(–)-Metasantonic acid: alteration of the hydrogen-bonding mode in a diastereomer of santonic acid

The title compound, (−)-(1R,3aS,4R,5S,7aS,9R)-octa­hydro-α,3a,5-trimethyl-6,8-dioxo-1,4-methano-1H-indene-1-acetic acid, C₁₅H₂₀O₄, aggregates in the solid state as a catemer, with the hydrogen-bonding following a 2₁ screw axis from each carboxyl to the ketone of a neighboring mol­ecule [O...O = 2.6595 (14) Å and O—H...O = 166 (2)°]. Two parallel counter-directional screw-related single-strand chains pass through the cell in the a direction. Compared with the case of its C-9 diastereomer, santonic acid, also a catemer, the hydrogen-bonding receptor in the title compound is not the [epsilon]- but the γ-ketone. Three inter­molecular C—H...O=C close contacts exist.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.027
• wR factor = 0.070
• Data-to-parameter ratio = 11.7

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT027_ALERT_3_A _diffrn_reflns_theta_full (too) Low ............      65.02 Deg.

Author Response: diffrn reflns theta full (too) Low...65.02\%. (Alert level A) and resolution (too) Low [sin\q/\l < 0.6] (Alert level C): this problem has arisen because initially we were told by the manufacturer of our newly installed Bruker Smart Apex II unit to collect our small-molecule data to 0.85\%A resolution (with copper K\a radiation). This yields a \q max. of ca. 65.02\%, less than the 67\% required by Acta. However, since the crystals of this compound are no longer available, we can only rely on the current data set.

Alert level C
THETM01_ALERT_3_C  The value of sine(theta_max)/wavelength is less than 0.590
            Calculated sin(theta_max)/wavelength =    0.5879
PLAT023_ALERT_3_C Resolution (too) Low [sin(th)/Lambda < 0.6].....      65.02 Deg.
PLAT062_ALERT_4_C Rescale T(min) & T(max) by .....................       0.99
PLAT153_ALERT_1_C The su's on the Cell Axes are Equal (x 100000) .         20 Ang.
PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........          1

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           65.02
           From the CIF: _reflns_number_total               2087
           Count of symmetry unique reflns         1343
           Completeness (_total/calc)            155.40%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       744
           Fraction of Friedel pairs measured     0.554
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C1     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C3A    = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C4     = .          R
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C5     = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C7A    = .          S
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C9     = .          R

   1 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   5 ALERT level C = Check and explain
   7 ALERT level G = General alerts; check

   7 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   3 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

---

Computing details

Data collection: APEX2 (Bruker, 2006); cell refinement: APEX2; data reduction: SAINT (Bruker, 2005); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Sheldrick, 2004); software used to prepare material for publication: SHELXTL.

(-)-(1R,3aS,4R,5S,7aS,9R)-octahydro-α,3a, 5-trimethyl-6,8-dioxo-1,4-methano-1H-indene-1-acetic acid

Crystal data

C15H20O4	Dx = 1.294 Mg m^−3
Mr = 264.31	Melting point: 442 K
Orthorhombic, P212121	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2ac 2ab	Cell parameters from 5501 reflections
a = 9.4191 (2) Å	θ = 5.2–65.0°
b = 11.7706 (2) Å	µ = 0.76 mm^−1
c = 12.2382 (2) Å	T = 100 K
V = 1356.83 (4) Å^3	Block, colourless
Z = 4	0.48 × 0.34 × 0.20 mm
F(000) = 568

Data collection

Bruker SMART CCD APEXII area-detector diffractometer	2087 independent reflections
Radiation source: fine-focus sealed tube	2083 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.019
φ and ω scans	θmax = 65.0°, θmin = 5.2°
Absorption correction: multi-scan (SADABS; Sheldrick, 2001)	h = −10→9
Tmin = 0.801, Tmax = 0.871	k = −13→13
5501 measured reflections	l = −14→12

Refinement

Refinement on F^2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F^2 > 2σ(F^2)] = 0.027	w = 1/[σ^2(Fo^2) + (0.0366P)^2 + 0.3873P] where P = (Fo^2 + 2Fc^2)/3
wR(F^2) = 0.070	(Δ/σ)max < 0.001
S = 1.07	Δρmax = 0.22 e Å^−3
2087 reflections	Δρmin = −0.17 e Å^−3
179 parameters	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0126 (7)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack (1983), 760 Friedel pairs
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.03 (17)

Special details

Experimental. 'crystal mounted on glass fiber using cyanoacrylate'

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 (Ų)

	x	y	z	Uiso*/Ueq
O1	1.11127 (14)	0.39877 (11)	0.85526 (9)	0.0370 (3)
C1	0.87272 (15)	0.48980 (12)	0.60643 (11)	0.0157 (3)
O2	0.97330 (11)	0.30371 (8)	0.57119 (8)	0.0190 (2)
C2	0.84590 (16)	0.53740 (13)	0.48906 (11)	0.0194 (3)
H2A	0.8322	0.4750	0.4358	0.023*
H2B	0.7616	0.5876	0.4876	0.023*
O3	0.66381 (12)	0.24693 (9)	0.66649 (9)	0.0266 (3)
C3A	1.07250 (16)	0.59518 (12)	0.56894 (12)	0.0190 (3)
C3	0.98313 (18)	0.60482 (13)	0.46435 (12)	0.0223 (3)
H3A	1.0341	0.5715	0.4013	0.027*
H3B	0.9610	0.6853	0.4480	0.027*
O4	0.63504 (12)	0.35601 (9)	0.51898 (8)	0.0226 (3)
H4B	0.590 (2)	0.2979 (18)	0.4977 (17)	0.034*
C4	1.12886 (16)	0.47129 (12)	0.57437 (12)	0.0174 (3)
H4A	1.1845	0.4502	0.5078	0.021*
C5	1.21274 (16)	0.44792 (13)	0.68177 (13)	0.0215 (3)
H5A	1.2888	0.5069	0.6874	0.026*
C6	1.11358 (16)	0.46435 (14)	0.77849 (12)	0.0226 (3)
C7A	0.95722 (15)	0.58931 (12)	0.65839 (12)	0.0179 (3)
H7AA	0.8988	0.6603	0.6580	0.021*
C7	1.01604 (17)	0.56690 (13)	0.77311 (12)	0.0211 (3)
H7A	1.0690	0.6348	0.7979	0.025*
H7B	0.9357	0.5551	0.8240	0.025*
C8	0.99017 (16)	0.40546 (12)	0.58266 (10)	0.0150 (3)
C9	0.74642 (15)	0.44151 (12)	0.67091 (12)	0.0175 (3)
H9A	0.7825	0.4195	0.7448	0.021*
C10	0.68052 (15)	0.33621 (12)	0.62013 (12)	0.0171 (3)
C11	0.62947 (16)	0.53067 (14)	0.68817 (13)	0.0234 (3)
H11A	0.5538	0.4983	0.7335	0.035*
H11B	0.5903	0.5533	0.6172	0.035*
H11C	0.6696	0.5974	0.7248	0.035*
C12	1.18231 (17)	0.68922 (13)	0.57944 (14)	0.0254 (4)
H12A	1.1346	0.7632	0.5782	0.038*
H12B	1.2494	0.6846	0.5184	0.038*
H12C	1.2338	0.6805	0.6485	0.038*
C13	1.28546 (17)	0.33196 (14)	0.68190 (15)	0.0280 (4)
H13A	1.3424	0.3239	0.7485	0.042*
H13B	1.3472	0.3256	0.6178	0.042*
H13C	1.2134	0.2720	0.6796	0.042*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.0455 (8)	0.0416 (7)	0.0241 (6)	0.0041 (6)	−0.0038 (5)	0.0091 (6)
C1	0.0169 (7)	0.0135 (7)	0.0167 (7)	0.0001 (6)	0.0003 (6)	−0.0009 (6)
O2	0.0197 (5)	0.0131 (5)	0.0240 (5)	0.0002 (4)	0.0005 (5)	−0.0015 (4)
C2	0.0204 (7)	0.0186 (7)	0.0192 (7)	0.0031 (6)	−0.0015 (6)	0.0041 (6)
O3	0.0283 (6)	0.0198 (6)	0.0316 (6)	−0.0052 (5)	−0.0048 (5)	0.0080 (5)
C3A	0.0219 (8)	0.0153 (7)	0.0199 (7)	−0.0019 (6)	0.0032 (6)	−0.0006 (6)
C3	0.0256 (8)	0.0181 (7)	0.0230 (7)	−0.0002 (6)	0.0015 (6)	0.0043 (6)
O4	0.0293 (6)	0.0166 (5)	0.0218 (5)	−0.0075 (5)	−0.0068 (5)	0.0007 (4)
C4	0.0174 (7)	0.0162 (7)	0.0186 (7)	−0.0015 (6)	0.0016 (6)	−0.0022 (6)
C5	0.0180 (7)	0.0208 (8)	0.0258 (8)	−0.0029 (6)	−0.0045 (6)	−0.0013 (6)
C6	0.0235 (8)	0.0241 (8)	0.0201 (7)	−0.0073 (7)	−0.0075 (6)	−0.0018 (7)
C7A	0.0192 (8)	0.0125 (7)	0.0220 (7)	0.0002 (6)	0.0017 (6)	−0.0008 (6)
C7	0.0226 (8)	0.0217 (8)	0.0189 (7)	−0.0054 (7)	0.0019 (6)	−0.0052 (6)
C8	0.0188 (7)	0.0157 (7)	0.0105 (6)	0.0008 (6)	−0.0012 (6)	0.0008 (6)
C9	0.0178 (7)	0.0188 (7)	0.0160 (6)	0.0005 (6)	−0.0002 (6)	0.0002 (6)
C10	0.0132 (7)	0.0176 (8)	0.0205 (7)	0.0014 (6)	0.0027 (6)	0.0010 (6)
C11	0.0183 (7)	0.0236 (8)	0.0282 (8)	−0.0001 (7)	0.0044 (7)	−0.0049 (7)
C12	0.0264 (8)	0.0192 (7)	0.0307 (8)	−0.0064 (7)	0.0069 (7)	−0.0013 (7)
C13	0.0213 (8)	0.0263 (8)	0.0363 (9)	0.0018 (7)	−0.0059 (7)	0.0011 (7)

Geometric parameters (Å, º)

O1—C6	1.216 (2)	C5—C6	1.520 (2)
C1—C8	1.5146 (19)	C5—C13	1.527 (2)
C1—C9	1.537 (2)	C5—H5A	1.0000
C1—C7A	1.552 (2)	C6—C7	1.518 (2)
C1—C2	1.5624 (19)	C7A—C7	1.532 (2)
O2—C8	1.2163 (18)	C7A—H7AA	1.0000
C2—C3	1.547 (2)	C7—H7A	0.9900
C2—H2A	0.9900	C7—H7B	0.9900
C2—H2B	0.9900	C9—C10	1.519 (2)
O3—C10	1.2047 (18)	C9—C11	1.536 (2)
C3A—C12	1.520 (2)	C9—H9A	1.0000
C3A—C3	1.536 (2)	C11—H11A	0.9800
C3A—C7A	1.543 (2)	C11—H11B	0.9800
C3A—C4	1.553 (2)	C11—H11C	0.9800
C3—H3A	0.9900	C12—H12A	0.9800
C3—H3B	0.9900	C12—H12B	0.9800
O4—C10	1.3304 (18)	C12—H12C	0.9800
O4—H4B	0.85 (2)	C13—H13A	0.9800
C4—C8	1.522 (2)	C13—H13B	0.9800
C4—C5	1.558 (2)	C13—H13C	0.9800
C4—H4A	1.0000
C8—C1—C9	114.94 (12)	C7—C7A—C1	115.52 (12)
C8—C1—C7A	101.46 (11)	C3A—C7A—C1	95.96 (11)
C9—C1—C7A	117.76 (12)	C7—C7A—H7AA	110.3
C8—C1—C2	100.17 (11)	C3A—C7A—H7AA	110.3
C9—C1—C2	118.66 (12)	C1—C7A—H7AA	110.3
C7A—C1—C2	100.89 (11)	C6—C7—C7A	113.29 (12)
C3—C2—C1	103.21 (12)	C6—C7—H7A	108.9
C3—C2—H2A	111.1	C7A—C7—H7A	108.9
C1—C2—H2A	111.1	C6—C7—H7B	108.9
C3—C2—H2B	111.1	C7A—C7—H7B	108.9
C1—C2—H2B	111.1	H7A—C7—H7B	107.7
H2A—C2—H2B	109.1	O2—C8—C1	124.90 (13)
C12—C3A—C3	112.92 (12)	O2—C8—C4	127.28 (13)
C12—C3A—C7A	116.82 (12)	C1—C8—C4	107.82 (11)
C3—C3A—C7A	102.05 (12)	C10—C9—C11	108.70 (12)
C12—C3A—C4	116.58 (13)	C10—C9—C1	114.09 (12)
C3—C3A—C4	107.00 (12)	C11—C9—C1	111.91 (12)
C7A—C3A—C4	99.68 (11)	C10—C9—H9A	107.3
C3A—C3—C2	104.90 (12)	C11—C9—H9A	107.3
C3A—C3—H3A	110.8	C1—C9—H9A	107.3
C2—C3—H3A	110.8	O3—C10—O4	123.29 (14)
C3A—C3—H3B	110.8	O3—C10—C9	124.92 (13)
C2—C3—H3B	110.8	O4—C10—C9	111.67 (12)
H3A—C3—H3B	108.8	C9—C11—H11A	109.5
C10—O4—H4B	107.9 (14)	C9—C11—H11B	109.5
C8—C4—C3A	100.80 (11)	H11A—C11—H11B	109.5
C8—C4—C5	106.80 (11)	C9—C11—H11C	109.5
C3A—C4—C5	112.04 (12)	H11A—C11—H11C	109.5
C8—C4—H4A	112.2	H11B—C11—H11C	109.5
C3A—C4—H4A	112.2	C3A—C12—H12A	109.5
C5—C4—H4A	112.2	C3A—C12—H12B	109.5
C6—C5—C13	112.85 (14)	H12A—C12—H12B	109.5
C6—C5—C4	108.83 (12)	C3A—C12—H12C	109.5
C13—C5—C4	112.72 (13)	H12A—C12—H12C	109.5
C6—C5—H5A	107.4	H12B—C12—H12C	109.5
C13—C5—H5A	107.4	C5—C13—H13A	109.5
C4—C5—H5A	107.4	C5—C13—H13B	109.5
O1—C6—C7	121.82 (15)	H13A—C13—H13B	109.5
O1—C6—C5	122.13 (15)	C5—C13—H13C	109.5
C7—C6—C5	116.05 (13)	H13A—C13—H13C	109.5
C7—C7A—C3A	113.78 (12)	H13B—C13—H13C	109.5

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H4B···O2^i	0.85 (2)	1.83 (2)	2.6595 (14)	166 (2)
C12—H12B···O1^ii	0.98	2.58	3.519 (2)	160
C7—H7A···O2^iii	0.99	2.58	3.3780 (18)	137
C12—H12C···O3^iii	0.98	2.58	3.497 (2)	155

Symmetry codes: (i) x−1/2, −y+1/2, −z+1; (ii) −x+5/2, −y+1, z−1/2; (iii) −x+2, y+1/2, −z+3/2.