12-{[4-(4-Bromo-phen-yl)piperazin-1-yl]meth-yl}-9α-hy-droxy-4,8-dimethyl-3,14-dioxatri-cyclo-[9.3.0.0(2,4)]tetra-dec-7-en-13-one.

The title compound, C25H33BrN2O4, was synthesized from 9α-hy-droxy-parthenolide (9α-hy-droxy-4,8-dimethyl-12-methylen-3,14-dioxa-tri-cyclo-[9.3.0.0(2,4)]tetra-dec-7-en-13-one), which was isolated from the chloro-form extract of the aerial parts of Anvillea radiata. The mol-ecule is built up from two fused five- and ten-membered rings with an additional ep-oxy ring system and a bromo-phenyl-piperazine group as a substituent. The ten-membered ring adopts an approximate chair-chair-chair conformation, while the piperazine ring displays a chair conformation and the five-membered ring shows an envelope conformation with the C atom closest to the hy-droxy group forming the flap. An intra-molecular O-H⋯N hydrogen bond stabilizes the mol-ecular conformation. The crystal packing features C-H⋯O hydrogen bonds, which link the mol-ecules into zigzag chains running along the b-axis direction.

Related literature

For background to the medicinal uses of the plant Anvillea radiata, see: Abdel Sattar et al. (1996 ▶); El Hassany et al. (2004 ▶); Qureshi et al. (1990 ▶). For the reactivity of this sesquiterpene, see: Neukirch et al. (2003 ▶); Hwang et al. (2006 ▶); Neelakantan et al. (2009 ▶). For the synthetic procedure, see: Moumou et al. (2010 ▶). For conformational analysis, see: Cremer & Pople (1975 ▶)

Experimental

Crystal data

C25H33BrN2O4

M = 505.44

Monoclinic,

a = 9.6790 (4) Å

b = 7.0710 (3) Å

c = 17.3117 (7) Å

β = 94.872 (2)°

V = 1180.54 (8) Å3

Z = 2

Mo Kα radiation

μ = 1.78 mm−1

T = 296 K

0.5 × 0.03 × 0.03 mm

Data collection

Bruker X8 APEX diffractometer

Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T min = 0.634, T max = 0.746

14527 measured reflections

5899 independent reflections

5216 reflections with I > 2σ(I)

R int = 0.024

Refinement

R[F 2 > 2σ(F 2)] = 0.030

wR(F 2) = 0.076

S = 1.03

5899 reflections

292 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.44 e Å−3

Δρmin = −0.44 e Å−3

Absolute structure: Flack & Bernardinelli (2000 ▶), 2614 Friedel pairs

Absolute structure parameter: 0.007 (5)

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT (Bruker, 2009 ▶); data reduction: SAINT; 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: PLATON (Spek, 2009 ▶) and publCIF (Westrip, 2010 ▶).

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536814006473/bt6970sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536814006473/bt6970Isup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S1600536814006473/bt6970Isup3.cml

CCDC reference: 993318

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

C25H33BrN2O4	F(000) = 528
Mr = 505.44	Dx = 1.422 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 5899 reflections
a = 9.6790 (4) Å	θ = 2.4–28.7°
b = 7.0710 (3) Å	µ = 1.78 mm−1
c = 17.3117 (7) Å	T = 296 K
β = 94.872 (2)°	Box, colourless
V = 1180.54 (8) Å3	0.5 × 0.03 × 0.03 mm
Z = 2

Bruker X8 APEX diffractometer	5899 independent reflections
Radiation source: fine-focus sealed tube	5216 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.024
φ and ω scans	θmax = 28.7°, θmin = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 2009)	h = −12→13
Tmin = 0.634, Tmax = 0.746	k = −9→9
14527 measured reflections	l = −23→23

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)] = 0.030	H-atom parameters constrained
wR(F2) = 0.076	w = 1/[σ2(Fo2) + (0.0313P)2] where P = (Fo2 + 2Fc2)/3
S = 1.03	(Δ/σ)max = 0.001
5899 reflections	Δρmax = 0.44 e Å−3
292 parameters	Δρmin = −0.44 e Å−3
1 restraint	Absolute structure: Flack & Bernardinelli (2000), 2614 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.007 (5)

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s involving l.s. planes.

	x	y	z	Uiso*/Ueq
Br1	0.81297 (2)	0.79383 (4)	−0.080172 (12)	0.06016 (9)
O1	0.06025 (14)	−0.47571 (19)	0.48432 (7)	0.0400 (3)
O3	0.29861 (12)	−0.1832 (2)	0.50486 (6)	0.0367 (3)
O4	0.34442 (13)	−0.25359 (19)	0.21350 (8)	0.0418 (3)
H4	0.4035	−0.1779	0.2306	0.063*
N1	0.53704 (14)	0.0338 (2)	0.29071 (8)	0.0302 (3)
N2	0.63915 (15)	0.2755 (2)	0.17458 (8)	0.0351 (3)
C1	0.20134 (15)	−0.2018 (3)	0.43565 (8)	0.0280 (3)
H1	0.1227	−0.1152	0.4376	0.034*
O2	0.51010 (17)	−0.0713 (3)	0.53716 (9)	0.0637 (5)
C11	0.40639 (17)	−0.0352 (2)	0.40481 (10)	0.0301 (3)
H11	0.3778	0.0978	0.4024	0.036*
C10	0.28736 (16)	−0.1544 (2)	0.36682 (9)	0.0257 (3)
H10	0.3270	−0.2728	0.3492	0.031*
C2	0.15415 (18)	−0.4034 (2)	0.43110 (10)	0.0302 (3)
H2	0.2277	−0.4925	0.4205	0.036*
C9	0.20719 (17)	−0.0612 (2)	0.29633 (10)	0.0275 (3)
H9A	0.2462	0.0630	0.2885	0.033*
H9B	0.1115	−0.0439	0.3075	0.033*
C20	0.66722 (19)	0.3843 (3)	0.11021 (10)	0.0333 (4)
C15	−0.1053 (2)	−0.3330 (3)	0.38362 (13)	0.0416 (4)
H15A	−0.1899	−0.3920	0.3961	0.062*
H15B	−0.1117	−0.3022	0.3294	0.062*
H15C	−0.0903	−0.2196	0.4136	0.062*
C8	0.21012 (17)	−0.1764 (2)	0.22029 (9)	0.0311 (3)
H8	0.1889	−0.0899	0.1766	0.037*
C7	0.09765 (18)	−0.3259 (3)	0.21770 (10)	0.0315 (3)
C14	−0.0380 (2)	−0.2547 (3)	0.18031 (13)	0.0460 (5)
H14A	−0.1099	−0.3441	0.1886	0.069*
H14B	−0.0312	−0.2393	0.1257	0.069*
H14C	−0.0595	−0.1353	0.2027	0.069*
C3	0.01452 (19)	−0.4672 (2)	0.40199 (10)	0.0319 (4)
C16	0.5343 (2)	0.2401 (3)	0.29620 (11)	0.0392 (4)
H16A	0.6185	0.2834	0.3253	0.047*
H16B	0.4563	0.2783	0.3242	0.047*
C17	0.5224 (2)	0.3318 (3)	0.21754 (11)	0.0421 (5)
H17A	0.4361	0.2940	0.1891	0.051*
H17B	0.5215	0.4683	0.2233	0.051*
C5	0.0058 (2)	−0.6297 (2)	0.27166 (12)	0.0395 (4)
H5A	0.0218	−0.7510	0.2478	0.047*
H5B	−0.0839	−0.5833	0.2507	0.047*
C6	0.1169 (2)	−0.4925 (2)	0.25258 (10)	0.0343 (4)
H6	0.2081	−0.5278	0.2666	0.041*
C13	0.54475 (19)	−0.0520 (3)	0.36882 (11)	0.0364 (4)
H13A	0.6166	0.0107	0.4020	0.044*
H13B	0.5696	−0.1844	0.3653	0.044*
C21	0.5923 (2)	0.5468 (3)	0.08862 (11)	0.0379 (4)
H21	0.5133	0.5762	0.1133	0.046*
C22	0.6333 (2)	0.6657 (3)	0.03105 (11)	0.0420 (4)
H22	0.5826	0.7745	0.0179	0.050*
C18	0.6578 (2)	−0.0185 (3)	0.24953 (12)	0.0387 (4)
H18A	0.6627	−0.1551	0.2451	0.046*
H18B	0.7419	0.0249	0.2786	0.046*
C4	0.0055 (2)	−0.6550 (2)	0.36027 (12)	0.0398 (4)
H4A	−0.0788	−0.7194	0.3717	0.048*
H4B	0.0835	−0.7333	0.3790	0.048*
C12	0.4169 (2)	−0.0961 (3)	0.48858 (11)	0.0389 (4)
C24	0.8214 (2)	0.4589 (4)	0.01092 (13)	0.0514 (5)
H24	0.8976	0.4280	−0.0158	0.062*
C23	0.7487 (2)	0.6225 (3)	−0.00648 (11)	0.0414 (4)
C19	0.6466 (2)	0.0693 (3)	0.16953 (11)	0.0383 (4)
H19A	0.7265	0.0336	0.1427	0.046*
H19B	0.5642	0.0220	0.1399	0.046*
C25	0.7808 (2)	0.3408 (3)	0.06823 (12)	0.0471 (5)
H25	0.8299	0.2297	0.0793	0.057*

	U11	U22	U33	U12	U13	U23
Br1	0.06273 (15)	0.07268 (15)	0.04532 (12)	−0.01813 (12)	0.00605 (9)	0.02022 (11)
O1	0.0448 (8)	0.0446 (7)	0.0312 (7)	−0.0100 (6)	0.0071 (6)	0.0077 (5)
O3	0.0389 (6)	0.0481 (7)	0.0232 (5)	−0.0105 (6)	0.0036 (4)	0.0038 (5)
O4	0.0341 (7)	0.0539 (8)	0.0390 (7)	0.0043 (6)	0.0129 (6)	−0.0079 (6)
N1	0.0268 (7)	0.0342 (7)	0.0301 (7)	0.0026 (6)	0.0059 (6)	0.0041 (6)
N2	0.0405 (8)	0.0358 (7)	0.0306 (7)	0.0071 (7)	0.0129 (6)	0.0049 (6)
C1	0.0287 (7)	0.0316 (7)	0.0241 (7)	−0.0003 (7)	0.0043 (5)	0.0015 (7)
O2	0.0577 (10)	0.0973 (13)	0.0334 (8)	−0.0328 (10)	−0.0125 (7)	0.0183 (9)
C11	0.0295 (9)	0.0359 (8)	0.0245 (8)	−0.0029 (7)	0.0003 (6)	0.0029 (6)
C10	0.0262 (8)	0.0286 (7)	0.0227 (7)	0.0038 (6)	0.0043 (6)	0.0011 (5)
C2	0.0328 (9)	0.0299 (7)	0.0283 (8)	0.0024 (7)	0.0045 (7)	0.0058 (6)
C9	0.0280 (8)	0.0271 (7)	0.0274 (8)	0.0050 (6)	0.0014 (6)	0.0022 (6)
C20	0.0325 (9)	0.0395 (9)	0.0281 (9)	0.0016 (7)	0.0033 (7)	0.0017 (7)
C15	0.0328 (10)	0.0442 (10)	0.0484 (12)	0.0042 (8)	0.0058 (8)	−0.0078 (9)
C8	0.0338 (8)	0.0362 (9)	0.0232 (7)	0.0060 (7)	0.0028 (6)	0.0036 (7)
C7	0.0332 (9)	0.0361 (8)	0.0252 (8)	0.0059 (7)	0.0015 (7)	−0.0057 (6)
C14	0.0394 (10)	0.0482 (11)	0.0478 (11)	0.0022 (8)	−0.0109 (8)	0.0045 (9)
C3	0.0338 (9)	0.0315 (8)	0.0310 (9)	−0.0022 (7)	0.0065 (7)	0.0005 (7)
C16	0.0476 (11)	0.0376 (9)	0.0346 (9)	0.0001 (7)	0.0158 (8)	−0.0007 (7)
C17	0.0503 (11)	0.0362 (10)	0.0428 (10)	0.0128 (8)	0.0219 (9)	0.0053 (8)
C5	0.0468 (11)	0.0280 (8)	0.0428 (11)	0.0010 (7)	−0.0005 (8)	−0.0059 (7)
C6	0.0372 (9)	0.0337 (8)	0.0321 (9)	0.0074 (7)	0.0035 (7)	−0.0058 (7)
C13	0.0274 (9)	0.0472 (10)	0.0343 (9)	−0.0015 (7)	0.0016 (7)	0.0097 (8)
C21	0.0371 (10)	0.0421 (9)	0.0353 (9)	0.0033 (8)	0.0073 (8)	0.0044 (8)
C22	0.0491 (12)	0.0412 (9)	0.0353 (10)	0.0011 (9)	0.0019 (8)	0.0077 (8)
C18	0.0330 (9)	0.0410 (10)	0.0435 (11)	0.0087 (8)	0.0119 (8)	0.0073 (8)
C4	0.0444 (11)	0.0303 (9)	0.0447 (11)	−0.0045 (7)	0.0047 (8)	0.0019 (7)
C12	0.0408 (11)	0.0483 (10)	0.0273 (9)	−0.0103 (8)	0.0003 (7)	0.0050 (8)
C24	0.0478 (12)	0.0690 (14)	0.0397 (11)	0.0096 (11)	0.0177 (9)	0.0107 (10)
C23	0.0443 (11)	0.0519 (12)	0.0275 (9)	−0.0110 (9)	−0.0005 (8)	0.0069 (8)
C19	0.0432 (11)	0.0365 (9)	0.0374 (10)	0.0094 (8)	0.0161 (8)	0.0013 (7)
C25	0.0480 (11)	0.0559 (13)	0.0396 (10)	0.0154 (9)	0.0160 (9)	0.0120 (9)

Br1—C23	1.9020 (19)	C8—H8	0.9800
O1—C2	1.442 (2)	C7—C6	1.329 (3)
O1—C3	1.457 (2)	C7—C14	1.500 (3)
O3—C12	1.351 (2)	C14—H14A	0.9600
O3—C1	1.465 (2)	C14—H14B	0.9600
O4—C8	1.424 (2)	C14—H14C	0.9600
O4—H4	0.8200	C3—C4	1.510 (3)
N1—C16	1.462 (3)	C16—C17	1.504 (3)
N1—C18	1.467 (2)	C16—H16A	0.9700
N1—C13	1.478 (2)	C16—H16B	0.9700
N2—C20	1.400 (2)	C17—H17A	0.9700
N2—C17	1.460 (2)	C17—H17B	0.9700
N2—C19	1.462 (3)	C5—C6	1.505 (3)
C1—C2	1.497 (3)	C5—C4	1.545 (3)
C1—C10	1.5473 (19)	C5—H5A	0.9700
C1—H1	0.9800	C5—H5B	0.9700
O2—C12	1.193 (3)	C6—H6	0.9300
C11—C12	1.508 (2)	C13—H13A	0.9700
C11—C13	1.529 (2)	C13—H13B	0.9700
C11—C10	1.530 (2)	C21—C22	1.387 (3)
C11—H11	0.9800	C21—H21	0.9300
C10—C9	1.538 (2)	C22—C23	1.374 (3)
C10—H10	0.9800	C22—H22	0.9300
C2—C3	1.473 (3)	C18—C19	1.513 (3)
C2—H2	0.9800	C18—H18A	0.9700
C9—C8	1.550 (2)	C18—H18B	0.9700
C9—H9A	0.9700	C4—H4A	0.9700
C9—H9B	0.9700	C4—H4B	0.9700
C20—C21	1.393 (3)	C24—C23	1.373 (3)
C20—C25	1.402 (2)	C24—C25	1.379 (3)
C15—C3	1.511 (3)	C24—H24	0.9300
C15—H15A	0.9600	C19—H19A	0.9700
C15—H15B	0.9600	C19—H19B	0.9700
C15—H15C	0.9600	C25—H25	0.9300
C8—C7	1.516 (3)
C2—O1—C3	61.05 (11)	O1—C3—C15	113.30 (14)
C12—O3—C1	111.57 (12)	C2—C3—C15	123.01 (16)
C8—O4—H4	109.5	C4—C3—C15	116.06 (17)
C16—N1—C18	107.64 (14)	N1—C16—C17	111.83 (16)
C16—N1—C13	110.47 (15)	N1—C16—H16A	109.2
C18—N1—C13	111.14 (14)	C17—C16—H16A	109.2
C20—N2—C17	117.81 (15)	N1—C16—H16B	109.2
C20—N2—C19	119.11 (14)	C17—C16—H16B	109.2
C17—N2—C19	110.26 (14)	H16A—C16—H16B	107.9
O3—C1—C2	107.50 (14)	N2—C17—C16	109.89 (15)
O3—C1—C10	105.06 (12)	N2—C17—H17A	109.7
C2—C1—C10	110.33 (13)	C16—C17—H17A	109.7
O3—C1—H1	111.2	N2—C17—H17B	109.7
C2—C1—H1	111.2	C16—C17—H17B	109.7
C10—C1—H1	111.2	H17A—C17—H17B	108.2
C12—C11—C13	112.33 (15)	C6—C5—C4	110.75 (16)
C12—C11—C10	104.05 (13)	C6—C5—H5A	109.5
C13—C11—C10	115.82 (14)	C4—C5—H5A	109.5
C12—C11—H11	108.1	C6—C5—H5B	109.5
C13—C11—H11	108.1	C4—C5—H5B	109.5
C10—C11—H11	108.1	H5A—C5—H5B	108.1
C11—C10—C9	114.56 (13)	C7—C6—C5	126.55 (18)
C11—C10—C1	102.89 (13)	C7—C6—H6	116.7
C9—C10—C1	115.83 (13)	C5—C6—H6	116.7
C11—C10—H10	107.7	N1—C13—C11	111.29 (14)
C9—C10—H10	107.7	N1—C13—H13A	109.4
C1—C10—H10	107.7	C11—C13—H13A	109.4
O1—C2—C3	59.99 (11)	N1—C13—H13B	109.4
O1—C2—C1	120.69 (14)	C11—C13—H13B	109.4
C3—C2—C1	125.25 (15)	H13A—C13—H13B	108.0
O1—C2—H2	113.5	C22—C21—C20	121.23 (17)
C3—C2—H2	113.5	C22—C21—H21	119.4
C1—C2—H2	113.5	C20—C21—H21	119.4
C10—C9—C8	113.85 (13)	C23—C22—C21	119.91 (19)
C10—C9—H9A	108.8	C23—C22—H22	120.0
C8—C9—H9A	108.8	C21—C22—H22	120.0
C10—C9—H9B	108.8	N1—C18—C19	110.06 (15)
C8—C9—H9B	108.8	N1—C18—H18A	109.6
H9A—C9—H9B	107.7	C19—C18—H18A	109.6
C21—C20—N2	122.36 (15)	N1—C18—H18B	109.6
C21—C20—C25	117.07 (17)	C19—C18—H18B	109.6
N2—C20—C25	120.38 (16)	H18A—C18—H18B	108.2
C3—C15—H15A	109.5	C3—C4—C5	111.61 (15)
C3—C15—H15B	109.5	C3—C4—H4A	109.3
H15A—C15—H15B	109.5	C5—C4—H4A	109.3
C3—C15—H15C	109.5	C3—C4—H4B	109.3
H15A—C15—H15C	109.5	C5—C4—H4B	109.3
H15B—C15—H15C	109.5	H4A—C4—H4B	108.0
O4—C8—C7	112.85 (15)	O2—C12—O3	121.57 (17)
O4—C8—C9	110.74 (14)	O2—C12—C11	128.41 (17)
C7—C8—C9	109.07 (12)	O3—C12—C11	109.99 (16)
O4—C8—H8	108.0	C23—C24—C25	119.72 (18)
C7—C8—H8	108.0	C23—C24—H24	120.1
C9—C8—H8	108.0	C25—C24—H24	120.1
C6—C7—C14	125.23 (18)	C24—C23—C22	120.37 (18)
C6—C7—C8	122.16 (17)	C24—C23—Br1	119.54 (15)
C14—C7—C8	112.24 (16)	C22—C23—Br1	120.05 (16)
C7—C14—H14A	109.5	N2—C19—C18	110.77 (16)
C7—C14—H14B	109.5	N2—C19—H19A	109.5
H14A—C14—H14B	109.5	C18—C19—H19A	109.5
C7—C14—H14C	109.5	N2—C19—H19B	109.5
H14A—C14—H14C	109.5	C18—C19—H19B	109.5
H14B—C14—H14C	109.5	H19A—C19—H19B	108.1
O1—C3—C2	58.95 (11)	C24—C25—C20	121.58 (19)
O1—C3—C4	115.59 (15)	C24—C25—H25	119.2
C2—C3—C4	116.57 (15)	C20—C25—H25	119.2

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4···N1	0.82	2.18	2.995 (4)	171
C1—H1···O1i	0.98	2.52	3.389 (3)	148
C15—H15C···O1i	0.96	2.47	3.410 (3)	167

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O4—H4⋯N1	0.82	2.18	2.995 (4)	171
C1—H1⋯O1i	0.98	2.52	3.389 (3)	148
C15—H15C⋯O1i	0.96	2.47	3.410 (3)	167

Symmetry code: (i) .