(5E)-1-Benzyl-5-(3,3,3-tri­chloro-2-oxo­propyl­idene)pyrrolidin-2-one

Alex Fabiani Claro Flores; Darlene Correia Flores; Juliano Rosa de Menezes Vicenti; Lucas Pizzuti; Patrick Teixeira Campos

doi:10.1107/S160053681400751X

. 2014 May 3;70(Pt 6):o629–o630. doi: 10.1107/S160053681400751X

(5E)-1-Benzyl-5-(3,3,3-trichloro-2-oxopropylidene)pyrrolidin-2-one

Alex Fabiani Claro Flores ^a,^*, Darlene Correia Flores ^a, Juliano Rosa de Menezes Vicenti ^a, Lucas Pizzuti ^b, Patrick Teixeira Campos ^c

PMCID: PMC4051069 PMID: 24940220

Abstract

In the crystal structure of the title compound, C₁₄H₁₂Cl₃NO₂, no classical hydrogen-bonding interactions are observed. The methylene fragments of the benzyl groups participate in non-classic hydrogen-bond interactions with the carbonyl O atoms of neighboring molecules, generating co-operative centrosymmetric dimers with R ₅ ⁵(10) ring motifs. The overall molecular arrangement in the unit cell seems to be highly influenced by secondary non-covalent weak C—Cl⋯π [Cl⋯Cg(phenyl ring) = 3.732 (2) Å] and C—O⋯π [O⋯Cg(pyrrolidine ring) = 2.985 (2) Å] contacts.

Related literature

For the synthesis of the title compound, see: Flores et al. (2008 ▶). For pharmacological effects, see: Van der Schyf et al. (2006 ▶). For non-classical weak contacts, see: Irving & Irving (1994 ▶); Bissantz et al. (2010 ▶). For related structures, see: Bandeira et al. (2013 ▶); de Oliveira et al. (2012 ▶); de Bittencourt et al. (2014 ▶).

Experimental

Crystal data

C₁₄H₁₂Cl₃NO₂
M _r = 332.60
Monoclinic,
a = 15.7822 (5) Å
b = 5.8465 (2) Å
c = 17.4107 (5) Å
β = 105.885 (1)°
V = 1545.15 (8) Å³
Z = 4
Mo Kα radiation
μ = 0.59 mm⁻¹
T = 293 K
0.83 × 0.23 × 0.19 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: gaussian (XPREP; Bruker, 2009 ▶) T _min = 0.814, T _max = 1.000
21458 measured reflections
5069 independent reflections
2436 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.054
wR(F ²) = 0.217
S = 1.00
5069 reflections
181 parameters
H-atom parameters constrained
Δρ_max = 0.43 e Å⁻³
Δρ_min = −0.51 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: DIAMOND (Brandenburg, 2006 ▶); software used to prepare material for publication: publCIF (Westrip, 2010 ▶).

Supplementary Material

Crystal structure: contains datablock(s) I, New_Global_Publ_Block. DOI: 10.1107/S160053681400751X/zq2220sup1.cif

e-70-0o629-sup1.cif^{(18KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681400751X/zq2220Isup2.hkl

e-70-0o629-Isup2.hkl^{(243.3KB, hkl)}

Click here for additional data file.^{(5.2KB, cml)}

Supporting information file. DOI: 10.1107/S160053681400751X/zq2220Isup3.cml

CCDC reference: 740177

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C8—H82⋯O71ⁱ	0.97	2.38	3.292 (3)	156

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors acknowledge the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Universal grant 6577818477962764–01), the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES-PROEX) and the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS, PqG grant 1016236) for financial support.

supplementary crystallographic information

1. Comment

Pyrrolidin-2-ones have received considerable attention due to their activity in CNS as nootropic drugs. Piracetam-like nootropics revert amnesia induced by scopolamine and other amnesing drugs, electroconvulsive shock and hypoxia with an unknown mechanism. In general, they show no affinity for the most important central receptors, but are able to modulate the action of these most important central neurotransmitters, in particular acetylcholine and glutamate. Extensive study of the modes of action of the 2-pyrrolidinones has revealed various pharmacological effects, with striking differences between drugs (Van der Schyf et al., 2006). This work is a continuation of the research on the synthesis of 1-[alkyl(aryl)]-5-(3,3,3-trihalo-2-oxopropylidene)pyrrolidin-2-nes (Flores et al., 2008). In the crystal structure of the title compound, C₁₄H₁₂O₂NCl₃ (Fig. 1), no classic hydrogen bonds are observed. There is a non-classic intramolecular hydrogen bond with a distance C8—H82···O71 of 2.442 Å, generating a S(5) ring motif (de Bittencourt et al., 2014). The molecule possesses two sites revealing an interesting geometric conformation: the plane defined by the aromatic ring (r.m.s. of 0.0032 Å) revealed a dihedral angle of 87.03 (8)° with respect to the second plane formed by C1/C2/O21/C3/C4/C5/C6/C7/N1/C8/O71 atoms (r.m.s. of 0.0978 Å; Bandeira et al., 2013; de Oliveira et al., 2012). This almost orthogonal configuration (Fig. 2) seems to be related with the crystal packing. In this context, the CH₂ fragment of the benzyl group participates in non-classic hydrogen bonding with carbonyl oxygen of the neighbor molecules. This feature generates co-operative centrosymmetric dimers related through inversion centers, displaying C8ⁱⁱ—H82ⁱⁱ···O71ⁱ distances of 2.382 Å in a R₅⁵(10) ring fashion (de Bittencourt et al., 2014). The overall molecular arrangement in the unit cell (Fig. 3) seems to be highly influenced by weak interactions, where O21ⁱⁱⁱ are clearly pointing to C(1) (2.985 Å), related to the centroid of the neighbor ring formed by C4ⁱⁱ/C5ⁱⁱ/C6ⁱⁱ/C7ⁱⁱ/N1ⁱⁱ atoms. Similarly, the centroid C(2) of the ring formed by C9^iv/C10^iv/C11^iv/C12^iv/C13^iv/C14^iv atoms from the benzyl fragment presented directional long range interactions with adjacent Cl11ⁱⁱ atoms (Irving & Irving, 1994; Bissantz et al., 2010), with distances of 3.732 Å (symmetry codes: (i) –x + 3/2, y + 1/2, –z + 3/2; (ii) x + 1/2, –y + 3/2, z–1/2; (iii) –x + 1, –y + 1, –z + 1; (iv) x, y + 1, z–1).

2. Experimental

To a stirred solution of methyl 7,7,7-trichloro-4-methoxy-6-oxo-3-heptenoate (5 mmol, 1.52 g) in CHCl₃ (5 ml) kept at 25 °C, was added benzylamine (Aldrich, 185701, 5.1 mmol, 0.58 ml) in CHCl₃ (5 ml). The mixture was stirred at 25 °C for 2 h. Then the solvent was evaporated and residue was dried under vacuum. The brown amorphous solid was recrystallized in hexane to furnish yellowish needles with 94% yield. M.p. 88 - 89°C. ¹H NMR (400 MHz, CDCl₃/TMS): δ 2.72 (m, 2H, H3), 3.34 (m, 2H, H4), 4.8 (s, 2H, H9), 6.2 (s, 1H, H6), 7.3 (m, 5H, Ph) p.p.m. ¹³C NMR (100 MHz, CDCl₃): 26.1, 27.5, 44.6, 91.7, 97.1, 127.6, 128.1, 128.9, 134.1, 166.4, 177.1, 180 p.p.m. Crystals were grown from a diluted hexane solution at room temperature.