4-chloro-3-methoxybenzenethiol synthesis

4synthesis methods

Product Name:4-chloro-3-methoxybenzenethiol
CAS Number:61150-48-9
Molecular formula:C7H7ClOS
Molecular Weight:174.65

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Yield:61150-48-9 60%

Reaction Conditions:

Stage #1: 1-bromo-3-chloro-5-methoxybenzenewith iodine;magnesium in tetrahydrofuran at 20; for 3 h;Inert atmosphere;Reflux;
Stage #2: with sulfur in tetrahydrofuran;

Steps:

71

Preparation 71 4-chloro-3-methoxybenzenethiolTo a room temperature solution of magnesium (366 mg, 15 mmol) in anhydrous tetrahydrofuran (2 ml_) under a nitrogen atmosphere was added a crystal of iodine. This was followed by the drop-wise addition of 3-bromo-5-chloroanisole (3.00 g, 13.5 mmol) in anhydrous tetrahydrofuran (9 ml_) over 30 minutes. The resultant black solution was then heated to reflux for 90 minutes. The reaction mixture was cooled to room temperature and stirred at ambient temperature for 1 hour. Sulphur (360 mg, 0.83 mmol) was then added. An exotherm was noted along with a colour change from a black to a grey solution. The reaction mixture was stirred for an hour then left to stand for 16 hours (convenience). The reaction mixture was heated to reflux for an hour then cooled back to room temperature before being poured into an ice (20 g) / water (20 ml_) / hydrogen chloride (37% aqueous solution) (5 ml_) solution. The aqueous solution was extracted with tert-butyl methyl ether (2 x 50 ml_), then the organic layers were combined and washed with sodium hydroxide (10% aqueous solution) (3 x 30 ml_). The combined aqueous extracts were treated with hydrogen chloride (37% aqueous solution) (5-10 ml_) and a white solid appeared. The aqueous was then re-extracted with tert-butyl methyl ether (3 x 50 ml_), and the combined organics were dried (sodium sulphate), and evaporated in vacuo to afford the title compound as a light yellow oil, 1.19 g, 60% yield.¹H NMR (DMSOd₆) δ: 3.82 (s, 3H), 5.62 (br s, 1 H), 6.86 (dd, 1 H), 7.10 (d, 1 H), 7.26 (d, 1 H) ppm. LRMS (ESI): m/z 172.79 [M(³⁵CI)-H]^" , 174.76 [M(³⁷CI)-H]^"

References:

WO2010/136940,2010,A1 Location in patent:Page/Page column 65-66

16817-43-9 Synthesis