Crystal structure of 7-hy-droxy-8-[(4-methyl-piperazin-1-yl)meth-yl]-2H-chromen-2-one.

In the title compound, C15H18N2O3, the coumarin ring is essentially planar, with an r.m.s. deviation of 0.012 Å. An intra-molecular O-H⋯N hydrogen bond forms an S(6) ring motif. The piperazine ring adopts a chair conformation. In the crystal, a C-H⋯O hydrogen bond generates a C(4) chain motif running along the c axis. The chain structure is stabilized by a C-H⋯π inter-action. The chains are linked by π-π inter-actions [centroid-centroid distance of 3.5745 (11) Å], forming a sheet structure parallel to the bc plane.

Chemical context

Coumarin (2H-chromen-2-one) derivatives have wide applications in diverse areas such as pharmaceuticals (Neyts et al., 2009 ▸), dyes (Hara et al., 2003 ▸) and liquid crystal (Schadt et al., 1996 ▸). Since piperazine is a heterocyclic and aliphatic di­amine, having a flexible structure and a high solubility not only in organic solvents but also in water, its derivatives form complexes with various metal ions in chair and boat conformations. For example, the piperazine ring in a dinuclear zinc(II) complex with a piperazine-based Schiff base adopts a chair form, whereas that in a mononuclear cobalt(III) complex with the same ligand is in a boat form (Cretu et al., 2015 ▸). Moreover, the piperazine ring has recently been utilized as a proton-recognition site in pH-sensitive fluorescent probes (Lee et al., 2014 ▸) and a linker bridging two chromophores in fluorescent ion-sensors (Srivastava et al., 2014 ▸; Jiang et al., 2011 ▸). We are attempting to develop water-soluble chemosensors based on coumarin, and report here the mol­ecular and crystal structure of the title compound.

Structural commentary

The mol­ecular structure of the title compound is shown in Fig. 1 ▸. The coumarin ring is almost planar with a maximum deviation of 0.023 (2) Å for atom C6. There is an intra­molecular O—H⋯N hydrogen bond involving the hy­droxy group (O1—H1) and a piperazine N atom (N4), generating an S(6) ring motif (Fig. 1 ▸ and Table 1 ▸). The piperazine ring adopts a chair conformation with puckering parameters: Q = 0.582 (2) Å, θ = 1.9 (2)° and φ = 22 (7)°. The C16—N4—C15—C14 and C19—N4—C15—C14 torsion angles are −78.8 (2) and 158.52 (16)°, respectively. The bond lengths and angles of the title compound are normal and agree with those values in other Mannich bases of 7-hy­droxy­coumarin (Leong & Vittal, 2010 ▸; Kobayashi et al., 2014 ▸).

Figure 1

The mol­ecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The intra­molecular O—H⋯N hydrogen bond is shown as a dashed line.

Table 1

Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the O3/C9–C13 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1⋯N4	1.02 (3)	1.66 (3)	2.607 (2)	153 (3)
C11—H11⋯O2i	0.93	2.59	3.239 (2)	128
C15—H15B⋯Cg1ii	0.97	2.99	3.802 (2)	142

Symmetry codes: (i) ; (ii) .

Supra­molecular features

In the crystal, mol­ecules are linked by a C—H⋯O hydrogen bond (C11—H11⋯O2i; symmetry code in Table 1 ▸), forming a C(4) chain motif running parallel to the c axis. A C—H⋯π inter­action (C15—H15B⋯Cg1ii; Cg1 is the centroid of the O3/C9–C13 ring; symmetry code in Table 1 ▸) is also observed in the chain (Fig. 2 ▸). The chains are linked through slipped parallel π–π inter­actions [Cg1⋯Cg1iii = 3.5745 (11) Å, inter-planar distance = 3.404 Å and slippage = 1.090 Å; symmetry code: (iii) −x, −y, −z + 1], forming a supra­molecular sheet parallel to the bc plane.

Figure 2

A view along the a axis of the crystal packing of the title compound. The hydrogen bonds and C—H⋯π inter­actions are shown as dashed lines. H atoms not involved in these inter­actions have been omitted for clarity.

Database survey

A search of the Cambridge Structural Database (CSD, Version 5.37; Groom et al., 2016 ▸) gave 1700 and 85 structures containing coumarin and 7-hy­droxy­coumarin, respectively. Of these structures, the compounds that resemble the title compound are N-(7-hy­droxy-4-methyl-8-coumarin­yl)-l-alanine (Leong & Vittal, 2010 ▸) and 8-{[bis­(pyridin-2-ylmeth­yl)amino]­meth­yl}-7-hy­droxy-2H-chromen-2-one (Kobayashi et al., 2014 ▸). A search for the fragment methyl­piperazine gave 666 hits, but none contained coumarin.

Synthesis and crystallization

The title compound was prepared by modification of the reported procedure (Mazzei et al., 2008 ▸). 1-Methyl­piperazine (0.64 g, 6.4 mmol) and formaldehyde (37% aqueous solution 0.64 mL, 0.64 mmol) in 50 ml of aceto­nitrile was stirred for 30 min at 333 K. To the product obtained was added 7-hy­droxy­coumarin (1.04 g, 0.64 mmol), and the mixture was heated for 3 h at 338 K. After the completion of the reaction, as indicated by TLC, the solvent was removed under vacuum. The residue was suspended in water and extracted with chloro­form, and the extract was washed with a saturated sodium chloride aqueous solution. The organic phase was separated, dried with anhydrous sodium sulfate, and the solvent was removed under vacuum to yield a yellow product. The product was recrystallized from aceto­nitrile solution to obtained colorless crystals of the title compound (yield: 76%). MS (m/z): [M + H]+, 275.1. Analysis calculated for C15H18N2O3: C 65.68, H 6.61, N 10.21%; found: C 65.40, H 6.45, N 10.06%.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. The hy­droxy H atom was located in a difference Fourier map and freely refined. The C-bound H atoms were positioned geometrically and refined using a riding model: C—H = 0.93–0.97 Å with U iso(H) = 1.2U eq(C).

Table 2

Experimental details

Crystal data
Chemical formula	C15H18N2O3
M r	274.31
Crystal system, space group	Monoclinic, P21/c
Temperature (K)	296
a, b, c (Å)	15.3519 (6), 9.4005 (4), 9.9702 (4)
β (°)	106.954 (1)
V (Å3)	1376.32 (10)
Z	4
Radiation type	Mo Kα
μ (mm−1)	0.09
Crystal size (mm)	0.20 × 0.10 × 0.10
Data collection
Diffractometer	Rigaku R-AXIS RAPID
Absorption correction	Multi-scan (ABSCOR; Higashi, 1995 ▸)
T min, T max	0.823, 0.991
No. of measured, independent and observed [F 2 > 2.0σ(F 2)] reflections	13237, 3136, 1566
R int	0.037
(sin θ/λ)max (Å−1)	0.648
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.042, 0.162, 1.05
No. of reflections	3136
No. of parameters	186
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.19, −0.18

Computer programs: RAPID-AUTO (Rigaku, 2006 ▸), SIR92 (Altomare et al., 1993 ▸), SHELXL97 (Sheldrick, 2008 ▸), PLATON (Spek, 2015 ▸), CrystalStructure (Rigaku, 2016 ▸).

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989016017217/is5461sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016017217/is5461Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989016017217/is5461Isup3.cml

CCDC reference: 1511659

Additional supporting information: crystallographic information; 3D view; checkCIF report

C15H18N2O3	F(000) = 584.00
Mr = 274.31	Dx = 1.324 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71075 Å
a = 15.3519 (6) Å	Cell parameters from 6828 reflections
b = 9.4005 (4) Å	θ = 3.0–27.4°
c = 9.9702 (4) Å	µ = 0.09 mm−1
β = 106.954 (1)°	T = 296 K
V = 1376.32 (10) Å3	Block, colorless
Z = 4	0.20 × 0.10 × 0.10 mm

Rigaku R-AXIS RAPID diffractometer	1566 reflections with F2 > 2.0σ(F2)
Detector resolution: 10.000 pixels mm-1	Rint = 0.037
ω scans	θmax = 27.4°, θmin = 3.0°
Absorption correction: multi-scan (ABSCOR; Higashi, 1995)	h = −19→19
Tmin = 0.823, Tmax = 0.991	k = −12→12
13237 measured reflections	l = −12→11
3136 independent reflections

Refinement on F2	Secondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.042	Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.162	H atoms treated by a mixture of independent and constrained refinement
S = 1.05	w = 1/[σ2(Fo2) + (0.0829P)2 + 0.0112P] where P = (Fo2 + 2Fc2)/3
3136 reflections	(Δ/σ)max < 0.001
186 parameters	Δρmax = 0.19 e Å−3
0 restraints	Δρmin = −0.18 e Å−3
Primary atom site location: structure-invariant direct methods

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 was performed using all reflections. The weighted R-factor (wR) and goodness of fit (S) are based on F2. R-factor (gt) are based on F. The threshold expression of F2 > 2.0 sigma(F2) is used only for calculating R-factor (gt).

	x	y	z	Uiso*/Ueq
O1	0.30930 (10)	−0.15085 (16)	0.50405 (16)	0.0643 (4)
O2	−0.04527 (10)	0.32032 (16)	0.48480 (15)	0.0652 (5)
O3	0.06794 (9)	0.17001 (13)	0.49705 (13)	0.0516 (4)
N4	0.26991 (10)	0.05030 (17)	0.31592 (15)	0.0490 (4)
N5	0.41058 (11)	0.13494 (18)	0.19673 (17)	0.0570 (5)
C6	0.24973 (13)	−0.0902 (2)	0.5650 (2)	0.0506 (5)
C7	0.25092 (14)	−0.1386 (2)	0.6984 (2)	0.0552 (5)
H7	0.2931	−0.2072	0.7432	0.066*
C8	0.19055 (13)	−0.0858 (2)	0.7631 (2)	0.0535 (5)
H8	0.1917	−0.1194	0.8513	0.064*
C9	0.12716 (12)	0.0182 (2)	0.69801 (18)	0.0471 (5)
C10	0.06032 (14)	0.0772 (2)	0.7567 (2)	0.0525 (5)
H10	0.0575	0.0456	0.8438	0.063*
C11	0.00197 (14)	0.1765 (2)	0.6887 (2)	0.0530 (5)
H11	−0.0407	0.2128	0.7294	0.064*
C12	0.00365 (13)	0.2289 (2)	0.5539 (2)	0.0507 (5)
C13	0.12898 (12)	0.0672 (2)	0.56609 (19)	0.0455 (5)
C14	0.18880 (12)	0.0155 (2)	0.49655 (18)	0.0484 (5)
C15	0.18271 (13)	0.0648 (2)	0.3490 (2)	0.0588 (6)
H15A	0.1365	0.0094	0.2822	0.071*
H15B	0.1639	0.1637	0.3387	0.071*
C16	0.33329 (15)	0.1654 (2)	0.3767 (2)	0.0638 (6)
H16A	0.3430	0.1690	0.4772	0.077*
H16B	0.3077	0.2557	0.3370	0.077*
C17	0.42259 (15)	0.1407 (3)	0.3465 (2)	0.0698 (7)
H17A	0.4645	0.2169	0.3876	0.084*
H17B	0.4490	0.0520	0.3893	0.084*
C18	0.34652 (13)	0.0235 (2)	0.1345 (2)	0.0565 (5)
H18A	0.3716	−0.0678	0.1719	0.068*
H18B	0.3370	0.0222	0.0340	0.068*
C19	0.25631 (13)	0.0457 (2)	0.16373 (19)	0.0558 (5)
H19A	0.2291	0.1341	0.1214	0.067*
H19B	0.2152	−0.0314	0.1227	0.067*
C20	0.49746 (16)	0.1123 (3)	0.1694 (3)	0.0822 (8)
H20A	0.5379	0.1894	0.2085	0.099*
H20B	0.4883	0.1082	0.0700	0.099*
H20C	0.5236	0.0245	0.2115	0.099*
H1	0.3043 (18)	−0.092 (3)	0.417 (3)	0.107 (9)*

	U11	U22	U33	U12	U13	U23
O1	0.0681 (10)	0.0675 (10)	0.0633 (10)	0.0177 (7)	0.0287 (8)	0.0060 (7)
O2	0.0673 (10)	0.0717 (10)	0.0621 (10)	0.0164 (8)	0.0276 (8)	0.0063 (8)
O3	0.0511 (8)	0.0612 (9)	0.0469 (8)	0.0076 (6)	0.0210 (6)	0.0021 (6)
N4	0.0470 (9)	0.0617 (10)	0.0418 (9)	−0.0007 (8)	0.0184 (7)	−0.0019 (7)
N5	0.0529 (10)	0.0658 (11)	0.0559 (10)	−0.0037 (8)	0.0217 (8)	0.0024 (8)
C6	0.0502 (11)	0.0537 (12)	0.0499 (11)	−0.0005 (9)	0.0179 (9)	−0.0016 (9)
C7	0.0526 (11)	0.0600 (13)	0.0510 (12)	0.0015 (10)	0.0119 (10)	0.0065 (10)
C8	0.0566 (12)	0.0598 (12)	0.0434 (10)	−0.0070 (10)	0.0137 (9)	0.0040 (9)
C9	0.0488 (10)	0.0532 (11)	0.0408 (10)	−0.0086 (9)	0.0155 (9)	−0.0037 (8)
C10	0.0577 (12)	0.0604 (12)	0.0420 (10)	−0.0081 (10)	0.0186 (9)	−0.0039 (9)
C11	0.0557 (12)	0.0601 (13)	0.0489 (11)	−0.0047 (10)	0.0242 (10)	−0.0075 (10)
C12	0.0495 (11)	0.0562 (12)	0.0496 (11)	−0.0030 (10)	0.0197 (10)	−0.0065 (9)
C13	0.0437 (10)	0.0484 (11)	0.0441 (11)	−0.0007 (8)	0.0126 (9)	−0.0013 (8)
C14	0.0460 (10)	0.0572 (12)	0.0437 (10)	0.0004 (9)	0.0159 (9)	−0.0001 (9)
C15	0.0518 (12)	0.0777 (15)	0.0508 (12)	0.0094 (10)	0.0210 (10)	0.0095 (10)
C16	0.0708 (14)	0.0702 (15)	0.0533 (12)	−0.0131 (11)	0.0226 (11)	−0.0149 (10)
C17	0.0592 (13)	0.0911 (18)	0.0593 (14)	−0.0175 (12)	0.0176 (11)	−0.0095 (12)
C18	0.0616 (12)	0.0662 (13)	0.0461 (11)	0.0004 (11)	0.0227 (10)	−0.0011 (9)
C19	0.0546 (12)	0.0709 (14)	0.0426 (11)	−0.0024 (10)	0.0153 (9)	−0.0028 (9)
C20	0.0641 (15)	0.105 (2)	0.0864 (18)	−0.0046 (14)	0.0366 (14)	0.0032 (15)

O1—C6	1.361 (2)	C10—H10	0.9300
O1—H1	1.02 (3)	C11—C12	1.438 (3)
O2—C12	1.215 (2)	C11—H11	0.9300
O3—C13	1.382 (2)	C13—C14	1.390 (2)
O3—C12	1.389 (2)	C14—C15	1.519 (2)
N4—C16	1.463 (2)	C15—H15A	0.9700
N4—C19	1.471 (2)	C15—H15B	0.9700
N4—C15	1.475 (2)	C16—C17	1.505 (3)
N5—C18	1.447 (2)	C16—H16A	0.9700
N5—C17	1.451 (3)	C16—H16B	0.9700
N5—C20	1.453 (3)	C17—H17A	0.9700
C6—C14	1.399 (3)	C17—H17B	0.9700
C6—C7	1.401 (3)	C18—C19	1.511 (2)
C7—C8	1.368 (3)	C18—H18A	0.9700
C7—H7	0.9300	C18—H18B	0.9700
C8—C9	1.399 (3)	C19—H19A	0.9700
C8—H8	0.9300	C19—H19B	0.9700
C9—C13	1.401 (2)	C20—H20A	0.9600
C9—C10	1.433 (3)	C20—H20B	0.9600
C10—C11	1.334 (3)	C20—H20C	0.9600
C6—O1—H1	105.1 (15)	N4—C15—H15A	109.1
C13—O3—C12	122.33 (15)	C14—C15—H15A	109.1
C16—N4—C19	109.05 (15)	N4—C15—H15B	109.1
C16—N4—C15	112.12 (15)	C14—C15—H15B	109.1
C19—N4—C15	111.59 (15)	H15A—C15—H15B	107.8
C18—N5—C17	109.58 (15)	N4—C16—C17	109.76 (16)
C18—N5—C20	111.11 (17)	N4—C16—H16A	109.7
C17—N5—C20	110.52 (18)	C17—C16—H16A	109.7
O1—C6—C14	121.37 (17)	N4—C16—H16B	109.7
O1—C6—C7	117.59 (18)	C17—C16—H16B	109.7
C14—C6—C7	121.03 (18)	H16A—C16—H16B	108.2
C8—C7—C6	120.47 (19)	N5—C17—C16	111.21 (18)
C8—C7—H7	119.8	N5—C17—H17A	109.4
C6—C7—H7	119.8	C16—C17—H17A	109.4
C7—C8—C9	120.69 (18)	N5—C17—H17B	109.4
C7—C8—H8	119.7	C16—C17—H17B	109.4
C9—C8—H8	119.7	H17A—C17—H17B	108.0
C8—C9—C13	117.62 (17)	N5—C18—C19	111.37 (16)
C8—C9—C10	124.42 (17)	N5—C18—H18A	109.4
C13—C9—C10	117.96 (18)	C19—C18—H18A	109.4
C11—C10—C9	121.20 (18)	N5—C18—H18B	109.4
C11—C10—H10	119.4	C19—C18—H18B	109.4
C9—C10—H10	119.4	H18A—C18—H18B	108.0
C10—C11—C12	121.47 (18)	N4—C19—C18	109.93 (15)
C10—C11—H11	119.3	N4—C19—H19A	109.7
C12—C11—H11	119.3	C18—C19—H19A	109.7
O2—C12—O3	116.46 (17)	N4—C19—H19B	109.7
O2—C12—C11	126.57 (18)	C18—C19—H19B	109.7
O3—C12—C11	116.97 (18)	H19A—C19—H19B	108.2
O3—C13—C14	116.53 (16)	N5—C20—H20A	109.5
O3—C13—C9	120.07 (16)	N5—C20—H20B	109.5
C14—C13—C9	123.38 (18)	H20A—C20—H20B	109.5
C13—C14—C6	116.77 (16)	N5—C20—H20C	109.5
C13—C14—C15	120.91 (17)	H20A—C20—H20C	109.5
C6—C14—C15	122.18 (16)	H20B—C20—H20C	109.5
N4—C15—C14	112.61 (16)
O1—C6—C7—C8	−177.60 (18)	O3—C13—C14—C15	−3.3 (3)
C14—C6—C7—C8	1.8 (3)	C9—C13—C14—C15	175.31 (17)
C6—C7—C8—C9	−0.6 (3)	O1—C6—C14—C13	178.06 (17)
C7—C8—C9—C13	−1.0 (3)	C7—C6—C14—C13	−1.3 (3)
C7—C8—C9—C10	178.61 (19)	O1—C6—C14—C15	2.5 (3)
C8—C9—C10—C11	179.86 (19)	C7—C6—C14—C15	−176.87 (18)
C13—C9—C10—C11	−0.6 (3)	C16—N4—C15—C14	−78.8 (2)
C9—C10—C11—C12	−0.1 (3)	C19—N4—C15—C14	158.52 (16)
C13—O3—C12—O2	178.67 (16)	C13—C14—C15—N4	155.52 (18)
C13—O3—C12—C11	−0.9 (3)	C6—C14—C15—N4	−29.1 (3)
C10—C11—C12—O2	−178.7 (2)	C19—N4—C16—C17	−59.0 (2)
C10—C11—C12—O3	0.8 (3)	C15—N4—C16—C17	176.87 (17)
C12—O3—C13—C14	179.00 (16)	C18—N5—C17—C16	−57.7 (2)
C12—O3—C13—C9	0.3 (3)	C20—N5—C17—C16	179.51 (18)
C8—C9—C13—O3	−179.94 (16)	N4—C16—C17—N5	59.5 (2)
C10—C9—C13—O3	0.4 (3)	C17—N5—C18—C19	57.0 (2)
C8—C9—C13—C14	1.5 (3)	C20—N5—C18—C19	179.46 (18)
C10—C9—C13—C14	−178.15 (17)	C16—N4—C19—C18	58.4 (2)
O3—C13—C14—C6	−178.98 (16)	C15—N4—C19—C18	−177.23 (16)
C9—C13—C14—C6	−0.3 (3)	N5—C18—C19—N4	−58.1 (2)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1···N4	1.02 (3)	1.66 (3)	2.607 (2)	153 (3)
C11—H11···O2i	0.93	2.59	3.239 (2)	128
C15—H15B···Cg1ii	0.97	2.99	3.802 (2)	142