Phosphorus oxychloride → 2-(Chloromethyl)-5-(4-methylphenyl)-1,3,4-oxadiazole

HRID 334515Notes

Reaction equation

HRID 334515 reaction equation
[Cl:1][CH2:2][C:3]([NH:5][NH:6][C:7](=[O:15])[C:8]1[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=1)=O.P(Cl)(Cl)(Cl)=O>C(#N)C>[Cl:1][CH2:2][C:3]1[O:15][C:7]([C:8]2[CH:9]=[CH:10][C:11]([CH3:14])=[CH:12][CH:13]=2)=[N:6][N:5]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 736971N'-(2-chloroacetyl)-4-methylbenzohydrazide

Product 1

HCID 7369732-(Chloromethyl)-5-(4-methylphenyl)-1,3,4-oxadiazoleYield 72.4%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 4-methylbenzohydrazide 14 (10 g, 66.59 mmol) and K2CO3 (16.57 g, 119.86 mmol) in acetonitrile (100 mL) was added 2-chloroacetyl chloride (9.02 g, 79.9 mmol) dropwise at ambient temperature. The resulting mixture was stirred at ambient temperature for 16 hours. The solid was collected, washed with H2O and ether, and dried to afford N′-(2-chloroacetyl)-4-methylbenzohydrazide 15 (13 g, 82%) which was used for the next step without further purification. A mixture of N′-(2-chloroacetyl)-4-methylbenzohydrazide 15 (6.0 g, 26.47 mmol) and phosphorous oxychloride (5.0 g, 32.84 mmol) in acetonitrile (20 mL) was stirred under reflux for 16 hours and concentrated. The residue was subjected to flush column chromatography eluting with 10-25% acetone/hexanes to give compound 16 (4 g). Yield: 72%.

Workup

  1. customwas used for the next step without further purification
  2. temperatureunder reflux for 16 hours
  3. concentrationconcentrated
  4. customto flush column chromatography
  5. washeluting with 10-25% acetone/hexanes

Sources & evidence

ORD record
ord-d8cef926cf654c9f9a0f2e30b686da86
Source dataset
uspto-grants-2014_11
Patent number
US08883827B2

Reaction notes

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