Jan., 1033
CONDENSATIONS O F ISaTIN WITH
[CONTRIBUTION FROM THE
ACETONE
NICHOLS LABORATORY OF NEWYORK
325 UNIVERSITY ]
Condensations of Isatin with Acetone by the Knoevenagel Method' BY F. BFUUDEWITH H. G. LINDWALL In a recent article it was shown2 that isatin and acetophenone will condense, in the presence of certain bases, to yield 3-hydroxy-3-phenacyloxindole. This reaction suggested the use of other methyl ketones like acetone. Isatin and acetone condense when present with small amounts of diethylamine to yield 3-acetonyl-3-hydroxyoxindole (I). The condensation involves the @-carbonylof the isatin molecule rather than the nitrogen, for N-methylisatin will also react with acetone to yield a product with chemical properties similar to those of (I). Compound (I) decomposes upon the application of heat, or upon being warmed with aqueous alcoholic potassium hydroxide solution, into isatin and acetone. This decomposition is evidently another example of a reversed aldol reaction. A longer period of heating with the potassium hydroxide solution results in the formation of 2-methylcinchoninic acid, not, apparently, through rearrangement of the 3-acetonyl-3-hydroxyoxindole, but rather through its decomposition into isatin and acetone followed by a Pfitzinger3 type of condensation of the acetone with the o-aminobenzoylformic acid, formed by the hydrolysis of the isatin. Treatment of I with certain acidic reagents effects the loss of one mole of water with the resulting formation of 3-acetonylideneoxindole (11), a highly colored red-orange compound. OH I
@-JCH~-CO-CH.
H
I
-
C=CH-CO-CHa
O J OH
I1
It might be expected that 11, upon ring opening through hydrolysis, would form 2-methylcinchoninic acid as a result of subsequent reaction of the ketone carbonyl with the nuclear NHI group. However, I1 could not be rearranged to the corresponding quinoline derivative by treatment with potassium hydroxide. This is in agreement with the failure of 3-phenacylideneoxindole and 3-phenacyloxindole to rearrange to cinchophen and 3,4dihydro-2-phenylcinchoninicacid, as noted in our previous paper. Therefore 3-acetonylideneoxindole cannot, apparently, be considered an intermediate in the Pfitzinger synthesis of 2-methylcinchoninic acid from isatin Abstract from a thesis presented by F. Braude in partial fulfilment of the requirements for the degree of Doctor of Philosophy at New Pork University. Lindwall and Maclennan, THISJOURNAL, 54, 4739 (1932). Pfitzinger, J . prakt. Chem.. 33, 100 (1886); 38, 583 (1888); 56, 283 (1897).
F. BKAUDE WITH H. G. LINDWALL
326
Vol. 5
