Benzonitrile → 7-Chloro-2-methyl-5-phenyl-5H-[1,2,4]triazolo[5,1-a]isoindol-5-amine

HRID 616907Notes

Reaction equation

HRID 616907 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]=[C:11]([CH3:13])[NH:10][N:9]=2)=[CH:4][CH:3]=1.C([Li])CCC.[C:19](#[N:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.[Cl-].[NH4+]>O1CCCC1.C(Cl)(Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]2[C:5](=[CH:4][CH:3]=1)[C:8]1=[N:12][C:11]([CH3:13])=[N:10][N:9]1[C:19]2([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[NH2:26]

Participants

7

Reactant 4

HCID 7505BenzonitrileHCID 25517Ammonium ChlorideHCID 124680223-(4-Chlorophenyl)-5-methyl-1H-1,2,4-triazoleHCID 178418339Butyllithium

Product 1

HCID 124680237-Chloro-2-methyl-5-phenyl-5H-[1,2,4]triazolo[5,1-a]isoindol-5-amineYield 49.1%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

2.0 g (10.3 mmol) of 3-(4-Chlorophenyl)-5-methyl-1H-1,2,4-triazole is dissolved in 50 ml of tetrahydrofuran (THF) (freshly distilled from lithium aluminum hydride) mechanically stirred in a 250 ml round-bottom 3-necked flask equipped with a septum and nitrogen inlet and cooled in an ice bath. 13.6 ml (22.7 mmol) of n-butyllithium (1.67 mol/liter in hexane) is injected with a syringe and the mixture is stirred in the ice bath for 30 minutes. 2.12 g (20.6 mmol) of benzonitrile is added in a little THF. After stirring for 30 minutes in the ice bath, and for 30 minutes at room temperature, the mixture is poured into a chilled stirred mixture of 100 ml of 2.5 M ammonium chloride and 200 ml of chloroform. The layers are separated and the aqueous layer washed with chloroform. The combined chloroform layers are washed with water and dried (Na2SO4). The chloroform is removed under vacuum and the residue is recrystallized from toluene to yield 1.5 g of the title compound, m.p. 173°-175°.

Workup

  1. distillationfreshly distilled from lithium aluminum hydride)
  2. customequipped with a septum and nitrogen inlet
  3. temperaturecooled in an ice bath
  4. additionthe mixture is poured into a chilled
  5. stirringstirred
  6. customThe layers are separated
  7. washthe aqueous layer washed with chloroform
  8. washThe combined chloroform layers are washed with water
  9. dry with materialdried (Na2SO4)
  10. customThe chloroform is removed under vacuum
  11. customthe residue is recrystallized from toluene

Sources & evidence

ORD record
ord-1e0a0395160e4ff49a21e09aabb2506a
Source dataset
uspto-grants-1978_02
Patent number
US04076823

Reaction notes

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