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Part – B Studies on isatin derivatives…..
presence of a Lewis acid, usually aluminum chloride or BF3.Et2O 35 , although
TiCl4 36 has also been used to give the corresponding isatin. Literature also
reveals different applications for the preparation of isatin derivatives using the
Stolle procedure. 37-41
4. The Martinet isatin synthesis
The Martinet procedure for the synthesis of indole-2,3-diones involves
the reaction of an aminoaromatic compound and either an oxomalonate ester
or its hydrate in the presence of an acid to yield a 3-(3-hydroxy-2oxindole)carboxylic
acid derivative which after oxidative decarboxylation
yields the respective isatin. This method was applied with success for the
synthesis of 5, 6-dimethoxyisatin from 4-aminoveratrole whereas the use of 2,
4-dimethoxyaniline was less successful 42 but it is readily applied to
naphthylamines. 43
5. The Gassman procedure
A fundamentally different and general procedure developed by
Gassman is another option for the synthesis of isatins. 44, 45 This methodology
consists in the formation and subsequent oxidation of an intermediate 3methylthio-2-oxindole
46-48 to give the corresponding substituted isatins in 40-
81% yield. Literature also reveals different applications for the preparation of
isatin derivatives using the Gassman procedure. 49
6. Metalation of anilide derivatives
A more recent method for the synthesis of isatins is based upon the
directed ortho-metalation (DoM) of N-pivaloyl-and N-(t-butoxycarbonyl)anilines.
The corresponding dianions are treated with diethyl oxalate and the
isatins are obtained after deprotection and cyclisation of the intermediate αketoesters.
This method has the advantage of being regioselective for the
synthesis of 4-substituted isatins from meta-substituted anilines where the
substituent is a metalation directing group (e.g. OMe). 50 (Fig. B.1.2) Literature
also reveals different applications for the preparation of isatin derivatives via
51, 52
metalation of anilide derivatives.
Department of Chemistry, Saurashtra University, Rajkot-360 005 115