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The title compound, C12H12N2O5, is a potential antiamnesic agent. The pyrrolidinone ring has an envelope conformation, and the central moiety is almost coplanar with the planes of the phenyl and pyrrolidinone rings. In the crystal structure, weak intermolecular C-H...O interactions link the mol­ecules into a complex network that can be described by R22(X) rings (X = 16, 20 and 26) and a C(12) chain.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S0108270103014823/sk1656sup1.cif
Contains datablocks I, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S0108270103014823/sk1656Isup2.hkl
Contains datablock I

CCDC reference: 221080

Comment top

The conformations of molecules with antiamnesic activity have attracted considerable interest (Amato, Bandoli, Grassi et al., 1991). This paper is intended to further develop our studies on the conformational properties of cognition activators. Cognition activators are drugs currently employed for the symptomatic treatment of pathological brain aging phenomena, which are usually referred to as senile cognitive decline or age-associated memory impairment (Gamzu et al., 1989; Bandoli et al., 1992). In the light of the growing incidence of such illnesses among the older population, several families of compounds are being tested in laboratory and clinical trials. The nootropics (mind-targeted) family is the forerunner in the field (Giurgea, 1982), and its key feature is the presence of the pyrrolidin-2-one ring. This moiety is a requisite for several active compounds currently used in therapy (piracetam, oxyracetam and pramiracetam). The ring-extended N-analogues of 2-pyrrilidinone, namely 3-aryl-2-piperazinone compounds, have been found to possess the characteristic nootropic pharmacological profile (Amato, Bandoli, Grassi et al., 1991). The present paper reports the the structure and conformation of of the title compound, (I), which was carried out to continue the investigation of a new class of antiamnesic agents (Thamotharan, Parthasarathi, Malik et al., 2003; Thamotharan, Parthasarathi, Gupta et al., 2003a,b,c).

The pyrrolidine ring in nootropics typically has a half-chair (C2, twist-envelope) conformation (Bandoli, Nicolini, Lumbroso et al., 1987; Bandoli, Nicolini, Pappalardo et al., 1987; Amato et al., 1990; Amato, Bandoli, Dolmella et al., 1991). In (I), however, the five-membered pyrrolidinone ring exhibits an envelope conformation, with atom C13 as the flap, a pseudo-rotation angle, Δ, of 86.6 (1)° and a maximum torsion angle, ϕm, of 31.5 (1)° for the atom sequence N10—C11—C12—C13—C14 (Rao et al., 1981). The dihedral angle between the mean planes through the phenyl and pyrrolinone rings is 6.41 (3)°. The mean plane of the central moiety, C1—O7—C8—C9—N10, is oriented at angles of 2.16 (4) and 6.37 (5)° with respect to the planes of the phenyl and pyrrolidinone rings, respectively. The nitro group is almost coplanar with the adjacent phenyl ring. The slightly enlarged exocyclic O7—C1—C2 bond angle [124.69 (9)°] probably results from a repulsive interaction between the H atoms on atoms C2 and C8 (H2···H81 = 2.30 Å and H2···H82 = 2.25 Å). Otherwise, the bond lengths and angles show no unusual features. The C1—O7—C8—C9 [−176.59 (8)°] and O7—C8—C9—N10 [−178.72 (8)°] torsion angles show that the central moiety has an antiperiplanar conformation.

In the crystal, atoms C3 and C12 act as donors for weak intermolecular C—H···O interactions with carbonyl atom O11 of the pyrrolidinone ring and atom O16 of the nitro group of a neighbouring centrosymmetrically related molecule, respectively. Each interaction links the molecules individually into dimers that have a graph-set motif (Bernstein et al., 1995) of R22(20) and R22(26), respectively (Fig. 2). Atom C5 is involved in an intermolecular C—H···O interaction with another carbonyl O atom (O9) of a different neighbouring centrosymmetrically related molecule. This interaction also produces loops that have a graph-set motif of R22(16). Atom C14 forms a weak intermolecular C—H···O interaction with atom O17 of the nitro group of an adjacent molecule. This interaction links the molecules into chains that run parallel to the c axis and have a graph-set motif of C(12).

Experimental top

A solution of (4-nitrophenoxy)acetylchloride (1.0 g) in dichloromethane was stirred with pyrrolidinone. Dichloromethane was removed and crushed ice was added to the contents. The solid residue obtained was filtered and crystallized from methanol, affording crystals of (I) (yield 0.78 g, 63.71%; m.p. 413–415 K).

Refinement top

All H atoms were placed in geometrically idealized positions (C—H = 0.95–0.99 Å) and were constrained to ride on their parent atoms with Uiso(H) values equal to 1.2Ueq(C).

Computing details top

Data collection: COLLECT (Nonius, 2000); cell refinement: DENZO–SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: PARST97 (Nardelli, 1995) and PLATON (Spek, 2003).

Figures top
[Figure 1] Fig. 1. A view of the molecule of (I), showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented by circles of arbitrary radii.
[Figure 2] Fig. 2. The connection of molecules of (I) into dimers. Atoms marked with an asterisk (*) or hash (#) are at the symmetry positions (-x − 1,-y + 1,-z + 1) and (-x + 1,-y,-z + 1), respectively.
1-[2-(4-Nitrophenoxy)acetyl]pyrrolidin-2-one top
Crystal data top
C12H12N2O5Z = 2
Mr = 264.24F(000) = 276
Triclinic, P1Dx = 1.507 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 5.2813 (1) ÅCell parameters from 3302 reflections
b = 8.7367 (2) Åθ = 2.0–30.0°
c = 12.9843 (3) ŵ = 0.12 mm1
α = 80.4656 (14)°T = 160 K
β = 81.4302 (12)°Prism, colourless
γ = 83.883 (1)°0.25 × 0.25 × 0.17 mm
V = 582.17 (2) Å3
Data collection top
Nonius KappaCCD
diffractometer
2701 reflections with I > 2σ(I)
Radiation source: Nonius FR591 sealed tube generatorRint = 0.033
Horizontally mounted graphite crystal monochromatorθmax = 30.0°, θmin = 2.4°
Detector resolution: 9 pixels mm-1h = 07
ϕ and ω scans with κ offsetsk = 1112
16366 measured reflectionsl = 1718
3393 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.043Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.126H-atom parameters constrained
S = 1.06 w = 1/[σ2(Fo2) + (0.0735P)2 + 0.0824P]
where P = (Fo2 + 2Fc2)/3
3393 reflections(Δ/σ)max < 0.001
172 parametersΔρmax = 0.36 e Å3
0 restraintsΔρmin = 0.26 e Å3
Crystal data top
C12H12N2O5γ = 83.883 (1)°
Mr = 264.24V = 582.17 (2) Å3
Triclinic, P1Z = 2
a = 5.2813 (1) ÅMo Kα radiation
b = 8.7367 (2) ŵ = 0.12 mm1
c = 12.9843 (3) ÅT = 160 K
α = 80.4656 (14)°0.25 × 0.25 × 0.17 mm
β = 81.4302 (12)°
Data collection top
Nonius KappaCCD
diffractometer
2701 reflections with I > 2σ(I)
16366 measured reflectionsRint = 0.033
3393 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0430 restraints
wR(F2) = 0.126H-atom parameters constrained
S = 1.06Δρmax = 0.36 e Å3
3393 reflectionsΔρmin = 0.26 e Å3
172 parameters
Special details top

Experimental. Solvent used: MeOH Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.719 (2) Frames collected: 352 Seconds exposure per frame: 46 Degrees rotation per frame: 2.0 Crystal-Detector distance (mm): 28.0

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 F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 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 (Å2) top
xyzUiso*/Ueq
O70.15309 (15)0.34954 (9)0.54930 (6)0.02594 (19)
O90.22285 (16)0.44936 (10)0.73114 (6)0.0297 (2)
O110.42580 (16)0.13590 (10)0.71998 (6)0.0301 (2)
O160.04202 (18)0.03989 (11)0.13850 (7)0.0373 (2)
O170.28845 (19)0.20168 (11)0.10914 (7)0.0373 (2)
N100.13145 (17)0.31977 (10)0.79120 (7)0.0219 (2)
N150.12317 (19)0.14158 (11)0.16452 (7)0.0260 (2)
C10.1311 (2)0.29202 (12)0.45630 (8)0.0214 (2)
C20.0669 (2)0.18582 (12)0.42193 (8)0.0235 (2)
H20.19830.14730.46450.028*
C30.0712 (2)0.13667 (12)0.32514 (9)0.0240 (2)
H30.20580.06520.30030.029*
C40.1245 (2)0.19388 (12)0.26572 (8)0.0216 (2)
C50.3230 (2)0.29975 (12)0.29858 (8)0.0225 (2)
H50.45460.33720.25600.027*
C60.3259 (2)0.34963 (12)0.39422 (8)0.0232 (2)
H60.45930.42270.41790.028*
C80.0375 (2)0.28918 (13)0.61578 (8)0.0239 (2)
H810.20950.31720.58070.029*
H820.04050.17430.63200.029*
C90.0330 (2)0.36052 (12)0.71558 (8)0.0217 (2)
C110.3410 (2)0.20721 (12)0.79208 (8)0.0233 (2)
C120.4296 (2)0.19012 (13)0.89878 (9)0.0275 (2)
H1210.61960.17880.89250.033*
H1220.36140.09830.94580.033*
C130.3218 (2)0.34010 (13)0.94052 (9)0.0270 (2)
H1310.44330.42190.91850.032*
H1320.28470.32231.01840.032*
C140.0746 (2)0.38539 (13)0.89048 (8)0.0246 (2)
H1410.07410.33930.93610.030*
H1420.03860.50000.87680.030*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O70.0267 (4)0.0302 (4)0.0219 (4)0.0061 (3)0.0090 (3)0.0072 (3)
O90.0250 (4)0.0345 (4)0.0287 (4)0.0098 (3)0.0067 (3)0.0070 (3)
O110.0308 (4)0.0312 (4)0.0291 (4)0.0107 (3)0.0081 (3)0.0117 (3)
O160.0340 (5)0.0435 (5)0.0366 (5)0.0089 (4)0.0041 (4)0.0204 (4)
O170.0446 (5)0.0426 (5)0.0265 (4)0.0092 (4)0.0155 (4)0.0091 (4)
N100.0222 (4)0.0224 (4)0.0213 (4)0.0037 (3)0.0055 (3)0.0050 (3)
N150.0269 (5)0.0270 (5)0.0245 (5)0.0002 (4)0.0037 (4)0.0058 (4)
C10.0224 (5)0.0206 (5)0.0212 (5)0.0013 (4)0.0031 (4)0.0029 (4)
C20.0215 (5)0.0240 (5)0.0252 (5)0.0021 (4)0.0072 (4)0.0031 (4)
C30.0225 (5)0.0215 (5)0.0274 (5)0.0019 (4)0.0037 (4)0.0044 (4)
C40.0224 (5)0.0217 (5)0.0209 (5)0.0008 (4)0.0028 (4)0.0045 (4)
C50.0205 (5)0.0234 (5)0.0231 (5)0.0016 (4)0.0052 (4)0.0024 (4)
C60.0206 (5)0.0248 (5)0.0237 (5)0.0019 (4)0.0036 (4)0.0039 (4)
C80.0247 (5)0.0241 (5)0.0233 (5)0.0028 (4)0.0082 (4)0.0034 (4)
C90.0221 (5)0.0213 (5)0.0209 (5)0.0006 (4)0.0042 (4)0.0012 (4)
C110.0224 (5)0.0223 (5)0.0253 (5)0.0028 (4)0.0057 (4)0.0047 (4)
C120.0268 (5)0.0295 (5)0.0273 (5)0.0058 (4)0.0106 (4)0.0062 (4)
C130.0248 (5)0.0322 (6)0.0258 (5)0.0034 (4)0.0076 (4)0.0092 (4)
C140.0236 (5)0.0287 (5)0.0220 (5)0.0038 (4)0.0037 (4)0.0080 (4)
Geometric parameters (Å, º) top
O7—C11.3679 (13)C4—C51.3882 (14)
O7—C81.4252 (12)C5—C61.3801 (15)
O9—C91.2141 (13)C5—H50.9500
O11—C111.2140 (13)C6—H60.9500
O16—N151.2293 (13)C8—C91.5102 (15)
O17—N151.2325 (13)C8—H810.9900
N10—C91.3848 (13)C8—H820.9900
N10—C111.4000 (13)C11—C121.5070 (15)
N10—C141.4742 (13)C12—C131.5229 (16)
N15—C41.4597 (14)C12—H1210.9900
C1—C21.3947 (15)C12—H1220.9900
C1—C61.4012 (14)C13—C141.5298 (15)
C2—C31.3902 (15)C13—H1310.9900
C2—H20.9500C13—H1320.9900
C3—C41.3834 (14)C14—H1410.9900
C3—H30.9500C14—H1420.9900
C1—O7—C8115.97 (8)O7—C8—H82110.3
C9—N10—C11127.95 (9)C9—C8—H82110.3
C9—N10—C14119.51 (8)H81—C8—H82108.6
C11—N10—C14112.18 (8)O9—C9—N10120.18 (9)
O16—N15—O17123.07 (10)O9—C9—C8123.20 (9)
O16—N15—C4118.67 (9)N10—C9—C8116.62 (9)
O17—N15—C4118.26 (9)O11—C11—N10125.01 (10)
O7—C1—C2124.69 (9)O11—C11—C12127.95 (10)
O7—C1—C6114.67 (9)N10—C11—C12107.01 (9)
C2—C1—C6120.64 (10)C11—C12—C13104.40 (9)
C3—C2—C1119.69 (9)C11—C12—H121110.9
C3—C2—H2120.2C13—C12—H121110.9
C1—C2—H2120.2C11—C12—H122110.9
C4—C3—C2118.64 (9)C13—C12—H122110.9
C4—C3—H3120.7H121—C12—H122108.9
C2—C3—H3120.7C12—C13—C14103.60 (9)
C3—C4—C5122.47 (10)C12—C13—H131111.0
C3—C4—N15119.03 (9)C14—C13—H131111.0
C5—C4—N15118.50 (9)C12—C13—H132111.0
C6—C5—C4118.87 (9)C14—C13—H132111.0
C6—C5—H5120.6H131—C13—H132109.0
C4—C5—H5120.6N10—C14—C13103.08 (8)
C5—C6—C1119.68 (10)N10—C14—H141111.1
C5—C6—H6120.2C13—C14—H141111.1
C1—C6—H6120.2N10—C14—H142111.1
O7—C8—C9106.89 (8)C13—C14—H142111.1
O7—C8—H81110.3H141—C14—H142109.1
C9—C8—H81110.3
C8—O7—C1—C22.70 (15)C11—N10—C9—O9172.30 (10)
C8—O7—C1—C6177.99 (9)C14—N10—C9—O90.17 (15)
O7—C1—C2—C3179.25 (10)C11—N10—C9—C87.67 (16)
C6—C1—C2—C30.02 (16)C14—N10—C9—C8179.86 (9)
C1—C2—C3—C40.68 (16)O7—C8—C9—O91.32 (15)
C2—C3—C4—C50.78 (17)O7—C8—C9—N10178.72 (8)
C2—C3—C4—N15179.32 (9)C9—N10—C11—O117.00 (18)
O16—N15—C4—C35.06 (15)C14—N10—C11—O11179.93 (10)
O17—N15—C4—C3174.99 (10)C9—N10—C11—C12171.17 (10)
O16—N15—C4—C5175.03 (10)C14—N10—C11—C121.76 (12)
O17—N15—C4—C54.92 (16)O11—C11—C12—C13161.51 (11)
C3—C4—C5—C60.18 (16)N10—C11—C12—C1320.39 (12)
N15—C4—C5—C6179.91 (9)C11—C12—C13—C1430.37 (12)
C4—C5—C6—C10.49 (16)C9—N10—C14—C13169.00 (9)
O7—C1—C6—C5179.92 (9)C11—N10—C14—C1317.41 (12)
C2—C1—C6—C50.58 (16)C12—C13—C14—N1028.89 (11)
C1—O7—C8—C9176.59 (8)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C3—H3···O11i0.952.493.4235 (13)166
C5—H5···O9ii0.952.403.0955 (13)130
C12—H121···O16i0.992.513.2837 (14)134
C14—H141···O17iii0.992.533.4406 (15)153
Symmetry codes: (i) x+1, y, z+1; (ii) x1, y+1, z+1; (iii) x, y, z+1.

Experimental details

Crystal data
Chemical formulaC12H12N2O5
Mr264.24
Crystal system, space groupTriclinic, P1
Temperature (K)160
a, b, c (Å)5.2813 (1), 8.7367 (2), 12.9843 (3)
α, β, γ (°)80.4656 (14), 81.4302 (12), 83.883 (1)
V3)582.17 (2)
Z2
Radiation typeMo Kα
µ (mm1)0.12
Crystal size (mm)0.25 × 0.25 × 0.17
Data collection
DiffractometerNonius KappaCCD
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
16366, 3393, 2701
Rint0.033
(sin θ/λ)max1)0.704
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.043, 0.126, 1.06
No. of reflections3393
No. of parameters172
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.36, 0.26

Computer programs: COLLECT (Nonius, 2000), DENZO–SMN (Otwinowski & Minor, 1997), DENZO-SMN and SCALEPACK (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Farrugia, 1997), PARST97 (Nardelli, 1995) and PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C3—H3···O11i0.952.493.4235 (13)166
C5—H5···O9ii0.952.403.0955 (13)130
C12—H121···O16i0.992.513.2837 (14)134
C14—H141···O17iii0.992.533.4406 (15)153
Symmetry codes: (i) x+1, y, z+1; (ii) x1, y+1, z+1; (iii) x, y, z+1.
 

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