Condensations of Isatin with Acetone by the Knoevenagel Method¹

Abstract

Condensations of Isatin with Acetone by the Knoevenagel Method1By F. Braude with H. G. LindwallIn 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 /3-carbonyl of 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 New York, N. Y.

Studies on the stereochemical assignment of 3-acylidene 2-oxindoles

“…4 3-Acylidene 2-oxindoles are easily prepared by a two-step aldol condensation sequence following the method of Braude and Lindwall. 8 Condensation of isatin with a small series of acetophenones provided oxindoles 5-8 and 12-16 in good overall yield and as single isomers (as judged by 1 H NMR spectroscopy). This method was readily extended to N-Me isatins 9 and delivered the heterocyclic compounds 9-11 and 17-18, with similarly high levels of stereocontrol.…”

A versatile synthetic methodology for the synthesis of tryptophols

“…Our investigation began with the preparation of 2a by the reaction of isatin (1a) in acetone in the presence of a catalytic quantity of diethylamine. 34 A solution of freshly prepared borane (1 M) in THF 35 (5 equiv.) was then added to a THF solution of 2a under a nitrogen atmosphere and externally cooled with an ice water bath (Equation 1).…”

“…IR (cm 21 ):3504, 3331, 3185, 2987, 1731, 1703, 1620, 1477, 1399, 1334, 1307, 1216, 1187, 1018, 775, 756. Mass, m/z (%): 235 (M þz , 4), 207(6), 191 (4), 162 (100), 148 (95), 147 (9), 146(34), 120(23), 119 (14), 92(20), 65 (14).1 H NMR (300 MHz, CDCl 3 , DMSO-d 6 ): d 1.23 [3H, d, H-11, J¼6.9 Hz], 3.17 [1H, d, H-8, J¼17.1 Hz], 3.49 [1H, d, H-8 0 , J¼17.1 Hz], 4.08 [1H, m, H-10], 4.83 [1H, d, C10 -OH, J¼5.1 Hz], 5.96 [1H, s, C3 -OH], 6.87 [1H, d, H-7, J¼ 7.7 Hz], 6.94 [1H, t, H-5, J¼7.5 Hz], 7.18 [1H, t, H-6, J¼7.6 Hz], 7.26 [1H, d, H-4, J¼7.3 Hz], 9.97 [1H, sl, NH]. 13 C NMR (75.5 MHz, CDCl 3 , DMSO-d 6 ): d 18.2 [p, C-11], 43.8 [s, C-8], 71.8 [t, C-10], 72.4 [q, C-3], 109.0 [t, C-7], 120.8 [t, C-5], 122.6 [t, C-6], 128.2 [t, C-4], 129.9 [q, C-3a], 141.2 [q, C-7a], 177.7 [q, C-2], 209.7 [q, C-9].…”

Synthesis and Structure–Activity Relationship Studies of Small Molecule Disruptors of EWS-FLI1 Interactions in Ewing’s Sarcoma

“…This was accomplished by treating 2 with concentrated sulfuric acid as shown in Scheme 2 (58% yield). 23 , 24 Of interest was the report that this methodology affords the Z isomer. 24 We confirmed and assigned the Z configuration of 10 by X-ray crystallography (Figure 2 ).…”