Crystal structure of isopropyl 2-hy­droxy-2-phenyl­acetate: a pharmacopoeia reference standard

The title compound is a pharmacopoeia reference standard for determining impurities in the drug Pregabalin, used for the treatment of epilepsy and diabetic neuropathic pain.

Key indicators

• Single-crystal X-ray study
• T = 100 K
• Mean [sigma](C-C) = 0.007 Å
• R factor = 0.090
• wR factor = 0.255
• Data-to-parameter ratio = 13.3

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds ...............     0.0073 Ang.
PLAT414_ALERT_2_C Short Intra D-H..H-X       H1O    ..  H7      ..       1.95 Ang.
PLAT761_ALERT_1_C CIF Contains no X-H Bonds ......................     Please Check
PLAT762_ALERT_1_C CIF Contains no X-Y-H or H-Y-H Angles ..........     Please Check
PLAT906_ALERT_3_C Large K value in the Analysis of Variance ......     21.488 Check
PLAT906_ALERT_3_C Large K value in the Analysis of Variance ......      4.128 Check
PLAT911_ALERT_3_C Missing # FCF Refl Between THmin & STh/L=  0.594         19 Report
PLAT934_ALERT_3_C Number of (Iobs-Icalc)/SigmaW > 10 Outliers ....          1 Check
PLAT978_ALERT_2_C Number C-C Bonds with Positive Residual Density.          0 Note

Alert level G
PLAT072_ALERT_2_G SHELXL First  Parameter in WGHT  Unusually Large       0.10 Report
PLAT793_ALERT_4_G The Model has Chirality at C7      (Centro SPGR)          R Verify
PLAT910_ALERT_3_G Missing # of FCF Reflection(s) Below Theta(Min)           3 Note
PLAT961_ALERT_5_G Dataset Contains no Negative Intensities .......     Please Check

   0 ALERT level A = Most likely a serious problem - resolve or explain
   0 ALERT level B = A potentially serious problem, consider carefully
   9 ALERT level C = Check. Ensure it is not caused by an omission or oversight
   4 ALERT level G = General information/check it is not something unexpected

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

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Computing details

Data collection: CrysAlis CCD (Agilent, 2012); cell refinement: CrysAlis CCD (Agilent, 2012); data reduction: CrysAlis RED (Agilent, 2012); program(s) used to solve structure: SHELXS2014 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2008); software used to prepare material for publication: SHELXL2014 (Sheldrick, 2015), PLATON (Spek, 2009) and publCIF (Westrip, 2010).

Isopropyl 2-hydroxy-2-phenylacetate

Crystal data

C11H14O3	F(000) = 416
Mr = 194.22	Dx = 1.278 Mg m^−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 11.872 (3) Å	Cell parameters from 403 reflections
b = 15.165 (4) Å	θ = 4.3–21.1°
c = 5.6079 (11) Å	µ = 0.09 mm^−1
β = 91.41 (2)°	T = 100 K
V = 1009.3 (4) Å^3	Needle, colourless
Z = 4	0.20 × 0.08 × 0.06 mm

Data collection

Agilent Xcalibur Sapphire3 diffractometer	1761 independent reflections
Radiation source: Enhance (Mo) X-ray Source	922 reflections with I > 2σ(I)
Detector resolution: 16.1827 pixels mm^-1	Rint = 0.101
ω–scan	θmax = 25.0°, θmin = 3.2°
Absorption correction: multi-scan (CrysAlis RED; Agilent, 2012)	h = −14→13
Tmin = 0.357, Tmax = 1.000	k = −17→18
5292 measured reflections	l = −5→6

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.090	Hydrogen site location: difference Fourier map
wR(F^2) = 0.255	H atoms treated by a mixture of independent and constrained refinement
S = 1.03	w = 1/[σ^2(Fo^2) + (0.1022P)^2] where P = (Fo^2 + 2Fc^2)/3
1761 reflections	(Δ/σ)max < 0.001
132 parameters	Δρmax = 0.30 e Å^−3
0 restraints	Δρmin = −0.26 e Å^−3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.

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

	x	y	z	Uiso*/Ueq
O1	0.8289 (3)	0.2748 (2)	0.4019 (6)	0.0456 (10)
H1O	0.845 (4)	0.252 (4)	0.534 (10)	0.068*
O2	0.8740 (3)	0.4013 (2)	0.0966 (6)	0.0476 (11)
O3	0.8375 (3)	0.5068 (2)	0.3667 (6)	0.0455 (10)
C1	0.5984 (5)	0.3361 (3)	0.3003 (9)	0.0443 (14)
H1	0.6314	0.3108	0.1638	0.053*
C2	0.4827 (5)	0.3407 (3)	0.3113 (9)	0.0479 (14)
H2	0.4368	0.3171	0.1856	0.057*
C3	0.4332 (5)	0.3801 (3)	0.5079 (9)	0.0492 (15)
H3	0.3535	0.3852	0.5142	0.059*
C4	0.4998 (5)	0.4111 (3)	0.6910 (9)	0.0467 (14)
H4	0.4658	0.4367	0.8262	0.056*
C5	0.6154 (5)	0.4061 (3)	0.6831 (9)	0.0419 (13)
H5	0.6600	0.4286	0.8122	0.050*
C6	0.6684 (4)	0.3679 (3)	0.4857 (8)	0.0387 (13)
C7	0.7937 (4)	0.3603 (3)	0.4744 (8)	0.0403 (13)
H7	0.8283	0.3743	0.6343	0.048*
C8	0.8399 (4)	0.4230 (3)	0.2895 (9)	0.0416 (13)
C9	0.8869 (5)	0.5744 (3)	0.2113 (9)	0.0452 (14)
H9	0.9599	0.5521	0.1494	0.054*
C10	0.8087 (5)	0.5957 (4)	0.0050 (9)	0.0565 (16)
H10A	0.7346	0.6120	0.0649	0.085*
H10B	0.8009	0.5440	−0.0989	0.085*
H10C	0.8394	0.6451	−0.0856	0.085*
C11	0.9094 (5)	0.6527 (3)	0.3724 (9)	0.0528 (15)
H11A	0.9489	0.6329	0.5183	0.079*
H11B	0.8378	0.6802	0.4136	0.079*
H11C	0.9562	0.6956	0.2897	0.079*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.074 (3)	0.030 (2)	0.0327 (19)	0.0060 (18)	0.0021 (18)	0.0017 (15)
O2	0.074 (3)	0.040 (2)	0.0298 (19)	−0.0036 (18)	0.0078 (18)	−0.0039 (15)
O3	0.068 (3)	0.035 (2)	0.0337 (19)	−0.0031 (18)	0.0107 (17)	−0.0007 (15)
C1	0.062 (4)	0.039 (3)	0.031 (3)	0.000 (3)	−0.003 (2)	0.003 (2)
C2	0.064 (4)	0.042 (3)	0.038 (3)	−0.001 (3)	−0.003 (3)	0.005 (2)
C3	0.055 (4)	0.046 (3)	0.047 (3)	−0.001 (3)	−0.001 (3)	0.009 (3)
C4	0.063 (4)	0.036 (3)	0.041 (3)	0.004 (3)	0.010 (3)	0.001 (2)
C5	0.065 (4)	0.027 (3)	0.033 (3)	−0.004 (3)	0.001 (2)	0.003 (2)
C6	0.055 (4)	0.033 (3)	0.029 (3)	−0.004 (2)	0.003 (2)	0.003 (2)
C7	0.060 (4)	0.031 (3)	0.030 (3)	−0.001 (3)	0.003 (2)	−0.004 (2)
C8	0.055 (4)	0.034 (3)	0.036 (3)	−0.002 (3)	−0.003 (2)	−0.002 (2)
C9	0.061 (4)	0.038 (3)	0.037 (3)	−0.006 (3)	0.012 (2)	0.001 (2)
C10	0.081 (4)	0.051 (4)	0.038 (3)	−0.015 (3)	0.001 (3)	0.010 (3)
C11	0.074 (4)	0.039 (3)	0.045 (3)	−0.008 (3)	0.002 (3)	−0.001 (2)

Geometric parameters (Å, º)

O1—C7	1.424 (6)	C3—C4	1.364 (8)
O2—C8	1.211 (5)	C4—C5	1.376 (8)
O3—C8	1.343 (6)	C5—C6	1.412 (7)
O3—C9	1.476 (6)	C6—C7	1.495 (7)
C1—C2	1.378 (7)	C7—C8	1.519 (7)
C1—C6	1.401 (7)	C9—C10	1.501 (8)
C2—C3	1.397 (7)	C9—C11	1.512 (7)
C8—O3—C9	117.1 (4)	O1—C7—C6	112.4 (4)
C2—C1—C6	121.6 (5)	O1—C7—C8	105.2 (4)
C1—C2—C3	119.8 (5)	C6—C7—C8	110.9 (4)
C4—C3—C2	119.6 (6)	O2—C8—O3	123.8 (5)
C3—C4—C5	121.1 (5)	O2—C8—C7	125.0 (4)
C4—C5—C6	120.8 (5)	O3—C8—C7	111.2 (4)
C1—C6—C5	117.0 (5)	O3—C9—C10	111.0 (4)
C1—C6—C7	121.0 (5)	O3—C9—C11	105.0 (4)
C5—C6—C7	121.9 (5)	C10—C9—C11	112.9 (5)
C6—C1—C2—C3	1.9 (8)	C1—C6—C7—C8	71.2 (6)
C1—C2—C3—C4	−2.1 (8)	C5—C6—C7—C8	−109.5 (5)
C2—C3—C4—C5	1.4 (8)	C9—O3—C8—O2	−4.3 (8)
C3—C4—C5—C6	−0.5 (7)	C9—O3—C8—C7	176.1 (4)
C2—C1—C6—C5	−0.9 (7)	O1—C7—C8—O2	15.9 (7)
C2—C1—C6—C7	178.4 (5)	C6—C7—C8—O2	−105.9 (6)
C4—C5—C6—C1	0.2 (7)	O1—C7—C8—O3	−164.5 (4)
C4—C5—C6—C7	−179.1 (4)	C6—C7—C8—O3	73.7 (5)
C1—C6—C7—O1	−46.2 (6)	C8—O3—C9—C10	76.8 (6)
C5—C6—C7—O1	133.0 (5)	C8—O3—C9—C11	−160.9 (5)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1O···O1^i	0.83 (6)	2.12 (5)	2.903 (2)	158 (5)
O1—H1O···O2^i	0.83 (6)	2.38 (6)	2.930 (5)	124 (5)
C9—H9···O2^ii	1.00	2.53	3.379 (7)	142

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