5-Iodo-2-thiophenecarbonitrile synthesis
- Product Name:5-Iodo-2-thiophenecarbonitrile
- CAS Number:18945-81-8
- Molecular formula:C5H2INS
- Molecular Weight:235.05
1003-31-2
18945-81-8
Under nitrogen protection, 2-cyanothiophene (1 mmol) was dissolved in anhydrous THF (1.5 mL) in a flame-dried flask. TMPMgCl-LiCl (1.0 M solution of THF, 1.8 mL, 1.8 mmol) was slowly added dropwise at 25 °C and the reaction mixture was stirred for 2 h (for substrate 1a, it is recommended that the metallization time be kept within 1 h). The completion of the metallization reaction was monitored by GC analysis, and an aliquot of the reaction solution was taken and quenched with anhydrous THF solution of iodine (I2) to terminate the reaction. Subsequently, a solution of anhydrous THF (2 mL) with electrophilic reagent (2 mmol) was slowly added dropwise at 0 °C, and the temperature was raised to 25 °C to continue stirring for 1 hour. Upon completion of the reaction, the reaction was quenched with saturated aqueous NaHCO3 solution. Extraction was carried out sequentially with NaHSO3 or NH4Cl solution (5 mL) and ethyl acetate (3 x 15 mL), the organic phases were combined and dried with anhydrous MgSO4. After filtration to remove the desiccant, the solvent was removed by distillation under reduced pressure to give the crude product 5-iodothiophene-2-carbonitrile.
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Yield:18945-81-8 88%
Reaction Conditions:
Stage #1: thiophene-2-carbonitrilewith 2,2,6,6-tetramethylpiperidinylmagnesium chloride lithium chloride complex in tetrahydrofuran at 25; for 2 h;
Stage #2: with iodine in tetrahydrofuran at 25; for 1 h;
Steps:
Typical procedure for metalation with TMPMgCl.LiCl followed by the reaction withelectrophiles (iodine, PhSeSePh and PhSSPh)
General procedure: In a flame-dried flask flushed with nitrogen, the heterocyclic nitrile (1 mmol) wasdissolved in THF (1.5 mL). TMPMgCl·LiCl (1.0 M in THF, 1.8 mL, 1.8 mmol) wasadded dropwise at 25°C and the mixture was stirred for 2h (for substrate 1a, metalationwas best performed in 1 h). The completion of the metalation was checked by GC analysisof reaction aliquots quenched with a solution of I2 in dry THF. After that, a solution ofthe electrophile (2 mmol) in THF (2 mL) was added dropwise at 0°C and the reactionstirred for 1 hour at 25°C. The reaction mixture was quenched with sat. aq. NaHSO3 orNH4Cl solution (5 mL), extracted with ethyl acetate (3x15 mL) and dried over anhydrousMgSO4. After the filtration, solvent was evaporated in vacuo.
References:
Dos Santos, Fernanda M.;Batista, Jo?o H. C.;Vessecchi, Ricardo;Clososki, Giuliano C. [Synlett,2015,vol. 26,# 20,art. no. ST-2015-S0611-C,p. 2795 - 2800] Location in patent:supporting information