3-(2-Amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydr-oxy-1-phenyl-indolin-2-one ethanol solvate.

In the title compound, C(18)H(16)N(4)O(3)·C(2)H(5)OH, mol-ecules are linked into chains by a series of inter-molecular N-H⋯O, N-H⋯N and O-H⋯O hydrogen bonds which stabilize the crystal structure. The indole and creatinine units make a dihedral angle of 56.45 (4)°. The title compound has two chiral centres. The crystal structure indicates the compound is racemic (RR and SS).

Related literature

For the biological activity of isatin and its derivatives, see: Pandeya et al. (2005 ▶). The endogenous oxindoles 5-hydroxy­oxindole and isatin are anti­proliferative and proapoptotic, see: Cane et al. (2000 ▶). For in vitro cytotoxicity evaluation of some substituted isatin derivatives, see: Vine et al. (2007 ▶). 2-Indol-3-yl-methyl­enequinuclidin-3-ols and NADPH oxidase activity has been reported by Sekhar et al. (2003 ▶), and novel substituted (Z)-2-(N-benzyl­indol-3-ylmethyl­ene)quinuclidin-3-one and (Z)-(±)-2-(N-benzyl­indol-3-yl methyl­ene)quinuclidin-3-ol derivatives as potent thermal sensitizing agents by Sonar et al. (2007 ▶). For the crystal and mol­ecular structure of isatin, see: Frolova et al. (1988 ▶). For the structure of 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxy­indolin-2-one monohydrate, see: Penthala et al. (2009 ▶) and 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 via a six-membered transition state has been described by Zimmerman & Traxler (1957 ▶).

Experimental

Crystal data

C18H16N4O3·C2H6O

M = 382.42

Triclinic,

a = 7.4912 (1) Å

b = 11.0018 (2) Å

c = 12.0835 (2) Å

α = 78.152 (1)°

β = 74.413 (1)°

γ = 74.090 (1)°

V = 913.15 (3) Å3

Z = 2

Cu Kα radiation

μ = 0.82 mm−1

T = 90 K

0.11 × 0.11 × 0.08 mm

Data collection

Bruker X8 Proteum diffractometer

Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006 ▶) T min = 0.828, T max = 0.938

13576 measured reflections

3294 independent reflections

3126 reflections with I > 2σ(I)

R int = 0.035

Refinement

R[F 2 > 2σ(F 2)] = 0.037

wR(F 2) = 0.098

S = 1.07

3294 reflections

258 parameters

H-atom parameters constrained

Δρmax = 0.37 e Å−3

Δρmin = −0.41 e Å−3

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: 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.

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809033881/hg2557sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809033881/hg2557Isup2.hkl

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

C18H16N4O3·C2H6O	Z = 2
Mr = 382.42	F(000) = 404
Triclinic, P1	Dx = 1.391 Mg m−3
Hall symbol: -P 1	Cu Kα radiation, λ = 1.54178 Å
a = 7.4912 (1) Å	Cell parameters from 9955 reflections
b = 11.0018 (2) Å	θ = 3.8–68.3°
c = 12.0835 (2) Å	µ = 0.82 mm−1
α = 78.152 (1)°	T = 90 K
β = 74.413 (1)°	Block, colourless
γ = 74.090 (1)°	0.11 × 0.11 × 0.08 mm
V = 913.15 (3) Å3

Bruker X8 Proteum diffractometer	3294 independent reflections
Radiation source: fine-focus rotating anode	3126 reflections with I > 2σ(I)
graded multilayer optics	Rint = 0.035
Detector resolution: 5.6 pixels mm-1	θmax = 68.3°, θmin = 3.8°
φ and ω scans	h = −9→9
Absorption correction: multi-scan (SADABS in APEX2; Bruker, 2006)	k = −13→10
Tmin = 0.828, Tmax = 0.938	l = −14→14
13576 measured reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.037	H-atom parameters constrained
wR(F2) = 0.098	w = 1/[σ^2^(Fo^2^) + (0.0501P)^2^ + 0.3708P] whereP = (Fo^2^ + 2Fc^2^)/3
S = 1.07	(Δ/σ)max < 0.001
3294 reflections	Δρmax = 0.37 e Å−3
258 parameters	Δρmin = −0.41 e Å−3
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.0068 (7)

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

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 R-factors(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.

	x	y	z	Uiso*/Ueq
O1	0.37921 (12)	0.08545 (8)	0.23487 (7)	0.0188 (2)
N1	0.16513 (14)	0.24923 (9)	0.32617 (8)	0.0159 (2)
C1	0.29249 (17)	0.19721 (11)	0.23418 (10)	0.0161 (3)
O2	0.50070 (12)	0.30752 (8)	0.07786 (7)	0.0202 (2)
H2	0.5529	0.3158	0.1284	0.030*
N2	0.03753 (14)	0.13607 (10)	0.04645 (8)	0.0174 (2)
C2	0.30826 (17)	0.30455 (11)	0.12863 (10)	0.0173 (3)
O3	−0.10708 (12)	0.31235 (9)	0.14096 (8)	0.0232 (2)
N3	0.26263 (14)	0.00056 (10)	−0.07643 (9)	0.0185 (2)
H3A	0.3780	−0.0201	−0.1202	0.022*
H3B	0.1798	−0.0454	−0.0697	0.022*
C3	0.18841 (17)	0.42116 (12)	0.18239 (10)	0.0178 (3)
N4	0.33379 (14)	0.17486 (10)	−0.02748 (8)	0.0175 (2)
C4	0.15762 (18)	0.54854 (12)	0.13580 (11)	0.0210 (3)
H4	0.2148	0.5746	0.0573	0.025*
C5	0.04026 (19)	0.63828 (12)	0.20688 (11)	0.0222 (3)
H5	0.0180	0.7266	0.1768	0.027*
C6	−0.04402 (18)	0.59920 (12)	0.32105 (11)	0.0212 (3)
H6	−0.1239	0.6615	0.3680	0.025*
C7	−0.01412 (17)	0.47040 (12)	0.36854 (10)	0.0183 (3)
H7	−0.0728	0.4437	0.4465	0.022*
C8	0.10411 (17)	0.38371 (11)	0.29745 (10)	0.0168 (3)
C9	0.12524 (17)	0.18231 (11)	0.44190 (10)	0.0161 (3)
C10	0.27258 (18)	0.12805 (11)	0.49893 (11)	0.0192 (3)
H10	0.3994	0.1339	0.4615	0.023*
C11	0.2316 (2)	0.06493 (12)	0.61182 (11)	0.0233 (3)
H11	0.3312	0.0268	0.6516	0.028*
C12	0.0459 (2)	0.05757 (12)	0.66629 (11)	0.0247 (3)
H12	0.0185	0.0150	0.7435	0.030*
C13	−0.10000 (19)	0.11217 (12)	0.60827 (11)	0.0233 (3)
H13	−0.2271	0.1071	0.6460	0.028*
C14	−0.06071 (18)	0.17416 (12)	0.49517 (11)	0.0195 (3)
H14	−0.1599	0.2105	0.4548	0.023*
C15	0.22403 (17)	0.28338 (11)	0.03230 (10)	0.0173 (3)
H15	0.2094	0.3626	−0.0256	0.021*
C16	0.03012 (17)	0.24701 (12)	0.08034 (10)	0.0175 (3)
C17	0.21402 (17)	0.09987 (11)	−0.02122 (10)	0.0162 (3)
C18	0.49912 (18)	0.18208 (12)	−0.12386 (10)	0.0207 (3)
H18A	0.5813	0.0964	−0.1304	0.031*
H18B	0.5707	0.2375	−0.1096	0.031*
H18C	0.4562	0.2172	−0.1962	0.031*
O1S	0.57472 (13)	0.29564 (10)	0.30873 (9)	0.0304 (3)
H1S	0.6853	0.2952	0.2685	0.046*
C1S	0.5142 (2)	0.39650 (15)	0.37674 (14)	0.0336 (3)
H1S1	0.5991	0.3811	0.4309	0.040*
H1S2	0.3837	0.3965	0.4237	0.040*
C2S	0.5151 (2)	0.52356 (16)	0.30585 (16)	0.0413 (4)
H2S1	0.6444	0.5248	0.2601	0.062*
H2S2	0.4729	0.5894	0.3570	0.062*
H2S3	0.4285	0.5405	0.2535	0.062*

	U11	U22	U33	U12	U13	U23
O1	0.0220 (4)	0.0146 (4)	0.0180 (4)	−0.0041 (3)	−0.0011 (3)	−0.0034 (3)
N1	0.0206 (5)	0.0124 (5)	0.0138 (5)	−0.0041 (4)	−0.0026 (4)	−0.0012 (4)
C1	0.0187 (6)	0.0160 (6)	0.0152 (6)	−0.0067 (5)	−0.0032 (5)	−0.0030 (4)
O2	0.0216 (5)	0.0249 (5)	0.0171 (4)	−0.0115 (4)	−0.0028 (3)	−0.0033 (3)
N2	0.0185 (5)	0.0188 (5)	0.0149 (5)	−0.0057 (4)	−0.0020 (4)	−0.0028 (4)
C2	0.0216 (6)	0.0160 (6)	0.0145 (6)	−0.0076 (5)	−0.0020 (5)	−0.0016 (5)
O3	0.0225 (5)	0.0246 (5)	0.0212 (5)	−0.0051 (4)	0.0000 (4)	−0.0080 (4)
N3	0.0177 (5)	0.0193 (5)	0.0199 (5)	−0.0067 (4)	−0.0011 (4)	−0.0068 (4)
C3	0.0231 (6)	0.0168 (6)	0.0160 (6)	−0.0068 (5)	−0.0061 (5)	−0.0026 (5)
N4	0.0191 (5)	0.0193 (5)	0.0151 (5)	−0.0075 (4)	0.0000 (4)	−0.0056 (4)
C4	0.0289 (7)	0.0183 (6)	0.0182 (6)	−0.0084 (5)	−0.0086 (5)	0.0002 (5)
C5	0.0306 (7)	0.0136 (6)	0.0253 (7)	−0.0054 (5)	−0.0126 (5)	−0.0003 (5)
C6	0.0253 (6)	0.0173 (6)	0.0234 (6)	−0.0017 (5)	−0.0096 (5)	−0.0068 (5)
C7	0.0220 (6)	0.0179 (6)	0.0165 (6)	−0.0048 (5)	−0.0061 (5)	−0.0033 (5)
C8	0.0215 (6)	0.0140 (6)	0.0173 (6)	−0.0058 (5)	−0.0071 (5)	−0.0017 (4)
C9	0.0236 (6)	0.0110 (5)	0.0131 (6)	−0.0043 (4)	−0.0017 (5)	−0.0028 (4)
C10	0.0230 (6)	0.0150 (6)	0.0188 (6)	−0.0033 (5)	−0.0032 (5)	−0.0042 (5)
C11	0.0337 (7)	0.0156 (6)	0.0194 (6)	−0.0009 (5)	−0.0089 (5)	−0.0024 (5)
C12	0.0409 (8)	0.0152 (6)	0.0154 (6)	−0.0078 (5)	−0.0014 (5)	−0.0011 (5)
C13	0.0280 (7)	0.0191 (6)	0.0206 (6)	−0.0099 (5)	0.0044 (5)	−0.0053 (5)
C14	0.0221 (6)	0.0162 (6)	0.0203 (6)	−0.0047 (5)	−0.0032 (5)	−0.0043 (5)
C15	0.0216 (6)	0.0165 (6)	0.0140 (6)	−0.0060 (5)	−0.0023 (5)	−0.0029 (4)
C16	0.0201 (6)	0.0190 (6)	0.0130 (5)	−0.0053 (5)	−0.0032 (5)	−0.0014 (4)
C17	0.0186 (6)	0.0179 (6)	0.0126 (5)	−0.0056 (5)	−0.0039 (4)	−0.0005 (4)
C18	0.0218 (6)	0.0246 (6)	0.0164 (6)	−0.0099 (5)	0.0011 (5)	−0.0054 (5)
O1S	0.0213 (5)	0.0303 (5)	0.0384 (6)	−0.0077 (4)	−0.0007 (4)	−0.0078 (4)
C1S	0.0254 (7)	0.0339 (8)	0.0426 (9)	−0.0049 (6)	−0.0067 (6)	−0.0115 (7)
C2S	0.0424 (9)	0.0358 (9)	0.0530 (10)	−0.0102 (7)	−0.0231 (8)	−0.0044 (7)

O1—C1	1.2226 (15)	C7—C8	1.3770 (17)
N1—C1	1.3658 (15)	C7—H7	0.9500
N1—C8	1.4220 (15)	C9—C14	1.3876 (18)
N1—C9	1.4353 (15)	C9—C10	1.3886 (18)
C1—C2	1.5531 (16)	C10—C11	1.3929 (18)
O2—C2	1.4136 (15)	C10—H10	0.9500
O2—H2	0.8400	C11—C12	1.386 (2)
N2—C16	1.3477 (16)	C11—H11	0.9500
N2—C17	1.3562 (15)	C12—C13	1.388 (2)
C2—C3	1.5071 (17)	C12—H12	0.9500
C2—C15	1.5472 (16)	C13—C14	1.3895 (18)
O3—C16	1.2314 (15)	C13—H13	0.9500
N3—C17	1.3123 (16)	C14—H14	0.9500
N3—H3A	0.8800	C15—C16	1.5419 (17)
N3—H3B	0.8800	C15—H15	1.0000
C3—C4	1.3794 (17)	C18—H18A	0.9800
C3—C8	1.3918 (17)	C18—H18B	0.9800
N4—C17	1.3546 (16)	C18—H18C	0.9800
N4—C15	1.4560 (15)	O1S—C1S	1.4181 (18)
N4—C18	1.4621 (15)	O1S—H1S	0.8400
C4—C5	1.3972 (18)	C1S—C2S	1.483 (2)
C4—H4	0.9500	C1S—H1S1	0.9900
C5—C6	1.3870 (19)	C1S—H1S2	0.9900
C5—H5	0.9500	C2S—H2S1	0.9800
C6—C7	1.3960 (18)	C2S—H2S2	0.9800
C6—H6	0.9500	C2S—H2S3	0.9800
C1—N1—C8	110.74 (10)	C12—C11—C10	120.23 (12)
C1—N1—C9	124.57 (10)	C12—C11—H11	119.9
C8—N1—C9	123.74 (10)	C10—C11—H11	119.9
O1—C1—N1	125.87 (11)	C11—C12—C13	120.17 (12)
O1—C1—C2	125.91 (10)	C11—C12—H12	119.9
N1—C1—C2	108.21 (10)	C13—C12—H12	119.9
C2—O2—H2	109.5	C12—C13—C14	120.17 (12)
C16—N2—C17	106.75 (10)	C12—C13—H13	119.9
O2—C2—C3	115.27 (10)	C14—C13—H13	119.9
O2—C2—C15	106.63 (9)	C9—C14—C13	119.20 (12)
C3—C2—C15	110.59 (10)	C9—C14—H14	120.4
O2—C2—C1	111.04 (9)	C13—C14—H14	120.4
C3—C2—C1	101.86 (9)	N4—C15—C16	100.87 (9)
C15—C2—C1	111.52 (9)	N4—C15—C2	114.64 (10)
C17—N3—H3A	120.0	C16—C15—C2	112.68 (9)
C17—N3—H3B	120.0	N4—C15—H15	109.4
H3A—N3—H3B	120.0	C16—C15—H15	109.4
C4—C3—C8	120.49 (11)	C2—C15—H15	109.4
C4—C3—C2	130.40 (11)	O3—C16—N2	127.04 (11)
C8—C3—C2	109.10 (10)	O3—C16—C15	123.08 (11)
C17—N4—C15	107.56 (10)	N2—C16—C15	109.88 (10)
C17—N4—C18	122.36 (10)	N3—C17—N4	123.26 (11)
C15—N4—C18	122.80 (10)	N3—C17—N2	122.16 (11)
C3—C4—C5	118.36 (11)	N4—C17—N2	114.58 (10)
C3—C4—H4	120.8	N4—C18—H18A	109.5
C5—C4—H4	120.8	N4—C18—H18B	109.5
C6—C5—C4	120.40 (11)	H18A—C18—H18B	109.5
C6—C5—H5	119.8	N4—C18—H18C	109.5
C4—C5—H5	119.8	H18A—C18—H18C	109.5
C5—C6—C7	121.51 (12)	H18B—C18—H18C	109.5
C5—C6—H6	119.2	C1S—O1S—H1S	109.5
C7—C6—H6	119.2	O1S—C1S—C2S	112.92 (14)
C8—C7—C6	117.14 (11)	O1S—C1S—H1S1	109.0
C8—C7—H7	121.4	C2S—C1S—H1S1	109.0
C6—C7—H7	121.4	O1S—C1S—H1S2	109.0
C7—C8—C3	122.10 (11)	C2S—C1S—H1S2	109.0
C7—C8—N1	128.13 (11)	H1S1—C1S—H1S2	107.8
C3—C8—N1	109.73 (10)	C1S—C2S—H2S1	109.5
C14—C9—C10	121.20 (11)	C1S—C2S—H2S2	109.5
C14—C9—N1	119.23 (11)	H2S1—C2S—H2S2	109.5
C10—C9—N1	119.56 (11)	C1S—C2S—H2S3	109.5
C9—C10—C11	119.02 (12)	H2S1—C2S—H2S3	109.5
C9—C10—H10	120.5	H2S2—C2S—H2S3	109.5
C11—C10—H10	120.5
C8—N1—C1—O1	174.88 (11)	C1—N1—C9—C10	57.36 (16)
C9—N1—C1—O1	5.70 (19)	C8—N1—C9—C10	−110.45 (13)
C8—N1—C1—C2	−5.06 (13)	C14—C9—C10—C11	−0.27 (18)
C9—N1—C1—C2	−174.24 (10)	N1—C9—C10—C11	179.09 (10)
O1—C1—C2—O2	−50.77 (15)	C9—C10—C11—C12	−0.49 (18)
N1—C1—C2—O2	129.18 (10)	C10—C11—C12—C13	0.53 (19)
O1—C1—C2—C3	−174.02 (12)	C11—C12—C13—C14	0.19 (19)
N1—C1—C2—C3	5.93 (12)	C10—C9—C14—C13	0.99 (18)
O1—C1—C2—C15	68.01 (15)	N1—C9—C14—C13	−178.38 (11)
N1—C1—C2—C15	−112.05 (11)	C12—C13—C14—C9	−0.94 (18)
O2—C2—C3—C4	53.97 (17)	C17—N4—C15—C16	4.68 (12)
C15—C2—C3—C4	−67.06 (16)	C18—N4—C15—C16	155.35 (10)
C1—C2—C3—C4	174.30 (13)	C17—N4—C15—C2	126.01 (10)
O2—C2—C3—C8	−125.10 (11)	C18—N4—C15—C2	−83.31 (13)
C15—C2—C3—C8	113.87 (11)	O2—C2—C15—N4	52.11 (12)
C1—C2—C3—C8	−4.77 (12)	C3—C2—C15—N4	178.14 (9)
C8—C3—C4—C5	0.01 (18)	C1—C2—C15—N4	−69.27 (13)
C2—C3—C4—C5	−178.97 (12)	O2—C2—C15—C16	166.73 (9)
C3—C4—C5—C6	−0.60 (19)	C3—C2—C15—C16	−67.24 (13)
C4—C5—C6—C7	0.32 (19)	C1—C2—C15—C16	45.36 (13)
C5—C6—C7—C8	0.56 (18)	C17—N2—C16—O3	178.51 (12)
C6—C7—C8—C3	−1.17 (18)	C17—N2—C16—C15	−1.87 (13)
C6—C7—C8—N1	176.39 (11)	N4—C15—C16—O3	177.90 (11)
C4—C3—C8—C7	0.91 (19)	C2—C15—C16—O3	55.19 (15)
C2—C3—C8—C7	−179.91 (11)	N4—C15—C16—N2	−1.74 (12)
C4—C3—C8—N1	−177.05 (11)	C2—C15—C16—N2	−124.45 (11)
C2—C3—C8—N1	2.13 (14)	C15—N4—C17—N3	172.92 (11)
C1—N1—C8—C7	−175.84 (12)	C18—N4—C17—N3	22.09 (18)
C9—N1—C8—C7	−6.55 (19)	C15—N4—C17—N2	−6.58 (13)
C1—N1—C8—C3	1.96 (14)	C18—N4—C17—N2	−157.41 (11)
C9—N1—C8—C3	171.25 (11)	C16—N2—C17—N3	−174.16 (11)
C1—N1—C9—C14	−123.26 (13)	C16—N2—C17—N4	5.35 (14)
C8—N1—C9—C14	68.92 (15)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O1S	0.84	2.19	2.9579 (14)	152
O2—H2···O3i	0.84	2.58	3.2440 (12)	137
N3—H3A···O1ii	0.88	2.02	2.8898 (13)	169
N3—H3B···N2iii	0.88	2.06	2.9391 (15)	174
O1S—H1S···O3i	0.84	1.89	2.7048 (13)	162

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O1S	0.84	2.19	2.9579 (14)	152
O2—H2⋯O3i	0.84	2.58	3.2440 (12)	137
N3—H3A⋯O1ii	0.88	2.02	2.8898 (13)	169
N3—H3B⋯N2iii	0.88	2.06	2.9391 (15)	174
O1S—H1S⋯O3i	0.84	1.89	2.7048 (13)	162

Symmetry codes: (i) ; (ii) ; (iii) .