Methane → 5-(4-Methylphenyl)-4,6-dichloro-2-(2-thienyl)pyrimidine

HRID 2318

Reaction equation

HRID 2318 reaction equation
[S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.C([Li])CCC.CCCCCC.[CH3:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2[C:25]([Cl:31])=[N:26][CH:27]=[N:28][C:29]=2[Cl:30])=[CH:20][CH:19]=1.ClC1C(=O)C(C#N)=C(C#N)C(=O)C=1Cl.C>O1CCCC1.O.C(O)(=O)C>[CH3:17][C:18]1[CH:19]=[CH:20][C:21]([C:24]2[C:29]([Cl:30])=[N:28][C:27]([C:2]3[S:1][CH:5]=[CH:4][CH:3]=3)=[N:26][C:25]=2[Cl:31])=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 297MethaneHCID 67752,3-Dichloro-5,6-dicyano-1,4-benzoquinoneHCID 8030ThiopheneHCID 219795544,6-Dichloro-5-(4-methylphenyl)pyrimidineHCID 178418244HCID 178418244, compound

Product 1

HCID 196895045-(4-Methylphenyl)-4,6-dichloro-2-(2-thienyl)pyrimidineYield 49.1%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
0 °C

Procedure

To a solution of thiophene (1.69 g) in anhydrous tetrahydrofuran (20 ml) is added dropwise a 1.6M n-butyl lithium/n-hexane solution (11.4 ml) at 0° C. under argon atmosphere over a period of 30 minutes. To the mixture is added dropwise and gradually a solution of 5-(4-methylphenyl)-4,6-dichloropyrimidine (4.0 g) in anhydrous tetrahydrofuran (5 ml) at -60° C. The mixture is warmed to 0° C., and stirred for 1.5 hour. After the reaction is complete, to the mixture are added acetic acid (1.5 g) and water (0.25 g), and further added thereto a solution of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (5.70 g) in tetrahydrofuran (5 ml), and the mixture is stirred at 0° C. for one hour. The mixture is treated with an active charcoal, and extracted with a mixture of ethyl acetate and aqueous citric acid solution. The extract is washed, dried and evaporated to remove the solvent. The residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=50:1) to give 5-(4-methylphenyl)-4,6-dichloro-2-(2-thienyl)pyrimidine (2.64 g) as powder.

Workup

  1. additionTo the mixture is added dropwise
  2. customat -60° C
  3. additionfurther added
  4. extractionextracted with a mixture of ethyl acetate and aqueous citric acid solution
  5. washThe extract is washed
  6. customdried
  7. customevaporated
  8. customto remove the solvent
  9. customThe residue is purified by silica gel column chromatography (solvent; n-hexane/ethyl acetate=50:1)

Sources & evidence

ORD record
ord-1ce4869becc14147b48b50fb8a727e75
Source dataset
uspto-grants-1998_03
Patent number
US05728706

Linked notes

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