Sodium Hydroxide → 1H-Benzimidazole, 2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]thio]-

HRID 35476Notes

Reaction equation

HRID 35476 reaction equation
[N:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[NH:3][C:2]=1[SH:10].Cl.Cl[CH2:13][C:14]1[C:19]([CH3:20])=[C:18]([O:21][CH3:22])[C:17]([CH3:23])=[CH:16][N:15]=1.[OH-].[Na+]>O>[CH3:22][O:21][C:18]1[C:17]([CH3:23])=[CH:16][N:15]=[C:14]([CH2:13][S:10][C:2]2[NH:1][C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[N:3]=2)[C:19]=1[CH3:20]

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 116942582-(Chloromethyl)-3,5-dimethyl-4-methoxypyridine hydrochlorideHCID 178527775HCID 178527775, compound

Product 1

HCID 106618911H-Benzimidazole, 2-[[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]thio]-

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

64.8 g of 2-benzimidazolethiol are suspended in 400 ml of alcohol and treated with 95.9 g of 2-chloromethyl-4-methoxy-3.5-dimethylpyridine hyrochloride while cooling with ice. Thereafter, a solution of 34.5 g of sodium hydroxide in 1.5 l of water is added dropwise thereto, the mixture is left to boil at reflux overnight and subsequently evaporated to dryness in vacuo. The residue is dissolved in 2.0 l of methylene chloride. The solution is washed firstly with 600 ml of 1.5N sodium hydroxide solution and then 3× with 2.2 l of water, dried over sodium sulphate and evaporated in vacuo. The crude product is purified on 1300 g of silica gel with ethyl acetate/methylene chloride (1:1) as the elution agent. Crystallization from methylene chloride/petroleum ether gives 2-[[(4-methoxy-3,5 -dimethyl-2-pyridyl)methyl]thio]benzimidazole of melting point 129°-131°.

Workup

  1. temperaturewhile cooling with ice
  2. waitthe mixture is left
  3. temperatureat reflux overnight
  4. customsubsequently evaporated to dryness in vacuo
  5. dissolutionThe residue is dissolved in 2.0 l of methylene chloride
  6. washThe solution is washed firstly with 600 ml of 1.5N sodium hydroxide solution
  7. dry with material3× with 2.2 l of water, dried over sodium sulphate
  8. customevaporated in vacuo
  9. customThe crude product is purified on 1300 g of silica gel with ethyl acetate/methylene chloride (1:1) as the elution agent
  10. customCrystallization from methylene chloride/petroleum ether

Sources & evidence

ORD record
ord-7ea7479b29fa46dc9a344fd2a0a58fe1
Source dataset
uspto-grants-1988_08
Patent number
US04766133

Reaction notes

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