organic compounds
Stable polymorph of morphine1
aInstitute of Pharmacy, University of Innsbruck, Innrain 52c, 6020 Innsbruck, Austria
*Correspondence e-mail: thomas.gelbrich@uibk.ac.at
In the stable polymorph of the title compound, C17H19NO3 [systematic name: (5α,6α)-7,8-didehydro-4,5-epoxy-17-methylmorphinan-3,6-diol], the molecular conformation is in agreement with the characteristics of previously reported morphine forms. The molecule displays the typical T-shape and its piperidine ring adopts a slightly distorted chair conformation. Intermolecular O—H⋯O hydrogen bonds link the molecules into helical chains parallel to the b axis. Intramolecular O—H⋯O hydrogen bonds are also observed.
Related literature
For related structures, see: Guguta et al. (2008); Gylbert (1973); Mackay & Hodgkin (1955); Bye (1976); Wongweichintana et al. (1984); Lutz & Spek (1998); Scheins et al. (2005); Gelbrich et al. (2012). For decriptions of morphine polymorphs, see: Kofler (1933); Kuhnert-Brandstätter et al. (1975). For a description of the Cambridge Structural Database, see: Allen (2002). For the program XPac, see: Gelbrich & Hursthouse (2005).
Experimental
Crystal data
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Refinement
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Data collection: CrysAlis PRO (Oxford Diffraction, 2003); cell CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Bruker, 1998) and Mercury (Bruno et al., 2002); software used to prepare material for publication: publCIF (Westrip, 2010).
Supporting information
https://doi.org/10.1107/S1600536812048945/im2413sup1.cif
contains datablocks I, global. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536812048945/im2413Isup2.hkl
Morphine was obtained from Heilmittelwerke Wien, Austria. Very thin, plate-shaped crystals of the stable polymorph were yielded from a
experiment carried out on a Kofler hot bench at approximately 150 °C, using two glass slides separated by a spacer ring of 1 cm height.All H atoms were identified in a difference map. Methyl H atoms were idealized and included as rigid groups allowed to rotate but not tip (C—H = 0.98 Å) and H atoms bonded to oxygen atoms (O—H = 0.84 Å), tertiary CH (C—H = 0.99 Å), secondary CH2 (C—H = 0.99 Å) and aromatic carbon atoms (C—H = 0.95 Å) were positioned geometrically. The temperature parameters of the methyl H atoms were set to Uiso(H) = 1.5 Ueq(C) of the parent carbon atom, for all other H atoms they were set to Uiso(H) = 1.2 Ueq(C or O).
Morphine is the main alkaloid of opium, the dried latex of the opium poppy (Papaver somniferum). The Cambridge Structural Database (CSD; version 5.33 and updates; Allen, 2002) contains a number of free base and salt structures of morphine: a monohydrate (Bye, 1976), a hydrochloride trihydrate (Gylbert, 1973), a hydroiodide dihydrate (Mackay & Hodgkin, 1955), a complex with β-phenylhydracrylic acid (Lutz & Spek, 1998) and a bis(morphinium) dihydrogensulfate pentahydrate (Wongweichintana et al., 1984). A hydrochloride anhydrate structure was recently reported by us (Gelbrich et al., 2012). The title structure was previously solved from powder data by Guguta et al. (2008), however the corresponding atomic coordinates are not available from the CSD or from supplementary materials accompanying this report.
According to Kofler (1933), morphine can exist in two distinct polymorphic modifications, and the characteristics of the crystals investigated by us match Kofler's description of the stable form. Our thermomicroscopy experiments have shown that the investigated crystals melt under decomposition at 254 °C (the applied heating rate was 5 °C per minute). This behaviour is in agreement with reports given by Kofler (1933) and Kuhnert-Brandstätter et al. (1975).
The geometry of the molecular morphine scaffold (Figure 1) with its five rings agrees with the characteristics of the related salt and free base structures mentioned above. The title structure displays two sets of O—H···O bonds, one of which is intramolecular and the other is intermolecular (Table 1). Intermolecular hydrogen bonds link the morphine molecules into an infinite helical chain that propagates parallel to the b-axis (Figure 2).
The packing of the geometrically inflexible morphine moieties in the title structure was compared with corresponding packing arrangements present in the six morphine forms mentioned above (Bye, 1976; Gelbrich et al., 2012; Gylbert, 1973; Mackay & Hodgkin, 1955; Lutz & Spek, 1998; Wongweichintana et al., 1984), using the program XPac (Gelbrich & Hursthouse, 2005). These comparisons have shown that the packing mode of morphine molecules in the stable form is unique and has no supramolecular constructs in common with any of the other structures in this group.
For related structures, see: Guguta et al. (2008); Gylbert (1973); Mackay & Hodgkin (1955); Bye (1976); Wongweichintana et al. (1984); Lutz & Spek (1998); Scheins et al. (2005); Gelbrich et al. (2012). For decriptions of morphine polymorphs, see: Kofler (1933); Kuhnert-Brandstätter et al. (1975). For a description of the Cambridge Structural Database, see: Allen (2002). For the program XPac, see: Gelbrich & Hursthouse (2005).
Data collection: CrysAlis PRO (Oxford Diffraction, 2003); cell
CrysAlis PRO (Oxford Diffraction, 2003); data reduction: CrysAlis PRO (Oxford Diffraction, 2003); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Bruker, 1998) and Mercury (Bruno et al., 2002); software used to prepare material for publication: publCIF (Westrip, 2010).C17H19NO3 | F(000) = 608 |
Mr = 285.33 | Dx = 1.407 Mg m−3 |
Orthorhombic, P212121 | Cu Kα radiation, λ = 1.54180 Å |
Hall symbol: P 2ac 2ab | Cell parameters from 1360 reflections |
a = 7.6989 (10) Å | θ = 3.2–68.2° |
b = 12.737 (4) Å | µ = 0.78 mm−1 |
c = 13.740 (4) Å | T = 173 K |
V = 1347.4 (6) Å3 | Plate, colourless |
Z = 4 | 0.15 × 0.10 × 0.03 mm |
Oxford Diffraction Xcalibur (Ruby, Gemini ultra) diffractometer | 1408 independent reflections |
Radiation source: Enhance (Mo) X-ray Source | 977 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.118 |
Detector resolution: 10.3575 pixels mm-1 | θmax = 68.2°, θmin = 4.7° |
ω scans | h = −9→8 |
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2003) | k = −14→15 |
Tmin = 0.624, Tmax = 1.000 | l = −16→16 |
13009 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)] = 0.068 | H-atom parameters constrained |
wR(F2) = 0.141 | w = 1/[σ2(Fo2) + (0.0112P)2 + 2.P] where P = (Fo2 + 2Fc2)/3 |
S = 1.01 | (Δ/σ)max < 0.001 |
1408 reflections | Δρmax = 0.27 e Å−3 |
192 parameters | Δρmin = −0.26 e Å−3 |
0 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: 0.0043 (4) |
C17H19NO3 | V = 1347.4 (6) Å3 |
Mr = 285.33 | Z = 4 |
Orthorhombic, P212121 | Cu Kα radiation |
a = 7.6989 (10) Å | µ = 0.78 mm−1 |
b = 12.737 (4) Å | T = 173 K |
c = 13.740 (4) Å | 0.15 × 0.10 × 0.03 mm |
Oxford Diffraction Xcalibur (Ruby, Gemini ultra) diffractometer | 1408 independent reflections |
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2003) | 977 reflections with I > 2σ(I) |
Tmin = 0.624, Tmax = 1.000 | Rint = 0.118 |
13009 measured reflections |
R[F2 > 2σ(F2)] = 0.068 | 0 restraints |
wR(F2) = 0.141 | H-atom parameters constrained |
S = 1.01 | Δρmax = 0.27 e Å−3 |
1408 reflections | Δρmin = −0.26 e Å−3 |
192 parameters |
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 > σ(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. The Flack x parameter (Flack, 1983) and the Hooft y parameter (Hooft et al., 2008) were both indeterminate due to a lack of significant resonant scattering. Accordingly, Friedel opposites were merged prior to the final refinement. [Flack, H. D. (1983). Acta Cryst. A39, 876–881; Hooft, R. W. W., Straver, L. H. & Spek, A. L. (2008). J. Appl. Cryst. 41, 96–103.] |
x | y | z | Uiso*/Ueq | ||
O1 | 0.0998 (5) | 0.6564 (3) | 0.7856 (3) | 0.0520 (12) | |
H1 | 0.0431 | 0.7103 | 0.7705 | 0.062* | |
O2 | 0.3165 (5) | 0.4742 (3) | 0.7958 (3) | 0.0466 (11) | |
O3 | 0.1429 (6) | 0.2969 (3) | 0.7838 (3) | 0.0546 (12) | |
H3 | 0.1096 | 0.3587 | 0.7941 | 0.066* | |
N1 | 0.8422 (6) | 0.4378 (4) | 0.5555 (4) | 0.0492 (14) | |
C1 | 0.3549 (8) | 0.6662 (5) | 0.5563 (5) | 0.0458 (15) | |
H1A | 0.3611 | 0.7068 | 0.4984 | 0.055* | |
C2 | 0.2382 (8) | 0.6935 (5) | 0.6290 (5) | 0.0466 (16) | |
H2 | 0.1665 | 0.7534 | 0.6198 | 0.056* | |
C3 | 0.2223 (7) | 0.6362 (5) | 0.7147 (5) | 0.0429 (15) | |
C4 | 0.3281 (7) | 0.5499 (4) | 0.7238 (5) | 0.0408 (14) | |
C5 | 0.2959 (8) | 0.2985 (5) | 0.7233 (5) | 0.0494 (17) | |
H5 | 0.3554 | 0.2293 | 0.7320 | 0.059* | |
C6 | 0.4208 (7) | 0.3836 (5) | 0.7615 (5) | 0.0462 (16) | |
H6 | 0.4902 | 0.3548 | 0.8168 | 0.055* | |
C7 | 0.2554 (9) | 0.3091 (5) | 0.6180 (5) | 0.0499 (17) | |
H7 | 0.1398 | 0.2980 | 0.5961 | 0.060* | |
C8 | 0.3781 (9) | 0.3338 (5) | 0.5537 (5) | 0.0506 (17) | |
H8 | 0.3524 | 0.3340 | 0.4861 | 0.061* | |
C9 | 0.6652 (8) | 0.4267 (5) | 0.5160 (5) | 0.0450 (15) | |
H9 | 0.6748 | 0.3841 | 0.4551 | 0.054* | |
C10 | 0.5732 (8) | 0.5321 (5) | 0.4878 (5) | 0.0491 (17) | |
H10A | 0.6630 | 0.5838 | 0.4686 | 0.059* | |
H10B | 0.4984 | 0.5194 | 0.4304 | 0.059* | |
C11 | 0.4634 (7) | 0.5792 (5) | 0.5682 (4) | 0.0410 (14) | |
C12 | 0.4530 (7) | 0.5257 (5) | 0.6546 (4) | 0.0386 (14) | |
C13 | 0.5465 (8) | 0.4258 (5) | 0.6810 (4) | 0.0415 (15) | |
C14 | 0.5584 (8) | 0.3617 (5) | 0.5888 (5) | 0.0466 (16) | |
H14 | 0.6227 | 0.2953 | 0.6033 | 0.056* | |
C15 | 0.7290 (7) | 0.4477 (5) | 0.7212 (5) | 0.0443 (15) | |
H15A | 0.7199 | 0.4948 | 0.7783 | 0.053* | |
H15B | 0.7818 | 0.3809 | 0.7432 | 0.053* | |
C16 | 0.8453 (8) | 0.4978 (5) | 0.6457 (5) | 0.0521 (17) | |
H16A | 0.8056 | 0.5704 | 0.6329 | 0.062* | |
H16B | 0.9657 | 0.5012 | 0.6708 | 0.062* | |
C17 | 0.9652 (8) | 0.4788 (6) | 0.4841 (5) | 0.060 (2) | |
H17A | 0.9335 | 0.5510 | 0.4672 | 0.090* | |
H17B | 0.9621 | 0.4350 | 0.4254 | 0.090* | |
H17C | 1.0826 | 0.4778 | 0.5117 | 0.090* |
U11 | U22 | U33 | U12 | U13 | U23 | |
O1 | 0.040 (2) | 0.053 (2) | 0.063 (3) | 0.012 (2) | 0.008 (2) | 0.002 (2) |
O2 | 0.031 (2) | 0.048 (2) | 0.060 (3) | 0.0019 (19) | 0.004 (2) | 0.000 (2) |
O3 | 0.040 (2) | 0.050 (2) | 0.074 (3) | −0.006 (2) | 0.014 (3) | −0.002 (2) |
N1 | 0.026 (2) | 0.063 (3) | 0.059 (3) | 0.001 (3) | 0.005 (2) | 0.003 (3) |
C1 | 0.040 (3) | 0.043 (3) | 0.055 (4) | 0.003 (3) | 0.002 (3) | 0.006 (3) |
C2 | 0.035 (3) | 0.044 (3) | 0.061 (5) | 0.008 (3) | −0.004 (3) | 0.000 (3) |
C3 | 0.027 (3) | 0.047 (3) | 0.055 (4) | 0.003 (3) | 0.003 (3) | −0.003 (3) |
C4 | 0.025 (3) | 0.046 (3) | 0.051 (4) | 0.000 (3) | 0.001 (3) | 0.000 (3) |
C5 | 0.034 (3) | 0.048 (4) | 0.066 (5) | −0.006 (3) | 0.009 (3) | −0.001 (3) |
C6 | 0.030 (3) | 0.048 (4) | 0.061 (4) | 0.000 (3) | −0.001 (3) | 0.003 (3) |
C7 | 0.039 (3) | 0.047 (4) | 0.064 (5) | −0.005 (3) | 0.006 (3) | −0.005 (3) |
C8 | 0.044 (3) | 0.052 (4) | 0.056 (4) | −0.005 (3) | 0.003 (3) | −0.008 (3) |
C9 | 0.037 (3) | 0.048 (4) | 0.050 (4) | 0.004 (3) | 0.003 (3) | −0.003 (3) |
C10 | 0.040 (3) | 0.058 (4) | 0.050 (4) | 0.008 (3) | 0.007 (3) | 0.006 (3) |
C11 | 0.030 (3) | 0.047 (3) | 0.045 (4) | 0.004 (3) | 0.003 (3) | −0.006 (3) |
C12 | 0.024 (3) | 0.044 (3) | 0.048 (4) | 0.002 (3) | −0.003 (3) | 0.001 (3) |
C13 | 0.030 (3) | 0.046 (3) | 0.048 (4) | 0.000 (3) | −0.002 (3) | 0.000 (3) |
C14 | 0.038 (3) | 0.038 (3) | 0.065 (5) | −0.001 (3) | −0.001 (3) | 0.002 (3) |
C15 | 0.032 (3) | 0.051 (4) | 0.050 (4) | 0.001 (3) | −0.005 (3) | 0.000 (3) |
C16 | 0.028 (3) | 0.064 (4) | 0.064 (4) | −0.003 (3) | 0.000 (3) | 0.000 (4) |
C17 | 0.033 (3) | 0.080 (5) | 0.066 (5) | 0.000 (4) | 0.008 (3) | 0.008 (4) |
O1—C3 | 1.380 (7) | C7—H7 | 0.9500 |
O1—H1 | 0.8400 | C8—C14 | 1.512 (9) |
O2—C4 | 1.385 (7) | C8—H8 | 0.9500 |
O2—C6 | 1.483 (7) | C9—C14 | 1.538 (9) |
O3—C5 | 1.442 (8) | C9—C10 | 1.566 (9) |
O3—H3 | 0.8400 | C9—H9 | 1.0000 |
N1—C16 | 1.456 (8) | C10—C11 | 1.516 (8) |
N1—C17 | 1.460 (8) | C10—H10A | 0.9900 |
N1—C9 | 1.474 (8) | C10—H10B | 0.9900 |
C1—C2 | 1.387 (9) | C11—C12 | 1.371 (8) |
C1—C11 | 1.397 (8) | C12—C13 | 1.507 (8) |
C1—H1A | 0.9500 | C13—C14 | 1.511 (9) |
C2—C3 | 1.390 (9) | C13—C15 | 1.535 (8) |
C2—H2 | 0.9500 | C14—H14 | 1.0000 |
C3—C4 | 1.374 (8) | C15—C16 | 1.512 (8) |
C4—C12 | 1.387 (8) | C15—H15A | 0.9900 |
C5—C7 | 1.486 (9) | C15—H15B | 0.9900 |
C5—C6 | 1.542 (8) | C16—H16A | 0.9900 |
C5—H5 | 1.0000 | C16—H16B | 0.9900 |
C6—C13 | 1.563 (9) | C17—H17A | 0.9800 |
C6—H6 | 1.0000 | C17—H17B | 0.9800 |
C7—C8 | 1.331 (9) | C17—H17C | 0.9800 |
C3—O1—H1 | 109.5 | C11—C10—C9 | 114.3 (5) |
C4—O2—C6 | 106.2 (4) | C11—C10—H10A | 108.7 |
C5—O3—H3 | 109.5 | C9—C10—H10A | 108.7 |
C16—N1—C17 | 112.0 (5) | C11—C10—H10B | 108.7 |
C16—N1—C9 | 112.2 (5) | C9—C10—H10B | 108.7 |
C17—N1—C9 | 112.7 (5) | H10A—C10—H10B | 107.6 |
C2—C1—C11 | 120.1 (6) | C12—C11—C1 | 117.4 (6) |
C2—C1—H1A | 119.9 | C12—C11—C10 | 117.9 (5) |
C11—C1—H1A | 119.9 | C1—C11—C10 | 124.2 (6) |
C1—C2—C3 | 122.3 (6) | C11—C12—C4 | 121.6 (5) |
C1—C2—H2 | 118.8 | C11—C12—C13 | 126.9 (5) |
C3—C2—H2 | 118.8 | C4—C12—C13 | 110.7 (5) |
C4—C3—O1 | 119.3 (6) | C12—C13—C14 | 106.5 (5) |
C4—C3—C2 | 116.4 (6) | C12—C13—C15 | 111.7 (5) |
O1—C3—C2 | 124.1 (5) | C14—C13—C15 | 110.1 (5) |
C3—C4—O2 | 125.7 (5) | C12—C13—C6 | 99.5 (5) |
C3—C4—C12 | 121.7 (6) | C14—C13—C6 | 116.4 (5) |
O2—C4—C12 | 112.4 (5) | C15—C13—C6 | 112.0 (5) |
O3—C5—C7 | 113.0 (5) | C13—C14—C8 | 109.8 (5) |
O3—C5—C6 | 108.9 (5) | C13—C14—C9 | 106.7 (5) |
C7—C5—C6 | 113.5 (5) | C8—C14—C9 | 114.2 (6) |
O3—C5—H5 | 107.0 | C13—C14—H14 | 108.7 |
C7—C5—H5 | 107.0 | C8—C14—H14 | 108.7 |
C6—C5—H5 | 107.0 | C9—C14—H14 | 108.7 |
O2—C6—C5 | 108.5 (5) | C16—C15—C13 | 111.9 (5) |
O2—C6—C13 | 107.1 (5) | C16—C15—H15A | 109.2 |
C5—C6—C13 | 112.8 (5) | C13—C15—H15A | 109.2 |
O2—C6—H6 | 109.5 | C16—C15—H15B | 109.2 |
C5—C6—H6 | 109.5 | C13—C15—H15B | 109.2 |
C13—C6—H6 | 109.5 | H15A—C15—H15B | 107.9 |
C8—C7—C5 | 121.3 (6) | N1—C16—C15 | 110.7 (5) |
C8—C7—H7 | 119.4 | N1—C16—H16A | 109.5 |
C5—C7—H7 | 119.4 | C15—C16—H16A | 109.5 |
C7—C8—C14 | 119.7 (6) | N1—C16—H16B | 109.5 |
C7—C8—H8 | 120.1 | C15—C16—H16B | 109.5 |
C14—C8—H8 | 120.1 | H16A—C16—H16B | 108.1 |
N1—C9—C14 | 107.8 (5) | N1—C17—H17A | 109.5 |
N1—C9—C10 | 115.3 (5) | N1—C17—H17B | 109.5 |
C14—C9—C10 | 112.4 (5) | H17A—C17—H17B | 109.5 |
N1—C9—H9 | 107.0 | N1—C17—H17C | 109.5 |
C14—C9—H9 | 107.0 | H17A—C17—H17C | 109.5 |
C10—C9—H9 | 107.0 | H17B—C17—H17C | 109.5 |
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O3i | 0.84 | 1.96 | 2.757 (6) | 159 |
O3—H3···O2 | 0.84 | 2.17 | 2.629 (6) | 114 |
Symmetry code: (i) −x, y+1/2, −z+3/2. |
Experimental details
Crystal data | |
Chemical formula | C17H19NO3 |
Mr | 285.33 |
Crystal system, space group | Orthorhombic, P212121 |
Temperature (K) | 173 |
a, b, c (Å) | 7.6989 (10), 12.737 (4), 13.740 (4) |
V (Å3) | 1347.4 (6) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 0.78 |
Crystal size (mm) | 0.15 × 0.10 × 0.03 |
Data collection | |
Diffractometer | Oxford Diffraction Xcalibur (Ruby, Gemini ultra) |
Absorption correction | Multi-scan (CrysAlis PRO; Oxford Diffraction, 2003) |
Tmin, Tmax | 0.624, 1.000 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 13009, 1408, 977 |
Rint | 0.118 |
(sin θ/λ)max (Å−1) | 0.602 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.068, 0.141, 1.01 |
No. of reflections | 1408 |
No. of parameters | 192 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.27, −0.26 |
Computer programs: CrysAlis PRO (Oxford Diffraction, 2003), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), XP in SHELXTL (Bruker, 1998) and Mercury (Bruno et al., 2002), publCIF (Westrip, 2010).
D—H···A | D—H | H···A | D···A | D—H···A |
O1—H1···O3i | 0.84 | 1.96 | 2.757 (6) | 159.4 |
O3—H3···O2 | 0.84 | 2.17 | 2.629 (6) | 114.4 |
Symmetry code: (i) −x, y+1/2, −z+3/2. |
Footnotes
1CAS number: 57–27–2.
Acknowledgements
We thank Volker Kahlenberg for access to the X-ray instrument used in this study. DEB acknowledges financial support from the Hertha Firnberg Programme of the Austrian Science Fund (FWF, project No. T593–N19).
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Morphine is the main alkaloid of opium, the dried latex of the opium poppy (Papaver somniferum). The Cambridge Structural Database (CSD; version 5.33 and updates; Allen, 2002) contains a number of free base and salt structures of morphine: a monohydrate (Bye, 1976), a hydrochloride trihydrate (Gylbert, 1973), a hydroiodide dihydrate (Mackay & Hodgkin, 1955), a complex with β-phenylhydracrylic acid (Lutz & Spek, 1998) and a bis(morphinium) dihydrogensulfate pentahydrate (Wongweichintana et al., 1984). A hydrochloride anhydrate structure was recently reported by us (Gelbrich et al., 2012). The title structure was previously solved from powder data by Guguta et al. (2008), however the corresponding atomic coordinates are not available from the CSD or from supplementary materials accompanying this report.
According to Kofler (1933), morphine can exist in two distinct polymorphic modifications, and the characteristics of the crystals investigated by us match Kofler's description of the stable form. Our thermomicroscopy experiments have shown that the investigated crystals melt under decomposition at 254 °C (the applied heating rate was 5 °C per minute). This behaviour is in agreement with reports given by Kofler (1933) and Kuhnert-Brandstätter et al. (1975).
The geometry of the molecular morphine scaffold (Figure 1) with its five rings agrees with the characteristics of the related salt and free base structures mentioned above. The title structure displays two sets of O—H···O bonds, one of which is intramolecular and the other is intermolecular (Table 1). Intermolecular hydrogen bonds link the morphine molecules into an infinite helical chain that propagates parallel to the b-axis (Figure 2).
The packing of the geometrically inflexible morphine moieties in the title structure was compared with corresponding packing arrangements present in the six morphine forms mentioned above (Bye, 1976; Gelbrich et al., 2012; Gylbert, 1973; Mackay & Hodgkin, 1955; Lutz & Spek, 1998; Wongweichintana et al., 1984), using the program XPac (Gelbrich & Hursthouse, 2005). These comparisons have shown that the packing mode of morphine molecules in the stable form is unique and has no supramolecular constructs in common with any of the other structures in this group.