2-{(E)-4-[4-(Trifluoro­meth­yl)phen­oxy]but-2-en­yloxy}phenyl N-methyl­carbamate

Hong-Ju Ma; Meng-Han Xu; Jian-Hua Zhang; Jian-Hong Li; Jun Ning

doi:10.1107/S1600536813001347

. 2013 Feb 2;69(Pt 3):o326–o327. doi: 10.1107/S1600536813001347

2-{(E)-4-[4-(Trifluoromethyl)phenoxy]but-2-enyloxy}phenyl N-methylcarbamate

Hong-Ju Ma ^a, Meng-Han Xu ^a, Jian-Hua Zhang ^a, Jian-Hong Li ^a, Jun Ning ^b,^*

PMCID: PMC3588498 PMID: 23476524

Abstract

In the title compound, C₁₉H₁₈F₃NO₄, which was designed and synthesized as a dual-site inhibitor of insect AChE (acetylcholinesterase), the dihedral angle between the methylcarbamate group and the benzene ring is 72.47 (6)°. In the crystal, inversion dimers are linked by pairs of N—H⋯O hydrogen bonds.

Related literature

For background to multivalent ligand-receptor interactions and their pharmaceutical applications, see: Carlier et al. (1999 ▶); Hu et al. (2002 ▶); Kitov et al. (2000 ▶); Kopytek et al. (2000 ▶); Kryger et al. (1999 ▶); Lee & Lee (1995 ▶); Luedtke et al. (2003 ▶); Mammen et al. (1998 ▶); Pang et al. (1996 ▶). For agrochemical applications of the cluster effect, see: Ma et al. (2010 ▶); Zhao et al. (2008 ▶, 2009 ▶). For the structure of AChE from Torpedo californica (TcAChe), see: Sussman et al. (1991 ▶); Harel et al. (1993 ▶).

Experimental

Crystal data

C₁₉H₁₈F₃NO₄
M _r = 381.34
Monoclinic,
a = 12.413 (3) Å
b = 9.3936 (19) Å
c = 16.202 (3) Å
β = 111.65 (3)°
V = 1755.9 (6) Å³
Z = 4
Cu Kα radiation
μ = 1.05 mm⁻¹
T = 173 K
0.47 × 0.30 × 0.25 mm

Data collection

Rigaku R-AXIS RAPID IP area-detector diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.639, T _max = 0.780
11613 measured reflections
3163 independent reflections
2615 reflections with I > 2σ(I)
R _int = 0.033

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.107
S = 1.07
3163 reflections
274 parameters
60 restraints
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Data collection: RAPID-AUTO (Rigaku 2001 ▶); cell refinement: RAPID-AUTO; data reduction: RAPID-AUTO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: XP in SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Click here for additional data file.^{(21.4KB, cif)}

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536813001347/mw2102sup1.cif

e-69-0o326-sup1.cif^{(21.4KB, cif)}

Click here for additional data file.^{(155.2KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813001347/mw2102Isup2.hkl

e-69-0o326-Isup2.hkl^{(155.2KB, hkl)}

Click here for additional data file.^{(6.9KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813001347/mw2102Isup3.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
N1—H1⋯O2ⁱ	0.88	2.22	3.072 (2)	163

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was partially supported by the National Natural Science Foundation of China (program No. 31201554), the China Postdoctoral Science Foundation (program No. 20110491174) and the Fundamental Research Funds for the Central Universities (program No. 2011QC086).

supplementary crystallographic information

Comment

Multivalent ligand-receptor interactions, known as the cluster effect, are defined as specific simultaneous associations of multiple ligands present on a molecular construct that bind to multiple receptors presented on a biological entity (Mammen et al., 1998; Lee et al., 1995). In biological systems, multivalent ligands often possess increased functional affinity for their targets compared with that of monovalent ligands (Kitov et al., 2000; Kopytek et al., 2000; Luedtke et al., 2003). Acetylcholinesterase (AChE; EC 3.1.1.7) is a key enzyme in the nervous system, terminating nerve impulses by catalyzing the hydrolysis of the neurotransmitter acetylcholine. X-ray crystallographic structural analysis of the AChE from Torpedo californica (TcAChe) has demonstrated that the active site lies near the bottom of a deep, narrow gorge that reaches half way into the protein and that 14 aromatic residues line a substantial portion of the surface of the gorge (Sussman et al., 1991). This cavity was named the 'active site gorge' with peripheral sites existing at the gorge mouth and Trp279 being the main site (Harel et al., 1993). On the basis of the structure of AChE, many potential dual-site binding inhibitors of AChE have been synthesized (Pang et al., 1996; Carlier et al., 1999; Hu et al., 2002) and demonstrated in drugs in order to treat or alleviate Alzheimer's disease (Kryger et al., 1999). In the area of pesticide, dual- or multiple-site inhibitors of insect AChE were designed and synthesized in our research group (Zhao et al.., 2008; Zhao et al., 2009). Recently, we synthesized novel carbamate derivatives as potential dual-binding site acetylcholinesterase inhibitors (Ma et al., 2010). The crystal structure of the title compound (I) is shown in Fig. 1.

Experimental

2-((E)-4-(4-(trifluoromethyl)phenoxy)but-2-enyloxy)phenyl methylcarbamate (0.2 g) was dissolved in 95% ethanol (50 ml) at room temperature. Colorless crystals of compound (I) were obtained through slow evaporation after two weeks.