Sodium Carbonate → 1-Methyl-2,4-bis(5-methylthiophen-2-yl)-1H-imidazole

HRID 1429115Notes

Reaction equation

HRID 1429115 reaction equation
I[C:2]1[N:3]([CH3:13])[CH:4]=[C:5]([C:7]2[S:8][C:9]([CH3:12])=[CH:10][CH:11]=2)[N:6]=1.[CH3:14][C:15]1[S:19][C:18](B2OC(C)(C)C(C)(C)O2)=[CH:17][CH:16]=1.C([O-])([O-])=O.[Na+].[Na+]>O.CN(C=O)C>[CH3:13][N:3]1[CH:4]=[C:5]([C:7]2[S:8][C:9]([CH3:12])=[CH:10][CH:11]=2)[N:6]=[C:2]1[C:18]1[S:19][C:15]([CH3:14])=[CH:16][CH:17]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 118169404,4,5,5-Tetramethyl-2-(5-methylthiophen-2-yl)-1,3,2-dioxaborolaneHCID 675118002-Iodo-1-methyl-4-(5-methylthiophen-2-yl)-1H-imidazole

Product 1

HCID 675108951-Methyl-2,4-bis(5-methylthiophen-2-yl)-1H-imidazoleYield 79%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-iodo-1-methyl-4-(5-methylthiophen-2-yl)-1H-imidazole 6 (1.31 g, 4.31 mmol), 5-methylthiophene-2-boronic acid pinacol ester (1.35 g, 6.03 mmol), Na2CO3 (1.80 g, 17.2 mmol) in H2O (10 mL) and DMF (40 mL) was degassed (N2 bubbling). Pd(PPh3)4 (125 mg) was added and the mixture was heated to reflux for 5 h. The mixture was allowed to cool to room temperature and concentrated. The mixture was diluted with EtOAc and H2O 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 10:90 then 15:85 then 20:80) to give 1-methyl-2,4-bis(5-methylthiophen-2-yl)-1H-imidazole 7 (930 mg, 79%) as a colourless solid. A portion of this material was further purified by, firstly, recrystallisation (EtOAc/hexanes) and, secondly, by sublimation (130° C., 10−6 mBar): m.p. 138-140° C. 1H NMR (CDCl3, 400 MHz) δ2.48 (d, J=0.7 Hz, 3H), 2.51 (d, J=0.7 Hz, 3H), 3.76 (s, 3H), 6.64-6.67 (m, 1H), 6.73-6.77 (m, 1H), 7.00 (s, 1H), 7.10 (d, J=3.4 Hz, 1H), 7.14 (d, J=3.4 Hz, 1H); 13C NMR (CDCl3, 100 MHz) δ15.2, 15.3, 34.5, 117.0, 122.1, 125.5, 125.6, 126.7, 136.3, 137.7, 141.5, 142.4; HRMS (EI) m/z 274.0589 C14H14N2S2 [M]+. requires 274.0593.

Workup

  1. customwas degassed (N2 bubbling)
  2. additionPd(PPh3)4 (125 mg) was added
  3. temperaturethe mixture was heated
  4. temperatureto reflux for 5 h
  5. concentrationconcentrated
  6. additionThe mixture was diluted with EtOAc and H2O
  7. customthe organic phase was separated
  8. extractionThe aqueous phase was re-extracted (EtOAc)
  9. washthe combined organics were washed (saturated aqueous NaCl)
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customto give a residue
  14. customThe residue was purified by flash chromatography (EtOAc/hexanes 10:90

Sources & evidence

ORD record
ord-f74fc4f070a74e7192738e43815b2e20
Source dataset
uspto-grants-2015_01
Patent number
US08937303B2

Reaction notes

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