organic compounds
rac-tert-Butyl{2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}azanium acrylate
aSchool of Chemical Engineering and Environment, Henan University of Technology, Zhengzhou 450001, People's Republic of China
*Correspondence e-mail: wenjuliu@haut.edu.cn
The title salt, C13H22NO3+·C3H3O2−, comprises one salbutamol cation and an acrylate anion. The acrylate anion is linked to the salbutamol cation via an O—H⋯O and an N—H⋯O hydrogen bond. The C=C group of the acrylate anion is disordered over two positions, with refined site occupancies of 0.812 (7) and 0.188 (7). The is stabilized by N—H⋯O and O—H⋯O hydrogen-bonding interactions.
Keywords: crystal structure; salbutamole acrylate; hydrogen bonds.
CCDC reference: 1563663
Structure description
Salbutamol is known as a short-action selective β2-adrenergic receptor agonist for the treatment of pulmonary diseases (Saleh et al., 2000). However, due to its low dissolution in water, salbutamol is usually transformed into its salt form with some acids to improve its solubility. The title compound is a novel salt of salbutamol.
The . The compound comprises a protonated salbutamol cation and a deprotonated acrylic acid anion which are linked via an O—H⋯O and an N—H⋯O hydrogen bond, forming an R22(9) motif (Table 1 and Fig. 1). In the crystal, cations and anions are linked by O—H⋯(O,N) hydrogen bonds, forming a three-dimensional network (Fig. 2).
of the title compound is shown in Fig. 1Synthesis and crystallization
Salbutamol (0.479 g, 2 mmol) was reacted with acrylic acid (0.144 g, 2 mmol) in 10 ml methanol. The mixture was stirred and the methanol was evaporated at room temperature, yielding salbutamol acrylate. After recrystallization of the raw product from ethanol, the crystals were dissolved in ethanol and the solution was filtered. Finally, the solvent was evaporated slowly and single crystals suitable for the diffraction experiment were obtained.
Refinement
Crystal data, data collection and structure . The C=C group of the acrylate anion is disordered over two positions, with refined site occupancies of 0.812 (7) and 0.188 (7). Bond lengths and angles involving the disordered atoms were restrained to be equal. H atoms were refined using a riding model, with aromatic C—H = 0.93 Å, methyl C—H = 0.96 Å, methylene C—H = 0.97 Å and tertiary C—H = 0.98 Å. Uiso(H) values were set at 1.5Ueq(C,O) for methyl and hydroxy groups and at 1.2Ueq(C,N) for the remaining atoms. The torsion angles of the hydroxy and methyl groups were allowed to refine.
details are summarized in Table 2Structural data
CCDC reference: 1563663
https://doi.org/10.1107/S2414314617011890/bt4060sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314617011890/bt4060Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2414314617011890/bt4060Isup3.cml
Data collection: APEX2 (Bruker, 2015); cell
SAINT (Bruker, 2015); data reduction: SAINT (Bruker, 2015); program(s) used to solve structure: SHELXT (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015b); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009).C13H22NO3+·C3H3O2− | F(000) = 672 |
Mr = 311.37 | Dx = 1.248 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
a = 9.5304 (4) Å | Cell parameters from 9984 reflections |
b = 11.9927 (5) Å | θ = 2.7–27.5° |
c = 14.5120 (7) Å | µ = 0.09 mm−1 |
β = 91.815 (2)° | T = 295 K |
V = 1657.82 (13) Å3 | Block, colourless |
Z = 4 | 0.4 × 0.3 × 0.2 mm |
CCD area detector diffractometer | 3468 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.023 |
phi and ω scans | θmax = 27.6°, θmin = 3.3° |
Absorption correction: multi-scan (SADABS; Bruker, 2015) | h = −12→12 |
Tmin = 0.719, Tmax = 0.746 | k = −15→15 |
39441 measured reflections | l = −18→18 |
3825 independent reflections |
Refinement on F2 | Primary atom site location: dual |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.046 | H-atom parameters constrained |
wR(F2) = 0.125 | w = 1/[σ2(Fo2) + (0.0548P)2 + 0.7417P] where P = (Fo2 + 2Fc2)/3 |
S = 1.04 | (Δ/σ)max < 0.001 |
3825 reflections | Δρmax = 0.39 e Å−3 |
224 parameters | Δρmin = −0.27 e Å−3 |
3 restraints |
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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
O1 | 0.08955 (11) | 0.29361 (8) | 0.85654 (7) | 0.0385 (2) | |
H1 | 0.1603 | 0.2851 | 0.8894 | 0.058* | |
O2 | −0.03078 (10) | −0.00530 (8) | 0.73205 (7) | 0.0388 (2) | |
H2 | −0.0449 | −0.0630 | 0.7028 | 0.058* | |
O3 | 0.32888 (12) | 0.27262 (10) | 0.45673 (7) | 0.0466 (3) | |
H3 | 0.3638 | 0.3271 | 0.4321 | 0.070* | |
O4 | 0.44223 (13) | 0.45453 (9) | 0.37554 (8) | 0.0500 (3) | |
N1 | 0.60151 (11) | 0.33496 (9) | 0.54666 (7) | 0.0299 (2) | |
H1A | 0.5788 | 0.4020 | 0.5678 | 0.036* | |
H1B | 0.5899 | 0.3369 | 0.4856 | 0.036* | |
O5 | 0.61642 (17) | 0.33915 (13) | 0.35229 (10) | 0.0711 (4) | |
C3 | 0.06403 (12) | 0.05912 (10) | 0.68766 (8) | 0.0278 (3) | |
C7 | 0.19586 (13) | 0.22911 (11) | 0.68475 (9) | 0.0295 (3) | |
H7 | 0.2221 | 0.2964 | 0.7121 | 0.035* | |
C2 | 0.10425 (12) | 0.15933 (10) | 0.73002 (8) | 0.0268 (2) | |
C6 | 0.24953 (13) | 0.20124 (11) | 0.59972 (9) | 0.0299 (3) | |
C8 | 0.34961 (13) | 0.28039 (11) | 0.55336 (9) | 0.0322 (3) | |
H8 | 0.3288 | 0.3568 | 0.5727 | 0.039* | |
C4 | 0.11790 (14) | 0.02944 (11) | 0.60353 (9) | 0.0332 (3) | |
H4 | 0.0915 | −0.0377 | 0.5760 | 0.040* | |
C10 | 0.75646 (13) | 0.31554 (12) | 0.56937 (11) | 0.0372 (3) | |
C1 | 0.04384 (15) | 0.18869 (11) | 0.82191 (9) | 0.0336 (3) | |
H1C | −0.0578 | 0.1891 | 0.8155 | 0.040* | |
H1D | 0.0702 | 0.1313 | 0.8663 | 0.040* | |
C5 | 0.21116 (14) | 0.09956 (11) | 0.56033 (9) | 0.0342 (3) | |
H5 | 0.2484 | 0.0784 | 0.5045 | 0.041* | |
C14 | 0.54440 (18) | 0.42130 (13) | 0.32981 (10) | 0.0425 (3) | |
C9 | 0.49975 (14) | 0.25237 (12) | 0.58317 (10) | 0.0354 (3) | |
H9A | 0.5077 | 0.2514 | 0.6500 | 0.042* | |
H9B | 0.5230 | 0.1785 | 0.5611 | 0.042* | |
C13 | 0.83340 (17) | 0.41218 (16) | 0.52486 (14) | 0.0549 (4) | |
H13A | 0.8128 | 0.4124 | 0.4597 | 0.082* | |
H13B | 0.9327 | 0.4036 | 0.5358 | 0.082* | |
H13C | 0.8031 | 0.4813 | 0.5511 | 0.082* | |
C12 | 0.8007 (2) | 0.20572 (16) | 0.52759 (16) | 0.0609 (5) | |
H12A | 0.7579 | 0.1453 | 0.5598 | 0.091* | |
H12B | 0.9009 | 0.1988 | 0.5327 | 0.091* | |
H12C | 0.7711 | 0.2035 | 0.4638 | 0.091* | |
C11 | 0.78183 (17) | 0.31788 (17) | 0.67316 (12) | 0.0541 (4) | |
H11A | 0.7478 | 0.3870 | 0.6973 | 0.081* | |
H11B | 0.8806 | 0.3113 | 0.6872 | 0.081* | |
H11C | 0.7331 | 0.2568 | 0.7006 | 0.081* | |
C15 | 0.5977 (3) | 0.4841 (2) | 0.24830 (16) | 0.0471 (7) | 0.812 (7) |
H15 | 0.6919 | 0.4772 | 0.2345 | 0.057* | 0.812 (7) |
C16 | 0.5186 (4) | 0.5469 (3) | 0.19678 (19) | 0.0701 (9) | 0.812 (7) |
H16A | 0.4241 | 0.5550 | 0.2093 | 0.084* | 0.812 (7) |
H16B | 0.5561 | 0.5842 | 0.1470 | 0.084* | 0.812 (7) |
C15A | 0.5151 (15) | 0.4941 (9) | 0.2405 (6) | 0.053 (3) | 0.188 (7) |
H15A | 0.4254 | 0.5194 | 0.2243 | 0.064* | 0.188 (7) |
C16A | 0.6210 (14) | 0.5165 (11) | 0.1918 (8) | 0.069 (4) | 0.188 (7) |
H16C | 0.7095 | 0.4902 | 0.2096 | 0.083* | 0.188 (7) |
H16D | 0.6094 | 0.5591 | 0.1385 | 0.083* | 0.188 (7) |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.0476 (6) | 0.0325 (5) | 0.0349 (5) | 0.0089 (4) | −0.0042 (4) | −0.0048 (4) |
O2 | 0.0392 (5) | 0.0306 (5) | 0.0473 (6) | −0.0095 (4) | 0.0115 (4) | 0.0010 (4) |
O3 | 0.0444 (6) | 0.0602 (7) | 0.0349 (5) | −0.0197 (5) | −0.0041 (4) | 0.0119 (5) |
O4 | 0.0610 (7) | 0.0387 (6) | 0.0514 (6) | 0.0049 (5) | 0.0162 (5) | 0.0048 (5) |
N1 | 0.0262 (5) | 0.0284 (5) | 0.0351 (5) | −0.0015 (4) | 0.0023 (4) | 0.0035 (4) |
O5 | 0.0847 (10) | 0.0674 (9) | 0.0627 (8) | 0.0246 (8) | 0.0264 (7) | 0.0068 (7) |
C3 | 0.0244 (5) | 0.0245 (5) | 0.0345 (6) | 0.0000 (4) | 0.0020 (4) | 0.0036 (5) |
C7 | 0.0291 (6) | 0.0276 (6) | 0.0317 (6) | −0.0040 (5) | −0.0005 (5) | −0.0014 (5) |
C2 | 0.0255 (5) | 0.0270 (6) | 0.0280 (6) | 0.0019 (4) | −0.0003 (4) | 0.0017 (4) |
C6 | 0.0255 (5) | 0.0315 (6) | 0.0328 (6) | −0.0028 (5) | 0.0015 (4) | 0.0029 (5) |
C8 | 0.0300 (6) | 0.0328 (6) | 0.0338 (6) | −0.0043 (5) | 0.0027 (5) | 0.0038 (5) |
C4 | 0.0361 (6) | 0.0258 (6) | 0.0378 (7) | −0.0017 (5) | 0.0033 (5) | −0.0043 (5) |
C10 | 0.0246 (6) | 0.0370 (7) | 0.0503 (8) | 0.0012 (5) | 0.0041 (5) | −0.0020 (6) |
C1 | 0.0387 (7) | 0.0324 (6) | 0.0299 (6) | 0.0015 (5) | 0.0039 (5) | 0.0014 (5) |
C5 | 0.0359 (6) | 0.0347 (7) | 0.0322 (6) | −0.0006 (5) | 0.0069 (5) | −0.0035 (5) |
C14 | 0.0602 (9) | 0.0360 (7) | 0.0318 (7) | −0.0045 (6) | 0.0101 (6) | −0.0046 (5) |
C9 | 0.0301 (6) | 0.0338 (7) | 0.0421 (7) | −0.0056 (5) | −0.0003 (5) | 0.0092 (5) |
C13 | 0.0365 (8) | 0.0535 (10) | 0.0755 (12) | −0.0114 (7) | 0.0156 (8) | 0.0007 (8) |
C12 | 0.0475 (9) | 0.0467 (9) | 0.0888 (14) | 0.0142 (7) | 0.0091 (9) | −0.0114 (9) |
C11 | 0.0361 (8) | 0.0702 (11) | 0.0554 (10) | 0.0000 (8) | −0.0105 (7) | 0.0037 (8) |
C15 | 0.0484 (14) | 0.0491 (12) | 0.0446 (13) | −0.0059 (11) | 0.0156 (10) | −0.0001 (9) |
C16 | 0.086 (2) | 0.0770 (18) | 0.0488 (14) | 0.0114 (15) | 0.0205 (13) | 0.0207 (14) |
C15A | 0.067 (8) | 0.059 (6) | 0.034 (5) | 0.020 (5) | 0.023 (5) | 0.015 (4) |
C16A | 0.078 (9) | 0.075 (8) | 0.055 (7) | −0.019 (7) | 0.009 (6) | 0.019 (6) |
O1—H1 | 0.8200 | C10—C11 | 1.518 (2) |
O1—C1 | 1.4183 (16) | C1—H1C | 0.9700 |
O2—H2 | 0.8200 | C1—H1D | 0.9700 |
O2—C3 | 1.3656 (14) | C5—H5 | 0.9300 |
O3—H3 | 0.8200 | C14—C15 | 1.504 (3) |
O3—C8 | 1.4130 (16) | C14—C15A | 1.580 (10) |
O4—C14 | 1.2602 (19) | C9—H9A | 0.9700 |
N1—H1A | 0.8900 | C9—H9B | 0.9700 |
N1—H1B | 0.8900 | C13—H13A | 0.9600 |
N1—C10 | 1.5208 (16) | C13—H13B | 0.9600 |
N1—C9 | 1.4950 (16) | C13—H13C | 0.9600 |
O5—C14 | 1.238 (2) | C12—H12A | 0.9600 |
C3—C2 | 1.3979 (17) | C12—H12B | 0.9600 |
C3—C4 | 1.3858 (18) | C12—H12C | 0.9600 |
C7—H7 | 0.9300 | C11—H11A | 0.9600 |
C7—C2 | 1.3895 (17) | C11—H11B | 0.9600 |
C7—C6 | 1.3914 (18) | C11—H11C | 0.9600 |
C2—C1 | 1.5108 (17) | C15—H15 | 0.9300 |
C6—C8 | 1.5179 (17) | C15—C16 | 1.288 (4) |
C6—C5 | 1.3908 (18) | C16—H16A | 0.9300 |
C8—H8 | 0.9800 | C16—H16B | 0.9300 |
C8—C9 | 1.5193 (18) | C15A—H15A | 0.9300 |
C4—H4 | 0.9300 | C15A—C16A | 1.279 (14) |
C4—C5 | 1.3876 (19) | C16A—H16C | 0.9300 |
C10—C13 | 1.526 (2) | C16A—H16D | 0.9300 |
C10—C12 | 1.515 (2) | ||
C1—O1—H1 | 109.5 | C4—C5—C6 | 120.62 (12) |
C3—O2—H2 | 109.5 | C4—C5—H5 | 119.7 |
C8—O3—H3 | 109.5 | O4—C14—C15 | 122.80 (17) |
H1A—N1—H1B | 107.2 | O4—C14—C15A | 97.9 (4) |
C10—N1—H1A | 108.0 | O5—C14—O4 | 122.95 (14) |
C10—N1—H1B | 108.0 | O5—C14—C15 | 114.02 (17) |
C9—N1—H1A | 108.0 | O5—C14—C15A | 137.5 (4) |
C9—N1—H1B | 108.0 | N1—C9—C8 | 111.61 (11) |
C9—N1—C10 | 117.27 (10) | N1—C9—H9A | 109.3 |
O2—C3—C2 | 117.08 (11) | N1—C9—H9B | 109.3 |
O2—C3—C4 | 122.65 (11) | C8—C9—H9A | 109.3 |
C4—C3—C2 | 120.27 (11) | C8—C9—H9B | 109.3 |
C2—C7—H7 | 119.0 | H9A—C9—H9B | 108.0 |
C2—C7—C6 | 121.92 (11) | C10—C13—H13A | 109.5 |
C6—C7—H7 | 119.0 | C10—C13—H13B | 109.5 |
C3—C2—C1 | 118.80 (11) | C10—C13—H13C | 109.5 |
C7—C2—C3 | 118.53 (11) | H13A—C13—H13B | 109.5 |
C7—C2—C1 | 122.66 (11) | H13A—C13—H13C | 109.5 |
C7—C6—C8 | 119.78 (11) | H13B—C13—H13C | 109.5 |
C5—C6—C7 | 118.42 (11) | C10—C12—H12A | 109.5 |
C5—C6—C8 | 121.79 (11) | C10—C12—H12B | 109.5 |
O3—C8—C6 | 109.18 (10) | C10—C12—H12C | 109.5 |
O3—C8—H8 | 108.8 | H12A—C12—H12B | 109.5 |
O3—C8—C9 | 111.64 (11) | H12A—C12—H12C | 109.5 |
C6—C8—H8 | 108.8 | H12B—C12—H12C | 109.5 |
C6—C8—C9 | 109.56 (11) | C10—C11—H11A | 109.5 |
C9—C8—H8 | 108.8 | C10—C11—H11B | 109.5 |
C3—C4—H4 | 119.9 | C10—C11—H11C | 109.5 |
C3—C4—C5 | 120.19 (12) | H11A—C11—H11B | 109.5 |
C5—C4—H4 | 119.9 | H11A—C11—H11C | 109.5 |
N1—C10—C13 | 105.57 (12) | H11B—C11—H11C | 109.5 |
C12—C10—N1 | 109.07 (12) | C14—C15—H15 | 118.5 |
C12—C10—C13 | 110.33 (14) | C16—C15—C14 | 122.9 (3) |
C12—C10—C11 | 112.05 (15) | C16—C15—H15 | 118.5 |
C11—C10—N1 | 109.59 (11) | C15—C16—H16A | 120.0 |
C11—C10—C13 | 110.03 (14) | C15—C16—H16B | 120.0 |
O1—C1—C2 | 113.46 (11) | H16A—C16—H16B | 120.0 |
O1—C1—H1C | 108.9 | C14—C15A—H15A | 121.7 |
O1—C1—H1D | 108.9 | C16A—C15A—C14 | 116.6 (12) |
C2—C1—H1C | 108.9 | C16A—C15A—H15A | 121.7 |
C2—C1—H1D | 108.9 | C15A—C16A—H16C | 120.0 |
H1C—C1—H1D | 107.7 | C15A—C16A—H16D | 120.0 |
C6—C5—H5 | 119.7 | H16C—C16A—H16D | 120.0 |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O3i | 0.82 | 1.98 | 2.7817 (14) | 166 |
O2—H2···O1ii | 0.82 | 1.96 | 2.7816 (14) | 174 |
O3—H3···O4 | 0.82 | 1.90 | 2.7194 (15) | 179 |
N1—H1A···O4iii | 0.89 | 1.92 | 2.8022 (16) | 171 |
N1—H1B···O5 | 0.89 | 1.96 | 2.8292 (18) | 166 |
Symmetry codes: (i) x, −y+1/2, z+1/2; (ii) −x, y−1/2, −z+3/2; (iii) −x+1, −y+1, −z+1. |
Funding information
Funding for this research was provided by: National Nature and Science Foundation of China (award No. 21206032); Science Foundation Henan University of Technology (award Nos. 2017RCJH09, 2017QNJH29); Science Foundation of Henan Province (award No. 2015GGJS-039).
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