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

Tetiana Matviiuk; Michel Baltas; Zoia Voitenko; Marian Gorichko; Christian Lherbet

doi:10.1107/S1600536813013779

. 2013 May 25;69(Pt 6):o963. doi: 10.1107/S1600536813013779

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

Tetiana Matviiuk ^a, Michel Baltas ^b, Zoia Voitenko ^a, Marian Gorichko ^a,^*, Christian Lherbet ^c

PMCID: PMC3685102 PMID: 23795121

Abstract

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 π-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.

Related literature

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

Crystal data

C₂₃H₁₈FNO₃
M _r = 375.38
Monoclinic,
a = 10.2048 (6) Å
b = 18.5170 (11) Å
c = 9.6164 (6) Å
β = 90.494 (4)°
V = 1817.07 (19) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 296 K
0.45 × 0.10 × 0.03 mm

Data collection

Bruker SMART APEXII CCD area-detector diffractometer
Absorption correction: numerical (SADABS; Bruker, 2008 ▶) T _min = 0.957, T _max = 0.997
8408 measured reflections
3205 independent reflections
1744 reflections with I > 2σ(I)
R _int = 0.081

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.104
S = 1.00
3205 reflections
261 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.24 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: APEX2 (Bruker, 2007 ▶); cell refinement: SAINT (Bruker, 2007 ▶); data reduction: SAINT; 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.

Supplementary Material

Click here for additional data file.^{(27.5KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813013779/mw2107sup1.cif

e-69-0o963-sup1.cif^{(27.5KB, cif)}

Click here for additional data file.^{(154KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813013779/mw2107Isup2.hkl

e-69-0o963-Isup2.hkl^{(154KB, hkl)}

Click here for additional data file.^{(7KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813013779/mw2107Isup3.cml

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
O1—H1O⋯O2ⁱ	0.98 (4)	1.71 (4)	2.682 (3)	175 (3)
N1—H1N⋯O3ⁱⁱ	0.88 (2)	2.02 (3)	2.891 (3)	172 (2)

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Symmetry codes: (i) Inline graphic ; (ii) .

supplementary crystallographic information

Comment

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).

Experimental

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.