2-Amino-5-(3,4-dimethoxy­benzyl­idene)-1-methyl­imidazol-4(5H)-one N,N-dimethyl­formamide monosolvate

The crystal structure of the title compound, C₁₃H₁₅N₃O₃·C₃H₇NO, was determined as part of a larger project focusing on creatinine derivatives as potential pharmaceuticals. The mol­ecule is essentially planar, in part because of intra­molecular hydrogen bonding. Inversion-related pairs of mol­ecules result from inter­molecular hydrogen bonding. The π systems of 2-amino-5-(3,4-dimethoxy­benzyl­idene)-1-methyl­imidazol-4(5H)-one and an inversion-related mol­ecule over­lap slightly, indicating a small amount of π–π stacking. Bond lengths, angles and torsion angles are consistent with similar structures, except in the imidazolone ring near the doubly bonded C atom, where significant differences occur.

S1. Comment

As part of a larger project focusing on creatinine derivatives as potential pharmaceuticals, the crystal structure of the title compound, (I) or ADBMI.DMF, was determined (Fig. 1). Intramolecular hydrogen bonding was observed between atoms O4 and H15A, O3 and H3, and O4 and H3B (Table 2, Fig. 1). A search of the Cambridge Structural Database (CSD, Version?; Allen, 2002) for structures similar to the seven-membered ring containing atoms O3 and H3, using the PLATON criteria for hydrogen bonding (Spek, 2009), gave 154 results, showing that aryl H atoms undergoing hydrogen bonding with carbonyl O atoms have been observed many times.

A computational evaluation was performed on ADBMI to investigate aryl hydrogen bonding further. Two rotamers (about the C4—C9 bond) of ADBMI were computed (rotamer A with atom H3 connected to atom O3, and rotamer B with atom H5 connected to atom O3), with the A conformation (as determined crystallographically) preferred. Two transition states were computed between the two rotamers with a barrier energy of 6.0 kcal mol^-1 (1 kcal mol^-1 = 4.184 kJ mol^-1) above the A rotamer. Two interactions exist between lone pairs and the C—H antibonding orbital in each rotamer between atoms O3 and H3, one with the sp-hybridized lone pair on O3 and one with the unhybridized lone pair. These interactions give total energies of 11.2 (rotamer A) and 8.4 kcal mol^-1 (rotamer B). The total energy of the A rotamer is approximately 92% of that of a water dimer (12.2 kcal mol^-1). Natural atomic charges were computed for atoms O3 and H3/H5 of each rotamer. These charges are -0.61 and 0.30 e, respectively, in rotamer A, and -0.61 and 0.29 e, respectively, in rotamer B. Utilizing these computational quantum molecular calculations in addition to the PLATON criteria for hydrogen bonding, it is concluded that the O3—H3 interaction is at least a weak hydrogen bond.

This hydrogen bond has an effect on the conformation of the compound within the crystalline and gas phase structures and may influence any possible in vivo properties of ADBMI, since rotation about the C4—C9 bond is restricted [C3—C4—C9—C10 = -3.4 (7)°]. Intermolecular hydrogen bonding is also observed with an inversion-related molecule at (2 - x, 1 - y, -z). The combination of these two inversion-related structures leads to interpenetrating non-coplanar planes throughout the crystal structure. The C14═O4···H3A angle (114°) is consistent with sp² hybridization on atom O4.

Excluding the H atoms, the molecular planarities for the entire structure of (I), the non-solvated molecule (ADBMI) and the DMF portion of the structure were determined. The r.m.s. values for these portions are 0.171, 0.067 and 0.003 Å, respectively, which shows the high degree of planarity in (I). The distance between the least-squares plane of ADBMI and that of a different inversion-related molecule at (1 - x, 1 - y, -z) was calculated to be 3.48 (7) Å. The distance between the centroids of the five-membered ring of ADBMI (Cg1B) and the six-membered ring of the inversion-related molecule (Cg1A) was calculated to be 3.763 Å. The N2A—Cg1B—Cg1A angle was calculated to be 69.7°. A perpendicular view of ADBMI and its inversion-related molecule showed an approximately 20% ring overlap (Pauling, 1960). The small difference between the least-squares plane distance and the centroid-to-centroid distance (0.283 Å) indicates only a small amount of shifting of the inversion-related molecule.

The two methoxy groups not only point in opposite directions, as would be expected (Ternay, 1976), but are essentially coplanar with the phenyl ring. Torsion angles for the dimethoxy portion of the molecule [C7—O2—C2—C1 = -171.2 (4)° and C8—O1—C1—C2 = 175.9 (3)°] are similar to the corresponding angles in the structure of 3,4-dimethoxyphenylacetic acid [175.6 (1) and 170.4 (1)°; Chopra et al., 2003].

The O3—C11, C10—C11, N2—C12 and C12—N1 bond lengths are within 3σ of those of creatinine (Bell et al., 1995; Allen, 2002). However, the N2—C10 and N1—C11 bond lengths are very different, with differences of 11.25σ and 6.88σ, respectively. These bond-length differences can be attributed to the fact that creatinine has two H atoms attached to atom C10, while in (I) atom C10, being doubly bonded to atom C9, has just one H atom. The plane angles in this region follow the same trend, with the angles changing around atom C10.

The same portion of the structure was also compared with 3-(2-amino-1-methyl-4-oxo-4,5-dihydro-1H-imidazol-5-yl)-3-hydroxyindolin-2-one monohydrate (AMIH; Penthala et al., 2009), a compound that has a portion very similar to the creatinine portion of ADBMI. For this compound, a similar pattern of bond lengths and angles emerged around atom C10 because of the absence of the double bond in AMIH. Another pattern noted is the change in the N1—C12 and N1—C11 bond lengths (3.05σ and 4.50σ, respectively). This can be attributed to some contribution of the tautomeric forms of AMIH, which would cause differences in the bond lengths, leading to larger differences between (I) and AMIH. When accounting for this, it can be noted that (I) follows (within 3σ) the pattern of bond lengths exhibited in creatinine and AMIH.

S2. Experimental

ADBMI was synthesized by coupling creatinine with 3,4-dimethoxybenzaldehyde to afford the desired arylidene in moderate yield (Wållberg et al., 2006; Johnson et al., 2006). Crystals of (I) were grown by slow vapor diffusion of diethyl ether into a solution of ADBMI in DMF. Geometries were computationally optimized in the gas phase using the M05-2X level of density functional theory (Zhao & Truhlar, 2006) with the 6-31+G(d,p) basis set (Hehre et al., 1972) using GAUSSIAN03 (Frisch et al., 2003). Natural bond orbital analysis (Weinhold, 1998; Weinhold & Landis, 2005) was used to generate localized orbitals, to quantify interactions between orbitals and to determine atomic charges. The crystal used was coated with Paratone-N.

S3. Refinement

The approximate positions of all of the H atoms were first obtained from a difference map. H atoms were then placed in ideal positions and refined as riding atoms, with rigid rotating groups for methyl H. No disordered H atom was observed. Bond lengths were constrained at C—H = 0.93 Å for aromatic and allyl C—H, 0.96 Å for methyl C—H and 0.97 Å for ethylinic C—H, and at N—H = 0.86 Å for N—H. U_iso(H) = 1.5U_eq(C) for methyl H and 1.2U_eq(C,N) for all other H.

In the final stages of refinement, a few very small or negative F_o values were deemed to be in strong disagreement with their F_c values. The 15 reflections were eliminated from the final refinement.

The percentage decay of the three standards was calculated as the average of their σ(I) values.

Computing details

Data collection: XSCANS (Bruker, 1996); cell refinement: XSCANS (Bruker, 1996); data reduction: XSCANS (Bruker, 1996); program(s) used to solve structure: SHELXS86 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL/PC (Sheldrick, 2008); software used to prepare material for publication: SHELXTL/PC (Sheldrick, 2008) and SHELXL97 (Sheldrick, 2008).

Figures

Fig. 1. The asymmetric unit of (I), showing the atom-numbering scheme and the inversion-related molecule at (2 - x, 1 - y, -z). Displacement ellipsoids are drawn at the 50% probability level. Only H atoms involved in hydrogen bonding and other H atoms attached to donor atoms are shown. Dashed lines indicate hydrogen bonds.

2-Amino-5-(3,4-dimethoxybenzylidene)-1-methylimidazol-4(5H)-one N,N-dimethylformamide monosolvate

Crystal data

C13H15N3O3·C3H7NO	F(000) = 712
Mr = 334.38	Dx = 1.315 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 66 reflections
a = 11.617 (3) Å	θ = 3.9–12.5°
b = 17.2235 (16) Å	µ = 0.10 mm^−1
c = 9.062 (1) Å	T = 293 K
β = 111.327 (10)°	Parallelpiped, yellow
V = 1689.0 (5) Å^3	0.41 × 0.40 × 0.23 mm
Z = 4

Data collection

Bruker P4 diffractometer	Rint = 0.055
Radiation source: normal-focus sealed tube	θmax = 25.3°, θmin = 1.9°
Graphite monochromator	h = −13→13
θ/2θ scans	k = −20→1
3866 measured reflections	l = −10→1
3009 independent reflections	3 standard reflections every 100 reflections
1192 reflections with I > 2σ(I)	intensity decay: 2.3%

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.057	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.144	H-atom parameters constrained
S = 0.97	w = 1/[σ^2(Fo^2) + (0.0511P)^2] where P = (Fo^2 + 2Fc^2)/3
3009 reflections	(Δ/σ)max < 0.001
217 parameters	Δρmax = 0.15 e Å^−3
0 restraints	Δρmin = −0.15 e Å^−3

Special details

Experimental. Crystal was coated with Paratone-N.

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 cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors (gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² 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 (Ų)

	x	y	z	Uiso*/Ueq
O1	0.3185 (2)	0.65076 (14)	0.4163 (4)	0.0749 (9)
O2	0.4999 (3)	0.71593 (15)	0.3680 (4)	0.0814 (10)
O3	0.7639 (2)	0.61403 (15)	0.1462 (3)	0.0669 (8)
N1	0.8701 (3)	0.52132 (17)	0.0647 (4)	0.0525 (8)
N2	0.7628 (3)	0.41487 (16)	0.0841 (4)	0.0502 (8)
N3	0.9282 (3)	0.40176 (17)	−0.0057 (4)	0.0617 (10)
H3A	0.9867	0.4235	−0.0276	0.074*
H3B	0.9170	0.3524	−0.0172	0.074*
C1	0.3856 (3)	0.6035 (2)	0.3583 (5)	0.0534 (10)
C2	0.4849 (4)	0.6383 (2)	0.3305 (5)	0.0535 (11)
C3	0.5587 (3)	0.5964 (2)	0.2720 (4)	0.0513 (10)
H3	0.6235	0.6207	0.2532	0.062*
C4	0.5368 (3)	0.5170 (2)	0.2401 (4)	0.0466 (10)
C5	0.4389 (3)	0.4841 (2)	0.2692 (5)	0.0576 (11)
H5	0.4232	0.4314	0.2492	0.069*
C6	0.3637 (3)	0.5263 (2)	0.3276 (5)	0.0604 (11)
H6	0.2982	0.5022	0.3450	0.072*
C7	0.5868 (4)	0.7571 (2)	0.3217 (6)	0.0904 (16)
H7A	0.5966	0.8087	0.3649	0.136*
H7B	0.5580	0.7599	0.2082	0.136*
H7C	0.6649	0.7307	0.3607	0.136*
C8	0.2120 (4)	0.6194 (2)	0.4366 (5)	0.0758 (13)
H8A	0.1752	0.6582	0.4816	0.114*
H8B	0.2353	0.5754	0.5062	0.114*
H8C	0.1535	0.6035	0.3356	0.114*
C9	0.6108 (3)	0.4668 (2)	0.1802 (4)	0.0515 (10)
H9A	0.5848	0.4153	0.1719	0.062*
C10	0.7068 (3)	0.4765 (2)	0.1343 (4)	0.0449 (9)
C11	0.7798 (3)	0.5455 (2)	0.1170 (4)	0.0501 (10)
C12	0.8558 (3)	0.4438 (2)	0.0451 (5)	0.0503 (10)
C13	0.7284 (4)	0.33330 (19)	0.0758 (5)	0.0645 (12)
H13A	0.7684	0.3053	0.0162	0.097*
H13B	0.6404	0.3284	0.0247	0.097*
H13C	0.7537	0.3123	0.1809	0.097*
O4	0.9627 (3)	0.24068 (15)	−0.0504 (4)	0.0840 (10)
N4	1.0997 (3)	0.1715 (2)	−0.1212 (4)	0.0640 (10)
C14	1.0425 (4)	0.2363 (2)	−0.1090 (5)	0.0696 (13)
H14	1.0644	0.2817	−0.1476	0.083*
C15	1.0712 (4)	0.0990 (2)	−0.0635 (5)	0.0847 (14)
H15A	1.0012	0.1058	−0.0323	0.127*
H15B	1.1410	0.0823	0.0261	0.127*
H15C	1.0523	0.0607	−0.1457	0.127*
C16	1.1923 (4)	0.1722 (3)	−0.1941 (6)	0.0863 (15)
H16A	1.2049	0.2245	−0.2216	0.129*
H16B	1.1646	0.1408	−0.2881	0.129*
H16C	1.2686	0.1518	−0.1210	0.129*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.081 (2)	0.0536 (17)	0.115 (3)	0.0027 (15)	0.066 (2)	−0.0051 (17)
O2	0.095 (2)	0.0437 (16)	0.137 (3)	−0.0081 (16)	0.080 (2)	−0.0138 (18)
O3	0.0772 (19)	0.0387 (15)	0.103 (2)	−0.0020 (13)	0.0547 (18)	−0.0058 (16)
N1	0.0558 (19)	0.0398 (18)	0.074 (2)	−0.0017 (17)	0.0375 (18)	−0.0025 (19)
N2	0.0526 (18)	0.0392 (18)	0.069 (2)	0.0023 (16)	0.0350 (18)	0.0008 (17)
N3	0.061 (2)	0.0441 (18)	0.094 (3)	0.0015 (17)	0.044 (2)	−0.0011 (19)
C1	0.060 (3)	0.047 (2)	0.068 (3)	0.008 (2)	0.040 (2)	0.000 (2)
C2	0.064 (3)	0.037 (2)	0.072 (3)	0.002 (2)	0.039 (2)	−0.001 (2)
C3	0.052 (2)	0.043 (2)	0.063 (3)	−0.0065 (19)	0.026 (2)	0.001 (2)
C4	0.050 (2)	0.042 (2)	0.051 (3)	−0.0005 (19)	0.022 (2)	0.002 (2)
C5	0.061 (2)	0.038 (2)	0.083 (3)	−0.004 (2)	0.038 (2)	−0.004 (2)
C6	0.058 (2)	0.051 (2)	0.084 (3)	−0.003 (2)	0.039 (2)	−0.003 (2)
C7	0.104 (4)	0.049 (3)	0.145 (5)	−0.013 (3)	0.077 (4)	0.002 (3)
C8	0.080 (3)	0.072 (3)	0.101 (4)	0.006 (2)	0.063 (3)	0.007 (3)
C9	0.056 (2)	0.040 (2)	0.062 (3)	0.0011 (19)	0.025 (2)	−0.004 (2)
C10	0.047 (2)	0.036 (2)	0.055 (3)	0.0052 (19)	0.024 (2)	0.003 (2)
C11	0.051 (2)	0.044 (2)	0.058 (3)	0.0023 (19)	0.023 (2)	0.002 (2)
C12	0.047 (2)	0.047 (2)	0.059 (3)	0.007 (2)	0.022 (2)	0.001 (2)
C13	0.071 (3)	0.038 (2)	0.095 (4)	0.000 (2)	0.043 (3)	−0.002 (2)
O4	0.084 (2)	0.0571 (18)	0.140 (3)	−0.0035 (16)	0.076 (2)	−0.0103 (18)
N4	0.062 (2)	0.054 (2)	0.086 (3)	0.0052 (19)	0.039 (2)	−0.001 (2)
C14	0.069 (3)	0.052 (3)	0.095 (4)	−0.006 (2)	0.038 (3)	0.002 (3)
C15	0.091 (3)	0.059 (3)	0.113 (4)	0.004 (3)	0.047 (3)	0.002 (3)
C16	0.066 (3)	0.103 (4)	0.104 (4)	0.002 (3)	0.048 (3)	−0.012 (3)

Geometric parameters (Å, º)

O1—C1	1.359 (4)	C7—H7A	0.96
O1—C8	1.422 (4)	C7—H7B	0.96
O2—C2	1.375 (4)	C7—H7C	0.96
O2—C7	1.417 (4)	C8—H8A	0.96
O3—C11	1.238 (4)	C8—H8B	0.96
N1—C12	1.348 (4)	C8—H8C	0.96
N1—C11	1.364 (4)	C9—C10	1.336 (4)
N2—C12	1.349 (4)	C9—H9A	0.93
N2—C10	1.404 (4)	C10—C11	1.500 (5)
N2—C13	1.455 (4)	C13—H13A	0.96
N3—C12	1.314 (4)	C13—H13B	0.96
N3—H3A	0.86	C13—H13C	0.96
N3—H3B	0.86	O4—C14	1.227 (4)
C1—C6	1.364 (5)	N4—C14	1.323 (5)
C1—C2	1.402 (5)	N4—C15	1.438 (5)
C2—C3	1.366 (5)	N4—C16	1.453 (4)
C3—C4	1.402 (5)	C14—H14	0.93
C3—H3	0.93	C15—H15A	0.96
C4—C5	1.380 (5)	C15—H15B	0.96
C4—C9	1.456 (5)	C15—H15C	0.96
C5—C6	1.381 (5)	C16—H16A	0.96
C5—H5	0.93	C16—H16B	0.96
C6—H6	0.93	C16—H16C	0.96
C1—O1—C8	118.1 (3)	H8B—C8—H8C	109.5
C2—O2—C7	117.0 (3)	C10—C9—C4	135.6 (3)
C12—N1—C11	105.9 (3)	C10—C9—H9A	112.2
C12—N2—C10	108.3 (3)	C4—C9—H9A	112.2
C12—N2—C13	125.1 (3)	C9—C10—N2	122.9 (3)
C10—N2—C13	126.6 (3)	C9—C10—C11	134.4 (3)
C12—N3—H3A	120.0	N2—C10—C11	102.7 (3)
C12—N3—H3B	120.0	O3—C11—N1	123.9 (3)
H3A—N3—H3B	120.0	O3—C11—C10	126.8 (3)
O1—C1—C6	125.0 (3)	N1—C11—C10	109.3 (3)
O1—C1—C2	116.1 (3)	N3—C12—N1	121.9 (4)
C6—C1—C2	119.0 (3)	N3—C12—N2	124.3 (3)
C3—C2—O2	124.7 (3)	N1—C12—N2	113.8 (3)
C3—C2—C1	121.1 (3)	N2—C13—H13A	109.5
O2—C2—C1	114.2 (3)	N2—C13—H13B	109.5
C2—C3—C4	120.3 (3)	H13A—C13—H13B	109.5
C2—C3—H3	119.8	N2—C13—H13C	109.5
C4—C3—H3	120.0	H13A—C13—H13C	109.5
C5—C4—C3	117.5 (3)	H13B—C13—H13C	109.5
C5—C4—C9	117.8 (3)	C14—N4—C15	120.8 (3)
C3—C4—C9	124.7 (3)	C14—N4—C16	120.6 (4)
C4—C5—C6	122.5 (3)	C15—N4—C16	118.7 (3)
C4—C5—H5	118.7	O4—C14—N4	124.8 (4)
C6—C5—H5	118.8	O4—C14—H14	117.6
C1—C6—C5	119.7 (4)	N4—C14—H14	117.6
C1—C6—H6	120.3	N4—C15—H15A	109.5
C5—C6—H6	120.1	N4—C15—H15B	109.5
O2—C7—H7A	109.5	H15A—C15—H15B	109.5
O2—C7—H7B	109.5	N4—C15—H15C	109.5
H7A—C7—H7B	109.5	H15A—C15—H15C	109.5
O2—C7—H7C	109.5	H15B—C15—H15C	109.5
H7A—C7—H7C	109.5	N4—C16—H16A	109.5
H7B—C7—H7C	109.5	N4—C16—H16B	109.5
O1—C8—H8A	109.5	H16A—C16—H16B	109.5
O1—C8—H8B	109.5	N4—C16—H16C	109.5
H8A—C8—H8B	109.5	H16A—C16—H16C	109.5
O1—C8—H8C	109.5	H16B—C16—H16C	109.5
H8A—C8—H8C	109.5
C8—O1—C1—C6	−4.6 (6)	C4—C9—C10—C11	−3.1 (7)
C8—O1—C1—C2	175.9 (3)	C12—N2—C10—C9	179.6 (3)
C7—O2—C2—C3	9.3 (6)	C13—N2—C10—C9	−0.8 (6)
C7—O2—C2—C1	−171.2 (4)	C12—N2—C10—C11	0.6 (4)
O1—C1—C2—C3	−179.9 (4)	C13—N2—C10—C11	−179.8 (4)
C6—C1—C2—C3	0.6 (6)	C12—N1—C11—O3	−179.2 (4)
O1—C1—C2—O2	0.5 (5)	C12—N1—C11—C10	1.5 (4)
C6—C1—C2—O2	−179.0 (4)	C9—C10—C11—O3	0.6 (7)
O2—C2—C3—C4	178.9 (4)	N2—C10—C11—O3	179.4 (4)
C1—C2—C3—C4	−0.6 (6)	C9—C10—C11—N1	179.9 (4)
C2—C3—C4—C5	0.3 (6)	N2—C10—C11—N1	−1.3 (4)
C2—C3—C4—C9	−179.0 (4)	C11—N1—C12—N3	179.6 (3)
C3—C4—C5—C6	0.0 (6)	C11—N1—C12—N2	−1.2 (4)
C9—C4—C5—C6	179.3 (4)	C10—N2—C12—N3	179.5 (3)
O1—C1—C6—C5	−179.7 (4)	C13—N2—C12—N3	−0.1 (6)
C2—C1—C6—C5	−0.3 (6)	C10—N2—C12—N1	0.3 (4)
C4—C5—C6—C1	0.0 (6)	C13—N2—C12—N1	−179.3 (4)
C5—C4—C9—C10	177.4 (4)	C15—N4—C14—O4	−0.3 (7)
C3—C4—C9—C10	−3.3 (7)	C16—N4—C14—O4	179.4 (4)
C4—C9—C10—N2	178.3 (4)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
C3—H3···O3	0.93	2.18	3.009 (4)	148
N3—H3A···N1^i	0.86	2.05	2.906 (4)	176
N3—H3B···O4	0.86	2.05	2.853 (4)	156
C15—H15A···O4	0.96	2.36	2.768 (5)	105

Symmetry code: (i) −x+2, −y+1, −z.