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In the title compound, C10H14BrNO3, the six-membered lactone ring is in a boat conformation, with the two carbonyl groups cis to one another across the boat basal plane. C—H...O hydrogen bonds and weak C—H...Br interactions stabilize the crystal structure.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S010827010401131X/ga1049sup1.cif
Contains datablocks global, I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S010827010401131X/ga1049Isup2.hkl
Contains datablock I

CCDC reference: 245891

Comment top

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).

Experimental top

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).

Refinement top

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).

Computing details top

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.

Figures top
[Figure 1] Fig. 1. A view of the molecular structure of (I), with the atomic numbering scheme. Displacement ellipsoids are drawn at the 50% probability level and H atoms are shown as small spheres of arbitrary radiis.
[Figure 2] Fig. 2. The molecular packing of (I). The stronger intramolecular contacts (Table 2) are shown as dashed lines.
3-bromomethyl-3-ethyl-1,4-dioxo-tetrahydro-pyrrolo[2,1-c][1,4]oxazine top
Crystal data top
C10H14BrNO3Dx = 1.571 Mg m3
Mr = 276.13Melting point = 377.7–379.2 K
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 1022 reflections
a = 8.897 (3) Åθ = 2.7–25.5°
b = 9.003 (3) ŵ = 3.51 mm1
c = 14.577 (5) ÅT = 293 K
V = 1167.6 (7) Å3Block, colourless
Z = 40.20 × 0.10 × 0.08 mm
F(000) = 560
Data collection top
Bruker SMART CCD area-detector
diffractometer
2055 independent reflections
Radiation source: fine-focus sealed X-ray tube1769 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.024
ϕ and ω scansθmax = 25.0°, θmin = 2.7°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)
h = 1010
Tmin = 0.541, Tmax = 0.767k = 910
4889 measured reflectionsl = 1317
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.030H-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 reflectionsΔρmax = 0.28 e Å3
137 parametersΔρmin = 0.30 e Å3
0 restraintsAbsolute structure: Flack (1983)
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: 0.020 (11), 847 Friedel pairs
Crystal data top
C10H14BrNO3V = 1167.6 (7) Å3
Mr = 276.13Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 8.897 (3) ŵ = 3.51 mm1
b = 9.003 (3) ÅT = 293 K
c = 14.577 (5) Å0.20 × 0.10 × 0.08 mm
Data collection top
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 = 0.767Rint = 0.024
4889 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.030H-atom parameters constrained
wR(F2) = 0.069Δρmax = 0.28 e Å3
S = 1.03Δρmin = 0.30 e Å3
2055 reflectionsAbsolute structure: Flack (1983)
137 parametersAbsolute structure parameter: 0.020 (11), 847 Friedel pairs
0 restraints
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br10.80402 (4)0.51072 (4)0.36941 (2)0.07046 (15)
C10.5775 (4)0.4325 (4)0.5639 (2)0.0509 (9)
C30.7446 (3)0.6497 (3)0.5450 (2)0.0432 (8)
C40.8695 (4)0.5589 (3)0.5883 (2)0.0424 (7)
C60.9469 (4)0.3245 (4)0.6597 (2)0.0569 (9)
H6A0.96900.36950.71870.068*
H6B1.04040.30850.62700.068*
C70.8619 (4)0.1793 (4)0.6719 (3)0.0667 (10)
H7A0.87190.14290.73420.080*
H7B0.89940.10430.63000.080*
C80.6983 (5)0.2172 (4)0.6505 (2)0.0597 (9)
H8A0.64450.13090.62780.072*
H8B0.64710.25560.70420.072*
C90.7130 (4)0.3356 (3)0.5765 (2)0.0442 (7)
H90.73590.28690.51800.053*
C100.7782 (4)0.6858 (3)0.4458 (2)0.0502 (8)
H10A0.86910.74510.44300.060*
H10B0.69660.74510.42130.060*
C110.7262 (4)0.7963 (3)0.5959 (2)0.0522 (8)
H11A0.81930.85190.59130.063*
H11B0.64830.85400.56590.063*
C120.6859 (6)0.7786 (4)0.6963 (2)0.0691 (10)
H12A0.59350.72430.70160.104*
H12B0.67420.87480.72380.104*
H12C0.76460.72550.72720.104*
N50.8448 (3)0.4178 (3)0.60642 (17)0.0437 (7)
O10.4528 (3)0.3842 (3)0.5623 (2)0.0832 (8)
O20.5986 (2)0.5775 (2)0.54905 (16)0.0494 (6)
O30.9889 (2)0.6207 (3)0.60803 (17)0.0617 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.0855 (2)0.0736 (3)0.0524 (2)0.0068 (3)0.00395 (17)0.0044 (2)
C10.045 (2)0.050 (2)0.058 (2)0.0072 (16)0.0064 (16)0.0004 (15)
C30.0364 (17)0.0392 (16)0.0540 (19)0.0043 (12)0.0031 (13)0.0022 (14)
C40.0405 (17)0.0450 (18)0.0416 (17)0.0041 (14)0.0006 (14)0.0033 (13)
C60.0562 (19)0.051 (2)0.064 (2)0.0076 (17)0.0146 (17)0.0074 (17)
C70.087 (3)0.050 (2)0.064 (2)0.005 (2)0.011 (2)0.0107 (17)
C80.064 (2)0.0473 (18)0.068 (2)0.0109 (19)0.000 (3)0.0077 (16)
C90.0470 (18)0.0385 (16)0.0470 (17)0.0069 (15)0.0052 (16)0.0021 (13)
C100.0512 (19)0.0478 (18)0.0516 (17)0.0068 (16)0.0025 (15)0.0053 (14)
C110.0507 (19)0.0384 (17)0.067 (2)0.0017 (15)0.0002 (17)0.0007 (15)
C120.088 (3)0.058 (2)0.061 (2)0.002 (2)0.008 (2)0.0030 (16)
N50.0406 (15)0.0385 (14)0.0521 (16)0.0006 (11)0.0096 (12)0.0054 (11)
O10.0449 (14)0.0724 (17)0.132 (2)0.0195 (13)0.0155 (15)0.0152 (17)
O20.0369 (12)0.0428 (12)0.0687 (16)0.0006 (10)0.0015 (11)0.0031 (11)
O30.0460 (13)0.0599 (15)0.0793 (17)0.0162 (11)0.0131 (12)0.0147 (12)
Geometric parameters (Å, º) top
Br1—C101.943 (3)C7—H7A0.9700
C1—O11.192 (4)C7—H7B0.9700
C1—O21.336 (4)C8—C91.521 (4)
C1—C91.500 (5)C8—H8A0.9700
C3—O21.454 (4)C8—H8B0.9700
C3—C101.511 (4)C9—N51.453 (4)
C3—C41.516 (4)C9—H90.9800
C3—C111.523 (4)C10—H10A0.9700
C4—O31.234 (4)C10—H10B0.9700
C4—N51.316 (4)C11—C121.516 (5)
C6—N51.462 (4)C11—H11A0.9700
C6—C71.520 (5)C11—H11B0.9700
C6—H6A0.9700C12—H12A0.9600
C6—H6B0.9700C12—H12B0.9600
C7—C81.527 (5)C12—H12C0.9600
O1—C1—O2118.9 (3)H8A—C8—H8B109.1
O1—C1—C9122.6 (3)N5—C9—C1112.9 (2)
O2—C1—C9118.4 (3)N5—C9—C8102.3 (3)
O2—C3—C10108.1 (3)C1—C9—C8115.2 (3)
O2—C3—C4113.4 (2)N5—C9—H9108.7
C10—C3—C4111.7 (2)C1—C9—H9108.7
O2—C3—C11105.8 (2)C8—C9—H9108.7
C10—C3—C11107.5 (3)C3—C10—Br1113.4 (2)
C4—C3—C11110.1 (3)C3—C10—H10A108.9
O3—C4—N5122.1 (3)Br1—C10—H10A108.9
O3—C4—C3119.0 (3)C3—C10—H10B108.9
N5—C4—C3118.8 (3)Br1—C10—H10B108.9
N5—C6—C7104.3 (3)H10A—C10—H10B107.7
N5—C6—H6A110.9C12—C11—C3113.9 (3)
C7—C6—H6A110.9C12—C11—H11A108.8
N5—C6—H6B110.9C3—C11—H11A108.8
C7—C6—H6B110.9C12—C11—H11B108.8
H6A—C6—H6B108.9C3—C11—H11B108.8
C6—C7—C8105.0 (3)H11A—C11—H11B107.7
C6—C7—H7A110.8C11—C12—H12A109.5
C8—C7—H7A110.8C11—C12—H12B109.5
C6—C7—H7B110.8H12A—C12—H12B109.5
C8—C7—H7B110.8C11—C12—H12C109.5
H7A—C7—H7B108.8H12A—C12—H12C109.5
C9—C8—C7102.7 (3)H12B—C12—H12C109.5
C9—C8—H8A111.2C4—N5—C9124.5 (3)
C7—C8—H8A111.2C4—N5—C6123.9 (3)
C9—C8—H8B111.2C9—N5—C6111.6 (2)
C7—C8—H8B111.2C1—O2—C3124.7 (3)
Br1—C10—C3—C459.6 (3)O2—C3—C11—C1262.4 (4)
Br1—C10—C3—O265.8 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C10—H10B···O3i0.972.253.206 (4)169
C12—H12C···Br1ii0.963.033.627 (4)122
C10—H10A···O2iii0.972.603.560 (4)173
C11—H11B···O3i0.972.913.721 (4)141
C7—H7A···O3iv0.972.623.512 (5)153
C9—H9···O1v0.982.733.544 (4)141
C7—H7B···O1v0.972.853.555 (5)131
C10—H10A···O30.972.863.074 (4)93
C12—H12C···O30.962.813.308 (5)113
C12—H12A···O20.962.592.914 (4)100
C11—H11A···O30.972.582.828 (4)94
Symmetry codes: (i) x1/2, 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, y1/2, z+3/2; (v) x+1/2, y+1/2, z+1.

Experimental details

Crystal data
Chemical formulaC10H14BrNO3
Mr276.13
Crystal system, space groupOrthorhombic, P212121
Temperature (K)293
a, b, c (Å)8.897 (3), 9.003 (3), 14.577 (5)
V3)1167.6 (7)
Z4
Radiation typeMo Kα
µ (mm1)3.51
Crystal size (mm)0.20 × 0.10 × 0.08
Data collection
DiffractometerBruker SMART CCD area-detector
diffractometer
Absorption correctionMulti-scan
(SADABS; Sheldrick, 1996)
Tmin, Tmax0.541, 0.767
No. of measured, independent and
observed [I > 2σ(I)] reflections
4889, 2055, 1769
Rint0.024
(sin θ/λ)max1)0.595
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.030, 0.069, 1.03
No. of reflections2055
No. of parameters137
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.28, 0.30
Absolute structureFlack (1983)
Absolute structure parameter0.020 (11), 847 Friedel pairs

Computer programs: SMART (Bruker, 1997), SMART, SAINT (Bruker, 1997) and SHELXTL (Bruker, 1998), SHELXS97 (Sheldrick, 1997), SHELXL97 (Sheldrick, 1997), SHELXTL.

Selected geometric parameters (Å, º) top
Br1—C101.943 (3)C4—N51.316 (4)
C1—O21.336 (4)C6—N51.462 (4)
C3—O21.454 (4)C9—N51.453 (4)
O2—C3—C4113.4 (2)C9—C8—C7102.7 (3)
C10—C3—C4111.7 (2)N5—C9—C1112.9 (2)
O2—C3—C11105.8 (2)C3—C10—Br1113.4 (2)
Br1—C10—C3—O265.8 (3)O2—C3—C11—C1262.4 (4)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C10—H10B···O3i0.972.253.206 (4)169
C12—H12C···Br1ii0.963.033.627 (4)122
C10—H10A···O2iii0.972.603.560 (4)173
Symmetry codes: (i) x1/2, 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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