research communications
S,4S,5R,7aR)-2,2,7-trimethyl-3a,4,5,7a-tetrahydro-1,3-benzodioxole-4,5-diol
and of (3aaCryssmat-Lab/Cátedra de Física/DETEMA, Facultad de Química, Universidad de la República, Montevideo, Uruguay, bGrupo INTERFASE, Universidad Industrial de Santander, Carrera 27, Calle 9, Ciudad Universitaria, Bucaramanga, Colombia, and cDepartamento de Química Orgánica, Facultad de Química, Universidad de la República, Montevideo, Uruguay
*Correspondence e-mail: leopoldo@fq.edu.uy
The 10H16O4, determined as 3aS,4S,5R,7aR on the basis of the synthetic pathway, was confirmed by X-ray diffraction. The molecule contains a five- and a six-membered ring that adopt twisted and envelope conformations, respectively. The dihedral angle between the mean planes of the rings is 76.80 (11)° as a result of their cis-fusion. In the crystal, molecules are linked by two pairs of O—H⋯O hydrogen bonds, forming chains along [010]. These chains are further connected by weaker C—H⋯O interactions along [100], creating (001) sheets that interact only by weak van der Waals forces.
of the title compound, CKeywords: crystal structure; epoxycyclohexenones; absolute configuration; chiral crystal; chemoenzymatic strategy.
CCDC reference: 1416687
1. Chemical context
Compounds containing an epoxycyclohexenone skeleton are very interesting, not only because of their wide spectrum of biological activities, but also because of their synthetically challenging chemical structures (Pandolfi et al., 2013). A biotransformation of toluene leads to a chiral diol (see Fig. 1) which is used as a precursor in enantioselective syntheses of epoxycyclohexenone compounds. Model compounds of the central core of ambuic acid (Labora et al., 2008), (+)- and (−)-bromoxone (Labora et al., 2010), an epoxyquinol analog (Heguaburu et al., 2010), gabosine A, ent-epoformin and ent-epiepoformin (Labora et al., 2011) have been prepared starting from the same precursor. The title compound, diol (3) (see Fig. 1) has been prepared from iodohydrin (1), which, as indicated earlier, can be easily synthesized via biotransformation of toluene (Carrera et al., 2007).
2. Structural commentary
Fig. 2 shows the molecule of the title compound. The of the title compound, determined as 3aS,4S,5R,7aR on the basis of the synthetic pathway, was confirmed by X-ray diffraction on the basis of of light atoms only. The five-membered ring (O1–C2–O3–C3A–C7A) adopts a twisted conformation with puckering parameters Q(2) = 0.342 (2) Å and φ = 122.1 (3)°. The six-membered ring (C3A–C4–C5–C6–C7–C7A) adopts an with atom C4 as the flap. In this case, the puckering parameters are Q = 0.466 (2) Å, θ = 52.1 (2) and φ = 50.8 (3)°. The fused rings are nearly perpendicular with a dihedral angle of 76.20 (11)° as a result of their cis-fusion.
3. Supramolecular features
In the ). In the [010] direction hydrogen bonds O41—H41⋯O3i and O51—H51⋯O41i [symmetry code: (i) −x, y + , −z + ] join molecules into chains that are further connected by weaker C7A—H7A⋯O51ii [symmetry code: (ii) x + 1, y, z] hydrogen bonds along [100], forming (001) sheets. Hydrogen bonds of the O—H⋯O type generate R22(10) motifs (Fig. 3). There are only weak acting between neighbouring (001) sheets.
the molecules are connected in the three crystallographic directions by intermolecular interactions of different strengths (Table 14. Database survey
A search of the Cambridge Structural Database (CSD Version 5.36 with one update; Groom & Allen, 2014) of the 3a,4,5,7a-tetrahydro-1,3-benzodioxole skeleton gave 30 hits, of which only 20 had no additional fused rings. In all cases, the six-membered ring displays an with atom C4 as a flap. The orientation of the flap with respect to the plane of the envelope can be determined from the C7—C7A—C3A—C4 or the H7A—C7A—C3A—H3A torsion angles (with very similar values due to the geometry of the cis-fused rings). The C7—C7A—C3A—C4 torsion angle is positive if the flap atom is located on the opposite side of the plane (defined by the remaining five atoms of the cyclohexene ring) to O1 and O3 of the 1,3-dioxole ring, as observed in the title compound [33.5 (2)°]. 12 of the 20 mentioned structures, show a positive torsion angle with minimum and maximum values of 17.2 and 36.4°, respectively. From analysis of the above-mentioned torsion angle and the equatorial/axial orientation of the C4 and C5 substituents in the 20 structures, there is no clear trend that allows the relative orientation of the flap to be predicted based only on the size or kind of the substituents.
5. Synthesis and crystallization
The synthesis of the title compound was carried out through the intermediate epoxide (2) (see Fig. 1). Iodohydrin (1) (0.6 mmol, 0.18 g) was dissolved in dry dichloromethane (5 mL) and 1,8-diazabicyclo[5.4.0]undec-7-en (DBU) (0.8 mmol, 0.12 g) was added at room temperature. The reaction was stirred for 24 h After completion of the reaction, the mixture was diluted with saturated NH4Cl solution (20 mL) and extracted with dichloromethane (3 x 10 mL). The combined organic layers were washed with saturated NaCl solution (10 mL), dried (Na2SO4) and filtered. Concentration of the filtrate, followed by flash (hexanes:ethyl acetate 93:7) yielded (2) (0.063 g, 60%). FT–IR (KBr): 2983, 2926, 2856, 1672, 1371. 1H-NMR (400 MHz, CDCl3) δ: 6.01 (m, 1H), 4.40 (m, 2H), 3.58 (m, 1H), 3.42 (t, J = 4.0 Hz, 1H), 1.91 (s, 3H), 1.53 (s, 3H), 1.41 (s, 1H). For the synthesis of diol (3), epoxide (2) (0.27 mmol, 0.05 g) was dissolved in THF (25 mL) and 10% KOH (aq., 25 mL) was added. This mixture was refluxed for 4 h. After completion of the reaction, the mixture was diluted with dichloromethane (20 mL) and the organic phase was washed with 10% HCl until neutralization, washed with saturated NaCl solution (10 mL), dried with (Na2SO4) and filtered. Concentration of the filtrate, followed by flash (ethyl acetate:hexanes 4:6) yielded (3) (0.02g, 52%). Crystals suitable for X-ray structure analysis were obtained by dissolving (3) in the minimum volume of ethyl acetate, adding hexanes until the solution became slightly turbid and slowly evaporating the solvent at room temperature. (m.p. = 385–386 K). FT–IR (KBr): 3402, 1637, 1371. 1H NMR (400 MHz, CDCl3) δ: 5.45 (s, 1H), 4.48 (m, 2H), 4.33 (m, 1H), 3.59 (m, 1H), 2.52 (bs, 1H), 2.30 (bs, 1H), 1.79 (s, 3H), 1.38 (s, 3H), 1.35 (s, 3H).
6. details
Crystal data, data collection and structure . H atoms bonded to C were placed in calculated positions (C—H = 0.95–1.00 Å) and included as riding contributions with isotropic displacement parameters set to 1.2–1.5 times of the Ueq of the parent atom. H atoms belonging to OH groups were located in ΔF maps and freely refined.
details are summarized in Table 2Supporting information
CCDC reference: 1416687
https://doi.org/10.1107/S2056989015014590/gk2644sup1.cif
contains datablocks I, New_Global_Publ_Block. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989015014590/gk2644Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989015014590/gk2644Isup3.cml
Data collection: APEX2 (Bruker, 2013); cell
SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015).C10H16O4 | F(000) = 432 |
Mr = 200.23 | Dx = 1.238 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54178 Å |
Hall symbol: P 2ac 2ab | θ = 3.8–66.7° |
a = 6.1230 (13) Å | µ = 0.79 mm−1 |
b = 7.5163 (17) Å | T = 293 K |
c = 23.347 (5) Å | Parallelepiped, colorless |
V = 1074.5 (4) Å3 | 0.28 × 0.18 × 0.14 mm |
Z = 4 |
Bruker D8 Venture/Photon 100 CMOS diffractometer | 1967 independent reflections |
Radiation source: Cu Incoatec microsource | 1951 reflections with I > 2σ(I) |
Helios X-ray optical focusing and monochromatization module | Rint = 0.030 |
Detector resolution: 10.4167 pixels mm-1 | θmax = 68.4°, θmin = 3.8° |
π and ω scans | h = −7→6 |
Absorption correction: multi-scan (SADABS; Bruker, 2013) | k = −9→9 |
Tmin = 0.643, Tmax = 0.752 | l = −28→28 |
29451 measured reflections |
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)] = 0.029 | w = 1/[σ2(Fo2) + (0.0278P)2 + 0.2133P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.078 | (Δ/σ)max < 0.001 |
S = 1.18 | Δρmax = 0.14 e Å−3 |
1967 reflections | Δρmin = −0.11 e Å−3 |
139 parameters | Extinction correction: SHELXL2014 (Sheldrick, 2015), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
0 restraints | Extinction coefficient: 0.0063 (9) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack x determined using 782 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013) |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.01 (3) |
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. |
x | y | z | Uiso*/Ueq | ||
O3 | 0.1718 (2) | 0.02424 (17) | 0.83031 (6) | 0.0431 (4) | |
C3A | 0.2609 (3) | 0.1964 (3) | 0.81761 (8) | 0.0379 (4) | |
H3A | 0.3868 | 0.1850 | 0.7919 | 0.045* | |
O1 | 0.4078 (3) | 0.0973 (2) | 0.90222 (7) | 0.0562 (5) | |
C7A | 0.3342 (3) | 0.2591 (3) | 0.87622 (8) | 0.0405 (5) | |
H7A | 0.4583 | 0.3403 | 0.8719 | 0.049* | |
H41 | −0.026 (5) | 0.337 (4) | 0.7201 (12) | 0.066 (9)* | |
H51 | −0.197 (5) | 0.545 (4) | 0.8006 (10) | 0.051 (8)* | |
O41 | 0.0349 (3) | 0.2538 (2) | 0.73585 (6) | 0.0499 (4) | |
O51 | −0.2609 (3) | 0.4552 (2) | 0.80767 (7) | 0.0488 (4) | |
C7 | 0.1596 (4) | 0.3484 (3) | 0.91126 (8) | 0.0403 (5) | |
C6 | −0.0366 (3) | 0.3793 (3) | 0.88973 (8) | 0.0415 (5) | |
H6 | −0.1387 | 0.4344 | 0.9133 | 0.050* | |
C23 | 0.4527 (6) | −0.1837 (4) | 0.85765 (13) | 0.0778 (9) | |
H23A | 0.5376 | −0.2248 | 0.8896 | 0.117* | |
H23B | 0.5475 | −0.1307 | 0.8297 | 0.117* | |
H23C | 0.3769 | −0.2824 | 0.8407 | 0.117* | |
C2 | 0.2898 (4) | −0.0479 (3) | 0.87792 (9) | 0.0484 (5) | |
C4 | 0.0914 (3) | 0.3159 (3) | 0.79142 (8) | 0.0358 (4) | |
H4 | 0.1557 | 0.4347 | 0.7873 | 0.043* | |
C5 | −0.1064 (3) | 0.3320 (2) | 0.83012 (9) | 0.0370 (4) | |
H5 | −0.1771 | 0.2152 | 0.8317 | 0.044* | |
C71 | 0.2246 (5) | 0.3979 (4) | 0.97104 (10) | 0.0621 (7) | |
H71A | 0.1042 | 0.4554 | 0.9898 | 0.093* | |
H71B | 0.3471 | 0.4775 | 0.9698 | 0.093* | |
H71C | 0.2639 | 0.2925 | 0.9919 | 0.093* | |
C22 | 0.1246 (6) | −0.1199 (4) | 0.91968 (12) | 0.0762 (9) | |
H22A | 0.1985 | −0.1646 | 0.9530 | 0.114* | |
H22B | 0.0437 | −0.2145 | 0.9019 | 0.114* | |
H22C | 0.0263 | −0.0266 | 0.9308 | 0.114* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O3 | 0.0525 (8) | 0.0324 (7) | 0.0444 (8) | 0.0017 (6) | −0.0105 (7) | −0.0019 (6) |
C3A | 0.0346 (9) | 0.0391 (10) | 0.0400 (10) | 0.0008 (8) | 0.0044 (8) | −0.0027 (8) |
O1 | 0.0621 (10) | 0.0478 (9) | 0.0587 (9) | 0.0118 (8) | −0.0243 (8) | −0.0051 (7) |
C7A | 0.0353 (9) | 0.0407 (10) | 0.0455 (10) | −0.0020 (9) | −0.0032 (9) | −0.0026 (9) |
O41 | 0.0668 (11) | 0.0458 (8) | 0.0372 (7) | 0.0157 (8) | −0.0080 (7) | −0.0020 (7) |
O51 | 0.0369 (8) | 0.0452 (9) | 0.0643 (10) | 0.0056 (7) | 0.0024 (7) | 0.0124 (7) |
C7 | 0.0482 (12) | 0.0349 (10) | 0.0377 (10) | −0.0064 (9) | 0.0036 (9) | −0.0010 (8) |
C6 | 0.0428 (11) | 0.0414 (11) | 0.0405 (10) | 0.0022 (9) | 0.0124 (9) | 0.0014 (9) |
C23 | 0.083 (2) | 0.0651 (17) | 0.0857 (19) | 0.0354 (16) | −0.0191 (16) | −0.0160 (15) |
C2 | 0.0605 (14) | 0.0390 (11) | 0.0456 (11) | 0.0103 (10) | −0.0116 (10) | −0.0022 (9) |
C4 | 0.0408 (10) | 0.0323 (9) | 0.0343 (9) | 0.0000 (8) | 0.0034 (8) | −0.0004 (7) |
C5 | 0.0323 (9) | 0.0323 (9) | 0.0465 (10) | 0.0003 (8) | 0.0031 (8) | 0.0047 (8) |
C71 | 0.0779 (17) | 0.0649 (15) | 0.0436 (12) | 0.0032 (15) | −0.0050 (12) | −0.0076 (11) |
C22 | 0.102 (2) | 0.0665 (17) | 0.0599 (15) | −0.0030 (18) | 0.0010 (15) | 0.0110 (13) |
O3—C2 | 1.433 (2) | C6—H6 | 0.9300 |
O3—C3A | 1.435 (2) | C23—C2 | 1.503 (3) |
C3A—C4 | 1.503 (3) | C23—H23A | 0.9600 |
C3A—C7A | 1.515 (3) | C23—H23B | 0.9600 |
C3A—H3A | 0.9800 | C23—H23C | 0.9600 |
O1—C2 | 1.427 (3) | C2—C22 | 1.505 (4) |
O1—C7A | 1.432 (3) | C4—C5 | 1.516 (3) |
C7A—C7 | 1.504 (3) | C4—H4 | 0.9800 |
C7A—H7A | 0.9800 | C5—H5 | 0.9800 |
O41—C4 | 1.421 (2) | C71—H71A | 0.9600 |
O41—H41 | 0.82 (3) | C71—H71B | 0.9600 |
O51—C5 | 1.424 (2) | C71—H71C | 0.9600 |
O51—H51 | 0.80 (3) | C22—H22A | 0.9600 |
C7—C6 | 1.323 (3) | C22—H22B | 0.9600 |
C7—C71 | 1.498 (3) | C22—H22C | 0.9600 |
C6—C5 | 1.499 (3) | ||
C2—O3—C3A | 108.04 (16) | O1—C2—C23 | 108.0 (2) |
O3—C3A—C4 | 111.11 (16) | O3—C2—C23 | 110.34 (19) |
O3—C3A—C7A | 101.91 (15) | O1—C2—C22 | 111.0 (2) |
C4—C3A—C7A | 112.71 (16) | O3—C2—C22 | 107.4 (2) |
O3—C3A—H3A | 110.3 | C23—C2—C22 | 113.9 (2) |
C4—C3A—H3A | 110.3 | O41—C4—C3A | 110.06 (15) |
C7A—C3A—H3A | 110.3 | O41—C4—C5 | 112.08 (17) |
C2—O1—C7A | 108.78 (15) | C3A—C4—C5 | 110.92 (15) |
O1—C7A—C7 | 111.85 (17) | O41—C4—H4 | 107.9 |
O1—C7A—C3A | 102.24 (16) | C3A—C4—H4 | 107.9 |
C7—C7A—C3A | 114.80 (16) | C5—C4—H4 | 107.9 |
O1—C7A—H7A | 109.2 | O51—C5—C6 | 112.15 (17) |
C7—C7A—H7A | 109.2 | O51—C5—C4 | 111.30 (16) |
C3A—C7A—H7A | 109.2 | C6—C5—C4 | 110.18 (16) |
C4—O41—H41 | 105.6 (19) | O51—C5—H5 | 107.7 |
C5—O51—H51 | 107.4 (19) | C6—C5—H5 | 107.7 |
C6—C7—C71 | 123.5 (2) | C4—C5—H5 | 107.7 |
C6—C7—C7A | 121.16 (18) | C7—C71—H71A | 109.5 |
C71—C7—C7A | 115.4 (2) | C7—C71—H71B | 109.5 |
C7—C6—C5 | 124.75 (18) | H71A—C71—H71B | 109.5 |
C7—C6—H6 | 117.6 | C7—C71—H71C | 109.5 |
C5—C6—H6 | 117.6 | H71A—C71—H71C | 109.5 |
C2—C23—H23A | 109.5 | H71B—C71—H71C | 109.5 |
C2—C23—H23B | 109.5 | C2—C22—H22A | 109.5 |
H23A—C23—H23B | 109.5 | C2—C22—H22B | 109.5 |
C2—C23—H23C | 109.5 | H22A—C22—H22B | 109.5 |
H23A—C23—H23C | 109.5 | C2—C22—H22C | 109.5 |
H23B—C23—H23C | 109.5 | H22A—C22—H22C | 109.5 |
O1—C2—O3 | 105.92 (16) | H22B—C22—H22C | 109.5 |
C2—O3—C3A—C4 | −151.43 (16) | C7A—O1—C2—C23 | 127.8 (2) |
C2—O3—C3A—C7A | −31.14 (19) | C7A—O1—C2—C22 | −106.6 (2) |
C2—O1—C7A—C7 | 95.1 (2) | C3A—O3—C2—O1 | 14.5 (2) |
C2—O1—C7A—C3A | −28.2 (2) | C3A—O3—C2—C23 | −102.1 (2) |
O3—C3A—C7A—O1 | 35.64 (18) | C3A—O3—C2—C22 | 133.2 (2) |
C4—C3A—C7A—O1 | 154.80 (17) | O3—C3A—C4—O41 | −68.3 (2) |
O3—C3A—C7A—C7 | −85.7 (2) | C7A—C3A—C4—O41 | 178.01 (16) |
C4—C3A—C7A—C7 | 33.5 (2) | O3—C3A—C4—C5 | 56.3 (2) |
O1—C7A—C7—C6 | −120.5 (2) | C7A—C3A—C4—C5 | −57.4 (2) |
C3A—C7A—C7—C6 | −4.6 (3) | C7—C6—C5—O51 | −147.6 (2) |
O1—C7A—C7—C71 | 59.4 (2) | C7—C6—C5—C4 | −23.0 (3) |
C3A—C7A—C7—C71 | 175.29 (19) | O41—C4—C5—O51 | −60.8 (2) |
C71—C7—C6—C5 | 179.8 (2) | C3A—C4—C5—O51 | 175.69 (16) |
C7A—C7—C6—C5 | −0.3 (3) | O41—C4—C5—C6 | 174.10 (15) |
C7A—O1—C2—O3 | 9.6 (2) | C3A—C4—C5—C6 | 50.6 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
O41—H41···O3i | 0.82 (3) | 2.04 (3) | 2.849 (2) | 171 (3) |
O51—H51···O41i | 0.80 (3) | 2.04 (3) | 2.826 (2) | 167 (2) |
C7A—H7A···O51ii | 0.98 | 2.44 | 3.299 (3) | 146 |
Symmetry codes: (i) −x, y+1/2, −z+3/2; (ii) x+1, y, z. |
Acknowledgements
The authors wish to thank ANII (EQC_2012_07), CSIC and the Facultad de Química for funds to purchase the diffractometer and the financial support of OPCW and PEDECIBA. MM and GT also thank ANII for their respective postdoctoral contracts (PD_NAC_2014_1_102409 and PD_NAC_2014_1_102498).
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