rac-Hy­droxy­isovaleric acid

Dasi, L.; Hosten, E.C.; Betz, R.

doi:10.1107/S2414314623010933

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 9| Part 1| January 2024| x231093

https://doi.org/10.1107/S2414314623010933

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rac-Hydroxyisovaleric acid

Lukhanyo Dasi,^a Eric Cyriel Hosten ^a and Richard Betz ^a ^*

^aNelson Mandela University, Summerstrand Campus, Department of Chemistry, University Way, Summerstrand, PO Box 77000, Port Elizabeth, 6031, South Africa
^*Correspondence e-mail: richard.betz@mandela.ac.za

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 19 December 2023; accepted 20 December 2023; online 5 January 2024)

This article is part of a collection of articles to commemorate the founding of the African Crystallographic Association and the 75th anniversary of the IUCr.

The title compound (systematic name: rac-2-hydroxy-3-methylbutanoic acid), C₅H₁₀O₃, is the constitutional isomer of α-hydroxybutanoic acid. In the crystal, hydrogen bonds involving the alcoholic hydroxyl group give rise to centrosymmetric dimers that are extended to sheets perpendicular to the crystallographic c axis.

Keywords: crystal structure; hydrogen bonding; hydroxycarboxylic acids.

CCDC reference: 2320961

Structure description

The Krebs Cycle – also known as Citric Acid Cycle – is at the centre of metabolic processes in aerobic organisms. It involves a number of hydroxycarboxylic acids that constitute intriguing chelating ligands for a variety of transition metals of pharmaceutical interest (McMurry, 2008 ). These potential ligands classify as chelate ligands, which have found widespread use in coordination chemistry due to the increased stability of coordination compounds they can form in comparison to monodentate ligands (Gade, 1998 ). Hydroxycarboxylic acids are a particularly interesting class of ligands as they offer two functional groups that, depending on the experimental conditions, can either act as fully neutral, fully anionic or mixed neutral-anionic donors. Upon varying the substitution pattern on the hydrocarbon backbone, the acidity of the respective hydroxyl groups can be fine-tuned over a wide range and they may, thus, serve as probes for establishing the rules in which pK_a range coordination to various central atoms can be observed. Furthermore, the steric pretence of potential substituents may give rise to unique coordination and bonding patterns. Given the multidentate nature of hydroxycarboxylic acids encountered in the Krebs Cycle it appears prudent to investigate simpler `cut outs' with a more limited number of donor sites to avoid complexer mixtures of reaction products in envisioned synthesis procedures, thus prompting the diffraction study of the title compound to allow for comparisons of metrical parameters of the free ligand and the ligand in envisioned coordination compounds. The present study falls into the ambit of our continued interest into structural aspects of alpha-hydroxycarboxylic acids such as 1-hydroxycyclopropanecarboxylic acid (Betz & Klüfers, 2007a ), 1-hydroxycyclobutanecarboxylic acid (Betz & Klüfers, 2007b ), 1-hydroxycyclopentanecarboxylic acid (Betz & Klüfers, 2007c ) or tert-butylglycolic acid (Betz et al., 2007 ). Furthermore, geometrical data for glycolic acid (Ellison et al., 1971 ; Pijper, 1971 ) and L-lactic acid (Schouten et al., 1994 ; Yang et al., 2021 ) is apparent in the literature while, to the best of our knowledge, none of the various hydroxy-n-butanoic acids have been subjected to diffraction studies. Only one report provides the crystal and molecular structure for gamma-hydroxybutanoic acid as a solvent molecule in a barium-supported tetraphenylimidodiphosphinato compound (Morales-Juarez et al., 2005 ).

The asymmetric unit of the title compound is shown in Fig. 1 and contains one complete molecule. C—O bond lengths are found to be 1.4175 (11) Å for the alcoholic hydroxyl group and 1.2064 (12) and 1.3143 (11) Å for the carboxylic acid group and, thus, lie in the normal range reported for other hydroxycarboxylic acids whose metrical parameters have been deposited with the Cambridge Structural Database (Groom et al., 2016 ). The alcoholic hydroxy group adopts a staggered conformation relative to the two terminal methyl groups with the relevant C—C—C—O torsional angles measuring −58.32 (11) and 66.60 (12)°.

Figure 1
The molecular structure of the title compound, with atom labels and anisotropic displacement ellipsoids (drawn at 50% probability level).

In the crystal, classical hydrogen bonds of the O—H⋯O type (Table 1) are apparent that involve all hydroxyl groups as donors and the oxygen atom of the alcoholic hydroxyl group and the carbonyl oxygen atom as acceptors. The hydrogen bonds supported by the alcoholic hydroxyl group as donor and the carbonyl oxygen atom as acceptor connect the individual molecules into centrosymmetric dimers, which are further extended to sheets perpendicular to the crystallographic c axis by means of the carboxylic acid's hydroxyl group as donor and the alcoholic hydroxyl group's oxygen atom as acceptor. In terms of graph-set analysis (Etter et al., 1990 ; Bernstein et al., 1995 ), the descriptor for these hydrogen bonds is C₁¹(5) R₂²(10) on the unary level. A depiction of the hydrogen-bonding pattern is shown in Fig. 2.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1—H1A⋯O3ⁱ	0.84	1.78	2.6143 (9)	169
O3—H3A⋯O2	0.84	2.32	2.7069 (10)	108
O3—H3A⋯O2ⁱⁱ	0.84	2.00	2.7597 (11)	150
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]$ ; (ii) .

Figure 2
Intermolecular hydrogen bonds (dotted blue lines), viewed along [001].

Synthesis and crystallization

The compound was obtained commercially (Fluka). Crystals suitable for the diffraction studies were taken directly from the provided material.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₅H₁₀O₃
M_r	118.13
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	200
a, b, c (Å)	10.9589 (4), 9.3280 (4), 12.7255 (6)
V (Å³)	1300.86 (10)
Z	8
Radiation type	Mo Kα
μ (mm⁻¹)	0.10
Crystal size (mm)	0.60 × 0.51 × 0.35

Data collection
Diffractometer	Bruker (2010 ) APEXII CCD
Absorption correction	Numerical (SADABS, Krause et al., 2015 )
T_min, T_max	0.928, 0.990
No. of measured, independent and observed [I > 2σ(I)] reflections	10603, 1620, 1366
R_int	0.017
(sin θ/λ)_max (Å⁻¹)	0.669

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.035, 0.107, 1.05
No. of reflections	1620
No. of parameters	79
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.35, −0.15
Computer programs: APEX2 and SAINT (Bruker, 2010), SHELXS97, SHELXL97 and SHELXTL (Sheldrick, 2008 )SHELXTL (Sheldrick, 2008), PLATON (Spek, 2020 ) and Mercury (Macrae et al., 2020 ).

Structural data

CCDC reference: 2320961

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314623010933/bt4145sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314623010933/bt4145Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314623010933/bt4145Isup3.cml

checkCIF report

Computing details top

rac-2-Hydroxy-3-methylbutanoic acid top

Crystal data top

C₅H₁₀O₃	D_x = 1.206 Mg m⁻³
M_r = 118.13	Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, Pbca	Cell parameters from 4732 reflections
a = 10.9589 (4) Å	θ = 3.2–28.1°
b = 9.3280 (4) Å	µ = 0.10 mm⁻¹
c = 12.7255 (6) Å	T = 200 K
V = 1300.86 (10) Å³	Blocks, colourless
Z = 8	0.60 × 0.51 × 0.35 mm
F(000) = 512

Data collection top

Bruker (2010) APEXII CCD diffractometer	1620 independent reflections
Radiation source: sealed tube	1366 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.017
φ and ω scans	θ_max = 28.4°, θ_min = 3.2°
Absorption correction: numerical (SADABS, Krause et al., 2015)	h = −11→14
T_min = 0.928, T_max = 0.990	k = −12→12
10603 measured reflections	l = −16→16

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)] = 0.035	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.107	H-atom parameters constrained
S = 1.05	w = 1/[σ²(F_o²) + (0.0586P)² + 0.2192P] where P = (F_o² + 2F_c²)/3
1620 reflections	(Δ/σ)_max < 0.001
79 parameters	Δρ_max = 0.35 e Å⁻³
0 restraints	Δρ_min = −0.15 e Å⁻³

Special details top

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.

Refinement. The carbon-bound H atom of the methine group was placed in a calculated position1 (C–H 1.00 Å) and was included in the refinement in the riding model approximation, with U(H) set to 1.2U_eq(C).

The H atoms of the methyl groups were allowed to rotate with a fixed angle around the C–C bond to best fit the experimental electron density (HFIX 137 in the SHELX program suite (Sheldrick, 2008)), with U(H) set to 1.5U_eq(C).

The H atoms of the hydroxyl groups were allowed to rotate with a fixed angle around the C–C bond to best fit the experimental electron density (HFIX 147 in the SHELX program suite (Sheldrick, 2008)), with U(H) set to 1.5U_eq(O).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.62325 (6)	0.36594 (8)	0.47438 (7)	0.0378 (2)
H1A	0.695518	0.348157	0.492101	0.066 (5)*
O2	0.59660 (8)	0.13436 (8)	0.51070 (8)	0.0464 (3)
O3	0.35374 (6)	0.15502 (8)	0.47493 (7)	0.0341 (2)
H3A	0.394355	0.078645	0.474626	0.049 (4)*
C1	0.55798 (9)	0.24797 (10)	0.47994 (8)	0.0288 (2)
C2	0.42861 (8)	0.26994 (9)	0.44097 (8)	0.0266 (2)
H2	0.396479	0.360413	0.472773	0.032*
C3	0.42813 (9)	0.28752 (12)	0.32116 (8)	0.0379 (3)
H3	0.486954	0.365679	0.303082	0.046*
C4	0.47104 (15)	0.15122 (17)	0.26654 (11)	0.0592 (4)
H4A	0.472586	0.166730	0.190382	0.089*
H4B	0.414942	0.072567	0.283046	0.089*
H4C	0.553206	0.126684	0.291045	0.089*
C5	0.30193 (13)	0.3343 (2)	0.28387 (12)	0.0647 (4)
H5A	0.303823	0.351007	0.207865	0.097*
H5B	0.278457	0.422888	0.319944	0.097*
H5C	0.242457	0.258894	0.299861	0.097*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0214 (3)	0.0242 (4)	0.0678 (5)	−0.0016 (3)	−0.0083 (3)	0.0040 (3)
O2	0.0317 (4)	0.0245 (4)	0.0830 (6)	0.0016 (3)	−0.0136 (4)	0.0091 (4)
O3	0.0187 (3)	0.0242 (4)	0.0593 (5)	0.0019 (2)	0.0065 (3)	0.0076 (3)
C1	0.0218 (4)	0.0216 (4)	0.0431 (5)	0.0010 (3)	−0.0013 (4)	−0.0008 (3)
C2	0.0192 (4)	0.0190 (4)	0.0417 (5)	0.0006 (3)	0.0001 (4)	0.0004 (3)
C3	0.0299 (5)	0.0418 (6)	0.0421 (6)	−0.0069 (4)	−0.0015 (4)	0.0056 (4)
C4	0.0572 (8)	0.0690 (9)	0.0514 (7)	−0.0101 (7)	0.0171 (6)	−0.0167 (6)
C5	0.0441 (7)	0.0949 (12)	0.0550 (7)	0.0007 (7)	−0.0172 (6)	0.0153 (7)

Geometric parameters (Å, º) top

O1—C1	1.3143 (11)	C3—C5	1.5257 (17)
O1—H1A	0.8400	C3—H3	1.0000
O2—C1	1.2064 (12)	C4—H4A	0.9800
O3—C2	1.4175 (11)	C4—H4B	0.9800
O3—H3A	0.8400	C4—H4C	0.9800
C1—C2	1.5159 (13)	C5—H5A	0.9800
C2—C3	1.5334 (14)	C5—H5B	0.9800
C2—H2	1.0000	C5—H5C	0.9800
C3—C4	1.5234 (18)

C1—O1—H1A	109.5	C5—C3—H3	107.7
C2—O3—H3A	109.5	C2—C3—H3	107.7
O2—C1—O1	124.19 (9)	C3—C4—H4A	109.5
O2—C1—C2	123.57 (9)	C3—C4—H4B	109.5
O1—C1—C2	112.22 (8)	H4A—C4—H4B	109.5
O3—C2—C1	109.83 (7)	C3—C4—H4C	109.5
O3—C2—C3	112.46 (8)	H4A—C4—H4C	109.5
C1—C2—C3	110.06 (8)	H4B—C4—H4C	109.5
O3—C2—H2	108.1	C3—C5—H5A	109.5
C1—C2—H2	108.1	C3—C5—H5B	109.5
C3—C2—H2	108.1	H5A—C5—H5B	109.5
C4—C3—C5	112.11 (12)	C3—C5—H5C	109.5
C4—C3—C2	111.31 (10)	H5A—C5—H5C	109.5
C5—C3—C2	110.05 (9)	H5B—C5—H5C	109.5
C4—C3—H3	107.7

O2—C1—C2—O3	17.39 (14)	O3—C2—C3—C4	−58.32 (11)
O1—C1—C2—O3	−163.81 (8)	C1—C2—C3—C4	64.49 (11)
O2—C1—C2—C3	−106.95 (12)	O3—C2—C3—C5	66.60 (12)
O1—C1—C2—C3	71.85 (10)	C1—C2—C3—C5	−170.59 (10)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
O1—H1A···O3ⁱ	0.84	1.78	2.6143 (9)	169
O3—H3A···O2	0.84	2.32	2.7069 (10)	108
O3—H3A···O2ⁱⁱ	0.84	2.00	2.7597 (11)	150

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

Acknowledgements

The authors thank Mrs Alida Gerryts for useful discussions.

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