₃I), to form TMEDA.

Reaction equation:

(Note: Detailed balanced equation can be included.)

Process conditions:

• Molar ratio (Methylating agent : Acetaldehyde amine) = 4:1

• Reaction temperature: 50–70 °C

• Reaction time: 6–8 hours

• Reaction medium: Typically methanol, acetonitrile, or ethyl acetate

Post-processing:

Neutralization of residual acidic byproducts (e.g., HI) → Extraction and phase separation → Vacuum distillation → Obtain TMEDA  product with purity ≥99%.

2. Process Optimization Directions

To improve production efficiency, reduce costs, and enhance product quality, the following optimization strategies are commonly applied:

Alternative Methylating Agents:

Methyl iodide is effective but costly and toxic. Alternatives include:

Dimethyl carbonate (DMC)

Methanol with catalytic systems

Chloromethane derivatives (requiring enhanced environmental controls)

Catalyst Selection and Environmental Control:

Use of Lewis acid catalysts or phase-transfer catalysts to improve methylation selectivity and reduce side reactions. Reactors must be corrosion- and explosion-resistant with sealed operation conditions.

Off-gas and Waste Treatment Systems:

Proper adsorption, combustion, or condensation recovery systems should be installed for ammonia, residual methyl iodide vapor, and solvent emissions to prevent environmental pollution.

3. Safety and Environmental Recommendations

• Maintain good ventilation and temperature control in reaction systems to prevent volatilization of methylating agents.

• Handle acidic byproducts such as hydrogen iodide carefully to avoid equipment corrosion.

• Continuous flow reactors are recommended to enhance safety and scalability.

• Process design must comply with relevant regulations such as the "Regulations on Safety Management of Hazardous Chemicals" and environmental protection laws.

Summary

Tetramethylethylenediamine is a versatile, high-value organic intermediate with a relatively mature production process. However, there remains room for improvement, especially in adopting greener methylation methods, upgrading equipment, and strengthening environmental protection measures. As demands for green chemistry, safe production, and efficient reactions continue to rise, companies can enhance competitiveness and product value by continuous process optimization.