Reaction #77868

Reaction equation

hydrazine hydrate

isatin

→

isatin hydrazone

Solvents

methanol

Conditions

Workup

1. 1
   Otherare prepared by a two-step reaction

Procedure

Chem. Educ. 1993, 70 (4), p. 332 discloses that 2-oxindoles are prepared by a two-step reaction, the first step of which comprises reacting isatin with hydrazine hydrate in anhydrous methanol to give the intermediate isatin hydrazone and isolating and purifying the intermediate. In the second step, the purified and dried intermediate is subjected to a Wolf-Kishner reduction in an anhydrous ethanol solution in the presence of a strong base such as sodium ethoxide. The yields achieved by this preparation method are up to about 69%. However, the disadvantage of this variant is the necessity of isolating, purifying and drying the intermediate before the reduction step can take place. A further disadvantage is the use of expensive, anhydrous ethanol as solvent because of the readiness of sodium ethoxide to react with water. A further preparation variant is described by Synth. Commun. 1994, 24 (20), p. 2835-41. In this variant, isatin is first dissolved in pure hydrazine and then reacted with pure hydrazine under reflux to give 2-oxindole in yields of up to 76%. However, this method requires a large quantity of pure hydrazine which serves as solvent and as reagent. When pure hydrazine is used, there is known to be a risk of explosion on heating or on reaction with oxidizing agents, so that particular safety measures have to be taken. An improvement suggested by U.S. Pat. No. 5,973,165 comprises preparing 2-oxindoles by reacting isatin with hydrazine hydrate in the presence of a weak base as catalyst and in a polar solvent. In order to obtain the desired end product in pure form, after the end of the reaction, 2-oxindole (purity about 97%) is first extracted, the extract is dried and then dissolved in a suitable solvent, and activated carbon is then added to the solution to decolorize it. After filtering off the activated carbon, 2-oxindole is crystallized out of the solution and obtained in a purity of 99.5%. The yields which are obtained by this process according to Example 1 are around 85%, but otherwise from 52 to 72%.

Source