supporting information


Acta Cryst. (2013). E69, o963    [ doi:10.1107/S1600536813013779 ]

2-(9H-Fluoren-9-yl)-4-(4-fluoro­anilino)-4-oxo­butanoic acid

T. Matviiuk, M. Baltas, Z. Voitenko, M. Gorichko and C. Lherbet

Abstract top

In the title compound, C23H18FNO3, the tricyclic 9-fluorenyl system is approximately planar (r.m.s. deviation = 0.0279 Å). The N-C(=O) bond length is comparatively short [1.359 (3) Å], which is typical for such conjugated systems. The N atom has a planar configuration [sum of bond angles= 359.8°] due to conjugation of its lone pair with the [pi]-system of the carbonyl group. In the crystal, a three-dimensional network is formed through N-H...O and O-H...O hydrogen bonds between the amide and carb­oxy­lic acid groups and carbonyl O-atom acceptors.

Comment top

Derivatives of the pyrrolidine-2,5-dione fragment are common structural motifs in medicinal chemistry (Patsalos, 2005; Rankin, et al., 1986). These molecules containing succinimide as a structural fragment were employed in drug design in response to their binding efficacy and low toxicity. Some pyrrolidine-2,5-dione derivatives were synthesized via interaction of succinic anhydride with different amines and futher cyclization, for example the synthesis of an nicotinic acetylcholine receptor antagonist (Carroll et al., 2007). Cyclic anhydrides of dicarboxylic acids react readily with amines forming dicarboxylic acid monoamides (Miller et al., 1951). Reaction of unsymmetrically substituted cyclic anhydrides may occur with formation of two possible regioisomers having the substituent either α or β to the amide group. (Stephani et al., 2002.; Galustyan et al., 2000). Herein, we report the regioselective synthesis and crystal structure of the title compound (II). The novel 2-(9H-fluoren-9-yl)-4-[(4-fluorophenyl)amino]-4-oxobutanoic acid, C23H18FNO3, (Fig. 1) is obtained as a product in the ring-opening reaction of 3-(9H-fluoren-9-yl)dihydrofuran-2,5-dione (I) (Clar, 1942) (see Fig. 2). The regioselectivity of the reaction depends on temperature. The reaction of anhydride (I) with p-F-aniline was carried out in dry THF at room temperature and a reactant ratio 1:1. Only one regioisomer (β-succinamic acid) was detected and isolated (91% yield). When the reaction was carried out at higher temperature (55 °C), a mixture of regioisomers was obtained.

In the structure of (II) (Fig. 1) the tricyclic 9-fluorenyl system C1—C13 is planar with an r.m.s. deviation of 0.0279 Å, wich is typical for this class of compounds. The N1—C17 bond distance is comparatively short (1.359 (3) Å) which is typical for such conjugated systems The N1 atom has a planar configuration, as the sum of bond angles on the N1 atom is 359.5 (17)°, due to conjugation of the lone pair of N1 atom with π-system of the carbonyl group. Molecules of compound (II) (Fig. 1) in the crystal are connected across a center of inversion by O1—H1···O2a hydrogen bonds forming dimers which are then connected into chains parallel to c by N1—H1N···O3b bonds (Table 1).

Related literature top

For the synthesis of various succinic anhydrides, see: Clar (1942). For biological studies on substituted succinimides, see: Carroll et al. (2007); Miller & Johns (1951); Patsalos (2005); Rankin et al. (1986). For the synthesis of substituted phenysuccinamic acids, see: Galustyan et al. (2000); Stephani et al. (2002).

Experimental top

The synthesis of the cyclic anhydride (I) (Fig. 2) was carried out according to the literature method (Clar, 1942). Compound (I) (92 mg, 0.35 mmol)was dissolved in dry THF, p-F-aniline (39 mg, 0.35 mmol) was added and the mixture was stirred overnight at room temperature. Thereafter, solvent was evaporated and the residue dissolved in a saturated solution of sodium hydrocarbonate, filtered and acidified with 1 N HCl. The resulting precipitate was filtered off and recrystalized from ethanol. White powder, yield: 113 mg, 86%; m.p.: 171–172 °C. 1H NMR (300 MHz, [D6]DMSO, δ): 1.28 (d, J = 15.6 Hz, 1 H), 2.15 (dd, J = 11.4 Hz, J = 15.9 Hz, 1 H), 3.85 (d, J = 10.5 Hz, 1 H), 4.52 (br. s, 1 H), 6.90–8.05 (m, 12 H), 9.70 (br. s, 1 H), 12.86 (br. s, 1 H); 13C{1H} NMR (75 MHz, CD3OD, δ): 32.6, 44.3, 49.4, 115.8, 116.1, 120.9, 121.1, 122.8, 122.9, 125.4, 126.1, 128.1, 128.6, 128.8, 128.9, 136.0, 142.6, 143.1, 144.7, 146.0, 160.0 (d, J = 241.8 Hz), 172.5, 177.2. 19 F NMR (282 MHz, CD3OD, δ): = -116.0.

Refinement top

Carboxylic acid and amide H-atoms were located in a difference-Fourier synthesis and both positional and displacement parameters were allowed to refine. Other hydrogen atoms were positioned geometrically, with C—H = 0.96–0.98 Å and were allowed to ride on their parent atoms, with Uiso(H) = 1.2Ueq(methine or methylene C) or 1.5Ueq(methyl C). In the absence of a suitable heavy atom, the absolute configuration of the title compound could not be determined.

Computing details top

Data collection: APEX2 (Bruker, 2007); cell refinement: SAINT (Bruker, 2007); data reduction: SAINT (Bruker, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure and atom numbering scheme for the title compound, showing 50% probability displacement ellipsoids.
[Figure 2] Fig. 2. The synthetic route to the title compound (II).
2-(9H-Fluoren-9-yl)-4-(4-fluoroanilino)-4-oxobutanoic acid top
Crystal data top
C23H18FNO3F(000) = 784
Mr = 375.38Dx = 1.372 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 10.2048 (6) ÅCell parameters from 8408 reflections
b = 18.5170 (11) Åθ = 2.3–25.0°
c = 9.6164 (6) ŵ = 0.10 mm1
β = 90.494 (4)°T = 296 K
V = 1817.07 (19) Å3Plate, colourless
Z = 40.45 × 0.10 × 0.03 mm
Data collection top
Bruker SMART APEXII CCD area-detector
diffractometer
3205 independent reflections
Radiation source: fine-focus sealed tube1744 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.081
ω scansθmax = 25.0°, θmin = 2.3°
Absorption correction: numerical
(SADABS; Bruker, 2008)
h = 1211
Tmin = 0.957, Tmax = 0.997k = 2219
8408 measured reflectionsl = 1111
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)] = 0.054Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.104H atoms treated by a mixture of independent and constrained refinement
S = 1.00 w = 1/[σ2(Fo2) + (0.027P)2]
where P = (Fo2 + 2Fc2)/3
3205 reflections(Δ/σ)max < 0.001
261 parametersΔρmax = 0.24 e Å3
0 restraintsΔρmin = 0.26 e Å3
Crystal data top
C23H18FNO3V = 1817.07 (19) Å3
Mr = 375.38Z = 4
Monoclinic, P21/cMo Kα radiation
a = 10.2048 (6) ŵ = 0.10 mm1
b = 18.5170 (11) ÅT = 296 K
c = 9.6164 (6) Å0.45 × 0.10 × 0.03 mm
β = 90.494 (4)°
Data collection top
Bruker SMART APEXII CCD area-detector
diffractometer
3205 independent reflections
Absorption correction: numerical
(SADABS; Bruker, 2008)
1744 reflections with I > 2σ(I)
Tmin = 0.957, Tmax = 0.997Rint = 0.081
8408 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0540 restraints
wR(F2) = 0.104H atoms treated by a mixture of independent and constrained refinement
S = 1.00Δρmax = 0.24 e Å3
3205 reflectionsΔρmin = 0.26 e Å3
261 parameters
Special details top

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
C180.0042 (3)0.33919 (14)0.9353 (3)0.0216 (7)
C140.2656 (2)0.11015 (14)0.9369 (3)0.0202 (7)
H140.27530.11040.83560.024*
C150.1482 (3)0.06320 (16)0.9696 (3)0.0229 (7)
C170.1516 (3)0.23277 (15)0.8999 (3)0.0203 (7)
C130.3918 (2)0.07796 (15)0.9989 (3)0.0214 (7)
H130.39190.02540.98640.026*
C110.5535 (3)0.10772 (16)0.7975 (3)0.0319 (8)
H110.50280.08420.73060.038*
C190.0347 (3)0.35150 (16)0.7993 (3)0.0296 (8)
H190.00540.32130.72880.035*
C70.5909 (3)0.14513 (15)1.0345 (3)0.0259 (7)
C200.1172 (3)0.40861 (16)0.7674 (3)0.0323 (8)
H200.14380.41700.67610.039*
C20.3348 (3)0.08065 (16)1.2646 (3)0.0330 (8)
H20.25980.05261.25380.040*
C40.4815 (3)0.14928 (17)1.4117 (3)0.0413 (9)
H40.50290.16761.49900.050*
C10.4133 (3)0.09618 (15)1.1518 (3)0.0236 (7)
C160.2473 (3)0.18896 (14)0.9832 (3)0.0202 (7)
H16A0.21930.18891.07940.024*
H16B0.33190.21280.98020.024*
C120.5141 (3)0.11031 (14)0.9341 (3)0.0231 (7)
C230.0407 (3)0.38466 (16)1.0388 (3)0.0341 (8)
H230.01580.37661.13080.041*
C210.1584 (3)0.45197 (17)0.8716 (4)0.0379 (9)
C30.3702 (3)0.10780 (17)1.3944 (3)0.0399 (9)
H30.31800.09781.47080.048*
C80.7078 (3)0.17802 (16)0.9971 (3)0.0346 (8)
H80.75910.20171.06330.042*
C90.7465 (3)0.17492 (17)0.8601 (4)0.0403 (9)
H90.82510.19620.83420.048*
C60.5273 (3)0.13700 (15)1.1689 (3)0.0280 (8)
C220.1219 (3)0.44173 (17)1.0068 (3)0.0441 (10)
H220.15140.47271.07600.053*
C100.6708 (3)0.14094 (17)0.7615 (3)0.0408 (9)
H100.69800.14010.66950.049*
C50.5615 (3)0.16381 (16)1.2995 (3)0.0371 (9)
H50.63730.19121.31120.045*
O30.13680 (18)0.22640 (10)0.77394 (19)0.0278 (5)
O20.15591 (18)0.00507 (11)1.0272 (2)0.0308 (5)
O10.0355 (2)0.09099 (11)0.9269 (2)0.0361 (6)
N10.0878 (2)0.28259 (13)0.9779 (2)0.0206 (6)
F10.23954 (19)0.50859 (10)0.83812 (19)0.0604 (6)
H1O0.038 (3)0.0582 (18)0.943 (3)0.086 (13)*
H1N0.106 (2)0.2840 (13)1.067 (3)0.025 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C180.0223 (17)0.0195 (18)0.0232 (17)0.0001 (14)0.0031 (14)0.0025 (14)
C140.0212 (17)0.0185 (17)0.0208 (16)0.0012 (13)0.0029 (13)0.0015 (13)
C150.0235 (18)0.0241 (19)0.0212 (16)0.0002 (15)0.0008 (14)0.0043 (15)
C170.0206 (17)0.0203 (18)0.0201 (17)0.0037 (14)0.0002 (14)0.0041 (14)
C130.0202 (17)0.0189 (17)0.0249 (17)0.0007 (13)0.0062 (14)0.0026 (14)
C110.0275 (19)0.033 (2)0.035 (2)0.0073 (16)0.0026 (16)0.0010 (16)
C190.0331 (19)0.0319 (19)0.0236 (18)0.0101 (16)0.0028 (15)0.0008 (15)
C70.0214 (17)0.0211 (18)0.0350 (19)0.0025 (14)0.0050 (16)0.0035 (15)
C200.036 (2)0.034 (2)0.0263 (18)0.0095 (17)0.0052 (16)0.0077 (16)
C20.0294 (19)0.036 (2)0.0334 (19)0.0054 (16)0.0049 (16)0.0091 (16)
C40.052 (2)0.043 (2)0.028 (2)0.0059 (19)0.0134 (19)0.0004 (17)
C10.0211 (17)0.0223 (18)0.0275 (18)0.0015 (14)0.0009 (15)0.0063 (14)
C160.0191 (17)0.0213 (17)0.0203 (16)0.0005 (13)0.0008 (13)0.0002 (13)
C120.0201 (17)0.0206 (17)0.0285 (18)0.0032 (13)0.0008 (15)0.0071 (14)
C230.050 (2)0.032 (2)0.0201 (17)0.0133 (17)0.0068 (16)0.0042 (15)
C210.035 (2)0.030 (2)0.048 (2)0.0173 (17)0.0076 (18)0.0156 (18)
C30.040 (2)0.053 (2)0.027 (2)0.0014 (18)0.0026 (17)0.0085 (17)
C80.0218 (18)0.036 (2)0.045 (2)0.0044 (15)0.0080 (17)0.0117 (17)
C90.0217 (19)0.044 (2)0.055 (2)0.0021 (16)0.0040 (19)0.0211 (19)
C60.0289 (19)0.0236 (19)0.0316 (19)0.0000 (15)0.0056 (16)0.0029 (15)
C220.066 (3)0.036 (2)0.031 (2)0.0247 (19)0.0153 (19)0.0060 (17)
C100.033 (2)0.049 (2)0.040 (2)0.0059 (18)0.0094 (18)0.0125 (19)
C50.033 (2)0.038 (2)0.040 (2)0.0025 (16)0.0096 (18)0.0042 (17)
O30.0411 (14)0.0281 (12)0.0141 (11)0.0038 (10)0.0010 (10)0.0011 (10)
O20.0260 (13)0.0231 (13)0.0430 (13)0.0037 (10)0.0082 (10)0.0084 (11)
O10.0187 (12)0.0319 (14)0.0576 (15)0.0008 (11)0.0042 (11)0.0148 (11)
N10.0266 (15)0.0235 (15)0.0116 (14)0.0062 (12)0.0018 (12)0.0010 (12)
F10.0747 (16)0.0495 (13)0.0572 (13)0.0380 (11)0.0059 (12)0.0156 (11)
Geometric parameters (Å, º) top
C18—C191.383 (4)C2—C11.385 (4)
C18—C231.385 (4)C2—C31.390 (4)
C18—N11.410 (3)C2—H20.9300
C14—C151.516 (3)C4—C31.380 (4)
C14—C131.535 (3)C4—C51.385 (4)
C14—C161.538 (3)C4—H40.9300
C14—H140.9800C1—C61.396 (4)
C15—O21.212 (3)C16—H16A0.9700
C15—O11.322 (3)C16—H16B0.9700
C17—O31.225 (3)C23—C221.377 (4)
C17—N11.359 (3)C23—H230.9300
C17—C161.497 (4)C21—C221.362 (4)
C13—C11.522 (4)C21—F11.373 (3)
C13—C121.522 (3)C3—H30.9300
C13—H130.9800C8—C91.380 (4)
C11—C121.378 (4)C8—H80.9300
C11—C101.391 (4)C9—C101.371 (4)
C11—H110.9300C9—H90.9300
C19—C201.384 (4)C6—C51.392 (4)
C19—H190.9300C22—H220.9300
C7—C81.390 (4)C10—H100.9300
C7—C121.396 (4)C5—H50.9300
C7—C61.458 (4)O1—H1O0.98 (4)
C20—C211.353 (4)N1—H1N0.88 (2)
C20—H200.9300
C19—C18—C23119.1 (3)C6—C1—C13110.3 (2)
C19—C18—N1124.5 (3)C17—C16—C14116.1 (2)
C23—C18—N1116.5 (3)C17—C16—H16A108.3
C15—C14—C13111.0 (2)C14—C16—H16A108.3
C15—C14—C16112.7 (2)C17—C16—H16B108.3
C13—C14—C16111.1 (2)C14—C16—H16B108.3
C15—C14—H14107.3H16A—C16—H16B107.4
C13—C14—H14107.3C11—C12—C7120.6 (3)
C16—C14—H14107.3C11—C12—C13128.6 (3)
O2—C15—O1122.7 (3)C7—C12—C13110.8 (2)
O2—C15—C14123.8 (3)C22—C23—C18120.5 (3)
O1—C15—C14113.5 (3)C22—C23—H23119.7
O3—C17—N1123.8 (3)C18—C23—H23119.7
O3—C17—C16123.5 (3)C20—C21—C22122.7 (3)
N1—C17—C16112.7 (2)C20—C21—F1118.0 (3)
C1—C13—C12101.3 (2)C22—C21—F1119.3 (3)
C1—C13—C14113.7 (2)C4—C3—C2121.1 (3)
C12—C13—C14112.1 (2)C4—C3—H3119.4
C1—C13—H13109.8C2—C3—H3119.4
C12—C13—H13109.8C9—C8—C7118.8 (3)
C14—C13—H13109.8C9—C8—H8120.6
C12—C11—C10118.7 (3)C7—C8—H8120.6
C12—C11—H11120.7C10—C9—C8121.0 (3)
C10—C11—H11120.7C10—C9—H9119.5
C18—C19—C20120.3 (3)C8—C9—H9119.5
C18—C19—H19119.9C5—C6—C1120.1 (3)
C20—C19—H19119.9C5—C6—C7130.7 (3)
C8—C7—C12120.1 (3)C1—C6—C7109.2 (3)
C8—C7—C6131.6 (3)C21—C22—C23118.6 (3)
C12—C7—C6108.3 (3)C21—C22—H22120.7
C21—C20—C19118.8 (3)C23—C22—H22120.7
C21—C20—H20120.6C9—C10—C11120.8 (3)
C19—C20—H20120.6C9—C10—H10119.6
C1—C2—C3118.7 (3)C11—C10—H10119.6
C1—C2—H2120.6C4—C5—C6119.2 (3)
C3—C2—H2120.6C4—C5—H5120.4
C3—C4—C5120.3 (3)C6—C5—H5120.4
C3—C4—H4119.9C15—O1—H1O112 (2)
C5—C4—H4119.9C17—N1—C18129.5 (2)
C2—C1—C6120.5 (3)C17—N1—H1N117.8 (17)
C2—C1—C13129.2 (3)C18—N1—H1N112.5 (17)
C13—C14—C15—O25.7 (4)C14—C13—C12—C7119.0 (3)
C16—C14—C15—O2131.0 (3)C19—C18—C23—C220.6 (5)
C13—C14—C15—O1175.6 (2)N1—C18—C23—C22179.5 (3)
C16—C14—C15—O150.3 (3)C19—C20—C21—C220.0 (5)
C15—C14—C13—C182.6 (3)C19—C20—C21—F1179.7 (3)
C16—C14—C13—C143.7 (3)C5—C4—C3—C20.9 (5)
C15—C14—C13—C12163.2 (2)C1—C2—C3—C40.2 (5)
C16—C14—C13—C1270.6 (3)C12—C7—C8—C90.6 (4)
C23—C18—C19—C200.2 (4)C6—C7—C8—C9177.5 (3)
N1—C18—C19—C20180.0 (3)C7—C8—C9—C100.8 (5)
C18—C19—C20—C210.2 (5)C2—C1—C6—C51.4 (4)
C3—C2—C1—C61.4 (4)C13—C1—C6—C5175.8 (3)
C3—C2—C1—C13175.2 (3)C2—C1—C6—C7179.9 (3)
C12—C13—C1—C2179.8 (3)C13—C1—C6—C72.9 (3)
C14—C13—C1—C259.7 (4)C8—C7—C6—C54.4 (5)
C12—C13—C1—C63.3 (3)C12—C7—C6—C5177.4 (3)
C14—C13—C1—C6117.1 (3)C8—C7—C6—C1177.1 (3)
O3—C17—C16—C1436.1 (4)C12—C7—C6—C11.1 (3)
N1—C17—C16—C14147.0 (2)C20—C21—C22—C230.5 (5)
C15—C14—C16—C1771.6 (3)F1—C21—C22—C23179.9 (3)
C13—C14—C16—C17163.1 (2)C18—C23—C22—C210.8 (5)
C10—C11—C12—C70.5 (4)C8—C9—C10—C110.9 (5)
C10—C11—C12—C13179.5 (3)C12—C11—C10—C90.7 (5)
C8—C7—C12—C110.4 (4)C3—C4—C5—C60.9 (5)
C6—C7—C12—C11178.1 (3)C1—C6—C5—C40.2 (4)
C8—C7—C12—C13179.6 (2)C7—C6—C5—C4178.6 (3)
C6—C7—C12—C131.1 (3)O3—C17—N1—C185.9 (5)
C1—C13—C12—C11176.4 (3)C16—C17—N1—C18171.1 (3)
C14—C13—C12—C1161.9 (4)C19—C18—N1—C174.0 (5)
C1—C13—C12—C72.6 (3)C23—C18—N1—C17176.1 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1O···O2i0.98 (4)1.71 (4)2.682 (3)175 (3)
N1—H1N···O3ii0.88 (2)2.02 (3)2.891 (3)172 (2)
Symmetry codes: (i) x, y, z+2; (ii) x, y+1/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC23H18FNO3
Mr375.38
Crystal system, space groupMonoclinic, P21/c
Temperature (K)296
a, b, c (Å)10.2048 (6), 18.5170 (11), 9.6164 (6)
β (°) 90.494 (4)
V3)1817.07 (19)
Z4
Radiation typeMo Kα
µ (mm1)0.10
Crystal size (mm)0.45 × 0.10 × 0.03
Data collection
DiffractometerBruker SMART APEXII CCD area-detector
diffractometer
Absorption correctionNumerical
(SADABS; Bruker, 2008)
Tmin, Tmax0.957, 0.997
No. of measured, independent and
observed [I > 2σ(I)] reflections
8408, 3205, 1744
Rint0.081
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.054, 0.104, 1.00
No. of reflections3205
No. of parameters261
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.24, 0.26

Computer programs: APEX2 (Bruker, 2007), SAINT (Bruker, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), SHELXTL (Sheldrick, 2008).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1O···O2i0.98 (4)1.71 (4)2.682 (3)175 (3)
N1—H1N···O3ii0.88 (2)2.02 (3)2.891 (3)172 (2)
Symmetry codes: (i) x, y, z+2; (ii) x, y+1/2, z+1/2.