2-Aminothiophenol → 5-(Benzothiazol-2-yl)-1-phenyl-2-(phenylmethoxy)methylbenzimidazole

HRID 74155Notes

Reaction equation

HRID 74155 reaction equation
[C:1]1([N:7]2[C:11]3[CH:12]=[CH:13][C:14]([C:16](O)=O)=[CH:15][C:10]=3[N:9]=[C:8]2[CH2:19][O:20][CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.[NH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][C:36]=1[SH:41]>O1CCCC1>[S:41]1[C:36]2[CH:37]=[CH:38][CH:39]=[CH:40][C:35]=2[N:34]=[C:16]1[C:14]1[CH:13]=[CH:12][C:11]2[N:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[C:8]([CH2:19][O:20][CH2:21][C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=3)=[N:9][C:10]=2[CH:15]=1

Participants

5

Reactant 3

HCID 87132-AminothiophenolHCID 65578Oxalyl chlorideHCID 675026181-Phenyl-2-(phenylmethoxy)methylbenzimidazole-5-carboxylic acid

Product 1

HCID 498212945-(Benzothiazol-2-yl)-1-phenyl-2-(phenylmethoxy)methylbenzimidazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A 4-neck flask (500 mL) equipped with a reflux condenser was charged with 1-pheny-2-(phenylmethoxy)methylbenzimidazole-5-carboxylic acid (see Working Example 1-1) (4.00 g, 11.16 mmol) and anhydrous tetrahydrofuran (63 mL), and after the addition of oxalyl chloride (1.65 g, 13.0 mmol), this was warmed to 50° C. and stirred for 3 hours. After cooling to room temperature, the solvent was distilled off under reduced pressure. Anhydrous THF (30 mL) was again added to the greenish-milky white semisolid residue, and after gradual addition of 2-aminobenzenethiol (1.40 g, 11.22 mmol), this was warmed to 50° C. and stirred for 16 hours. After cooling to room temperature, the precipitated crystals were filtered off and washed with saturated aqueous sodium hydrogen carbonate solution (approx. 20 mL), and the precipitated solid was filtered off to yield a mixture of starting material and the title compound (2.43 g, an approx. 1:1 mixture of starting material/title compound, based on 1H-NMR). The filtrate was allowed to stand for a further 16 hours at room temperature and the precipitated crystals were filtered off, washed with saturated aqueous potassium carbonate solution, washed with distilled water, and then dried under reduced pressure with heating to yield the title compound (0.82 g, 16% yield) as a white powder.

Workup

  1. customA 4-neck flask (500 mL) equipped with a reflux condenser
  2. temperatureAfter cooling to room temperature
  3. distillationthe solvent was distilled off under reduced pressure
  4. additionAnhydrous THF (30 mL) was again added to the greenish-milky white semisolid residue
  5. temperaturethis was warmed to 50° C.
  6. stirringstirred for 16 hours
  7. temperatureAfter cooling to room temperature
  8. filtrationthe precipitated crystals were filtered off
  9. washwashed with saturated aqueous sodium hydrogen carbonate solution (approx. 20 mL)
  10. filtrationthe precipitated solid was filtered off
  11. customto yield
  12. additiona mixture of starting material

Sources & evidence

ORD record
ord-27ce1a6ab9f64aa686b294c77f7a9853
Source dataset
uspto-grants-2014_09
Patent number
US08829035B2

Reaction notes

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