Sodium Hydroxide → 3-Phenyl-5-(2-thienyl)-1,2,4-oxadiazole

HRID 919361Notes

Reaction equation

HRID 919361 reaction equation
[C:1](=[N:9][OH:10])([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.[OH-].[Na+].[S:31]1[CH:35]=[CH:34][CH:33]=[C:32]1[C:36](Cl)=O>CC1CCCO1.O>[C:2]1([C:1]2[N:8]=[C:36]([C:32]3[S:31][CH:35]=[CH:34][CH:33]=3)[O:10][N:9]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 14798Sodium Hydroxide2×HCID 69186N'-HydroxybenzenecarboximidamideHCID 789282-Thiophenecarbonyl chlorideHCID 2723671Tetrabutylammonium Hydroxide

Product 1

HCID 6956793-Phenyl-5-(2-thienyl)-1,2,4-oxadiazoleYield 95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 73012-MethyltetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A 39.45% solution of benzamide oxime in 2-methyltetrahydrofuran (33.34 g) was charged to a 100 mL flask, followed by water (9.0 g), 40% aqueous solution of tetrabutylammonium hydroxide (1.02 g), and 51% sodium hydroxide (3.52 g, 0.045 moles). To this mixture was added 2-thiophenecarbonyl chloride (13.83 g, 0.0936 moles) and 51% sodium hydroxide (7.33 g, 0.0935 moles) simultaneously over a 30 minute period while heating to about 70° C. The reaction was complete in less than 80 minutes. The aqueous salt phase was removed, water was added (30 g), and the 2-methyltetrahydrofuran partly removed by atmospheric distillation (13.5 mL). An additional amount (32 g) of hot water was added, and the remainder of the 2-methyltetrahydrofuran was distilled out, during which time the product, 3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole, precipitated. The aqueous slurry of 3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole was filtered, washed with water and dried overnight in a vacuum oven to yield 3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole, 20.47 g, 99.1% pure, 95.0% yield.

Workup

  1. waitThe reaction was complete in less than 80 minutes
  2. customThe aqueous salt phase was removed
  3. additionwater was added (30 g)
  4. customthe 2-methyltetrahydrofuran partly removed by atmospheric distillation (13.5 mL)
  5. additionAn additional amount (32 g) of hot water was added
  6. distillationthe remainder of the 2-methyltetrahydrofuran was distilled out, during which time the product, 3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole
  7. customprecipitated
  8. filtrationThe aqueous slurry of 3-phenyl-5-(2-thienyl)-1,2,4-oxadiazole was filtered
  9. washwashed with water
  10. customdried overnight in a vacuum oven

Sources & evidence

ORD record
ord-2cbb971da95c48e89137f2db117d3248
Source dataset
uspto-grants-2016_03
Patent number
US09273037B2

Reaction notes

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