Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807035003/fl2147sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807035003/fl2147Isup2.hkl |
CCDC reference: 657844
Key indicators
- Single-crystal X-ray study
- T = 100 K
- R factor = 0.038
- wR factor = 0.104
- Data-to-parameter ratio = 13.6
checkCIF/PLATON results
No syntax errors found No errors found in this datablock
Compound (I) has not previously been reported. The methyl ester of cyclohexanone-4-acetic acid (see Acknowledgments) was converted to its pyrrolidine enamine and then treated with methyl vinyl ketone as described by Stork et al. (1963). The usual workup and isolation yielded directly the crystalline methyl ester of (I), which was then saponified. Crystals of (I) suitable for X-ray were obtained from ether/CH2Cl2, mp 423 K. The stereochemistry obtained for C4a versus C6 arises during the synthesis, probably as the result of equilibrations occurring during saponification or earlier (House et al., 1965), as (I) is clearly the stabler of the two epimers possible.
The solid-state (KBr) infrared spectrum of (I) has C=O absorptions at 1724 & 1633 cm-1, with a peak separation typical of the shifts seen in catemers, due, respectively, to removal of H bonding from the acid C=O and addition of H bonding to the ketone; an alkene shoulder appears at ca 1618 cm-1. In CHCl3 solution, where dimers predominate, these bands appear, respectively, at 1710, 1662 and 1621 cm-1.
All H atoms for (I) were found in electron density difference maps. The O—H was constrained to an idealized position with distance fixed at 0.84 Å and Uiso(H) = 1.5Ueq(O). The methylene and methine Hs were placed in geometrically idealized positions and constrained to ride on their parent C atoms with C—H distances of 0.99 and 1.00 Å, respectively, and Uiso(H) = 1.2Ueq(C).
Among the five hydrogen-bonding modes known for ketocarboxylic acids, the commonest involves centrosymmetric dimerization. However, we have shown that when centrosymmetry is thwarted or disfavored, the frequency of acid-to-ketone catemers increases. Thus, among chiral non-racemates this chain-mode actually predominates, and its occurrence also rises markedly among conformationally constrained molecules. The latter is the case for compound (I), whose structure and hydrogen-bonding pattern we report here.
Fig. 1 shows the asymmetric unit, whose only conformational options lie in the side-chain. The C2—C9 staggering requires that C10 be involved in a gauche interaction with an equatorial proton either at C1 or at C3. Compared to alkane systems in which all centers are tetrahedral, such gauche arrangements are less serious here because the sp2 hybridization at the carboxyl diminishes the steric repulsions involved. Within the asymmetric unit, any energy advantage to the arrangement actually found [torsion angle C3—C2—C9—C10 = 64.16 (15)°] appears negligible and the observed choice is probably dictated by packing considerations. The remaining available rotation yields a C2—C9—C10—O2 torsion angle of 38.58 (19)° for the carboxyl group.
The disordering of bond lengths and angles often seen in carboxyl dimers is not possible in (I), which is not dimeric. Thus its C—O bond lengths [O2—C10 = 1.2054 (18) and O3—C10 = 1.3213 (17) Å] and C—C—O angles [O2—C10—C9 = 124.23 (12) and O3—C10—C9 = 112.41 (12) °] are typical of those in highly ordered dimeric carboxyls (Borthwick, 1980).
Fig. 2 shows the centrosymmetric packing of the cell, with extra molecules included to illustrate the acid-to-ketone hydrogen-bonding scheme. Each carboxylic acid is linked to the ketone in a molecule translationally related in both the a and c directions, so that the chains advance at an angle to the cell axes, along the [101] direction. The four hydrogen-bonding chains passing through the cell are of alternating handedness. Starting at the origin, the order of the directional alignment of these four chains with respect to the a axis is + + - -. The racemate aggregates in the solid as translational acid-to-ketone hydrogen-bonding catemers [O···O = 2.6793 (14)Å and O—H···O = 163°].
We characterize the geometry of H bonding to carbonyls using a combination of the H···O=C angle and the H···O=C—C torsion angle. These describe the approach of the H atom to the receptor O in terms of its deviation from, respectively, C=O axiality (ideal = 120°) and planarity with the carbonyl (ideal = 0°). In (I) these angles are 124.8 & 0.1°.
One intermolecular C—H···O close contact was found involving the carboxyl oxygen [H7B—O2 = 2.53; C7—O2 = 3.4758 (17) Å; C7—H7B—O2 = 161 °]. This distance lies within the 2.6-Å range we standardly survey for such packing interactions (Steiner, 1997).
For related literature, see: Borthwick (1980); House et al. (1965); Steiner (1997); Stork et al. (1963).
Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXTL (Sheldrick, 2004); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.
C12H16O3 | F(000) = 448 |
Mr = 208.26 | Dx = 1.292 Mg m−3 |
Monoclinic, P21/c | Melting point: 423 K |
Hall symbol: -P 2ybc | Cu Kα radiation, λ = 1.54178 Å |
a = 7.5832 (2) Å | Cell parameters from 5950 reflections |
b = 16.9532 (4) Å | θ = 5.9–68.1° |
c = 8.3785 (2) Å | µ = 0.75 mm−1 |
β = 96.323 (1)° | T = 100 K |
V = 1070.58 (5) Å3 | Block, colourless |
Z = 4 | 0.33 × 0.28 × 0.22 mm |
Bruker SMART APEXII CCD area-detector diffractometer | 1879 independent reflections |
Radiation source: fine-focus sealed tube | 1818 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.017 |
φ and ω scans | θmax = 68.1°, θmin = 5.9° |
Absorption correction: multi-scan (SADABS; Sheldrick, 2001) | h = −9→9 |
Tmin = 0.790, Tmax = 0.853 | k = −18→19 |
5950 measured reflections | l = −10→9 |
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)] = 0.038 | H-atom parameters constrained |
wR(F2) = 0.104 | w = 1/[σ2(Fo2) + (0.0518P)2 + 0.5351P] where P = (Fo2 + 2Fc2)/3 |
S = 1.05 | (Δ/σ)max < 0.001 |
1879 reflections | Δρmax = 0.24 e Å−3 |
138 parameters | Δρmin = −0.18 e Å−3 |
0 restraints | Extinction correction: SHELXTL (Sheldrick, 2004), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.0015 (4) |
C12H16O3 | V = 1070.58 (5) Å3 |
Mr = 208.26 | Z = 4 |
Monoclinic, P21/c | Cu Kα radiation |
a = 7.5832 (2) Å | µ = 0.75 mm−1 |
b = 16.9532 (4) Å | T = 100 K |
c = 8.3785 (2) Å | 0.33 × 0.28 × 0.22 mm |
β = 96.323 (1)° |
Bruker SMART APEXII CCD area-detector diffractometer | 1879 independent reflections |
Absorption correction: multi-scan (SADABS; Sheldrick, 2001) | 1818 reflections with I > 2σ(I) |
Tmin = 0.790, Tmax = 0.853 | Rint = 0.017 |
5950 measured reflections |
R[F2 > 2σ(F2)] = 0.038 | 0 restraints |
wR(F2) = 0.104 | H-atom parameters constrained |
S = 1.05 | Δρmax = 0.24 e Å−3 |
1879 reflections | Δρmin = −0.18 e Å−3 |
138 parameters |
Experimental. crystal mounted on cryoloop using Paratone-N |
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 | 0.33270 (13) | 0.62327 (6) | 1.12458 (11) | 0.0253 (3) | |
C1 | 0.51750 (16) | 0.66286 (8) | 0.51501 (15) | 0.0199 (3) | |
H1A | 0.4298 | 0.6718 | 0.4202 | 0.024* | |
H1B | 0.5558 | 0.7151 | 0.5586 | 0.024* | |
O2 | 0.90901 (13) | 0.56090 (6) | 0.22963 (14) | 0.0340 (3) | |
C2 | 0.67798 (17) | 0.62052 (8) | 0.46056 (15) | 0.0197 (3) | |
H2A | 0.6371 | 0.5698 | 0.4079 | 0.024* | |
O3 | 1.04100 (14) | 0.67826 (6) | 0.24051 (14) | 0.0346 (3) | |
H3 | 1.1187 | 0.6536 | 0.1965 | 0.052* | |
C3 | 0.81062 (17) | 0.60176 (8) | 0.60609 (16) | 0.0224 (3) | |
H3A | 0.8576 | 0.6517 | 0.6553 | 0.027* | |
H3B | 0.9115 | 0.5718 | 0.5707 | 0.027* | |
C4A | 0.55889 (17) | 0.59049 (8) | 0.77883 (16) | 0.0199 (3) | |
C4 | 0.72564 (17) | 0.55353 (9) | 0.73159 (16) | 0.0237 (3) | |
H4A | 0.6977 | 0.5001 | 0.6882 | 0.028* | |
H4B | 0.8120 | 0.5477 | 0.8284 | 0.028* | |
C5 | 0.52730 (17) | 0.59475 (8) | 0.93349 (16) | 0.0212 (3) | |
H5A | 0.6199 | 0.5814 | 1.0147 | 0.025* | |
C6 | 0.35638 (18) | 0.61914 (8) | 0.98126 (16) | 0.0205 (3) | |
C7 | 0.20938 (17) | 0.63442 (8) | 0.84973 (16) | 0.0230 (3) | |
H7A | 0.1229 | 0.6715 | 0.8888 | 0.028* | |
H7B | 0.1467 | 0.5844 | 0.8203 | 0.028* | |
C8A | 0.42640 (16) | 0.61828 (8) | 0.64259 (15) | 0.0194 (3) | |
H8AA | 0.3684 | 0.5705 | 0.5902 | 0.023* | |
C8 | 0.28119 (17) | 0.66910 (8) | 0.70197 (16) | 0.0216 (3) | |
H8A | 0.1826 | 0.6747 | 0.6149 | 0.026* | |
H8B | 0.3292 | 0.7224 | 0.7282 | 0.026* | |
C9 | 0.76216 (18) | 0.67094 (8) | 0.33847 (17) | 0.0231 (3) | |
H9A | 0.6693 | 0.6862 | 0.2515 | 0.028* | |
H9B | 0.8092 | 0.7199 | 0.3918 | 0.028* | |
C10 | 0.91038 (17) | 0.62978 (8) | 0.26540 (15) | 0.0205 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0254 (5) | 0.0284 (6) | 0.0232 (5) | −0.0011 (4) | 0.0073 (4) | −0.0009 (4) |
C1 | 0.0182 (6) | 0.0209 (7) | 0.0206 (6) | 0.0022 (5) | 0.0016 (5) | 0.0008 (5) |
O2 | 0.0282 (6) | 0.0243 (6) | 0.0520 (7) | −0.0004 (4) | 0.0152 (5) | −0.0066 (5) |
C2 | 0.0183 (6) | 0.0192 (7) | 0.0221 (7) | 0.0009 (5) | 0.0037 (5) | 0.0004 (5) |
O3 | 0.0302 (6) | 0.0287 (6) | 0.0489 (7) | −0.0064 (4) | 0.0218 (5) | −0.0073 (5) |
C3 | 0.0166 (6) | 0.0264 (7) | 0.0248 (7) | 0.0032 (5) | 0.0040 (5) | 0.0008 (5) |
C4A | 0.0181 (6) | 0.0167 (7) | 0.0248 (7) | −0.0002 (5) | 0.0027 (5) | 0.0019 (5) |
C4 | 0.0200 (7) | 0.0275 (8) | 0.0238 (7) | 0.0062 (5) | 0.0031 (5) | 0.0040 (6) |
C5 | 0.0187 (6) | 0.0207 (7) | 0.0238 (7) | 0.0008 (5) | 0.0011 (5) | 0.0024 (5) |
C6 | 0.0221 (7) | 0.0155 (7) | 0.0244 (7) | −0.0028 (5) | 0.0053 (5) | −0.0003 (5) |
C7 | 0.0166 (6) | 0.0259 (7) | 0.0272 (7) | 0.0010 (5) | 0.0053 (5) | −0.0007 (5) |
C8A | 0.0167 (6) | 0.0196 (7) | 0.0220 (7) | 0.0003 (5) | 0.0022 (5) | −0.0014 (5) |
C8 | 0.0156 (6) | 0.0245 (7) | 0.0247 (7) | 0.0027 (5) | 0.0017 (5) | 0.0007 (5) |
C9 | 0.0224 (7) | 0.0217 (7) | 0.0260 (7) | 0.0018 (5) | 0.0061 (5) | 0.0009 (5) |
C10 | 0.0197 (7) | 0.0221 (8) | 0.0195 (6) | 0.0004 (5) | 0.0016 (5) | 0.0023 (5) |
O1—C6 | 1.2356 (17) | C4A—C8A | 1.5105 (18) |
C1—C2 | 1.5253 (17) | C4—H4A | 0.9900 |
C1—C8A | 1.5341 (18) | C4—H4B | 0.9900 |
C1—H1A | 0.9900 | C5—C6 | 1.4578 (18) |
C1—H1B | 0.9900 | C5—H5A | 0.9500 |
O2—C10 | 1.2054 (18) | C6—C7 | 1.5012 (19) |
C2—C9 | 1.5260 (18) | C7—C8 | 1.5243 (18) |
C2—C3 | 1.5263 (18) | C7—H7A | 0.9900 |
C2—H2A | 1.0000 | C7—H7B | 0.9900 |
O3—C10 | 1.3213 (17) | C8A—C8 | 1.5241 (17) |
O3—H3 | 0.8400 | C8A—H8AA | 1.0000 |
C3—C4 | 1.5293 (18) | C8—H8A | 0.9900 |
C3—H3A | 0.9900 | C8—H8B | 0.9900 |
C3—H3B | 0.9900 | C9—C10 | 1.5088 (18) |
C4A—C5 | 1.3454 (19) | C9—H9A | 0.9900 |
C4A—C4 | 1.5029 (18) | C9—H9B | 0.9900 |
C2—C1—C8A | 114.33 (11) | O1—C6—C5 | 120.78 (12) |
C2—C1—H1A | 108.7 | O1—C6—C7 | 121.87 (12) |
C8A—C1—H1A | 108.7 | C5—C6—C7 | 117.27 (11) |
C2—C1—H1B | 108.7 | C6—C7—C8 | 111.10 (11) |
C8A—C1—H1B | 108.7 | C6—C7—H7A | 109.4 |
H1A—C1—H1B | 107.6 | C8—C7—H7A | 109.4 |
C1—C2—C9 | 110.08 (11) | C6—C7—H7B | 109.4 |
C1—C2—C3 | 109.66 (11) | C8—C7—H7B | 109.4 |
C9—C2—C3 | 111.39 (11) | H7A—C7—H7B | 108.0 |
C1—C2—H2A | 108.5 | C4A—C8A—C8 | 111.96 (11) |
C9—C2—H2A | 108.5 | C4A—C8A—C1 | 111.54 (10) |
C3—C2—H2A | 108.5 | C8—C8A—C1 | 110.24 (11) |
C10—O3—H3 | 109.5 | C4A—C8A—H8AA | 107.6 |
C2—C3—C4 | 111.73 (11) | C8—C8A—H8AA | 107.6 |
C2—C3—H3A | 109.3 | C1—C8A—H8AA | 107.6 |
C4—C3—H3A | 109.3 | C8A—C8—C7 | 112.50 (11) |
C2—C3—H3B | 109.3 | C8A—C8—H8A | 109.1 |
C4—C3—H3B | 109.3 | C7—C8—H8A | 109.1 |
H3A—C3—H3B | 107.9 | C8A—C8—H8B | 109.1 |
C5—C4A—C4 | 121.35 (12) | C7—C8—H8B | 109.1 |
C5—C4A—C8A | 122.47 (12) | H8A—C8—H8B | 107.8 |
C4—C4A—C8A | 116.10 (11) | C10—C9—C2 | 113.47 (11) |
C4A—C4—C3 | 112.87 (11) | C10—C9—H9A | 108.9 |
C4A—C4—H4A | 109.0 | C2—C9—H9A | 108.9 |
C3—C4—H4A | 109.0 | C10—C9—H9B | 108.9 |
C4A—C4—H4B | 109.0 | C2—C9—H9B | 108.9 |
C3—C4—H4B | 109.0 | H9A—C9—H9B | 107.7 |
H4A—C4—H4B | 107.8 | O2—C10—O3 | 123.33 (12) |
C4A—C5—C6 | 122.52 (12) | O2—C10—C9 | 124.23 (12) |
C4A—C5—H5A | 118.7 | O3—C10—C9 | 112.41 (12) |
C6—C5—H5A | 118.7 |
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O1i | 0.84 | 1.86 | 2.6793 (14) | 163 |
C7—H7B···O2ii | 0.99 | 2.53 | 3.4758 (17) | 161 |
Symmetry codes: (i) x+1, y, z−1; (ii) −x+1, −y+1, −z+1. |
Experimental details
Crystal data | |
Chemical formula | C12H16O3 |
Mr | 208.26 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 100 |
a, b, c (Å) | 7.5832 (2), 16.9532 (4), 8.3785 (2) |
β (°) | 96.323 (1) |
V (Å3) | 1070.58 (5) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.75 |
Crystal size (mm) | 0.33 × 0.28 × 0.22 |
Data collection | |
Diffractometer | Bruker SMART APEXII CCD area-detector |
Absorption correction | Multi-scan (SADABS; Sheldrick, 2001) |
Tmin, Tmax | 0.790, 0.853 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 5950, 1879, 1818 |
Rint | 0.017 |
(sin θ/λ)max (Å−1) | 0.602 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.038, 0.104, 1.05 |
No. of reflections | 1879 |
No. of parameters | 138 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.24, −0.18 |
Computer programs: APEX2 (Bruker, 2006), APEX2, SAINT (Bruker, 2005), SHELXTL (Sheldrick, 2004), SHELXTL.
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O1i | 0.84 | 1.86 | 2.6793 (14) | 163 |
C7—H7B···O2ii | 0.99 | 2.53 | 3.4758 (17) | 161 |
Symmetry codes: (i) x+1, y, z−1; (ii) −x+1, −y+1, −z+1. |
Among the five hydrogen-bonding modes known for ketocarboxylic acids, the commonest involves centrosymmetric dimerization. However, we have shown that when centrosymmetry is thwarted or disfavored, the frequency of acid-to-ketone catemers increases. Thus, among chiral non-racemates this chain-mode actually predominates, and its occurrence also rises markedly among conformationally constrained molecules. The latter is the case for compound (I), whose structure and hydrogen-bonding pattern we report here.
Fig. 1 shows the asymmetric unit, whose only conformational options lie in the side-chain. The C2—C9 staggering requires that C10 be involved in a gauche interaction with an equatorial proton either at C1 or at C3. Compared to alkane systems in which all centers are tetrahedral, such gauche arrangements are less serious here because the sp2 hybridization at the carboxyl diminishes the steric repulsions involved. Within the asymmetric unit, any energy advantage to the arrangement actually found [torsion angle C3—C2—C9—C10 = 64.16 (15)°] appears negligible and the observed choice is probably dictated by packing considerations. The remaining available rotation yields a C2—C9—C10—O2 torsion angle of 38.58 (19)° for the carboxyl group.
The disordering of bond lengths and angles often seen in carboxyl dimers is not possible in (I), which is not dimeric. Thus its C—O bond lengths [O2—C10 = 1.2054 (18) and O3—C10 = 1.3213 (17) Å] and C—C—O angles [O2—C10—C9 = 124.23 (12) and O3—C10—C9 = 112.41 (12) °] are typical of those in highly ordered dimeric carboxyls (Borthwick, 1980).
Fig. 2 shows the centrosymmetric packing of the cell, with extra molecules included to illustrate the acid-to-ketone hydrogen-bonding scheme. Each carboxylic acid is linked to the ketone in a molecule translationally related in both the a and c directions, so that the chains advance at an angle to the cell axes, along the [101] direction. The four hydrogen-bonding chains passing through the cell are of alternating handedness. Starting at the origin, the order of the directional alignment of these four chains with respect to the a axis is + + - -. The racemate aggregates in the solid as translational acid-to-ketone hydrogen-bonding catemers [O···O = 2.6793 (14)Å and O—H···O = 163°].
We characterize the geometry of H bonding to carbonyls using a combination of the H···O=C angle and the H···O=C—C torsion angle. These describe the approach of the H atom to the receptor O in terms of its deviation from, respectively, C=O axiality (ideal = 120°) and planarity with the carbonyl (ideal = 0°). In (I) these angles are 124.8 & 0.1°.
One intermolecular C—H···O close contact was found involving the carboxyl oxygen [H7B—O2 = 2.53; C7—O2 = 3.4758 (17) Å; C7—H7B—O2 = 161 °]. This distance lies within the 2.6-Å range we standardly survey for such packing interactions (Steiner, 1997).