supplementary materials


is5016 scheme

Acta Cryst. (2012). E68, o35-o36    [ doi:10.1107/S1600536811051269 ]

2-Bromo-4-(3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-yl)-6-methoxyphenol

M. Hariono, N. Ngah, H. A. Wahab and A. S. Abdul Rahim

Abstract top

In the title compound, C18H20BrNO3, the oxazolidine ring adopts an envelope conformation with the N atom at the flap position. The mean plane of oxazolidine ring makes dihedral angles of 82.96 (13) and 70.97 (12)°, respectively, with the phenyl and benzene rings. In the crystal, adjacent molecules are connected via O-H...O and C-H...O hydrogen bonds and C-H...[pi] interactions into a zigzag chain along the b axis.

Comment top

Oxazolidine compounds are important in understanding drug behaviour in medicinal chemistry (Duffy et al., 2004). Derivatives of oxazolidine have shown inhibitory effects for several diseases or condition such as β-adrenoreseptor antagonist (Moloney et al., 1998), influenza antiviral (Wang et al., 2010; Nakano et al., 2010), antinflammatory agents (Fulop et al., 2004) and antihyperglycemic (Panneerselvam, 2011). In this paper, we report the X-ray crystal structure of the title oxazolidine compound, (I).

The title compound, C18H20BrNO3, consists of two aromatic rings which are connected through oxazolidine ring (Fig. 1). The molecule is similar with those reported by Asaruddin et al. (2010), in that only the present of Br atom at β position of 3-hydroxy-4-methoxyphenyl ring is different. The oxazolidine ring (O1/C7–C9/N1) adopts an envelope conformation with puckering parameters of Q = 0.433 (2) Å and φ = 107.3 (3)°. The N1 atom is at the flap position and it deviates from the mean plane through the remaining four atoms by 0.651 (2) Å. The C1–C6 phenyl and C10–C15 benzene rings make dihedral angles of 82.96 (13) and 70.97 (12)°, respectively, with the mean plane of oxazolidine ring. The bond lengths and angles are in normal ranges (Allen et al., 1987) and in agreement with those reported by Asaruddin et al. (2010).

In the crystal structure, adjacent molecules are connected via intermolecular O2—H2···O1 and C15—H15A···O2 hydrogen bonds and C18—H18A···Cg2 interactions (Table 1) to form a chain along the [010] direction; Cg2 is the centroid of the C1–C6 ring.

Related literature top

For the synthesis and closely related structures, see: Asaruddin et al. (2010); Diwischeck et al. (2003); Khruscheva et al. (1997); Duffy et al. (2004). For therapeutic properties of oxazolidine derivatives, see: Moloney et al. (1998); Wang et al. (2010); Nakano et al. (2010); Fulop et al. (2004); Panneerselvam (2011). For standard bond lengths, see: Allen et al. (1987). For the low-temperature device used in the data collection, see: Cosier & Glazer (1986).

Experimental top

Following a modified method (Asaruddin et al., 2010; Diwischeck et al., 2003; Khruscheva et al., 1997), (1S,2S)-2-methylamino-1-phenylpropan-1-ol (0.17 g, 1 mmol) was mixed with 3-bromo-4-hydroxy-5-methoxybenzaldehyde (0.23 g, 1 mmol) in a two-round neck bottom flask. The mixture was dissolved in methanol (4 ml) and molecular sieve 4Å (0.1 g) was added to the reaction mixture then the solution was refluxed at 333 K for 6 h. The solution was filtered and the solvent was evaporated in vacuo to give a crude product which was then recrystallized three times from methanol to give colourless blocks with a yield 11%. These were washed with n-hexane and dried overnight to afford single crystals suitable for X-ray analysis.

Refinement top

X-ray data were collected at 100 K (Cosier & Glazer, 1986). The hydroxyl H atom was located in a difference map and refined freely [O2—H2 = 0.8499 (10) Å]. Other H atoms were positioned geometrically and refined using riding model with C—H = 0.95–1.00 Å and Uiso(H)=1.2 or 1.5Ueq(C). A rotating group model was applied for methyl group.

Computing details top

Data collection: APEX2 (Bruker, 2009); cell refinement: SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXTL (Sheldrick, 2008); program(s) used to refine structure: SHELXTL (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title compound, with displacement ellipsoids are drawn at the 50% probability level.
[Figure 2] Fig. 2. The molecular packing of the title compound viewed down the a axis.
2-Bromo-4-(3,4-dimethyl-5-phenyl-1,3-oxazolidin-2-yl)-6-methoxyphenol top
Crystal data top
C18H20BrNO3F(000) = 776
Mr = 378.26Dx = 1.430 Mg m3
Orthorhombic, P212121Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2abCell parameters from 8965 reflections
a = 7.8056 (4) Åθ = 2.0–24.9°
b = 11.9034 (6) ŵ = 2.35 mm1
c = 18.9109 (9) ÅT = 100 K
V = 1757.07 (15) Å3Block, colourless
Z = 40.50 × 0.36 × 0.23 mm
Data collection top
Bruker SMART APEXII CCD area-detector
diffractometer
3074 independent reflections
Radiation source: fine-focus sealed tube2935 reflections with I > 2σ(I)
graphiteRint = 0.037
Detector resolution: 83.66 pixels mm-1θmax = 24.9°, θmin = 2.0°
φ and ω scanh = 99
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
k = 1414
Tmin = 0.383, Tmax = 0.618l = 2222
10569 measured reflections
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)] = 0.023H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.056 w = 1/[σ2(Fo2) + (0.0197P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.08(Δ/σ)max = 0.001
3074 reflectionsΔρmax = 0.32 e Å3
215 parametersΔρmin = 0.26 e Å3
1 restraintAbsolute structure: Flack (1983), 1283 Friedel pairs
Primary atom site location: structure-invariant direct methodsFlack parameter: 0.004 (7)
Crystal data top
C18H20BrNO3V = 1757.07 (15) Å3
Mr = 378.26Z = 4
Orthorhombic, P212121Mo Kα radiation
a = 7.8056 (4) ŵ = 2.35 mm1
b = 11.9034 (6) ÅT = 100 K
c = 18.9109 (9) Å0.50 × 0.36 × 0.23 mm
Data collection top
Bruker SMART APEXII CCD area-detector
diffractometer
3074 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2009)
2935 reflections with I > 2σ(I)
Tmin = 0.383, Tmax = 0.618Rint = 0.037
10569 measured reflectionsθmax = 24.9°
Refinement top
R[F2 > 2σ(F2)] = 0.023H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.056Δρmax = 0.32 e Å3
S = 1.08Δρmin = 0.26 e Å3
3074 reflectionsAbsolute structure: Flack (1983), 1283 Friedel pairs
215 parametersFlack parameter: 0.004 (7)
1 restraint
Special details top

Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open=flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Br10.58037 (3)0.865565 (17)0.942297 (10)0.02402 (8)
O10.2217 (2)0.40943 (12)0.84900 (7)0.0161 (3)
O20.6507 (2)0.85865 (13)0.78478 (7)0.0187 (3)
O30.5513 (2)0.71024 (11)0.68917 (7)0.0195 (3)
N10.0154 (3)0.54199 (15)0.83295 (9)0.0179 (4)
C10.0051 (3)0.1430 (2)0.85221 (12)0.0259 (5)
H1A0.01400.13810.80270.031*
C20.0108 (4)0.0473 (2)0.89404 (16)0.0362 (7)
H2A0.04160.02240.87320.043*
C30.0182 (4)0.0542 (2)0.96587 (14)0.0365 (7)
H3A0.00720.01100.99440.044*
C40.0633 (4)0.1557 (2)0.99672 (12)0.0341 (6)
H4A0.08310.16001.04620.041*
C50.0792 (4)0.25110 (19)0.95494 (11)0.0257 (5)
H5A0.11100.32050.97600.031*
C60.0490 (3)0.24580 (18)0.88251 (10)0.0191 (5)
C70.0610 (3)0.34994 (17)0.83700 (10)0.0170 (5)
H7A0.05630.32650.78620.020*
C80.1793 (3)0.52295 (17)0.86771 (10)0.0165 (5)
H8A0.16300.52770.92010.020*
C90.0781 (3)0.43775 (18)0.84969 (10)0.0191 (5)
H9A0.10980.43790.90090.023*
C100.3140 (3)0.60567 (17)0.84574 (10)0.0152 (5)
C110.3775 (3)0.68157 (17)0.89478 (11)0.0167 (5)
H11A0.34340.67640.94290.020*
C120.4899 (3)0.76443 (18)0.87389 (10)0.0162 (5)
C130.5436 (3)0.77558 (17)0.80434 (10)0.0153 (4)
C140.4837 (3)0.69524 (17)0.75520 (10)0.0149 (4)
C150.3686 (3)0.61278 (17)0.77486 (10)0.0153 (4)
H15A0.32640.56110.74070.018*
C160.2384 (3)0.4204 (2)0.80546 (13)0.0302 (6)
H16A0.32660.47410.82020.045*
H16B0.28080.34370.81220.045*
H16C0.21120.43240.75540.045*
C170.0712 (3)0.64373 (18)0.85614 (11)0.0258 (5)
H17A0.00130.70900.84610.039*
H17B0.09310.63940.90710.039*
H17C0.18020.65130.83090.039*
C180.5220 (3)0.62188 (19)0.63849 (10)0.0224 (5)
H18A0.59040.63610.59600.034*
H18B0.40030.61990.62590.034*
H18C0.55540.54960.65910.034*
H20.659 (3)0.856 (2)0.74000 (15)0.022 (6)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.03139 (14)0.02299 (12)0.01767 (10)0.00772 (11)0.00524 (10)0.00103 (8)
O10.0127 (8)0.0156 (7)0.0200 (7)0.0001 (7)0.0011 (6)0.0004 (5)
O20.0203 (8)0.0183 (8)0.0176 (7)0.0032 (7)0.0025 (6)0.0005 (6)
O30.0228 (10)0.0188 (8)0.0171 (6)0.0038 (7)0.0049 (7)0.0016 (5)
N10.0126 (10)0.0177 (10)0.0234 (8)0.0018 (8)0.0014 (8)0.0019 (7)
C10.0216 (13)0.0234 (12)0.0328 (11)0.0021 (11)0.0001 (10)0.0009 (10)
C20.0318 (16)0.0194 (13)0.0574 (16)0.0070 (12)0.0011 (14)0.0022 (11)
C30.0310 (16)0.0269 (14)0.0517 (15)0.0027 (12)0.0041 (13)0.0184 (11)
C40.0358 (16)0.0388 (15)0.0278 (11)0.0018 (14)0.0042 (12)0.0111 (10)
C50.0295 (14)0.0222 (11)0.0252 (10)0.0001 (11)0.0019 (12)0.0020 (8)
C60.0132 (13)0.0196 (11)0.0245 (10)0.0004 (10)0.0034 (10)0.0023 (8)
C70.0159 (12)0.0190 (11)0.0160 (8)0.0046 (10)0.0001 (9)0.0016 (8)
C80.0167 (13)0.0180 (11)0.0150 (9)0.0035 (10)0.0007 (9)0.0005 (8)
C90.0143 (11)0.0219 (11)0.0211 (9)0.0030 (11)0.0023 (10)0.0026 (8)
C100.0110 (11)0.0163 (11)0.0184 (9)0.0043 (9)0.0003 (8)0.0024 (8)
C110.0165 (12)0.0177 (10)0.0159 (9)0.0022 (9)0.0006 (9)0.0031 (8)
C120.0146 (12)0.0173 (11)0.0167 (9)0.0016 (9)0.0039 (9)0.0036 (8)
C130.0105 (12)0.0149 (10)0.0204 (9)0.0012 (9)0.0012 (9)0.0026 (7)
C140.0118 (11)0.0167 (11)0.0163 (9)0.0040 (9)0.0005 (9)0.0015 (8)
C150.0149 (11)0.0136 (11)0.0174 (9)0.0034 (9)0.0026 (9)0.0004 (7)
C160.0171 (13)0.0353 (14)0.0383 (12)0.0027 (12)0.0068 (12)0.0025 (10)
C170.0178 (12)0.0250 (12)0.0345 (11)0.0039 (14)0.0010 (11)0.0037 (9)
C180.0256 (12)0.0229 (12)0.0186 (9)0.0033 (11)0.0040 (9)0.0058 (9)
Geometric parameters (Å, °) top
Br1—C121.903 (2)C7—H7A1.0000
O1—C81.435 (3)C8—C101.499 (3)
O1—C71.458 (3)C8—H8A1.0000
O2—C131.347 (3)C9—C161.519 (4)
O2—H20.8499 (10)C9—H9A1.0000
O3—C141.367 (2)C10—C111.386 (3)
O3—C181.441 (2)C10—C151.409 (3)
N1—C171.455 (3)C11—C121.378 (3)
N1—C81.456 (3)C11—H11A0.9500
N1—C91.474 (3)C12—C131.387 (3)
C1—C21.392 (3)C13—C141.413 (3)
C1—C61.394 (3)C14—C151.382 (3)
C1—H1A0.9500C15—H15A0.9500
C2—C31.379 (4)C16—H16A0.9800
C2—H2A0.9500C16—H16B0.9800
C3—C41.387 (4)C16—H16C0.9800
C3—H3A0.9500C17—H17A0.9800
C4—C51.389 (3)C17—H17B0.9800
C4—H4A0.9500C17—H17C0.9800
C5—C61.391 (3)C18—H18A0.9800
C5—H5A0.9500C18—H18B0.9800
C6—C71.512 (3)C18—H18C0.9800
C7—C91.526 (3)
C8—O1—C7107.31 (16)N1—C9—H9A109.2
C13—O2—H2107.2 (18)C16—C9—H9A109.2
C14—O3—C18116.80 (16)C7—C9—H9A109.2
C17—N1—C8113.71 (18)C11—C10—C15119.30 (19)
C17—N1—C9113.94 (18)C11—C10—C8119.56 (18)
C8—N1—C9101.95 (17)C15—C10—C8120.99 (18)
C2—C1—C6120.4 (2)C12—C11—C10120.15 (19)
C2—C1—H1A119.8C12—C11—H11A119.9
C6—C1—H1A119.8C10—C11—H11A119.9
C3—C2—C1119.8 (2)C11—C12—C13122.20 (19)
C3—C2—H2A120.1C11—C12—Br1119.62 (15)
C1—C2—H2A120.1C13—C12—Br1118.16 (16)
C2—C3—C4120.5 (2)O2—C13—C12121.22 (18)
C2—C3—H3A119.7O2—C13—C14121.44 (18)
C4—C3—H3A119.7C12—C13—C14117.32 (19)
C3—C4—C5119.7 (2)O3—C14—C15126.11 (18)
C3—C4—H4A120.2O3—C14—C13112.63 (18)
C5—C4—H4A120.2C15—C14—C13121.26 (18)
C4—C5—C6120.5 (2)C14—C15—C10119.68 (19)
C4—C5—H5A119.7C14—C15—H15A120.2
C6—C5—H5A119.7C10—C15—H15A120.2
C5—C6—C1119.1 (2)C9—C16—H16A109.5
C5—C6—C7120.85 (18)C9—C16—H16B109.5
C1—C6—C7120.07 (18)H16A—C16—H16B109.5
O1—C7—C6111.27 (17)C9—C16—H16C109.5
O1—C7—C9104.75 (16)H16A—C16—H16C109.5
C6—C7—C9115.34 (19)H16B—C16—H16C109.5
O1—C7—H7A108.4N1—C17—H17A109.5
C6—C7—H7A108.4N1—C17—H17B109.5
C9—C7—H7A108.4H17A—C17—H17B109.5
O1—C8—N1103.74 (17)N1—C17—H17C109.5
O1—C8—C10112.86 (18)H17A—C17—H17C109.5
N1—C8—C10112.88 (17)H17B—C17—H17C109.5
O1—C8—H8A109.1O3—C18—H18A109.5
N1—C8—H8A109.1O3—C18—H18B109.5
C10—C8—H8A109.1H18A—C18—H18B109.5
N1—C9—C16113.81 (18)O3—C18—H18C109.5
N1—C9—C7101.0 (2)H18A—C18—H18C109.5
C16—C9—C7113.98 (18)H18B—C18—H18C109.5
C6—C1—C2—C30.5 (5)C6—C7—C9—N1149.13 (17)
C1—C2—C3—C40.0 (5)O1—C7—C9—C16148.90 (18)
C2—C3—C4—C50.0 (5)C6—C7—C9—C1688.4 (2)
C3—C4—C5—C60.5 (5)O1—C8—C10—C11129.0 (2)
C4—C5—C6—C11.0 (4)N1—C8—C10—C11113.7 (2)
C4—C5—C6—C7178.2 (3)O1—C8—C10—C1555.5 (3)
C2—C1—C6—C51.0 (4)N1—C8—C10—C1561.8 (3)
C2—C1—C6—C7178.2 (2)C15—C10—C11—C121.4 (3)
C8—O1—C7—C6124.92 (17)C8—C10—C11—C12174.2 (2)
C8—O1—C7—C90.36 (18)C10—C11—C12—C130.0 (3)
C5—C6—C7—O150.7 (3)C10—C11—C12—Br1178.39 (17)
C1—C6—C7—O1130.1 (2)C11—C12—C13—O2178.6 (2)
C5—C6—C7—C968.4 (3)Br1—C12—C13—O23.0 (3)
C1—C6—C7—C9110.7 (2)C11—C12—C13—C142.5 (3)
C7—O1—C8—N127.71 (18)Br1—C12—C13—C14175.97 (16)
C7—O1—C8—C10150.23 (16)C18—O3—C14—C1510.8 (3)
C17—N1—C8—O1167.85 (16)C18—O3—C14—C13169.59 (19)
C9—N1—C8—O144.77 (18)O2—C13—C14—O32.2 (3)
C17—N1—C8—C1069.6 (2)C12—C13—C14—O3176.71 (19)
C9—N1—C8—C10167.27 (17)O2—C13—C14—C15177.4 (2)
C17—N1—C9—C1671.3 (2)C12—C13—C14—C153.6 (3)
C8—N1—C9—C16165.77 (19)O3—C14—C15—C10178.0 (2)
C17—N1—C9—C7166.13 (17)C13—C14—C15—C102.3 (3)
C8—N1—C9—C743.20 (18)C11—C10—C15—C140.2 (3)
O1—C7—C9—N126.45 (18)C8—C10—C15—C14175.3 (2)
Hydrogen-bond geometry (Å, °) top
Cg2 is the centroid of the C1–C6 phenyl ring.
D—H···AD—HH···AD···AD—H···A
O2—H2···O1i0.85 (1)2.03 (1)2.7853 (19)148 (2)
C15—H15A···O2ii0.952.463.232 (3)138
C18—H18A···Cg2i0.982.963.679 (3)131
Symmetry codes: (i) −x+1, y+1/2, −z+3/2; (ii) −x+1, y−1/2, −z+3/2.
Table 1
Hydrogen-bond geometry (Å, °)
top
Cg2 is the centroid of the C1–C6 phenyl ring.
D—H···AD—HH···AD···AD—H···A
O2—H2···O1i0.85 (1)2.03 (1)2.7853 (19)148 (2)
C15—H15A···O2ii0.952.463.232 (3)138
C18—H18A···Cg2i0.982.963.679 (3)131
Symmetry codes: (i) −x+1, y+1/2, −z+3/2; (ii) −x+1, y−1/2, −z+3/2.
Acknowledgements top

MH, HAW and ASAR acknowledge Malaysia Ministry of Science, Technology and Innovations (MOSTI) for funding the synthetic chemistry work under 304/PFARMASI/650544/I121. MH thanks Universiti Sains Malaysia for the award of a postgraduate fellowship.

references
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