research communications
The first c]oxazole ring system
of the pyrrolo[1,2-aDepartment of Chemistry, Faculty of Science, Zawia University, PO Box 16168, Zawia, Libya, and bDepartment of Chemistry, The University of Sheffield, Dainton Building, Sheffield S3 7HF, UK
*Correspondence e-mail: craig.robertson@sheffield.ac.uk
The title compound, C7H4F3NO2, 3-trifluoromethyl-1H-pyrrolo[1,2-c]oxazol-1-one, is the first of the pyrrolo[1,2-c]oxazole ring system: the fused ring system is almost planar (r.m.s. deviation = 0.006 Å). In the crystal, weak C—H⋯O and C—H⋯F hydrogen bonds link the molecules into [001] chains and π–π stacking interactions consolidate the structure.
Keywords: crystal structure; pyrrolo[1,2-c]oxazole; hydrogen bonds.
CCDC reference: 1919738
1. Chemical context
In the context of an approach to the synthesis of proline-derived 3 by the proposed palladium-catalyzed Negishi coupling of organozinc reagent 1 with protected 4-hydroxyproline-derived acid chloride 2, we needed access to a suitably N,O-diprotected 4-hydroxyproline derivative (Fig. 1). Our initial choice was to use TFA protection, since related cross-coupling reactions with the TFA-protected proline acid chloride had been successful (Deboves et al. 2001), and so the preparation of N,O-bis-trifluoroacetyl-4-hydroxy-L-proline 4 was attempted. The preparation of this compound had been reported, but without a detailed procedure (Mori et al., 1986).
Treatment of (2S,4R)-4-hydroxyproline with trifluoroacetic anhydride TFAA (3 eq.) in dichloromethane at 273 K, followed by heating at reflux, gave a mixture of two compounds, which could be separated by (Fig. 2). The more polar compound was the desired bis-TFA protected (2S,4R)-4-hydroxyproline 4 (47%), and the less polar material was an unknown by-product 5 (52%). This latter unknown compound exhibited signals in the aromatic region of the 1H NMR spectrum, suggesting that the hydroxy group had been eliminated and a pyrrole derivative had been formed. The obtained for 5 showed a base peak at m/z 190 (100%), and the IR spectrum exhibited a stretching frequency in the carbonyl region at 1781 cm−1. A was obtained (see below), which confirmed that the compound was a new bicycle, a rare representative of the pyrrolo[1,2-c]oxazole ring system as first described by Katritzky et al. (2004).
When the reaction was repeated under milder conditions, omitting the period of heating under reflux, the desired bis-TFA protected 4-hydroxy-L-proline 4 was obtained in near quantitative yield, suggesting that it was partially converted into the novel pyrrolo[1,2-c]oxazole 5 under reflux conditions, presumably by elimination from an intermediate of structure 6.
2. Structural commentary
Compound 5 crystallizes in the monoclinic P21/c: its comprises of a single molecule (Fig. 3). The fused bicyclic aromatic system is almost planar [r.m.s. deviation = 0.006 Å; dihedral angle between the five-membered rings = 0.86 (6)°]. Atom C7, which bears the fluorine atoms, is displaced from the ring plane by 1.282 (1) Å and F3 lies anti to O1 [O1—C1—C7—F3 = −176.33 (8)°]. In the arbitrarily chosen asymmetric molecule, the stereogenic centre C1 has an R configuration but crystal symmetry generates a racemic mixture.
3. Supramolecular features
In the crystal, two weak hydrogen bonds (Table 1) are observed between 5 and the adjacent molecule related by the (x, −y + , z − ). These form between the sp3 hydrogen atom H1 and the carbonyl oxygen atom O2 and the aromatic proton H6 and F1 of the triflomethyl group: together, they generate an [001] chain. The molecules pack in sheets parallel to the (010) plane with alternating layers of interdigitated CF3 groups and π–π stacked ring systems (Fig. 4). The shortest π–π stacking interaction between centrosymmetrically related N1/C3–C6 rings has a centroid–centroid separation of 3.5785 (7) Å with a vertical distance of 3.4196 (5) Å and a shift of 1.017 Å with an inter-planar angle of 0°.
4. Database survey
A search in the Cambridge Structural Database (CSD, V5.40, update February 2019; Groom et al., 2016) was performed to confirm that there have been no previous crystal structures of the pyrrolo[1,2-c]oxazole ring system.
5. Synthesis and crystallization
Trifluoroacetic anhydride (0.33 ml, 2.31 mmol, 2.1 eq) was added dropwise to a stirred solution of trans-4-hydroxy-L-proline (144 mg, 1.1 mmol) in CH2Cl2 (2 ml) at 273 K. The reaction mixture was warmed to room temperature, and then heated under reflux for 1.5 h. The excess of CH2Cl2 was removed under reduced pressure to give a crude product that was purified by (petrol:ethyl acetate, 80:20%) to give 3-trifluoromethyl-1H-pyrrolo[1,2-c]oxazol-1-one (0.11 g, 52%) as a white powder, m.p. 338–340 K; Rf 0.27 (petrol:ethyl acetate, 80:20%); vmax(film)/cm−1 3150, 2977, 2918, 1781, 1548, 1318, 1276; δH (400 MHz; CDCl3) 6.20 (1H, q, J = 3.5), 6.62 (1H, dd, J = 2.5, 4.0), 6.91 (1H, dd, J = 1.0, 4.0), 7.12–7.15 (1H, m); δC (100 MHz; CDCl3) 111.2, 118.7, 119.2, 120.3 (CF3, q, J = 283.0), 121.7, 156.7. Analysis calculated for C7H3NO2F3: C, 43.9; H, 2.1; N, 7.3. Found: C, 43.92; H, 2.16; N, 7.10. m/z (ES−) 190 (M − H)−, 100%). Found: [M − H]− 190.0115 C7H3NO2F3 requires 190.0116. Recrystallization from petroleum ether:ethyl acetate 80:20% solution led to colourless blocks of 5.
The mass balance (47%) was the known bis-TFA-4-hydroxy-L-proline 4 (Mori et al., 1986).
6. Refinement
Crystal data, data collection and structure . The H atoms were positioned geometrically (C—H = 0.93 Å for sp2 aromatic and 0.98 Å for sp3 methine CH atoms) and refined as riding atoms with relative isotropic displacement parameters Uiso(H) = 1.2Ueq of the parent atoms.
details are summarized in Table 2Supporting information
CCDC reference: 1919738
https://doi.org/10.1107/S2056989019011095/hb7843sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989019011095/hb7843Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989019011095/hb7843Isup3.cml
Data collection: APEX2 (Bruker, 2009); cell
SAINT (Bruker, 2009); data reduction: SAINT (Bruker, 2009); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C7H4F3NO2 | F(000) = 384 |
Mr = 191.11 | Dx = 1.732 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 8.2767 (5) Å | Cell parameters from 9927 reflections |
b = 8.5106 (5) Å | θ = 3.1–27.6° |
c = 10.5500 (7) Å | µ = 0.18 mm−1 |
β = 99.443 (3)° | T = 100 K |
V = 733.07 (8) Å3 | Block, colourless |
Z = 4 | 0.43 × 0.32 × 0.32 mm |
Bruker APEXII CCD diffractometer | 1595 reflections with I > 2σ(I) |
φ and ω scans | Rint = 0.033 |
Absorption correction: multi-scan (SADABS; Bruker, 2009) | θmax = 27.5°, θmin = 2.5° |
Tmin = 0.700, Tmax = 0.746 | h = −10→10 |
13286 measured reflections | k = −11→11 |
1681 independent reflections | l = −13→13 |
Refinement on F2 | 0 restraints |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.030 | H-atom parameters constrained |
wR(F2) = 0.078 | w = 1/[σ2(Fo2) + (0.0348P)2 + 0.3122P] where P = (Fo2 + 2Fc2)/3 |
S = 1.08 | (Δ/σ)max < 0.001 |
1681 reflections | Δρmax = 0.39 e Å−3 |
118 parameters | Δρmin = −0.30 e Å−3 |
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 | ||
N1 | 0.20468 (11) | 0.42629 (11) | 0.56351 (8) | 0.0174 (2) | |
O1 | 0.14217 (9) | 0.27976 (9) | 0.72729 (7) | 0.01878 (18) | |
O2 | 0.08840 (11) | 0.47329 (9) | 0.86114 (7) | 0.02351 (19) | |
C1 | 0.19006 (13) | 0.26514 (12) | 0.60398 (10) | 0.0173 (2) | |
H1 | 0.107086 | 0.208458 | 0.544158 | 0.021* | |
C2 | 0.12893 (12) | 0.43833 (12) | 0.76072 (10) | 0.0176 (2) | |
C3 | 0.17020 (12) | 0.52963 (12) | 0.65500 (9) | 0.0168 (2) | |
C4 | 0.18460 (13) | 0.68045 (13) | 0.61032 (10) | 0.0197 (2) | |
H4 | 0.167818 | 0.773574 | 0.652411 | 0.024* | |
C5 | 0.22998 (13) | 0.66468 (14) | 0.48775 (11) | 0.0221 (2) | |
H5 | 0.248941 | 0.747088 | 0.434193 | 0.027* | |
C6 | 0.24167 (14) | 0.50640 (14) | 0.46028 (10) | 0.0215 (2) | |
H6 | 0.269396 | 0.463188 | 0.385775 | 0.026* | |
C7 | 0.35527 (14) | 0.18148 (13) | 0.61947 (11) | 0.0211 (2) | |
F1 | 0.34284 (9) | 0.03455 (8) | 0.66179 (7) | 0.03022 (19) | |
F2 | 0.46888 (8) | 0.25554 (9) | 0.70256 (7) | 0.03067 (19) | |
F3 | 0.40810 (8) | 0.17430 (9) | 0.50653 (7) | 0.02723 (18) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0210 (4) | 0.0154 (4) | 0.0160 (4) | −0.0006 (3) | 0.0032 (3) | 0.0002 (3) |
O1 | 0.0248 (4) | 0.0147 (4) | 0.0178 (4) | −0.0008 (3) | 0.0064 (3) | 0.0003 (3) |
O2 | 0.0321 (4) | 0.0207 (4) | 0.0193 (4) | 0.0014 (3) | 0.0089 (3) | −0.0002 (3) |
C1 | 0.0204 (5) | 0.0153 (5) | 0.0163 (5) | −0.0018 (4) | 0.0034 (4) | −0.0002 (4) |
C2 | 0.0179 (5) | 0.0149 (5) | 0.0195 (5) | −0.0003 (4) | 0.0019 (4) | 0.0002 (4) |
C3 | 0.0168 (5) | 0.0167 (5) | 0.0169 (5) | −0.0008 (4) | 0.0023 (4) | −0.0014 (4) |
C4 | 0.0180 (5) | 0.0166 (5) | 0.0243 (5) | −0.0009 (4) | 0.0024 (4) | 0.0014 (4) |
C5 | 0.0201 (5) | 0.0217 (5) | 0.0243 (5) | −0.0020 (4) | 0.0028 (4) | 0.0071 (4) |
C6 | 0.0242 (5) | 0.0241 (5) | 0.0168 (5) | −0.0007 (4) | 0.0049 (4) | 0.0039 (4) |
C7 | 0.0229 (5) | 0.0185 (5) | 0.0221 (5) | 0.0003 (4) | 0.0044 (4) | 0.0000 (4) |
F1 | 0.0360 (4) | 0.0185 (4) | 0.0383 (4) | 0.0071 (3) | 0.0122 (3) | 0.0059 (3) |
F2 | 0.0220 (3) | 0.0351 (4) | 0.0319 (4) | 0.0010 (3) | −0.0045 (3) | −0.0043 (3) |
F3 | 0.0265 (4) | 0.0300 (4) | 0.0275 (4) | 0.0021 (3) | 0.0113 (3) | −0.0018 (3) |
N1—C1 | 1.4474 (13) | C3—C4 | 1.3792 (15) |
N1—C3 | 1.3700 (13) | C4—H4 | 0.9300 |
N1—C6 | 1.3617 (14) | C4—C5 | 1.4108 (15) |
O1—C1 | 1.4262 (12) | C5—H5 | 0.9300 |
O1—C2 | 1.4036 (13) | C5—C6 | 1.3846 (16) |
O2—C2 | 1.2000 (13) | C6—H6 | 0.9300 |
C1—H1 | 0.9800 | C7—F1 | 1.3374 (13) |
C1—C7 | 1.5265 (15) | C7—F2 | 1.3339 (13) |
C2—C3 | 1.4456 (14) | C7—F3 | 1.3363 (13) |
C3—N1—C1 | 111.31 (8) | C3—C4—H4 | 127.0 |
C6—N1—C1 | 138.68 (9) | C3—C4—C5 | 106.00 (9) |
C6—N1—C3 | 110.01 (9) | C5—C4—H4 | 127.0 |
C2—O1—C1 | 110.98 (8) | C4—C5—H5 | 125.6 |
N1—C1—H1 | 111.1 | C6—C5—C4 | 108.82 (10) |
N1—C1—C7 | 110.90 (9) | C6—C5—H5 | 125.6 |
O1—C1—N1 | 103.62 (8) | N1—C6—C5 | 106.68 (10) |
O1—C1—H1 | 111.1 | N1—C6—H6 | 126.7 |
O1—C1—C7 | 108.73 (8) | C5—C6—H6 | 126.7 |
C7—C1—H1 | 111.1 | F1—C7—C1 | 110.80 (9) |
O1—C2—C3 | 106.55 (8) | F2—C7—C1 | 111.87 (9) |
O2—C2—O1 | 120.33 (9) | F2—C7—F1 | 107.88 (9) |
O2—C2—C3 | 133.12 (10) | F2—C7—F3 | 108.00 (9) |
N1—C3—C2 | 107.54 (9) | F3—C7—C1 | 110.14 (9) |
N1—C3—C4 | 108.48 (9) | F3—C7—F1 | 108.01 (9) |
C4—C3—C2 | 143.96 (10) | ||
N1—C1—C7—F1 | 177.53 (8) | C1—O1—C2—O2 | 179.38 (9) |
N1—C1—C7—F2 | 57.11 (12) | C1—O1—C2—C3 | −0.12 (11) |
N1—C1—C7—F3 | −63.02 (11) | C2—O1—C1—N1 | −0.25 (11) |
N1—C3—C4—C5 | −0.21 (12) | C2—O1—C1—C7 | 117.77 (9) |
O1—C1—C7—F1 | 64.22 (11) | C2—C3—C4—C5 | −178.20 (14) |
O1—C1—C7—F2 | −56.21 (11) | C3—N1—C1—O1 | 0.55 (11) |
O1—C1—C7—F3 | −176.33 (8) | C3—N1—C1—C7 | −115.95 (9) |
O1—C2—C3—N1 | 0.46 (11) | C3—N1—C6—C5 | −0.03 (12) |
O1—C2—C3—C4 | 178.46 (14) | C3—C4—C5—C6 | 0.20 (13) |
O2—C2—C3—N1 | −178.94 (11) | C4—C5—C6—N1 | −0.11 (13) |
O2—C2—C3—C4 | −0.9 (2) | C6—N1—C1—O1 | −178.81 (12) |
C1—N1—C3—C2 | −0.64 (11) | C6—N1—C1—C7 | 64.69 (16) |
C1—N1—C3—C4 | −179.40 (8) | C6—N1—C3—C2 | 178.91 (9) |
C1—N1—C6—C5 | 179.34 (11) | C6—N1—C3—C4 | 0.15 (12) |
D—H···A | D—H | H···A | D···A | D—H···A |
C1—H1···O2i | 0.98 | 2.46 | 3.2683 (13) | 140 |
C6—H6···F1i | 0.93 | 2.53 | 3.4065 (13) | 156 |
Symmetry code: (i) x, −y+1/2, z−1/2. |
Acknowledgements
We thank Zawia University for support (MMZ).
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