2-[2-(2-Azidoethoxy)ethoxy]ethanamine

Description

Azido-PEG2-amine is a bifunctional crosslinker containing an amino and an azide group. The amino group is reactive with carboxylic acids, activated NHS esters,. The azide(N3) group can react with alkyne, BCN, DBCO via Click Chemistry to yield a stable triazole linkage.

Synthesis

2-[2-(2-Hydroxyethoxy)ethoxy]ethyl chloride (15 g, 88.9 mmol), NaI(4.06 g, 27.1 mmol), and NaN₃ (45.3 mg, 697 mmol) were dissolved in distilled water (90 mL), and the solution was stirred for 48 h at 50 °C. The reaction mixture extracted with ethyl acetate for three times. The organic layer was dried over Na₂SO₄ , and evaporated to collect 2-[2-(2-azidoethoxy)ethoxy]ethanol (14.0 g, 90.1%) as a yellow oil.To the solution 2-[2-(2-azidoethoxy)ethoxy]ethanol (8 g, 45.7 mmol) in THF (22.4 mL), 6 M NaOH(20.8 mL) and TsCl (13.1 g, 68.6 mmol) were added at 0 °C. The reaction mixture was stirred for 1 h at room temperature under nitrogen atmosphere. The solution was then extracted with diethyl ether four times, and the organic layer was washed with 1 M NaOH. After evaporation of the organic layer,2-[2-(2-azidoethoxy)ethoxy]ethyl tosylate (16.8 g, 98.6%) was obtained as a yellow oil.Finally, ammonia solution (28%, 14.8 mL, 365 mol) was added to the 2-[2-(2-azidoethoxy)ethoxy]-ethyl tosylate (8 g, 24.3 mmol) dissolved in THF (95.9 mL), and reaction mixture was stirred for 96 h at 40 °C. After the reaction, distilled water (50 mL) was added to the solution. The mixture was washed with diethyl ether and then extracted with dichloromethane. The organic layer was dried over NaSO₄ and evaporated to obtain 2-[2-(2-azidoethoxy)ethoxy]ethanamine (2.49 g, 58.8%) as a yellow oil.