Diphenylamine → Isatin

HRID 1382492Notes

Reaction equation

HRID 1382492 reaction equation
[C:1](Cl)(=[O:5])[C:2](Cl)=[O:3].[C:7]1([NH:13]C2C=CC=CC=2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1>C1(C)C=CC=CC=1>[NH:13]1[C:7]2[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=2)[C:2](=[O:3])[C:1]1=[O:5]

Participants

4

Reactant 2

HCID 11487DiphenylamineHCID 65578Oxalyl chloride

Product 1

HCID 7054Isatin

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of oxalyl chloride (175 mL, 254.6 g, 2.01M) was cooled to 5°, and a solution of diphenylamine (320 g, 1.89M) in toluene (580 mL) added over 8 minutes. The mixture was heated to 50°-65° for 74 minutes. The mixture was then heated to 125° to distill toluene and excess oxalyl chloride; total distillate collected was 630 mL. The solution was then refluxed at 125°±2° for 20 hours to form indoline-2,3-dione. The mixture was cooled to 104°, and a solution of 4-picoline (215 mL, 205.7 g, 2.21M) in acetic acid (750 mL) was added over 17 minutes. The mixture was heated to 130° to remove excess toluene via acetic acid/toluene azeotrope. Additional acetic acid (750 mL) was added during the distillation. A total of 875 mL distillate containing 260 mL toluene was collected. The mixture was cooled to 115°, and acetic anhydride (360 mL, 389.5 g, 3.81M) added over 10 minutes while heating to 120°-130°. The mixture was stirred at 120°±2° for 1.75 hours, and then cooled to 76°. Water (530 mL) was added over 7 minutes followed by isopropanol (430 mL) while maintaining the temperature between 82° and 63°. The mixture was cooled to ambient temperature overnight, then to 0°-5°. The crude product was collected by filtration, washed with isopropanol (2.16 l) and water 1.64 l). Drying in a vacuum oven at 80°-90° yielded the title compound (422.6 g, 75%) as an orange crystalline solid. M.P.: 160.1°-161.9°.

Workup

  1. temperatureThe mixture was heated to 50°-65° for 74 minutes
  2. temperatureThe mixture was then heated to 125°
  3. distillationto distill toluene and excess oxalyl chloride
  4. distillationtotal distillate collected
  5. temperatureThe solution was then refluxed at 125°±2° for 20 hours

Sources & evidence

ORD record
ord-af4218b8dfab4595a4ee10987624588e
Source dataset
uspto-grants-1989_02
Patent number
US04806651

Reaction notes

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