24932-48-7

White solid

1,2-Dibromo-4,5-dimethylbenzene is used as a reagent in the synthesis of Thalidomide (T338850); an inhibitor of FGF-induced angiogenesis and replication of human immunodeficiency virus type 1. Also a teratogenic sedative and immunomodulatory agent used primarily in combination with dexamethasone to treat multiple myeloma.

The general procedure for the synthesis of 1,2-dibromo-4,5-dimethylbenzene from o-xylene was as follows: 1-methoxy-3,5-dimethylbenzene (100 mg, 0.73 mmol), N-bromosuccinimide (NBS, 260 mg, 1.46 mmol), and a stainless steel ball (5 mm in diameter) were placed in a 10 mL stainless steel grinding jar. The ball milling reaction was carried out and the progress of the reaction was monitored by thin layer chromatography (TLC) and proton nuclear magnetic resonance (1H NMR). Upon completion of the reaction, the reaction mixture was transferred to 30 mL of ethyl acetate and cooled at 0 °C. The product in the filtrate and the precipitated spent succinimide were separated by filtration through filter paper. The filtrate was concentrated under vacuum to give 250 mg (85% yield) of 1,2-dibromo-4,5-xylene (2b) as a colorless powder. To test the efficiency of the large-scale reaction, a monobromination reaction with 1.3 g of 1-methoxy-3,5-dimethylbenzene was also carried out for a reaction time of 1 h. The product was isolated in 87% yield. During the reaction, the grinding equipment was suspended and a small sample was removed from the reaction tank for TLC and 1H NMR analysis, after which the reaction was continued, and the time of this operation was not included in the total reaction time.

[1] Tetrahedron, 2002, vol. 58, # 46, p. 9413 - 9422
[2] Tetrahedron Letters, 2014, vol. 55, # 13, p. 2154 - 2156
[3] Tetrahedron Letters, 2015, vol. 55, # 13, p. 2154 - 2156
[4] Journal of the American Chemical Society, 1993, vol. 115, # 13, p. 5422 - 5429
[5] Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 1, p. 227 - 231