3-Hydroxy-3-[(2-methylpropanoyl)methyl]indolin-2-one

The title compound, C13H15NO3, was synthesized by the Aldol reaction of isatin and 3-methylbutan-2-one refluxing in methanol catalyzed by dimethylamine. The packing of the molecules in the crystal structure features intermolecular N—H⋯O and O—H⋯O hydrogen bonds.

The title compound, C 13 H 15 NO 3 , was synthesized by the Aldol reaction of isatin and 3-methylbutan-2-one refluxing in methanol catalyzed by dimethylamine. The packing of the molecules in the crystal structure features intermolecular N-HÁ Á ÁO and O-HÁ Á ÁO hydrogen bonds.

Comment
Isatin, an endogenous compound in mammalian tissues and body fluids (Glover, et al., 1988), has caught great attention of many researchers as a versatile lead molecule for designing of potential drugs (Pandeya, et al., 2000;Sun, et al., 1998;Teitz, et al., 1994). In our previous study, 3-hydroxy-3-(2-oxo-propyl)-1,3-dihydro-indol-2-one, yielded from the Aldol reaction of isatin with acetone, was found to be a new chemical activator against tobacco mosaic virus (TMV) infection (Li, 2008). In tobacco plant, external application of 3-hydroxy-3-(2-oxo-propyl)-1,3-dihydro-indol-2-one results in restriction of TMV multiplication and spread, accumulation of salicylic acid level expression of PR-1 gene, and activation and increase of phenylalanine ammonia-lyase (PAL) activity. With these findings, some analogs need to be synthesized for structure activity relationship research to find more potent molecules.
One of these analogs, 3-hydroxy-3-(3-methyl-2-oxo-butyl)-1,3-dihydro-indol-2-one (compound I), was synthesized by the Aldol reaction of isatin with 3-methyl-butan-2-one. In order to provide the structural information of compound I, we studied its crystal structure. The title compound was synthesized in a one step Aldol reaction of isatin (0.01 mmol) with 3methyl-butan-2-one, according to the reported method (Garden et al., 2002). The molar ratio of isatin: 3-methyl-butan-2-one = 1:3 refluxed in methanol gave compound I in 72% yield, and colorless crystals of compound I were obtained in ethanol by recrystallization. The values of the geometric parameters of compound I are within normal ranges and experimental errors.
The molecular structure of compound I is illustrated in Fig. 1. In the molecule, the 2-oxo-indole ring is planar, and the angle between hydroxyl group and 3-methyl-2-oxo-butyl group is 105.10 (12)°. The intermolecular interactions are primarily responsible for the formation of the crystal structure of compound I. Each molecule is fixed by four hydrogen bond of other three molecules. N1-H1 acts as a hydrogen bond donor, and O1 is a hydrogen bond accepter. To O2-H2, it acts as both a hydrogen bond donor and a hydrogen bond accepter, which connects with two molecules by O-H···O and O···H-N with the angle of 119.21 (9)°. There is no anticipated intramolecular hydrogen bond between O2-H2 and O3, and O3 is not involved in any hydrogen bond (Fig. 2).
supplementary materials sup-2 Refinement All H atoms were positioned geometrically, with C-H = 0.93-0.98 Å, and refined using riding model, with U iso (H) = 1.2U eq (carrier). Fig. 1. An ORTEP-3 drawing of compound I, with the atom-numbering scheme and 30% probability displacement ellipsoids.  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.