N,N,N',N'-Tetramethylethylenediamine: Synthesis, application and precautions

General description

N,N,N',N'-Tetramethylethylenediamine (TEMED) is a kind of bidentate tertiary amine Lewis base with good solvating properties. N,N,N',N'-Tetramethylethylenediamine is widely employed both as a ligand for metal ions and as a catalyst in organic polymerisation. It has a role as a chelator and a catalyst. It can be used as an additive to stabilize and activate organometallic reagents and inorganic salts; N,N,N',N'-Tetramethylethylenediamine can enhances the rate of metalation of a variety of aromatic and unsaturated systems as well as influencing the regiochemical outcome of these reactions. Meanwhile, it can be effectively used as a neutral amine in base catalyzed reactions. Its appearance is as follows:

Figure 1 The appearance of N,N,N',N'-Tetramethylethylenediamine

Synthesis

N,N,N',N'-Tetramethylethylenediamine was synthesized with the slight modifications of the literature procedures [1]. Dry NHMe2 gas was passed into dry THF (40 mL) in a screw-top pressure tube at 0°C till the volume of the resulting solution was roughly doubled (~90 mL). Dibromoalkane (6 g) was added through syringe and stirred for 24 h at room temperature for completion of reaction. The pressure tube was cooled and the reaction mixture was transferred into a RB and then it was washed with CHCl3. White precipitate appeared, solution was kept in water bath to remove excess NHMe2 followed by removal of solvent. Then reaction mixture was diluted with CHCl3 followed by washing with NaOH (2 M, 100 mL) solution. CHCl3 layer was collected and passed through anhydrous Na2SO4 followed by drying. Light yellow gummy liquid, yield quantitative. N,N,N',N'-Tetramethylethylenediamine: 1H NMR (400 MHz, CDCl3): δ 1.458 (m, -CH2-CH2-NMe2, 4H), 2.246 (t, terminal CH3- and -CH2-NMe2, 16H).

Application

N,N,N',N'-Tetramethylethylenediamine, a simple electron-donating ligand, has also been reported for the synthesis of quantum dots with higher fluorescence efficiency due to the coordination of amines [2]. Therefore, it has potential for the enhancement of photoluminescent intensity of quantum dots, which might be effective in photoluminescent imaging of proteins after PAGE [3]. N,N,N',N'-Tetramethylethylenediamine can activates organolithium reagents through an erstwhile perception of enhanced chelating ability, but more likely through presentation of a more labile environment [4]. The use of N,N,N',N'-Tetramethylethylenediamine dramatically improve the reactivity of aryl- and alkylcopper reagents. It not only stabilizes and solubilizes the organocopper reagent but also facilitates the trapping of the resulting enolates, thereby affording silyl enol ethers in excellent yields. In many cases the addition of Lewis bases such as TMEDA increases the rate of cyclization. The complexing properties of N,N,N',N'-Tetramethylethylenediamine have made it possible to prepare and handle salts which are otherwise air and moisture sensitive. Thus Zinc Chloride in the presence of one equivalent of TMEDA forms a crystalline air stable solid, ZnCl2·TMEDA, which with three equivalents of an alkyllithium reagent is converted into trialkylzinclithium [5].

Precautions

N,N,N',N'-Tetramethylethylenediamine should be used directly after distilling. However, it may be stored under nitrogen and transferred by using a syringe and septum cap as required. For most applications the amine is removed during aqueous workup simply by washing with water owing to its high water solubility. Use in a fume hood. N,N,N',N'-Tetramethylethylenediamine is a skin and severe eye irritant: mildly toxic through skin contact and moderately toxic through ingestion. N,N,N',N'-Tetramethylethylenediamine is flammable when exposed to heat or flame and can react with oxidizing agents. Upon heating to decomposition, N,N,N',N'-Tetramethylethylenediamine will emit toxic fumes of NO x.

References

[1]Hoque et al. Aggregation Properties of Amide Bearing Cleavable Gemini Surfactants by Small Angle Neutron Scattering and Conductivity Studies. Journal of Physical Chemistry B (2012), 116(32), 9718-9726.

[2]Jun YW, Koo JE, Cheon J (2000) One-step synthesis of size tuned zinc selenide quantum dots via a temperature controlled molecular precursor approach. Chem Commun:1243–1244.

[3]Na N, Liu L, Taes YEC, Zhang CL, Huang BR, Liu YL, Ma L, Ouyang J (2010) Direct CdTe quantum-dot-based fluorescence imaging of human serum proteins. Small 6:1589–1592.

[4]Wake?eld, B. J. The Chemistry of Organolithium Compounds; Pergamon: Oxford, 1974.

[5]Watson, R. A.; Kjonaas, R. A., Tetrahedron Lett. 1986, 27, 1437. Isobe, M.; Kondo, S.; Nagasawa, N.; Goto, T., Chem. Lett. 1977, 679.

You may like