The title compound is a resolved chiral ester derivative of mandelic acid containing an acetate group and a carboxylic acid group, which engage in intermolecular hydrogen bonding, forming chains extending parallel to [001].
Keywords: crystal structure, absolute structure, hydrogen bonding, mandelic acid ester derivative
Abstract
The title compound [systematic name: (R)-(−)-2-acetoxy-2-phenylacetic acid], C10H10O4, is a resolved chiral ester derivative of mandelic acid. The compound contains an acetate group and a carboxylic acid group, which engage in intermolecular hydrogen bonding, forming chains extending parallel to [001] with a short donor–acceptor hydrogen-bonding distance of 2.676 (2) Å.
Chemical context
Chiral, resolved carboxylic acids have played an important role as chiral NMR shift reagents (Lovely & Wenzel, 2008 ▸; Parker, 1991 ▸). The title compound, (R)-(−)-2-acetoxy-2-phenylacetic acid (I), commonly known as (R)-O-acetylmandelic acid, is a chiral, resolved derivative of mandelic acid. The compound may be synthesized by acetylation of the parent α-hydroxy acid with acetic anhydride in pyridine (Ornelas et al., 2013 ▸). When racemic, resolution of the compound with free amino acids has been demonstrated (Szeleczky et al., 2015 ▸). The title compound has been employed as a chiral NMR shift reagent (Parker, 1991 ▸).
Structural commentary
The molecular structure of the title compound (Fig. 1 ▸) shows the R confguration about carbon atom C1, and that the molecule does not engage in intramolecular or pairwise hydrogen bonding. The absolute structure parameters confirm the R assignment, with Flack x = −0.01 (4) and Hooft y = −0.02 (4), calculated with PLATON (Spek, 2009 ▸).
Figure 1.
A view of (R)-(−)-2-acetoxy-2-phenylacetic acid (I) with the atom-numbering scheme. Displacement ellipsoids are shown at the 50% probability level.
Supramolecular features
The molecules pack together in the solid state via van der Waals forces and hydrogen bonding between the carboxylic acid OH group and the carbonyl oxygen atom of the ester on a neighboring molecule, O1—H1⋯O4i [symmetry code (i) −x + 
, −y + 1, z − ] with a donor–acceptor distance of 2.676 (2) Å (Table 1 ▸). These interactions create zigzag hydrogen-bonded chains that extend parallel to the c axis of the unit cell (Fig. 2 ▸). Notably, there is no face-to-face or edge-to-face π-stacking.
Table 1. Hydrogen-bond geometry (Å, °).
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| O1—H1⋯O4i | 0.85 (2) | 1.84 (2) | 2.6761 (16) | 165 (2) |
Symmetry code: (i) 
.
Figure 2.
A view of the intermolecular hydrogen bonding in (R)-(−)-2-acetoxy-2-phenylacetic acid (I) that forms a one-dimensional chain. Symmetry code: (i) −x + , −y + 1, z − .
Database survey
The Cambridge Structural Database (Groom et al., 2016 ▸) contains several related mandelic acid ester structures. Related structures of resolved mandelic acid esters that differ by the nature of the ester group include (2S)-[(2S)-2-hydroxy-2-phenylethanoyloxy]phenylacetic acid (Mughal et al., 2004 ▸) and (1R,2R,3S,4S)-2-[(R)-mandeloxycarbonyl]bicyclo(2.2.1)heptane-3-carboxylic acid (Ohtani et al., 1991 ▸). The hydrogen bonding in the former differs from (I), forming an intermolecular chain with the carboxylic acid groups further cross-linked by hydrogen bonding of the alcohol moiety with the ester, whereas the latter compound exhibits pairwise dimerization of the carboxylic acid groups. A related structure with a tert-butyl ester and substituents on the phenyl ring, (S,E)-2-[2-(3-methoxy-3-oxoprop-1-en-1-yl)-4-(trifluoromethyl)phenyl]-2-(pivaloyloxy)acetic acid (Xiao et al., 2016 ▸), exhibits a similar one-dimensional intermolecular carboxylic acid OH⋯ester carbonyl hydrogen-bonding motif to that found in the title compound.
Synthesis and crystallization
(R)-(−)-2-acetoxy-2-phenylacetic acid (99%) was purchased from Aldrich Chemical Company, USA, and was used as received.
Analytical data
1H NMR (Bruker Avance 300 MHz, CDCl3): δ 2.19 (s, 3 H, CH3), 5.93 (s, 1H, CH), 7.36–7.42 (m, 3 H, Caryl H), 7.45–7.51 (m, 2H, Caryl H), 11.76 (br s, 1H, OH). 13C NMR (13C{1H}, 75.5 MHz, CDCl3): δ 20.59 (CH3), 74.02 (CH), 127.62 (C arylH), 128.86 (C arylH), 129.49 (C arylH), 132.98 (C aryl), 170.38 (CO), 174.55 (CO). IR (Thermo Nicolet iS50, ATR, cm−1): 3483 (w), 3014 (v br, O—H str), 2708 (w), 2588 (w), 1752 (v s, C=O str), 1686 (v s, C=O str), 1498 (w), 1461 (w), 1412 (m), 1382 (s), 1321 (m), 1277 (s), 1259 (s), 1206 (s), 1182 (s), 1045 (s), 996 (m), 967 (m), 919 (m), 888 (m), 767 (s), 734 (s), 700 (s), 642 (m), 616 (w), 603 (w), 583 (w), 525 (s), 487 (w). GC/MS (Hewlett-Packard MS 5975/GC 7890): M-18+ = 176 (calc. exact mass 194.06 - water = 176).
Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. All non-hydrogen atoms were refined anisotropically. Hydrogen atoms on carbon were included in calculated positions and refined using a riding model with C–H = 0.95, 0.98 and 1.00 Å and U iso(H) = 1.2, 1.5 and 1.2 × U eq(C) of the aryl, methyl and methine C atoms, respectively. The position of the carboxylic acid hydrogen atom was found in the difference map and the atom refined semi-freely using a distance restraint d(O—H) = 0.84 Å, and U iso(H) = 1.2U eq(O).
Table 2. Experimental details.
| Crystal data | |
| Chemical formula | C10H10O4 |
| M r | 194.18 |
| Crystal system, space group | Orthorhombic, P212121 |
| Temperature (K) | 125 |
| a, b, c (Å) | 9.1047 (10), 10.0086 (11), 10.5871 (11) |
| V (Å3) | 964.75 (18) |
| Z | 4 |
| Radiation type | Cu Kα |
| μ (mm−1) | 0.88 |
| Crystal size (mm) | 0.26 × 0.26 × 0.17 |
| Data collection | |
| Diffractometer | Bruker APEXII CCD |
| Absorption correction | Multi-scan (SADABS; Bruker, 2013 ▸) |
| T min, T max | 0.74, 0.86 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 8953, 1698, 1693 |
| R int | 0.030 |
| (sin θ/λ)max (Å−1) | 0.595 |
| Refinement | |
| R[F 2 > 2σ(F 2)], wR(F 2), S | 0.025, 0.062, 1.10 |
| No. of reflections | 1698 |
| No. of parameters | 131 |
| No. of restraints | 1 |
| H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
| Δρmax, Δρmin (e Å−3) | 0.19, −0.19 |
| Absolute structure | Flack x determined using 691 quotients [(I +)−(I −)]/[(I +)+(I −)] (Parsons et al., 2013 ▸); Hooft y calculated with PLATON (Spek, 2009 ▸) |
| Absolute structure parameter | −0.01 (4) |
Supplementary Material
Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989016008653/pk2580sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016008653/pk2580Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989016008653/pk2580Isup3.cml
CCDC reference: 1482445
Additional supporting information: crystallographic information; 3D view; checkCIF report
Acknowledgments
This work was supported by Vassar College. X-ray facilities were provided by the US National Science Foundation (Grant Nos. 0521237 and 0911324 to JMT). We acknowledge the Salmon Fund of Vassar College for funding publication expenses.
supplementary crystallographic information
Crystal data
| C10H10O4 | Dx = 1.337 Mg m−3 |
| Mr = 194.18 | Cu Kα radiation, λ = 1.54178 Å |
| Orthorhombic, P212121 | Cell parameters from 8300 reflections |
| a = 9.1047 (10) Å | θ = 4.2–66.6° |
| b = 10.0086 (11) Å | µ = 0.88 mm−1 |
| c = 10.5871 (11) Å | T = 125 K |
| V = 964.75 (18) Å3 | Block, colourless |
| Z = 4 | 0.26 × 0.26 × 0.17 mm |
| F(000) = 408 |
Data collection
| Bruker APEXII CCD diffractometer | 1698 independent reflections |
| Radiation source: Cu IuS micro-focus source | 1693 reflections with I > 2σ(I) |
| Detector resolution: 8.3333 pixels mm-1 | Rint = 0.030 |
| φ and ω scans | θmax = 66.6°, θmin = 6.1° |
| Absorption correction: multi-scan (SADABS; Bruker, 2013) | h = −10→10 |
| Tmin = 0.74, Tmax = 0.86 | k = −11→11 |
| 8953 measured reflections | l = −12→12 |
Refinement
| Refinement on F2 | Hydrogen site location: mixed |
| Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
| R[F2 > 2σ(F2)] = 0.025 | w = 1/[σ2(Fo2) + (0.0336P)2 + 0.1385P] where P = (Fo2 + 2Fc2)/3 |
| wR(F2) = 0.062 | (Δ/σ)max < 0.001 |
| S = 1.10 | Δρmax = 0.19 e Å−3 |
| 1698 reflections | Δρmin = −0.19 e Å−3 |
| 131 parameters | Absolute structure: Flack x determined using 691 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013); Hooft y calculated with PLATON (Spek, 2009) |
| 1 restraint | Absolute structure parameter: −0.01 (4) |
Special details
| 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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| O1 | 0.42132 (13) | 0.46237 (13) | 0.08956 (12) | 0.0329 (3) | |
| H1 | 0.355 (2) | 0.479 (2) | 0.035 (2) | 0.039* | |
| O2 | 0.35211 (12) | 0.66275 (12) | 0.16115 (11) | 0.0286 (3) | |
| O3 | 0.50941 (12) | 0.63319 (11) | 0.37499 (9) | 0.0235 (3) | |
| O4 | 0.29716 (12) | 0.53107 (12) | 0.42058 (10) | 0.0273 (3) | |
| C1 | 0.53382 (16) | 0.53625 (15) | 0.27588 (13) | 0.0200 (3) | |
| H1A | 0.5199 | 0.4438 | 0.3097 | 0.024* | |
| C2 | 0.69072 (15) | 0.55447 (14) | 0.23211 (13) | 0.0184 (3) | |
| C3 | 0.79939 (18) | 0.47071 (16) | 0.27844 (16) | 0.0272 (4) | |
| H3A | 0.7744 | 0.3988 | 0.3329 | 0.033* | |
| C4 | 0.94513 (18) | 0.49242 (17) | 0.2450 (2) | 0.0346 (4) | |
| H4A | 1.0198 | 0.4358 | 0.2776 | 0.042* | |
| C5 | 0.98206 (18) | 0.59621 (18) | 0.16417 (17) | 0.0326 (4) | |
| H5A | 1.0818 | 0.6109 | 0.1418 | 0.039* | |
| C6 | 0.87356 (18) | 0.67809 (18) | 0.11641 (16) | 0.0303 (4) | |
| H6A | 0.8985 | 0.7482 | 0.0599 | 0.036* | |
| C7 | 0.72770 (17) | 0.65833 (17) | 0.15078 (14) | 0.0242 (3) | |
| H7A | 0.6534 | 0.7157 | 0.1187 | 0.029* | |
| C8 | 0.42388 (15) | 0.56275 (15) | 0.16993 (14) | 0.0201 (3) | |
| C9 | 0.38220 (17) | 0.62321 (16) | 0.43773 (14) | 0.0237 (3) | |
| C10 | 0.3600 (2) | 0.7365 (2) | 0.52655 (17) | 0.0364 (4) | |
| H10A | 0.4523 | 0.7555 | 0.5707 | 0.055* | |
| H10B | 0.2842 | 0.7128 | 0.5883 | 0.055* | |
| H10C | 0.329 | 0.8158 | 0.4792 | 0.055* |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| O1 | 0.0273 (6) | 0.0350 (6) | 0.0363 (6) | 0.0053 (5) | −0.0144 (5) | −0.0139 (5) |
| O2 | 0.0270 (6) | 0.0289 (6) | 0.0298 (6) | 0.0060 (5) | −0.0008 (5) | −0.0001 (5) |
| O3 | 0.0209 (5) | 0.0298 (6) | 0.0198 (5) | −0.0061 (4) | 0.0051 (4) | −0.0055 (4) |
| O4 | 0.0232 (5) | 0.0335 (6) | 0.0253 (6) | −0.0066 (5) | 0.0058 (4) | 0.0003 (5) |
| C1 | 0.0197 (7) | 0.0209 (7) | 0.0193 (7) | −0.0032 (6) | 0.0012 (6) | −0.0020 (6) |
| C2 | 0.0171 (7) | 0.0207 (7) | 0.0173 (7) | −0.0019 (6) | −0.0001 (5) | −0.0046 (6) |
| C3 | 0.0249 (8) | 0.0232 (8) | 0.0334 (8) | 0.0001 (7) | −0.0030 (7) | 0.0014 (7) |
| C4 | 0.0214 (7) | 0.0329 (9) | 0.0496 (11) | 0.0066 (7) | −0.0035 (8) | −0.0042 (8) |
| C5 | 0.0184 (7) | 0.0424 (9) | 0.0370 (9) | −0.0037 (7) | 0.0061 (7) | −0.0119 (8) |
| C6 | 0.0276 (8) | 0.0394 (9) | 0.0238 (8) | −0.0093 (8) | 0.0042 (7) | 0.0016 (7) |
| C7 | 0.0215 (7) | 0.0301 (8) | 0.0210 (7) | −0.0005 (6) | −0.0010 (6) | 0.0037 (6) |
| C8 | 0.0149 (7) | 0.0237 (7) | 0.0216 (7) | −0.0034 (6) | 0.0036 (5) | −0.0010 (6) |
| C9 | 0.0213 (7) | 0.0315 (8) | 0.0184 (7) | −0.0036 (7) | 0.0033 (6) | 0.0021 (6) |
| C10 | 0.0390 (10) | 0.0389 (10) | 0.0311 (9) | −0.0082 (9) | 0.0139 (8) | −0.0076 (8) |
Geometric parameters (Å, º)
| O1—C8 | 1.3168 (19) | C3—H3A | 0.95 |
| O1—H1 | 0.852 (19) | C4—C5 | 1.387 (3) |
| O2—C8 | 1.1989 (19) | C4—H4A | 0.95 |
| O3—C9 | 1.3389 (18) | C5—C6 | 1.380 (3) |
| O3—C1 | 1.4463 (17) | C5—H5A | 0.95 |
| O4—C9 | 1.218 (2) | C6—C7 | 1.391 (2) |
| C1—C2 | 1.5128 (19) | C6—H6A | 0.95 |
| C1—C8 | 1.527 (2) | C7—H7A | 0.95 |
| C1—H1A | 1.0 | C9—C10 | 1.487 (2) |
| C2—C3 | 1.386 (2) | C10—H10A | 0.98 |
| C2—C7 | 1.391 (2) | C10—H10B | 0.98 |
| C3—C4 | 1.391 (2) | C10—H10C | 0.98 |
| C8—O1—H1 | 107.2 (15) | C4—C5—H5A | 120.1 |
| C9—O3—C1 | 116.28 (11) | C5—C6—C7 | 120.22 (16) |
| O3—C1—C2 | 106.65 (11) | C5—C6—H6A | 119.9 |
| O3—C1—C8 | 108.41 (11) | C7—C6—H6A | 119.9 |
| C2—C1—C8 | 111.91 (12) | C6—C7—C2 | 119.95 (14) |
| O3—C1—H1A | 109.9 | C6—C7—H7A | 120.0 |
| C2—C1—H1A | 109.9 | C2—C7—H7A | 120.0 |
| C8—C1—H1A | 109.9 | O2—C8—O1 | 125.26 (14) |
| C3—C2—C7 | 119.87 (14) | O2—C8—C1 | 124.01 (14) |
| C3—C2—C1 | 119.51 (13) | O1—C8—C1 | 110.72 (12) |
| C7—C2—C1 | 120.54 (13) | O4—C9—O3 | 122.18 (14) |
| C2—C3—C4 | 119.76 (15) | O4—C9—C10 | 125.84 (14) |
| C2—C3—H3A | 120.1 | O3—C9—C10 | 111.98 (13) |
| C4—C3—H3A | 120.1 | C9—C10—H10A | 109.5 |
| C5—C4—C3 | 120.37 (16) | C9—C10—H10B | 109.5 |
| C5—C4—H4A | 119.8 | H10A—C10—H10B | 109.5 |
| C3—C4—H4A | 119.8 | C9—C10—H10C | 109.5 |
| C6—C5—C4 | 119.83 (15) | H10A—C10—H10C | 109.5 |
| C6—C5—H5A | 120.1 | H10B—C10—H10C | 109.5 |
| C9—O3—C1—C2 | −172.13 (12) | C4—C5—C6—C7 | 1.1 (3) |
| C9—O3—C1—C8 | 67.21 (15) | C5—C6—C7—C2 | −1.0 (3) |
| O3—C1—C2—C3 | 98.10 (15) | C3—C2—C7—C6 | −0.2 (2) |
| C8—C1—C2—C3 | −143.51 (14) | C1—C2—C7—C6 | 176.71 (15) |
| O3—C1—C2—C7 | −78.78 (16) | O3—C1—C8—O2 | 13.69 (19) |
| C8—C1—C2—C7 | 39.62 (18) | C2—C1—C8—O2 | −103.65 (16) |
| C7—C2—C3—C4 | 1.1 (2) | O3—C1—C8—O1 | −167.43 (12) |
| C1—C2—C3—C4 | −175.84 (16) | C2—C1—C8—O1 | 75.23 (15) |
| C2—C3—C4—C5 | −0.9 (3) | C1—O3—C9—O4 | 6.3 (2) |
| C3—C4—C5—C6 | −0.2 (3) | C1—O3—C9—C10 | −173.19 (13) |
Hydrogen-bond geometry (Å, º)
| D—H···A | D—H | H···A | D···A | D—H···A |
| O1—H1···O4i | 0.85 (2) | 1.84 (2) | 2.6761 (16) | 165 (2) |
| C10—H10B···O1ii | 0.98 | 2.56 | 3.312 (2) | 133 |
Symmetry codes: (i) −x+1/2, −y+1, z−1/2; (ii) −x+1/2, −y+1, z+1/2.
References
- Bruker (2013). SAINT, SADABS and APEX2. Bruker AXS Inc., Madison, Wisconsin, USA.
- Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.
- Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. [DOI] [PMC free article] [PubMed]
- Lovely, A. E. & Wenzel, T. J. (2008). Chirality, 20, 370–378. [DOI] [PubMed]
- Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466–470.
- Mughal, R. K., Pritchard, R. G. & Davey, R. J. (2004). Acta Cryst. E60, o232–o233.
- Ohtani, M., Matsuura, T., Watanabe, F. & Narisada, M. (1991). J. Org. Chem. 56, 4120–4123.
- Ornelas, A., Korczynska, M., Ragumani, S., Kumaran, D., Narindoshvili, T., Shoichet, B. K., Swaminathan, S. & Raushel, F. M. (2013). Biochemistry, 52, 228–238. [DOI] [PMC free article] [PubMed]
- Parker, D. (1991). Chem. Rev. 91, 1441–1457.
- Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. [DOI] [PMC free article] [PubMed]
- Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [DOI] [PubMed]
- Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.
- Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.
- Spek, A. L. (2009). Acta Cryst. D65, 148–155. [DOI] [PMC free article] [PubMed]
- Szeleczky, Z., Bagi, P., Pálovics, E. & Fogassy, E. (2015). Tetrahedron Asymmetry, 26, 377–384.
- Xiao, K.-J., Chu, L. & Yu, J.-Q. (2016). Angew. Chem. Int. Ed. 55, 2856–2860. [DOI] [PMC free article] [PubMed]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S2056989016008653/pk2580sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989016008653/pk2580Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989016008653/pk2580Isup3.cml
CCDC reference: 1482445
Additional supporting information: crystallographic information; 3D view; checkCIF report