Tetramethylethylenediamine

Tetramethylethylenediamine (TMEDA or TEMED) is a chemical compound with the formula (CH₃)₂NCH₂CH₂N(CH₃)₂. This species is derived from ethylenediamine by replacement of the four amine hydrogens with four methyl groups. It is a colorless liquid, although old samples often appear yellow. Its odor is similar to that of rotting fish.^[4]

Tetramethylethylenediamine

Names
Preferred IUPAC name N,N,N′,N′-Tetramethylethane-1,2-diamine[1]
Identifiers
CAS Number	110-18-9 Y
3D model (JSmol)	Interactive image
Abbreviations	TMEDA, TEMED
Beilstein Reference	1732991
ChEBI	CHEBI:32850 N
ChemSpider	7746 N
ECHA InfoCard	100.003.405
EC Number	203-744-6
Gmelin Reference	2707
MeSH	N,N,N',N'-tetramethylethylenediamine
PubChem CID	8037
RTECS number	KV7175000
UNII	K90JUB7941 Y
UN number	2372
CompTox Dashboard (EPA)	DTXSID5026122
InChI InChI=1S/C6H16N2/c1-7(2)5-6-8(3)4/h5-6H2,1-4H3 N Key: KWYHDKDOAIKMQN-UHFFFAOYSA-N N
SMILES CN(C)CCN(C)C
Properties
Chemical formula	C6H16N2
Molar mass	116.208 g·mol−1
Appearance	Colorless liquid
Odor	Fishy, ammoniacal
Density	0.7765 g mL−1 (at 20 °C)
Melting point	−58.6 °C; −73.6 °F; 214.5 K
Boiling point	121.1 °C; 249.9 °F; 394.2 K
Solubility in water	Miscible
Acidity (pKa)	8.97
Basicity (pKb)	5.85
Refractive index (nD)	1.4179 (20 °C)[2]
Hazards
GHS labelling:
Pictograms
Signal word	Danger
Hazard statements	H225, H302, H314, H332
Precautionary statements	P210, P280, P305+P351+P338, P310
NFPA 704 (fire diamond)	2 4 1
Flash point	20 °C (68 °F; 293 K)
Explosive limits	0.98–9.08%
Lethal dose or concentration (LD, LC):
LD50 (median dose)	5.39 g kg−1 (dermal, rabbit) 268 mg kg−1 (oral, rat) [3]
Related compounds
Related amines	Triethylenetetramine
Related compounds	Tetraacetylethylenediamine Ethylenediaminetetraacetic acid Ethambutol
Supplementary data page
Tetramethylethylenediamine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). N verify (what is YN ?) Infobox references

As a reagent in synthesis

TMEDA is widely employed as a ligand for metal ions. It forms stable complexes with many metal halides, e.g. zinc chloride and copper(I) iodide, giving complexes that are soluble in organic solvents. In such complexes, TMEDA serves as a bidentate ligand.

TMEDA has an affinity for lithium ions.^[4] When mixed with n-butyllithium, TMEDA's nitrogen atoms coordinate to the lithium, forming a cluster of higher reactivity than the tetramer or hexamer that n-butyllithium normally adopts. BuLi/TMEDA is able to metallate or even doubly metallate many substrates including benzene, furan, thiophene, N-alkylpyrroles, and ferrocene.^[4] Many anionic organometallic complexes have been isolated as their [Li(tmeda)₂]⁺ complexes.^[5] In such complexes [Li(tmeda)₂]⁺ behaves like a quaternary ammonium salt, such as [NEt₄]⁺.

TMEDA adduct of lithium bis(trimethylsilyl)amide Notice that the diamine is a bidentate ligand.^[6]

sec-Butyllithium/TMEDA is a useful combination in organic synthesis where the n-butyl analogue adds to substrate. TMEDA is still capable of forming a metal complex with Li in this case as mentioned above.

In molecular biology

TEMED is a common reagent in molecular biology laboratories, as a polymerizing agent for polyacrylamide gels in the protein analysis technique SDS-PAGE.^[7]

Other uses

The complexes (TMEDA)Ni(CH₃)₂ and [(TMEDA)Ni(o-tolyl)Cl] illustrate the use of tmeda to stabilize homogeneous catalysts.^{[8] [9]}

Synthesis of [(TMEDA)Ni(o-tolyl)Cl]

Related compounds

• H₂NCMe₂−CMe₂NH₂, also referred to as tetramethylethylenediamine.^[10]
• Bis(dimethylamino)methane, Me₂NCH₂NMe₂

References

1. "N,N,N′,N′-tetramethylethylenediamine – Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 16 September 2004. Retrieved 30 June 2012.
2. Lide, David R., ed. (2009). CRC Handbook of Chemistry and Physics (90th ed.). Boca Raton, Florida: CRC Press. ISBN 978-1-4200-9084-0.
3. "MSDS" (PDF).^{[permanent dead link‍]}
4. Haynes, R. K.; Vonwiller, S. C.; Luderer, M. R. (2006). "N,N,N′,N′-Tetramethylethylenediamine". In Paquette, L. (ed.). N,N,N′,N′-Tetramethylethylenediamine. Encyclopedia of Reagents for Organic Synthesis. New York: J. Wiley & Sons. doi:10.1002/047084289X.rt064.pub2. ISBN 0471936235.
5. Morse, P. M.; Girolami, G. S. (1989). "Are d⁰ ML₆ Complexes Always Octahedral? The X-ray Structure of Trigonal Prismatic [Li(tmed)]₂[ZrMe₆]". Journal of the American Chemical Society. 111 (11): 4114–4116. doi:10.1021/ja00193a061.
6. Henderson, K. W.; Dorigo, A. E.; Liu, Q.-L.; Williard, P. G. (1997). "Effect of Polydentate Donor Molecules on Lithium Hexamethyldisilazide Aggregation: An X-ray Crystallographic and a Combination Semiempirical PM3/Single Point ab Initio Theoretical Study". J. Am. Chem. Soc. 119 (49): 11855. doi:10.1021/ja971920t.
7. Manns, Joanne M. (2011). "SDS-Polyacrylamide Gel Electrophoresis (SDS-PAGE) of Proteins". Current Protocols in Microbiology. 22. doi:10.1002/9780471729259.mca03ms22.
8. Shields, Jason D.; Gray, Erin E.; Doyle, Abigail G. (2015-05-01). "A Modular, Air-Stable Nickel Precatalyst". Organic Letters. 17 (9): 2166–2169. doi:10.1021/acs.orglett.5b00766. PMC 4719147. PMID 25886092.
9. Magano, Javier; Monfette, Sebastien (2015-04-17). "Development of an Air-Stable, Broadly Applicable Nickel Source for Nickel-Catalyzed Cross-Coupling". ACS Catalysis. 5 (5): 3120–3123. doi:10.1021/acscatal.5b00498.
10. Jackson, W.Gregory; Rahman, A.F.M.Mokhlesur; Wong, M.Anthony (2004). "Solvent Exchange, Solvent Interchange, Aquation and Isomerisation Reactions of cis- and trans-[Co(tmen)₂(NCMe)₂]³⁺ in Water, Me₂SO and MeCN: Kinetics and Stereochemistry". Inorganica Chimica Acta. 357 (3): 665–676. doi:10.1016/j.ica.2003.05.010.