rac-tert-But­yl{2-hy­droxy-2-[4-hy­droxy-3-(hy­droxy­meth­yl)phen­yl]eth­yl}aza­nium acrylate

Liu, W.; Yu, L.

doi:10.1107/S2414314617011890

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 2| Part 8| August 2017| x171189

https://doi.org/10.1107/S2414314617011890

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rac-tert-Butyl{2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}azanium acrylate

Wenju Liu ^a ^* and Linda Yu ^a

^aSchool of Chemical Engineering and Environment, Henan University of Technology, Zhengzhou 450001, People's Republic of China
^*Correspondence e-mail: wenjuliu@haut.edu.cn

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 4 August 2017; accepted 16 August 2017; online 21 August 2017)

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 crystal structure 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 asymmetric unit of the title compound is shown in Fig. 1. 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).

Table 1
Hydrogen-bond geometry (Å, °)

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) $[x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}]$ ; (ii) $[-x, y-{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (iii) -x+1, -y+1, -z+1.

Figure 1
Perspective view of the cation and anion of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 50% probability level. The minor-occupied sites of the disordered atoms are not shown.

Figure 2
The crystal packing of the title compound, viewed perpendicular to the bc plane. N—H⋯O and O—H⋯O hydrogen bonds are shown as dashed lines. The minor-occupied sites of the disordered atoms are not shown.

Synthesis 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 refinement details are summarized in Table 2. 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. U_iso(H) values were set at 1.5U_eq(C,O) for methyl and hydroxy groups and at 1.2U_eq(C,N) for the remaining atoms. The torsion angles of the hydroxy and methyl groups were allowed to refine.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₃H₂₂NO₃⁺·C₃H₃O₂⁻
M_r	311.37
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	295
a, b, c (Å)	9.5304 (4), 11.9927 (5), 14.5120 (7)
β (°)	91.815 (2)
V (Å³)	1657.82 (13)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.09
Crystal size (mm)	0.4 × 0.3 × 0.2

Data collection
Diffractometer	Bruker APEXII CCD area detector
Absorption correction	Multi-scan (SADABS; Bruker, 2015 )
T_min, T_max	0.719, 0.746
No. of measured, independent and observed [I > 2σ(I)] reflections	39441, 3825, 3468
R_int	0.023
(sin θ/λ)_max (Å⁻¹)	0.651

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.046, 0.125, 1.04
No. of reflections	3825
No. of parameters	224
No. of restraints	3
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.39, −0.27
Computer programs: APEX2 (Bruker, 2015), SAINT (Bruker, 2015), SHELXT (Sheldrick, 2015a ), SHELXL2014 (Sheldrick, 2015b ) and OLEX2 (Dolomanov et al., 2009 ).

Structural data

CCDC reference: 1563663

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2414314617011890/bt4060sup1.cif

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

checkCIF report

Computing details top

Data collection: APEX2 (Bruker, 2015); cell refinement: 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).

rac-tert-Butyl{2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl}azanium acrylate top

Crystal data top

C₁₃H₂₂NO₃⁺·C₃H₃O₂⁻	F(000) = 672
M_r = 311.37	D_x = 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

Data collection top

CCD area detector diffractometer	3468 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.023
phi and ω scans	θ_max = 27.6°, θ_min = 3.3°
Absorption correction: multi-scan (SADABS; Bruker, 2015)	h = −12→12
T_min = 0.719, T_max = 0.746	k = −15→15
39441 measured reflections	l = −18→18
3825 independent reflections

Refinement top

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(F_o²) + (0.0548P)² + 0.7417P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max < 0.001
3825 reflections	Δρ_max = 0.39 e Å⁻³
224 parameters	Δρ_min = −0.27 e Å⁻³
3 restraints

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.

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

	x	y	z	U_iso*/U_eq	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)

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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

Hydrogen-bond geometry (Å, º) top

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).

References

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