Acta Cryst. (2008). E64, o631 [ doi:10.1107/S1600536808004868 ]
In the title compound, C12H14N2O, the middle C atom in the propanol chain is a chiral center and possesses an S absolute configuration, according to the synthesis. In the crystal structure, intermolecular O-H
N hydrogen bonds link the molecules into a chain along the b axis.
Since enantiopure amines are easily available and the chiral carbon has little risk of the racemization, they are usually applied for the preparation of chiral imidazole derivatives by cyclocondensation of ring fragments (Matsuoka et al., 2006). The methyl 2-(1H-imidazol-1-yl)-3-phenylpropanoate was easily prepared according to a literature procedure (Bao et al., 2003). Thereafter, NaBH4 (1.52 g, 40 mmol) was added to methyl 2-(1H-imidazol-1-yl)-3-phenylpropanoate (2.16 g, 10.0 mmol) in ethanol (150 ml) at 273 K over 30 min. The mixture was stirred at 333 K for another 20 h and then evaporated under vacuum. The residue was diluted with 20 ml saturated K2CO3 and extracted with 50 ml e thyl acetate. The organic layer was dried over anhydrous Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel eluting with CH2Cl2/CH3OH (20/1, V/V), and then recrystallized from CH2Cl2 to give colorless crystals. Yield: 86%, mp 359–361 K, 1H NMR (300 MHz, CDCl3): δ 2.94–3.17 (dd, J=13.8 Hz, 7.7 Hz, 2H), 3.78–3.88 (m, 2H), 4.13–4.29 (m, 1H.), 6.88 (m, 2H), 7.02 (m, 2H), 7.28 (s, 1H), 7.03–7.26 (m, 5H). 13C NMR (75 MHz, CDCl3): δ 38.41, 62.26, 64.21, 117.61, 126.99, 128.59, 128.76, 128.90, 136.47, 137.10 p.p.m..
All H atoms were positioned geometrically and refined in the riding model approximation with C—H = 0.93, 0.97 Å and O—H = 0.82 Å. Since there is no atom heavier than oxygen it was not possible to determine the absolute structure exactly. However, the chiral carbon does not directly participate in the cyclocondensation in this reaction (Matsuoka et al., 2006). Herein, the desired product (S)-2-(1H-imidazol-1-yl)-3-phenylpropanol was obtained starting from (S)-2-amino-3-phenylpropanoic acid, whose absolute configuration (S) is consistent with the starting material.
Data collection: DIFRAC (Gabe & White, 1993); cell refinement: DIFRAC (Gabe & White, 1993); data reduction: NRCVAX (Gabe et al., 1989); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2003).
![[Figure 1]](./ez2119fig1thm.gif)
| Fig. 1. The molecular structure of (I), showing 30% probability displacement ellipsoids and the atomic numbering. |
| C12H14N2O | F000 = 216 |
| Mr = 202.25 | Dx = 1.186 Mg m−3 |
| Monoclinic, P21 | Mo Kα radiation λ = 0.71073 Å |
| Hall symbol: P 2yb | Cell parameters from 26 reflections |
| a = 8.021 (4) Å | θ = 4.6–7.8º |
| b = 6.069 (3) Å | µ = 0.08 mm−1 |
| c = 11.629 (5) Å | T = 293 (2) K |
| β = 90.13 (5)º | Block, colorless |
| V = 566.1 (5) Å3 | 0.40 × 0.33 × 0.23 mm |
| Z = 2 |
| Enraf–Nonius CAD-4 diffractometer | Rint = 0.055 |
| Radiation source: fine-focus sealed tube | θmax = 25.4º |
| Monochromator: graphite | θmin = 1.8º |
| T = 293(2) K | h = −9→0 |
| ω/2θ scans | k = −7→7 |
| Absorption correction: none | l = −13→14 |
| 1909 measured reflections | 3 standard reflections |
| 1146 independent reflections | every 200 reflections |
| 826 reflections with I > 2σ(I) | intensity decay: 1.2% |
| 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)] = 0.036 | H-atom parameters constrained |
| wR(F2) = 0.090 | w = 1/[σ2(Fo2) + (0.0335P)2 + 0.0435P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.05 | (Δ/σ)max < 0.001 |
| 1146 reflections | Δρmax = 0.13 e Å−3 |
| 142 parameters | Δρmin = −0.12 e Å−3 |
| 1 restraint | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
| Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.045 (8) |
| C12H14N2O | V = 566.1 (5) Å3 |
| Mr = 202.25 | Z = 2 |
| Monoclinic, P21 | Mo Kα |
| a = 8.021 (4) Å | µ = 0.08 mm−1 |
| b = 6.069 (3) Å | T = 293 (2) K |
| c = 11.629 (5) Å | 0.40 × 0.33 × 0.23 mm |
| β = 90.13 (5)º |
| Enraf–Nonius CAD-4 diffractometer | Rint = 0.055 |
| Absorption correction: none | 3 standard reflections |
| 1909 measured reflections | every 200 reflections |
| 1146 independent reflections | intensity decay: 1.2% |
| 826 reflections with I > 2σ(I) |
| R[F2 > 2σ(F2)] = 0.036 | H-atom parameters constrained |
| wR(F2) = 0.090 | Δρmax = 0.13 e Å−3 |
| S = 1.05 | Δρmin = −0.12 e Å−3 |
| 1146 reflections | Absolute structure: ? |
| 142 parameters | Flack parameter: ? |
| 1 restraint | Rogers parameter: ? |
Experimental. In the crystal structure, there is not any heavy atom than silicon, so we can't get the absolute structure exactly. However, the chiral carbon does not directly participate in the cyclocondensation in this reaction (Matsuoka et al., Tetrahedron. 2006, 62, 8199–8206). From starting material (S)-2-amino-3-phenylpropanoic acid, it give (S)-2-(1H-imidazol-1-yl)-3-phenylpropanol as product, whose absolute configuration (S) is consistent with the absolute structure characterized by X-ray structure analysis. |
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 | ||
| O1 | 0.6488 (3) | 0.9519 (5) | −0.06637 (15) | 0.0601 (7) | |
| H1 | 0.7178 | 1.0460 | −0.0835 | 0.086 (15)* | |
| N1 | 0.8556 (3) | 0.8538 (4) | 0.13967 (17) | 0.0418 (6) | |
| N2 | 1.1263 (3) | 0.7863 (6) | 0.1257 (2) | 0.0651 (9) | |
| C1 | 0.7787 (4) | 0.7337 (7) | 0.4142 (2) | 0.0628 (10) | |
| H1B | 0.8315 | 0.8693 | 0.4069 | 0.073 (4)* | |
| C2 | 0.8278 (4) | 0.5915 (8) | 0.5001 (3) | 0.0747 (12) | |
| H2 | 0.9137 | 0.6313 | 0.5497 | 0.073 (4)* | |
| C3 | 0.7501 (5) | 0.3908 (7) | 0.5128 (3) | 0.0725 (12) | |
| H3 | 0.7824 | 0.2955 | 0.5714 | 0.073 (4)* | |
| C4 | 0.6247 (5) | 0.3324 (7) | 0.4383 (2) | 0.0680 (10) | |
| H4 | 0.5716 | 0.1970 | 0.4464 | 0.073 (4)* | |
| C5 | 0.5773 (4) | 0.4746 (6) | 0.3512 (2) | 0.0565 (9) | |
| H5 | 0.4935 | 0.4324 | 0.3003 | 0.073 (4)* | |
| C6 | 0.6522 (3) | 0.6781 (6) | 0.3385 (2) | 0.0456 (8) | |
| C7 | 0.5912 (3) | 0.8393 (6) | 0.2488 (2) | 0.0498 (8) | |
| H7A | 0.6073 | 0.9875 | 0.2780 | 0.046 (4)* | |
| H7B | 0.4723 | 0.8176 | 0.2383 | 0.046 (4)* | |
| C8 | 0.6752 (3) | 0.8225 (6) | 0.1318 (2) | 0.0431 (7) | |
| H8 | 0.6550 | 0.6738 | 0.1021 | 0.040 (7)* | |
| C9 | 0.5963 (3) | 0.9848 (6) | 0.0484 (2) | 0.0517 (8) | |
| H9A | 0.4760 | 0.9703 | 0.0520 | 0.046 (4)* | |
| H9B | 0.6248 | 1.1335 | 0.0719 | 0.046 (4)* | |
| C10 | 0.9385 (4) | 1.0364 (6) | 0.1796 (2) | 0.0514 (9) | |
| H1A | 0.8907 | 1.1653 | 0.2075 | 0.073 (4)* | |
| C11 | 1.1038 (4) | 0.9919 (7) | 0.1705 (2) | 0.0607 (10) | |
| H11 | 1.1892 | 1.0874 | 0.1917 | 0.073 (4)* | |
| C12 | 0.9738 (4) | 0.7106 (6) | 0.1088 (2) | 0.0542 (8) | |
| H12 | 0.9510 | 0.5720 | 0.0785 | 0.073 (4)* |
| U11 | U22 | U33 | U12 | U13 | U23 | |
| O1 | 0.0642 (15) | 0.0700 (16) | 0.0462 (11) | −0.0137 (15) | −0.0054 (9) | 0.0087 (11) |
| N1 | 0.0410 (12) | 0.0430 (15) | 0.0414 (11) | 0.0035 (14) | −0.0051 (9) | −0.0040 (11) |
| N2 | 0.0411 (16) | 0.088 (3) | 0.0659 (16) | 0.0082 (17) | −0.0038 (12) | −0.0079 (17) |
| C1 | 0.057 (2) | 0.066 (3) | 0.0656 (19) | −0.009 (2) | −0.0107 (15) | 0.0151 (19) |
| C2 | 0.065 (2) | 0.093 (3) | 0.066 (2) | −0.001 (2) | −0.0198 (18) | 0.017 (2) |
| C3 | 0.085 (3) | 0.075 (3) | 0.058 (2) | 0.016 (3) | 0.0044 (18) | 0.0208 (19) |
| C4 | 0.101 (3) | 0.050 (2) | 0.0522 (17) | 0.001 (2) | 0.0205 (18) | 0.0072 (19) |
| C5 | 0.074 (2) | 0.050 (2) | 0.0459 (15) | −0.004 (2) | 0.0051 (14) | −0.0072 (16) |
| C6 | 0.0442 (16) | 0.050 (2) | 0.0429 (15) | −0.0001 (17) | 0.0058 (12) | 0.0041 (14) |
| C7 | 0.0440 (16) | 0.056 (2) | 0.0496 (15) | 0.0050 (18) | −0.0027 (12) | −0.0008 (16) |
| C8 | 0.0419 (15) | 0.0454 (19) | 0.0419 (13) | 0.0001 (16) | −0.0061 (11) | −0.0023 (14) |
| C9 | 0.0467 (17) | 0.056 (2) | 0.0527 (15) | 0.0023 (19) | −0.0078 (12) | 0.0072 (16) |
| C10 | 0.0512 (19) | 0.051 (2) | 0.0519 (16) | −0.0015 (18) | −0.0039 (14) | −0.0075 (15) |
| C11 | 0.0465 (19) | 0.081 (3) | 0.0544 (16) | −0.007 (2) | −0.0072 (13) | −0.002 (2) |
| C12 | 0.056 (2) | 0.060 (2) | 0.0471 (15) | 0.012 (2) | −0.0004 (13) | −0.0109 (16) |
| O1—C9 | 1.415 (3) | C4—H4 | 0.9300 |
| O1—H1 | 0.8200 | C5—C6 | 1.382 (5) |
| N1—C12 | 1.336 (4) | C5—H5 | 0.9300 |
| N1—C10 | 1.372 (4) | C6—C7 | 1.511 (4) |
| N1—C8 | 1.462 (3) | C7—C8 | 1.522 (3) |
| N2—C12 | 1.321 (4) | C7—H7A | 0.9700 |
| N2—C11 | 1.364 (5) | C7—H7B | 0.9700 |
| C1—C2 | 1.377 (5) | C8—C9 | 1.519 (4) |
| C1—C6 | 1.383 (4) | C8—H8 | 0.9800 |
| C1—H1B | 0.9300 | C9—H9A | 0.9700 |
| C2—C3 | 1.376 (6) | C9—H9B | 0.9700 |
| C2—H2 | 0.9300 | C10—C11 | 1.358 (4) |
| C3—C4 | 1.373 (5) | C10—H1A | 0.9300 |
| C3—H3 | 0.9300 | C11—H11 | 0.9300 |
| C4—C5 | 1.384 (5) | C12—H12 | 0.9300 |
| C9—O1—H1 | 109.5 | C8—C7—H7A | 108.4 |
| C12—N1—C10 | 105.8 (2) | C6—C7—H7B | 108.4 |
| C12—N1—C8 | 127.0 (3) | C8—C7—H7B | 108.4 |
| C10—N1—C8 | 127.2 (3) | H7A—C7—H7B | 107.5 |
| C12—N2—C11 | 104.6 (3) | N1—C8—C9 | 111.5 (2) |
| C2—C1—C6 | 121.1 (4) | N1—C8—C7 | 112.0 (2) |
| C2—C1—H1B | 119.4 | C9—C8—C7 | 110.0 (2) |
| C6—C1—H1B | 119.4 | N1—C8—H8 | 107.7 |
| C3—C2—C1 | 120.3 (3) | C9—C8—H8 | 107.7 |
| C3—C2—H2 | 119.9 | C7—C8—H8 | 107.7 |
| C1—C2—H2 | 119.9 | O1—C9—C8 | 112.7 (3) |
| C4—C3—C2 | 119.5 (3) | O1—C9—H9A | 109.0 |
| C4—C3—H3 | 120.3 | C8—C9—H9A | 109.0 |
| C2—C3—H3 | 120.3 | O1—C9—H9B | 109.0 |
| C3—C4—C5 | 120.1 (4) | C8—C9—H9B | 109.0 |
| C3—C4—H4 | 120.0 | H9A—C9—H9B | 107.8 |
| C5—C4—H4 | 120.0 | C11—C10—N1 | 106.6 (3) |
| C6—C5—C4 | 121.1 (3) | C11—C10—H1A | 126.7 |
| C6—C5—H5 | 119.4 | N1—C10—H1A | 126.7 |
| C4—C5—H5 | 119.4 | C10—C11—N2 | 110.0 (3) |
| C5—C6—C1 | 117.9 (3) | C10—C11—H11 | 125.0 |
| C5—C6—C7 | 120.8 (3) | N2—C11—H11 | 125.0 |
| C1—C6—C7 | 121.2 (3) | N2—C12—N1 | 113.0 (3) |
| C6—C7—C8 | 115.5 (3) | N2—C12—H12 | 123.5 |
| C6—C7—H7A | 108.4 | N1—C12—H12 | 123.5 |
| D—H···A | D—H | H···A | D···A | D—H···A |
| O1—H1···N2i | 0.82 | 1.98 | 2.802 (4) | 177 |
| Symmetry codes: (i) −x+2, y+1/2, −z. |
| D—H···A | D—H | H···A | D···A | D—H···A |
| O1—H1···N2i | 0.82 | 1.98 | 2.802 (4) | 177 |
| Symmetry codes: (i) −x+2, y+1/2, −z. |
The authors are grateful to the National Natural Science Foundation of China (grant No. 20602027) for financial support.
Bao, W. L., Wang, Z. M. & Li, Y. X. (2003). J. Org. Chem. 68, 591–593.
Baudequin, C., Baudoux, J., Levillain, J., Cahard, D., Gaumont, A. C. & Plaquevent, J. C. (2003). Tetrahedron Asymmetry, 14, 3081–3093.
Burnett, M. N. & Johnson, C. K. (1996). ORTEPIII. Report ORNL-6895. Oak Ridge National Laboratory, Tennessee, USA.
Gabe, E. J., Le Page, Y., Charland, J.-P., Lee, F. L. & White, P. S. (1989). J. Appl. Cryst. 22, 384–387.
Gabe, E. J. & White, P. S. (1993). DIFRAC. American Crystallographic Association, Pittsburgh Meeting. Abstract PA104.
Lan, J. B., Chen, L., Yu, X. Q., You, J. S. & Xie, R. G. (2004). Chem. Commun. pp. 188–189.
Matsuoka, Y., Ishida, Y., Sasaki, D. & Saigo, K. (2006). Tetrahedron, 62, 8199–8206.
Nair, V., Bindu, S. & Sreekumar, V. (2004). Angew. Chem. Int. Ed. 43, 5130–5135.
Sambrook, M. R., Beer, P. D., Wisner, J. A., Paul, R. L., Cowley, A. R., Szemes, F. & Drew, M. G. B. (2005). J. Am. Chem. Soc. 127, 2292–2302.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Spek, A. L. (2003). J. Appl. Cryst. 36, 7–13.
Wang, W. H., Xi, P. H., Su, X. Y., Lan, J. B., Mao, Z. H., You, J. S. & Xie, R. G. (2007). Cryst. Growth Des. 7, 741–746.
You, J. S., Yu, X. Q., Zhang, G. L., Xiang, Q. X., Lan, J. B. & Xie, R. G. (2001). Chem. Commun. pp. 1816–1817.
Imidazoles are an important group in biological systems, and their derivatives have attracted widespread interest due to their application as precursors for imidazolium-based ionic liquids (Baudequin et al., 2003), N-heterocyclic carbenes (Nair et al., 2004) and molecular sensors (Sambrook et al., 2005). We have focused our interest on the synthesis and applications of imidazole derivatives (Lan et al., 2004; Wang et al., 2007) and have reported several chiral cyclophanes and chiral molecular tweezers containing imidazole residues as receptors for the enantioselective recognition of amino acids or their derivatives (You et al., 2001). Here, we report the crystal structure of the title compound, (I), which is a basic unit in the construction of chiral receptors and could be applied in the preparation of chair heterocyclic carbenes and ionic liquids.
In the structure of (I), the hydroxyl group and the imidazol-1-yl nitrogen atom are hydrogen bonded via an intermolecular O—H···N hydrogen bond as illustrated in Table 1 to result in the formation of a helical chain.