A. 1-Ethyl-3-(3-dimethylamino)propylcarbodiimide. A solution of 100 g. (1.41 moles) of ethyl isocyanate (Note 1) in 750 ml. of methylene chloride is prepared in a 5-l. three-necked flask equipped with a mechanical stirrer, an immersion thermometer, and a 500-ml., pressure-equalizing, addition funnel (Note 2). The flask and its contents are cooled to 5° in an ice bath, and a solution of 144 g. (1.41 moles) of N,N-dimethyl-1,3-propanediamine in 250 ml. of methylene chloride is added through the addition funnel at a rate such that the reaction temperature does not exceed 10° (Note 3). On completion of this addition 500 ml. of triethylamine is added to the flask, and a solution of 300 g. (1.6 moles) of p-toluenesulfonyl chloride in 300 ml. of methylene chloride is placed in the addition funnel and added to the reaction mixture, again at a rate such that the temperature does not exceed 10° (Note 4). After completion of the second addition, the ice bath is replaced with a heating mantle and the addition funnel with a reflux condenser; the reaction mixture is then heated under gentle reflux for 3 hours. Anhydrous sodium carbonate (400 g.) is added to the cooled reaction mixture, followed by 3.5 l. of ice water. The mixture is stirred vigorously for 30 minutes, after which the phases are allowed to separate, and the lower, organic phase is drawn off through a tube into a 2-l. suction flask. The aqueous phase is then extracted with three 500-ml. portions of methylene chloride (Note 5). The original methylene chloride phase and the extracts are combined and dried over anhydrous magnesium sulfate. The solvents are removed under reduced pressure, and the dark brown residue is distilled under reduced pressure through a 15-cm. Vigreux column to give 1-ethyl-3-(3-dimethylamino)propylcarbodiimide, b.p. 52–55° (0.3–0.4 mm.), n²⁵D 1.4591. The yield is 110–118 g. (50–54%) (Note 6).

B. 1-Ethyl-3-(3-dimethylamino)propylcarbodiimide hydrochloride. A suspension of 34.6 g. (0.300 mole) of pyridine hydrochloride (Note 7) in 280 ml. of methylene chloride is prepared in a 1-l. Erlenmeyer flask. To this is slowly added 46.5 g. (0.300 mole) of 1-ethyl-3-(3-dimethylamino)propylcarbodiimide. The resulting solution is diluted with anhydrous ether (Note 8) and stored at 0–5° for 16–20 hours. The crystalline product is collected by filtration in a dry atmosphere (Note 9), washed with a little anhydrous ether, and dried under reduced pressure over phosphorus pentoxide. The yield is 50.5–55.5 g. (88–96.5%), m.p. 104–109° (Note 10) and (Note 11). This material is sufficiently pure for most purposes.

C. 1-Ethyl-3-(3-dimethylamino)propylcarbodiimide methiodide. A solution of 30.0 g. (0.193 mole) of 1-ethyl-3-(3-dimethylamino)propylcarbodiimide in 750 ml. of anhydrous ether is prepared in a 2-l. Erlenmeyer flask. To this is slowly added from an addition funnel a solution of 30.0 g. (0.21 mole) of methyl iodide in 100 ml. of ether. The mixture is stored in the dark for 48 hours, after which the crystalline product is collected by filtration, washed with ether, and dried. The product, m.p. 94–95°, weighs 50.5–52.5 g. (88–91.5%) (Note 12).