Symmetrical Anhydrides

Abstract

A solution of tert-butyloxycarbonyl-l-phenylalanine (5.30 g, 20 mmol) in dichloromethane (200 ml) is placed into a 500 ml round bottom flask provided with a drying tube filled with cotton. The solution is cooled in an ice water bath and stirred vigorously with a magnetic stirrer. The water soluble carbodiimide [3] N-ethyl-N’-3-dimethylaminopropylcarbodiimide hydrochloride (1.92 g, 10 mmol) is added and stirring is continued at ice bath temperature for 2 hours. The solvent is evaporated in vacuo at a bath temperature of 0 °C and the residue dissolved in a mixture of ethyl acetate (200 ml) and water (100 ml) to which a few pieces of ice have been added. The organic layer is washed twice with ice water (100 ml each time), then with 0.5 N KHCO₃ and finally with saturated sodium chloride solution, always with pieces of ice added. The solution is dried over MgSO₄ while cooled in an ice-water bath, filtered and the solvent removed in vacuo at a bath temperature of 0 °C. The residue is crystalline or crystallizes on storage in the cold (− 5 °C). The anhydride is washed with a 20:1 mixture of hexane and ether and dried in vacuo. The product, 3.9 g (76%), melts at 95–97 °C; [α] ²³_D − 32.8° (c 2, CHC1₃) [4]. In the i.r. spectrum, in addition to the urethane carbonyl band (1710 cm⁻¹) two carbonyl bands, characteristic for anhydrides, appear at 1750 cm⁻¹ and 1830 cm⁻¹.