1-Bromo-2-(10β-dihydro-artemisin-oxy)ethane.

The title compound, C(17)H(27)BrO(5), DEB, is a derivative of artemisinin which is used in malara therapy. The OR-group at C12 is cis to the CH(3)-group at C11 and axially oriented on ring D which has a chair conformation. The crystal packing is stabilized by several weak inter-molecular C-H⋯O inter-actions, which combine to form a C-H-O bonded network parallel to (001).

Related literature

For background to malaria, see: World Health Organisation (2008 ▶). For the effective of artemisinin analogs against malaria, see: Ploypradith (2004 ▶). For the crystal structure of artemisinin, see: Kuhn & Wang (2008 ▶) and of dihydro­artemisinin (DHA), see: Luo et al. (1984 ▶). Jasinski et al. (2008a ▶) redetermined the structure of DHA as well as characterizing the second polymer of β-arteether (Jasinski et al., 2008b ▶). For the reaction of DEB with amines, see: Li et al. (2000 ▶). For the synthesis of artemisinin hybrids, see: Walsh et al. (2007 ▶); Basco et al. (2001 ▶); Grelepois et al. (2005 ▶); Gupta et al. (2002 ▶). For puckering analysis, see: Cremer & Pople (1975 ▶); Evans & Boeyens (1989 ▶).

Experimental

Crystal data

C17H27BrO5

M = 391.30

Monoclinic,

a = 9.2836 (2) Å

b = 9.1103 (2) Å

c = 10.2999 (2) Å

β = 90.395 (1)°

V = 871.11 (3) Å3

Z = 2

Mo Kα radiation

μ = 2.38 mm−1

T = 173 K

0.44 × 0.41 × 0.08 mm

Data collection

Bruker APEXII CCD diffractometer

Absorption correction: integration (XPREP; Bruker, 2005 ▶) T min = 0.420, T max = 0.832

13762 measured reflections

4196 independent reflections

3432 reflections with I > 2σ(I)

R int = 0.068

Refinement

R[F 2 > 2σ(F 2)] = 0.034

wR(F 2) = 0.078

S = 0.95

4196 reflections

211 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.61 e Å−3

Δρmin = −0.35 e Å−3

Absolute structure: Flack (1983 ▶), 1966 Friedel pairs

Flack parameter: −0.012 (7)

Data collection: APEX2 (Bruker, 2005 ▶); cell refinement: SAINT (Bruker, 2005 ▶); 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, 1997 ▶) and SCHAKAL99 (Keller, 1999 ▶); software used to prepare material for publication: WinGX (Farrugia, 1999 ▶) and PLATON (Spek, 2009 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810029090/jj2039sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810029090/jj2039Isup2.hkl

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

C17H27BrO5	F(000) = 408
Mr = 391.30	Dx = 1.492 Mg m−3
Monoclinic, P21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2yb	Cell parameters from 6155 reflections
a = 9.2836 (2) Å	θ = 2.9–28.2°
b = 9.1103 (2) Å	µ = 2.38 mm−1
c = 10.2999 (2) Å	T = 173 K
β = 90.395 (1)°	Plate, colourless
V = 871.11 (3) Å3	0.44 × 0.41 × 0.08 mm
Z = 2

Bruker APEXII CCD diffractometer	4196 independent reflections
Radiation source: fine-focus sealed tube	3432 reflections with I > 2σ(I)
graphite	Rint = 0.068
φ and ω scans	θmax = 28.0°, θmin = 2.0°
Absorption correction: integration (XPREP; Bruker, 2005)	h = −12→12
Tmin = 0.420, Tmax = 0.832	k = −12→12
13762 measured reflections	l = −13→13

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)] = 0.034	H-atom parameters constrained
wR(F2) = 0.078	w = 1/[σ2(Fo2) + (0.0405P)2] where P = (Fo2 + 2Fc2)/3
S = 0.95	(Δ/σ)max = 0.001
4196 reflections	Δρmax = 0.61 e Å−3
211 parameters	Δρmin = −0.35 e Å−3
1 restraint	Absolute structure: Flack (1983), 1966 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: −0.012 (7)

Experimental. 1H NMR (600.17 MHz; CDCl3; Me4Si): δH 5.46 (s, 1H, H-5), 4.82 (d, J = 3.4 Hz, 1H, H-12), 4.09 (ddd, J = 11.8, 6.6, 5.5 Hz, 1H, H-16α), 3.79 – 3.73 (m, 1H, H-16β), 3.51 – 3.47 (m, 2H, H-17), 2.66 – 2.59 (m, 1H, H-11), 2.39 – 2.30 (m, 1H, H-3α), 2.01 (ddd, J = 14.6, 4.7, 3.1 Hz, 1H, H-3β), 1.92 – 1.81 (m, 2H, H-2α; H-8α), 1.73 (ddd, J = 14.2, 7.7, 3.6 Hz, 1H, H-8β), 1.62 (dq, J = 13.2, 3.3 Hz, 1H, H-9β), 1.47 (qdd, J = 12.0, 8.9, 4.1 Hz, 2H, H-2α; H-7), 1.41 (s, 3H, H-15), 1.36 – 1.28 (m, 1H, H-10), 1.22 (td, J = 11.5, 6.6 Hz, 1H, H-1), 0.93 (d, J = 6.4 Hz, 3H, H-13), 0.91 (d, J = 7.4 Hz, 3H, H-14), 0.87 (dd, J = 13.3, 3.6 Hz, 3H, H-9α). 13C NMR (150.913 MHz; CDCl3; Me4Si): δC 104.10 (C-4), 102.02 (C-12), 88.12 (C-5), 81.07 (C-6), 68.14 (C-16), 52.54 (C-1), 44.33 (C-7), 37.36 (C-10), 36.37 (C-3), 34.63 (C-11), 31.41 (C-17), 30.86 (C-11), 26.12 (C-15), 24.62 (C-2), 24.33 (C-8), 20.34 (C-14), 12.95 (C-13).

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.

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
C1	0.4624 (2)	0.8858 (2)	0.7096 (2)	0.0219 (6)
H1	0.4971	0.9825	0.6759	0.026*
C2	0.5821 (3)	0.8288 (3)	0.8003 (2)	0.0240 (5)
H2A	0.5667	0.7224	0.8142	0.029*
H2B	0.6756	0.8404	0.7558	0.029*
C3	0.5930 (2)	0.9028 (3)	0.9323 (2)	0.0254 (5)
H3A	0.6188	1.0072	0.9196	0.030*
H3B	0.6717	0.8561	0.9828	0.030*
C4	0.4535 (2)	0.8946 (3)	1.0112 (2)	0.0236 (6)
C5	0.2721 (2)	0.7966 (3)	0.8734 (2)	0.0193 (5)
H5	0.2584	0.7047	0.8217	0.023*
C6	0.3193 (2)	0.9184 (3)	0.7817 (2)	0.0199 (4)
C7	0.1958 (2)	0.9600 (3)	0.6879 (2)	0.0221 (5)
H7	0.2231	1.0558	0.6476	0.027*
C8	0.1822 (3)	0.8494 (3)	0.5770 (2)	0.0293 (6)
H8A	0.1553	0.7523	0.6126	0.035*
H8B	0.1046	0.8812	0.5168	0.035*
C9	0.3227 (3)	0.8356 (3)	0.5027 (2)	0.0286 (6)
H9A	0.3101	0.7640	0.4312	0.034*
H9B	0.3472	0.9317	0.4638	0.034*
C10	0.4453 (3)	0.7860 (3)	0.5903 (2)	0.0268 (6)
H10	0.4230	0.6847	0.6215	0.032*
C11	0.0559 (3)	0.9877 (3)	0.7641 (2)	0.0246 (5)
H11	0.0758	1.0741	0.8214	0.030*
C12	0.0223 (3)	0.8610 (3)	0.8544 (2)	0.0230 (5)
H12	−0.0616	0.8898	0.9092	0.028*
C13	−0.0724 (3)	1.0314 (3)	0.6780 (3)	0.0347 (6)
H13A	−0.1037	0.9465	0.6266	0.052*
H13B	−0.0436	1.1110	0.6196	0.052*
H13C	−0.1520	1.0647	0.7327	0.052*
C14	0.5866 (3)	0.7794 (4)	0.5130 (3)	0.0378 (7)
H14A	0.5710	0.7232	0.4331	0.057*
H14B	0.6613	0.7317	0.5658	0.057*
H14C	0.6173	0.8792	0.4911	0.057*
C15	0.4802 (3)	0.8852 (3)	1.1564 (2)	0.0318 (7)
H15A	0.5460	0.9638	1.1832	0.048*
H15B	0.5231	0.7898	1.1776	0.048*
H15C	0.3886	0.8959	1.2022	0.048*
C16	−0.0657 (3)	0.6166 (3)	0.8603 (2)	0.0281 (6)
H16A	−0.1615	0.6395	0.8966	0.034*
H16B	0.0026	0.6017	0.9333	0.034*
C17	−0.0743 (3)	0.4798 (3)	0.7792 (3)	0.0290 (6)
H17A	−0.1326	0.4995	0.7003	0.035*
H17B	−0.1227	0.4014	0.8292	0.035*
Br1	0.11699 (3)	0.41341 (4)	0.72890 (3)	0.04547 (10)
O1	0.37137 (18)	0.76784 (19)	0.97365 (16)	0.0221 (4)
O2	0.34641 (18)	1.05261 (18)	0.85662 (16)	0.0241 (4)
O3	0.3660 (2)	1.02082 (18)	0.99572 (17)	0.0234 (4)
O4	0.13965 (17)	0.82985 (18)	0.93755 (15)	0.0225 (4)
O5	−0.01788 (17)	0.73579 (18)	0.78053 (15)	0.0235 (4)

	U11	U22	U33	U12	U13	U23
C1	0.0195 (11)	0.0211 (16)	0.0252 (11)	−0.0027 (9)	0.0061 (9)	0.0001 (10)
C2	0.0186 (12)	0.0237 (12)	0.0298 (13)	0.0011 (10)	0.0059 (10)	−0.0033 (11)
C3	0.0193 (10)	0.0246 (12)	0.0322 (12)	−0.0011 (13)	0.0004 (9)	−0.0026 (14)
C4	0.0208 (11)	0.0207 (15)	0.0292 (12)	0.0039 (11)	−0.0004 (9)	−0.0050 (11)
C5	0.0199 (12)	0.0195 (12)	0.0185 (12)	−0.0010 (10)	−0.0003 (10)	0.0001 (10)
C6	0.0187 (9)	0.0162 (9)	0.0250 (11)	−0.0016 (13)	0.0032 (8)	−0.0007 (13)
C7	0.0211 (11)	0.0202 (12)	0.0250 (13)	−0.0024 (9)	0.0015 (10)	0.0066 (10)
C8	0.0266 (14)	0.0357 (13)	0.0255 (13)	−0.0069 (11)	0.0003 (11)	0.0059 (12)
C9	0.0343 (15)	0.0308 (14)	0.0206 (13)	−0.0052 (11)	0.0046 (11)	0.0010 (11)
C10	0.0322 (14)	0.0241 (12)	0.0243 (13)	−0.0034 (11)	0.0078 (11)	−0.0021 (11)
C11	0.0199 (12)	0.0233 (12)	0.0307 (14)	−0.0003 (10)	−0.0024 (11)	0.0005 (11)
C12	0.0174 (11)	0.0239 (11)	0.0277 (13)	−0.0015 (9)	0.0029 (10)	−0.0020 (10)
C13	0.0219 (13)	0.0359 (16)	0.0463 (17)	0.0016 (11)	−0.0030 (12)	0.0072 (14)
C14	0.0356 (16)	0.0446 (17)	0.0331 (15)	0.0036 (13)	0.0099 (13)	−0.0098 (13)
C15	0.0280 (12)	0.0380 (19)	0.0294 (13)	0.0083 (11)	−0.0025 (10)	−0.0077 (12)
C16	0.0265 (13)	0.0291 (14)	0.0287 (14)	−0.0081 (10)	0.0059 (11)	0.0050 (11)
C17	0.0243 (12)	0.0301 (13)	0.0326 (14)	−0.0061 (11)	0.0003 (11)	0.0075 (11)
Br1	0.03348 (15)	0.03086 (14)	0.0721 (2)	0.00014 (15)	0.00489 (12)	−0.00932 (17)
O1	0.0188 (9)	0.0213 (9)	0.0262 (10)	0.0004 (7)	−0.0008 (7)	0.0009 (8)
O2	0.0249 (9)	0.0177 (8)	0.0296 (10)	−0.0009 (7)	−0.0010 (8)	−0.0022 (7)
O3	0.0239 (9)	0.0236 (10)	0.0228 (9)	0.0051 (7)	0.0001 (7)	−0.0055 (8)
O4	0.0188 (8)	0.0270 (9)	0.0219 (8)	−0.0001 (7)	0.0026 (7)	0.0006 (7)
O5	0.0195 (8)	0.0254 (9)	0.0255 (9)	−0.0045 (7)	0.0014 (7)	0.0030 (7)

C1—C10	1.536 (3)	C9—H9B	0.9900
C1—C2	1.538 (3)	C10—C14	1.539 (3)
C1—C6	1.556 (3)	C10—H10	1.0000
C1—H1	1.0000	C11—C12	1.515 (3)
C2—C3	1.520 (3)	C11—C13	1.533 (4)
C2—H2A	0.9900	C11—H11	1.0000
C2—H2B	0.9900	C12—O4	1.410 (3)
C3—C4	1.535 (3)	C12—O5	1.420 (3)
C3—H3A	0.9900	C12—H12	1.0000
C3—H3B	0.9900	C13—H13A	0.9800
C4—O3	1.416 (3)	C13—H13B	0.9800
C4—O1	1.435 (3)	C13—H13C	0.9800
C4—C15	1.517 (3)	C14—H14A	0.9800
C5—O1	1.404 (3)	C14—H14B	0.9800
C5—O4	1.433 (3)	C14—H14C	0.9800
C5—C6	1.523 (3)	C15—H15A	0.9800
C5—H5	1.0000	C15—H15B	0.9800
C6—O2	1.467 (3)	C15—H15C	0.9800
C6—C7	1.541 (3)	C16—O5	1.434 (3)
C7—C8	1.528 (4)	C16—C17	1.502 (4)
C7—C11	1.543 (4)	C16—H16A	0.9900
C7—H7	1.0000	C16—H16B	0.9900
C8—C9	1.522 (4)	C17—Br1	1.949 (3)
C8—H8A	0.9900	C17—H17A	0.9900
C8—H8B	0.9900	C17—H17B	0.9900
C9—C10	1.517 (4)	O2—O3	1.472 (2)
C9—H9A	0.9900
C10—C1—C2	110.89 (19)	C9—C10—C1	111.9 (2)
C10—C1—C6	114.27 (19)	C9—C10—C14	110.0 (2)
C2—C1—C6	112.98 (18)	C1—C10—C14	110.7 (2)
C10—C1—H1	106.0	C9—C10—H10	108.0
C2—C1—H1	106.0	C1—C10—H10	108.0
C6—C1—H1	106.0	C14—C10—H10	108.0
C3—C2—C1	115.91 (19)	C12—C11—C13	113.0 (2)
C3—C2—H2A	108.3	C12—C11—C7	111.41 (19)
C1—C2—H2A	108.3	C13—C11—C7	113.7 (2)
C3—C2—H2B	108.3	C12—C11—H11	106.0
C1—C2—H2B	108.3	C13—C11—H11	106.0
H2A—C2—H2B	107.4	C7—C11—H11	106.0
C2—C3—C4	113.6 (2)	O4—C12—O5	111.26 (19)
C2—C3—H3A	108.8	O4—C12—C11	111.38 (19)
C4—C3—H3A	108.8	O5—C12—C11	109.76 (19)
C2—C3—H3B	108.8	O4—C12—H12	108.1
C4—C3—H3B	108.8	O5—C12—H12	108.1
H3A—C3—H3B	107.7	C11—C12—H12	108.1
O3—C4—O1	108.64 (17)	C11—C13—H13A	109.5
O3—C4—C15	104.26 (19)	C11—C13—H13B	109.5
O1—C4—C15	107.6 (2)	H13A—C13—H13B	109.5
O3—C4—C3	112.7 (2)	C11—C13—H13C	109.5
O1—C4—C3	110.2 (2)	H13A—C13—H13C	109.5
C15—C4—C3	113.08 (19)	H13B—C13—H13C	109.5
O1—C5—O4	105.13 (17)	C10—C14—H14A	109.5
O1—C5—C6	113.71 (18)	C10—C14—H14B	109.5
O4—C5—C6	112.52 (18)	H14A—C14—H14B	109.5
O1—C5—H5	108.4	C10—C14—H14C	109.5
O4—C5—H5	108.4	H14A—C14—H14C	109.5
C6—C5—H5	108.4	H14B—C14—H14C	109.5
O2—C6—C5	109.27 (16)	C4—C15—H15A	109.5
O2—C6—C7	104.4 (2)	C4—C15—H15B	109.5
C5—C6—C7	110.62 (18)	H15A—C15—H15B	109.5
O2—C6—C1	105.43 (17)	C4—C15—H15C	109.5
C5—C6—C1	114.0 (2)	H15A—C15—H15C	109.5
C7—C6—C1	112.44 (17)	H15B—C15—H15C	109.5
C8—C7—C6	111.4 (2)	O5—C16—C17	109.00 (18)
C8—C7—C11	115.0 (2)	O5—C16—H16A	109.9
C6—C7—C11	110.25 (19)	C17—C16—H16A	109.9
C8—C7—H7	106.6	O5—C16—H16B	109.9
C6—C7—H7	106.6	C17—C16—H16B	109.9
C11—C7—H7	106.6	H16A—C16—H16B	108.3
C9—C8—C7	111.3 (2)	C16—C17—Br1	111.10 (18)
C9—C8—H8A	109.4	C16—C17—H17A	109.4
C7—C8—H8A	109.4	Br1—C17—H17A	109.4
C9—C8—H8B	109.4	C16—C17—H17B	109.4
C7—C8—H8B	109.4	Br1—C17—H17B	109.4
H8A—C8—H8B	108.0	H17A—C17—H17B	108.0
C10—C9—C8	111.6 (2)	C5—O1—C4	113.13 (18)
C10—C9—H9A	109.3	C6—O2—O3	111.59 (16)
C8—C9—H9A	109.3	C4—O3—O2	109.64 (16)
C10—C9—H9B	109.3	C12—O4—C5	115.10 (17)
C8—C9—H9B	109.3	C12—O5—C16	112.52 (17)
H9A—C9—H9B	108.0
C10—C1—C2—C3	−170.2 (2)	C2—C1—C10—C14	−59.8 (3)
C6—C1—C2—C3	−40.4 (3)	C6—C1—C10—C14	171.1 (2)
C1—C2—C3—C4	57.3 (3)	C8—C7—C11—C12	75.3 (3)
C2—C3—C4—O3	−94.8 (3)	C6—C7—C11—C12	−51.6 (3)
C2—C3—C4—O1	26.8 (3)	C8—C7—C11—C13	−53.7 (3)
C2—C3—C4—C15	147.3 (2)	C6—C7—C11—C13	179.4 (2)
O1—C5—C6—O2	−56.7 (2)	C13—C11—C12—O4	−176.3 (2)
O4—C5—C6—O2	62.7 (2)	C7—C11—C12—O4	54.3 (3)
O1—C5—C6—C7	−171.20 (19)	C13—C11—C12—O5	60.0 (3)
O4—C5—C6—C7	−51.8 (3)	C7—C11—C12—O5	−69.4 (2)
O1—C5—C6—C1	60.9 (2)	O5—C16—C17—Br1	68.7 (2)
O4—C5—C6—C1	−179.69 (19)	O4—C5—O1—C4	−93.8 (2)
C10—C1—C6—O2	−159.21 (19)	C6—C5—O1—C4	29.7 (3)
C2—C1—C6—O2	72.8 (2)	O3—C4—O1—C5	32.8 (2)
C10—C1—C6—C5	80.9 (2)	C15—C4—O1—C5	145.10 (19)
C2—C1—C6—C5	−47.1 (3)	C3—C4—O1—C5	−91.2 (2)
C10—C1—C6—C7	−46.0 (3)	C5—C6—O2—O3	18.1 (2)
C2—C1—C6—C7	−174.0 (2)	C7—C6—O2—O3	136.50 (16)
O2—C6—C7—C8	163.64 (17)	C1—C6—O2—O3	−104.81 (18)
C5—C6—C7—C8	−78.9 (2)	O1—C4—O3—O2	−72.2 (2)
C1—C6—C7—C8	49.8 (3)	C15—C4—O3—O2	173.27 (17)
O2—C6—C7—C11	−67.5 (2)	C3—C4—O3—O2	50.3 (2)
C5—C6—C7—C11	50.0 (3)	C6—O2—O3—C4	42.6 (2)
C1—C6—C7—C11	178.7 (2)	O5—C12—O4—C5	65.7 (2)
C6—C7—C8—C9	−56.9 (3)	C11—C12—O4—C5	−57.1 (2)
C11—C7—C8—C9	176.8 (2)	O1—C5—O4—C12	−179.24 (18)
C7—C8—C9—C10	59.5 (3)	C6—C5—O4—C12	56.5 (2)
C8—C9—C10—C1	−54.3 (3)	O4—C12—O5—C16	62.4 (2)
C8—C9—C10—C14	−177.7 (2)	C11—C12—O5—C16	−173.86 (19)
C2—C1—C10—C9	177.06 (19)	C17—C16—O5—C12	−167.5 (2)
C6—C1—C10—C9	48.0 (3)

D—H···A	D—H	H···A	D···A	D—H···A
C15—H15B···O2i	0.98	2.50	3.434 (3)	159
C16—H16A···O3ii	0.99	2.46	3.285 (3)	141
C17—H17B···O4ii	0.99	2.50	3.282 (3)	136

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C15—H15B⋯O2i	0.98	2.50	3.434 (3)	159
C16—H16A⋯O3ii	0.99	2.46	3.285 (3)	141
C17—H17B⋯O4ii	0.99	2.50	3.282 (3)	136

Symmetry codes: (i) ; (ii) .