N,N,N',N'-Tetramethylethylenediamine
[CAS# 110-18-9]

Identification

• Classification: Organic raw materials >> Amino compound >> Acyclic monoamines, polyamines and their derivatives and salts
• Name: N,N,N',N'-Tetramethylethylenediamine
• Synonyms: 1,2-Di(dimethylamino)ethane; TEMED; TMEDA
• Molecular Formula: C₆H₁₆N₂
• Molecular Weight: 116.20
• CAS Registry Number: 110-18-9
• EC Number: 203-744-6
• SMILES: CN(C)CCN(C)C

Properties

• Density: 0.8±0.1 g/cm³ Calc.^*, 0.775 g/mL (Expl.)
• Melting point: -55 °C (Expl.)
• Boiling point: 121.0 °C 760 mmHg (Calc.)^*, 120 - 122 °C (Expl.)
• Flash point: 10.0 °C (Calc.)^*, 20 °C (Expl.)
• Index of refraction: 1.438 (Calc.)^*, 1.418 (Expl.)
• Water solubility: miscible

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS02;GHS05;GHS06;GHS07;GHS09 Danger
• Risk Statements: H225-H302-H302-H314-H318-H331-H332-H411
• Safety Statements: P210-P233-P240-P241-P242-P243-P260-P261-P264-P264+P265-P270-P271-P273-P280-P301+P317-P301+P330+P331-P302+P361+P354-P303+P361+P353-P304+P340-P305+P354+P338-P316-P317-P321-P330-P363-P370+P378-P391-P403+P233-P403+P235-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Flammable liquids	Flam. Liq.	2	H225
Skin corrosion	Skin Corr.	1B	H314
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H332
Serious eye damage	Eye Dam.	1	H318
Chronic hazardous to the aquatic environment	Aquatic Chronic	2	H411
Acute toxicity	Acute Tox.	3	H331
Acute toxicity	Acute Tox.	3	H301
Acute toxicity	Acute Tox.	4	H312
Specific target organ toxicity - single exposure	STOT SE	1	H370

• Transport Information: UN 2924; UN 2372

Discovery and Applications

N,N,N',N'-Tetramethylethylenediamine, commonly abbreviated as TMEDA, is an organic compound widely recognized for its role as a bidentate ligand and as a complexing agent in coordination and organometallic chemistry. Its chemical formula is C₆H₁₆N₂, and it consists of an ethylenediamine backbone in which all four nitrogen-bound hydrogen atoms have been replaced with methyl groups. This substitution enhances its basicity and steric profile, making it particularly useful in a variety of synthetic applications.

TMEDA was first reported in the mid-20th century as a product of efforts to synthesize tertiary diamines with distinct coordination properties. Its value was quickly recognized in the field of organolithium chemistry, where it functions as a chelating ligand. By coordinating to lithium cations, TMEDA modulates the aggregation state of lithium reagents such as n-butyllithium or lithium diisopropylamide (LDA), significantly enhancing their reactivity and selectivity. The presence of TMEDA typically reduces the degree of aggregation of these lithium reagents from tetrameric or hexameric species to monomeric or dimeric forms, which are more reactive in deprotonation and nucleophilic addition reactions.

In synthetic organic chemistry, TMEDA is used to promote lithiation reactions at positions on aromatic or heteroaromatic rings that are otherwise less reactive. For instance, in directed ortho-lithiation, TMEDA is added to coordinate with lithium and assist in the generation of carbanions at specific positions, allowing for selective functionalization of complex substrates. This has made TMEDA an essential additive in the preparation of pharmaceuticals, agrochemicals, and functional materials.

Beyond its use in organolithium chemistry, TMEDA is employed in the formation of transition metal complexes. It acts as a neutral, nitrogen-donor ligand in complexes with metals such as nickel, copper, and iron. These complexes have found utility in homogeneous catalysis, including reactions like cross-coupling, olefin polymerization, and hydrosilylation. TMEDA's relatively small steric bulk, coupled with its strong electron-donating properties, allows for fine control over the electronic environment of the metal center.

TMEDA also serves in polymer chemistry, particularly in the polymerization of alkyl methacrylates and other monomers via anionic or radical mechanisms. It can act as a co-catalyst or stabilizer in such reactions, improving control over molecular weight and polymer architecture. Additionally, it is sometimes used in coordination with Grignard reagents or as an additive in electrochemical processes to modulate ion transport and electrode behavior.

In the laboratory, TMEDA is a colorless to pale yellow liquid with a characteristic amine-like odor. It is miscible with many organic solvents and is generally handled under anhydrous conditions due to its hygroscopic nature and potential to absorb moisture from the air. TMEDA is flammable and should be handled with appropriate precautions to avoid inhalation or skin contact.

While TMEDA is primarily a laboratory reagent, its role in enabling key synthetic transformations highlights its importance in the development of both industrial and academic chemistry. Its discovery and widespread use underscore the impact that well-designed small molecules can have in controlling reactivity and selectivity in complex chemical systems.

References

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2024. Synthesis and Structure of Ag(I) Complexes with Tris(3,5-Dimethylpyrazol-1-yl)Methane and beta-Diketones. Journal of Structural Chemistry, 65(11).
DOI: 10.1134/s0022476624110180