supplementary materials


pv2627 scheme

Acta Cryst. (2013). E69, o778    [ doi:10.1107/S1600536813010477 ]

3-Hydroxy-1-[(morpholin-4-yl)methyl]pyridazin-6(1H)-one

P. R. Santhi, G. Selvanathan, G. Poongothai, T. Srinivasan and D. Velmurugan

Abstract top

In the title compound, C9H13N3O3, the morpholine ring adopts a chair conformation and its mean plane makes a dihedral angle of 68.00 (11)° with the pyridazine ring. The carbonyl O atom deviates from the plane of the pyridazine ring by 0.0482 (12) Å. An intramolecular C-H...O hydrogen bond occurs. In the crystal, molecules are linked by O-H...O and C-H...O hydrogen bonds, forming chains along [1-10].

Comment top

Morpholine derivatives possess anticancer and antimicrobial activities (Lan et al., 2010; Raparti et al., 2009). In the title compound (Fig. 1), the morpholine ring (N3/O3/C6-C9) adopts a chair conformation. The morpholine ring makes a dihedral angle of 68.00 (11)° with the pyridazin ring (N1/N2/C1-C4). The hydroxyl oxygen atom O1 attached with the pyridazin ring deviates by 0.0242 (13)Å. The oxygen atom O2 attached with the pyridazin ring deviates by 0.0482 (12)Å. The packing of the crystal is stabilised by intermolcular O—H···O hydrogen bonds and weak intramolecular C—H···O hydrogen bonds (Fig. 2 & Table 1).

Related literature top

For the biological activity of morpholine derivatives, see: Lan et al. (2010); Raparti et al. (2009). For a related structure, see: Wang et al. (2012).

Experimental top

The new Mannich base morpholino methyl maleic hydrazide(MMMH) was synthesised by introducing morpholino methyl moiety in place of active hydrogen atom attached to nitrogen of maleic hydrazide through Mannich reaction. An equimolar mixture of maleic hydrazide (11.20 g), formaldehyde (3.00 g) and morpholine (8.7 g) was dissolved in 400 ml of ethanol and refluxed for about 5 hours. The formation of the product MMMH and the completion of the reaction was identified by the formation of a clear solution. The resulting solution was concentrated to 200 ml by distillation under reduced pressure. The concentrate on cooling yielded a colourless crystalline solid, the crude product (20.6g) that was first washed with ethanol and then ether and dried in vacuum oven. The compound MMMH was dissolved in hot ethanol and the homogeneous solution was allowed to evaporate slowly. After two weeks the colourless crystalline solid separated out which was washed with minimum amount of ethanol and then dried in a vaccum oven; a crystal was chosen for X-ray diffraction studies from this sample.

Refinement top

All C-bound H atoms were positioned geometrically and refined using a riding model, with C—H = 0.93 and 0.97 Å, for aryl and methylene H-atoms, respectively. The hydroxyl H-atoms were included at geometrically calculated positions with O—H = 0.82 Å. The H-atoms are constrained to ride on their parent atoms, with Uiso(H) = 1.2 times Ueq(C/O).

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); 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: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, showing displacement ellipsoids drawn at the 30% probability level. H atoms are presented as small spheres of arbitrary radius.
[Figure 2] Fig. 2. The crystal packing of the title compound viewed down a axis. H-atoms not involved in H-bonds have been excluded for clarity.
3-Hydroxy-1-[(morpholin-4-yl)methyl]pyridazin-6(1H)-one top
Crystal data top
C9H13N3O3Z = 2
Mr = 211.22F(000) = 224
Triclinic, P1Dx = 1.372 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 5.2110 (3) ÅCell parameters from 2530 reflections
b = 5.4165 (4) Åθ = 1.1–28.4°
c = 18.4544 (12) ŵ = 0.11 mm1
α = 87.232 (2)°T = 293 K
β = 83.993 (6)°Block, colourless
γ = 80.862 (4)°0.30 × 0.25 × 0.20 mm
V = 511.18 (6) Å3
Data collection top
Bruker SMART APEXII area-detector
diffractometer
2530 independent reflections
Radiation source: fine-focus sealed tube1679 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.027
ω and φ scansθmax = 28.4°, θmin = 1.1°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 66
Tmin = 0.969, Tmax = 0.979k = 77
8839 measured reflectionsl = 2424
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.051Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.158H-atom parameters constrained
S = 1.07 w = 1/[σ2(Fo2) + (0.0734P)2 + 0.1237P]
where P = (Fo2 + 2Fc2)/3
2530 reflections(Δ/σ)max < 0.001
136 parametersΔρmax = 0.31 e Å3
0 restraintsΔρmin = 0.23 e Å3
Crystal data top
C9H13N3O3γ = 80.862 (4)°
Mr = 211.22V = 511.18 (6) Å3
Triclinic, P1Z = 2
a = 5.2110 (3) ÅMo Kα radiation
b = 5.4165 (4) ŵ = 0.11 mm1
c = 18.4544 (12) ÅT = 293 K
α = 87.232 (2)°0.30 × 0.25 × 0.20 mm
β = 83.993 (6)°
Data collection top
Bruker SMART APEXII area-detector
diffractometer
2530 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
1679 reflections with I > 2σ(I)
Tmin = 0.969, Tmax = 0.979Rint = 0.027
8839 measured reflectionsθmax = 28.4°
Refinement top
R[F2 > 2σ(F2)] = 0.051H-atom parameters constrained
wR(F2) = 0.158Δρmax = 0.31 e Å3
S = 1.07Δρmin = 0.23 e Å3
2530 reflectionsAbsolute structure: ?
136 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

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 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 > 2sigma(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
C10.2321 (3)0.5749 (3)0.10380 (9)0.0350 (4)
C20.3128 (3)0.3529 (3)0.06412 (9)0.0393 (4)
H20.22340.31830.02570.047*
C30.5197 (3)0.1956 (3)0.08329 (9)0.0397 (4)
H30.57540.04930.05800.048*
C40.6579 (3)0.2491 (3)0.14265 (9)0.0341 (4)
C50.6847 (3)0.5467 (3)0.23871 (9)0.0382 (4)
H5A0.86980.48200.23160.046*
H5B0.66700.72780.23560.046*
C60.6498 (5)0.2102 (4)0.32915 (12)0.0650 (6)
H6A0.83430.15200.31660.078*
H6B0.55100.11630.30180.078*
C70.5809 (7)0.1687 (6)0.40974 (14)0.0896 (9)
H7A0.61720.00860.42210.108*
H7B0.68880.25410.43670.108*
C80.2589 (6)0.5165 (7)0.41244 (14)0.0896 (9)
H8A0.36270.60650.43940.107*
H8B0.07610.57670.42690.107*
C90.3172 (4)0.5693 (5)0.33187 (11)0.0609 (6)
H9A0.20660.48830.30460.073*
H9B0.28210.74800.32140.073*
N10.3486 (3)0.6309 (2)0.15815 (7)0.0350 (3)
N20.5574 (2)0.4640 (2)0.17747 (7)0.0326 (3)
N30.5895 (3)0.4751 (3)0.31060 (8)0.0430 (4)
O10.0275 (2)0.7323 (2)0.08280 (7)0.0511 (4)
H10.00280.85300.10920.077*
O20.8565 (2)0.1128 (2)0.16258 (7)0.0484 (4)
O30.3137 (5)0.2588 (5)0.43038 (10)0.1016 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0322 (8)0.0339 (8)0.0352 (8)0.0063 (6)0.0032 (6)0.0019 (6)
C20.0397 (9)0.0387 (9)0.0382 (9)0.0042 (7)0.0095 (7)0.0088 (7)
C30.0432 (10)0.0327 (9)0.0403 (9)0.0070 (7)0.0066 (7)0.0111 (7)
C40.0337 (8)0.0291 (8)0.0366 (8)0.0037 (6)0.0019 (6)0.0027 (6)
C50.0377 (9)0.0374 (9)0.0411 (9)0.0050 (7)0.0100 (7)0.0064 (7)
C60.0911 (17)0.0508 (13)0.0530 (12)0.0103 (12)0.0110 (11)0.0064 (10)
C70.132 (3)0.0806 (19)0.0567 (15)0.0218 (18)0.0130 (16)0.0188 (13)
C80.0836 (19)0.125 (3)0.0571 (15)0.0191 (18)0.0134 (13)0.0112 (16)
C90.0515 (12)0.0807 (16)0.0503 (12)0.0107 (11)0.0010 (9)0.0100 (11)
N10.0349 (7)0.0299 (7)0.0373 (7)0.0065 (5)0.0063 (6)0.0043 (5)
N20.0314 (7)0.0292 (7)0.0353 (7)0.0039 (5)0.0066 (5)0.0042 (5)
N30.0480 (9)0.0448 (9)0.0375 (8)0.0066 (7)0.0093 (6)0.0049 (6)
O10.0495 (8)0.0477 (8)0.0504 (8)0.0227 (6)0.0192 (6)0.0131 (6)
O20.0417 (7)0.0458 (7)0.0523 (8)0.0175 (6)0.0137 (6)0.0091 (6)
O30.1169 (18)0.1262 (19)0.0662 (12)0.0507 (15)0.0097 (11)0.0167 (12)
Geometric parameters (Å, º) top
C1—N11.297 (2)C6—H6A0.9700
C1—O11.3341 (18)C6—H6B0.9700
C1—C21.421 (2)C7—O31.419 (4)
C2—C31.331 (2)C7—H7A0.9700
C2—H20.9300C7—H7B0.9700
C3—C41.437 (2)C8—O31.410 (4)
C3—H30.9300C8—C91.509 (3)
C4—O21.2497 (18)C8—H8A0.9700
C4—N21.360 (2)C8—H8B0.9700
C5—N31.425 (2)C9—N31.449 (3)
C5—N21.4892 (19)C9—H9A0.9700
C5—H5A0.9700C9—H9B0.9700
C5—H5B0.9700N1—N21.3660 (17)
C6—N31.452 (3)O1—H10.8200
C6—C71.508 (3)
N1—C1—O1119.33 (14)C6—C7—H7A109.4
N1—C1—C2123.26 (14)O3—C7—H7B109.4
O1—C1—C2117.41 (14)C6—C7—H7B109.4
C3—C2—C1118.37 (15)H7A—C7—H7B108.0
C3—C2—H2120.8O3—C8—C9111.8 (2)
C1—C2—H2120.8O3—C8—H8A109.3
C2—C3—C4120.80 (14)C9—C8—H8A109.3
C2—C3—H3119.6O3—C8—H8B109.3
C4—C3—H3119.6C9—C8—H8B109.3
O2—C4—N2120.60 (14)H8A—C8—H8B107.9
O2—C4—C3124.21 (14)N3—C9—C8108.85 (19)
N2—C4—C3115.19 (13)N3—C9—H9A109.9
N3—C5—N2116.93 (13)C8—C9—H9A109.9
N3—C5—H5A108.1N3—C9—H9B109.9
N2—C5—H5A108.1C8—C9—H9B109.9
N3—C5—H5B108.1H9A—C9—H9B108.3
N2—C5—H5B108.1C1—N1—N2117.12 (12)
H5A—C5—H5B107.3C4—N2—N1125.20 (13)
N3—C6—C7109.2 (2)C4—N2—C5121.09 (13)
N3—C6—H6A109.8N1—N2—C5113.57 (12)
C7—C6—H6A109.8C5—N3—C9115.28 (15)
N3—C6—H6B109.8C5—N3—C6115.05 (15)
C7—C6—H6B109.8C9—N3—C6110.95 (18)
H6A—C6—H6B108.3C1—O1—H1109.5
O3—C7—C6111.4 (2)C8—O3—C7109.8 (2)
O3—C7—H7A109.4
N1—C1—C2—C30.6 (3)C1—N1—N2—C42.5 (2)
O1—C1—C2—C3178.72 (16)C1—N1—N2—C5178.12 (14)
C1—C2—C3—C40.0 (3)N3—C5—N2—C494.05 (18)
C2—C3—C4—O2178.44 (17)N3—C5—N2—N190.12 (17)
C2—C3—C4—N21.7 (2)N2—C5—N3—C961.2 (2)
N3—C6—C7—O357.7 (3)N2—C5—N3—C669.9 (2)
O3—C8—C9—N358.1 (3)C8—C9—N3—C5170.26 (19)
O1—C1—N1—N2179.85 (14)C8—C9—N3—C656.7 (2)
C2—C1—N1—N20.5 (2)C7—C6—N3—C5170.00 (19)
O2—C4—N2—N1177.10 (14)C7—C6—N3—C956.9 (3)
C3—C4—N2—N13.0 (2)C9—C8—O3—C759.2 (3)
O2—C4—N2—C51.8 (2)C6—C7—O3—C858.9 (3)
C3—C4—N2—C5178.32 (14)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O2i0.821.772.5777 (16)167
C2—H2···O1ii0.932.553.478 (2)175
C5—H5A···O20.972.442.772 (2)100
Symmetry codes: (i) x1, y+1, z; (ii) x, y+1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1···O2i0.821.772.5777 (16)167
C2—H2···O1ii0.932.553.478 (2)175
C5—H5A···O20.972.442.772 (2)100
Symmetry codes: (i) x1, y+1, z; (ii) x, y+1, z.
Acknowledgements top

The authors thank the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection. TS thanks the DST for an Inspire fellowship. The UGC (SAP–CAS) is acknowleged for departmental facilities.

references
References top

Bruker (2008). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.

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

Lan, P., Chen, W. N., Xiao, G. K., Sun, P. H. & Chen, W. M. (2010). Bioorg. Med. Chem. Lett. 20, 6764–6772.

Raparti, V., Chitre, T., Bothara, K., Kumar, V., Dangre, S., Khachane, C., Gore, S. & Deshmane, B. (2009). Eur. J. Med. Chem. 44, 3954–3960.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D 65, 148–155.

Wang, L.-J., Li, W.-W., Yang, S.-Y. & Yang, L. (2012). Acta Cryst. E68, o1235.