2-[(2-Oxopyrrolidin-1-yl)­carbonyl­methyl]-2,3-di­hydro-1H-iso­indole-1,3-dione: an antiamnesic agent

The title compound, C₁₄H₁₂N₂O₄, is a potential antiamnesic agent. The pyrrolidinone ring has an envelope conformation. The dihedral angle between the N-substituted phthal­imide moiety and the pyrrolidinone ring is 77.16 (5)°. In the solid state, symmetry-related mol­ecules are linked by weak intermol­ecular C—H...O interactions, forming a continuous chain.

Key indicators

• Single-crystal X-ray study
• T = 160 K
• Mean [sigma](C-C) = 0.003 Å
• R factor = 0.047
• wR factor = 0.128
• Data-to-parameter ratio = 13.6

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry

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S1. Comment

The conformations of molecules with anti-amnesic activity have attracted considerable interest (Amato et al., 1991), and the structure determination of the title compound, (I), was carried out to continue the investigation of a new class of anti-amnesic agents (Thamotharan, Parthasarathi, Malik et al., 2003; Thamotharan, Parthasarathi, Gupta et al., 2003).

Fig. 1 shows the asymmetric unit of (I) with the atom-numbering scheme. The geometric parameters of the N-substituted phthalimide moiety in (I) are almost the same as those in 2-(5-chloropyridin-2-yl)-2,3-dihydro-1H-isoindole-1,3-dione (Holband et al., 2001). The angles C5—C4—C9 [117.2 (2)°] and C6—C7—C8 [117.4 (2)°] are significantly smaller than the other angles in the benzene ring. Similar observations have been made in related structures (Christensen & Thom, 1971, and references therein). This angular distortioncan be explained by the strain caused by fusion with the five-membered ring.

In (I), the five-membered pyrrolidinone ring exhibits an envelope conformation, with atom C15 as the flap, a pseudo-rotation angle Δ = 270.3 (2)° and a maximum torsion angle ϕ_m = 30.7 (1)° for the atom sequence N12—C13—C14—C15—C16 (Rao et al., 1981). The dihedral angle between the N-substituted phthalimide moiety and pyrrolidinone ring is 77.16 (5)°. The planar central moiety, N2—C10—C11—N12, is oriented at angles of 7.62 (11) and 84.67 (10)° with respect to the pyrrolidinone and N-substituted phthalimide moieties, respectively.

In the crystal structure, atom C15 acts as a donor for a weak intermolecular C—H···O interaction with carbonyl atom O1 of an adjacent molecule. This interaction links the molecules into a chain, which runs parallel to the b axis and has a graph-set motif of C(9) (Bernstein et al., 1995). Atom C16 has a weak intermolecular C—H···O interaction with carbonyl atom O13 of a different adjacent molecule. This interaction also links the molecules into a chain, which runs parallel to the b axis and has a graph-set motif of C(5) (Table 1) (Bernstein et al., 1995). A short intermolecular contact is observed, O3···C1ⁱ 2.883 (3) Å [symmetry code: (i) −x + 1/2, y + 1/2, z].

S2. Experimental

A solution of (1,3-dioxo-1,3-dihydroisoindole-2-yl)acetyl chloride (1.0 g) in dichloromethane was stirred with pyrrolidinone. The dichloromethane was removed and crushed ice was added to the contents. The solid residue obtained was filtered and crystallized from methanol to afford crystals of (I) (yield 0.81 g, 66.5%; m.p. 473 K).

S3. Refinement

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

Computing details

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: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Version 1.07; Farrugia, 1997); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2003).

Figures

Fig. 1. 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.

2-[(2-Oxopyrrolidin-1-yl)carbonylmethyl]-2,3-dihydro-1H-isoindole-1,3-dione

Crystal data

C14H12N2O4	Dx = 1.448 Mg m^−3
Mr = 272.26	Melting point: 473 K
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 2839 reflections
a = 10.7480 (2) Å	θ = 2.0–26.0°
b = 8.3280 (1) Å	µ = 0.11 mm^−1
c = 27.9084 (4) Å	T = 160 K
V = 2498.06 (7) Å^3	Plate, colourless
Z = 8	0.18 × 0.18 × 0.05 mm
F(000) = 1136

Data collection

Nonius KappaCCD diffractometer	1620 reflections with I > 2σ(I)
Radiation source: Nonius FR591 sealed tube generator	Rint = 0.067
Horizontally mounted graphite crystal monochromator	θmax = 26.0°, θmin = 2.4°
Detector resolution: 9 pixels mm^-1	h = 0→13
ω scans with κ offsets	k = 0→10
29914 measured reflections	l = −34→0
2459 independent reflections

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.047	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.129	H-atom parameters constrained
S = 1.03	w = 1/[σ^2(Fo^2) + (0.0681P)^2 + 0.4733P] where P = (Fo^2 + 2Fc^2)/3
2459 reflections	(Δ/σ)max < 0.001
181 parameters	Δρmax = 0.17 e Å^−3
0 restraints	Δρmin = −0.19 e Å^−3

Special details

Experimental. Solvent used: MeOH Cooling Device: Oxford Cryosystems Cryostream 700 Crystal mount: glued on a glass fibre Mosaicity (°.): 0.538 (1) Frames collected: 793 Seconds exposure per frame: 77 Degrees rotation per frame: 0.7 Crystal-Detector distance (mm): 42.0

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	−0.04618 (14)	0.14043 (17)	0.59049 (5)	0.0458 (4)
O3	0.27434 (14)	0.49855 (18)	0.58283 (5)	0.0459 (4)
O11	−0.01451 (14)	0.48029 (17)	0.66903 (5)	0.0446 (4)
O13	0.25931 (14)	0.20034 (18)	0.73247 (5)	0.0481 (4)
N2	0.11528 (14)	0.32121 (18)	0.59882 (5)	0.0316 (4)
N12	0.08877 (15)	0.37071 (17)	0.73097 (5)	0.0308 (4)
C1	0.02859 (18)	0.2310 (2)	0.57284 (7)	0.0332 (5)
C3	0.18932 (19)	0.4147 (2)	0.56920 (7)	0.0328 (5)
C4	0.1863 (2)	0.4463 (3)	0.47650 (7)	0.0423 (5)
H4	0.2515	0.5231	0.4752	0.051*
C5	0.1286 (2)	0.3916 (3)	0.43516 (7)	0.0488 (6)
H5	0.1540	0.4328	0.4050	0.059*
C6	0.0350 (2)	0.2784 (3)	0.43711 (8)	0.0486 (6)
H6	−0.0022	0.2422	0.4082	0.058*
C7	−0.0060 (2)	0.2164 (3)	0.48057 (7)	0.0427 (5)
H7	−0.0703	0.1382	0.4819	0.051*
C8	0.05035 (19)	0.2726 (2)	0.52169 (6)	0.0329 (5)
C9	0.14500 (18)	0.3841 (2)	0.51966 (6)	0.0325 (5)
C10	0.14576 (19)	0.2922 (2)	0.64844 (6)	0.0345 (5)
H101	0.2345	0.3186	0.6538	0.041*
H102	0.1342	0.1767	0.6556	0.041*
C11	0.06652 (18)	0.3901 (2)	0.68244 (7)	0.0325 (5)
C13	0.18439 (19)	0.2856 (2)	0.75308 (7)	0.0369 (5)
C14	0.1779 (2)	0.3192 (3)	0.80590 (7)	0.0461 (6)
H141	0.2411	0.3996	0.8154	0.055*
H142	0.1912	0.2198	0.8247	0.055*
C15	0.0468 (2)	0.3842 (3)	0.81345 (7)	0.0473 (6)
H151	−0.0123	0.2963	0.8207	0.057*
H152	0.0449	0.4632	0.8399	0.057*
C16	0.0154 (2)	0.4634 (2)	0.76604 (7)	0.0384 (5)
H161	−0.0747	0.4557	0.7591	0.046*
H162	0.0402	0.5779	0.7660	0.046*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0429 (9)	0.0496 (9)	0.0450 (9)	−0.0089 (8)	−0.0024 (7)	0.0101 (7)
O3	0.0514 (10)	0.0470 (9)	0.0394 (9)	−0.0128 (8)	−0.0014 (7)	−0.0051 (7)
O11	0.0486 (9)	0.0499 (9)	0.0352 (9)	0.0154 (8)	−0.0018 (7)	0.0027 (7)
O13	0.0457 (9)	0.0581 (9)	0.0405 (9)	0.0131 (8)	−0.0038 (7)	0.0012 (7)
N2	0.0375 (10)	0.0346 (9)	0.0228 (9)	−0.0010 (8)	0.0002 (7)	0.0002 (7)
N12	0.0390 (9)	0.0301 (8)	0.0233 (9)	0.0015 (8)	0.0002 (7)	0.0004 (7)
C1	0.0342 (11)	0.0327 (11)	0.0327 (11)	0.0026 (9)	−0.0023 (9)	0.0009 (9)
C3	0.0385 (12)	0.0297 (10)	0.0302 (11)	0.0024 (9)	0.0018 (9)	−0.0028 (9)
C4	0.0486 (13)	0.0461 (13)	0.0322 (12)	0.0052 (11)	0.0062 (10)	0.0033 (10)
C5	0.0617 (16)	0.0573 (14)	0.0275 (12)	0.0177 (13)	0.0019 (11)	0.0030 (10)
C6	0.0585 (15)	0.0562 (14)	0.0310 (12)	0.0165 (13)	−0.0097 (11)	−0.0104 (11)
C7	0.0475 (13)	0.0435 (12)	0.0370 (12)	0.0064 (10)	−0.0102 (10)	−0.0083 (10)
C8	0.0383 (11)	0.0324 (11)	0.0280 (11)	0.0069 (9)	−0.0028 (9)	−0.0029 (8)
C9	0.0397 (11)	0.0318 (10)	0.0260 (11)	0.0053 (9)	0.0007 (9)	−0.0010 (8)
C10	0.0391 (11)	0.0389 (11)	0.0254 (11)	0.0029 (9)	−0.0025 (9)	0.0004 (9)
C11	0.0347 (11)	0.0328 (10)	0.0302 (11)	−0.0007 (10)	−0.0002 (9)	0.0020 (9)
C13	0.0392 (12)	0.0351 (11)	0.0366 (12)	−0.0025 (10)	0.0007 (10)	−0.0002 (10)
C14	0.0574 (14)	0.0510 (13)	0.0299 (12)	−0.0032 (12)	−0.0063 (10)	0.0010 (10)
C15	0.0654 (15)	0.0459 (13)	0.0305 (12)	0.0023 (12)	0.0042 (11)	−0.0025 (10)
C16	0.0461 (13)	0.0344 (11)	0.0346 (12)	0.0002 (10)	0.0070 (10)	−0.0046 (9)

Geometric parameters (Å, º)

O1—C1	1.207 (2)	C6—C7	1.390 (3)
O3—C3	1.211 (2)	C6—H6	0.9500
O11—C11	1.209 (2)	C7—C8	1.380 (3)
O13—C13	1.218 (2)	C7—H7	0.9500
N2—C3	1.387 (2)	C8—C9	1.379 (3)
N2—C1	1.399 (2)	C10—C11	1.514 (3)
N2—C10	1.443 (2)	C10—H101	0.9900
N12—C11	1.385 (2)	C10—H102	0.9900
N12—C13	1.392 (3)	C13—C14	1.502 (3)
N12—C16	1.475 (2)	C14—C15	1.524 (3)
C1—C8	1.488 (3)	C14—H141	0.9900
C3—C9	1.484 (3)	C14—H142	0.9900
C4—C9	1.384 (3)	C15—C16	1.516 (3)
C4—C5	1.387 (3)	C15—H151	0.9900
C4—H4	0.9500	C15—H152	0.9900
C5—C6	1.380 (3)	C16—H161	0.9900
C5—H5	0.9500	C16—H162	0.9900
C3—N2—C1	112.00 (16)	N2—C10—C11	112.54 (16)
C3—N2—C10	122.39 (16)	N2—C10—H101	109.1
C1—N2—C10	123.94 (15)	C11—C10—H101	109.1
C11—N12—C13	128.34 (17)	N2—C10—H102	109.1
C11—N12—C16	119.70 (15)	C11—C10—H102	109.1
C13—N12—C16	111.52 (15)	H101—C10—H102	107.8
O1—C1—N2	124.56 (18)	O11—C11—N12	119.97 (17)
O1—C1—C8	129.92 (18)	O11—C11—C10	123.09 (17)
N2—C1—C8	105.52 (16)	N12—C11—C10	116.93 (16)
O3—C3—N2	124.70 (18)	O13—C13—N12	125.12 (18)
O3—C3—C9	129.32 (18)	O13—C13—C14	127.08 (19)
N2—C3—C9	105.94 (16)	N12—C13—C14	107.80 (17)
C9—C4—C5	117.2 (2)	C13—C14—C15	104.18 (17)
C9—C4—H4	121.4	C13—C14—H141	110.9
C5—C4—H4	121.4	C15—C14—H141	110.9
C6—C5—C4	121.2 (2)	C13—C14—H142	110.9
C6—C5—H5	119.4	C15—C14—H142	110.9
C4—C5—H5	119.4	H141—C14—H142	108.9
C5—C6—C7	121.3 (2)	C16—C15—C14	103.84 (17)
C5—C6—H6	119.4	C16—C15—H151	111.0
C7—C6—H6	119.4	C14—C15—H151	111.0
C8—C7—C6	117.4 (2)	C16—C15—H152	111.0
C8—C7—H7	121.3	C14—C15—H152	111.0
C6—C7—H7	121.3	H151—C15—H152	109.0
C9—C8—C7	121.24 (18)	N12—C16—C15	103.45 (16)
C9—C8—C1	108.19 (16)	N12—C16—H161	111.1
C7—C8—C1	130.56 (19)	C15—C16—H161	111.1
C8—C9—C4	121.61 (18)	N12—C16—H162	111.1
C8—C9—C3	108.32 (16)	C15—C16—H162	111.1
C4—C9—C3	130.05 (19)	H161—C16—H162	109.0
C3—N2—C1—O1	179.98 (18)	O3—C3—C9—C8	176.3 (2)
C10—N2—C1—O1	14.4 (3)	N2—C3—C9—C8	−1.5 (2)
C3—N2—C1—C8	−0.2 (2)	O3—C3—C9—C4	−2.1 (4)
C10—N2—C1—C8	−165.72 (16)	N2—C3—C9—C4	−179.95 (19)
C1—N2—C3—O3	−176.99 (18)	C3—N2—C10—C11	104.0 (2)
C10—N2—C3—O3	−11.2 (3)	C1—N2—C10—C11	−91.9 (2)
C1—N2—C3—C9	1.0 (2)	C13—N12—C11—O11	−173.23 (18)
C10—N2—C3—C9	166.82 (16)	C16—N12—C11—O11	−1.5 (3)
C9—C4—C5—C6	−0.8 (3)	C13—N12—C11—C10	7.9 (3)
C4—C5—C6—C7	0.8 (3)	C16—N12—C11—C10	179.58 (16)
C5—C6—C7—C8	0.2 (3)	N2—C10—C11—O11	1.2 (3)
C6—C7—C8—C9	−1.0 (3)	N2—C10—C11—N12	−179.98 (15)
C6—C7—C8—C1	−179.83 (19)	C11—N12—C13—O13	−7.2 (3)
O1—C1—C8—C9	179.0 (2)	C16—N12—C13—O13	−179.49 (18)
N2—C1—C8—C9	−0.8 (2)	C11—N12—C13—C14	172.47 (18)
O1—C1—C8—C7	−2.1 (4)	C16—N12—C13—C14	0.2 (2)
N2—C1—C8—C7	178.08 (19)	O13—C13—C14—C15	−162.0 (2)
C7—C8—C9—C4	1.0 (3)	N12—C13—C14—C15	18.3 (2)
C1—C8—C9—C4	−179.97 (17)	C13—C14—C15—C16	−29.0 (2)
C7—C8—C9—C3	−177.60 (17)	C11—N12—C16—C15	168.35 (16)
C1—C8—C9—C3	1.4 (2)	C13—N12—C16—C15	−18.6 (2)
C5—C4—C9—C8	0.0 (3)	C14—C15—C16—N12	28.8 (2)
C5—C4—C9—C3	178.21 (19)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C15—H152···O1^i	0.99	2.44	3.426 (3)	175
C16—H162···O13^ii	0.99	2.56	3.261 (3)	128

Symmetry codes: (i) −x, y+1/2, −z+3/2; (ii) −x+1/2, y+1/2, z.