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Acta Crystallogr Sect E Struct Rep Online. 2009 August 1; 65(Pt 8): o2020–o2021.
Published online 2009 July 29. doi:  10.1107/S1600536809029353
PMCID: PMC2977435

Carvedilol dihydrogen phosphate hemihydrate: a powder study

Abstract

In the cation of the title compound [systematic name: 3-(9H-carbazol-4-yl­oxy)-2-hydr­oxy-N-[2-(2-methoxy­phen­oxy)eth­yl]propan-1-aminium dihydrogen phosphate hemihydrate], C24H27N2O4 +·H2PO4 ·0.5H2O, the mean planes of the tricyclic ring system and the benzene ring form a dihedral angle of 87.2 (2)°. In the crystal structure, the solvent water mol­ecule is situated on a twofold rotation axis linking two cations via O—H(...)O and N—H(...)O hydrogen bonds. The anions contribute to the formation O—H(...)O and N—H(...)O hydrogen bonds between the anions and cations, which consolidate the crystal packing.

Related literature

For the synthesis of the title compound, claimed as Form I, see: Brook et al. (2005 [triangle]). For the crystal structures of two polymorphs of the carvedilol free base, see: Chen et al. (1998 [triangle]); Yathirajan et al. (2007 [triangle]). For details of the indexing algorithm, see: Visser (1969 [triangle]). The methodology of bond-restrained Rietveld refinement used in this study was the same as described by Chernyshev et al. (2003 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o2020-scheme1.jpg

Experimental

Crystal data

  • C24H27N2O4 +·H2PO4 ·0.5H2O
  • M r = 513.47
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2020-efi1.jpg
  • a = 26.600 (2) Å
  • b = 12.3767 (12) Å
  • c = 16.5101 (15) Å
  • β = 106.662 (11)°
  • V = 5207.2 (8) Å3
  • Z = 8
  • Cu Kα1 radiation
  • μ = 1.38 mm−1
  • T = 295 K
  • Specimen shape: flat sheet
  • 15 × 1 × 1 mm
  • Specimen prepared at 101 kPa
  • Specimen prepared at 295 K
  • Particle morphology: no specific habit, light grey

Data collection

  • Guinier G670 image plate camera
  • Specimen mounting: thin layer in the specimen holder of the camera
  • Specimen mounted in transmission mode
  • Scan method: continuous
  • min = 5.0, 2θmax = 75.0°
  • Increment in 2θ = 0.01°

Refinement

  • R p = 0.026
  • R wp = 0.035
  • R exp = 0.014
  • R B = 0.064
  • S = 2.43
  • Wavelength of incident radiation: 1.54059 Å
  • Excluded region(s): none
  • Profile function: split-type pseudo-Voigt (Toraya, 1986 [triangle])
  • 1346 reflections
  • 157 parameters
  • 125 restraints
  • H-atom parameters not refined
  • Preferred orientation correction: March-Dollase (Dollase, 1986 [triangle]); direction of preferred orientation 100, texture parameter r = 1.038 (5)

Data collection: G670 Imaging Plate Guinier Camera Software (Huber, 2002 [triangle]); cell refinement: MRIA (Zlokazov & Chernyshev, 1992 [triangle]); data reduction: G670 Imaging Plate Guinier Camera Software; method used to solve structure: simulated annealing (Zhukov et al., 2001 [triangle]); program(s) used to refine structure: MRIA; molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: MRIA and SHELXL97 (Sheldrick, 2008 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809029353/lh2866sup1.cif

Rietveld powder data: contains datablocks I. DOI: 10.1107/S1600536809029353/lh2866Isup2.rtv

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

Acknowledgments

VVC and YAV acknowledge the International Centre for Diffraction Data (ICDD) for supporting this study (GiA 03–06).

supplementary crystallographic information

Comment

Earlier, the crystal structures of two polymorphs of carvedilol free base have been reported (Chen et al., 1998; Yathirajan et al., 2007). Herein we report the crystal structure of the title compound (I), also known as carvedilol dihydrogen phosphate hemihydrate, Form I (Brook et al., 2005).

In (I) (Fig. 1), all bond lengths and angles in the cation are comparable with those reported earlier for two monoclinic polymorphs of carvedilol free base (Chen et al., 1998; Yathirajan et al., 2007). The mean planes of tricycle and benzene ring form a dihedral angle of 87.2 (2)°. The crystalline water molecule is situated on a twofold rotational axis linking two cations via O—H···O and N—H···O hydrogen bonds (Table 1). The anions contribute to formation O—H···O and N—H···O hydrogen bonds (Table 1) between the anions and cations giving rise to three-dimensional hydrogen-bonding network.

Experimental

The title compound was synthesized in accordance with the known procedure, invented by Brook et al. (2005) for Form I.

Refinement

During the exposure, the specimen was spun in its plane to improve particle statistics. The monoclinic unit-cell dimensions were determined with the indexing program ITO (Visser, 1969), M20=35, using the first 30 peak positions. The space group C2/c was chosen on the basis of systematic extinction rules and confirmed later by the crystal structure solution. The structure of (I) was solved by simulated annealing procedure (Zhukov et al., 2001) and refined following the methodology described in details elsewhere (Chernyshev et al., 2003) by the subsequent bond-restrained Rietveld refinement with the program MRIA (Zlokazov & Chernyshev, 1992). All non-H atoms were refined isotropically: two overall Uiso parameters were refined for the cation, and two Uiso parameters were refined for the anion - one for P and one for all O atoms. All H atoms were placed in geometrically calculated positions and not refined. The diffraction profiles and the differences between the measured and calculated profiles are shown in Fig. 2.

Figures

Fig. 1.
The molecular structure of (I) with the atomic numbering and 40% displacement spheres. H atoms are not shown.
Fig. 2.
The Rietveld plot, showing the observed and difference profiles for (I). The reflection positions are shown above the difference profile.

Crystal data

C24H27N2O4+·H2PO4·0.5H2OF(000) = 2168
Mr = 513.47Dx = 1.310 Mg m3
Monoclinic, C2/cCu Kα1 radiation, λ = 1.54059 Å
Hall symbol: -C 2ycµ = 1.38 mm1
a = 26.600 (2) ÅT = 295 K
b = 12.3767 (12) ÅParticle morphology: no specific habit
c = 16.5101 (15) Ålight grey
β = 106.662 (11)°flat_sheet, 15 × 1 mm
V = 5207.2 (8) Å3Specimen preparation: Prepared at 295 K and 101 kPa
Z = 8

Data collection

Guinier G670 diffractometerData collection mode: transmission
Radiation source: line-focus sealed tubeScan method: continuous
Curved Germanium (111)min = 5.00°, 2θmax = 75.00°, 2θstep = 0.01°
Specimen mounting: thin layer in the specimen holder of the camera

Refinement

Refinement on InetProfile function: split-type pseudo-Voigt (Toraya, 1986)
Least-squares matrix: full with fixed elements per cycle157 parameters
Rp = 0.026125 restraints
Rwp = 0.03527 constraints
Rexp = 0.014H-atom parameters not refined
RBragg = 0.064Weighting scheme based on measured s.u.'s
χ2 = 5.928(Δ/σ)max = 0.004
7001 data pointsBackground function: Chebyshev polynomial up to the 5th order
Excluded region(s): nonePreferred orientation correction: March-Dollase (Dollase, 1986); direction of preferred orientation 100, texture parameter r = 1.038(5)

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

xyzUiso*/Ueq
C10.1090 (10)0.7439 (16)0.8662 (14)0.096 (9)*
H1A0.12180.67230.85850.115*
H1B0.13390.77710.91460.115*
C20.1044 (9)0.8122 (14)0.7871 (12)0.096 (9)*
H20.11100.88880.80120.115*
C30.1405 (11)0.7694 (13)0.7371 (13)0.096 (9)*
H3A0.12890.69800.71530.115*
H3B0.13860.81670.68950.115*
C40.2317 (10)0.7415 (15)0.7495 (11)0.078 (7)*
C50.2335 (8)0.7825 (16)0.6713 (14)0.078 (7)*
H50.20690.82730.64020.094*
C60.2761 (11)0.7553 (13)0.6398 (12)0.078 (7)*
H60.27450.77660.58510.094*
C70.3201 (9)0.6987 (17)0.6859 (15)0.078 (7)*
H70.35020.69220.66840.094*
C80.3156 (9)0.6522 (16)0.7609 (13)0.078 (7)*
N90.3515 (8)0.5885 (13)0.8183 (10)0.078 (7)*
H90.37970.56220.81070.094*
C100.3351 (9)0.5734 (15)0.8899 (14)0.078 (7)*
C110.3572 (11)0.5123 (16)0.9629 (15)0.078 (7)*
H110.38900.47660.97030.094*
C120.3304 (12)0.5062 (17)1.0244 (15)0.078 (7)*
H120.34540.46821.07410.094*
C130.2814 (10)0.5561 (14)1.0128 (12)0.078 (7)*
H130.26460.55221.05500.094*
C140.2580 (9)0.6116 (13)0.9379 (14)0.078 (7)*
H140.22430.63930.92800.094*
C150.2854 (11)0.6256 (15)0.8773 (13)0.078 (7)*
C160.2737 (10)0.6768 (16)0.7952 (12)0.078 (7)*
O170.1930 (7)0.7639 (11)0.7893 (9)0.078 (7)*
O180.0509 (8)0.7940 (12)0.7362 (9)0.096 (9)*
H180.04790.83420.69570.144*
N190.0560 (8)0.7353 (13)0.8820 (11)0.096 (9)*
H19A0.04350.80220.88510.115*
H19B0.03370.70150.83790.115*
C200.0576 (10)0.6750 (16)0.9617 (14)0.096 (9)*
H20A0.08070.71241.00980.115*
H20B0.07180.60320.95920.115*
C210.0031 (11)0.6657 (15)0.9737 (12)0.096 (9)*
H21A0.00510.63431.02830.115*
H21B−0.01330.73620.97010.115*
O22−0.0260 (7)0.5974 (11)0.9071 (8)0.096 (9)*
C23−0.0747 (10)0.5587 (16)0.9079 (13)0.096 (9)*
C24−0.0925 (12)0.4644 (14)0.8587 (14)0.096 (9)*
C25−0.1401 (9)0.4201 (15)0.8616 (15)0.096 (9)*
H25−0.15240.35770.83090.115*
C26−0.1699 (10)0.4678 (16)0.9099 (12)0.096 (9)*
H26−0.20320.44120.90620.115*
C27−0.1502 (9)0.5542 (17)0.9631 (14)0.096 (9)*
H27−0.16770.57961.00060.115*
C28−0.1033 (11)0.6023 (14)0.9590 (12)0.096 (9)*
H28−0.09110.66400.99070.115*
O29−0.0584 (8)0.4261 (12)0.8162 (9)0.096 (9)*
C30−0.0784 (11)0.3728 (16)0.7357 (14)0.096 (9)*
H30A−0.04970.35140.71500.144*
H30B−0.10080.42150.69610.144*
H30C−0.09810.31010.74240.144*
P31−0.0045 (5)1.0448 (8)0.8733 (7)0.063 (6)*
O320.0094 (8)0.9380 (12)0.9182 (10)0.124 (11)*
O330.0409 (8)1.0822 (11)0.8416 (11)0.124 (11)*
H330.03731.05240.79600.186*
O34−0.0127 (8)1.1325 (13)0.9331 (10)0.124 (11)*
H34−0.02441.10160.96780.186*
O35−0.0536 (9)1.0330 (11)0.7999 (9)0.124 (11)*
O360.00000.5716 (11)0.75000.076 (7)*
H36−0.01030.53100.78360.114*

Geometric parameters (Å, °)

P31—O351.51 (2)C12—C131.40 (4)
P31—O341.52 (2)C13—C141.40 (3)
P31—O331.52 (2)C14—C151.41 (3)
P31—O321.509 (18)C15—C161.45 (3)
O17—C41.40 (3)C20—C211.52 (4)
O17—C31.42 (3)C23—C281.40 (3)
O18—C21.45 (3)C23—C241.42 (3)
O22—C231.38 (3)C24—C251.39 (4)
O22—C211.43 (2)C25—C261.41 (3)
O29—C241.38 (3)C26—C271.39 (3)
O29—C301.44 (3)C27—C281.40 (4)
O18—H180.82C1—H1A0.97
O33—H330.82C1—H1B0.97
O34—H340.82C2—H20.98
O36—H360.85C3—H3A0.97
O36—H36i0.85C3—H3B0.97
N9—C101.39 (3)C5—H50.93
N9—C81.38 (3)C6—H60.93
N19—C11.51 (3)C7—H70.93
N19—C201.50 (3)C11—H110.93
N9—H90.86C12—H120.93
N19—H19A0.90C13—H130.93
N19—H19B0.90C14—H140.93
C1—C21.53 (3)C20—H20B0.97
C2—C31.53 (3)C20—H20A0.97
C4—C161.41 (3)C21—H21B0.97
C4—C51.40 (3)C21—H21A0.97
C5—C61.42 (4)C25—H250.93
C6—C71.39 (3)C26—H260.93
C7—C81.40 (3)C27—H270.93
C8—C161.42 (4)C28—H280.93
C10—C151.43 (4)C30—H30A0.96
C10—C111.40 (3)C30—H30B0.96
C11—C121.40 (4)C30—H30C0.96
O34—P31—O35109.7 (13)O29—C24—C25128.2 (18)
O32—P31—O35110.0 (11)C24—C25—C26121.3 (19)
O32—P31—O33109.2 (13)C25—C26—C27121 (2)
O32—P31—O34111.5 (11)C26—C27—C28118 (2)
O33—P31—O34106.4 (12)C23—C28—C27120.8 (19)
O33—P31—O35110.0 (12)N19—C1—H1B109.77
C3—O17—C4117.0 (16)N19—C1—H1A109.78
C21—O22—C23120.0 (18)H1A—C1—H1B108.18
C24—O29—C30120 (2)C2—C1—H1A109.73
C2—O18—H18103.23C2—C1—H1B109.71
P31—O33—H33106.53C1—C2—H2111.50
P31—O34—H34105.88C3—C2—H2111.46
H36—O36—H36i107.52O18—C2—H2111.57
C8—N9—C10110 (2)O17—C3—H3A109.57
C1—N19—C20113.1 (18)C2—C3—H3A109.48
C10—N9—H9125.12C2—C3—H3B109.48
C8—N9—H9125.17O17—C3—H3B109.59
C1—N19—H19B108.95H3A—C3—H3B108.18
H19A—N19—H19B107.79C4—C5—H5120.24
C20—N19—H19B108.92C6—C5—H5120.11
C1—N19—H19A108.90C7—C6—H6118.16
C20—N19—H19A109.00C5—C6—H6118.07
N19—C1—C2109.6 (19)C6—C7—H7122.62
C1—C2—C3111.1 (17)C8—C7—H7122.59
O18—C2—C1103.5 (18)C10—C11—H11120.69
O18—C2—C3107.3 (16)C12—C11—H11120.78
O17—C3—C2110.5 (16)C11—C12—H12119.21
O17—C4—C16116.1 (17)C13—C12—H12119.26
C5—C4—C16118 (2)C12—C13—H13120.07
O17—C4—C5125.8 (19)C14—C13—H13120.07
C4—C5—C6120 (2)C13—C14—H14120.01
C5—C6—C7123.8 (19)C15—C14—H14119.97
C6—C7—C8115 (2)C21—C20—H20A109.42
N9—C8—C16108.4 (18)C21—C20—H20B109.44
C7—C8—C16123 (2)H20A—C20—H20B107.96
N9—C8—C7128 (2)N19—C20—H20A109.38
N9—C10—C11131 (2)N19—C20—H20B109.33
N9—C10—C15108.6 (18)O22—C21—H21A110.63
C11—C10—C15121 (2)C20—C21—H21B110.63
C10—C11—C12119 (2)O22—C21—H21B110.54
C11—C12—C13122 (2)C20—C21—H21A110.55
C12—C13—C14120 (2)H21A—C21—H21B108.76
C13—C14—C15120 (2)C26—C25—H25119.37
C10—C15—C16106 (2)C24—C25—H25119.29
C14—C15—C16135 (2)C25—C26—H26119.69
C10—C15—C14119.1 (19)C27—C26—H26119.59
C4—C16—C8120.1 (18)C26—C27—H27120.79
C4—C16—C15133 (2)C28—C27—H27120.75
C8—C16—C15107 (2)C27—C28—H28119.57
N19—C20—C21111.3 (19)C23—C28—H28119.65
O22—C21—C20105.7 (18)O29—C30—H30B109.47
O22—C23—C28123.0 (19)O29—C30—H30C109.44
C24—C23—C28121 (2)H30A—C30—H30C109.53
O22—C23—C24116 (2)H30B—C30—H30C109.45
C23—C24—C25117 (2)H30A—C30—H30B109.43
O29—C24—C23114 (2)O29—C30—H30A109.50

Symmetry codes: (i) −x, y, −z+3/2.

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N19—H19A···O320.902.062.93 (2)165
N19—H19B···O360.902.183.04 (2)159
N9—H9···O35ii0.861.872.72 (3)168
O18—H18···O32i0.822.423.15 (2)148
O18—H18···O35i0.822.463.02 (2)126
O33—H33···O35i0.821.772.53 (2)153
O34—H34···O32iii0.821.872.58 (2)144
O36—H36···O220.852.342.887 (15)122
O36—H36···O290.852.002.80 (2)155
C21—H21B···O34iii0.972.242.91 (2)125

Symmetry codes: (ii) x+1/2, y−1/2, z; (i) −x, y, −z+3/2; (iii) −x, −y+2, −z+2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: LH2866).

References

  • Brook, C. S., Chen, W., Dell’Orco, P. C., Katrincic, L. M., Lovet, A. M., Oh, C. K., Spoors, P. G. & Werner, C. (2005). US Patent No. 20050240027A1.
  • Chen, W.-M., Zeng, L.-M., Yu, K.-B. & Xu, J.-H. (1998). Jiegou Huaxue, 17, 325–328.
  • Chernyshev, V. V., Machon, D., Fitch, A. N., Zaitsev, S. A., Yatsenko, A. V., Shmakov, A. N. & Weber, H.-P. (2003). Acta Cryst. B59, 787–793. [PubMed]
  • Dollase, W. A. (1986). J. Appl. Cryst.19, 267–272.
  • Huber (2002). G670 Imaging Plate Guinier Camera Software Huber Diffraktionstechnik GmbH, Rimsting, Germany.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Toraya, H. (1986). J. Appl. Cryst.19, 440–447.
  • Visser, J. W. (1969). J. Appl. Cryst.2, 89–95.
  • Yathirajan, H. S., Bindya, S., Sreevidya, T. V., Narayana, B. & Bolte, M. (2007). Acta Cryst. E63, o542–o544.
  • Zhukov, S. G., Chernyshev, V. V., Babaev, E. V., Sonneveld, E. J. & Schenk, H. (2001). Z. Kristallogr. 216, 5–9.
  • Zlokazov, V. B. & Chernyshev, V. V. (1992). J. Appl. Cryst.25, 447–451.

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