4-Acetyl-3,3-diethyl-5-hydr-oxy-2-morpholino-2,3-dihydro-1-benzofuran.

In the title compound, C(18)H(25)NO(4), the benzofuran ring is almost planar and the morpholino ring displays a chair conformation. The packing of compound has a one-dimensional structure constructed through inter-molecular O-H⋯O hydrogen bonds. The conformation is stabilized by intra-molecular C-H⋯N and C-H⋯O inter-actions.

Related literature

For biological activity, see: Araya-Maturana et al. (2002 ▶, 2006 ▶). For related structures, see: Dusausoy et al. (1973 ▶); Filarowski et al. (2005 ▶); Huang et al. (2004 ▶). For the synthesis, see: Castro et al. (1983 ▶). For hydrogen bonding, see: Desiraju (2002 ▶). For puckering parameters, see: Cremer & Pople, 1975 ▶).

Experimental

Crystal data

C18H25NO4

M = 319.39

Orthorhombic,

a = 7.7769 (2) Å

b = 19.4256 (5) Å

c = 22.3875 (6) Å

V = 3382.10 (15) Å3

Z = 8

Mo Kα radiation

μ = 0.09 mm−1

T = 150 (2) K

0.43 × 0.30 × 0.30 mm

Data collection

Siemens SMART CCD area-detector diffractometer

Absorption correction: multi-scan (SADABS; Bruker 1999 ▶) T min = 0.963, T max = 0.974

19635 measured reflections

2988 independent reflections

2537 reflections with I > 2σ(I)

R int = 0.027

Refinement

R[F 2 > 2σ(F 2)] = 0.037

wR(F 2) = 0.099

S = 1.04

2988 reflections

215 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.22 e Å−3

Δρmin = −0.15 e Å−3

Data collection: SMART-NT (Bruker, 2001 ▶); cell refinement: SAINT-NT (Bruker, 1999 ▶); data reduction: SAINT-NT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL-NT (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL-NT.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808034065/pv2104sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808034065/pv2104Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C18H25NO4	F000 = 1376
Mr = 319.39	Dx = 1.255 Mg m−3
Orthorhombic, Pbca	Mo Kα radiation λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 6371 reflections
a = 7.7769 (2) Å	θ = 2.3–24.8º
b = 19.4256 (5) Å	µ = 0.09 mm−1
c = 22.3875 (6) Å	T = 150 (2) K
V = 3382.10 (15) Å3	Block, colorless
Z = 8	0.43 × 0.30 × 0.30 mm

Siemens SMART CCD area-detector diffractometer	2988 independent reflections
Radiation source: fine-focus sealed tube	2537 reflections with I > 2σ(I)
Monochromator: graphite	Rint = 0.027
T = 150(2) K	θmax = 25.0º
φ and ω scans	θmin = 1.8º
Absorption correction: part of the refinement model (ΔF)(SADABS; Bruker 1999)	h = −9→9
Tmin = 0.963, Tmax = 0.974	k = −23→23
19635 measured reflections	l = −26→26

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.037	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.099	w = 1/[σ2(Fo2) + (0.0508P)2 + 1.1025P] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max = 0.001
2988 reflections	Δρmax = 0.22 e Å−3
215 parameters	Δρmin = −0.15 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

Experimental. Proton and 13C NMR spectra were acquired using a Bruker AVANCE DRX 300 spectrometer operating at 300.13 MHz (1H) or 75.47 MHz (13 C). All measurements were carried out at a probe temperature of 300 K.1H-RMN(CDCl3): 0.65(3H, t, J = 7 Hz); 1.05(3H, t, J = 7 Hz); 1.59–1.85 (4H, m, 2XCH2-CH3); 2.55(3H, S, CH3CO); 2.51–2.61(2H, m, CH2); 2.66–2.78(2H, m, CH2); 3.55–3.70(4H, m, 2XCH2); 4.71(1H, s, CH); 6.19(1H, s broad, OH); 6.56(1H, d, J = 8.5 Hz); 6.62(1H, d, J = 8.5 Hz).13C-RMN(CDCl3): 8.36; 10.18; 25.45; 32.68; 32.90; 49.81; 52.00; 66.93; 106.51; 109.63; 115.36; 126.63; 129.92; 146.31; 153.25; 205.62.

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.Least-squares planes (x,y,z in crystal coordinates) and deviations from them (* indicates atom used to define plane)7.0500 (0.0020) x + 7.3246 (0.0105) y + 4.2493 (0.0126) z = 12.9211 (0.0092)* -0.0040 (0.0010) C4 * 0.0120 (0.0009) C5 * -0.0103 (0.0010) C6 * 0.0006 (0.0010) C7 * 0.0076 (0.0011) C8 * -0.0059 (0.0010) C9Rms deviation of fitted atoms = 0.00781.4062(0.0062) x + 16.5869(0.0074) y - 10.9267(0.0135) z = 13.1527(0.0123)Angle to previous plane (with approximate e.s.d.) =S 66.84 (0.06)* 0.0007 (0.0003) C5 * -0.0022 (0.0011) C14 * 0.0007 (0.0003) C15 * 0.0009 (0.0004) O3

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.

	x	y	z	Uiso*/Ueq
O1	0.80326 (14)	0.80844 (5)	0.31337 (4)	0.0345 (3)
C2	0.74318 (19)	0.78750 (7)	0.37275 (6)	0.0280 (3)
H20	0.8428	0.7659	0.3939	0.034*
N1	0.60986 (15)	0.73632 (6)	0.36854 (5)	0.0270 (3)
C16	0.6798 (2)	0.66749 (7)	0.35651 (7)	0.0328 (3)
H16A	0.7712	0.6567	0.3859	0.039*
H16B	0.7314	0.6664	0.3161	0.039*
C17	0.5395 (2)	0.61465 (8)	0.36064 (7)	0.0360 (4)
H17A	0.5879	0.5684	0.3527	0.043*
H17B	0.4913	0.6146	0.4016	0.043*
O4	0.40535 (14)	0.62893 (5)	0.31851 (5)	0.0367 (3)
C18	0.3362 (2)	0.69617 (7)	0.32890 (7)	0.0355 (4)
H18A	0.2827	0.6976	0.3690	0.043*
H18B	0.2457	0.7059	0.2990	0.043*
C19	0.47396 (19)	0.75074 (8)	0.32496 (6)	0.0320 (3)
H19A	0.5232	0.7514	0.2842	0.038*
H19B	0.4232	0.7965	0.3331	0.038*
C3	0.69878 (18)	0.85594 (7)	0.40661 (6)	0.0264 (3)
C10	0.53656 (19)	0.85133 (7)	0.44592 (6)	0.0292 (3)
H10A	0.5118	0.8978	0.4619	0.035*
H10B	0.4385	0.8380	0.4202	0.035*
C11	0.5450 (2)	0.80105 (8)	0.49828 (7)	0.0399 (4)
H11A	0.5757	0.7552	0.4835	0.060*
H11B	0.4327	0.7991	0.5180	0.060*
H11C	0.6321	0.8167	0.5269	0.060*
C12	0.85520 (19)	0.87683 (8)	0.44551 (7)	0.0328 (3)
H12A	0.8271	0.9205	0.4661	0.039*
H12B	0.8713	0.8412	0.4767	0.039*
C13	1.0247 (2)	0.88622 (10)	0.41292 (8)	0.0492 (4)
H13A	1.0583	0.8427	0.3942	0.074*
H13B	1.1136	0.9004	0.4414	0.074*
H13C	1.0117	0.9217	0.3821	0.074*
C4	0.67804 (17)	0.90534 (7)	0.35435 (6)	0.0248 (3)
C5	0.61288 (17)	0.97222 (7)	0.35094 (6)	0.0239 (3)
C14	0.55496 (19)	1.01250 (7)	0.40490 (6)	0.0262 (3)
O3	0.65792 (14)	1.02913 (5)	0.44311 (4)	0.0361 (3)
C15	0.3689 (2)	1.03120 (8)	0.40908 (7)	0.0356 (4)
H15A	0.3477	1.0554	0.4468	0.053*
H15B	0.2990	0.9893	0.4077	0.053*
H15C	0.3381	1.0612	0.3755	0.053*
C6	0.60992 (18)	1.00459 (7)	0.29479 (6)	0.0257 (3)
O2	0.54332 (14)	1.07011 (5)	0.29248 (5)	0.0315 (3)
C7	0.67545 (19)	0.97197 (7)	0.24488 (6)	0.0303 (3)
H7	0.6743	0.9951	0.2075	0.036*
C8	0.7427 (2)	0.90606 (7)	0.24851 (7)	0.0333 (3)
H8	0.7885	0.8837	0.2143	0.040*
C9	0.74103 (18)	0.87401 (7)	0.30338 (6)	0.0284 (3)
H2	0.562 (3)	1.0879 (10)	0.2559 (10)	0.063 (6)*

	U11	U22	U33	U12	U13	U23
O1	0.0429 (6)	0.0272 (5)	0.0333 (6)	0.0089 (5)	0.0125 (5)	0.0046 (4)
C2	0.0319 (7)	0.0258 (7)	0.0265 (7)	0.0034 (6)	0.0022 (6)	0.0045 (6)
N1	0.0327 (6)	0.0213 (6)	0.0270 (6)	0.0044 (5)	−0.0028 (5)	0.0003 (5)
C16	0.0385 (8)	0.0254 (7)	0.0344 (8)	0.0067 (6)	−0.0023 (7)	−0.0021 (6)
C17	0.0466 (9)	0.0255 (7)	0.0359 (8)	0.0036 (7)	−0.0054 (7)	−0.0019 (6)
O4	0.0447 (6)	0.0306 (6)	0.0349 (6)	0.0018 (5)	−0.0063 (5)	−0.0089 (4)
C18	0.0387 (8)	0.0343 (8)	0.0334 (8)	0.0064 (7)	−0.0059 (7)	−0.0076 (6)
C19	0.0398 (8)	0.0288 (7)	0.0274 (7)	0.0075 (7)	−0.0043 (6)	−0.0005 (6)
C3	0.0305 (7)	0.0222 (7)	0.0263 (7)	0.0007 (6)	0.0004 (6)	0.0026 (5)
C10	0.0362 (8)	0.0248 (7)	0.0265 (7)	−0.0007 (6)	0.0046 (6)	0.0005 (6)
C11	0.0569 (10)	0.0318 (8)	0.0311 (8)	−0.0051 (7)	0.0082 (7)	0.0046 (6)
C12	0.0366 (8)	0.0286 (8)	0.0333 (8)	−0.0005 (6)	−0.0056 (6)	0.0051 (6)
C13	0.0362 (9)	0.0511 (11)	0.0603 (11)	−0.0074 (8)	−0.0052 (8)	0.0048 (9)
C4	0.0241 (7)	0.0252 (7)	0.0252 (7)	−0.0020 (5)	0.0009 (5)	0.0029 (5)
C5	0.0245 (7)	0.0216 (7)	0.0257 (7)	−0.0044 (5)	0.0000 (5)	0.0007 (5)
C14	0.0360 (8)	0.0176 (6)	0.0249 (7)	−0.0042 (6)	−0.0015 (6)	0.0031 (5)
O3	0.0437 (6)	0.0339 (6)	0.0306 (6)	−0.0042 (5)	−0.0063 (5)	−0.0040 (4)
C15	0.0388 (9)	0.0380 (8)	0.0301 (8)	0.0050 (7)	0.0022 (6)	−0.0037 (6)
C6	0.0279 (7)	0.0207 (7)	0.0284 (7)	−0.0036 (6)	−0.0025 (6)	0.0022 (5)
O2	0.0446 (6)	0.0210 (5)	0.0288 (5)	0.0013 (4)	−0.0005 (5)	0.0042 (4)
C7	0.0374 (8)	0.0304 (7)	0.0231 (7)	−0.0019 (6)	0.0032 (6)	0.0066 (6)
C8	0.0406 (8)	0.0314 (8)	0.0278 (7)	0.0028 (6)	0.0106 (7)	0.0008 (6)
C9	0.0301 (7)	0.0238 (7)	0.0314 (7)	0.0023 (6)	0.0055 (6)	0.0018 (6)

O1—C9	1.3808 (17)	C11—H11A	0.9800
O1—C2	1.4665 (16)	C11—H11B	0.9800
C2—N1	1.4395 (18)	C11—H11C	0.9800
C2—C3	1.5690 (19)	C12—C13	1.518 (2)
C2—H20	1.0000	C12—H12A	0.9900
N1—C19	1.4654 (18)	C12—H12B	0.9900
N1—C16	1.4683 (17)	C13—H13A	0.9800
C16—C17	1.501 (2)	C13—H13B	0.9800
C16—H16A	0.9900	C13—H13C	0.9800
C16—H16B	0.9900	C4—C9	1.3828 (19)
C17—O4	1.4338 (18)	C4—C5	1.3966 (19)
C17—H17A	0.9900	C5—C6	1.4057 (18)
C17—H17B	0.9900	C5—C14	1.5082 (18)
O4—C18	1.4315 (17)	C14—O3	1.2154 (17)
C18—C19	1.510 (2)	C14—C15	1.494 (2)
C18—H18A	0.9900	C15—H15A	0.9800
C18—H18B	0.9900	C15—H15B	0.9800
C19—H19A	0.9900	C15—H15C	0.9800
C19—H19B	0.9900	C6—O2	1.3752 (16)
C3—C4	1.5218 (18)	C6—C7	1.382 (2)
C3—C10	1.5409 (19)	O2—H2	0.90 (2)
C3—C12	1.550 (2)	C7—C8	1.385 (2)
C10—C11	1.5270 (19)	C7—H7	0.9500
C10—H10A	0.9900	C8—C9	1.377 (2)
C10—H10B	0.9900	C8—H8	0.9500
C9—O1—C2	106.92 (10)	C10—C11—H11A	109.5
N1—C2—O1	111.21 (11)	C10—C11—H11B	109.5
N1—C2—C3	117.28 (11)	H11A—C11—H11B	109.5
O1—C2—C3	105.85 (10)	C10—C11—H11C	109.5
N1—C2—H20	107.4	H11A—C11—H11C	109.5
O1—C2—H20	107.4	H11B—C11—H11C	109.5
C3—C2—H20	107.4	C13—C12—C3	116.30 (13)
C2—N1—C19	115.54 (11)	C13—C12—H12A	108.2
C2—N1—C16	111.96 (11)	C3—C12—H12A	108.2
C19—N1—C16	108.62 (11)	C13—C12—H12B	108.2
N1—C16—C17	110.01 (12)	C3—C12—H12B	108.2
N1—C16—H16A	109.7	H12A—C12—H12B	107.4
C17—C16—H16A	109.7	C12—C13—H13A	109.5
N1—C16—H16B	109.7	C12—C13—H13B	109.5
C17—C16—H16B	109.7	H13A—C13—H13B	109.5
H16A—C16—H16B	108.2	C12—C13—H13C	109.5
O4—C17—C16	110.86 (12)	H13A—C13—H13C	109.5
O4—C17—H17A	109.5	H13B—C13—H13C	109.5
C16—C17—H17A	109.5	C9—C4—C5	119.53 (12)
O4—C17—H17B	109.5	C9—C4—C3	108.62 (12)
C16—C17—H17B	109.5	C5—C4—C3	131.84 (12)
H17A—C17—H17B	108.1	C4—C5—C6	118.09 (12)
C18—O4—C17	110.06 (11)	C4—C5—C14	123.18 (12)
O4—C18—C19	111.39 (12)	C6—C5—C14	118.64 (12)
O4—C18—H18A	109.4	O3—C14—C15	121.94 (13)
C19—C18—H18A	109.4	O3—C14—C5	120.33 (13)
O4—C18—H18B	109.4	C15—C14—C5	117.73 (12)
C19—C18—H18B	109.4	C14—C15—H15A	109.5
H18A—C18—H18B	108.0	C14—C15—H15B	109.5
N1—C19—C18	109.80 (12)	H15A—C15—H15B	109.5
N1—C19—H19A	109.7	C14—C15—H15C	109.5
C18—C19—H19A	109.7	H15A—C15—H15C	109.5
N1—C19—H19B	109.7	H15B—C15—H15C	109.5
C18—C19—H19B	109.7	O2—C6—C7	122.20 (12)
H19A—C19—H19B	108.2	O2—C6—C5	116.99 (12)
C4—C3—C10	112.89 (11)	C7—C6—C5	120.79 (12)
C4—C3—C12	110.49 (11)	C6—O2—H2	109.1 (13)
C10—C3—C12	109.69 (11)	C6—C7—C8	121.04 (13)
C4—C3—C2	100.72 (10)	C6—C7—H7	119.5
C10—C3—C2	114.01 (11)	C8—C7—H7	119.5
C12—C3—C2	108.70 (11)	C9—C8—C7	117.80 (13)
C11—C10—C3	116.13 (13)	C9—C8—H8	121.1
C11—C10—H10A	108.3	C7—C8—H8	121.1
C3—C10—H10A	108.3	C8—C9—O1	123.93 (12)
C11—C10—H10B	108.3	C8—C9—C4	122.71 (13)
C3—C10—H10B	108.3	O1—C9—C4	113.36 (12)
H10A—C10—H10B	107.4
O1—C2—C3—C4	19.89 (13)	C10—C3—C4—C9	−134.46 (13)
C2—C3—C4—C9	−12.49 (15)	C12—C3—C4—C9	102.28 (14)
C3—C4—C9—O1	0.16 (17)	C10—C3—C4—C5	46.6 (2)
N1—C16—C17—O4	59.38 (15)	C12—C3—C4—C5	−76.61 (19)
O4—C18—C19—N1	−58.28 (15)	C2—C3—C4—C5	168.61 (14)
C9—O1—C2—N1	107.54 (12)	C9—C4—C5—C6	1.7 (2)
C9—O1—C2—C3	−20.87 (14)	C3—C4—C5—C6	−179.54 (13)
O1—C2—N1—C19	−46.17 (15)	C9—C4—C5—C14	−174.88 (13)
C3—C2—N1—C19	75.82 (15)	C3—C4—C5—C14	3.9 (2)
O1—C2—N1—C16	78.87 (13)	C4—C5—C14—O3	64.89 (18)
C3—C2—N1—C16	−159.14 (12)	C6—C5—C14—O3	−111.63 (15)
C2—N1—C16—C17	172.46 (11)	C4—C5—C14—C15	−115.53 (15)
C19—N1—C16—C17	−58.76 (15)	C6—C5—C14—C15	67.95 (17)
C16—C17—O4—C18	−58.14 (16)	C4—C5—C6—O2	179.26 (12)
C17—O4—C18—C19	57.71 (15)	C14—C5—C6—O2	−4.04 (19)
C2—N1—C19—C18	−175.35 (11)	C4—C5—C6—C7	−2.3 (2)
C16—N1—C19—C18	57.90 (15)	C14—C5—C6—C7	174.40 (13)
N1—C2—C3—C4	−104.83 (13)	O2—C6—C7—C8	179.62 (13)
N1—C2—C3—C10	16.35 (17)	C5—C6—C7—C8	1.3 (2)
O1—C2—C3—C10	141.07 (11)	C6—C7—C8—C9	0.4 (2)
N1—C2—C3—C12	139.05 (12)	C7—C8—C9—O1	179.80 (13)
O1—C2—C3—C12	−96.23 (13)	C7—C8—C9—C4	−1.1 (2)
C4—C3—C10—C11	178.14 (12)	C2—O1—C9—C8	−167.31 (14)
C12—C3—C10—C11	−58.16 (16)	C2—O1—C9—C4	13.50 (16)
C2—C3—C10—C11	63.99 (16)	C5—C4—C9—C8	0.0 (2)
C4—C3—C12—C13	−52.74 (17)	C3—C4—C9—C8	−179.04 (14)
C10—C3—C12—C13	−177.83 (13)	C5—C4—C9—O1	179.21 (12)
C2—C3—C12—C13	56.91 (16)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2···O4i	0.90 (2)	1.86 (2)	2.7639 (14)	177 (2)
C11—H11A···N1	0.98	2.61	3.205 (2)	119
C12—H12A···O3	0.99	2.54	3.333 (2)	137
C15—H15C···O2	0.98	2.46	3.037 (2)	118

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2⋯O4i	0.90 (2)	1.86 (2)	2.7639 (14)	177 (2)
C11—H11A⋯N1	0.98	2.61	3.205 (2)	119
C12—H12A⋯O3	0.99	2.54	3.333 (2)	137
C15—H15C⋯O2	0.98	2.46	3.037 (2)	118

Symmetry code: (i) .