Uses
N-(2-Bromoethyl)-1,3-propanediamine Dihydrobromide is a useful reagent in the preparation of Amifostine, a cytoprotector from aminoethanol and acrylonitrile.
Synthesis
The general procedure for the synthesis of N-(2-bromoethyl)-1,3-propanediamine dihydrobromide from N-hydroxyethyl-1,3-propanediamine was carried out as follows: cyclobutanesulfone (14.2 kg) and 2-(3-aminopropylamino)ethanol (1.29 kg, 10.9 mol) were added in a 20 L glass reactor and the reaction temperature was maintained at 90 °C. Nitrogen was passed into the solution through a Hasteloy C dip tube, followed by the slow addition of anhydrous hydrogen bromide (1.77 kg, 21.9 mol in total) below the liquid level. During the addition, the reaction temperature was raised to 119 °C and after continuous stirring for 15 min, the solution was allowed to stand overnight at 110 °C under nitrogen protection. Using a Masterflex pump and 1/8-inch diameter Teflon tubing, the solution temperature was raised to 120 °C within 1 h and phosphorus tribromide (1.034 kg, 3.82 mol) was added. The tubing was flushed into the reactor with additional cyclobutyl sulfone (0.60 kg). Nitrogen was bubbled through the dip tube into the reaction solution for 1 h at 120 °C to remove excess hydrogen bromide. Half of the hot cyclobutanesulfone solution was transferred to a 30L reactor containing acetone (16.8 kg) through 1/2-inch diameter PTFE tubing, and after stirring for 15 minutes, the mixture was transferred to a polyethylene bench-top vacuum filtration funnel and filtered under nitrogen protection. Acetone (16.9 kg) was added again to the 30L reactor and after nitrogen purge, the remaining hot cyclobutanesulfone solution was transferred from the 20L reactor to the 30L reactor, stirred and filtered. More acetone (6.8 kg) was added to the 30L reactor, nitrogen purged and heated to 50°C. After careful pouring of the hot acetone into a funnel, the combined solids were washed and filtered. The hot acetone washing step was repeated to effectively remove the cyclobutanesulfone. Finally, the product was dried under vacuum at about 74 °C to constant weight to afford N-(2-bromoethyl)-1,3-propanediamine dihydrobromide (3.58 kg, 10.4 mol, 96% yield).
