supplementary materials


tk5257 scheme

Acta Cryst. (2013). E69, o1571    [ doi:10.1107/S160053681302566X ]

2-[(E)-(Morpholin-4-ylimino)methyl]-6-(morpholin-4-ylmethyl)phenol

M. Akkurt, A. Jarrahpour, M. M. Chermahini, M. Aberi and O. Büyükgüngör

Abstract top

The title compound, C16H23N3O3, contains two morpholine rings, each of which adopts a chair conformation. The molecular conformation is stabilized by an intramolecular O-H...N hydrogen bond, leading to a S(6) ring. In the crystal, molecules are linked into zigzag chains along the c-axis direction by C-H...O and C-H...[pi] interactions.

Comment top

Schiff bases are formed by the condensation of a primary amine with a carbonyl compound (Dhar & Taploo, 1982). They are widely used for industrial purposes and also exhibit a broad range of biological activities (Silva et al., 2011). The morpholine moiety has been utilized extensively by the pharmaceutical industry in drug design, often because of the improvement in pharmacokinetic properties it can con­fer. The World Drug Index contains well over 100 drugs incorporating this structural feature, including its presence as a side-chain, scaffold, and within fused-ring systems. The biological utility of molecules containing the morpholine moiety is wide-ranging (Nelson et al., 2004). Therefore, Schiff base (I), which has the two morpholine rings, was synthesized and its X-ray structure is reported here.

The two morpholine rings (N1/O1/C1–C4 and N3/O3/C13–C16) of (I), Fig. 1, adopt a chair conformation with puckering parameters (Cremer & Pople, 1975) of QT = 0.564 (3) Å, θ = 180.0 (2)°, φ = 163 (33)° and QT = 0.553 (2) Å, θ = 4.6 (2)°, φ = 19 (3)°, respectively. The N1–C5–C6–C7, C5–C6–C7–O2, O2–C7–C8–C12 and C8–C12–N2–N3 torsion angles are -158.0 (2), 0.6 (3), -1.0 (3) and 179.97 (19)°, respectively.

An intramolecular O—H···N hydrogen bond (Table 1) stabilizes the molecular conformation of (I), forming a pseudo six-membered ring with a graph set motif S(6) (Bernstein et al., 1995). In the crystal structure, C—H···O hydrogen bonds link the molecules into infinite one-dimensional chains along [001], with a C(4) graph-set motif (Table 1, Fig. 2). Additional C—H···π interactions also assist in the stabilization of the chain.

Related literature top

For background to Schiff bases and their applications, see: Dhar & Taploo (1982); Nelson et al. (2004); Silva et al. (2011). For ring puckering parameters, see: Cremer & Pople (1975). For hydrogen-bond motifs, see: Bernstein et al. (1995).

Experimental top

A mixture of 2-hydroxy-3-(morpholinomethyl)benzaldehyde (1.0 mmol) and morpholin-4-amine (1.0 mmol) was refluxed in EtOH for 4 h. After cooling the solution, the precipitate formed was filtered and recrystallized from ethanol to give yellow crystals in 82% yield. M. pt: 407–409 K. IR (KBr) cm-1: 1612 (C=N). 1H-NMR (250 MHz, CDCl3), δ (p.p.m.): 2.57, 3.15 (CH2N, t, 8H, J=5 Hz), 3.66 (CH2, s, 2H), 3.75, 3.88 (CH2O, t, 8H, J=5 Hz), 6.84 (aromatic H, t, 1H, J=7.5 Hz), 7.23 (aromatic H, d, 2H, J=7.5 Hz), 7.80 (HC=N, s, 1H), 11.71 (OH, s, 1H). 13C-NMR (62.9 MHz, CDCl3), δ (p.p.m): 51.8, 53.3 (CH2N), 57.6 (CH2), 66.2, 66.7 (CH2O), 118.8–139.1 (aromatic carbons), 156.0 (C=N).

Refinement top

All H atoms were located geometrically with O—H = 0.82 Å, and C—H = 0.93 and 0.97 Å, and refined using a riding model with Uiso(H) = 1.2Ueq(C) for the aromatic- and methylene-H atoms, and Uiso(H) = 1.5Ueq(O) for the hydroxyl-H atom.

Computing details top

Data collection: X-AREA (Stoe & Cie, 2002); cell refinement: X-AREA (Stoe & Cie, 2002); data reduction: X-RED32 (Stoe & Cie, 2002); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) with the atom-labelling scheme and 30% probability displacement ellipsoids.
[Figure 2] Fig. 2. Packing diagram of (I) viewed down the a axis. Hydrogen bonds are indicated by broken lines. H atoms not participating in hydrogen bonding have been omitted for clarity.
2-[(E)-(Morpholin-4-ylimino)methyl]-6-(morpholin-4-ylmethyl)phenol top
Crystal data top
C16H23N3O3F(000) = 656
Mr = 305.37Dx = 1.278 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 17755 reflections
a = 9.0074 (6) Åθ = 2.2–27.3°
b = 15.7781 (14) ŵ = 0.09 mm1
c = 11.3083 (7) ÅT = 296 K
β = 99.052 (5)°Shapeless, yellow
V = 1587.1 (2) Å30.51 × 0.32 × 0.09 mm
Z = 4
Data collection top
STOE IPDS 2
diffractometer
3289 independent reflections
Radiation source: sealed X-ray tube, 12 x 0.4 mm long-fine focus1955 reflections with I > 2σ(I)
Plane graphite monochromatorRint = 0.089
Detector resolution: 6.67 pixels mm-1θmax = 26.5°, θmin = 2.2°
ω–scansh = 1111
Absorption correction: integration
(X-RED32; Stoe & Cie, 2002)
k = 1919
Tmin = 0.961, Tmax = 0.990l = 1414
23637 measured reflections
Refinement top
Refinement on F20 restraints
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.058H-atom parameters constrained
wR(F2) = 0.123 W = 1/[Σ2(FO2) + (0.0519P)2] WHERE P = (FO2 + 2FC2)/3
S = 1.03(Δ/σ)max < 0.001
3289 reflectionsΔρmax = 0.13 e Å3
199 parametersΔρmin = 0.12 e Å3
Crystal data top
C16H23N3O3V = 1587.1 (2) Å3
Mr = 305.37Z = 4
Monoclinic, P21/cMo Kα radiation
a = 9.0074 (6) ŵ = 0.09 mm1
b = 15.7781 (14) ÅT = 296 K
c = 11.3083 (7) Å0.51 × 0.32 × 0.09 mm
β = 99.052 (5)°
Data collection top
STOE IPDS 2
diffractometer
3289 independent reflections
Absorption correction: integration
(X-RED32; Stoe & Cie, 2002)
1955 reflections with I > 2σ(I)
Tmin = 0.961, Tmax = 0.990Rint = 0.089
23637 measured reflectionsθmax = 26.5°
Refinement top
R[F2 > 2σ(F2)] = 0.058H-atom parameters constrained
wR(F2) = 0.123Δρmax = 0.13 e Å3
S = 1.03Δρmin = 0.12 e Å3
3289 reflectionsAbsolute structure: ?
199 parametersAbsolute structure parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles

Refinement. Refinement on F2 for ALL reflections except those flagged by the user for potential systematic errors. Weighted R-factors wR and all goodnesses of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The observed criterion of F2 > σ(F2) is used only for calculating -R-factor-obs 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
O10.7886 (2)0.05694 (15)0.26574 (16)0.0912 (9)
O20.46117 (17)0.15800 (11)0.73906 (12)0.0586 (5)
O30.15802 (19)0.22570 (11)1.21636 (13)0.0659 (6)
N10.7555 (2)0.12192 (11)0.49469 (14)0.0497 (6)
N20.3995 (2)0.13953 (12)0.95782 (15)0.0500 (6)
N30.2980 (2)0.14585 (12)1.03797 (14)0.0514 (6)
C10.7095 (3)0.03684 (16)0.4572 (2)0.0669 (9)
C20.8012 (4)0.00352 (19)0.3670 (2)0.0838 (11)
C30.8362 (4)0.1393 (2)0.3018 (2)0.0859 (13)
C40.7453 (3)0.17607 (16)0.38952 (19)0.0614 (8)
C50.6625 (3)0.15608 (18)0.57868 (19)0.0667 (9)
C60.7055 (3)0.12328 (14)0.70585 (18)0.0523 (8)
C70.5991 (2)0.12627 (13)0.78287 (18)0.0467 (7)
C80.6357 (2)0.09994 (13)0.90283 (18)0.0452 (7)
C90.7809 (3)0.07110 (14)0.9425 (2)0.0562 (8)
C100.8869 (3)0.06887 (16)0.8678 (2)0.0629 (9)
C110.8489 (3)0.09507 (15)0.7501 (2)0.0600 (9)
C120.5296 (3)0.10624 (14)0.98800 (18)0.0501 (8)
C130.2093 (3)0.22298 (16)1.01350 (19)0.0584 (9)
C140.0910 (3)0.22850 (19)1.0939 (2)0.0691 (10)
C150.2348 (3)0.14835 (18)1.2391 (2)0.0707 (10)
C160.3593 (3)0.13650 (15)1.16513 (18)0.0566 (8)
H1A0.604000.037100.422300.0800*
H1B0.721600.000300.526500.0800*
H20.407900.156700.791500.0880*
H2A0.905800.000400.403600.1010*
H2B0.766800.052900.342200.1010*
H3A0.827700.175700.231900.1030*
H3B0.941200.137700.338000.1030*
H4A0.782300.232300.413200.0740*
H4B0.641100.181100.352200.0740*
H5A0.558300.141800.550300.0800*
H5B0.670800.217400.579500.0800*
H90.806600.052901.021300.0670*
H100.983800.049900.896000.0750*
H110.921200.093700.699800.0720*
H120.557200.085701.065400.0600*
H13A0.161300.223200.930500.0700*
H13B0.274800.272001.026400.0700*
H14A0.035100.280901.078200.0830*
H14B0.021100.181701.076800.0830*
H15A0.163600.102201.222400.0850*
H15B0.277400.145601.323300.0850*
H16A0.437500.178401.188000.0680*
H16B0.403400.080601.179600.0680*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.1117 (17)0.1190 (17)0.0446 (10)0.0059 (13)0.0173 (10)0.0190 (11)
O20.0528 (9)0.0838 (11)0.0411 (8)0.0177 (8)0.0129 (7)0.0064 (8)
O30.0724 (12)0.0822 (12)0.0457 (9)0.0009 (9)0.0178 (8)0.0106 (8)
N10.0550 (11)0.0584 (12)0.0378 (9)0.0049 (9)0.0141 (8)0.0022 (8)
N20.0553 (12)0.0586 (11)0.0379 (9)0.0038 (9)0.0128 (8)0.0032 (8)
N30.0578 (11)0.0657 (12)0.0339 (9)0.0087 (10)0.0168 (8)0.0046 (8)
C10.0723 (17)0.0674 (16)0.0628 (15)0.0028 (13)0.0164 (13)0.0056 (13)
C20.101 (2)0.085 (2)0.0652 (17)0.0133 (17)0.0121 (16)0.0203 (16)
C30.086 (2)0.122 (3)0.0555 (16)0.0115 (19)0.0288 (15)0.0107 (17)
C40.0664 (15)0.0706 (16)0.0480 (13)0.0028 (13)0.0118 (11)0.0105 (12)
C50.0764 (17)0.0838 (17)0.0434 (13)0.0302 (14)0.0202 (12)0.0073 (12)
C60.0625 (15)0.0575 (14)0.0383 (11)0.0173 (11)0.0119 (10)0.0016 (10)
C70.0533 (14)0.0458 (12)0.0409 (11)0.0097 (10)0.0070 (10)0.0036 (9)
C80.0555 (14)0.0405 (11)0.0396 (11)0.0037 (10)0.0075 (10)0.0008 (9)
C90.0722 (16)0.0564 (14)0.0390 (12)0.0141 (12)0.0053 (11)0.0014 (10)
C100.0619 (16)0.0742 (16)0.0509 (14)0.0248 (13)0.0036 (12)0.0025 (12)
C110.0608 (16)0.0727 (16)0.0494 (13)0.0222 (12)0.0177 (11)0.0032 (12)
C120.0702 (17)0.0460 (12)0.0352 (11)0.0021 (11)0.0122 (11)0.0006 (9)
C130.0563 (15)0.0766 (17)0.0433 (12)0.0045 (12)0.0110 (11)0.0012 (12)
C140.0611 (16)0.099 (2)0.0503 (14)0.0016 (14)0.0181 (12)0.0086 (14)
C150.094 (2)0.0805 (18)0.0419 (13)0.0078 (16)0.0245 (13)0.0040 (13)
C160.0771 (16)0.0586 (15)0.0355 (11)0.0008 (12)0.0129 (11)0.0013 (10)
Geometric parameters (Å, º) top
O1—C21.412 (3)C15—C161.512 (4)
O1—C31.409 (4)C1—H1A0.9700
O2—C71.359 (2)C1—H1B0.9700
O3—C141.422 (3)C2—H2A0.9700
O3—C151.406 (3)C2—H2B0.9700
O2—H20.8200C3—H3A0.9700
N1—C11.449 (3)C3—H3B0.9700
N1—C51.465 (3)C4—H4A0.9700
N1—C41.456 (3)C4—H4B0.9700
N2—N31.389 (2)C5—H5A0.9700
N2—C121.281 (3)C5—H5B0.9700
N3—C161.464 (3)C9—H90.9300
N3—C131.458 (3)C10—H100.9300
C1—C21.505 (4)C11—H110.9300
C3—C41.499 (4)C12—H120.9300
C5—C61.520 (3)C13—H13A0.9700
C6—C71.394 (3)C13—H13B0.9700
C6—C111.383 (4)C14—H14A0.9700
C7—C81.407 (3)C14—H14B0.9700
C8—C121.463 (3)C15—H15A0.9700
C8—C91.391 (3)C15—H15B0.9700
C9—C101.371 (4)C16—H16A0.9700
C10—C111.384 (3)C16—H16B0.9700
C13—C141.508 (4)
C2—O1—C3109.51 (19)O1—C3—H3B109.00
C14—O3—C15109.05 (18)C4—C3—H3A109.00
C7—O2—H2109.00C4—C3—H3B109.00
C1—N1—C5111.37 (19)H3A—C3—H3B108.00
C4—N1—C5110.18 (18)N1—C4—H4A110.00
C1—N1—C4109.06 (17)N1—C4—H4B110.00
N3—N2—C12121.63 (17)C3—C4—H4A110.00
N2—N3—C16116.65 (18)C3—C4—H4B110.00
C13—N3—C16112.40 (17)H4A—C4—H4B108.00
N2—N3—C13109.48 (17)N1—C5—H5A109.00
N1—C1—C2111.1 (2)N1—C5—H5B109.00
O1—C2—C1111.0 (2)C6—C5—H5A109.00
O1—C3—C4112.1 (3)C6—C5—H5B109.00
N1—C4—C3110.0 (2)H5A—C5—H5B108.00
N1—C5—C6113.7 (2)C8—C9—H9119.00
C5—C6—C7118.8 (2)C10—C9—H9119.00
C5—C6—C11122.4 (2)C9—C10—H10120.00
C7—C6—C11118.66 (19)C11—C10—H10120.00
O2—C7—C8121.49 (17)C6—C11—H11119.00
C6—C7—C8120.84 (18)C10—C11—H11119.00
O2—C7—C6117.64 (18)N2—C12—H12119.00
C7—C8—C9118.25 (18)C8—C12—H12119.00
C9—C8—C12119.24 (19)N3—C13—H13A110.00
C7—C8—C12122.43 (18)N3—C13—H13B110.00
C8—C9—C10121.4 (2)C14—C13—H13A109.00
C9—C10—C11119.6 (2)C14—C13—H13B110.00
C6—C11—C10121.3 (2)H13A—C13—H13B108.00
N2—C12—C8121.17 (18)O3—C14—H14A109.00
N3—C13—C14110.6 (2)O3—C14—H14B109.00
O3—C14—C13110.7 (2)C13—C14—H14A110.00
O3—C15—C16113.1 (2)C13—C14—H14B110.00
N3—C16—C15109.4 (2)H14A—C14—H14B108.00
N1—C1—H1A109.00O3—C15—H15A109.00
N1—C1—H1B109.00O3—C15—H15B109.00
C2—C1—H1A109.00C16—C15—H15A109.00
C2—C1—H1B109.00C16—C15—H15B109.00
H1A—C1—H1B108.00H15A—C15—H15B108.00
O1—C2—H2A109.00N3—C16—H16A110.00
O1—C2—H2B109.00N3—C16—H16B110.00
C1—C2—H2A109.00C15—C16—H16A110.00
C1—C2—H2B109.00C15—C16—H16B110.00
H2A—C2—H2B108.00H16A—C16—H16B108.00
O1—C3—H3A109.00
C2—O1—C3—C459.1 (3)N1—C5—C6—C7158.0 (2)
C3—O1—C2—C158.2 (3)C5—C6—C11—C10177.2 (2)
C14—O3—C15—C1660.8 (3)C11—C6—C7—O2176.9 (2)
C15—O3—C14—C1361.0 (3)C5—C6—C7—O20.6 (3)
C1—N1—C4—C355.5 (3)C7—C6—C11—C101.0 (3)
C4—N1—C1—C255.8 (3)C11—C6—C7—C81.0 (3)
C5—N1—C4—C3178.0 (2)C5—C6—C7—C8177.3 (2)
C1—N1—C5—C678.8 (2)O2—C7—C8—C9177.62 (19)
C4—N1—C5—C6160.1 (2)O2—C7—C8—C121.0 (3)
C5—N1—C1—C2177.6 (2)C6—C7—C8—C12176.8 (2)
C12—N2—N3—C1617.4 (3)C6—C7—C8—C90.2 (3)
C12—N2—N3—C13146.5 (2)C7—C8—C12—N22.9 (3)
N3—N2—C12—C8179.97 (19)C12—C8—C9—C10176.1 (2)
C13—N3—C16—C1550.3 (3)C7—C8—C9—C100.6 (3)
N2—N3—C13—C14176.21 (18)C9—C8—C12—N2173.7 (2)
C16—N3—C13—C1452.5 (3)C8—C9—C10—C110.6 (4)
N2—N3—C16—C15177.92 (19)C9—C10—C11—C60.3 (4)
N1—C1—C2—O158.0 (3)N3—C13—C14—O357.5 (3)
O1—C3—C4—N158.4 (3)O3—C15—C16—N355.1 (3)
N1—C5—C6—C1125.8 (3)
Hydrogen-bond geometry (Å, º) top
Cg3 is the centroid of the C6–C11 benzene ring.
D—H···AD—HH···AD···AD—H···A
O2—H2···N20.821.912.636 (2)146
C13—H13A···O3i0.972.553.416 (3)149
C4—H4A···Cg3i0.972.873.646 (3)138
Symmetry code: (i) x, y+1/2, z1/2.
Hydrogen-bond geometry (Å, º) top
Cg3 is the centroid of the C6–C11 benzene ring.
D—H···AD—HH···AD···AD—H···A
O2—H2···N20.821.912.636 (2)146
C13—H13A···O3i0.972.553.416 (3)149
C4—H4A···Cg3i0.972.873.646 (3)138
Symmetry code: (i) x, y+1/2, z1/2.
Acknowledgements top

The authors acknowledge the Faculty of Arts and Sciences, Ondokuz Mayıs University, Turkey, for the use of the Stoe IPDS 2 diffractometer (purchased under grant F.279 of the University Research Fund).

references
References top

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Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854.

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