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3,6-Bis(5’-bromo-3’-indolyl)-1,4-dimethypiperazine-2,5-dione

Department of Chemistry, Georgia Southern University, Statesboro, GA 30460, USA
*
Author to whom correspondence should be addressed.
Molbank 2009, 2009(4), M627; https://doi.org/10.3390/M627
Submission received: 22 September 2009 / Accepted: 7 October 2009 / Published: 9 October 2009

Abstract

:
The one-pot synthesis of 3,6-bis(5’-bromo-3’-indolyl)-1,4-dimethylpiperazine-2,5-dione is reported. Sarcosine anhydride is brominated and immediately reacted with 5-bromoindole to produce the product, which is characterized by 1H NMR, MS and microanalysis.

Graphical Abstract

1. Introduction

Isolated from the marine sponge series Dragmacidin, Hexadella, and Spongosorites, unique bis-indolylpiperazine alkaloids have received significant attention in recent years for their antiviral, cytotoxic, and anti-inflammatory properties [1,2,3,4,5,6,7,8,9,10]. The dragmacidin series of alkaloids each contain a central piperazine ring with indole units attached at the 2- and 5- positions. The corresponding author successfully synthesized the first member of the dragmacidin series [11] and recently reported an improved procedure for preparing 1,4-dimethylpiperazine-2,5-dione, an important precursor [12]. We now report the synthesis of 3,6-bis(5’-bromo-3’-indolyl)-1,4-dimethylpiperazine-2,5-dione (3), a novel bis-indolylpiperazinedione utilizing the newly-developed procedure. This product will be utilized in the preparation of novel dragmacidin derivatives.

2. Results and Discussion

The synthesis of 3 is shown in Scheme 1. Bromine is directly added to 1 with heat and the illumination of a sun lamp. After one hour, the solution is cooled to provide the dibrominated product as an unstable precipitate. This precipitate is then reacted with 5-bromoindole in DMF to produce 3. In conclusion, an important precursor to a dragmacidin derivative has been prepared by efficient means.
Molbank 2009 m627 sch001

3. Experimental Section

To a solution of sarcosine anhydride (1) (1.50 g, 10.6 mmol) in o-dichlorobenzene (15 mL), at 150°C, was added dropwise Br2 (2.5 mL, 96.6 mmoL), under illumination of a sun lamp. The solution was heated for 1 h and then cooled to room temperature. The solution was decanted leaving beige crystals (2). To a solution of 5-bromoindole (2.21 g, 11.3 mmol) in DMF (20 mL) was slowly added 2 (1.50 g, 5.0 mmol), while the reaction temperature was maintained at room temperature with a water bath. The reaction mixture was stirred for 18 h, concentrated and diluted with methanol. The resulting solid was filtered to yield the product (3) as a white crystalline solid (1.92 g; 72.5%): mp > 250°C. 1H NMR (d6-DMSO): 2.67 (s, 3H), 5.64 (s, 1H), 7.25 (dd, 1H, J = 1.9, 8.6), 7.39 (d, 1H, J = 8.7), 7.49 (d, 1H, J = 2.5), 7.69 (d, 1H, J = 1.8), 9.67 (bs, 1H); MS: 532 (m+, 17.3), 530 (54.5), 528 (51.3), 335 (100.0), 333 (99.9), 307 (31.9), 305 (30.7), 239 (47.9), 237 (91.8), 235 (68.0), 209 (30.6), 207 (30.9), 197 (30.2), 195 (29.7); Anal. Calcd. For C22H16Br2N4O2: C, 48.84; H, 3.42; N, 10.57. Found: C, 49.80; H, 3.50; N, 10.64. Sarcosine anhydride (99.5%) was obtained from Acros Organics, and 5-bromoindole (99%) was obtained from Sigma-Aldrich, Inc.

Supplementary materials

Supplementary File 1Supplementary File 2Supplementary File 3

Acknowledgements

This work was supported by the Allen E. Paulson College of Science and Technology Scholars Program and the Department of Chemistry at Georgia Southern University, and the Cava research group at The University of Alabama.

References and Notes

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MDPI and ACS Style

Crooke, S.; Davis-McGibony, M.; Whitlock, C. 3,6-Bis(5’-bromo-3’-indolyl)-1,4-dimethypiperazine-2,5-dione. Molbank 2009, 2009, M627. https://doi.org/10.3390/M627

AMA Style

Crooke S, Davis-McGibony M, Whitlock C. 3,6-Bis(5’-bromo-3’-indolyl)-1,4-dimethypiperazine-2,5-dione. Molbank. 2009; 2009(4):M627. https://doi.org/10.3390/M627

Chicago/Turabian Style

Crooke, Stephen, Michele Davis-McGibony, and Christine Whitlock. 2009. "3,6-Bis(5’-bromo-3’-indolyl)-1,4-dimethypiperazine-2,5-dione" Molbank 2009, no. 4: M627. https://doi.org/10.3390/M627

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