Abstract
The presence of LiCl allows the convenient preparation of magnesiated imidazoles starting
from unprotected iodoimidazoles. They react with various electrophiles in satisfactory
yields.
Key words
magnesium - heterocycles - organometallic reagents - imidazole - exchange reaction
References and Notes
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Typical Procedure for the Synthesis of 4-Iodo-5-(methylsulfanyl)-1
H
-imidazole (
3i)
H -imidazole (1b , 640 mg, 2.00 mmol) was placed in a dry and argon-flushed Schlenk tube equipped with
a magnetic stirring bar and a septum. A solution of LiCl in THF (0.5 M, 4.0 mL, 2.0
mmol, 1.0 equiv) was added and after stirring 5 min at r.t., the resulting slurry
was cooled to -20 °C and MeMgCl (3.0 M in THF, 0.7 mL, 2.0 mmol, 1.0 equiv) was added
dropwise. After completion of the addition, the mixture was stirred at -20 °C for
further 20 min. Then, i -PrMgCl·LiCl (1.3 M in THF, 1.7 mL, 2.2 mmol, 1.1 equiv) was added slowly and the
resulting mixture was allowed to warm to r.t. The exchange reaction was monitored
by TLC (samples quenched with MeOH, silica plates; CH2 Cl2 -MeOH, 19:1) versus the starting material and was usually complete after 45 min. The
resulting slurry was cooled to -20 °C and (S )-methyl methanesulfonothioate (610 mg, 2.40 mmol, 1.20 equiv) was added neat at this
temperature, then the mixture was allowed to warm to r.t. After the completion of
the reaction (TLC monitoring) the reaction mixture was poured on H2 O (20 mL ) and sat. aq NH4 Cl (20 mL), and the aqueous layer was extracted with CH2 Cl2 (3 × 40 mL). The combined CH2 Cl2 layers were dried (Na2 SO4 ) and evaporated in vacuo. Flash column chromatography (silica gel, CH2 Cl2 -MeOH, 19:1) afforded 4-iodo-5-(methylsulfanyl)-1H -imidazole (3i ) as colorless solid (mp 126.1-128.4 °C).
