Water → Thymol

Temperature

0 °C

2-Isopropyl-5-nitro-aniline (1.89 g, 10.49 mmol) was added dropwise to a mixture of conc.H2SO4 (9 mL) and H2O (50 mL). This reaction mixture was cooled to 0° C. and a solution of NaNO2 (763 mg, 11.06 mmol) in H2O (2 mL) was added. The reaction mixture was stirred for 10 minutes and then 1 g of urea was added to decompose the excess NaNO2, followed by the addition of 10 mL of 1:2 conc.H2SO4: H2O. The reaction mixture was then refluxed for 10 minutes, cooled to room temperature and extracted with EtOAc, washed with brine, dried over MgSO4, filtered and concentrated. The residue was then purified via silica gel column chromatography using 10 to 20% EtOAc in hexanes to obtain 2-isopropyl-5-methyl-phenol (1.41 g, 89%). 1H NMR (400 MHz, CDCl3) δ 7.79 (dd, J=8.5, 2.3 Hz, 1H), 7.63 (d, J=2.3 Hz, 1H), 7.33 (d, J=8.5 Hz, 1H), 7.26 (s, 1H), 3.39-3.18 (m, 1H), 1.29-1.26 (m, 6H).

1. additionfollowed by the addition of 10 mL of 1:2 conc
2. temperatureThe reaction mixture was then refluxed for 10 minutes
3. temperaturecooled to room temperature
4. extractionextracted with EtOAc
5. washwashed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was then purified via silica gel column chromatography

ORD record

ord-020052a254ba464faa30cd4f914c0a06

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08354427B2