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Part – B Studies on isatin derivatives…..
7. Miscellaneous procedures
Fig. B.1.2
Many other alternate procedures for the preparation of isatins are
discussed in last few years. 53-98
B.4 N-ALKYLATION ON ISATIN
Many methods have been devised for the N-alkylation of isatins. These
derivatives are commonly synthesized from the reaction of the sodium salt of
isatin with alkyl halides or sulphates. 99, 100 Various methods for the
preparation of this salt have been reported, and include the reaction of isatin
with sodium hydride, in toluene, 101 DMF, 102-133 Dioxane, 134 135, 136
DMSO,
THF. 137-142 In case of carbonates it includes, the use of potassium carbonate
in DMF, 108, 133, 143-155 acetone, 156-158 acetonirile, 159, 160 chloroform, 161 while
the use of cesium carbonate in acetonitrile, 160 DMF, 162 and the use of
sodium carbonate in acetone. 163, 164 165, 166
Strong bases like NaOH with DMF
and methanol 166 and KOH with DMF, 167, 168 DMSO, 169 ethanol 170-173 and
methanol 174-176 are also used for N-alkylation of isatin. TEA is also used for
N-acylation with Benzene 103, 177 while DMF, 178 and THF 179 is used with TEA
for alkylation. Sodium methoxide is used with acetonitrile, 180 methanol 181 and
sodium ethoxide with ethanol. 103, 182, 183 In the later case an aldol reaction of
the solvent also occurs with the C3 carbonyl of the isatin derivative. Heating in
ortho-dichlorobenzene results in a retro-aldol reaction and the obtention of the
N-alkylated isatin. The use of CaH2 in DMF has been reported 184-187 and this
method was used for the synthesis of both mono and bis-N-alkylisatins. These
Department of Chemistry, Saurashtra University, Rajkot-360 005 116