Reaction #77872

Reaction equation

isatin

hydrazine hydrate

→

isatin hydrazone

Solvents

2-ethylhexanol

Conditions

Workup

1. 1
   workup.ADDITIONwere added within 15 minutes
2. 2
   Temperatureto increase from 23° C. to 45° C.
3. 3
   Otheran intensely orange suspension to form
4. 4
   TemperatureThe reaction mixture was heated further

Procedure

400.6 g of isatin (2.72 mol, purity 98.2%) were initially charged into a 2 l double jacket vessel and 2000 ml of 2-ethylhexanol were added. With stirring (KPG, 250 rpm), 131 ml of hydrazine hydrate (135.2 g, 2.70 mol, purity 100.6%) were added within 15 minutes, which caused the temperature to increase from 23° C. to 45° C. and an intensely orange suspension to form. The reaction mixture was heated further and held at 50° C. for 60 minutes to form isatin hydrazone (yellow suspension). 61.2 g of DABCO (0.55 mol, 98%) were then added and the reaction solution continuously heated up to 130° C. which resulted in the onset of nitrogen cleavage above about 100° C. At the same time, the water (reaction water+hydrate water+2-ethylhexanol, 114.7 g altogether) was discharged. This resulted in refluxing and foaming of the reaction mixture. The reaction mixture was held at 130° C. until complete conversion (5 h). 1500 ml of 2-ethylhexanol were then distilled off at 90-95° C. (20-30 mbar, contained 0.02% by weight of hydrazine), the reaction solution was cooled to 50° C. and admixed with 732 g of MTBE and then cooled slowly with stirring to crystallize the 2-oxindole (from 130° C. to 50° C. in 3 h, then left to stand overnight at room temperature). The crystals were filtered off, washed with 3×50 ml of cold MTBE (5° C.) and sucked to dryness. 328.1 g of damp product were obtained which was dried for about 48 hours in a vacuum drying cabinet (80-90° C. and 50-65 mbar) to constant weight. Altogether, 298.7 g of dry 2-oxindole product (light brown) were obtained which corresponded to an overall yield of 83.1%.

Source