Aniline → N-Phenyl-p-toluidine
Reaction equation
Cl[C:2]1[CH:7]=[CH:6][C:5](C)=[CH:4][C:3]=1[N+:9]([O-])=O.N[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[C:19]([O-])(=O)C.[Na+]>>[CH3:19][C:13]1[CH:18]=[CH:17][C:16]([NH:9][C:3]2[CH:2]=[CH:7][CH:6]=[CH:5][CH:4]=2)=[CH:15][CH:14]=1Participants
Procedure
A mixture of 4-chloro-3-nitrotoluene (II: R'=4-Me, halogen=Cl) (1.00 mL, 7.56 mmol), aniline (III: R1' =H) (6.89 mL, 0.075 mmol) and sodium acetate (1.24 g, 0.015 mol) was refluxed under nitrogen for 18 hours. The cooled product was partitioned between EtOAc and water, and the organic portion was washed with 2N HCl, then brine, and worked up to give an oil which was chromatographed on silica gel. Elution with petroleum ether gave the 4-methyldiphenylamine (VI: R'=4-Me, R1' =H) as an orange oil (1.01 g, 58%) which was used directly. A solution of this (1.01 g, 4.42 mmol) in 1:1 MeOH/EtOAc (60 mL) was hydrogenated over 5% Pd--C for 3 hours. After removal of the catalyst and concentration to dryness under reduced pressure, the residue was dissolved in 2-methoxyethanol (100 mL) containing formamidine acetate (0.92 g, 8.84 mmol) and the solution refluxed for 3 hours. After removal of the solvent under reduced pressure, the residue was partitioned between EtOAc and water. The organic portion was worked up to give an oil which was chromatographed on silica gel. Elution with EtOAc/petroleum ether (1:5) gave foreruns, while EtOAc/petroleum ether (1:1) gave Example 12 (0.91 g, 98%). HCl salt: mp (MeOH/Et2O) 196-200° C.
Workup
- customThe cooled product was partitioned between EtOAc and water
- washthe organic portion was washed with 2N HCl
- customto give an oil which
- customwas chromatographed on silica gel
- washElution with petroleum ether
Sources & evidence
- ORD record
- ord-66a24930e2b5467899328ae932e4ad73
- Source dataset
- uspto-grants-1999_11
- Patent number
- US05990146
Reaction notes
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