3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxy­indolin-2-one monohydrate

Narsimha Reddy Penthala; Thirupathi Reddy Yerram Reddy; Sean Parkin; Peter A Crooks

doi:10.1107/S1600536809004875

. 2009 Feb 21;65(Pt 3):o552. doi: 10.1107/S1600536809004875

3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxyindolin-2-one monohydrate

Narsimha Reddy Penthala ^a, Thirupathi Reddy Yerram Reddy ^a, Sean Parkin ^b, Peter A Crooks ^a,^*

PMCID: PMC2968573 PMID: 21582211

Abstract

Two chiral centres exist in the title compound, C₁₂H₁₂N₄O₃·H₂O. Molecules are linked into chains by series of intermolecular N—H⋯O and O—H⋯N hydrogen bonds, which causes supramolecular aggregation. Two chiral centres are formed in the title compound. The indole and creatinine moieties make a dihedral angle of 56.75 (4)°. The crystal structure of the compound indicates the presence of equimolar enantiomers (RR and SS) in the crystal structure.

Related literature

For 2-indol-3-yl-methylenequinuclidin-3-ols NADPH oxidase activity, see: Sekhar et al. (2003 ▶). For novel substituted (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents, see: Sonar et al. (2007 ▶). For the crystal and molecular structure of isatin, see: Frolova et al. (1988 ▶). For the structure of 1,1′-diacetyl-3-hydroxy-2,2′,3,3′-tetrahydro-3,3′-bi(1H-indole)-2,2′-dione, see: Usman et al. (2002 ▶). The aldol condensation enolate mechanism by six-membered transition states has been described by Zimmerman & Traxler (1957 ▶).

Experimental

Crystal data

C₁₂H₁₂N₄O₃·H₂O
M _r = 278.27
Monoclinic,
a = 8.3514 (1) Å
b = 10.7166 (2) Å
c = 13.9679 (2) Å
β = 104.755 (1)°
V = 1208.88 (3) Å³
Z = 4
Cu Kα radiation
μ = 0.99 mm⁻¹
T = 90 K
0.20 × 0.15 × 0.06 mm

Data collection

Bruker X8 Proteum diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.780, T _max = 0.943
17255 measured reflections
2181 independent reflections
2121 reflections with I > 2σ(I)
R _int = 0.035

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.088
S = 1.04
2181 reflections
191 parameters
3 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.26 e Å⁻³
Δρ_min = −0.27 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: APEX2 and SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97 and local procedures.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809004875/hg2475sup1.cif

e-65-0o552-sup1.cif^{(18.9KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809004875/hg2475Isup2.hkl

e-65-0o552-Isup2.hkl^{(107.3KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1Wⁱ	0.88	1.96	2.8128 (15)	163
O8—H8⋯N12ⁱⁱ	0.84	1.97	2.7984 (14)	170
N11—H11A⋯O13ⁱⁱⁱ	0.88	2.17	3.0371 (15)	171
N11—H11B⋯O1^iv	0.88	2.13	2.8678 (15)	141
O1W—H1W⋯O8	0.847 (18)	2.049 (18)	2.8812 (14)	167.4 (19)
O1W—H2W⋯O13^v	0.861 (18)	2.233 (18)	3.0702 (14)	164.1 (19)

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) .

Acknowledgments

This investigation was supported by the NIH/National Cancer Institute [grant No. PO1CA104457 (to PAC)] and by the NSF [MRI grant No. CHE 0319176 (to SP)].

supplementary crystallographic information

Comment

In our endeavor to design and synthesize novel radiosensitizers such as (Z)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-one and (Z)-(±)-2-(N-benzylindol-3-ylmethylene)quinuclidin-3-ol derivatives (Sekhar et al., 2003; Sonar et al., 2007), we have undertaken the design, synthesis and structural analysis of a series of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3- hydroxyindolin-2-one analogs with different substituents on the indole moiety. The primary goal for X-ray analysis of the title compound is to confirm the stereochemistry of the molecule and to obtain detailed information on the structural conformation that may be useful in structure–activity relationship (SAR) analysis. The title compound was prepared by the aldol condensation of indol-2,3-dione (isatin) with 2-amino-1-methyl-1H-imidazol-4(5H)-one (creatinine) in the presence of sodium acetate in acetic acid under microwave irradiation. The compound was crystallized from 2% aqueous glycol. This aldol condensation reaction proceeds by the formation of the E-enolate, as per the Zimmerman–Traxler model (Zimmerman & Traxler, 1957), which favors anti products, and leads to the formation of equimolar RR and SS enantiomers. The molecular structure and the atom-numbering scheme are shown in Fig. 1. The isatin ring is planar (r.m.s. deviation = 0.0112 (10) Å) with bond distances and angles comparable with those previously reported for other isatin derivatives (Frolova et al., 1988; Usman et al., 2002). Atoms C₈ and C₉ are the two chiral centers of the title compound. The X-ray studies revealed that the obtained compound is racemic (having equimolar RR and SS enantiomers). The indole and creatinine moieties make a dihedral angle of 56.75 (4)°. Intermolecular N—H···O and O—H···N hydrogen bonds stabilize the crystal structure and form a supramolecular architecture.

Experimental

A mixture of isatin (1 mmol), creatinine (1.1 mmol) and sodium acetate (1.2 mmol) in acetic acid (1 ml) were irradiated in a domestic microwave oven for 40 sec with intermittent cooling every 10 sec. The reaction mixture was allowed to cool to room temperature, 10 ml of saturated sodium bicarbonate solution was added, and the mixture was stirred for 10 minutes. The precipitate thus obtained was collected by filtration, washed with cold water and dried, to afford the crude product. Crystallization from 2% aqueous glycol gave a light yellow crystalline product of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H- imidazol-5-yl)-3-hydroxyindolin-2-one monohydrate that was suitable for X-ray analysis. ¹H NMR (DMSO-d₆): δ 3.13 (s, 3H), 4.06 (s, 1H), 6.37 (s, 1H, OH), 6.73–6.75 (d, J = 7.5 Hz, 1H), 6.84–6.89 (t, J = 7.5 Hz, 1H), 7.04–7.06 (d, J = 7.5 Hz, 1H), 7.15–7.21 (t, J = 7.8 Hz, 1H), 7.51 (bs, 2H, NH₂), 10.23 (s, 1H, NH) p.p.m.; ¹³C NMR (DMSO-d₆): δ 32.59, 69.44, 76.28, 109.49, 121.1, 123.95, 127.98,129.34, 142.66, 171.76, 175.71, 182.26 p.p.m.