Bis{(E)-3-[(diethylmethylammonio)methyl]-N-[3-(N,N-dimethylsulfamoyl)-1-methylpyridin-4-ylidene]-4-methoxyanilinium} tetraiodide pentahydrate

The title compound, 2C21H34N4O3S2+·4I−·5H2O, was prepared exclusively as the E isomer by methylation of the corresponding N-phenylpyridin-4-amine. There are two symmetry-independent molecules in the asymmetric unit with no significant differences in bond lengths and angles. The aromatic rings are not coplanar with the pyridin-4-imine groups, as indicated by the C—N—C—C torsion angles of 47.7 (7) and 132.6 (5)°.

The title compound, 2C 21 H 34 N 4 O 3 S 2+ Á4I À Á5H 2 O, was prepared exclusively as the E isomer by methylation of the corresponding N-phenylpyridin-4-amine. There are two symmetryindependent molecules in the asymmetric unit with no significant differences in bond lengths and angles. The aromatic rings are not coplanar with the pyridin-4-imine groups, as indicated by the C-N-C-C torsion angles of 47.7 (7) and 132.6 (5) . H atoms treated by a mixture of independent and constrained refinement Á max = 2.07 e Å À3 Á min = À1.42 e Å À3 Table 1 Hydrogen-bond geometry (Å , ).

Comment
Malaria is accounted as one of the major diseases worldwide, and for which few efficient drugs are known today [Bjorkman and Bhattarai, 2005]. 4(1H)-Pyridones are currently being developed as important and potential antimalarial agents, capable of inhibiting the bc 1 complex, at the oxidation site (Q o site) level in the Plasmodium falciparum mitochondrion [Yeates et al., 2008]. As part of our project towards the synthesis of 4(1H)-pyridone bioisosteric scaffolds, the (1H-pyridin-4-ylidene)amine scaffold was studied.
The title compound was prepared by reaction of the corresponding N-phenylpyridin-4-amine with methyl iodide. Interestingly, only the E isomer of the compound was obtained, as it was previously observed for amodiaquine analogues [Lopes et al., 2004]. There are two symmetry-independent molecules in the asymmetric unit with no significant differences in bond lengths and angles. The observed imine bond distances C4-N14 and C44-N54 are longer than the expected by ca 0.035 Å [Wang et al., 2008 andDjedouani et al., 2008], a consequence of the imine group being protonated. The aromatic rings are not coplanar relatively to the pyridin-4-imine moieties, as indicated by the C4-N14-C15-C16 and C44-N54-C55-C56 dihedral angles of 47.7 (7)° and 132.6 (5)°, respectively. The molecules are hydrogen-bonded through the imine nitrogen atoms at N14 and N54, acting as donors towards the sulfonyl oxygen atoms O9 and O19 of each sulfonamide moiety, respectively. The (1H-pyridin-4-ylidene)amine scaffold is nearly planar and the C5-C4-N14-C15 dihedral angle is 7.9 (7)° for one of the molecules, whereas the C43-C44-N54-C55 dihedral angle on the other molecule is -14.1 (7)°.

Experimental
The title compound was prepared at room temperature by reacting 2-[(diethylamino)methyl]-4-(pyridin-4-ylamino)phenol with methyl iodide in the presence of NaH in DMF. Crystals were grown from water.

Refinement
The hydroxy H atoms for the water solvent molecules were initially located in a difference Fourier map, but their distances were constrained with DFIX at 0.9 Å from the O atom and with DANG at 2.5 Å from the other H water atom. The hydrogen atoms linked to the charged N14 and N54 atoms were located in a difference Fourier map, but the distances N-H were constrained at 0.9 Å, in order to get the refinement stabilization. The rest of the H atoms were positioned geometrically and included as riding atoms with C-H = 0.95 or 0.98 Å and U iso (H)= 1.2 or 1.5 times U eq (C).

Special details
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The 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 > 2σ(F 2 ) is used only for calculating Rfactors(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.