3-(2,3,5,6,7,8-Hexahydro-1H-cyclopenta[b]quinolin-9-yl)-1,5-bis(4-methoxyphenyl)biuret

Ipidacrine (2,3,5,6,7,8-hexahydro-1H-cyclopenta[b]quinolin-9-amine) was reacted with 4-methoxyphenyl isocyanate to give the title compound, C28H30N4O4. An intramolecular N—H⋯O hydrogen bond results in an essentially planar [r.m.s. deviation from the mean plane is 0.126 (1) Å] conformation for the biuret unit. The central ring of the quinoline unit is twisted by 78.2 (1)° with respect to the biuret mean plane, whereas the two 4-methoxybenzene rings are twisted out of this plane by 24.3 (1)° and 48.5 (1)°, resulting in an overall propeller-like structure. An intermolecular N—H⋯N hydrogen bond between the biuret NH atom and the quinoline ring nitrogen defines the crystal packing.

quinolin-9-amine) was reacted with 4-methoxyphenyl isocyanate to give the title compound, C 28 H 30 N 4 O 4 . An intramolecular N-HÁ Á ÁO hydrogen bond results in an essentially planar [r.m.s. deviation from the mean plane is 0.126 (1) Å ] conformation for the biuret unit. The central ring of the quinoline unit is twisted by 78.2 (1) with respect to the biuret mean plane, whereas the two 4-methoxybenzene rings are twisted out of this plane by 24.3 (1) and 48.5 (1) , resulting in an overall propeller-like structure. An intermolecular N-HÁ Á ÁN hydrogen bond between the biuret NH atom and the quinoline ring nitrogen defines the crystal packing.
Due to the partial double bond character of the terminal biuret C-N bonds, A 1,3 strain is incurred between the buiret carbonyl groups and the bulky p-methoxyphenyl rings. These interactions cause the p-methoxyphenyl rings to twist out of plane with respect to the biuret moiety by approximately 24.3 (1)° and 48.5 (1)°. The bulkier quinoline moiety is substituted at N1, which forms a partial double bond with both C1 and C2. It develops A 1,3 strain with two groups, one with p-methoxyphenylamino group, the other with one of the biuret carbonyl group. As a consequence, it is twisted close to perpendicular (78.2 (1)°) to the buiret plane. The steric congestion among the three aromatic substituents around the biuret moiety drives (I) to adopt an overall propeller-like structure.
In the present crystal structure for the title compound (I), these two p-methoxyphenyl rings are not geometrically equivalent. However, the 1 H NMR spectrum of (I) shows only one set of peaks for the protons of a p-methoxyphenyl group. This observation suggests that the hydrogen bonds for O1···H4 and O3···H2 are in fast exchange in solution and that the rotational barrier around the internal C-N bond of the biuret group is not significant under ambient condition. Since the biuret moiety deviates slightly from a planar conformation, there is helicity along the biuret backbone (N2-C1-N2-C21-N4). The interconversion of the two hydrogen bonding pairs (between O1···H4 and O3···H2) represents the interconversion of two corresponding helical conformations of (I), making the molecule dynamically racemic in solution.

Experimental
The title compound was prepared by reacting ipidacrine (20.0 mg, 0.11 mmol) and 4-methoxyphenyl isocyanate (23.9 mg, 0.16 mmol) in dichloromethane (0.5 ml) at room temperature for 18 h. The resultant reaction mixture was concentrated in vacuo and was purified by flash chromatography (2 % MeOH/CH 2 Cl 2 ) to afford the title compound I (18.1 mg; 33.8 % yield). Crystals suitable for X-ray diffraction were obtained by slow evaporation of the solution of (I) in MeCN. 1  The value of the absolute structure parameter is meaningless because of its large s.u. value (Flack's x = -0.01 (14)). Therefore, the merging of Friedel pair data was performed before the final refinement cycles. The methylene, methyl and phenyl H atoms were positioned using the HFIX 23, HFIX 137 and HFIX 43 instructions, with C-H = 0.99, 0.98 and 0.95 Å, respectively. In addition, the amide H atoms were positioned using the HFIX 43 instructions, with N-H = 0.88 Å. These C-and N-bound H atoms were also refined as a riding model, with U iso (H) = 1.2U eq (C or N). Fig. 1. The molecular structure of (I). The ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres with arbitrary radii. The hydrogen bond is indicated by a dashed line.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 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.