Iodine → 2-Iodo-4-(5-methylthiophen-2-yl)-1-trityl-1H-imidazole

HRID 1429111Notes

Reaction equation

HRID 1429111 reaction equation
[CH3:1][C:2]1[S:6][C:5]([C:7]2[N:8]=[CH:9][N:10]([C:12]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH:11]=2)=[CH:4][CH:3]=1.[Li]CCCC.[I:36]I.[NH4+].[Cl-]>C1COCC1>[I:36][C:9]1[N:10]([C:12]([C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)([C:19]2[CH:20]=[CH:21][CH:22]=[CH:23][CH:24]=2)[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:11]=[C:7]([C:5]2[S:6][C:2]([CH3:1])=[CH:3][CH:4]=2)[N:8]=1

Participants

6

Reactant 4

HCID 807IodineHCID 25517Ammonium ChlorideHCID 675105464-(5-methylthiophen-2-yl)-1-trityl-1H-imidazoleHCID 178418339Butyllithium

Product 1

HCID 675120362-Iodo-4-(5-methylthiophen-2-yl)-1-trityl-1H-imidazoleYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-50 °C

Procedure

A mixture of 4-(5-methylthiophen-2-yl)-1-trityl-1H-imidazole (2.20 g, 5.42 mmol) in THF (100 mL) was cooled to −78° C. nBuLi mL of a 1.6 M solution in hexanes, 6.2 mmol) was added dropwise (˜2 min) and the pale yellow solution was allowed to warm to −50° C. (over ˜1 h) and then re-cooled to −78° C. I2 (2.74 g, 10.4 mmol) was added and the mixture was allowed to warm to room temperature (over ˜4 h) and stirred overnight. Saturated aqueous NH4Cl (2 mL) was added and the mixture was concentrated to ˜10 mL. The mixture was diluted with EtOAc, H2O, saturated aqueous Na2S2O3 and the organic phase was separated. The aqueous phase was re-extracted (EtOAc) and the combined organics were washed (saturated aqueous NaCl), dried (MgSO4), filtered and concentrated to give a residue. The residue was purified by flash chromatography (EtOAc/hexanes 5:95 then 15:85) to give 2-iodo-4-(5-methylthiophen-2-yl)-1-trityl-1H-imidazole 2 (1.72 g, 60%) as a colourless solid. 1H NMR (CDCl3, 400 MHz) δ2.45 (s, 3H), 6.60-6.64 (m, 1H), 6.94 (s, 1H), 6.99 (d, J=3.5 Hz, 1H), 7.19-7.39 (m, 15H); 13C NMR (CDCl3, 100 MHz) δ15.3, 90.6, 120.4, 122.3, 125.5, 125.6, 127.2, 128.1, 130.8, 134.2, 138.1, 138.2, 141.4, 146.8; HRMS (EI) m/z 532.0459 C27H21N2IS [M]+. requires 532.0465.

Workup

  1. additionwas added dropwise (˜2 min)
  2. temperaturere-cooled to −78° C
  3. temperatureto warm to room temperature (over ˜4 h)
  4. concentrationthe mixture was concentrated to ˜10 mL
  5. additionThe mixture was diluted with EtOAc, H2O, saturated aqueous Na2S2O3
  6. customthe organic phase was separated
  7. extractionThe aqueous phase was re-extracted (EtOAc)
  8. washthe combined organics were washed (saturated aqueous NaCl)
  9. dry with materialdried (MgSO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give a residue
  13. customThe residue was purified by flash chromatography (EtOAc/hexanes 5:95

Sources & evidence

ORD record
ord-90c7fb0b2b5f4153a0cbf45bc6a9f987
Source dataset
uspto-grants-2015_01
Patent number
US08937303B2

Reaction notes

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