Isatin, ketone nucleophiles

The word enamine was coined in 1927 by Wittig [27], However, at that time, enamines were usually not considered as reactive intermediates. An early example of enamine catalysis that was not explicitly recognized as enamine-based reaction was the reaction of isatin with ketone nucleophiles (acetone and acetophenone), first pnblished by Lindwall and coworkers in 1932 [28, 31]. Later, the interconversion of imininm ions and enamines in enzymatic reactions was recognized by Westheimer [32, 354]. The first person to propose a modem enamine-based... 

The reaction of isatins with ketones leading to 4-quinolinecarboxylic acids is carried out in the presence of strong nucleophiles (sodium hydroxide or potassium hydroxide). For this reason the generally accepted mechanism of the process is the following. The isatins 1 are converted by the action of alkalis into the salts of... 

Carbonyl not adjacent to heteroatom. Carbonyl groups not adjacent to a heteroatom are less stabilized by resonance and react with the relatively weakly nucleophilic ketonic reagents. If carbonyl groups of both types are present, as in 319 (Z = O, NH), then the carbonyl group not adjacent to the heteroatom is preferentially attacked. Thus, isatin and indoxyl and their O- and S-analogues (319, 322) react with hydroxylamine, hydrazine, phenylhydrazine, semicarbazide, etc., to give oximes, hydrazones, phenylhydrazones, semicarbazones, etc. (322 323 319 324). 

Addition of 2,5-dihydro-2,2-dimethyl-5,5-bis(propylthio)-l,3,4-oxadiazole in refluxing benzene and an aryl isocyanate releases the bis(propylthio)carbene in situ which then adds easily to the aryl isocyanate to yield a substituted isatin with the ketone functionality protected as a thioacetal (eq 4)7 Ring closure also occurred when the 2,5-dihydro-2,2-dimethyl-5,5-bis(propylthio)-1,3,4-oxadiazole carbene precursor was added to 1-naphthyl isocyanate in refluxing acetonitrile (eq 5)7 Formation of thioacetal protected isatin products are unique to the bis(propylthio)carbene as other nucleophilic carbenes added to aryl isocyanates afforded only modest yields of hydantoin products. ... 

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