The results of a single-crystal X-ray experiment and density functional theory calculations performed for the title compound, C20H22O4, demonstrate that the lowest energy conformation of this molecule does not contain C2 molecular symmetry.
Supporting information
CCDC reference: 169947
Compound (I) was synthesized from L-diethyl tartrate (IV) in seven steps.
Conversion of (IV) to its acetonide followed by reduction with
diisobutylaluminum hydride and addition of vinylmagnesium bromide gave a
bis(allylic alcohol) (V) as a 71:23:6 mixture of diastereomers in a 72% yield.
Benzylation of (V) was followed by hydrolysis of the isopropylidene ketal to
give the diol in a 92% yield, which was then acetylated with acetic anhydride
to provide the bis(acetate), (VI). Separation of the three stereoisomers was
possible at this stage by chromatography on silica gel, providing the desired
isomer in 55% yield along with 35% of the two undesired isomers. Subjection of
diene (VI) to ring-closing metathesis with 3 mol% of a
1,3-dimesityl-4,5-dyhydroimidazol-2-ylidene substituted second generation
Grubbs' catalyst (Scholl et al., 1999) in refluxing benzene gave the
(+)-conduritol E derivative in a 93% yield along with 3% of unreacted starting
material. Cleavage of the acetate esters in basic methanol then provided the
title compound (I) in a 96% yield. The overall yield of the seven-step
synthesis was 36%.
Data collection: SMART (Siemens, 1996); cell refinement: SMART; data reduction: SHELXTL (Sheldrick, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL; software used to prepare material for publication: SHELXTL.
Crystal data top
C20H22O4 | Dx = 1.314 Mg m−3 |
Mr = 326.38 | Mo Kα radiation, λ = 0.71073 Å |
Orthorhombic, P212121 | Cell parameters from 1921 reflections |
a = 8.5979 (9) Å | θ = 2.0–50.0° |
b = 10.109 (1) Å | µ = 0.09 mm−1 |
c = 18.9828 (18) Å | T = 173 K |
V = 1649.9 (3) Å3 | Block, colourless |
Z = 4 | 0.62 × 0.62 × 0.40 mm |
F(000) = 696 | |
Data collection top
Bruker CCD-1000 area detector diffractometer | 1869 independent reflections |
Radiation source: fine-focus sealed tube | 1625 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.018 |
ϕ and ω scans | θmax = 26.4°, θmin = 2.3° |
Absorption correction: empirical (using intensity measurements) (SADABS; Blessing, 1995) | h = −10→10 |
Tmin = 0.946, Tmax = 0.965 | k = 0→12 |
3184 measured reflections | l = 0→22 |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.033 | Hydrogen site location: inferred from neighbouring sites |
wR(F2) = 0.079 | H-atom parameters constrained |
S = 1.00 | w = 1/[σ2(Fo2) + (0.0473P)2] where P = (Fo2 + 2Fc2)/3 |
1869 reflections | (Δ/σ)max < 0.001 |
219 parameters | Δρmax = 0.16 e Å−3 |
0 restraints | Δρmin = −0.14 e Å−3 |
Crystal data top
C20H22O4 | V = 1649.9 (3) Å3 |
Mr = 326.38 | Z = 4 |
Orthorhombic, P212121 | Mo Kα radiation |
a = 8.5979 (9) Å | µ = 0.09 mm−1 |
b = 10.109 (1) Å | T = 173 K |
c = 18.9828 (18) Å | 0.62 × 0.62 × 0.40 mm |
Data collection top
Bruker CCD-1000 area detector diffractometer | 1869 independent reflections |
Absorption correction: empirical (using intensity measurements) (SADABS; Blessing, 1995) | 1625 reflections with I > 2σ(I) |
Tmin = 0.946, Tmax = 0.965 | Rint = 0.018 |
3184 measured reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.033 | 0 restraints |
wR(F2) = 0.079 | H-atom parameters constrained |
S = 1.00 | Δρmax = 0.16 e Å−3 |
1869 reflections | Δρmin = −0.14 e Å−3 |
219 parameters | |
Special details top
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 | x | y | z | Uiso*/Ueq | |
O1 | 0.49733 (18) | 0.89156 (12) | 0.06757 (7) | 0.0317 (4) | |
O2 | 0.50548 (19) | 1.08578 (13) | 0.16656 (8) | 0.0369 (4) | |
H2 | 0.4920 | 1.1075 | 0.1243 | 0.055* | |
O3 | 0.34986 (16) | 0.82285 (14) | 0.27480 (8) | 0.0331 (4) | |
H3 | 0.4086 | 0.7678 | 0.2946 | 0.050* | |
O4 | 0.61733 (17) | 0.87617 (13) | 0.35123 (6) | 0.0294 (3) | |
C1 | 0.6922 (2) | 0.8380 (2) | 0.23195 (10) | 0.0298 (5) | |
H1 | 0.7884 | 0.8020 | 0.2474 | 0.036* | |
C2 | 0.6417 (2) | 0.8068 (2) | 0.16817 (11) | 0.0300 (5) | |
H2A | 0.7064 | 0.7538 | 0.1390 | 0.036* | |
C3 | 0.4883 (2) | 0.8506 (2) | 0.13992 (10) | 0.0274 (4) | |
H3A | 0.4137 | 0.7750 | 0.1433 | 0.033* | |
C4 | 0.4217 (2) | 0.96691 (18) | 0.18099 (10) | 0.0274 (5) | |
H4 | 0.3099 | 0.9793 | 0.1681 | 0.033* | |
C5 | 0.4347 (2) | 0.9397 (2) | 0.25963 (10) | 0.0267 (4) | |
H5 | 0.3872 | 1.0152 | 0.2860 | 0.032* | |
C6 | 0.6051 (2) | 0.92721 (19) | 0.28076 (10) | 0.0269 (5) | |
H6 | 0.6539 | 1.0170 | 0.2793 | 0.032* | |
C7 | 0.4894 (3) | 0.7851 (2) | 0.01935 (10) | 0.0340 (5) | |
H7A | 0.3921 | 0.7348 | 0.0270 | 0.041* | |
H7B | 0.5782 | 0.7245 | 0.0272 | 0.041* | |
C8 | 0.4936 (2) | 0.8369 (2) | −0.05522 (10) | 0.0282 (4) | |
C9 | 0.5592 (2) | 0.7603 (2) | −0.10810 (11) | 0.0333 (5) | |
H9 | 0.6035 | 0.6767 | −0.0972 | 0.040* | |
C10 | 0.5599 (2) | 0.8061 (2) | −0.17714 (11) | 0.0382 (6) | |
H10 | 0.6045 | 0.7536 | −0.2134 | 0.046* | |
C11 | 0.4966 (3) | 0.9269 (2) | −0.19314 (12) | 0.0394 (5) | |
H11 | 0.4982 | 0.9581 | −0.2403 | 0.047* | |
C12 | 0.4305 (3) | 1.0033 (2) | −0.14100 (11) | 0.0397 (6) | |
H12 | 0.3851 | 1.0863 | −0.1523 | 0.048* | |
C13 | 0.4307 (3) | 0.9583 (2) | −0.07210 (11) | 0.0340 (5) | |
H13 | 0.3870 | 1.0117 | −0.0360 | 0.041* | |
C14 | 0.6098 (3) | 0.9794 (2) | 0.40260 (10) | 0.0362 (5) | |
H14A | 0.5345 | 1.0475 | 0.3870 | 0.043* | |
H14B | 0.7131 | 1.0219 | 0.4070 | 0.043* | |
C15 | 0.5607 (2) | 0.92596 (19) | 0.47313 (10) | 0.0263 (4) | |
C16 | 0.4230 (3) | 0.8572 (2) | 0.48053 (12) | 0.0367 (5) | |
H16 | 0.3620 | 0.8381 | 0.4401 | 0.044* | |
C17 | 0.3728 (3) | 0.8157 (2) | 0.54590 (12) | 0.0459 (6) | |
H17 | 0.2769 | 0.7698 | 0.5504 | 0.055* | |
C18 | 0.4624 (3) | 0.8410 (2) | 0.60502 (12) | 0.0448 (6) | |
H18 | 0.4285 | 0.8119 | 0.6501 | 0.054* | |
C19 | 0.6004 (3) | 0.9084 (2) | 0.59835 (11) | 0.0405 (6) | |
H19 | 0.6619 | 0.9264 | 0.6388 | 0.049* | |
C20 | 0.6496 (2) | 0.9500 (2) | 0.53252 (10) | 0.0326 (5) | |
H20 | 0.7456 | 0.9958 | 0.5281 | 0.039* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
O1 | 0.0476 (8) | 0.0297 (7) | 0.0179 (8) | −0.0041 (7) | 0.0001 (7) | −0.0007 (6) |
O2 | 0.0558 (9) | 0.0268 (7) | 0.0282 (8) | −0.0035 (7) | −0.0034 (8) | 0.0038 (6) |
O3 | 0.0331 (8) | 0.0341 (8) | 0.0320 (9) | −0.0018 (6) | 0.0014 (7) | 0.0028 (7) |
O4 | 0.0408 (8) | 0.0296 (7) | 0.0178 (7) | 0.0016 (7) | −0.0019 (6) | −0.0013 (6) |
C1 | 0.0274 (10) | 0.0371 (11) | 0.0250 (12) | 0.0058 (9) | 0.0010 (9) | 0.0030 (9) |
C2 | 0.0334 (11) | 0.0308 (11) | 0.0258 (12) | 0.0051 (9) | 0.0074 (9) | −0.0011 (9) |
C3 | 0.0369 (11) | 0.0280 (10) | 0.0174 (10) | −0.0027 (10) | 0.0002 (9) | 0.0019 (9) |
C4 | 0.0304 (10) | 0.0260 (10) | 0.0260 (12) | 0.0025 (9) | −0.0024 (9) | −0.0004 (8) |
C5 | 0.0310 (10) | 0.0249 (10) | 0.0242 (11) | 0.0018 (9) | 0.0028 (9) | −0.0028 (8) |
C6 | 0.0338 (11) | 0.0277 (10) | 0.0193 (10) | −0.0008 (9) | −0.0023 (9) | 0.0007 (8) |
C7 | 0.0462 (12) | 0.0287 (10) | 0.0271 (12) | −0.0017 (10) | 0.0007 (11) | −0.0019 (9) |
C8 | 0.0283 (10) | 0.0327 (10) | 0.0235 (11) | −0.0067 (9) | −0.0027 (9) | −0.0006 (9) |
C9 | 0.0320 (11) | 0.0355 (11) | 0.0324 (13) | −0.0012 (9) | −0.0020 (10) | −0.0044 (10) |
C10 | 0.0330 (11) | 0.0560 (15) | 0.0255 (13) | −0.0069 (11) | 0.0031 (10) | −0.0137 (11) |
C11 | 0.0425 (12) | 0.0561 (14) | 0.0195 (11) | −0.0125 (13) | −0.0036 (10) | 0.0037 (11) |
C12 | 0.0474 (13) | 0.0387 (12) | 0.0330 (13) | −0.0008 (11) | −0.0122 (11) | 0.0027 (11) |
C13 | 0.0387 (11) | 0.0388 (12) | 0.0246 (12) | 0.0029 (10) | −0.0021 (10) | −0.0043 (9) |
C14 | 0.0563 (14) | 0.0303 (11) | 0.0220 (12) | −0.0063 (10) | 0.0015 (11) | −0.0041 (9) |
C15 | 0.0324 (10) | 0.0240 (9) | 0.0224 (11) | 0.0028 (9) | 0.0012 (9) | −0.0022 (8) |
C16 | 0.0377 (12) | 0.0396 (12) | 0.0327 (13) | −0.0035 (10) | −0.0025 (11) | −0.0064 (10) |
C17 | 0.0459 (13) | 0.0458 (13) | 0.0459 (15) | −0.0173 (12) | 0.0133 (12) | −0.0040 (12) |
C18 | 0.0667 (17) | 0.0371 (12) | 0.0306 (13) | −0.0039 (12) | 0.0125 (12) | 0.0022 (11) |
C19 | 0.0565 (15) | 0.0417 (13) | 0.0232 (12) | 0.0005 (11) | −0.0056 (11) | −0.0015 (10) |
C20 | 0.0333 (11) | 0.0369 (11) | 0.0275 (13) | −0.0039 (10) | −0.0004 (10) | −0.0039 (9) |
Geometric parameters (Å, º) top
O1—C7 | 1.414 (2) | C8—C9 | 1.387 (3) |
O1—C3 | 1.437 (2) | C9—C10 | 1.390 (3) |
O2—C4 | 1.428 (2) | C9—H9 | 0.9500 |
O2—H2 | 0.8400 | C10—C11 | 1.371 (3) |
O3—C5 | 1.418 (2) | C10—H10 | 0.9500 |
O3—H3 | 0.8400 | C11—C12 | 1.377 (3) |
O4—C14 | 1.430 (2) | C11—H11 | 0.9500 |
O4—C6 | 1.437 (2) | C12—C13 | 1.385 (3) |
C1—C2 | 1.324 (3) | C12—H12 | 0.9500 |
C1—C6 | 1.494 (3) | C13—H13 | 0.9500 |
C1—H1 | 0.9500 | C14—C15 | 1.504 (3) |
C2—C3 | 1.492 (3) | C14—H14A | 0.9900 |
C2—H2A | 0.9500 | C14—H14B | 0.9900 |
C3—C4 | 1.522 (3) | C15—C16 | 1.380 (3) |
C3—H3A | 1.0000 | C15—C20 | 1.384 (3) |
C4—C5 | 1.522 (3) | C16—C17 | 1.379 (3) |
C4—H4 | 1.0000 | C16—H16 | 0.9500 |
C5—C6 | 1.524 (3) | C17—C18 | 1.385 (3) |
C5—H5 | 1.0000 | C17—H17 | 0.9500 |
C6—H6 | 1.0000 | C18—C19 | 1.374 (3) |
C7—C8 | 1.510 (3) | C18—H18 | 0.9500 |
C7—H7A | 0.9900 | C19—C20 | 1.385 (3) |
C7—H7B | 0.9900 | C19—H19 | 0.9500 |
C8—C13 | 1.379 (3) | C20—H20 | 0.9500 |
| | | |
C7—O1—C3 | 113.38 (14) | C13—C8—C7 | 121.13 (19) |
C4—O2—H2 | 109.5 | C9—C8—C7 | 119.65 (18) |
C5—O3—H3 | 109.5 | C8—C9—C10 | 119.9 (2) |
C14—O4—C6 | 111.67 (14) | C8—C9—H9 | 120.1 |
C2—C1—C6 | 123.14 (18) | C10—C9—H9 | 120.1 |
C2—C1—H1 | 118.4 | C11—C10—C9 | 120.3 (2) |
C6—C1—H1 | 118.4 | C11—C10—H10 | 119.9 |
C1—C2—C3 | 123.20 (19) | C9—C10—H10 | 119.9 |
C1—C2—H2A | 118.4 | C10—C11—C12 | 120.2 (2) |
C3—C2—H2A | 118.4 | C10—C11—H11 | 119.9 |
O1—C3—C2 | 112.43 (16) | C12—C11—H11 | 119.9 |
O1—C3—C4 | 106.71 (15) | C11—C12—C13 | 119.6 (2) |
C2—C3—C4 | 112.22 (16) | C11—C12—H12 | 120.2 |
O1—C3—H3A | 108.4 | C13—C12—H12 | 120.2 |
C2—C3—H3A | 108.4 | C8—C13—C12 | 120.8 (2) |
C4—C3—H3A | 108.4 | C8—C13—H13 | 119.6 |
O2—C4—C5 | 107.64 (16) | C12—C13—H13 | 119.6 |
O2—C4—C3 | 111.21 (16) | O4—C14—C15 | 110.96 (16) |
C5—C4—C3 | 109.59 (15) | O4—C14—H14A | 109.4 |
O2—C4—H4 | 109.5 | C15—C14—H14A | 109.4 |
C5—C4—H4 | 109.5 | O4—C14—H14B | 109.4 |
C3—C4—H4 | 109.5 | C15—C14—H14B | 109.4 |
O3—C5—C4 | 108.17 (16) | H14A—C14—H14B | 108.0 |
O3—C5—C6 | 111.82 (17) | C16—C15—C20 | 118.66 (19) |
C4—C5—C6 | 110.11 (16) | C16—C15—C14 | 120.80 (19) |
O3—C5—H5 | 108.9 | C20—C15—C14 | 120.48 (18) |
C4—C5—H5 | 108.9 | C17—C16—C15 | 120.9 (2) |
C6—C5—H5 | 108.9 | C17—C16—H16 | 119.6 |
O4—C6—C1 | 108.89 (15) | C15—C16—H16 | 119.6 |
O4—C6—C5 | 110.19 (16) | C16—C17—C18 | 119.9 (2) |
C1—C6—C5 | 111.64 (17) | C16—C17—H17 | 120.0 |
O4—C6—H6 | 108.7 | C18—C17—H17 | 120.0 |
C1—C6—H6 | 108.7 | C19—C18—C17 | 119.8 (2) |
C5—C6—H6 | 108.7 | C19—C18—H18 | 120.1 |
O1—C7—C8 | 110.00 (16) | C17—C18—H18 | 120.1 |
O1—C7—H7A | 109.7 | C18—C19—C20 | 119.8 (2) |
C8—C7—H7A | 109.7 | C18—C19—H19 | 120.1 |
O1—C7—H7B | 109.7 | C20—C19—H19 | 120.1 |
C8—C7—H7B | 109.7 | C15—C20—C19 | 120.9 (2) |
H7A—C7—H7B | 108.2 | C15—C20—H20 | 119.6 |
C13—C8—C9 | 119.21 (19) | C19—C20—H20 | 119.6 |
| | | |
C6—C1—C2—C3 | −3.8 (3) | O1—C7—C8—C13 | −31.6 (3) |
C7—O1—C3—C2 | 83.1 (2) | O1—C7—C8—C9 | 149.55 (19) |
C7—O1—C3—C4 | −153.49 (18) | C13—C8—C9—C10 | −0.4 (3) |
C1—C2—C3—O1 | 138.4 (2) | C7—C8—C9—C10 | 178.5 (2) |
C1—C2—C3—C4 | 18.1 (3) | C8—C9—C10—C11 | 0.2 (3) |
O1—C3—C4—O2 | −51.4 (2) | C9—C10—C11—C12 | −0.5 (3) |
C2—C3—C4—O2 | 72.2 (2) | C10—C11—C12—C13 | 1.0 (3) |
O1—C3—C4—C5 | −170.27 (15) | C9—C8—C13—C12 | 0.9 (3) |
C2—C3—C4—C5 | −46.7 (2) | C7—C8—C13—C12 | −177.9 (2) |
O2—C4—C5—O3 | 179.13 (15) | C11—C12—C13—C8 | −1.2 (3) |
C3—C4—C5—O3 | −59.8 (2) | C6—O4—C14—C15 | 157.99 (17) |
O2—C4—C5—C6 | −58.4 (2) | O4—C14—C15—C16 | −56.5 (3) |
C3—C4—C5—C6 | 62.7 (2) | O4—C14—C15—C20 | 126.4 (2) |
C14—O4—C6—C1 | 150.68 (17) | C20—C15—C16—C17 | 1.4 (3) |
C14—O4—C6—C5 | −86.6 (2) | C14—C15—C16—C17 | −175.7 (2) |
C2—C1—C6—O4 | 140.6 (2) | C15—C16—C17—C18 | −1.1 (4) |
C2—C1—C6—C5 | 18.7 (3) | C16—C17—C18—C19 | 0.6 (4) |
O3—C5—C6—O4 | −48.4 (2) | C17—C18—C19—C20 | −0.3 (3) |
C4—C5—C6—O4 | −168.66 (15) | C16—C15—C20—C19 | −1.2 (3) |
O3—C5—C6—C1 | 72.7 (2) | C14—C15—C20—C19 | 175.9 (2) |
C4—C5—C6—C1 | −47.5 (2) | C18—C19—C20—C15 | 0.7 (3) |
C3—O1—C7—C8 | 177.88 (17) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O2i | 0.84 | 2.12 | 2.920 (2) | 160 |
Symmetry code: (i) −x+1, y−1/2, −z+1/2. |
Experimental details
Crystal data |
Chemical formula | C20H22O4 |
Mr | 326.38 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 173 |
a, b, c (Å) | 8.5979 (9), 10.109 (1), 18.9828 (18) |
V (Å3) | 1649.9 (3) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.62 × 0.62 × 0.40 |
|
Data collection |
Diffractometer | Bruker CCD-1000 area detector diffractometer |
Absorption correction | Empirical (using intensity measurements) (SADABS; Blessing, 1995) |
Tmin, Tmax | 0.946, 0.965 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 3184, 1869, 1625 |
Rint | 0.018 |
(sin θ/λ)max (Å−1) | 0.625 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.033, 0.079, 1.00 |
No. of reflections | 1869 |
No. of parameters | 219 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.16, −0.14 |
Selected geometric parameters (Å, º) topO1—C7 | 1.414 (2) | O3—C5 | 1.418 (2) |
O2—C4 | 1.428 (2) | O4—C14 | 1.430 (2) |
| | | |
C1—C2—C3—C4 | 18.1 (3) | O1—C7—C8—C13 | −31.6 (3) |
C2—C1—C6—C5 | 18.7 (3) | O4—C14—C15—C16 | −56.5 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O3—H3···O2i | 0.84 | 2.12 | 2.920 (2) | 160 |
Symmetry code: (i) −x+1, y−1/2, −z+1/2. |
We have synthesized the chiral title molecule, (I), during the course of our work on the synthesis of natural products related to marine sponge extracts. Herein we report the structure of (I), discuss its molecular symmetry, and present results of density functional theory (DFT) (Schrödinger Inc., 1998) calculations. \sch
The absolute stereochemistry of the chiral centers is assigned 3S, 4R, 5R, and 6S from knowledge of the synthesis. The benzyloxy groups occupy pseudoequatorial positions while the hydroxyl substituents are located in axial positions. Unfavorable steric interactions are minimized when the bulky substituents occupy pseudoequatorial positions and this feature is similarly observed in the related compounds 3,5-dicyano-6-(2-methoxy-1,1,2-trimethylpropyl)cyclohexene, (II), cis-1,3-dicyano-4-(2-methoxy-1,1,2-trimethylpropyl)cyclohexene, and cis-1,5-dicyano-4-(2-methoxy-1,1,2-trimethylpropyl)cyclohexene (Borg et al., 1984).
The conformation of the cyclohexene ring in (I) is a half-chair. Atoms C1, C2, C3, and C6 are planar within 0.02 Å. Atoms C4 and C5 are located 0.372 (4) and 0.388 (4) Å above and below this plane, respectively. The C2—C1—C6—C5 and C1—C2—C3—C4 torsion angles are 18.7 (3) and 18.1 (3)°, correspondingly. Relevant torsion angles in the related structures, (II), 5-n-butyl-3-hydroxymethyl-6-methylcyclohexen-4-ol (Batey et al., 1999), (+)-(1S,2S,3S,6R,1'S)-methyl-2-(1-hydroxyethyl)- 3-hydroxymethyl-6-methyl-4-cyclohexene-1-carboxylate, and (+)-(1S, 2S, 3S, 6R,1'S,1''R)-methyl-2,3-bis(1-hydroxyethyl)-6-methyl-4-cyclohexene- 1-carboxylate (Ainsworth et al., 1995) range from 5.9 to 25.4°. Notably, the DFT calculated torsion angles C2—C1—C6—C5 (13.9°) and C1—C2—C3—C4 (13.9°) of cyclohexene (III) fall in the middle of this range.
Several statistically significant differences are observed in the chemically equivalent bond lengths and torsion angles of (I). The O2—C4 distance [1.428 (2) Å] is 0.010 Å longer than the related O3—C5 distance [1.418 (2) Å]. In 4574 relevant compounds containing 8321 Csp3—OH bonds reported to the Cambridge Structural Database (CSD) (Allen & Kennard, 1993), the corresponding values averaged 1.424 (15) Å. Additionally, the O4—C14 distance [1.430 (2) Å] is 0.016 Å longer than O1—C7 [1.414 (2) Å], and the torsion angles O1—C7—C8—C13 [-31.6 (3)°] and O4—C14—C15—C16 [-56.5 (3)°] are substantially different. To account for these discrepancies, several DFT geometry optimizations were performed on molecules of (I) and (III). Results of calculations for one molecule of (III) verify its optimal geometry to be C2 symmetric. However, this is not observed in the case of (I). The DFT calculated molecular parameters of (I) are in close agreement with the experimentally observed values. One exception to this is that the calculated O1—C7—C8—C13 and O4—C14—C15—C16 torsion angles are 41.0 and 69.4°, respectively. Although π-stacking interactions are not observed, other crystal packing forces likely contribute to this difference. To test the hypothesis that the C2 symmetric geometry of (I) is not the lowest in energy, DFT calculations were carried out for (I) by starting from the symmetrical conformation and consecutively lifting all of the symmetry constraints. In the progress of optimization the molecule departed from the symmetrical conformation. Additionally, DFT calculations were performed on (I) with two additional water molecules fixed at the observed O3.·O2[1 - x, y - 1/2, 1/2 - z] and O2.·O3[1 - x, y + 1/2, 1/2 - z] distances to simulate possible hydrogen bonding in the structure. This structure optimization did not fully converge. [The maximum displacement (2.13×10-2) and r.m.s. displacement (7.88×10-3) values were above the standard threshold values of 1.8×10-3 and 1.2×10-3 respectively, which in turn, is indicative of a flat minimum on the potential energy surface.] Consequently, it is concluded that hydrogen bonding probably does not contribute significantly to this symmetry lowering.
Weak hydrogen-bonding interactions between the hydroxyl substituents of symmetry-related molecules in the lattice of (I) are likely. An intermolecular hydrogen-bonding interaction is observed between donor atom O3 and acceptor atom O2[1 - x, y - 1/2, 1/2 - z], Table 2. The corresponding values for 2222 compounds with 3998 similar hydrogen bonds in structures reported to the CSD comprised 2.79 (9) Å and 166 (7)°. The longer O···O separation in (I) is indicative of a weaker hydrogen bond. Interestingly, the chemically equivalent intermolecular O2.·H—O3 hydrogen-bonding interaction is not observed and also confirms the lack of C2 molecular symmetry. Results of this study demonstrate that the C1 molecular symmetry of (I) is determined by its conformational stability rather than by packing forces alone.