(S)-(2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl)acetic acid

The title compound, C₇H₁₀O₅, was obtained from the reaction of (S)-malic acid and 2,2-dimethoxy­propane using p-TsOH as acid catalyst. The mol­ecule is enanti­omerically pure, as determined from optical rotation. The dioxolanone ring is a slightly distorted plane with the methyl­enecarb­oxy group equatorial. The carb­oxy group is syn to the face of the ring and anti to the ring H atom. Mol­ecules are linked by O—H...O hydrogen bonds between the hydr­oxy group of the carboxyl group and the dioxolane carbonyl O atom, generating helices parallel to b. Only the S enantio­mer is present in the crystal structure, which is consistent with the starting material and its synthetic sequence.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.025
• wR factor = 0.064
• Data-to-parameter ratio = 11.0

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT027_ALERT_3_A _diffrn_reflns_theta_full (too) Low ............      62.90 Deg.

Author Response: Data was collected to the collision limits of the Oxford Diffraction Gemini Ultra. The instrument has two x-ray sources which restricts the range of the 2theta arm more than the typical single source instrument. This is especially true with the Sapphire 3 detector, which was originally optimized for use on single source Mo instruments where 2theta range is not an issue.

Alert level C
THETM01_ALERT_3_C  The value of sine(theta_max)/wavelength is less than 0.590
            Calculated sin(theta_max)/wavelength =    0.5782
PLAT023_ALERT_3_C Resolution (too) Low [sin(th)/Lambda < 0.6].....      63.06 Deg.
PLAT850_ALERT_2_C Check Flack Parameter Exact Value 0.00 and su ..       0.18

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           63.06
           From the CIF: _reflns_number_total               1262
           Count of symmetry unique reflns          693
           Completeness (_total/calc)            182.11%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured       569
           Fraction of Friedel pairs measured     0.821
           Are heavy atom types Z>Si present         no
PLAT791_ALERT_1_G Confirm the Absolute Configuration of C2     = .          S
PLAT860_ALERT_3_G Note: Number of Least-Squares Restraints .......          1

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

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

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S1. Comment

(S)-Malic acid is a convenient starting material from the chiral pool and has been used in a variety of important natural and unnatural synthetic targets (Green et al., 1995; Kim et al., 1997; Mulzer et al., 2000). The reported syntheses of many phytosiderophores and their analogs have utilized the title compound (I) (Ohfune et al., 1981; Shioiri et al., 1995; Shioiri et al., 1997). We are interested in the preparation of a variety of phytosiderophores and their analogs for our ongoing transport studies (Stocksdale et al., 2005). Stereospecific requirements of phytosiderophores on iron-uptake by rice plants have been studied. Enantiomers of the natural phytosiderophores resulted in significantly less iron-uptake (Oida et al., 1989). Thus, absolute configuration of the title compound was important in our continued transport studies. Our preparation of the title compound was adapted from the literature (Green et al., 1995).

The asymmetric unit of the structure comprises one crystallographically independent molecule of S absolute configuration. The Flack parameter, which refined to 0.00 (18), is not inconsistent with the know absolute configuration of the starting material, (S)-malic acid, and our synthetic sequence should have maintained this stereocenter.

Inspection of the crystal structure reveals molecules linked along the unique axis, b, by O—H···O hydrogen bonds. The network along the b axis is a helix and, as expected from the space goup, two molecular units form one turn of the helix. Each molecule has two sites for hydrogen bonding: the hydroxy group of the carboxylic acid, O4–H41, and the dioxolanone carbonyl, O2. The O2–O4' intermolecular distance is 2.707 Å.

Related literature

The crystal structures of racemic malic acid and the (-)-enantiomer are known (van der Sluis & Kroon, 1985, 1989). While the space group of the (-)-enantiomer is P2₁, its absolute configuration could not be determined from anomalous dispersion. The crystal structures of at least one simple dioxolanone derivative of (-)-malic acid is also known (Pang et al., 1997). For related literature, see: Clegg (2003); Green et al. (1995); Kim et al. (1997); Mulzer et al. (2000); Ohfune et al. (1981); Oida et al. (1989); Shioiri et al. (1995, 1997); Stocksdale et al. (2005).

S2. Experimental

p-Toluenesulfonic acid (0.600 g, 3.2 mmol) was added to a room temperature stirred suspension of (S)-malic acid (30.0 g, 224 mmol) in 2,2-dimethoxypropane (75 ml, 610 mmol). After 30 minutes, the reaction mixture was diluted with CH₂Cl₂ (75 ml) and water (75 ml). The resulting organic layer was separated, and the aqueous layer was extracted with CH₂Cl₂ (3 x 50 ml). The combined organic layers were dried (Na₂SO₄), filtered, and concentrated to give a white solid. Recrystallization with 2:1 ethyl acetate/hexanes gave 21.8 g (56%) of compound I as colorless needles. ¹H NMR (400 MHz, CDCl₃) δ 8.13 (br s, 1H), 4.69 (dd, 1H, J = 6.7 Hz, J = 3.7 Hz), 2.98 (dd, 1H, J = 17.4 Hz, J = 3.7 Hz), 2.84 (dd, 1H, J = 17.4 Hz, J = 6.7 Hz), 1.60 (s, 3H), 1.55 (s, 3H); ¹³C NMR (100 MHz, CDCl₃) δ 174.93, 171.87, 111.38, 70.35, 35.94, 26.71, 25.80; IR (TF) 3270, 3000, 2940, 1765, 1740, 1385 cm^-1; mp 380 - 382 K (lit. (Green et al., 1995) 388 - 390 K); [α]_D²⁹³ = +7.2 (0.93, CHCl₃) (lit. (Green et al., 1995) [α]_D²⁹⁵ = +6.9 (0.94, CHCl₃).

S3. Refinement

Data was collected to the collision limits of the Oxford Diffraction Gemini Ultra with Sapphire 3 detector. The carboxy hydrogen (H41) was located in a difference electron-density map and the isotropic atomic displacement parameters were refined independently. A riding model was used for the all other hydrogen atoms.

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2004); cell refinement: CrysAlis RED (Oxford Diffraction, 2004); data reduction: CrysAlis RED; program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

	Fig. 1. View of (I) (50% probability displacement ellipsoids).
	Fig. 2. A view of the packing of (I) and the helical hydrogen-bonded network.

(S)-(2,2-Dimethyl-5-oxo-1,3-dioxolan-4-yl)acetic acid

Crystal data

C7H10O5	F(000) = 184
Mr = 174.15	Dx = 1.455 Mg m^−3
Monoclinic, P21	Cu Kα radiation, λ = 1.54184 Å
Hall symbol: P 2yb	Cell parameters from 1522 reflections
a = 5.2406 (11) Å	θ = 4.4–57.7°
b = 7.8236 (14) Å	µ = 1.09 mm^−1
c = 9.718 (2) Å	T = 100 K
β = 94.20 (2)°	Prism, colourless
V = 397.37 (14) Å^3	0.28 × 0.19 × 0.12 mm
Z = 2

Data collection

Oxford Diffraction Gemini Ultra diffractometer	Rint = 0.041
φ and ω scans	θmax = 63.1°, θmin = 4.6°
Absorption correction: analytical (CrysAlis RED; Oxford Diffraction, 2004)	h = −6→6
Tmin = 0.762, Tmax = 0.891	k = −8→9
7654 measured reflections	l = −11→11
1262 independent reflections	2 standard reflections every 50 reflections
1213 reflections with I > 2σ(I)	intensity decay: <2

Refinement

Refinement on F^2	H atoms treated by a mixture of independent and constrained refinement
Least-squares matrix: full	w = 1/[σ^2(Fo^2) + (0.0398P)^2 + 0.0537P] where P = (Fo^2 + 2Fc^2)/3
R[F^2 > 2σ(F^2)] = 0.025	(Δ/σ)max < 0.001
wR(F^2) = 0.064	Δρmax = 0.14 e Å^−3
S = 1.13	Δρmin = −0.2 e Å^−3
1262 reflections	Absolute structure: Flack (1983), with 575 Friedel pairs
115 parameters	Absolute structure parameter: 0.00 (18)
1 restraint

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
C1	0.6680 (3)	0.1093 (2)	0.21710 (16)	0.0198 (3)
C2	0.9076 (3)	0.1467 (2)	0.30831 (18)	0.0192 (4)
H2	1.0549	0.0825	0.2736	0.023*
C3	0.8910 (3)	0.1093 (2)	0.46061 (15)	0.0205 (3)
H3A	0.8504	−0.0131	0.4729	0.025*
H3B	1.0587	0.1326	0.5108	0.025*
C4	0.6886 (3)	0.2171 (2)	0.52035 (17)	0.0195 (3)
C5	0.8131 (3)	0.3752 (2)	0.16201 (16)	0.0193 (3)
C6	0.9868 (3)	0.3752 (2)	0.04477 (16)	0.0245 (4)
H6A	1.1133	0.467	0.0589	0.037*
H6B	0.8849	0.3937	−0.0426	0.037*
H6C	1.075	0.265	0.0419	0.037*
C7	0.6774 (3)	0.5421 (2)	0.18230 (17)	0.0248 (4)
H7A	0.5539	0.5277	0.2525	0.037*
H7B	0.5871	0.5774	0.095	0.037*
H7C	0.8027	0.6298	0.2126	0.037*
O1	0.61925 (19)	0.24126 (16)	0.13314 (10)	0.0207 (3)
O2	0.5412 (2)	−0.02001 (15)	0.21109 (12)	0.0264 (3)
O3	0.4856 (2)	0.25122 (18)	0.45951 (10)	0.0276 (3)
O4	0.7556 (2)	0.26832 (15)	0.64876 (11)	0.0232 (3)
O5	0.9441 (2)	0.32571 (14)	0.28877 (12)	0.0201 (3)
H41	0.623 (5)	0.326 (3)	0.679 (2)	0.046 (7)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
C1	0.0251 (8)	0.0160 (8)	0.0188 (7)	−0.0001 (7)	0.0058 (6)	−0.0011 (6)
C2	0.0230 (7)	0.0129 (9)	0.0220 (8)	0.0007 (6)	0.0028 (6)	0.0007 (7)
C3	0.0229 (8)	0.0159 (8)	0.0224 (8)	0.0001 (7)	0.0008 (6)	0.0019 (6)
C4	0.0233 (8)	0.0136 (8)	0.0218 (7)	−0.0048 (6)	0.0027 (6)	0.0029 (6)
C5	0.0208 (7)	0.0146 (9)	0.0220 (8)	−0.0030 (6)	−0.0016 (6)	0.0011 (6)
C6	0.0264 (8)	0.0228 (9)	0.0241 (8)	−0.0001 (7)	0.0015 (7)	0.0005 (7)
C7	0.0299 (8)	0.0186 (9)	0.0257 (8)	0.0033 (7)	0.0013 (7)	0.0005 (7)
O1	0.0237 (6)	0.0172 (5)	0.0208 (5)	−0.0038 (5)	−0.0008 (4)	0.0017 (5)
O2	0.0357 (6)	0.0187 (6)	0.0249 (6)	−0.0088 (5)	0.0027 (5)	−0.0004 (5)
O3	0.0218 (6)	0.0343 (7)	0.0263 (6)	0.0046 (6)	−0.0001 (5)	−0.0022 (6)
O4	0.0263 (6)	0.0212 (7)	0.0220 (5)	0.0004 (5)	0.0015 (4)	−0.0034 (5)
O5	0.0242 (6)	0.0139 (6)	0.0214 (5)	−0.0028 (4)	−0.0030 (4)	0.0017 (4)

Geometric parameters (Å, º)

C1—O2	1.209 (2)	C5—O5	1.4196 (19)
C1—O1	1.329 (2)	C5—O1	1.4720 (19)
C1—C2	1.512 (2)	C5—C7	1.507 (2)
C2—O5	1.4281 (18)	C5—C6	1.510 (2)
C2—C3	1.518 (2)	C6—H6A	0.98
C2—H2	1	C6—H6B	0.98
C3—C4	1.505 (2)	C6—H6C	0.98
C3—H3A	0.99	C7—H7A	0.98
C3—H3B	0.99	C7—H7B	0.98
C4—O3	1.208 (2)	C7—H7C	0.98
C4—O4	1.333 (2)	O4—H41	0.89 (3)
O2—C1—O1	122.66 (14)	O1—C5—C7	108.44 (12)
O2—C1—C2	128.34 (15)	O5—C5—C6	112.02 (12)
O1—C1—C2	108.89 (13)	O1—C5—C6	107.58 (12)
O5—C2—C1	103.03 (14)	C7—C5—C6	114.54 (14)
O5—C2—C3	109.67 (14)	C5—C6—H6A	109.5
C1—C2—C3	115.47 (13)	C5—C6—H6B	109.5
O5—C2—H2	109.5	H6A—C6—H6B	109.5
C1—C2—H2	109.5	C5—C6—H6C	109.5
C3—C2—H2	109.5	H6A—C6—H6C	109.5
C4—C3—C2	111.14 (13)	H6B—C6—H6C	109.5
C4—C3—H3A	109.4	C5—C7—H7A	109.5
C2—C3—H3A	109.4	C5—C7—H7B	109.5
C4—C3—H3B	109.4	H7A—C7—H7B	109.5
C2—C3—H3B	109.4	C5—C7—H7C	109.5
H3A—C3—H3B	108	H7A—C7—H7C	109.5
O3—C4—O4	123.61 (16)	H7B—C7—H7C	109.5
O3—C4—C3	123.72 (15)	C1—O1—C5	109.70 (11)
O4—C4—C3	112.65 (13)	C4—O4—H41	107.5 (15)
O5—C5—O1	104.73 (12)	C5—O5—C2	108.79 (13)
O5—C5—C7	109.01 (12)
O2—C1—C2—O5	−169.91 (16)	C2—C1—O1—C5	−1.06 (17)
O1—C1—C2—O5	13.89 (17)	O5—C5—O1—C1	−12.36 (15)
O2—C1—C2—C3	−50.4 (2)	C7—C5—O1—C1	−128.64 (13)
O1—C1—C2—C3	133.42 (15)	C6—C5—O1—C1	106.97 (14)
O5—C2—C3—C4	54.09 (17)	O1—C5—O5—C2	21.49 (15)
C1—C2—C3—C4	−61.72 (19)	C7—C5—O5—C2	137.37 (14)
C2—C3—C4—O3	38.3 (2)	C6—C5—O5—C2	−94.81 (15)
C2—C3—C4—O4	−142.86 (14)	C1—C2—O5—C5	−21.72 (15)
O2—C1—O1—C5	−177.52 (14)	C3—C2—O5—C5	−145.19 (12)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O4—H41···O2^i	0.89 (3)	1.86 (3)	2.7067 (16)	156 (2)

Symmetry code: (i) −x+1, y+1/2, −z+1.