Reaction #77873

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

40.39 g of isatin (0.27 mol, purity 98.2%) were initially charged into a 500 ml four-neck flask and 200 ml of 2-ethylhexanol were added. With stirring (KPG, 250 rpm), 13.1 ml of hydrazine hydrate (13.5 g, 0.27 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). Afterwards, 6.12 g of DABCO (55 mmol, 98%) were added and the reaction mixture heated for a further about 0.5 hour until the DABCO had dissolved. The suspension was then charged in portions into 35 ml of 2-ethylhexanol in a receiver vessel which had been preheated to 145-150° C. Since addition of the cold suspension to the preheated 2-ethylhexanol resulted in an immediate temperature decrease which slowed the nitrogen elimination, the isatin hydrazone suspension was added in portions of each about 5 ml at intervals of 2-3 min to avoid this, so that the temperature in the receiver could be maintained in the target range of 140-145° C. Occasionally, an extension of the interval of up to 5 min was necessary. During the metering in (1.5-2 h), the reaction suspension foamed vigorously, particularly at the end of the reaction. During the nitrogen elimination, about 6.5 g of a biphasic mixture of water and some 2-ethylhexanol were distilled off. In this distillate 1, no hydrazine was found. The reaction mixture was held until complete conversion (about another 1.5 hours) at 140-145° C. (IPC control, GC: complete consumption of the hydrazone at 0.1-0.2 area %). 185 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 55° C. and 80 g of MTBE were added. The reaction solution was cooled to 5° C. (in 0.5-1 h, then left to stand overnight at RT) to crystallize the 2-oxindole. The crystals were filtered off, washed with 3×5 ml of cold MTBE (0° C.) and sucked to dryness. 30.0 g of damp product were obtained which were dried for about 48 hours in a vacuum drying cupboard (80-90° C. and 50-65 mbar) to constant weight. Altogether, 23.9 g of dry 2-oxindole product (light brown) were obtained which corresponded to an overall yield of 66.5%.

Source