3-Ethyl-2-methyl-5-methylene-6,7-dihydroindol-4(5H)-one

The title compound, C12H15NO, a degradation product of molindone hydrochloride, was prepared by the reaction of molindone with methyl iodide and subsequent reaction of the resulting quaternary ammonium salt with 2N aqueous sodium hydroxide. The newly formed double bond is exocyclic in nature and the carbonyl group is conjugated with the π-electrons of the pyrrole ring. The six-membered ring is in the half-chair conformation. The H atom attached to the N atom is involved in an intermolecular hydrogen bond with the O atom of a screw-related molecule, thus forming a continuous chain.

The title compound, C 12 H 15 NO, a degradation product of molindone hydrochloride, was prepared by the reaction of molindone with methyl iodide and subsequent reaction of the resulting quaternary ammonium salt with 2N aqueous sodium hydroxide. The newly formed double bond is exocyclic in nature and the carbonyl group is conjugated with theelectrons of the pyrrole ring. The six-membered ring is in the half-chair conformation. The H atom attached to the N atom is involved in an intermolecular hydrogen bond with the O atom of a screw-related molecule, thus forming a continuous chain.
Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: OM2194).

Comment
The Mannich condensation reaction is frequently used in the synthesis of pharmaceutical compounds. One such example is the synthesis of molindone, an antipsychotic agent. During stability studies and development of an assay for molindone hydrochloride, a degradation product was identified as 3-ethyl-2-methyl-5-methylene-6,7-dihydro-5H-indol-4-one (Dudzinski et al., 1973). Molindone has UV absorption peaks at 255 nm and 299 nm; these UV wavelengths can be used quantitatively for quantifying the drug substance. However, preliminary studies indicated that chemical degradation (as evidenced by color and precipitate formation) was not accompanied by a decrease in UV absorption, suggesting that the degradation product had a similar chromophore to molindone. The title compound was prepared by the reaction of molindone free base with methyl iodide and subsequent reaction of the resulting quaternary ammonium salt with 2 N aqueous sodium hydroxide. The structure of the resulting compound, 3-ethyl-2-methyl-5-methylene-6,7-dihydro-5H-indol-4-one, was initially characterized by NMR spectroscopy and shown to be identical to the degradation product of molindone hydrochloride. To confirm the exocyclic nature of newly formed double bond and to identify chromophoric group in the molecule responsible for its UV absorption profile, its crystal structure was determined by X-ray analysis.
The molecular structure and the atom-numbering scheme are shown in Fig. 1 indicates that the newly formed double bond is exocyclic in nature. Further, it is evident from the bond lengths of C5-C6 and C6-C7 [1.5058 (15) and 1.4327 (15) Å, respectively] that the carbonyl group is conjugated with the π-electrons of pyrrole ring and not π-electrons of the exocyclic double. This explains why molindone and its degradation product, the title compound exhibit similar UV absorption. The mode of packing along the b direction is illustrated in Fig. 2. The H atom attached to atom N1 is involved in an intermolecular hydrogen bond [2.7749 (12) Å] with atom O1 of an inversion-related molecule, thus forming a continuous chain.

Experimental
A mixture of molindone (0.276 g, 1 mmol) and excess methyl iodide (2 ml) was stirred at ambient temperature. After completion of the reaction, unreacted methyl iodide was evaporated, and the crude quaternary ammonium salt was then mixed with 2 N aqueous sodium hydroxide (10 ml) and stirred for 1 h at ambient temperature. The resulting precipitate was collected by filtration and washed with water. Recrystallization from ethanol afforded the title compound as colorless crystalline product, which was suitable for X-ray analysis.  3-Ethyl-2-methyl-5-methylene-6,7-dihydroindol-4(5H)-one 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 > 2σ(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq O1 0.68573 (