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

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.

In the title compound, C 19 H 18 F 3 NO 4 , 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-HÁ Á ÁO hydrogen bonds.

2-{(E)-4-[4-(Trifluoromethyl)phenoxy]but-2-enyloxy}phenyl N-methylcarbamate
Hong-Ju Ma, Meng-Han Xu, Jian-Hua Zhang, Jian-Hong Li and Jun Ning 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.

Refinement
The trifluoromethyl group showed orientational disorder with two resolved alternative sites which were refined independently leading to a 71:29 occupancy ratio. All non-hydrogen atoms were refined with anisotropic displacement parameters. The carbon-bound H atoms were placed at calculated positions, with C-H = 0.93 -0.98 Å, and were included in the refinement in the riding model approximation with Uiso(H) set to 1.2 -1.5Ueq(C).  The molecular structure of the title compound showing 50% probability displacement ellipsoids and the atom-numbering scheme.

Special details
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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 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 (Å 2 )
x y z U iso */U eq Occ. (