Synthesis
The general procedure for the synthesis of 2-((2-aminoethyl)amino)acetic acid from ethylenediamine and chloroacetic acid is as follows:
Example 8: Preparation of [(2-aminoethyl)amino]acetic acid (3) in DMSO
1. Preparation of chloroacetic acid solution: chloroacetic acid (500.0 g, 5.29 mol) was dissolved in DMSO (515.6 g).
2. Reaction setup: ethylenediamine (3537mL, 52.9mol) was added to a 5L flask equipped with a nitrogen inlet, mechanical stirrer, thermocouple and peristaltic metering pump. Begin cooling with ice water.
3. Dropwise addition of chloroacetic acid solution: chloroacetic acid solution in DMSO was slowly added to ethylenediamine via a metering pump. The reaction conditions are shown in Table 1.
Table 1: Reaction conditions during addition of chloroacetic acid solution to ethylenediamine
| No. | Time | Temperature (°C) | Pressure (Torr) |
|------|--------|----------|-----------|
| 1 | 10:51 | 17 | - |
| 2 | 11:28 | 18 | - |
| 3 | 12:18 | 16 | 720 |
| 4 | 13:38 | 11 | 625 | 4 | 13:38 | 11 | 625
| 5 | 14:35 | 12 | 550 | 4 | 13:38 | 11 | 625 | 4
6 | 15:17 | 10 | 490 | 7 | 16:08 | 16:08
| 7 | 16:08 | 8 | 420 | 8 | 8:59 | 8 | 8:59 | 8 | 8:59 | 8 | 8:59
| 8 | 8:59* | 19 | 0 |
*Time represents the next day.
4. Concentration of reaction mixture: The reaction mixture was concentrated by rotary evaporation (50-60 °C, 14-21 Torr) to remove ethylenediamine. The total amount of distillate collected was 2400mL.
5. Toluene treatment: Toluene (900 mL) was added to the residue and the mixture was further concentrated by rotary evaporation (60 °C, 30 Torr).
6. Transfer and cooling: The residue was transferred to a 5L flask using DMSO (3kg). The internal temperature was 28°C and the mixture was cloudy. Cooling (ice/water) was started.
7. Overnight stirring: the reaction mixture was stirred overnight.
8. filtration and washing: the resulting suspension was filtered through filter paper. The flask and solid were washed with DMSO (2 x 500mL). The solid was subsequently washed with isopropanol (2 x 500mL) and tert-butyl methyl ether (2 x 500mL).
9. Drying: The solid was dried at ambient temperature under high vacuum for 18 h. 10.
10. Product collection: 2-((2-aminoethyl)amino)acetic acid (3) was obtained as a white solid (480.4 g, 4.07 mol) in 77% yield.
