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

Kaori Sakurai; Keiichi Noguchi; Koichiro Nishibe

doi:10.1107/S1600536810006057

. 2010 Feb 20;66(Pt 3):o655. doi: 10.1107/S1600536810006057

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

Kaori Sakurai ^a,^*, Keiichi Noguchi ^a, Koichiro Nishibe ^a

PMCID: PMC2983504 PMID: 21580406

Abstract

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.

Related literature

For related structures, see: Roh & Jeong (2000 ▶); Harrison (2007 ▶).

Experimental

Crystal data

C₂₈H₃₀N₄O₄
M _r = 486.56
Monoclinic,
a = 22.4514 (4) Å
b = 12.7128 (2) Å
c = 8.83183 (16) Å
β = 105.526 (1)°
V = 2428.80 (8) Å³
Z = 4
Cu Kα radiation
μ = 0.73 mm⁻¹
T = 193 K
0.45 × 0.25 × 0.10 mm

Data collection

Rigaku R-AXIS RAPID diffractometer
Absorption correction: numerical (ABSCOR; Higashi, 1999 ▶) T _min = 0.754, T _max = 0.929
19342 measured reflections
2235 independent reflections
2168 reflections with I > 2σ(I)
R _int = 0.022

Refinement

R[F ² > 2σ(F ²)] = 0.028
wR(F ²) = 0.072
S = 1.09
2235 reflections
328 parameters
2 restraints
H-atom parameters constrained
Δρ_max = 0.17 e Å⁻³
Δρ_min = −0.15 e Å⁻³

Data collection: PROCESS-AUTO (Rigaku, 1998 ▶); cell refinement: PROCESS-AUTO; data reduction: CrystalStructure (Rigaku/MSC, 2004 ▶); program(s) used to solve structure: SIR2004 (Burla et al., 2005 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810006057/fj2281sup1.cif

e-66-0o655-sup1.cif^{(25.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810006057/fj2281Isup2.hkl

e-66-0o655-Isup2.hkl^{(107.6KB, hkl)}

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
N2—H2⋯O3	0.88	1.97	2.623 (3)	130
N4—H4⋯N3ⁱ	0.88	2.26	2.961 (2)	137

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was funded by the Japan Science and Technology Agency (JST). Ipidacrine was generously provided by Professor Kazuo Nagasawa.

supplementary crystallographic information

Comment

The title compound (I) (Fig. 1) was obtained as a side product in the synthesis of ipidacrine urea derivatives.

In the biuret moiety of (I), there are two types of C—N bonds, both of which display a partial double bond character. Their bond lengths are between 1.47 Å (for typical C—N bonds) and 1.28 Å (for C═N bonds) (Allen et al. 1987). The terminal C1—N2 and C21—N4 bonds are shorter (1.340 (3) and 1.343 (3) Å) than the internal C1—N1 and C21–N1 bonds (1.429 (2) and 1.415 (3) Å). O3 is involved in the hydrogen bonding with H2, forming a six-membered ring, which is consistent with solid state structures of other biuret compounds (Harrison, 2007; Roh and Jeong, 2000). However, the biuret moiety of (I) is not completely planar as the dihedral angle for O3–C21–N1–C1 is 8.8 (3)°.

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 ¹H 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/CH₂Cl₂) 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. ¹H NMR (CDCl₃) δ 7.28 (d, J = 8.96 Hz, 4H), δ (d, J = 8.96 Hz, 4H), δ 3.82 (s, 1H), δ 3.10 (dd, J = 7.54 Hz, 2H), δ 2.94-3.00 (m, 4H), δ 2.71 (m, 2H), δ 2.18 (m, 2H), δ 1.87 (m, 4H). ESI-MS calcd for C₂₈H₃₁N₄O₄ (M+H⁺) 487.23, found 487.22.