5-BROMO-2,2-DIMETHYL-1,3-BENZODIOXOLE

5-BROMO-2,2-DIMETHYL-1,3-BENZODIOXOLE Property

Boiling point:

97-102 °C(Press: 8 Torr)

Density 

1.475±0.06 g/cm3(Predicted)

storage temp. 

2-8°C

Appearance

Colorless to light yellow Liquid

InChI

InChI=1S/C9H9BrO2/c1-9(2)11-7-4-3-6(10)5-8(7)12-9/h3-5H,1-2H3

InChIKey

DBVCFVNYPVLZKX-UHFFFAOYSA-N

SMILES

O1C2=CC=C(Br)C=C2OC1(C)C

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

5-BROMO-2,2-DIMETHYL-1,3-BENZODIOXOLE Chemical Properties,Usage,Production

Uses

5-Bromo-2,2-dimethylbenzo[d][1,3]dioxole is used as a reactant in the preparation of phenanthridine-based Bcl-XL inhibitors.

Synthesis

General procedure for the synthesis of 5-bromo-2,2-dimethylbenzo[d][1,3]dioxolane from 2,2-dimethylbenzo[d][1,3]dioxolane: 2,2-dimethyl-2H-1,3-benzo[d]dioxolane (1.00 g, 6.66 mmol) was dissolved in anhydrous N,N-dimethylformamide (20 mL). N-bromosuccinimide (1.19 g, 6.66 mmol) was added batchwise at room temperature. The reaction mixture was stirred at the same temperature overnight. Analysis by liquid chromatography-mass spectrometry (LCMS) showed almost complete consumption of the starting material. The reaction process was difficult to monitor by TLC as the starting material and the product had the same Rf value on thin layer chromatography (TLC). Upon completion of the reaction, the mixture was diluted with water, appropriate amount of saturated saline was added, followed by ethyl acetate for extraction. The organic and aqueous phases were separated and the organic phase was dried with anhydrous magnesium sulfate, filtered and concentrated to dryness. The crude product was purified by silica gel column chromatography with the eluent cyclohexane/ethyl acetate (95:5, v/v). The product-containing fraction was collected and concentrated to dryness to afford 5-bromo-2,2-dimethyl-2H-1,3-benzodioxole (1.32 g, 86% yield) as a colorless oil.1H NMR (300 MHz, DMSO-d6, δ/ppm): 1.63 (s, 6H), 6.79 (d, 1H, J = 8.1Hz), 6.95 (dd , 1H, J = 8.1Hz, J = 2.1Hz), 7.06 (d, 1H, J = 2.1Hz).

References

[1] Bioorganic and Medicinal Chemistry Letters, 2003, vol. 13, # 22, p. 4133 - 4137
[2] Patent: WO2018/138362, 2018, A1. Location in patent: Page/Page column 68; 130; 131
[3] Heterocycles, 2014, vol. 88, # 2, p. 1121 - 1133
[4] ChemMedChem, 2018, vol. 13, # 21, p. 2332 - 2348
[5] Molecules, 2015, vol. 20, # 5, p. 8654 - 8665