Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S010827010401131X/ga1049sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S010827010401131X/ga1049Isup2.hkl |
CCDC reference: 245891
To a stirred solution of (S)—N-ethylacryloylproline (20 mmol, 3.94 g) in anhydrous dimethylformamide (DMF, 40 ml) was added N-bromosuccimide (40 mmol, 7.12 g) in portions under argon at room temperature. The reaction mixture was stirred for 24 h and then evaporated to dryness under reduced pressure. The residue was diluted with water (60 ml) and extracted with ethyl acetate (20 ml × 3). The combined organic phase was washed with saturated NaHCO3 solution (30 ml), water (30 ml) and brine (30 ml), and then dried over MgSO4 before being evaporated to dryness. The residue was crystallized from ethyl acetate to give (I) in 76% yield (m.p. 377.7–379.2 K). A single-crystal of (I) suitable for X-ray diffraction was grown from a solution in methanol by slow evaporation. Spectroscopic analysis: 1H NMR (CDCl3, TMS, internal reference): δ 4.51 (dd, 1H, NCHCO), 3.89, 3.61 (d, 2H, CH2Br), 3.73, 3.60 (m, 2H, CH2N), 1.82–2.50 (m, 6H, 3× CH2), 0.93 (t, 3H, CH3).
H atoms were positioned from difference fourier map and then treated as riding atoms, with C—H distances of 0.97 (CH2) and 0.96 Å (CH3), and Uiso(H) values of 1.2 (CH2) or 1.5 (CH3) times Ueq(C).
Data collection: SMART (Bruker, 1997); cell refinement: SMART; data reduction: SAINT (Bruker, 1997) and SHELXTL (Bruker, 1998); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.
C10H14BrNO3 | Dx = 1.571 Mg m−3 |
Mr = 276.13 | Melting point = 377.7–379.2 K |
Orthorhombic, P212121 | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 1022 reflections |
a = 8.897 (3) Å | θ = 2.7–25.5° |
b = 9.003 (3) Å | µ = 3.51 mm−1 |
c = 14.577 (5) Å | T = 293 K |
V = 1167.6 (7) Å3 | Block, colourless |
Z = 4 | 0.20 × 0.10 × 0.08 mm |
F(000) = 560 |
Bruker SMART CCD area-detector diffractometer | 2055 independent reflections |
Radiation source: fine-focus sealed X-ray tube | 1769 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.024 |
ϕ and ω scans | θmax = 25.0°, θmin = 2.7° |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | h = −10→10 |
Tmin = 0.541, Tmax = 0.767 | k = −9→10 |
4889 measured reflections | l = −13→17 |
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) = 0.069 | w = 1/[σ2(Fo2) + (0.0392P)2] where P = (Fo2 + 2Fc2)/3 |
S = 1.03 | (Δ/σ)max < 0.001 |
2055 reflections | Δρmax = 0.28 e Å−3 |
137 parameters | Δρmin = −0.30 e Å−3 |
0 restraints | Absolute structure: Flack (1983) |
Primary atom site location: structure-invariant direct methods | Absolute structure parameter: 0.020 (11), 847 Friedel pairs |
C10H14BrNO3 | V = 1167.6 (7) Å3 |
Mr = 276.13 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 8.897 (3) Å | µ = 3.51 mm−1 |
b = 9.003 (3) Å | T = 293 K |
c = 14.577 (5) Å | 0.20 × 0.10 × 0.08 mm |
Bruker SMART CCD area-detector diffractometer | 2055 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 1996) | 1769 reflections with I > 2σ(I) |
Tmin = 0.541, Tmax = 0.767 | Rint = 0.024 |
4889 measured reflections |
R[F2 > 2σ(F2)] = 0.030 | H-atom parameters constrained |
wR(F2) = 0.069 | Δρmax = 0.28 e Å−3 |
S = 1.03 | Δρmin = −0.30 e Å−3 |
2055 reflections | Absolute structure: Flack (1983) |
137 parameters | Absolute structure parameter: 0.020 (11), 847 Friedel pairs |
0 restraints |
x | y | z | Uiso*/Ueq | ||
Br1 | 0.80402 (4) | 0.51072 (4) | 0.36941 (2) | 0.07046 (15) | |
C1 | 0.5775 (4) | 0.4325 (4) | 0.5639 (2) | 0.0509 (9) | |
C3 | 0.7446 (3) | 0.6497 (3) | 0.5450 (2) | 0.0432 (8) | |
C4 | 0.8695 (4) | 0.5589 (3) | 0.5883 (2) | 0.0424 (7) | |
C6 | 0.9469 (4) | 0.3245 (4) | 0.6597 (2) | 0.0569 (9) | |
H6A | 0.9690 | 0.3695 | 0.7187 | 0.068* | |
H6B | 1.0404 | 0.3085 | 0.6270 | 0.068* | |
C7 | 0.8619 (4) | 0.1793 (4) | 0.6719 (3) | 0.0667 (10) | |
H7A | 0.8719 | 0.1429 | 0.7342 | 0.080* | |
H7B | 0.8994 | 0.1043 | 0.6300 | 0.080* | |
C8 | 0.6983 (5) | 0.2172 (4) | 0.6505 (2) | 0.0597 (9) | |
H8A | 0.6445 | 0.1309 | 0.6278 | 0.072* | |
H8B | 0.6471 | 0.2556 | 0.7042 | 0.072* | |
C9 | 0.7130 (4) | 0.3356 (3) | 0.5765 (2) | 0.0442 (7) | |
H9 | 0.7359 | 0.2869 | 0.5180 | 0.053* | |
C10 | 0.7782 (4) | 0.6858 (3) | 0.4458 (2) | 0.0502 (8) | |
H10A | 0.8691 | 0.7451 | 0.4430 | 0.060* | |
H10B | 0.6966 | 0.7451 | 0.4213 | 0.060* | |
C11 | 0.7262 (4) | 0.7963 (3) | 0.5959 (2) | 0.0522 (8) | |
H11A | 0.8193 | 0.8519 | 0.5913 | 0.063* | |
H11B | 0.6483 | 0.8540 | 0.5659 | 0.063* | |
C12 | 0.6859 (6) | 0.7786 (4) | 0.6963 (2) | 0.0691 (10) | |
H12A | 0.5935 | 0.7243 | 0.7016 | 0.104* | |
H12B | 0.6742 | 0.8748 | 0.7238 | 0.104* | |
H12C | 0.7646 | 0.7255 | 0.7272 | 0.104* | |
N5 | 0.8448 (3) | 0.4178 (3) | 0.60642 (17) | 0.0437 (7) | |
O1 | 0.4528 (3) | 0.3842 (3) | 0.5623 (2) | 0.0832 (8) | |
O2 | 0.5986 (2) | 0.5775 (2) | 0.54905 (16) | 0.0494 (6) | |
O3 | 0.9889 (2) | 0.6207 (3) | 0.60803 (17) | 0.0617 (7) |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1 | 0.0855 (2) | 0.0736 (3) | 0.0524 (2) | 0.0068 (3) | 0.00395 (17) | −0.0044 (2) |
C1 | 0.045 (2) | 0.050 (2) | 0.058 (2) | −0.0072 (16) | −0.0064 (16) | −0.0004 (15) |
C3 | 0.0364 (17) | 0.0392 (16) | 0.0540 (19) | −0.0043 (12) | 0.0031 (13) | 0.0022 (14) |
C4 | 0.0405 (17) | 0.0450 (18) | 0.0416 (17) | −0.0041 (14) | 0.0006 (14) | 0.0033 (13) |
C6 | 0.0562 (19) | 0.051 (2) | 0.064 (2) | 0.0076 (17) | −0.0146 (17) | 0.0074 (17) |
C7 | 0.087 (3) | 0.050 (2) | 0.064 (2) | 0.005 (2) | −0.011 (2) | 0.0107 (17) |
C8 | 0.064 (2) | 0.0473 (18) | 0.068 (2) | −0.0109 (19) | 0.000 (3) | 0.0077 (16) |
C9 | 0.0470 (18) | 0.0385 (16) | 0.0470 (17) | −0.0069 (15) | −0.0052 (16) | −0.0021 (13) |
C10 | 0.0512 (19) | 0.0478 (18) | 0.0516 (17) | 0.0068 (16) | −0.0025 (15) | 0.0053 (14) |
C11 | 0.0507 (19) | 0.0384 (17) | 0.067 (2) | 0.0017 (15) | 0.0002 (17) | 0.0007 (15) |
C12 | 0.088 (3) | 0.058 (2) | 0.061 (2) | 0.002 (2) | 0.008 (2) | −0.0030 (16) |
N5 | 0.0406 (15) | 0.0385 (14) | 0.0521 (16) | 0.0006 (11) | −0.0096 (12) | 0.0054 (11) |
O1 | 0.0449 (14) | 0.0724 (17) | 0.132 (2) | −0.0195 (13) | −0.0155 (15) | 0.0152 (17) |
O2 | 0.0369 (12) | 0.0428 (12) | 0.0687 (16) | 0.0006 (10) | −0.0015 (11) | 0.0031 (11) |
O3 | 0.0460 (13) | 0.0599 (15) | 0.0793 (17) | −0.0162 (11) | −0.0131 (12) | 0.0147 (12) |
Br1—C10 | 1.943 (3) | C7—H7A | 0.9700 |
C1—O1 | 1.192 (4) | C7—H7B | 0.9700 |
C1—O2 | 1.336 (4) | C8—C9 | 1.521 (4) |
C1—C9 | 1.500 (5) | C8—H8A | 0.9700 |
C3—O2 | 1.454 (4) | C8—H8B | 0.9700 |
C3—C10 | 1.511 (4) | C9—N5 | 1.453 (4) |
C3—C4 | 1.516 (4) | C9—H9 | 0.9800 |
C3—C11 | 1.523 (4) | C10—H10A | 0.9700 |
C4—O3 | 1.234 (4) | C10—H10B | 0.9700 |
C4—N5 | 1.316 (4) | C11—C12 | 1.516 (5) |
C6—N5 | 1.462 (4) | C11—H11A | 0.9700 |
C6—C7 | 1.520 (5) | C11—H11B | 0.9700 |
C6—H6A | 0.9700 | C12—H12A | 0.9600 |
C6—H6B | 0.9700 | C12—H12B | 0.9600 |
C7—C8 | 1.527 (5) | C12—H12C | 0.9600 |
O1—C1—O2 | 118.9 (3) | H8A—C8—H8B | 109.1 |
O1—C1—C9 | 122.6 (3) | N5—C9—C1 | 112.9 (2) |
O2—C1—C9 | 118.4 (3) | N5—C9—C8 | 102.3 (3) |
O2—C3—C10 | 108.1 (3) | C1—C9—C8 | 115.2 (3) |
O2—C3—C4 | 113.4 (2) | N5—C9—H9 | 108.7 |
C10—C3—C4 | 111.7 (2) | C1—C9—H9 | 108.7 |
O2—C3—C11 | 105.8 (2) | C8—C9—H9 | 108.7 |
C10—C3—C11 | 107.5 (3) | C3—C10—Br1 | 113.4 (2) |
C4—C3—C11 | 110.1 (3) | C3—C10—H10A | 108.9 |
O3—C4—N5 | 122.1 (3) | Br1—C10—H10A | 108.9 |
O3—C4—C3 | 119.0 (3) | C3—C10—H10B | 108.9 |
N5—C4—C3 | 118.8 (3) | Br1—C10—H10B | 108.9 |
N5—C6—C7 | 104.3 (3) | H10A—C10—H10B | 107.7 |
N5—C6—H6A | 110.9 | C12—C11—C3 | 113.9 (3) |
C7—C6—H6A | 110.9 | C12—C11—H11A | 108.8 |
N5—C6—H6B | 110.9 | C3—C11—H11A | 108.8 |
C7—C6—H6B | 110.9 | C12—C11—H11B | 108.8 |
H6A—C6—H6B | 108.9 | C3—C11—H11B | 108.8 |
C6—C7—C8 | 105.0 (3) | H11A—C11—H11B | 107.7 |
C6—C7—H7A | 110.8 | C11—C12—H12A | 109.5 |
C8—C7—H7A | 110.8 | C11—C12—H12B | 109.5 |
C6—C7—H7B | 110.8 | H12A—C12—H12B | 109.5 |
C8—C7—H7B | 110.8 | C11—C12—H12C | 109.5 |
H7A—C7—H7B | 108.8 | H12A—C12—H12C | 109.5 |
C9—C8—C7 | 102.7 (3) | H12B—C12—H12C | 109.5 |
C9—C8—H8A | 111.2 | C4—N5—C9 | 124.5 (3) |
C7—C8—H8A | 111.2 | C4—N5—C6 | 123.9 (3) |
C9—C8—H8B | 111.2 | C9—N5—C6 | 111.6 (2) |
C7—C8—H8B | 111.2 | C1—O2—C3 | 124.7 (3) |
Br1—C10—C3—C4 | 59.6 (3) | O2—C3—C11—C12 | 62.4 (4) |
Br1—C10—C3—O2 | −65.8 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
C10—H10B···O3i | 0.97 | 2.25 | 3.206 (4) | 169 |
C12—H12C···Br1ii | 0.96 | 3.03 | 3.627 (4) | 122 |
C10—H10A···O2iii | 0.97 | 2.60 | 3.560 (4) | 173 |
C11—H11B···O3i | 0.97 | 2.91 | 3.721 (4) | 141 |
C7—H7A···O3iv | 0.97 | 2.62 | 3.512 (5) | 153 |
C9—H9···O1v | 0.98 | 2.73 | 3.544 (4) | 141 |
C7—H7B···O1v | 0.97 | 2.85 | 3.555 (5) | 131 |
C10—H10A···O3 | 0.97 | 2.86 | 3.074 (4) | 93 |
C12—H12C···O3 | 0.96 | 2.81 | 3.308 (5) | 113 |
C12—H12A···O2 | 0.96 | 2.59 | 2.914 (4) | 100 |
C11—H11A···O3 | 0.97 | 2.58 | 2.828 (4) | 94 |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+1, z+1/2; (iii) x+1/2, −y+3/2, −z+1; (iv) −x+2, y−1/2, −z+3/2; (v) x+1/2, −y+1/2, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C10H14BrNO3 |
Mr | 276.13 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 293 |
a, b, c (Å) | 8.897 (3), 9.003 (3), 14.577 (5) |
V (Å3) | 1167.6 (7) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 3.51 |
Crystal size (mm) | 0.20 × 0.10 × 0.08 |
Data collection | |
Diffractometer | Bruker SMART CCD area-detector diffractometer |
Absorption correction | Multi-scan (SADABS; Sheldrick, 1996) |
Tmin, Tmax | 0.541, 0.767 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4889, 2055, 1769 |
Rint | 0.024 |
(sin θ/λ)max (Å−1) | 0.595 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.030, 0.069, 1.03 |
No. of reflections | 2055 |
No. of parameters | 137 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.28, −0.30 |
Absolute structure | Flack (1983) |
Absolute structure parameter | 0.020 (11), 847 Friedel pairs |
Computer programs: SMART (Bruker, 1997), SMART, SAINT (Bruker, 1997) and SHELXTL (Bruker, 1998), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL.
Br1—C10 | 1.943 (3) | C4—N5 | 1.316 (4) |
C1—O2 | 1.336 (4) | C6—N5 | 1.462 (4) |
C3—O2 | 1.454 (4) | C9—N5 | 1.453 (4) |
O2—C3—C4 | 113.4 (2) | C9—C8—C7 | 102.7 (3) |
C10—C3—C4 | 111.7 (2) | N5—C9—C1 | 112.9 (2) |
O2—C3—C11 | 105.8 (2) | C3—C10—Br1 | 113.4 (2) |
Br1—C10—C3—O2 | −65.8 (3) | O2—C3—C11—C12 | 62.4 (4) |
D—H···A | D—H | H···A | D···A | D—H···A |
C10—H10B···O3i | 0.97 | 2.25 | 3.206 (4) | 169 |
C12—H12C···Br1ii | 0.96 | 3.03 | 3.627 (4) | 122 |
C10—H10A···O2iii | 0.97 | 2.60 | 3.560 (4) | 173 |
Symmetry codes: (i) x−1/2, −y+3/2, −z+1; (ii) −x+3/2, −y+1, z+1/2; (iii) x+1/2, −y+3/2, −z+1. |
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The (S)- or (R)-1,4-dioxo-tetrahydro-pyrrolo[2,1-c][1,4]oxazine analogues, prepared from α,β-unsaturated acids with (S)- or (R)-proline via a highly asymmetric bromolactonization reaction, are useful as versatile synthetic blocks for many active products (Kirkovsky et al.,2000; Jew et al., 2000; Corey, 1987). In our studies of the asymmetric total synthesis of the camptothecin analogues with anticancer activities, crystals of the new title compound, (I), a key chiral building block for the preparation of these types of compounds, has been obtained from the asymmetric bromolactonization of (S)—N-ethylacryloylproline with N-bromosuccimide in an anhydrous DMF solution.
The bond lengths and angles in (I) have normal values (Table 1) compared with those achieved by MM2 calculation (CS ChemOffice, 2001), except that the C4—N5 bond length [1.316 (4) Å] is shorter than the theoretical value (1.359 Å). The chiral centre at atom C3 (S) is characterized by the Br1—C10—C3—O2 [−65.8 (3)°] and O2—C3—C11—C12 [62.4 (4)°] torsion angles, thus confirming reported experimental results (Jew et al., 1979; Hayashi et al., 1981). The configuration of (I) is the same as that of a closely related structure 3-bromomethyl-3-methyl-1,4-dioxo-3,4,6,7,8,8a-tetrahydro-1H- pyrrolo[2,1-c][1,4]oxazine (23 in Crout et al., 1991). To further confirm the S configuration preference in the asymmetric bromolactonization reaction of α,β-unsaturated acids with (S)-proline, the energies of (S)- and (R)-configuration products of the title bromolactone (I) and compound 23 were calculated using the HYPERCHEM 5.0 program (Hypercube, Inc., 1998) at the semi-empirical AM1 computational level; an r.m.s. gradient for the forces acting on each atom of 0.05 kcal.mol−1 Å−1 was employed as the convergence criterion. The final energies of (S)-bromolactones (−2866.84 and −2587.61 a.u.) were slightly lower than those of (R)-bromolactones (−2864.90, −2586.73 a.u.) for (I) and compound 23, respectively. Thus, qualitatively, there is an energy advantage in the (S)-configuration bromolactone.
The lactone ring of (I) adopts a boat conformation (Fig. 1). Atoms O1 and O3 of the two carbonyl groups are at distances of 0.118 (6) and 0.140 (5) Å, respectively, from the boat basal plane, which indicates that the two CO groups have a cis orientation. Atoms C9 and C3 are 0.295 (5) and 0.193 (5) Å, respectively, from the boat plane (N5/C4/O2/C1). The pyrrolidine ring is in an envelope conformation, the flap atom C8 lying 0.559 (6) Å from the C7/C6/N5/C9 plane.
The packing structure of (I) involves weak C10—H10B···O3 and very weak C10—H10A···O2 hydrogen bonds (Table 2). These are responsible for the formation of dimer aggregates, additionally stabilized by weak C12—H12C···Br1 interactions (Fig. 2).