(E)-13-(4-Amino-phen-yl)parthenolide.

The title compound, C21H25NO3 [systematic name: (3aS,9aR,10aR,10bS,E)-3-[(E)-4-(4-amino-benzyl-idene)-6,9a-dimethyl-3a,4,5,8,9,9a,10a,10b-octa-hydro-oxireno[2',3':9,10]cyclo-deca-[1,2-b]furan-2(3H)-one] was obtained from the reaction of parthenolide [synonym: 4,5-ep-oxy-germacra-1(10),11(13)-dieno-12,6-lactone] with 4-iodo-aniline under Heck reaction conditions. It was identified as the E-isomer (conformation about the exocyclic methyl-idene C=C bond; the conformation about the C=C bond in the ten-membered ring is also E). The mol-ecule is built up from fused ten-, five- (lactone) and three-membered (epoxide) rings with a 4-amino-phenyl group as a substituent. The ten-membered ring displays an approximate chair-chair conformation, while the lactone ring has an envelope conformation with the C atom bonded to the ring O atom as the flap. The dihedral angle between the benzene ring of the 4-amino-phenyl moiety and the lactone ring mean plane is 23.50 (8)°. In the crystal, mol-ecules are linked via N-H⋯O hydrogen bonds, between the amine group and the lactone and epoxide ring O atoms, forming chains propagating along the b-axis direction. Adjacent chains are linked via C-H⋯O inter-actions, forming an undulating two-dimensional network lying parallel to the plane (001). The absolute structure of the mol-ecule in the crystal was confirmed by resonance scattering [Flack parameter = 0.03 (3)].

Related literature

For the biological activity of parthenolide, see: Hall et al. (1979 ▶). For the biological activity of parthenolide derivatives similar to the title compound, see: Hanson et al. (1970 ▶); Hehner et al. (1998 ▶); Kupchan et al. (1971 ▶); Nasim et al. (2011 ▶); Neelakantan et al. (2009 ▶); Oka et al. (2007 ▶); Ralstin et al. (2006 ▶); Rodriguez et al. (1976 ▶); Sun et al. (2006 ▶). For the synthesis and crystal structures of similar mol­ecules, see: Han et al. (2009 ▶).

Experimental

Crystal data

C21H25NO3

M = 339.42

Orthorhombic,

a = 8.5619 (1) Å

b = 11.8846 (2) Å

c = 17.7457 (3) Å

V = 1805.71 (5) Å3

Z = 4

Cu Kα radiation

μ = 0.66 mm−1

T = 90 K

0.20 × 0.16 × 0.12 mm

Data collection

Bruker X8 Proteum diffractometer

Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T min = 0.843, T max = 0.956

25400 measured reflections

3296 independent reflections

3267 reflections with I > 2σ(I)

R int = 0.033

Refinement

R[F 2 > 2σ(F 2)] = 0.027

wR(F 2) = 0.070

S = 1.06

3296 reflections

234 parameters

H atoms treated by a mixture of independent and constrained refinement

Δρmax = 0.13 e Å−3

Δρmin = −0.14 e Å−3

Absolute structure: Flack x parameter determined using 1383 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▶)

Absolute structure parameter: 0.03 (3)

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL.

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813028730/su2647sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813028730/su2647Isup2.hkl

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

C21H25NO3	Dx = 1.249 Mg m−3
Mr = 339.42	Melting point = 512–514 K
Orthorhombic, P212121	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2ab	Cell parameters from 9832 reflections
a = 8.5619 (1) Å	θ = 5.2–68.0°
b = 11.8846 (2) Å	µ = 0.66 mm−1
c = 17.7457 (3) Å	T = 90 K
V = 1805.71 (5) Å3	Block, colourless
Z = 4	0.20 × 0.16 × 0.12 mm
F(000) = 728

Bruker X8 Proteum diffractometer	3296 independent reflections
Radiation source: fine-focus rotating anode	3267 reflections with I > 2σ(I)
Detector resolution: 5.6 pixels mm-1	Rint = 0.033
φ and ω scans	θmax = 68.2°, θmin = 5.7°
Absorption correction: multi-scan (SADABS; Sheldrick, 1996)	h = −10→10
Tmin = 0.843, Tmax = 0.956	k = −11→14
25400 measured reflections	l = −21→15

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.027	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.070	w = 1/[σ2(Fo2) + (0.0401P)2 + 0.303P] where P = (Fo2 + 2Fc2)/3
S = 1.06	(Δ/σ)max < 0.001
3296 reflections	Δρmax = 0.13 e Å−3
234 parameters	Δρmin = −0.14 e Å−3
0 restraints	Absolute structure: Flack parameter determined using 1383 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.03 (3)

Experimental. Spectroscopic data for the title compound: 1H NMR (400 MHz, CDCl3): δ 7.54-7.55 (d, J=2.8 Hz, 1H), 7.23-7.26 (d, J=8.4 Hz, 2H), 6.68-6.70 (d, J=8.0 Hz, 2H), 5.28-5.30 (d, J=11.2 Hz, 1H), 4.02 (brs, 2H), 3.91-3.95 (t, J=8.0Hz, 1H), 3.25 (m, 1H), 2.82-2.84 (d, J=8.8 Hz, 1H), 2.28-2.45 (m, 1H), 2.14-2.24 (m, 5H), 1.69 (s, 3H), 1.61 (s, 1H), 1.43-1.45 (m, 1H), 1.31(s, 3H); 13C NMR (100 MHz,CDCl3) δ 171.63, 148.15, 138.64, 134.79, 132.17, 125.12, 124.03, 123.29, 114.42, 82.71, 66.62, 61.58, 46.98, 41.88, 36.10, 29.33, 24.33, 17.49, 17.36 ppm.

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.

	x	y	z	Uiso*/Ueq
O1	0.69671 (14)	0.83851 (9)	0.57032 (6)	0.0269 (3)
O2	0.57735 (14)	0.71820 (9)	0.43765 (6)	0.0247 (3)
O3	0.57901 (15)	0.65318 (10)	0.31945 (6)	0.0276 (3)
N1	0.48608 (19)	−0.03270 (12)	0.45455 (10)	0.0323 (3)
H1A	0.539 (3)	−0.055 (2)	0.4989 (14)	0.049*
H2B	0.495 (3)	−0.077 (2)	0.4135 (14)	0.049*
C1	0.61245 (19)	0.79003 (14)	0.63430 (9)	0.0255 (4)
C2	0.7040 (2)	0.76874 (16)	0.70559 (9)	0.0321 (4)
H1	0.7143	0.8397	0.7344	0.038*
H2A	0.8102	0.7420	0.6926	0.038*
C3	0.6202 (2)	0.67944 (15)	0.75440 (9)	0.0325 (4)
H3A	0.6881	0.6579	0.7972	0.039*
H3B	0.5227	0.7117	0.7752	0.039*
C4	0.5821 (2)	0.57669 (14)	0.70835 (9)	0.0277 (4)
H4	0.6688	0.5325	0.6928	0.033*
C5	0.4420 (2)	0.53993 (13)	0.68657 (8)	0.0248 (3)
C6	0.4284 (2)	0.44729 (13)	0.62863 (8)	0.0259 (3)
H6A	0.3432	0.3957	0.6438	0.031*
H6B	0.5268	0.4035	0.6282	0.031*
C7	0.39551 (19)	0.49041 (13)	0.54839 (8)	0.0237 (3)
H7A	0.3090	0.5455	0.5508	0.028*
H7B	0.3597	0.4263	0.5172	0.028*
C8	0.53600 (18)	0.54638 (12)	0.50866 (8)	0.0198 (3)
H8	0.6346	0.5178	0.5321	0.024*
C9	0.53593 (18)	0.67758 (12)	0.51252 (8)	0.0209 (3)
H9	0.4293	0.7050	0.5263	0.025*
C10	0.65311 (18)	0.72056 (12)	0.56849 (8)	0.0219 (3)
H10	0.7423	0.6679	0.5775	0.026*
C11	0.56586 (19)	0.63346 (13)	0.38588 (8)	0.0225 (3)
C12	0.54277 (18)	0.52539 (12)	0.42479 (8)	0.0207 (3)
C13	0.53493 (19)	0.43138 (13)	0.38311 (8)	0.0223 (3)
H13	0.5363	0.4441	0.3303	0.027*
C14	0.2884 (2)	0.58698 (15)	0.71301 (10)	0.0321 (4)
H14A	0.3071	0.6429	0.7526	0.048*
H14B	0.2236	0.5260	0.7331	0.048*
H14C	0.2345	0.6227	0.6706	0.048*
C15	0.4537 (2)	0.84179 (14)	0.64419 (9)	0.0301 (4)
H15A	0.4639	0.9142	0.6702	0.045*
H15B	0.3878	0.7913	0.6741	0.045*
H15C	0.4057	0.8537	0.5947	0.045*
C16	0.52461 (18)	0.31328 (13)	0.40450 (9)	0.0228 (3)
C17	0.5641 (2)	0.27104 (12)	0.47583 (8)	0.0253 (3)
H17	0.6003	0.3214	0.5136	0.030*
C18	0.5517 (2)	0.15768 (13)	0.49238 (9)	0.0276 (3)
H18	0.5777	0.1314	0.5414	0.033*
C19	0.50076 (19)	0.08115 (13)	0.43735 (10)	0.0266 (3)
C20	0.46429 (19)	0.12208 (14)	0.36578 (9)	0.0266 (3)
H20	0.4306	0.0715	0.3276	0.032*
C21	0.47670 (19)	0.23526 (13)	0.35002 (9)	0.0245 (3)
H21	0.4521	0.2611	0.3008	0.029*

	U11	U22	U33	U12	U13	U23
O1	0.0341 (6)	0.0208 (5)	0.0258 (6)	−0.0064 (5)	0.0045 (5)	−0.0028 (5)
O2	0.0368 (6)	0.0174 (5)	0.0199 (5)	−0.0020 (5)	0.0000 (5)	0.0017 (4)
O3	0.0358 (6)	0.0279 (6)	0.0190 (5)	−0.0027 (5)	−0.0006 (5)	0.0043 (4)
N1	0.0364 (8)	0.0191 (7)	0.0415 (8)	−0.0011 (6)	0.0020 (7)	0.0013 (6)
C1	0.0310 (8)	0.0222 (7)	0.0232 (8)	−0.0057 (6)	0.0029 (6)	−0.0029 (6)
C2	0.0339 (9)	0.0375 (9)	0.0248 (8)	−0.0065 (8)	−0.0004 (7)	−0.0055 (7)
C3	0.0343 (9)	0.0430 (10)	0.0201 (8)	−0.0023 (8)	−0.0030 (7)	0.0005 (7)
C4	0.0320 (8)	0.0297 (8)	0.0212 (7)	0.0066 (7)	0.0028 (7)	0.0048 (6)
C5	0.0342 (9)	0.0220 (7)	0.0183 (7)	0.0041 (7)	0.0033 (7)	0.0048 (6)
C6	0.0346 (9)	0.0194 (7)	0.0236 (7)	0.0020 (7)	0.0069 (7)	0.0046 (6)
C7	0.0269 (8)	0.0203 (7)	0.0238 (8)	−0.0003 (6)	0.0024 (6)	0.0014 (6)
C8	0.0237 (8)	0.0164 (7)	0.0191 (7)	0.0006 (6)	0.0002 (6)	0.0006 (5)
C9	0.0266 (8)	0.0175 (7)	0.0185 (7)	0.0021 (6)	0.0016 (6)	0.0008 (5)
C10	0.0261 (7)	0.0177 (7)	0.0220 (7)	−0.0004 (6)	0.0016 (6)	0.0014 (6)
C11	0.0256 (8)	0.0206 (7)	0.0212 (7)	0.0012 (6)	−0.0012 (6)	−0.0002 (6)
C12	0.0229 (7)	0.0194 (7)	0.0197 (7)	−0.0002 (6)	−0.0007 (6)	0.0014 (6)
C13	0.0254 (8)	0.0233 (8)	0.0183 (7)	0.0023 (6)	−0.0002 (6)	0.0009 (6)
C14	0.0346 (9)	0.0279 (8)	0.0340 (9)	0.0007 (8)	0.0070 (7)	−0.0037 (7)
C15	0.0374 (9)	0.0242 (8)	0.0287 (8)	0.0011 (7)	0.0045 (7)	−0.0054 (7)
C16	0.0260 (8)	0.0196 (7)	0.0229 (7)	0.0015 (6)	0.0009 (6)	−0.0024 (6)
C17	0.0325 (8)	0.0198 (7)	0.0235 (7)	0.0036 (7)	−0.0022 (7)	−0.0033 (6)
C18	0.0329 (9)	0.0235 (7)	0.0265 (8)	0.0046 (7)	−0.0001 (7)	0.0014 (6)
C19	0.0242 (7)	0.0192 (7)	0.0365 (9)	0.0005 (6)	0.0031 (7)	−0.0004 (7)
C20	0.0256 (8)	0.0229 (8)	0.0314 (8)	−0.0004 (6)	−0.0019 (7)	−0.0060 (6)
C21	0.0265 (8)	0.0242 (8)	0.0229 (7)	0.0016 (6)	−0.0011 (6)	−0.0031 (6)

O1—C10	1.4510 (18)	C8—C12	1.5101 (19)
O1—C1	1.4634 (19)	C8—C9	1.561 (2)
O2—C11	1.3667 (18)	C8—H8	1.0000
O2—C9	1.4573 (17)	C9—C10	1.501 (2)
O3—C11	1.2072 (18)	C9—H9	1.0000
N1—C19	1.393 (2)	C10—H10	1.0000
N1—H1A	0.94 (2)	C11—C12	1.472 (2)
N1—H2B	0.90 (2)	C12—C13	1.342 (2)
C1—C10	1.472 (2)	C13—C16	1.457 (2)
C1—C15	1.502 (2)	C13—H13	0.9500
C1—C2	1.510 (2)	C14—H14A	0.9800
C2—C3	1.547 (2)	C14—H14B	0.9800
C2—H1	0.9900	C14—H14C	0.9800
C2—H2A	0.9900	C15—H15A	0.9800
C3—C4	1.505 (2)	C15—H15B	0.9800
C3—H3A	0.9900	C15—H15C	0.9800
C3—H3B	0.9900	C16—C21	1.401 (2)
C4—C5	1.334 (3)	C16—C17	1.403 (2)
C4—H4	0.9500	C17—C18	1.383 (2)
C5—C14	1.504 (2)	C17—H17	0.9500
C5—C6	1.511 (2)	C18—C19	1.404 (2)
C6—C7	1.539 (2)	C18—H18	0.9500
C6—H6A	0.9900	C19—C20	1.395 (2)
C6—H6B	0.9900	C20—C21	1.378 (2)
C7—C8	1.545 (2)	C20—H20	0.9500
C7—H7A	0.9900	C21—H21	0.9500
C7—H7B	0.9900
C10—O1—C1	60.67 (10)	C10—C9—C8	111.63 (12)
C11—O2—C9	110.56 (11)	O2—C9—H9	109.7
C19—N1—H1A	114.0 (15)	C10—C9—H9	109.7
C19—N1—H2B	112.6 (15)	C8—C9—H9	109.7
H1A—N1—H2B	118 (2)	O1—C10—C1	60.08 (9)
O1—C1—C10	59.25 (9)	O1—C10—C9	121.02 (12)
O1—C1—C15	112.05 (13)	C1—C10—C9	123.89 (14)
C10—C1—C15	122.43 (14)	O1—C10—H10	113.8
O1—C1—C2	117.39 (14)	C1—C10—H10	113.8
C10—C1—C2	116.62 (15)	C9—C10—H10	113.8
C15—C1—C2	116.15 (14)	O3—C11—O2	120.44 (14)
C1—C2—C3	110.08 (14)	O3—C11—C12	129.80 (14)
C1—C2—H1	109.6	O2—C11—C12	109.72 (12)
C3—C2—H1	109.6	C13—C12—C11	118.35 (13)
C1—C2—H2A	109.6	C13—C12—C8	132.77 (14)
C3—C2—H2A	109.6	C11—C12—C8	108.87 (12)
H1—C2—H2A	108.2	C12—C13—C16	131.43 (14)
C4—C3—C2	110.68 (13)	C12—C13—H13	114.3
C4—C3—H3A	109.5	C16—C13—H13	114.3
C2—C3—H3A	109.5	C5—C14—H14A	109.5
C4—C3—H3B	109.5	C5—C14—H14B	109.5
C2—C3—H3B	109.5	H14A—C14—H14B	109.5
H3A—C3—H3B	108.1	C5—C14—H14C	109.5
C5—C4—C3	128.15 (15)	H14A—C14—H14C	109.5
C5—C4—H4	115.9	H14B—C14—H14C	109.5
C3—C4—H4	115.9	C1—C15—H15A	109.5
C4—C5—C14	125.04 (14)	C1—C15—H15B	109.5
C4—C5—C6	120.33 (15)	H15A—C15—H15B	109.5
C14—C5—C6	114.58 (15)	C1—C15—H15C	109.5
C5—C6—C7	113.64 (12)	H15A—C15—H15C	109.5
C5—C6—H6A	108.8	H15B—C15—H15C	109.5
C7—C6—H6A	108.8	C21—C16—C17	117.15 (14)
C5—C6—H6B	108.8	C21—C16—C13	118.40 (14)
C7—C6—H6B	108.8	C17—C16—C13	124.42 (14)
H6A—C6—H6B	107.7	C18—C17—C16	121.43 (15)
C6—C7—C8	115.03 (13)	C18—C17—H17	119.3
C6—C7—H7A	108.5	C16—C17—H17	119.3
C8—C7—H7A	108.5	C17—C18—C19	120.49 (15)
C6—C7—H7B	108.5	C17—C18—H18	119.8
C8—C7—H7B	108.5	C19—C18—H18	119.8
H7A—C7—H7B	107.5	N1—C19—C20	121.19 (15)
C12—C8—C7	114.12 (13)	N1—C19—C18	120.33 (16)
C12—C8—C9	102.02 (11)	C20—C19—C18	118.47 (15)
C7—C8—C9	114.19 (12)	C21—C20—C19	120.52 (15)
C12—C8—H8	108.7	C21—C20—H20	119.7
C7—C8—H8	108.7	C19—C20—H20	119.7
C9—C8—H8	108.7	C20—C21—C16	121.91 (15)
O2—C9—C10	109.13 (12)	C20—C21—H21	119.0
O2—C9—C8	106.91 (11)	C16—C21—H21	119.0
C10—O1—C1—C15	−115.61 (15)	C8—C9—C10—O1	166.95 (12)
C10—O1—C1—C2	106.19 (17)	O2—C9—C10—C1	121.71 (15)
O1—C1—C2—C3	−158.44 (14)	C8—C9—C10—C1	−120.33 (15)
C10—C1—C2—C3	−91.06 (18)	C9—O2—C11—O3	171.96 (15)
C15—C1—C2—C3	65.05 (19)	C9—O2—C11—C12	−9.99 (16)
C1—C2—C3—C4	51.03 (19)	O3—C11—C12—C13	0.4 (3)
C2—C3—C4—C5	−110.84 (19)	O2—C11—C12—C13	−177.46 (14)
C3—C4—C5—C14	−8.7 (3)	O3—C11—C12—C8	179.14 (17)
C3—C4—C5—C6	168.64 (15)	O2—C11—C12—C8	1.33 (18)
C4—C5—C6—C7	−98.81 (18)	C7—C8—C12—C13	−50.8 (2)
C14—C5—C6—C7	78.79 (18)	C9—C8—C12—C13	−174.49 (17)
C5—C6—C7—C8	73.72 (17)	C7—C8—C12—C11	130.63 (13)
C6—C7—C8—C12	144.91 (13)	C9—C8—C12—C11	6.96 (17)
C6—C7—C8—C9	−98.26 (15)	C11—C12—C13—C16	174.88 (16)
C11—O2—C9—C10	135.27 (13)	C8—C12—C13—C16	−3.6 (3)
C11—O2—C9—C8	14.39 (16)	C12—C13—C16—C21	163.27 (17)
C12—C8—C9—O2	−12.50 (15)	C12—C13—C16—C17	−18.8 (3)
C7—C8—C9—O2	−136.12 (12)	C21—C16—C17—C18	−2.0 (2)
C12—C8—C9—C10	−131.78 (13)	C13—C16—C17—C18	−179.96 (16)
C7—C8—C9—C10	104.60 (15)	C16—C17—C18—C19	0.9 (3)
C1—O1—C10—C9	113.87 (16)	C17—C18—C19—N1	−179.03 (16)
C15—C1—C10—O1	98.02 (16)	C17—C18—C19—C20	0.4 (2)
C2—C1—C10—O1	−107.50 (15)	N1—C19—C20—C21	178.82 (16)
O1—C1—C10—C9	−109.26 (15)	C18—C19—C20—C21	−0.6 (2)
C15—C1—C10—C9	−11.2 (2)	C19—C20—C21—C16	−0.5 (2)
C2—C1—C10—C9	143.25 (15)	C17—C16—C21—C20	1.8 (2)
O2—C9—C10—O1	49.00 (18)	C13—C16—C21—C20	179.88 (15)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···O1i	0.94 (2)	2.25 (3)	3.133 (2)	156 (2)
N1—H2B···O2i	0.90 (2)	2.57 (2)	3.077 (2)	116 (2)
C2—H2A···O3ii	0.99	2.63	3.372 (2)	132

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯O1i	0.94 (2)	2.25 (3)	3.133 (2)	156 (2)
N1—H2B⋯O2i	0.90 (2)	2.57 (2)	3.077 (2)	116 (2)
C2—H2A⋯O3ii	0.99	2.63	3.372 (2)	132

Symmetry codes: (i) ; (ii) .