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Acta Cryst. (2009). E65, o1298-o1299    [ doi:10.1107/S1600536809017413 ]

5-[(3,4-Dimethoxybenzyl)aminomethylene]-2,2-dimethyl-1,3-dioxane-4,6-dione

R. Li, J.-Y. Shi, Z.-Y. Ding, Y.-Q. Wei and J. Ding

Abstract top

The title compound, C15H17NO6, is approximately planar, with dihedral angles of 3.11 (4) and 2.12 (4)° between the connecting aminomethylene unit and the planar part of the dioxane ring, and between the dimethoxybenzyl ring and the aminomethylene group, respectively. The dioxane ring exhibits a half-boat conformation, in which the C atom between the dioxane O atoms is 0.5471 (8) Å out of the plane. The molecule has an intramolecular N-H...O hydrogen bond which may stabilize the planar conformation. In the crystal, weak intermolecular C-H...O hydrogen-bonding contacts, result in the formation of sheets parallel to the ab plane.

Comment top

The 4(1H)quinolone structure plays an extremely important role in the field of pharmaceutical chemistry. These compounds have been used as precursors for anticancer agents, anti-malarial agents and reversible (H+/K+) ATPase inhibitors (Ruchelman et al.,2003). 5-arylaminomethylene-2,2-dimethyl-1,3-dioxane-4,6-diones are the key intermediates which can be used to synthesize the 4(1H)quinolone derivatives by thermolysis (Cassis et al., 1985).

In the structure of the title molecule (Fig. 1), it is approximately planar with the dihedral angles of 3.11 (4)° and 2.12 (4)° between the connecting aminomethylene unit and the planar part of the dioxane ring, and between the dimethoxybenzyl ring and the aminomethylene group, respectively. Besides, the dioxane ring of the title compound exhibits a half-boat conformation, in which the C atom between the dioxane O atoms is -0.5471 (8) Å out-of-plane.

The intramolecular N—H···O hydrogen bond (Table 1) is stabilizing the planar conformation in the molecule. Intermolecular weak C—H···O hydrogen bonding contacts (Table 1) result in the formation of sheets running parallel to the a-b plane in the crystal structure (Fig. 2).

Related literature top

For the synthesis of related compounds, see: Cassis et al. (1985). For the synthesis of related antitumor precursors, see Ruchelman et al. (2003). For the structure of 5-(aminomethylene)-2,2-dimethyl-1,3-dioxane-4,6-dione, see: da Silva et al. (2006). For Meldrum's acid, see: Meldrum (1908).

Experimental top

A solution of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) and methylorthoformate was heated to reflux for two hours and immediately the arylamine was added in an equimolar amount relative to Meldrum's acid. The mixture was heated under reflux for another 5–8 h; single recrystallization from methanol gave the corresponding arylaminomethylene derivative as analytically pure material.

Refinement top

H atoms were positioned geometrically (C—H = 0.93–0.98 Å) and refined using a riding model, with Uiso(H) = 1.2–1.5Ueq(C).

Computing details top

Data collection: DIFRAC (Gabe & White, 1993); cell refinement: DIFRAC (Gabe & White, 1993); data reduction: NRCVAX (Gabe et al., 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, with displacement ellipsoids drawn at the 30% probability level.
[Figure 2] Fig. 2. A packing diagram of the title compound showing the layer-like aggregation of the title molecules in the unit cell.
5-[(3,4-Dimethoxybenzyl)aminomethylene]-2,2-dimethyl-1,3-dioxane-4,6-dione top
Crystal data top
C15H17NO6F000 = 648
Mr = 307.30Dx = 1.391 Mg m−3
Monoclinic, P21/cMo Kα radiation
λ = 0.71073 Å
a = 6.270 (4) ÅCell parameters from 29 reflections
b = 12.486 (4) Åθ = 4.4–7.7º
c = 19.529 (5) ŵ = 0.11 mm−1
β = 106.31 (3)ºT = 292 K
V = 1467.3 (11) Å3Block, yellow
Z = 40.44 × 0.38 × 0.18 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.008
Radiation source: fine-focus sealed tubeθmax = 25.4º
Monochromator: graphiteθmin = 2.0º
T = 292 Kh = −7→7
ω/2θ scansk = −15→0
Absorption correction: nonel = −23→8
2852 measured reflections3 standard reflections
2657 independent reflections every 150 reflections
1675 reflections with I > 2σ(I) intensity decay: 1.8%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.056H atoms treated by a mixture of
independent and constrained refinement
wR(F2) = 0.160  w = 1/[σ2(Fo2) + (0.0954P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.03(Δ/σ)max < 0.001
2657 reflectionsΔρmax = 0.21 e Å−3
207 parametersΔρmin = −0.26 e Å−3
Primary atom site location: structure-invariant direct methodsExtinction correction: none
Crystal data top
C15H17NO6V = 1467.3 (11) Å3
Mr = 307.30Z = 4
Monoclinic, P21/cMo Kα
a = 6.270 (4) ŵ = 0.11 mm−1
b = 12.486 (4) ÅT = 292 K
c = 19.529 (5) Å0.44 × 0.38 × 0.18 mm
β = 106.31 (3)º
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.008
Absorption correction: none3 standard reflections
2852 measured reflections every 150 reflections
2657 independent reflections intensity decay: 1.8%
1675 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.056207 parameters
wR(F2) = 0.160H atoms treated by a mixture of
independent and constrained refinement
S = 1.03Δρmax = 0.21 e Å−3
2657 reflectionsΔρmin = −0.26 e Å−3
Special details top

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 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 (Å2) top
xyzUiso*/Ueq
O10.0589 (3)0.78796 (12)0.14968 (8)0.0456 (5)
O2−0.0296 (3)0.60397 (13)0.13307 (9)0.0489 (5)
O30.3798 (3)0.84242 (14)0.22145 (9)0.0522 (5)
O40.2084 (3)0.47579 (14)0.18214 (10)0.0623 (6)
O51.4467 (3)0.80170 (14)0.40934 (10)0.0544 (5)
O61.5852 (3)0.60587 (14)0.42558 (9)0.0503 (5)
N10.7059 (3)0.69339 (19)0.27469 (10)0.0403 (5)
H1N0.677 (4)0.761 (2)0.2721 (13)0.046 (8)*
C1−0.2969 (4)0.7333 (2)0.08019 (14)0.0523 (7)
H1A−0.37970.67670.05130.078*
H1B−0.32420.79940.05400.078*
H1C−0.34270.74040.12290.078*
C20.0406 (5)0.7062 (3)0.03595 (15)0.0674 (9)
H2A0.19660.69030.05170.101*
H2B0.01870.77490.01310.101*
H2C−0.03430.65230.00270.101*
C3−0.0529 (4)0.70753 (19)0.09947 (12)0.0411 (6)
C40.2670 (4)0.7662 (2)0.19222 (12)0.0389 (6)
C50.3347 (4)0.65633 (19)0.20110 (11)0.0374 (6)
C60.1782 (4)0.5710 (2)0.17241 (13)0.0422 (6)
C70.5461 (4)0.6272 (2)0.24184 (12)0.0398 (6)
H70.57780.55440.24640.048*
C80.9280 (4)0.66471 (19)0.31291 (11)0.0374 (6)
C91.0729 (4)0.74811 (19)0.34299 (11)0.0388 (6)
H91.02190.81840.33840.047*
C101.2914 (4)0.72663 (18)0.37956 (11)0.0392 (6)
C111.3659 (4)0.61937 (18)0.38805 (11)0.0370 (6)
C121.2204 (4)0.5382 (2)0.35779 (12)0.0442 (6)
H121.26960.46760.36260.053*
C131.0014 (4)0.5605 (2)0.32015 (12)0.0445 (6)
H130.90500.50510.30000.053*
C141.3812 (5)0.9112 (2)0.39922 (15)0.0588 (8)
H14A1.33070.92660.34910.088*
H14B1.50560.95620.42120.088*
H14C1.26310.92450.42050.088*
C151.6708 (4)0.4995 (2)0.43247 (14)0.0535 (7)
H15A1.59730.45770.46030.080*
H15B1.82750.50120.45570.080*
H15C1.64510.46810.38600.080*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0390 (10)0.0379 (10)0.0492 (10)0.0012 (8)−0.0054 (8)−0.0002 (7)
O20.0380 (10)0.0398 (10)0.0585 (11)−0.0059 (8)−0.0036 (8)0.0011 (8)
O30.0468 (11)0.0371 (10)0.0602 (11)−0.0067 (8)−0.0054 (9)−0.0021 (8)
O40.0517 (12)0.0318 (11)0.0890 (14)−0.0007 (8)−0.0040 (10)0.0002 (9)
O50.0456 (11)0.0377 (10)0.0634 (11)−0.0014 (8)−0.0120 (8)−0.0020 (8)
O60.0388 (10)0.0459 (11)0.0550 (10)0.0053 (8)−0.0052 (8)−0.0005 (8)
N10.0345 (12)0.0390 (13)0.0417 (11)0.0005 (9)0.0012 (9)0.0041 (9)
C10.0384 (15)0.0603 (18)0.0493 (15)−0.0006 (13)−0.0025 (12)0.0020 (13)
C20.0541 (18)0.097 (2)0.0504 (15)−0.0023 (17)0.0130 (13)−0.0022 (16)
C30.0356 (13)0.0432 (14)0.0392 (12)−0.0032 (11)0.0017 (10)0.0001 (11)
C40.0371 (13)0.0408 (14)0.0357 (12)−0.0019 (11)0.0050 (10)0.0021 (10)
C50.0334 (13)0.0383 (13)0.0366 (12)−0.0023 (10)0.0034 (10)0.0010 (10)
C60.0338 (14)0.0417 (15)0.0471 (14)−0.0016 (11)0.0045 (11)−0.0025 (11)
C70.0364 (14)0.0424 (14)0.0382 (12)−0.0001 (11)0.0063 (11)0.0013 (10)
C80.0329 (13)0.0404 (14)0.0346 (12)0.0006 (11)0.0024 (9)0.0052 (10)
C90.0410 (14)0.0334 (13)0.0377 (12)0.0042 (11)0.0038 (10)0.0017 (10)
C100.0413 (14)0.0378 (14)0.0329 (11)−0.0028 (11)0.0011 (10)−0.0024 (10)
C110.0335 (13)0.0419 (14)0.0320 (11)0.0059 (11)0.0031 (10)0.0034 (10)
C120.0432 (15)0.0351 (14)0.0492 (14)0.0050 (11)0.0045 (11)0.0021 (11)
C130.0425 (15)0.0371 (14)0.0468 (14)−0.0042 (11)0.0011 (11)0.0043 (11)
C140.0604 (18)0.0389 (15)0.0644 (17)−0.0048 (13)−0.0030 (14)−0.0025 (13)
C150.0455 (16)0.0508 (16)0.0572 (15)0.0149 (13)0.0030 (12)0.0028 (13)
Geometric parameters (Å, °) top
O1—C41.363 (3)C2—H2C0.9600
O1—C31.441 (3)C4—C51.432 (3)
O2—C61.376 (3)C5—C71.389 (3)
O2—C31.439 (3)C5—C61.450 (3)
O3—C41.227 (3)C7—H70.9300
O4—C61.211 (3)C8—C131.374 (4)
O5—C101.359 (3)C8—C91.398 (3)
O5—C141.425 (3)C9—C101.382 (3)
O6—C111.375 (3)C9—H90.9300
O6—C151.424 (3)C10—C111.413 (3)
N1—C71.318 (3)C11—C121.380 (3)
N1—C81.428 (3)C12—C131.392 (4)
N1—H1N0.86 (3)C12—H120.9300
C1—C31.504 (4)C13—H130.9300
C1—H1A0.9600C14—H14A0.9600
C1—H1B0.9600C14—H14B0.9600
C1—H1C0.9600C14—H14C0.9600
C2—C31.513 (4)C15—H15A0.9600
C2—H2A0.9600C15—H15B0.9600
C2—H2B0.9600C15—H15C0.9600
C4—O1—C3118.37 (18)N1—C7—C5126.0 (2)
C6—O2—C3118.82 (19)N1—C7—H7117.0
C10—O5—C14117.26 (19)C5—C7—H7117.0
C11—O6—C15117.28 (19)C13—C8—C9120.2 (2)
C7—N1—C8126.4 (2)C13—C8—N1122.7 (2)
C7—N1—H1N117.7 (17)C9—C8—N1117.1 (2)
C8—N1—H1N115.9 (17)C10—C9—C8120.4 (2)
C3—C1—H1A109.5C10—C9—H9119.8
C3—C1—H1B109.5C8—C9—H9119.8
H1A—C1—H1B109.5O5—C10—C9125.1 (2)
C3—C1—H1C109.5O5—C10—C11115.5 (2)
H1A—C1—H1C109.5C9—C10—C11119.5 (2)
H1B—C1—H1C109.5O6—C11—C12125.4 (2)
C3—C2—H2A109.5O6—C11—C10115.3 (2)
C3—C2—H2B109.5C12—C11—C10119.3 (2)
H2A—C2—H2B109.5C11—C12—C13121.0 (2)
C3—C2—H2C109.5C11—C12—H12119.5
H2A—C2—H2C109.5C13—C12—H12119.5
H2B—C2—H2C109.5C8—C13—C12119.7 (2)
O2—C3—O1110.38 (17)C8—C13—H13120.1
O2—C3—C1105.8 (2)C12—C13—H13120.1
O1—C3—C1106.7 (2)O5—C14—H14A109.5
O2—C3—C2110.5 (2)O5—C14—H14B109.5
O1—C3—C2109.8 (2)H14A—C14—H14B109.5
C1—C3—C2113.5 (2)O5—C14—H14C109.5
O3—C4—O1117.1 (2)H14A—C14—H14C109.5
O3—C4—C5125.1 (2)H14B—C14—H14C109.5
O1—C4—C5117.8 (2)O6—C15—H15A109.5
C7—C5—C4121.5 (2)O6—C15—H15B109.5
C7—C5—C6117.6 (2)H15A—C15—H15B109.5
C4—C5—C6120.7 (2)O6—C15—H15C109.5
O4—C6—O2117.6 (2)H15A—C15—H15C109.5
O4—C6—C5127.0 (2)H15B—C15—H15C109.5
O2—C6—C5115.4 (2)
C6—O2—C3—O1−48.6 (3)C6—C5—C7—N1−176.7 (2)
C6—O2—C3—C1−163.7 (2)C7—N1—C8—C13−0.4 (4)
C6—O2—C3—C273.1 (3)C7—N1—C8—C9179.0 (2)
C4—O1—C3—O245.3 (3)C13—C8—C9—C100.7 (4)
C4—O1—C3—C1159.8 (2)N1—C8—C9—C10−178.8 (2)
C4—O1—C3—C2−76.8 (3)C14—O5—C10—C9−2.9 (4)
C3—O1—C4—O3162.7 (2)C14—O5—C10—C11177.2 (2)
C3—O1—C4—C5−19.1 (3)C8—C9—C10—O5178.4 (2)
O3—C4—C5—C7−3.9 (4)C8—C9—C10—C11−1.7 (3)
O1—C4—C5—C7178.1 (2)C15—O6—C11—C121.5 (3)
O3—C4—C5—C6171.1 (2)C15—O6—C11—C10−177.0 (2)
O1—C4—C5—C6−6.9 (3)O5—C10—C11—O60.3 (3)
C3—O2—C6—O4−158.5 (2)C9—C10—C11—O6−179.6 (2)
C3—O2—C6—C524.7 (3)O5—C10—C11—C12−178.3 (2)
C7—C5—C6—O42.9 (4)C9—C10—C11—C121.9 (4)
C4—C5—C6—O4−172.3 (3)O6—C11—C12—C13−179.4 (2)
C7—C5—C6—O2179.3 (2)C10—C11—C12—C13−1.0 (4)
C4—C5—C6—O24.2 (3)C9—C8—C13—C120.2 (4)
C8—N1—C7—C5−175.7 (2)N1—C8—C13—C12179.6 (2)
C4—C5—C7—N1−1.6 (4)C11—C12—C13—C80.0 (4)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O30.86 (3)2.11 (3)2.744 (3)130 (2)
C9—H9···O4i0.932.403.309 (4)164
C15—H15C···O3ii0.962.593.528 (4)166
Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) −x+2, y−1/2, −z+1/2.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1N···O30.86 (3)2.11 (3)2.744 (3)130 (2)
C9—H9···O4i0.932.403.309 (4)164
C15—H15C···O3ii0.962.593.528 (4)166
Symmetry codes: (i) −x+1, y+1/2, −z+1/2; (ii) −x+2, y−1/2, −z+1/2.
Acknowledgements top

This research was supported financially by the State Key Laboratory of Drug Research (Shanghai Institute of Materia Medica, Chinese Academy of Sciences).

references
References top

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Meldrum, A. N. (1908). J. Chem. Soc. Trans. 93, 598–601.

Ruchelman, A. L., Singh, S. K., Ray, A., Wu, X. H., Yang, J. M., Li, T. K., Liu, A., Liu, L. F. & LaVoie, E. J. (2003). Bioorg. Med. Chem. 11, 2061–2073.

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