Bromine → 3-Bromo-5-tert-butyl-2-hydroxybenzaldehyde

HRID 1526769Notes

Reaction equation

[C:1]([C:5]1[CH:12]=[C:9]([CH:10]=[O:11])[C:8]([OH:13])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].[Br:14]Br.CC(=O)OCC.CCCCCCC>C(O)(=O)C>[Br:14][C:7]1[CH:6]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:12]=[C:9]([CH:10]=[O:11])[C:8]=1[OH:13]

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 5-tert-butylsalicylaldehyde (3.03 g, 16.97 mmol) in acetic acid (3.5 mL) was added a solution of bromine (0.90 mL, 17.56 mmol) in acetic acid (8.5 mL) dropwise within 15 min. The reaction mixture was stirred at room temperature for 3 h at 50° C. and was monitored by TLC (EA/heptane:1:4) and analytical HPLC analysis. Analytical HPLC analysis of the reaction mixture after 2.5 h shows the desired product ˜68% and the unreacted starting material ˜32%. A second batch of bromine (0.15 mL) in acetic acid (3 mL) was added and the reaction mixture was stirred at 50° C. for another 15 h. Analytical HPLC analysis of the reaction mixture after overnight stirring shows the desired product ˜96% and still shows the starting material ˜4%. The reaction mixture was diluted with dichloromethane (50 mL) and the organic layer was washed with 39% sodium bisulfite solution (1×10 mL), water, saturated NaHCO3 and brine. The organic layer was dried over anhydrous sodium sulfate, filtered and evaporated in vacuo to give the crude desired product as a pale yellow crystalline solid (4.6150 g). Purification of the crude product by Silica-gel flash chromatography on silica gel column and elution with 0-5% ethyl acetate in n-heptane afforded the desired product as a pale yellow crystalline solid (4.07 g, 93% yield). 1H NMR (400 MHz, CDCl3): δ 1.33 (s, 9H, t-Bu-), 7.49 (s, 1H, H-4), 7.81 (d, 1H, H-6), 9.85 (s, 1H, —CHO), 11.41 (s, 1H, —OH). 1H NMR of the isolated product was identical with that of a previously reported sample of the product (Girsch et al., 2008) LC-MS analysis of the product in negative mode shows the desired product's mass: m/z 255 (79BrM+−H) and m/z 257 (81BrM+−H). GC-MS analysis of the product in CI mode (Methane) shows the desired product's mass: m/z 256 (79BrM+) and m/z 258 (81BrM+).

Workup

waitAnalytical HPLC analysis of the reaction mixture after 2.5 h shows

Sources & evidence

ORD record: ord-c8ed1ddbb1d74ee8bf8859aa097a54a9
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085606B2

Reaction notes

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