{2-Hydr-oxy-3-[4-(2-methoxy-ethyl)-phen-oxy]prop-yl}isopropyl-ammonium hemisuccinate.

Metoprolol, a widely used adrenoreceptor blocking drug, is commonly administered as the succinate or tartrate salt. The structure of metoprolol succinate, C(15)H(26)NO(3) (+)·0.5C(4)H(4)O(4) (2-), is characterized by the presence of ribbons in which cations, generated by N-protonation of the metoprolol mol-ecules, are hydrogen bonded to succinate anions. The dicarboxylic acid transfers its H atoms to two metoprolol mol-ecules; the asymmetric unit contains one cation and half an anion, the latter possessing twofold rotational symmetry. There are localized nets of O-H⋯O and N-H⋯O hydrogen bonds along a ribbon, within centrosymmetric arrangements formed by pairs of metoprolol cations and pairs of anions, each of the latter contributing with one of its carboxyl groups to the localized net. This arrangement is repeated along the ribbon by the operation of the twofold axis bis-ecting the anion, as well as by the lattice translation.

Related literature

For general information on the medical applications of metoprolol, see: Benfield et al. (1986 ▶); Moses & Borer (1981 ▶); Brogden et al. (1977 ▶); Hainer & Sugg (2007 ▶); Ragnarsson et al. (1987 ▶); Sandberg et al. (1988 ▶).

Experimental

Crystal data

C15H26NO3 +·0.5C4H4O4 2−

M = 326.40

Monoclinic,

a = 26.2630 (4) Å

b = 7.9396 (2) Å

c = 17.4629 (4) Å

β = 107.348 (2)°

V = 3475.68 (13) Å3

Z = 8

Cu Kα radiation

μ = 0.75 mm−1

T = 200 K

0.60 × 0.20 × 0.06 mm

Data collection

Oxford Diffraction Xcalibur PX Ultra CCD diffractometer

Absorption correction: multi-scan (ABSPACK in CrysAlisPro RED; Oxford Diffraction, 2006 ▶) T min = 0.732, T max = 0.956

22961 measured reflections

3408 independent reflections

3108 reflections with I > 2σ(I)

R int = 0.028

Refinement

R[F 2 > 2σ(F 2)] = 0.045

wR(F 2) = 0.124

S = 1.06

3408 reflections

226 parameters

12 restraints

H-atom parameters constrained

Δρmax = 0.21 e Å−3

Δρmin = −0.19 e Å−3

Data collection: CrysAlisPro CCD (Oxford Diffraction, 2006 ▶); cell refinement: CrysAlisPro CCD; data reduction: CrysAlisPro RED (Oxford Diffraction, 2006 ▶); program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 (Farrugia, 1997 ▶) and PLATON (Spek, 2009 ▶); software used to prepare material for publication: SHELXL97, WinGX (Farrugia, 1999 ▶) and PARST (Nardelli, 1995 ▶).

Crystal structure: contains datablocks global, I. DOI: 10.1107/S160053680901856X/pk2162sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S160053680901856X/pk2162Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C15H26NO3+·0.5C4H4O42−	F(000) = 1416
Mr = 326.40	Dx = 1.248 Mg m−3
Monoclinic, C2/c	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -C 2yc	Cell parameters from 14350 reflections
a = 26.2630 (4) Å	θ = 5.0–72.4°
b = 7.9396 (2) Å	µ = 0.75 mm−1
c = 17.4629 (4) Å	T = 200 K
β = 107.348 (2)°	Elongated plate, colorless
V = 3475.68 (13) Å3	0.60 × 0.20 × 0.06 mm
Z = 8

Oxford Diffraction Xcalibur PX Ultra CCD diffractometer	3408 independent reflections
Radiation source: fine-focus sealed tube	3108 reflections with I > 2σ(I)
Oxford Diffraction Enhance ULTRA assembly	Rint = 0.028
Detector resolution: 8.1241 pixels mm-1	θmax = 72.7°, θmin = 5.3°
ω scans	h = −32→32
Absorption correction: multi-scan (ABSPACK in CrysAlis PRO RED; Oxford Diffraction, 2006)	k = −9→9
Tmin = 0.732, Tmax = 0.956	l = −21→18
22961 measured reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.045	H-atom parameters constrained
wR(F2) = 0.124	w = 1/[σ2(Fo2) + (0.0619P)2 + 2.6692P] where P = (Fo2 + 2Fc2)/3
S = 1.06	(Δ/σ)max < 0.001
3408 reflections	Δρmax = 0.21 e Å−3
226 parameters	Δρmin = −0.19 e Å−3
12 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00076 (10)

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.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

	x	y	z	Uiso*/Ueq	Occ. (<1)
C1	0.32938 (5)	0.08129 (18)	0.64968 (8)	0.0315 (3)
C2	0.34141 (5)	0.01034 (19)	0.72575 (9)	0.0349 (3)
H2	0.3768	−0.0250	0.7526	0.042*
C3	0.30174 (6)	−0.00870 (19)	0.76236 (9)	0.0350 (3)
H3	0.3104	−0.0570	0.8144	0.042*
C4	0.24918 (5)	0.04133 (18)	0.72460 (8)	0.0321 (3)
C5	0.23807 (6)	0.1099 (2)	0.64854 (9)	0.0357 (3)
H5	0.2026	0.1439	0.6213	0.043*
C6	0.27752 (6)	0.1304 (2)	0.61068 (9)	0.0371 (3)
H6	0.2689	0.1778	0.5584	0.044*
O1	0.37140 (4)	0.09661 (14)	0.61815 (6)	0.0375 (3)
C7	0.36075 (6)	0.1715 (2)	0.54105 (8)	0.0370 (3)	0.907 (3)
H71	0.3487	0.2893	0.5423	0.044*	0.907 (3)
H72	0.3325	0.1081	0.5012	0.044*	0.907 (3)
C8	0.41267 (6)	0.1664 (2)	0.51900 (9)	0.0317 (4)	0.907 (3)
H8	0.4259	0.0477	0.5219	0.038*	0.907 (3)
O2	0.39950 (4)	0.22479 (17)	0.43853 (7)	0.0407 (4)	0.907 (3)
H2O	0.4199	0.1797	0.4155	0.061*	0.907 (3)
C9	0.45477 (6)	0.27692 (19)	0.57594 (9)	0.0349 (3)	0.907 (3)
H91	0.4457	0.3971	0.5641	0.042*	0.907 (3)
H92	0.4553	0.2546	0.6320	0.042*	0.907 (3)
C7'	0.36075 (6)	0.1715 (2)	0.54105 (8)	0.0370 (3)	0.093 (3)
H71'	0.3402	0.2759	0.5413	0.044*	0.093 (3)
H72'	0.3370	0.0940	0.5019	0.044*	0.093 (3)
C8'	0.4070 (4)	0.2166 (17)	0.5093 (7)	0.0317 (4)	0.093 (3)
H8'	0.3968	0.2943	0.4621	0.038*	0.093 (3)
O2'	0.4208 (5)	0.0535 (14)	0.4903 (7)	0.043 (3)*	0.093 (3)
H2'	0.4039	0.0311	0.4424	0.065*	0.093 (3)
C9'	0.45477 (6)	0.27692 (19)	0.57594 (9)	0.0349 (3)	0.093 (3)
H91'	0.4514	0.4002	0.5814	0.042*	0.093 (3)
H92'	0.4532	0.2250	0.6267	0.042*	0.093 (3)
N	0.50840 (4)	0.24135 (15)	0.56677 (7)	0.0311 (3)
H1N	0.5056	0.2456	0.5130	0.037*
H2N	0.5178	0.1330	0.5839	0.037*
C10	0.55297 (6)	0.3574 (2)	0.61095 (9)	0.0367 (3)
H10	0.5452	0.4731	0.5877	0.044*
C11	0.60366 (6)	0.2938 (2)	0.59633 (10)	0.0463 (4)
H111	0.6133	0.1844	0.6226	0.069*
H112	0.6326	0.3744	0.6184	0.069*
H113	0.5979	0.2815	0.5385	0.069*
C12	0.55708 (7)	0.3651 (3)	0.69955 (10)	0.0487 (4)
H121	0.5605	0.2507	0.7216	0.073*
H122	0.5249	0.4181	0.7061	0.073*
H123	0.5885	0.4314	0.7281	0.073*
C13	0.20539 (6)	0.0195 (2)	0.76350 (9)	0.0375 (3)
H131	0.1726	0.0738	0.7291	0.045*
H132	0.1979	−0.1023	0.7658	0.045*
C14	0.21768 (7)	0.0914 (2)	0.84700 (10)	0.0427 (4)	0.942 (5)
H141	0.2478	0.0302	0.8844	0.051*	0.942 (5)
H142	0.2273	0.2120	0.8472	0.051*	0.942 (5)
O3	0.17048 (7)	0.0715 (2)	0.87015 (10)	0.0595 (6)	0.942 (5)
C15	0.17273 (11)	0.1557 (3)	0.94139 (14)	0.0731 (7)	0.942 (5)
H151	0.2006	0.1053	0.9859	0.110*	0.942 (5)
H152	0.1382	0.1461	0.9519	0.110*	0.942 (5)
H153	0.1809	0.2749	0.9363	0.110*	0.942 (5)
C14'	0.21768 (7)	0.0914 (2)	0.84700 (10)	0.0427 (4)	0.058 (5)
H143	0.2570	0.0876	0.8696	0.051*	0.058 (5)
H144	0.2080	0.2122	0.8398	0.051*	0.058 (5)
O3'	0.1975 (8)	0.0335 (14)	0.9084 (11)	0.038 (6)*	0.058 (5)
C15'	0.17273 (11)	0.1557 (3)	0.94139 (14)	0.0731 (7)	0.058 (5)
H154	0.1401	0.1092	0.9494	0.110*	0.058 (5)
H155	0.1636	0.2525	0.9050	0.110*	0.058 (5)
H156	0.1969	0.1920	0.9931	0.110*	0.058 (5)
C16	0.50084 (5)	−0.18399 (18)	0.86196 (8)	0.0307 (3)
C17	0.52161 (6)	−0.1855 (2)	0.78974 (8)	0.0380 (3)
H171	0.5445	−0.0854	0.7923	0.046*
H172	0.5441	−0.2867	0.7926	0.046*
O4	0.46519 (4)	−0.07642 (13)	0.86371 (6)	0.0372 (3)
O5	0.52021 (4)	−0.28659 (14)	0.91717 (6)	0.0430 (3)

	U11	U22	U33	U12	U13	U23
C1	0.0271 (6)	0.0390 (7)	0.0318 (7)	−0.0020 (5)	0.0136 (5)	−0.0015 (6)
C2	0.0280 (6)	0.0432 (8)	0.0338 (7)	0.0009 (6)	0.0100 (5)	0.0023 (6)
C3	0.0324 (7)	0.0431 (8)	0.0311 (7)	−0.0010 (6)	0.0117 (5)	0.0030 (6)
C4	0.0303 (7)	0.0363 (7)	0.0324 (7)	−0.0022 (5)	0.0136 (5)	−0.0024 (6)
C5	0.0272 (6)	0.0447 (8)	0.0361 (7)	0.0017 (6)	0.0107 (6)	0.0013 (6)
C6	0.0323 (7)	0.0487 (9)	0.0315 (7)	0.0013 (6)	0.0115 (6)	0.0049 (6)
O1	0.0293 (5)	0.0535 (6)	0.0340 (5)	0.0016 (4)	0.0157 (4)	0.0066 (4)
C7	0.0311 (7)	0.0529 (9)	0.0300 (7)	−0.0016 (6)	0.0136 (6)	0.0029 (6)
C8	0.0310 (7)	0.0402 (11)	0.0265 (7)	0.0013 (7)	0.0125 (6)	0.0035 (7)
O2	0.0367 (6)	0.0593 (8)	0.0300 (6)	0.0071 (5)	0.0157 (5)	0.0061 (5)
C9	0.0323 (7)	0.0409 (8)	0.0359 (8)	−0.0019 (6)	0.0170 (6)	−0.0016 (6)
C7'	0.0311 (7)	0.0529 (9)	0.0300 (7)	−0.0016 (6)	0.0136 (6)	0.0029 (6)
C8'	0.0310 (7)	0.0402 (11)	0.0265 (7)	0.0013 (7)	0.0125 (6)	0.0035 (7)
C9'	0.0323 (7)	0.0409 (8)	0.0359 (8)	−0.0019 (6)	0.0170 (6)	−0.0016 (6)
N	0.0296 (6)	0.0377 (6)	0.0290 (6)	−0.0030 (5)	0.0132 (5)	−0.0003 (5)
C10	0.0352 (7)	0.0433 (8)	0.0342 (7)	−0.0086 (6)	0.0143 (6)	−0.0051 (6)
C11	0.0331 (8)	0.0720 (11)	0.0372 (8)	−0.0087 (7)	0.0158 (6)	−0.0074 (8)
C12	0.0401 (8)	0.0724 (12)	0.0373 (9)	−0.0115 (8)	0.0169 (7)	−0.0167 (8)
C13	0.0323 (7)	0.0452 (8)	0.0395 (8)	−0.0027 (6)	0.0177 (6)	0.0009 (6)
C14	0.0455 (8)	0.0484 (9)	0.0421 (8)	0.0002 (7)	0.0251 (7)	0.0009 (7)
O3	0.0598 (11)	0.0758 (10)	0.0593 (11)	−0.0063 (8)	0.0428 (9)	−0.0093 (8)
C15	0.1075 (18)	0.0667 (13)	0.0690 (14)	0.0119 (13)	0.0630 (14)	0.0016 (11)
C14'	0.0455 (8)	0.0484 (9)	0.0421 (8)	0.0002 (7)	0.0251 (7)	0.0009 (7)
C15'	0.1075 (18)	0.0667 (13)	0.0690 (14)	0.0119 (13)	0.0630 (14)	0.0016 (11)
C16	0.0314 (7)	0.0360 (7)	0.0260 (7)	−0.0034 (5)	0.0106 (5)	−0.0038 (5)
C17	0.0337 (7)	0.0535 (9)	0.0303 (7)	0.0025 (6)	0.0150 (6)	0.0017 (6)
O4	0.0383 (5)	0.0404 (6)	0.0370 (6)	0.0025 (4)	0.0173 (4)	−0.0002 (4)
O5	0.0512 (6)	0.0502 (7)	0.0313 (5)	0.0110 (5)	0.0179 (5)	0.0078 (5)

C1—O1	1.3778 (16)	N—H1N	0.9200
C1—C6	1.385 (2)	N—H2N	0.9200
C1—C2	1.390 (2)	C10—C11	1.515 (2)
C2—C3	1.3834 (19)	C10—C12	1.520 (2)
C2—H2	0.9500	C10—H10	1.0000
C3—C4	1.398 (2)	C11—H111	0.9800
C3—H3	0.9500	C11—H112	0.9800
C4—C5	1.384 (2)	C11—H113	0.9800
C4—C13	1.5099 (18)	C12—H121	0.9800
C5—C6	1.395 (2)	C12—H122	0.9800
C5—H5	0.9500	C12—H123	0.9800
C6—H6	0.9500	C13—C14	1.509 (2)
O1—C7	1.4214 (17)	C13—H131	0.9900
C7—C8	1.5241 (19)	C13—H132	0.9900
C7—H71	0.9900	C14—O3	1.4228 (19)
C7—H72	0.9900	C14—H141	0.9900
C8—O2	1.4210 (19)	C14—H142	0.9900
C8—C9	1.525 (2)	O3—C15	1.398 (2)
C8—H8	1.0000	C15—H151	0.9800
O2—H2O	0.8400	C15—H152	0.9800
C9—N	1.4913 (17)	C15—H153	0.9800
C9—H91	0.9900	C16—O5	1.2487 (17)
C9—H92	0.9900	C16—O4	1.2744 (17)
C8'—O2'	1.410 (9)	C16—C17	1.5161 (18)
C8'—H8'	1.0000	C17—C17i	1.508 (3)
O2'—H2'	0.8400	C17—H171	0.9900
N—C10	1.5086 (18)	C17—H172	0.9900
O1—C1—C6	124.49 (13)	C10—N—H2N	108.2
O1—C1—C2	115.91 (12)	H1N—N—H2N	107.4
C6—C1—C2	119.60 (12)	N—C10—C11	107.28 (12)
C3—C2—C1	119.88 (13)	N—C10—C12	110.72 (12)
C3—C2—H2	120.1	C11—C10—C12	112.69 (13)
C1—C2—H2	120.1	N—C10—H10	108.7
C2—C3—C4	121.64 (13)	C11—C10—H10	108.7
C2—C3—H3	119.2	C12—C10—H10	108.7
C4—C3—H3	119.2	C10—C11—H111	109.5
C5—C4—C3	117.41 (12)	C10—C11—H112	109.5
C5—C4—C13	120.40 (13)	H111—C11—H112	109.5
C3—C4—C13	122.18 (13)	C10—C11—H113	109.5
C4—C5—C6	121.80 (13)	H111—C11—H113	109.5
C4—C5—H5	119.1	H112—C11—H113	109.5
C6—C5—H5	119.1	C10—C12—H121	109.5
C1—C6—C5	119.66 (13)	C10—C12—H122	109.5
C1—C6—H6	120.2	H121—C12—H122	109.5
C5—C6—H6	120.2	C10—C12—H123	109.5
C1—O1—C7	117.42 (10)	H121—C12—H123	109.5
O1—C7—C8	106.85 (12)	H122—C12—H123	109.5
O1—C7—H71	110.4	C14—C13—C4	114.78 (12)
C8—C7—H71	110.4	C14—C13—H131	108.6
O1—C7—H72	110.4	C4—C13—H131	108.6
C8—C7—H72	110.4	C14—C13—H132	108.6
H71—C7—H72	108.6	C4—C13—H132	108.6
O2—C8—C7	105.59 (12)	H131—C13—H132	107.5
O2—C8—C9	111.85 (13)	O3—C14—C13	106.20 (14)
C7—C8—C9	110.43 (12)	O3—C14—H141	110.5
O2—C8—H8	109.6	C13—C14—H141	110.5
C7—C8—H8	109.6	O3—C14—H142	110.5
C9—C8—H8	109.6	C13—C14—H142	110.5
N—C9—C8	110.19 (12)	H141—C14—H142	108.7
N—C9—H91	109.6	C15—O3—C14	112.98 (17)
C8—C9—H91	109.6	O5—C16—O4	123.48 (12)
N—C9—H92	109.6	O5—C16—C17	118.19 (12)
C8—C9—H92	109.6	O4—C16—C17	118.32 (12)
H91—C9—H92	108.1	C17i—C17—C16	113.99 (15)
O2'—C8'—H8'	113.4	C17i—C17—H171	108.8
C8'—O2'—H2'	109.5	C16—C17—H171	108.8
C9—N—C10	116.31 (11)	C17i—C17—H172	108.8
C9—N—H1N	108.2	C16—C17—H172	108.8
C10—N—H1N	108.2	H171—C17—H172	107.6
C9—N—H2N	108.2
O1—C1—C2—C3	179.49 (13)	O1—C7—C8—O2	173.83 (12)
C6—C1—C2—C3	−0.8 (2)	O1—C7—C8—C9	−65.09 (17)
C1—C2—C3—C4	0.2 (2)	O2—C8—C9—N	−75.80 (16)
C2—C3—C4—C5	0.5 (2)	C7—C8—C9—N	166.91 (12)
C2—C3—C4—C13	179.31 (14)	C8—C9—N—C10	171.96 (12)
C3—C4—C5—C6	−0.6 (2)	C9—N—C10—C11	177.49 (12)
C13—C4—C5—C6	−179.44 (14)	C9—N—C10—C12	54.15 (17)
O1—C1—C6—C5	−179.62 (14)	C5—C4—C13—C14	−128.73 (16)
C2—C1—C6—C5	0.7 (2)	C3—C4—C13—C14	52.5 (2)
C4—C5—C6—C1	0.0 (2)	C4—C13—C14—O3	175.14 (14)
C6—C1—O1—C7	1.5 (2)	C13—C14—O3—C15	−170.64 (17)
C2—C1—O1—C7	−178.87 (13)	O5—C16—C17—C17i	132.10 (11)
C1—O1—C7—C8	−177.63 (12)	O4—C16—C17—C17i	−49.01 (14)

D—H···A	D—H	H···A	D···A	D—H···A
O2—H2O···O4ii	0.84	1.88	2.7231 (15)	179
N—H2N···O4i	0.92	1.89	2.7961 (16)	170
N—H1N···O5ii	0.92	1.85	2.7448 (15)	162

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O2—H2O⋯O4i	0.84	1.88	2.7231 (15)	179
N—H2N⋯O4ii	0.92	1.89	2.7961 (16)	170
N—H1N⋯O5i	0.92	1.85	2.7448 (15)	162

Symmetry codes: (i) ; (ii) .