sarcosine anhydride (Aldrich)
o-dichlorobenzene (Aldrich)
bromine (Aldrich, 99.5%)
hexanes (Aldrich)
indole (Aldrich)
N,N-dimethylformamide (Aldrich)
methanol (Fisher)

To a solution of sarcosine anhydride (3.75 g, 26.4 mmol) in o-dichloromethane (15 mL), at 150°C, was added dropwise Br₂ (3.0 mL, 58.1 mmol) in o-dichlorobenzene (6 mL), under illumination of a sun lamp. The solution was heated for 1 h and then cooled to room temperature. A stream of N₂ was bubbled through the reaction mixture for 10 min, and the solution was diluted with hexanes. The resulting beige crystals of 3,6-dibromo-1,4-dimethylpiperazine-2,5-dione were filtered and rinsed with hexanes (7.06 g; 89.1%). To a solution of indole (0.30 g, 2.6 mmol) in N,N-dimethylformamide (3 mL) was added 3,6-dibromo-1,4-dimethylpiperazine-2,5-dione (0.30 g, 1.0 mmol). The reaction mixture was stirred overnight, diluted with methanol and filtered to yield the bisindolyl product as a white, crystalline solid (0.34 g; 91.4%).

The reaction is an efficient way of adding indoles to the 3- and 6- positions of sarcosine anhydrides. A number of substituted indoles were utilized successfully. The 3,6-dibromo-1,4-dimethylpiperazine-2,5-dione is relatively unstable and should be reacted immediately.

mp > 250°C; ¹H NMR (d₆-DMSO): 2.66 (s, 3H), 5.62 (s, 1H), 7.03 (t, 1H, J = 7.4), 7.13 (t, 1H, J = 7.4), 7.46 (m, 3H), 11.20 (s, 1H); MS: 372 (m⁺, 24.6), 255 (100.0), 227 (30.4), 159 (28.4), 157 (56.2).

Whitlock, C. R. "Synthetic Approaches to the Dragmacidin Alkaloids." Dissertation, The University of Alabama, 1994.

Trown, P. W. Biochem. Biophys. Res. Commun. 1968, 33, 402.