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ISSN: 2056-9890

Crystal structure of naltrexone chloride solvates with ethanol, propan-2-ol, and 2-methyl­propan-2-ol

aChemistry Department, SUNY Buffalo State, 1300 Elmwood Ave, Buffalo, NY 14222, USA
*Correspondence e-mail: nazareay@buffalostate.edu

Edited by J. P. Jasinsk, Keene State College, USA (Received 31 May 2017; accepted 7 June 2017; online 13 June 2017)

Naltrexone [systematic name: 17-(cyclo­propyl­meth­yl)-3,14-di­hydroxy-4,5α-epoxymorphinan-6-one] is an opioid receptor competitive antagonist that has been widely used to prevent relapse in opioid- and alcohol-dependent subjects. Its chloride salt forms non-isomorphic solvates with ethanol (C20H24NO4+·Cl·C2H5OH) (I), propan-2-ol (C20H24NO4+·Cl·C3H7OH) (II), and 2-methyl­propan-2-ol (C20H24NO4+·Cl·C4H9OH) (III). The naltrexone cation can be described as a T-shape made out of two ring systems, a tetra­hydro-2H-naphtho­[1,8-bc]furan system and a deca­hydro­isoquinolinium subunit, that are nearly perpendicular to one another. The flexible cyclo­propyl­methyl group can adopt various different conformations in response to its surroundings: an increase of available space around cyclo­propyl­methyl group may allow it to adopt a more favorable conformation. In all these structures, the alcohol mol­ecules occupy infinite solvent-filled channels. All three compounds described are attractive crystalline forms for unambiguous identification of naltrexone chloride after isolation from a pharmaceutical form. Compound (III) was refined as a two-component twin.

1. Chemical context

Alcohol and opiate dependence are potentially life-threatening disorders associated with adverse physical and societal effects including poor social functioning, familial problems, and crime (Compton & Volkow, 2006[Compton, W. M. & Volkow, N. D. (2006). Drug Alcohol Depend. 81, 103-107.]). One strategy suggested to address these issues is the inclusion of receptor antagonists that reduce, and can even reverse, the euphoric effects of the drug sought by abusers. Naltrexone [systematic name: 17-(cyclo­propyl­meth­yl)-3,14-di­hydroxy-4,5α-ep­oxy-morphinan-6-one] is an opioid receptor competitive antagonist that has been widely used to prevent relapse in heroin and other opioid-dependent subjects, and has been found to reduce cravings in alcohol-dependent subjects (Roozen et al., 2006[Roozen, H. G., de Waart, R., van der Windt, D. A. W. M., van den Brink, W., de Jong, C. A. J. & Kerkhof, A. J. F. M. (2006). Eur. Neuropsychopharmacol. 16, 311-323.]). Its structure-related analogue oxymorphone is a potent μ-agonist, which differs from naltrexone only in having an N-methyl group in place of an N-cyclo­propyl­methyl group (Amato et al., 1990[Amato, M. E., Bandoli, G., Grassi, A., Nicolini, M. & Pappalardo, G. C. (1990). J. Chem. Soc. Perkin Trans. 2, pp. 1757-1762.]). Elucidation of the conformational profile of naltrexone is of fundamental importance in order to determine mol­ecular requirements for the specific binding affinities of this drug, particularly through the possible position of groups responsible for pharmacological action.

The most common pharmaceutical form of this compound is naltrexone hydro­chloride tablets. The introduction of new crystalline forms of an active pharmaceutical compound provides an opportunity to improve the performance characteristics of a pharmaceutical product. There is a need for new crystalline forms of naltrexone hydro­chloride (Nichols et al., 2013[Nichols, G. A., Menze, M. R. & Mannino, A. (2013). US Patent US 8399475 B2.]) as well for new analytical methods of its unambiguous identification. This communication is a continuation of our work on analytical crystallography of opiate compounds (Gauchat & Naza­renko, 2017[Gauchat, E. & Nazarenko, A. Y. (2017). Acta Cryst. E73, 63-67.]).

[Scheme 1]

2. Structural commentary

In all cases, inter­action with the alcohol mol­ecules does not affect the geometry of the methorphan ring system (Fig. 1[link]), leaving the shape of the organic mol­ecule intact. The bond lengths and angles in the alcohol solvates are not far from expected values and are generally close to those reported for the hydrate structure (Ledain et al., 1992[Ledain, A. C., Madsen, B. W., Skelton, B. W. & White, A. H. (1992). Aust. J. Chem. 45, 635-640.]).

[Figure 1]
Figure 1
The numbering scheme of the naltrexone cation in the ethanol solvate structure (I)[link], with 50% probability ellipsoids. All other naltrexone cations have the same numbering scheme (100 added to each atom number in a second naltrexone cation in structure III).

There are four six-membered rings and a five-membered ring in a naltrexone mol­ecule. The aromatic ring is close to planar, with deviations less than 0.03 Å in all cases. The cyclo­hexadiene ring can be described as a half-chair shifted towards an envelope conformation: atoms C10, C11, C12 and C13 are adjacent to the aromatic ring and therefore almost planar while C9 and C14 deviate from this plane in opposite directions (see Table 1[link] for puckering parameters). A similar observation is true for the di­hydro­furane five-membered ring, which is almost inter­mediate between an envelope and a half-chair with C5 and C13 deviating from the mean plane in opposite directions.

Table 1
Ring puckering analysis (Å, °) of five- and six-membered rings

Ring A di­hydro­furan (atoms O2/C4/C12/C13/C5), ring B piperidine (atoms N1/C9/C14/C13/C15/C16), ring C cyclo­hexa­none (atoms C5/C6/C7/C8/C13/C14) and ring D cyclo­hexadiene (atoms C9/C10/C11/C12/C13/C14).

Ring parameter (I) (II) (III) cation 1 (III) cation 2
A Q 0.341 (2) 0.340 (3) 0.313 (3) 0.341 (3)
  φ 314.5 (4) 314.3 (5) 310.6 (5) 314.4 (5)
B Q 0.637 (2) 0.624 (3) 0.637 (3) 0.636 (3)
  θ 11.28 (18) 10.9 (3) 9.3 (3) 9.6 (3)
  φ 101.0 (9) 110.8 (14) 102.1 (15) 97.6 (15)
C Q 0.546 (3) 0.509 (3) 0.509 (3) 0.516 (3)
  θ 157.3 (2) 157.7 (3) 155.8 (3) 158.5 (3)
  φ 322.5 (7) 343.9 (10) 349.1 (9) 340.4 (10)
D Q 0.495 (2) 0.502 (3) 0.499 (3) 0.508 (3)
  θ 131.6 (2) 134.1 (3) 134.2 (3) 132.1 (3)
  φ 121.2 (3) 122.7 (5) 123.7 (5) 122.4 (4)

The cyclo­hexa­none and piperidine rings both have chair conformations, with cyclo­hexa­none visibly shifted towards half-chair. These two rings are nearly coplanar. As a result, the naltrexone cation can be described as having two ring systems: a phenyl ring with adjacent ep­oxy and cyclo­hexadiene rings (tetra­hydro-2H-naphtho­[1,8-bc]furan system, atoms O2/C1–C4/ C9–C13) and cyclo­hexa­none plus piperidine rings (deca­hydro­isoquinolinium moiety, atoms N1/C5–C9/C13–C16). They are nearly perpendicular to each other, thus forming the well-established T-shape common to morphine, naloxene, and numerous similar mol­ecules (Darling et al., 1982[Darling, S. D., Kolb, V. M., Mandel, G. S. & Mandel, N. S. (1982). J. Pharm. Sci. 71, 763-767.]; Klein et al., 1987[Klein, C. L., Majeste, R. J. & Stevens, E. D. (1987). J. Am. Chem. Soc. 109, 6675-6681.]; Gelbrich et al., 2012[Gelbrich, T., Braun, D. E. & Griesser, U. J. (2012). Acta Cryst. E68, o3358-o3359.]). The angle between two mean planes is 83.9 (1)° for EtOH (I)[link], 83.4 (1)° for i-PrOH (II)[link] and 82.5 (1) and 84.3 (1)° for the two cations in t-BuOH (III)[link] solvate.

What is responsible for switching from a potent opiate agonist (morphine and oxymorphone) to a potent competitive antagonist (naloxene and naltrexone)? It seems certain that changes in a relatively rigid oxymorphone cation are not liable. Overlay calculations show that all three naltrexone solvates fit the same shape (Fig. 2[link]), with r.m.s. deviations being 0.09 (EtOH/i-PrOH), 0.06 and 0.11 Å (EtOH/t-BuOH). The same overlay with an oxymorphone cation (refcode BIZGAS) shows r.m.s. deviations of 0.10 to 0.13 Å and 0.13 Å for naloxene (refcode NALOXC02). It should be taken into account that, in these cases, the temperature of the experiment was different, which obviously increases the discrepancy. Even when we compare morphine (refcode EFASAH; Gelbrich et al., 2012[Gelbrich, T., Braun, D. E. & Griesser, U. J. (2012). Acta Cryst. E68, o3358-o3359.]) and oxymorphone and morphine and naltrexone, the fit is almost identical: r.m.s. deviations of 0.36 and 0.35 Å, respectively, with larger discrepancies coming from obvious structural differences between the phenol group of morphine and a cyclo­hexa­none fragment in oxymorphone and naltrexone. The only flexible locations in the oxymorphone cation are oxygen O1 of the carbonyl group and the orientation of two hydroxyl groups (oxygen atoms O3 and O4), which all potentially form strong hydrogen bonds.

[Figure 2]
Figure 2
Overlay of all four naltrexone cations studied in this work with the cyclo­propyl group omitted.

Therefore, the simplest explanation of antagonist activity is the presence of a small `flat' fragment attached to an N-methyl group: cyclo­propyl in naltrexone or vinyl in naloxene. The link between this small rigid fragment and the oxymorphone cation is flexible: as a result, we see different orientations of the cyclo­propane ring in various solvates of naltrexone. These orientations can be systemized in two groups. First, an overlay of the hydrate (refcode PABCEA) and the ethanol solvate (this work) shows very similar conformations for these two structures (Fig. 3[link]). The orientation of the cyclo­propyl group in the iso-propanol and tert-butanol solvates is also almost the same (Fig. 4[link]). However, these two groups significantly differ from each other (Fig. 5[link]). The angle between the cyclo­propyl group plane and the mean plane of the cyclo­hexa­none and piperidine rings can serve as a qu­anti­tative measure of the methyl­cyclo­propyl fragment orientation. This angle is 36.1° (formate, H2O), 38.6° (H2O), 48.6° (EtOH), 71.7° (i-PrOH), 83.5° and 84.6°Å (t-BuOH); the first two values were calculated from Scheins et al. (2007[Scheins, S., Messerschmidt, M., Morgenroth, W., Paulmann, C. & Luger, P. (2007). J. Phys. Chem. A, 111, 5499-5508.]) and Ledain et al. (1992[Ledain, A. C., Madsen, B. W., Skelton, B. W. & White, A. H. (1992). Aust. J. Chem. 45, 635-640.]). Thus, the conformation of the methyl­cyclo­propyl fragment is very sensitive to its environment.

[Figure 3]
Figure 3
Overlay of both naltrexone cations of the tert-butanol solvate (III)[link] (red and green) and of the propan-2-ol solvate (II)[link] (usual color scheme). The orientation of the cyclo­propyl group is similar in all three cases.
[Figure 4]
Figure 4
Overlay of the naltrexone cations of the ethanol solvate (I)[link] and the tetra­hydrate (refcode PABCEA). The orientation of the cyclo­propyl group is similar in both cases.
[Figure 5]
Figure 5
Overlay of the naltrexone cations of the ethanol solvate (I)[link] and propanol solvate (II)[link]. The orientation of the cyclo­propyl group is visibly different.

3. Supra­molecular features

The way in which a solvate mol­ecule inter­acts with a naltrexone cation is different in all cases studied. Obviously, the strongest possible inter­action is a hydrogen bond associated with the hydroxyl group of the alcohol mol­ecule. However, naltrexone hydro­chloride is an ionic compound and electrostatic inter­action between a positively charged bulk cation and a chloride ion plays an essential role in crystal formation. Electrostatic potential data (Scheins et al., 2007[Scheins, S., Messerschmidt, M., Morgenroth, W., Paulmann, C. & Luger, P. (2007). J. Phys. Chem. A, 111, 5499-5508.]) show more or less uniform positive charge for most of the cation surface, with the obvious exception of the negatively charged oxygen atoms.

In the ethanol solvate (I)[link], the ethanol mol­ecule is disordered; however, both orientations show strong hydrogen bonds with the chloride anion and no direct inter­action with the naltrexone cation. The chloride ion is surrounded by hydroxyl groups belonging to two different cations (Fig. 6[link], Table 1[link]). Inter­estingly, there is no hydrogen bond between the chloride ion and the formally positively charged protonated ammonium nitro­gen atom N1. Instead, there is a strong hydrogen bond between N1 and oxygen atom O1 of the carbonyl group belonging to another cation (Table 2[link]). As a result, the naltrexone cations form infinite chains along the [010] direction. These chains are bound together via hydrogen bonds involving a chloride ion (Fig. 6[link]), forming a layer in the (001) plane. Two pairs of these twin chains surround an infinite channel going along [010] axis containing the chloride ions and ethanol mol­ecules (Fig. 7[link]), thus forming a double layer in the (001) plane. These layers are bound to each other only by weak van der Waals inter­actions, despite the overall positive charge of the cation chains. The shortest contact involves an O2 oxygen atom of one layer and an H15A hydrogen atom of another, and has an O—H separation of 2.60 (2) Å, which is above threshold of hydrogen bonding.

Table 2
Hydrogen-bond geometry (Å, °) for (I)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯O1i 0.85 (3) 2.23 (2) 2.870 (2) 133 (2)
O3—H3⋯Cl01 0.80 (2) 2.23 (2) 3.0297 (17) 171 (2)
O4—H4⋯Cl01ii 0.81 (3) 2.36 (3) 3.1279 (17) 159 (3)
O5—H5A⋯Cl01 0.84 2.33 3.160 (2) 169
Symmetry codes: (i) x, y-1, z; (ii) x+1, y-1, z.
[Figure 6]
Figure 6
Hydrogen bonds around the chloride ion in the ethanol solvate (I)[link].
[Figure 7]
Figure 7
Packing diagram of the ion associates in the ethanol solvate (I)[link], viewed along [010]. There is a visible gap between the bilayers. Chloride ions (green) and ethanol mol­ecules are highlighted.

In the propan-2-ol solvate (II)[link], the alcohol mol­ecule is also partially disordered. Both orientations make hydrogen bonds with ether oxygen atom, O2, of the di­hydro­furan ring (Fig. 8[link]). In this structure, a chloride ion is surrounded by two hydroxyl groups and the protonated nitro­gen atom N1, all belonging to different naltrexone cations (Fig. 9[link], Table 3[link]). These inter­actions result in a three-dimensional network, which has solvent-filled infinite channels oriented along the [100] direction (Fig. 10[link]).

Table 3
Hydrogen-bond geometry (Å, °) for (II)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯Cl1i 0.87 (3) 2.34 (3) 3.102 (3) 146 (1)
O3—H3⋯Cl1ii 0.75 (4) 2.32 (4) 3.066 (3) 169 (4)
O4—H4⋯Cl1 0.85 (4) 2.21 (4) 3.054 (2) 177 (3)
O5—H5A⋯O2 1.00 (6) 2.00 (5) 2.921 (4) 154 (6)
Symmetry codes: (i) [x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z+1]; (ii) [-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].
[Figure 8]
Figure 8
A dashed line indicates the O—H⋯O hydrogen bond connecting a propan-2-ol mol­ecule to an ether group of the naltrexone cation in (II)[link]. The minor component of the disordered propanol mol­ecule is omitted for clarity.
[Figure 9]
Figure 9
N—H⋯Cl and O—H⋯Cl hydrogen bonds around the chloride ion in the propan-2-ol solvate (II)[link]. Note that three different cations are connected.
[Figure 10]
Figure 10
Packing diagram of the naltrexone ion associates in the propan-2-ol solvate (II)[link], viewed along [100]. The chloride ions (green) and solvent mol­ecules are highlighted.

In the 2-methyl­propan-2-ol (tert-butanol) solvate (III)[link], two tert-butanol mol­ecules are connected via inter­molecular hydrogen bonds; one of them makes a hydrogen bond to oxygen atom O2 (Fig. 11[link]) of the naltrexone cation. The same hydroxyl group is located close to another oxygen atom, O3, but the H5A⋯O3 separation (2.774 Å) is too long to be considered a real hydrogen bond. Another naltrexone cation in the same structure does not make direct hydrogen bonds to any solvate mol­ecule. Similar to the propanol solvate, both crystallographically independent chloride ions are surrounded by two hydroxyl groups and protonated nitro­gen atoms N1 and N101, all belonging to different naltrexone cations (Table 4[link]). Again, the resulting three-dimensional network forms solvent-filled channels along the [100] direction (Fig. 12[link]). Contrary to the ethanol solvate, in the propanol and tert-butanol solvates, sequences of chloride ions occupy locations which are separate from the solvent-filled channels.

Table 4
Hydrogen-bond geometry (Å, °) for (III)[link]

D—H⋯A D—H H⋯A DA D—H⋯A
N1—H1⋯Cl1i 0.99 (3) 2.43 (3) 3.245 (3) 140 (3)
O3—H3⋯Cl1 0.84 (4) 2.20 (3) 2.999 (2) 162 (2)
O4—H4⋯Cl2ii 0.86 (3) 2.21 (3) 3.063 (2) 175 (1)
O5—H5A⋯O2 0.87 (5) 2.09 (3) 2.902 (3) 154 (4)
O6—H6⋯O5 0.84 2.03 2.867 (4) 174
N101—H101⋯Cl2iii 0.84 (2) 2.57 (2) 3.239 (3) 138 (2)
O103—H103⋯Cl2 0.87 (4) 2.15 (3) 3.002 (2) 164 (3)
O104—H104⋯Cl1 0.87 (3) 2.16 (3) 3.026 (2) 175 (1)
Symmetry codes: (i) [-x+1, y+{\script{1\over 2}}, -z+1]; (ii) x, y, z+1; (iii) [-x, y-{\script{1\over 2}}, -z].
[Figure 11]
Figure 11
O—H⋯O hydrogen bonds connecting the tert-butanol mol­ecules in (III)[link] to each other and to the ether group of a naltrexone cation.
[Figure 12]
Figure 12
Packing diagram of the naltrexone ion associates in the 2-methyl­propan-2-ol (tert-butanol) solvate (III)[link], viewed along [100]. The chloride ions (green) and solvent mol­ecules are highlighted.

In the tetra­hydrate (refcode PABCEA; Ledain et al., 1992[Ledain, A. C., Madsen, B. W., Skelton, B. W. & White, A. H. (1992). Aust. J. Chem. 45, 635-640.]) and formate hydrate (refcode YIGREM; Scheins et al., 2007[Scheins, S., Messerschmidt, M., Morgenroth, W., Paulmann, C. & Luger, P. (2007). J. Phys. Chem. A, 111, 5499-5508.]), naltrexone cations form a chain via the protonated nitro­gen atom and an oxygen atom of a carbonyl group, similar to what we see in the ethanol solvate. Water mol­ecules and chloride ions also occupy a channel, this time along [001]. However, contrary to the ethanol solvate, the tetra­hydrate structure does not exhibit a layered layout.

It is worth mentioning that in the ethanol solvate of oxymorphone hydro­chloride (Darling et al., 1982[Darling, S. D., Kolb, V. M., Mandel, G. S. & Mandel, N. S. (1982). J. Pharm. Sci. 71, 763-767.]), the ethanol mol­ecule makes a weak hydrogen bond with the phenolic hy­droxy group (atom O3 in our numbering scheme).

A plausible assumption is that inter­action with an alcohol solvate mol­ecule (or absence of it) does not affect significantly the structure of the naltrexone cation. Obviously, the presence of a strong hydrogen bond at the cyclo­hexa­none carbonyl oxygen atom O1 (e.g., hydrate and ethanol solvate) is important; this affects the geometry of the cyclo­hexa­none moiety and, possibly, the orientation of the methyl­cyclo­propyl residue. Another significant factor is the size of a solvent-filled void. An increase of available space around the cyclo­propyl­methyl group may allow it to adopt a more favorable conformation.

4. Database survey

There are three reported naltrexone structures deposited in the Cambridge Structural Database (CSD Version 5.37; Groom et al., 2016[Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171-179.]). Of these, two report the structures of the chloride salt at room temperature (refcodes XINSAP and PABCEA), one of which (Sugimoto et al., 2007[Sugimoto, K., Dinnebier, R. E. & Zakrzewski, M. (2007). J. Pharm. Sci. 96, 3316-3323.]) is a powder structure of its anhydrous salt and the other (Ledain et al., 1992[Ledain, A. C., Madsen, B. W., Skelton, B. W. & White, A. H. (1992). Aust. J. Chem. 45, 635-640.]) a single-crystal investigation of tetra­hydrate. A high-quality charge-density investigation of the neutral naltrexone mol­ecule and protonated naltrexone formate (refcodes YIGRAI and YIGREM; Scheins et al., 2007[Scheins, S., Messerschmidt, M., Morgenroth, W., Paulmann, C. & Luger, P. (2007). J. Phys. Chem. A, 111, 5499-5508.]) was performed at 100 K. A room-temperature structure of naltrexone malonate (refcode JEXRAF; Amato et al., 1990[Amato, M. E., Bandoli, G., Grassi, A., Nicolini, M. & Pappalardo, G. C. (1990). J. Chem. Soc. Perkin Trans. 2, pp. 1757-1762.]) is also known. The existence of various solvates of naltrexone chloride was reported from powder data (Nichols et al., 2013[Nichols, G. A., Menze, M. R. & Mannino, A. (2013). US Patent US 8399475 B2.]); however, no structural results were provided.

The crystal structure of oxymorphone hydro­chloride monohydrate ethanol solvate (refcode BIZGAS) is also known (Darling et al., 1982[Darling, S. D., Kolb, V. M., Mandel, G. S. & Mandel, N. S. (1982). J. Pharm. Sci. 71, 763-767.]). The experimental electron-density distribution of naloxone hydro­chloride dihydrate (refcode NALOXC02), another similar potent opiate antagonist, was described by Klein et al. (1987[Klein, C. L., Majeste, R. J. & Stevens, E. D. (1987). J. Am. Chem. Soc. 109, 6675-6681.]).

5. Synthesis and crystallization

Naltrexone hydro­chloride (INTAS Ltd, India) was obtained as a mixture with lactose. The target compound was extracted from its starting form by recrystallization in ethanol, iso-propanol, and tert-butanol. FTIR and Raman spectra of purified samples were consistent with database data for naltrexone hydro­chloride. A GC–MS study showed one single peak on the chromatogram with m/z: 341(M+), 300 (M − C3H5), 286 (M − C4H7). A portion of the extracted naltrexone was then derivatized using penta­fluoro­propionic anhydride (PFPA), resulting in a corresponding di­penta­fluoro­propionate (m/z): 633 (M), 592 (M − C3H5), 486 (M − C3F5O). This is consistent with the existence of two hydroxyl groups in the naltrexone mol­ecule and confirms the correct chemical formula.

Nevertheless, diffractograms obtained from the crystallized material were all different from each other and from known naltrexone hydro­chloride hydrate and naltrexone hydro­chloride crystals (Ledain et al., 1992[Ledain, A. C., Madsen, B. W., Skelton, B. W. & White, A. H. (1992). Aust. J. Chem. 45, 635-640.]; Sugimoto et al., 2007[Sugimoto, K., Dinnebier, R. E. & Zakrzewski, M. (2007). J. Pharm. Sci. 96, 3316-3323.]; Nichols et al., 2013[Nichols, G. A., Menze, M. R. & Mannino, A. (2013). US Patent US 8399475 B2.]). The quality of some of the solvate crystals was sufficient for single crystal investigation. Herein we report the results obtained.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 5[link].

Table 5
Experimental details

  (I) (II) (III)
Crystal data
Chemical formula C20H24NO4+·Cl·C2H6O C20H24NO4+·Cl·C3H8O C20H24NO4+·ClC4H10O
Mr 423.92 437.94 451.97
Crystal system, space group Monoclinic, P21 Orthorhombic, P212121 Monoclinic, P21
Temperature (K) 173 173 173
a, b, c (Å) 8.6885 (7), 7.9478 (6), 15.3417 (10) 8.0297 (10), 15.5449 (17), 17.560 (4) 8.8487 (4), 17.3281 (9), 15.5702 (8)
α, β, γ (°) 90, 103.908 (2), 90 90, 90, 90 90, 92.702 (2), 90
V3) 1028.35 (13) 2191.9 (6) 2384.7 (2)
Z 2 4 4
Radiation type Mo Kα Mo Kα Cu Kα
μ (mm−1) 0.22 0.21 1.70
Crystal size (mm) 0.56 × 0.13 × 0.06 0.2 × 0.16 × 0.15 0.26 × 0.22 × 0.20
 
Data collection
Diffractometer Bruker PHOTON-100 CMOS Bruker PHOTON-100 CMOS Bruker PHOTON-100 CMOS
Absorption correction Multi-scan (SADABS; Bruker, 2015[Bruker (2015). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Multi-scan (SADABS; Bruker, 2015[Bruker (2015). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Multi-scan (TWINABS; Bruker, 2012[Bruker (2012). TWINABS. Bruker AXS Inc., Madison, Wisconsin, USA.])
Tmin, Tmax 0.891, 1.000 0.925, 0.986  
No. of measured, independent and observed [I > 2σ(I)] reflections 33845, 5866, 5008 48846, 5327, 4481 9642, 9642, 8820
Rint 0.042 0.043  
(sin θ/λ)max−1) 0.700 0.665 0.625
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.082, 1.03 0.045, 0.112, 1.09 0.033, 0.079, 1.04
No. of reflections 5866 5327 9642
No. of parameters 305 313 581
No. of restraints 10 16 1
H-atom treatment H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.32, −0.24 0.33, −0.34 0.20, −0.17
Absolute structure Flack x determined using 2015 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) Flack x determined using 1682 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.]) Flack x determined using 3828 quotients [(I+)−(I)]/[(I+)+(I)] (Parsons et al., 2013[Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249-259.])
Absolute structure parameter −0.017 (18) −0.028 (18) −0.004 (5)
Computer programs: APEX2 and SAINT (Bruker, 2013[Bruker (2013). APEX2 and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA.]), SHELXT (Sheldrick, 2015a[Sheldrick, G. M. (2015a). Acta Cryst. A71, 3-8.]), SHELXL2014 (Sheldrick, 2015b[Sheldrick, G. M. (2015b). Acta Cryst. C71, 3-8.]), OLEX2 (Dolomanov et al., 2009[Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339-341.]), Mercury (Macrae et al., 2006[Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453-457.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]).

In the ethanol solvate (I)[link], the solvent mol­ecules are disordered with occupancies being approximately in a 2:1 ratio [0.66 (3):0.34 (3)]. Rigid body restrains (RIGU) were applied during refinement. In the propanol solvate (II)[link], the occupancy of the minor component of a disordered solvent mol­ecule is only 0.178 (9), which required additional constraints (EXYZ and EADP) on the position of the hy­droxy group atoms. The tert-butanol solvate structure (III)[link] was refined as a two-component twin (twin matrix: −1.000 0.000 0.000 −0.001 −1.000 0.000 0.164 0.000 1.000). There is visible flexibility in positions of the methyl groups of the tertiary tert-butanol mol­ecules, which results in larger displacement parameters and could be potentially treated as disorder. However, we do not see the need for additional over-complication of the refinement procedure.

Hydrogen atoms of the hydroxyl groups were refined with riding coordinates and stretchable bonds. Hydrogen atoms of the protonated amine were refined isotropically or with riding coordinates and stretchable bonds, with Uiso = 1.2Uiso(N) in all cases. All other hydrogen atoms were refined with riding coordinates, with Uiso = 1.5Uiso(C) for methyl groups and Uiso = 1.2Uiso(C) for all others.

Supporting information


Computing details top

For all compounds, data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); 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) and Mercury (Macrae et al., 2006) for (I); OLEX2 (Dolomanov et al., 2009) for (II), (III). Software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009) and PLATON (Spek, 2009) for (I); OLEX2 (Dolomanov et al., 2009) for (II), (III).

(I) 17-(Cyclopropylmethyl)-3,14-dihydroxy-4,5a-epoxymorphinan-6-one hydrochloride ethanol monosolvate top
Crystal data top
C20H24NO4+·Cl·C2H6OF(000) = 452
Mr = 423.92Dx = 1.369 Mg m3
Monoclinic, P21Mo Kα radiation, λ = 0.71073 Å
a = 8.6885 (7) ÅCell parameters from 3107 reflections
b = 7.9478 (6) Åθ = 2.9–26.4°
c = 15.3417 (10) ŵ = 0.22 mm1
β = 103.908 (2)°T = 173 K
V = 1028.35 (13) Å3Needle, colourless
Z = 20.56 × 0.13 × 0.06 mm
Data collection top
Bruker PHOTON-100 CMOS
diffractometer
5008 reflections with I > 2σ(I)
Radiation source: sealed tubeRint = 0.042
φ and ω scansθmax = 29.9°, θmin = 2.9°
Absorption correction: multi-scan
(SADABS; Bruker, 2015)
h = 1212
Tmin = 0.891, Tmax = 1.000k = 1011
33845 measured reflectionsl = 2121
5866 independent reflections
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.038 w = 1/[σ2(Fo2) + (0.0403P)2 + 0.1718P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.082(Δ/σ)max < 0.001
S = 1.03Δρmax = 0.32 e Å3
5866 reflectionsΔρmin = 0.24 e Å3
305 parametersAbsolute structure: Flack x determined using 2015 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
10 restraintsAbsolute structure parameter: 0.017 (18)
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
xyzUiso*/UeqOcc. (<1)
O10.8998 (2)0.8845 (2)0.08336 (11)0.0259 (4)
O20.64317 (17)0.68560 (19)0.04754 (10)0.0203 (3)
O30.42853 (18)0.8802 (2)0.12744 (11)0.0223 (3)
H30.401 (3)0.943 (3)0.1618 (14)0.033*
O41.03919 (19)0.29776 (19)0.11509 (10)0.0190 (3)
H41.129 (4)0.273 (3)0.1404 (13)0.029*
N10.8634 (2)0.1391 (2)0.20958 (11)0.0163 (3)
H10.923 (3)0.101 (3)0.1776 (17)0.020*
C10.6310 (3)0.5970 (3)0.31115 (15)0.0210 (5)
H1A0.6326 (3)0.5760 (7)0.3709 (19)0.025*
C20.5273 (3)0.7163 (3)0.26364 (15)0.0214 (5)
H20.456 (2)0.7737 (17)0.2936 (9)0.026*
C30.5215 (2)0.7569 (3)0.17401 (15)0.0190 (4)
C40.6221 (2)0.6658 (3)0.13365 (13)0.0170 (4)
C50.7949 (2)0.6061 (3)0.04998 (14)0.0170 (4)
H50.7973 (3)0.5645 (12)0.0074 (16)0.020*
C60.9275 (3)0.7348 (3)0.08214 (14)0.0184 (4)
C71.0886 (3)0.6620 (3)0.11905 (15)0.0238 (4)
H7A1.1658 (16)0.7513 (18)0.1360 (4)0.029*
H7B1.1194 (7)0.5929 (14)0.0741 (9)0.029*
C81.0822 (3)0.5547 (3)0.20189 (15)0.0192 (4)
H8A1.186 (2)0.5160 (8)0.2306 (6)0.023*
H8B1.0434 (8)0.6210 (13)0.2440 (8)0.023*
C90.9473 (2)0.2976 (3)0.25188 (13)0.0149 (4)
H91.052 (3)0.2645 (9)0.2875 (9)0.018*
C100.8594 (2)0.3851 (3)0.31563 (14)0.0177 (4)
H10A0.8098 (9)0.2985 (16)0.3456 (6)0.021*
H10B0.9375 (14)0.4451 (11)0.3623 (9)0.021*
C110.7335 (2)0.5080 (3)0.26984 (14)0.0165 (4)
C120.7207 (2)0.5434 (3)0.18062 (14)0.0157 (4)
C130.8071 (2)0.4592 (3)0.11827 (13)0.0144 (4)
C140.9728 (2)0.4048 (3)0.17174 (13)0.0145 (4)
C150.7130 (2)0.3023 (3)0.07757 (14)0.0175 (4)
H15A0.609 (2)0.3349 (7)0.0464 (6)0.021*
H15B0.7633 (10)0.2520 (10)0.0356 (8)0.021*
C160.7020 (2)0.1746 (3)0.14941 (14)0.0197 (4)
H16A0.6339 (13)0.2165 (8)0.1845 (7)0.024*
H16B0.6575 (9)0.0730 (19)0.1217 (5)0.024*
C170.8565 (3)0.0007 (3)0.27469 (15)0.0217 (5)
H17A0.7851 (15)0.0308 (7)0.3109 (7)0.026*
H17B0.8148 (9)0.100 (2)0.2417 (7)0.026*
C181.0151 (3)0.0406 (3)0.33484 (16)0.0248 (5)
H181.100 (3)0.0555 (5)0.3062 (9)0.030*
C191.0167 (4)0.1523 (4)0.41391 (19)0.0374 (6)
H19A0.917 (2)0.1882 (10)0.4233 (3)0.045*
H19B1.100 (2)0.233 (2)0.4301 (4)0.045*
C201.0588 (4)0.0293 (4)0.42825 (17)0.0360 (6)
H20A1.166 (3)0.0567 (8)0.4528 (6)0.043*
H20B0.9850 (17)0.1009 (17)0.4460 (5)0.043*
O50.6227 (2)1.1314 (4)0.42038 (13)0.0522 (6)
H5A0.55521.14650.37170.078*0.66 (3)
H5B0.55461.14130.37150.078*0.34 (3)
C210.5677 (11)1.0028 (15)0.4713 (7)0.046 (2)0.66 (3)
H21A0.5584 (11)0.888 (5)0.4362 (15)0.055*0.66 (3)
H21B0.454 (4)1.0348 (19)0.4790 (7)0.055*0.66 (3)
C21A0.557 (3)1.049 (5)0.4808 (19)0.086 (9)0.34 (3)
H21C0.46440.98300.44840.103*0.34 (3)
H21D0.52081.13160.51960.103*0.34 (3)
C220.6769 (13)0.9820 (15)0.5609 (6)0.0408 (19)0.66 (3)
H22A0.781 (4)0.955 (5)0.5540 (6)0.061*0.66 (3)
H22B0.640 (3)0.893 (4)0.5925 (16)0.061*0.66 (3)
H22C0.681 (4)1.085 (4)0.5942 (15)0.061*0.66 (3)
C22A0.673 (3)0.937 (3)0.5356 (18)0.054 (5)0.34 (3)
H22D0.70090.84890.49780.081*0.34 (3)
H22E0.62720.88620.58190.081*0.34 (3)
H22F0.76761.00140.56420.081*0.34 (3)
Cl010.34066 (7)1.14944 (8)0.24667 (4)0.03172 (15)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0362 (9)0.0179 (8)0.0254 (9)0.0005 (7)0.0110 (7)0.0014 (7)
O20.0210 (7)0.0243 (9)0.0158 (7)0.0047 (6)0.0047 (6)0.0021 (6)
O30.0208 (8)0.0216 (8)0.0240 (8)0.0054 (7)0.0046 (6)0.0015 (7)
O40.0186 (7)0.0218 (8)0.0187 (7)0.0034 (6)0.0084 (6)0.0018 (6)
N10.0202 (8)0.0133 (8)0.0168 (8)0.0008 (7)0.0073 (6)0.0004 (7)
C10.0236 (11)0.0245 (11)0.0165 (10)0.0017 (8)0.0081 (9)0.0008 (8)
C20.0202 (11)0.0233 (11)0.0233 (11)0.0021 (9)0.0102 (9)0.0028 (9)
C30.0148 (10)0.0191 (10)0.0225 (10)0.0004 (8)0.0033 (8)0.0018 (8)
C40.0165 (9)0.0190 (10)0.0154 (9)0.0019 (8)0.0036 (7)0.0010 (8)
C50.0203 (10)0.0177 (10)0.0138 (9)0.0021 (8)0.0059 (8)0.0005 (7)
C60.0257 (11)0.0185 (10)0.0141 (10)0.0019 (8)0.0105 (8)0.0008 (8)
C70.0218 (10)0.0198 (10)0.0316 (12)0.0051 (10)0.0100 (9)0.0036 (10)
C80.0181 (10)0.0180 (10)0.0210 (10)0.0034 (8)0.0035 (8)0.0000 (8)
C90.0160 (9)0.0130 (9)0.0155 (9)0.0013 (8)0.0036 (7)0.0006 (8)
C100.0217 (10)0.0181 (10)0.0138 (9)0.0002 (9)0.0054 (8)0.0001 (8)
C110.0172 (10)0.0170 (10)0.0159 (10)0.0017 (8)0.0051 (8)0.0020 (8)
C120.0140 (9)0.0158 (10)0.0178 (10)0.0018 (8)0.0050 (8)0.0027 (8)
C130.0160 (10)0.0145 (10)0.0134 (9)0.0016 (7)0.0050 (7)0.0005 (7)
C140.0150 (9)0.0153 (10)0.0136 (10)0.0004 (7)0.0044 (7)0.0013 (8)
C150.0178 (10)0.0180 (10)0.0156 (9)0.0019 (8)0.0018 (8)0.0018 (8)
C160.0192 (10)0.0192 (11)0.0204 (10)0.0052 (8)0.0045 (8)0.0026 (9)
C170.0313 (12)0.0151 (10)0.0210 (10)0.0046 (9)0.0110 (9)0.0013 (9)
C180.0330 (13)0.0196 (11)0.0244 (12)0.0040 (9)0.0121 (10)0.0034 (9)
C190.0511 (17)0.0309 (15)0.0312 (14)0.0082 (12)0.0120 (12)0.0132 (11)
C200.0440 (16)0.0339 (14)0.0253 (13)0.0051 (12)0.0008 (11)0.0028 (11)
O50.0357 (10)0.0836 (18)0.0374 (11)0.0014 (12)0.0089 (8)0.0167 (12)
C210.029 (3)0.073 (5)0.034 (3)0.009 (4)0.002 (3)0.000 (3)
C21A0.068 (10)0.131 (18)0.076 (13)0.042 (10)0.054 (9)0.059 (13)
C220.037 (3)0.060 (5)0.025 (3)0.007 (3)0.006 (3)0.000 (3)
C22A0.053 (8)0.058 (11)0.056 (11)0.003 (8)0.023 (9)0.008 (8)
Cl010.0290 (3)0.0350 (3)0.0319 (3)0.0134 (3)0.0090 (2)0.0008 (3)
Geometric parameters (Å, º) top
O1—C61.215 (3)C12—C131.507 (3)
O2—C41.386 (2)C13—C141.538 (3)
O2—C51.454 (2)C13—C151.539 (3)
O3—H30.80 (3)C15—H15A0.949 (18)
O3—C31.359 (3)C15—H15B0.949 (18)
O4—H40.81 (3)C15—C161.518 (3)
O4—C141.433 (2)C16—H16A0.950 (18)
N1—H10.85 (3)C16—H16B0.950 (18)
N1—C91.521 (3)C17—H17A0.960 (19)
N1—C161.509 (3)C17—H17B0.960 (19)
N1—C171.505 (3)C17—C181.497 (3)
C1—H1A0.93 (3)C18—H180.95 (3)
C1—C21.388 (3)C18—C191.500 (3)
C1—C111.402 (3)C18—C201.498 (4)
C2—H20.97 (3)C19—H19A0.96 (2)
C2—C31.402 (3)C19—H19B0.96 (2)
C3—C41.390 (3)C19—C201.492 (4)
C4—C121.379 (3)C20—H20A0.95 (2)
C5—H50.95 (3)C20—H20B0.95 (2)
C5—C61.531 (3)O5—H5A0.8400
C5—C131.555 (3)O5—H5B0.8400
C6—C71.494 (3)O5—C211.437 (10)
C7—H7A0.968 (19)O5—C21A1.37 (2)
C7—H7B0.968 (19)C21—H21A1.05 (4)
C7—C81.543 (3)C21—H21B1.05 (4)
C8—H8A0.956 (18)C21—C221.480 (13)
C8—H8B0.956 (18)C21A—H21C0.9900
C8—C141.524 (3)C21A—H21D0.9900
C9—H90.98 (2)C21A—C22A1.44 (4)
C9—C101.543 (3)C22—H22A0.96 (3)
C9—C141.555 (3)C22—H22B0.96 (3)
C10—H10A0.983 (18)C22—H22C0.96 (3)
C10—H10B0.983 (18)C22A—H22D0.9800
C10—C111.509 (3)C22A—H22E0.9800
C11—C121.376 (3)C22A—H22F0.9800
C4—O2—C5104.64 (15)O4—C14—C9107.99 (16)
C3—O3—H3109.5O4—C14—C13107.76 (16)
C14—O4—H4109.5C8—C14—C9112.67 (16)
C9—N1—H1104.3 (17)C8—C14—C13112.20 (17)
C16—N1—H1108.6 (17)C13—C14—C9106.39 (16)
C16—N1—C9112.68 (17)C13—C15—H15A109.3
C17—N1—H1104.2 (17)C13—C15—H15B109.3
C17—N1—C9114.83 (15)H15A—C15—H15B108.0
C17—N1—C16111.38 (16)C16—C15—C13111.55 (17)
C2—C1—H1A119.7C16—C15—H15A109.3
C2—C1—C11120.7 (2)C16—C15—H15B109.3
C11—C1—H1A119.7N1—C16—C15110.95 (16)
C1—C2—H2118.7N1—C16—H16A109.4
C1—C2—C3122.6 (2)N1—C16—H16B109.4
C3—C2—H2118.7C15—C16—H16A109.4
O3—C3—C2123.96 (19)C15—C16—H16B109.4
O3—C3—C4119.97 (19)H16A—C16—H16B108.0
C4—C3—C2116.1 (2)N1—C17—H17A109.0
O2—C4—C3127.38 (19)N1—C17—H17B109.0
C12—C4—O2111.74 (17)H17A—C17—H17B107.8
C12—C4—C3120.84 (19)C18—C17—N1112.82 (18)
O2—C5—H5110.5C18—C17—H17A109.0
O2—C5—C6109.01 (16)C18—C17—H17B109.0
O2—C5—C13104.95 (15)C17—C18—H18116.2
C6—C5—H5110.5C17—C18—C19116.9 (2)
C6—C5—C13111.12 (17)C17—C18—C20119.7 (2)
C13—C5—H5110.5C19—C18—H18116.2
O1—C6—C5121.5 (2)C20—C18—H18116.2
O1—C6—C7123.0 (2)C20—C18—C1959.68 (18)
C7—C6—C5115.32 (18)C18—C19—H19A117.8
C6—C7—H7A110.1C18—C19—H19B117.8
C6—C7—H7B110.1H19A—C19—H19B114.9
C6—C7—C8108.08 (17)C20—C19—C1860.09 (17)
H7A—C7—H7B108.4C20—C19—H19A117.8
C8—C7—H7A110.1C20—C19—H19B117.8
C8—C7—H7B110.1C18—C20—H20A117.7
C7—C8—H8A109.9C18—C20—H20B117.7
C7—C8—H8B109.9C19—C20—C1860.23 (18)
H8A—C8—H8B108.3C19—C20—H20A117.7
C14—C8—C7108.99 (18)C19—C20—H20B117.7
C14—C8—H8A109.9H20A—C20—H20B114.9
C14—C8—H8B109.9C21—O5—H5A109.5
N1—C9—H9107.5C21A—O5—H5B109.5
N1—C9—C10112.62 (16)O5—C21—H21A109.4
N1—C9—C14105.16 (15)O5—C21—H21B109.4
C10—C9—H9107.5O5—C21—C22111.2 (7)
C10—C9—C14116.16 (17)H21A—C21—H21B108.0
C14—C9—H9107.5C22—C21—H21A109.4
C9—C10—H10A108.7C22—C21—H21B109.4
C9—C10—H10B108.7O5—C21A—H21C109.6
H10A—C10—H10B107.6O5—C21A—H21D109.6
C11—C10—C9114.23 (17)O5—C21A—C22A110 (2)
C11—C10—H10A108.7H21C—C21A—H21D108.1
C11—C10—H10B108.7C22A—C21A—H21C109.6
C1—C11—C10125.78 (18)C22A—C21A—H21D109.6
C12—C11—C1115.99 (19)C21—C22—H22A109.5
C12—C11—C10118.16 (18)C21—C22—H22B109.5
C4—C12—C13108.85 (17)C21—C22—H22C109.5
C11—C12—C4123.76 (19)H22A—C22—H22B109.5
C11—C12—C13127.38 (19)H22A—C22—H22C109.5
C12—C13—C597.49 (16)H22B—C22—H22C109.5
C12—C13—C14109.36 (16)C21A—C22A—H22D109.5
C12—C13—C15108.69 (16)C21A—C22A—H22E109.5
C14—C13—C5118.28 (16)C21A—C22A—H22F109.5
C14—C13—C15109.06 (16)H22D—C22A—H22E109.5
C15—C13—C5113.06 (17)H22D—C22A—H22F109.5
O4—C14—C8109.61 (16)H22E—C22A—H22F109.5
O1—C6—C7—C8113.2 (2)C6—C5—C13—C1432.8 (2)
O2—C4—C12—C11174.46 (19)C6—C5—C13—C15161.98 (16)
O2—C4—C12—C135.8 (2)C6—C7—C8—C1465.5 (2)
O2—C5—C6—O115.5 (3)C7—C8—C14—O464.8 (2)
O2—C5—C6—C7159.27 (16)C7—C8—C14—C9174.96 (17)
O2—C5—C13—C1233.70 (19)C7—C8—C14—C1354.9 (2)
O2—C5—C13—C14150.48 (16)C9—N1—C16—C1555.4 (2)
O2—C5—C13—C1580.3 (2)C9—N1—C17—C1851.0 (2)
O3—C3—C4—O20.7 (3)C9—C10—C11—C1176.4 (2)
O3—C3—C4—C12178.14 (19)C9—C10—C11—C126.8 (3)
N1—C9—C10—C1187.3 (2)C10—C9—C14—O4173.55 (16)
N1—C9—C14—O448.3 (2)C10—C9—C14—C865.3 (2)
N1—C9—C14—C8169.51 (16)C10—C9—C14—C1358.1 (2)
N1—C9—C14—C1367.15 (19)C10—C11—C12—C4173.06 (19)
N1—C17—C18—C19167.9 (2)C10—C11—C12—C137.3 (3)
N1—C17—C18—C2099.2 (3)C11—C1—C2—C31.5 (3)
C1—C2—C3—O3175.7 (2)C11—C12—C13—C5156.2 (2)
C1—C2—C3—C42.4 (3)C11—C12—C13—C1432.7 (3)
C1—C11—C12—C44.1 (3)C11—C12—C13—C1586.3 (2)
C1—C11—C12—C13175.5 (2)C12—C13—C14—O4169.02 (16)
C2—C1—C11—C10175.2 (2)C12—C13—C14—C870.2 (2)
C2—C1—C11—C121.7 (3)C12—C13—C14—C953.4 (2)
C2—C3—C4—O2177.5 (2)C12—C13—C15—C1662.3 (2)
C2—C3—C4—C120.1 (3)C13—C5—C6—O1130.7 (2)
C3—C4—C12—C113.3 (3)C13—C5—C6—C744.1 (2)
C3—C4—C12—C13176.38 (19)C13—C15—C16—N150.5 (2)
C4—O2—C5—C686.73 (19)C14—C9—C10—C1134.0 (2)
C4—O2—C5—C1332.4 (2)C14—C13—C15—C1656.9 (2)
C4—C12—C13—C524.1 (2)C15—C13—C14—O450.3 (2)
C4—C12—C13—C14147.62 (17)C15—C13—C14—C8171.03 (17)
C4—C12—C13—C1593.4 (2)C15—C13—C14—C965.34 (19)
C5—O2—C4—C3160.5 (2)C16—N1—C9—C1064.0 (2)
C5—O2—C4—C1217.1 (2)C16—N1—C9—C1463.42 (19)
C5—C6—C7—C861.5 (2)C16—N1—C17—C18179.37 (18)
C5—C13—C14—O480.7 (2)C17—N1—C9—C1065.0 (2)
C5—C13—C14—C840.0 (2)C17—N1—C9—C14167.63 (16)
C5—C13—C14—C9163.64 (16)C17—N1—C16—C15173.89 (17)
C5—C13—C15—C16169.37 (17)C17—C18—C19—C20110.3 (3)
C6—C5—C13—C1283.98 (18)C17—C18—C20—C19105.6 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O1i0.85 (3)2.23 (2)2.870 (2)133 (2)
O3—H3···Cl010.80 (2)2.23 (2)3.0297 (17)171 (2)
O4—H4···Cl01ii0.81 (3)2.36 (3)3.1279 (17)159 (3)
O5—H5A···Cl010.842.333.160 (2)169
Symmetry codes: (i) x, y1, z; (ii) x+1, y1, z.
(II) 17-(Cyclopropylmethyl)-3,14-dihydroxy-4,5a-epoxymorphinan-6-one hydrochloride propan-2-ol monosolvate top
Crystal data top
C20H24NO4+·Cl·C3H8ODx = 1.327 Mg m3
Mr = 437.94Mo Kα radiation, λ = 0.71073 Å
Orthorhombic, P212121Cell parameters from 9935 reflections
a = 8.0297 (10) Åθ = 2.9–27.3°
b = 15.5449 (17) ŵ = 0.21 mm1
c = 17.560 (4) ÅT = 173 K
V = 2191.9 (6) Å3Block, colourless
Z = 40.2 × 0.16 × 0.15 mm
F(000) = 936
Data collection top
Bruker PHOTON-100 CMOS
diffractometer
4481 reflections with I > 2σ(I)
Radiation source: sealedtubeRint = 0.043
φ and ω scansθmax = 28.2°, θmin = 2.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2015)
h = 1010
Tmin = 0.925, Tmax = 0.986k = 2019
48846 measured reflectionsl = 2322
5327 independent reflections
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.045 w = 1/[σ2(Fo2) + (0.0589P)2 + 0.6347P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.112(Δ/σ)max < 0.001
S = 1.09Δρmax = 0.33 e Å3
5327 reflectionsΔρmin = 0.34 e Å3
313 parametersAbsolute structure: Flack x determined using 1682 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
16 restraintsAbsolute structure parameter: 0.028 (18)
Primary atom site location: structure-invariant direct methods
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
xyzUiso*/UeqOcc. (<1)
Cl10.47836 (9)0.21061 (5)0.49145 (4)0.02955 (19)
O10.6306 (3)0.63086 (16)0.64326 (15)0.0468 (7)
O20.3209 (3)0.61657 (13)0.70324 (11)0.0291 (5)
O30.3306 (3)0.67460 (13)0.86078 (13)0.0334 (5)
H30.366 (6)0.6819 (6)0.900 (2)0.050*
O40.3504 (3)0.38140 (14)0.55436 (11)0.0264 (5)
H40.390 (4)0.335 (3)0.5370 (11)0.040*
N10.1648 (3)0.29790 (15)0.66310 (13)0.0211 (5)
H10.1568 (4)0.2926 (3)0.614 (2)0.025*
C10.3664 (4)0.4365 (2)0.87554 (18)0.0340 (7)
H1A0.3784 (7)0.3966 (19)0.9112 (17)0.041*
C20.3557 (4)0.5228 (2)0.89661 (18)0.0332 (7)
H20.3587 (4)0.5365 (6)0.947 (2)0.040*
C30.3405 (4)0.58920 (19)0.84301 (17)0.0270 (6)
C40.3334 (4)0.56354 (18)0.76731 (16)0.0238 (6)
C50.3665 (4)0.56083 (18)0.63904 (16)0.0268 (6)
H50.30630.57980.59210.032*
C60.5551 (4)0.5665 (2)0.62618 (17)0.0297 (7)
C70.6358 (4)0.4886 (2)0.59096 (19)0.0329 (7)
H7A0.754 (3)0.4958 (3)0.59106 (19)0.040*
H7B0.6002 (10)0.4832 (2)0.5393 (15)0.040*
C80.5905 (4)0.4063 (2)0.6348 (2)0.0297 (7)
H8A0.6445 (16)0.3595 (13)0.6134 (6)0.036*
H8B0.6246 (11)0.4112 (2)0.6850 (14)0.036*
C90.3481 (3)0.31327 (17)0.67995 (16)0.0225 (6)
H90.410 (2)0.2633 (18)0.6615 (7)0.027*
C100.3822 (4)0.32180 (19)0.76624 (17)0.0281 (6)
H10A0.3107 (19)0.2836 (11)0.7926 (7)0.034*
H10B0.493 (3)0.3042 (5)0.7759 (3)0.034*
C110.3584 (4)0.41151 (19)0.79858 (16)0.0260 (6)
C120.3361 (4)0.47756 (18)0.74739 (15)0.0225 (6)
C130.3061 (3)0.46997 (18)0.66287 (15)0.0221 (6)
C140.4028 (4)0.39240 (18)0.63174 (16)0.0224 (6)
C150.1182 (4)0.45591 (18)0.64836 (16)0.0241 (6)
H15A0.0585 (16)0.5021 (12)0.6684 (5)0.029*
H15B0.0987 (7)0.45401 (18)0.5961 (14)0.029*
C160.0577 (4)0.37308 (19)0.68449 (17)0.0256 (6)
H16A0.0577 (4)0.3791 (2)0.7357 (14)0.031*
H16B0.048 (3)0.3628 (3)0.6695 (4)0.031*
C170.0959 (4)0.21569 (19)0.69674 (16)0.0268 (6)
H17A0.0837 (5)0.2231 (3)0.7508 (14)0.032*
H17B0.013 (3)0.2055 (3)0.6758 (5)0.032*
C180.2021 (4)0.1386 (2)0.68222 (18)0.0295 (7)
H180.304 (5)0.1384 (2)0.7058 (11)0.035*
C190.1196 (4)0.0523 (2)0.6740 (2)0.0366 (8)
H19A0.1726 (17)0.0060 (15)0.6936 (7)0.044*
H19B0.007 (4)0.0503 (2)0.6769 (2)0.044*
C200.1953 (4)0.0949 (2)0.6060 (2)0.0338 (7)
H20A0.126 (2)0.1168 (7)0.5707 (11)0.041*
H20B0.290 (3)0.0727 (7)0.5874 (6)0.041*
O50.1923 (4)0.7903 (2)0.67974 (16)0.0566 (7)0.822 (9)
C210.1900 (8)0.7764 (6)0.5993 (3)0.0505 (15)0.822 (9)
H210.29360.74530.58370.061*0.822 (9)
C220.0361 (8)0.7211 (4)0.5788 (3)0.0660 (17)0.822 (9)
H22A0.03350.71130.52370.099*0.822 (9)
H22B0.04270.66580.60530.099*0.822 (9)
H22C0.06540.75140.59440.099*0.822 (9)
C230.1858 (10)0.8624 (3)0.5619 (3)0.072 (2)0.822 (9)
H23A0.18420.85510.50650.108*0.822 (9)
H23B0.08570.89340.57800.108*0.822 (9)
H23C0.28490.89530.57660.108*0.822 (9)
H5A0.225 (9)0.735 (3)0.704 (4)0.108*0.822 (9)
O5A0.1923 (4)0.7903 (2)0.67974 (16)0.0566 (7)0.178 (9)
C21A0.141 (4)0.779 (3)0.6008 (12)0.0505 (15)0.178 (9)
H21A0.10500.71730.59670.061*0.178 (9)
C22A0.014 (4)0.832 (3)0.5812 (19)0.107 (14)0.178 (9)
H22D0.04430.82300.52780.160*0.178 (9)
H22E0.10660.81510.61410.160*0.178 (9)
H22F0.01040.89360.58930.160*0.178 (9)
C23A0.275 (4)0.790 (4)0.543 (2)0.16 (3)0.178 (9)
H23D0.22810.78050.49170.242*0.178 (9)
H23E0.32090.84780.54610.242*0.178 (9)
H23F0.36330.74740.55190.242*0.178 (9)
H5AA0.225 (9)0.735 (3)0.704 (4)0.242*0.178 (9)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0358 (4)0.0311 (3)0.0218 (3)0.0075 (3)0.0072 (3)0.0006 (3)
O10.0546 (16)0.0411 (14)0.0448 (15)0.0170 (12)0.0121 (13)0.0147 (11)
O20.0420 (12)0.0249 (10)0.0203 (10)0.0035 (9)0.0011 (9)0.0013 (8)
O30.0428 (13)0.0330 (11)0.0243 (11)0.0032 (10)0.0005 (10)0.0113 (9)
O40.0321 (11)0.0275 (11)0.0196 (10)0.0017 (9)0.0008 (9)0.0048 (8)
N10.0197 (11)0.0263 (12)0.0171 (11)0.0015 (10)0.0018 (9)0.0030 (9)
C10.0434 (19)0.0380 (17)0.0207 (15)0.0049 (15)0.0086 (14)0.0040 (13)
C20.0412 (18)0.0409 (18)0.0174 (15)0.0099 (15)0.0029 (13)0.0066 (12)
C30.0257 (14)0.0307 (16)0.0246 (15)0.0044 (12)0.0001 (12)0.0064 (12)
C40.0239 (14)0.0270 (14)0.0206 (14)0.0004 (12)0.0002 (12)0.0005 (11)
C50.0381 (16)0.0259 (15)0.0163 (13)0.0026 (13)0.0015 (12)0.0019 (11)
C60.0395 (18)0.0301 (15)0.0194 (14)0.0061 (13)0.0013 (12)0.0021 (12)
C70.0295 (16)0.0347 (17)0.0347 (17)0.0055 (13)0.0085 (14)0.0047 (14)
C80.0228 (14)0.0294 (16)0.0370 (18)0.0026 (12)0.0020 (13)0.0054 (14)
C90.0194 (13)0.0230 (14)0.0252 (14)0.0018 (11)0.0017 (11)0.0036 (11)
C100.0314 (16)0.0272 (14)0.0259 (15)0.0010 (12)0.0112 (13)0.0041 (12)
C110.0255 (14)0.0281 (15)0.0244 (14)0.0031 (12)0.0061 (12)0.0007 (12)
C120.0209 (13)0.0287 (14)0.0179 (13)0.0007 (12)0.0018 (11)0.0028 (11)
C130.0238 (14)0.0243 (14)0.0181 (13)0.0012 (11)0.0012 (11)0.0030 (11)
C140.0243 (14)0.0243 (14)0.0187 (13)0.0023 (11)0.0010 (11)0.0028 (11)
C150.0265 (15)0.0279 (15)0.0180 (13)0.0065 (12)0.0036 (11)0.0025 (11)
C160.0181 (13)0.0345 (16)0.0241 (14)0.0033 (11)0.0006 (11)0.0073 (12)
C170.0299 (15)0.0295 (15)0.0211 (14)0.0040 (13)0.0025 (11)0.0021 (12)
C180.0311 (16)0.0322 (16)0.0252 (15)0.0037 (13)0.0056 (13)0.0023 (13)
C190.0325 (17)0.0314 (17)0.046 (2)0.0024 (14)0.0065 (15)0.0041 (15)
C200.0368 (18)0.0321 (17)0.0324 (17)0.0032 (14)0.0023 (14)0.0029 (13)
O50.0643 (18)0.0561 (16)0.0493 (16)0.0071 (15)0.0032 (14)0.0064 (14)
C210.054 (4)0.056 (3)0.041 (2)0.013 (4)0.011 (2)0.0018 (19)
C220.065 (3)0.067 (4)0.066 (3)0.006 (3)0.015 (3)0.011 (3)
C230.117 (6)0.050 (3)0.049 (3)0.015 (3)0.002 (3)0.007 (2)
O5A0.0643 (18)0.0561 (16)0.0493 (16)0.0071 (15)0.0032 (14)0.0064 (14)
C21A0.054 (4)0.056 (3)0.041 (2)0.013 (4)0.011 (2)0.0018 (19)
C22A0.089 (15)0.14 (3)0.09 (2)0.052 (18)0.023 (14)0.02 (2)
C23A0.090 (18)0.27 (6)0.13 (3)0.09 (3)0.06 (2)0.10 (4)
Geometric parameters (Å, º) top
O1—C61.208 (4)C15—H15A0.93 (2)
O2—C41.398 (3)C15—H15B0.93 (2)
O2—C51.468 (3)C15—C161.515 (4)
O3—H30.76 (4)C16—H16A0.90 (2)
O3—C31.366 (4)C16—H16B0.90 (2)
O4—H40.84 (4)C17—H17A0.96 (2)
O4—C141.433 (3)C17—H17B0.96 (2)
N1—H10.86 (3)C17—C181.493 (4)
N1—C91.520 (4)C18—H180.91 (4)
N1—C161.499 (4)C18—C191.502 (5)
N1—C171.513 (4)C18—C201.502 (5)
C1—H1A0.89 (4)C19—H19A0.90 (3)
C1—C21.394 (5)C19—H19B0.90 (3)
C1—C111.408 (4)C19—C201.495 (5)
C2—H20.91 (4)C20—H20A0.90 (3)
C2—C31.403 (5)C20—H20B0.90 (3)
C3—C41.389 (4)O5—C211.429 (6)
C4—C121.382 (4)O5—H5A0.99 (3)
C5—H51.0000C21—H211.0000
C5—C61.534 (5)C21—C221.547 (10)
C5—C131.551 (4)C21—C231.490 (10)
C6—C71.506 (4)C22—H22A0.9800
C7—H7A0.95 (3)C22—H22B0.9800
C7—H7B0.95 (3)C22—H22C0.9800
C7—C81.537 (5)C23—H23A0.9800
C8—H8A0.93 (3)C23—H23B0.9800
C8—H8B0.93 (3)C23—H23C0.9800
C8—C141.523 (4)O5A—C21A1.46 (2)
C9—H90.98 (3)O5A—H5AA0.99 (3)
C9—C101.545 (4)C21A—H21A1.0000
C9—C141.557 (4)C21A—C22A1.54 (3)
C10—H10A0.95 (3)C21A—C23A1.49 (2)
C10—H10B0.95 (3)C22A—H22D0.9800
C10—C111.518 (4)C22A—H22E0.9800
C11—C121.376 (4)C22A—H22F0.9800
C12—C131.508 (4)C23A—H23D0.9800
C13—C141.535 (4)C23A—H23E0.9800
C13—C151.545 (4)C23A—H23F0.9800
C4—O2—C5104.6 (2)C13—C15—H15B109.4
C3—O3—H3109.5H15A—C15—H15B108.0
C14—O4—H4109.5C16—C15—C13111.4 (2)
C9—N1—H1106.3C16—C15—H15A109.4
C16—N1—H1106.3C16—C15—H15B109.4
C16—N1—C9112.6 (2)N1—C16—C15111.9 (2)
C16—N1—C17110.6 (2)N1—C16—H16A109.2
C17—N1—H1106.3N1—C16—H16B109.2
C17—N1—C9114.3 (2)C15—C16—H16A109.2
C2—C1—H1A119.4C15—C16—H16B109.2
C2—C1—C11121.1 (3)H16A—C16—H16B107.9
C11—C1—H1A119.4N1—C17—H17A108.8
C1—C2—H2118.8N1—C17—H17B108.8
C1—C2—C3122.4 (3)H17A—C17—H17B107.7
C3—C2—H2118.8C18—C17—N1113.8 (2)
O3—C3—C2124.6 (3)C18—C17—H17A108.8
O3—C3—C4119.7 (3)C18—C17—H17B108.8
C4—C3—C2115.7 (3)C17—C18—H18115.7
C3—C4—O2127.1 (3)C17—C18—C19118.7 (3)
C12—C4—O2111.6 (2)C17—C18—C20119.6 (3)
C12—C4—C3121.3 (3)C19—C18—H18115.7
O2—C5—H5109.8C20—C18—H18115.7
O2—C5—C6109.0 (2)C20—C18—C1959.7 (2)
O2—C5—C13104.6 (2)C18—C19—H19A117.8
C6—C5—H5109.8C18—C19—H19B117.8
C6—C5—C13113.6 (2)H19A—C19—H19B114.9
C13—C5—H5109.8C20—C19—C1860.2 (2)
O1—C6—C5120.4 (3)C20—C19—H19A117.8
O1—C6—C7123.5 (3)C20—C19—H19B117.8
C7—C6—C5116.1 (3)C18—C20—H20A117.8
C6—C7—H7A109.4C18—C20—H20B117.8
C6—C7—H7B109.4C19—C20—C1860.2 (2)
C6—C7—C8111.2 (3)C19—C20—H20A117.8
H7A—C7—H7B108.0C19—C20—H20B117.8
C8—C7—H7A109.4H20A—C20—H20B114.9
C8—C7—H7B109.4C21—O5—H5A107 (4)
C7—C8—H8A109.8O5—C21—H21109.4
C7—C8—H8B109.8O5—C21—C22108.9 (5)
H8A—C8—H8B108.2O5—C21—C23107.5 (6)
C14—C8—C7109.5 (3)C22—C21—H21109.4
C14—C8—H8A109.8C23—C21—H21109.4
C14—C8—H8B109.8C23—C21—C22112.2 (5)
N1—C9—H9107.7C21—C22—H22A109.5
N1—C9—C10112.1 (2)C21—C22—H22B109.5
N1—C9—C14107.0 (2)C21—C22—H22C109.5
C10—C9—H9107.7H22A—C22—H22B109.5
C10—C9—C14114.5 (2)H22A—C22—H22C109.5
C14—C9—H9107.7H22B—C22—H22C109.5
C9—C10—H10A108.5C21—C23—H23A109.5
C9—C10—H10B108.5C21—C23—H23B109.5
H10A—C10—H10B107.5C21—C23—H23C109.5
C11—C10—C9115.0 (2)H23A—C23—H23B109.5
C11—C10—H10A108.5H23A—C23—H23C109.5
C11—C10—H10B108.5H23B—C23—H23C109.5
C1—C11—C10127.3 (3)C21A—O5A—H5AA112 (5)
C12—C11—C1115.3 (3)O5A—C21A—H21A105.5
C12—C11—C10117.2 (2)O5A—C21A—C22A112 (3)
C4—C12—C13108.8 (2)O5A—C21A—C23A116 (3)
C11—C12—C4123.9 (3)C22A—C21A—H21A105.5
C11—C12—C13127.2 (3)C23A—C21A—H21A105.5
C12—C13—C598.3 (2)C23A—C21A—C22A112 (3)
C12—C13—C14109.3 (2)C21A—C22A—H22D109.5
C12—C13—C15109.2 (2)C21A—C22A—H22E109.5
C14—C13—C5117.4 (2)C21A—C22A—H22F109.5
C14—C13—C15108.9 (2)H22D—C22A—H22E109.5
C15—C13—C5112.9 (2)H22D—C22A—H22F109.5
O4—C14—C8109.9 (3)H22E—C22A—H22F109.5
O4—C14—C9109.8 (2)C21A—C23A—H23D109.5
O4—C14—C13106.4 (2)C21A—C23A—H23E109.5
C8—C14—C9111.9 (2)C21A—C23A—H23F109.5
C8—C14—C13112.1 (2)H23D—C23A—H23E109.5
C13—C14—C9106.5 (2)H23D—C23A—H23F109.5
C13—C15—H15A109.4H23E—C23A—H23F109.5
O1—C6—C7—C8128.6 (3)C6—C5—C13—C1431.7 (3)
O2—C4—C12—C11175.7 (3)C6—C5—C13—C15159.7 (2)
O2—C4—C12—C136.0 (3)C6—C7—C8—C1461.6 (4)
O2—C5—C6—O128.1 (4)C7—C8—C14—O461.7 (3)
O2—C5—C6—C7152.6 (2)C7—C8—C14—C9176.1 (2)
O2—C5—C13—C1233.5 (3)C7—C8—C14—C1356.5 (3)
O2—C5—C13—C14150.4 (2)C9—N1—C16—C1553.8 (3)
O2—C5—C13—C1581.5 (3)C9—N1—C17—C1847.9 (3)
O3—C3—C4—O21.8 (5)C9—C10—C11—C1174.0 (3)
O3—C3—C4—C12177.3 (3)C9—C10—C11—C1210.2 (4)
N1—C9—C10—C1185.6 (3)C10—C9—C14—O4174.2 (2)
N1—C9—C14—O449.3 (3)C10—C9—C14—C863.5 (3)
N1—C9—C14—C8171.7 (2)C10—C9—C14—C1359.3 (3)
N1—C9—C14—C1365.5 (3)C10—C11—C12—C4171.7 (3)
N1—C17—C18—C19148.5 (3)C10—C11—C12—C1310.2 (4)
N1—C17—C18—C2079.0 (3)C11—C1—C2—C31.5 (5)
C1—C2—C3—O3179.6 (3)C11—C12—C13—C5157.5 (3)
C1—C2—C3—C41.2 (5)C11—C12—C13—C1434.5 (4)
C1—C11—C12—C44.6 (5)C11—C12—C13—C1584.6 (4)
C1—C11—C12—C13173.5 (3)C12—C13—C14—O4171.8 (2)
C2—C1—C11—C10174.6 (3)C12—C13—C14—C867.9 (3)
C2—C1—C11—C121.3 (5)C12—C13—C14—C954.7 (3)
C2—C3—C4—O2179.0 (3)C12—C13—C15—C1661.9 (3)
C2—C3—C4—C122.0 (4)C13—C5—C6—O1144.3 (3)
C3—C4—C12—C115.1 (5)C13—C5—C6—C736.4 (4)
C3—C4—C12—C13173.2 (3)C13—C15—C16—N150.9 (3)
C4—O2—C5—C690.0 (3)C14—C9—C10—C1136.5 (4)
C4—O2—C5—C1331.9 (3)C14—C13—C15—C1657.4 (3)
C4—C12—C13—C524.2 (3)C15—C13—C14—O452.5 (3)
C4—C12—C13—C14147.2 (2)C15—C13—C14—C8172.8 (3)
C4—C12—C13—C1593.7 (3)C15—C13—C14—C964.5 (3)
C5—O2—C4—C3164.1 (3)C16—N1—C9—C1065.5 (3)
C5—O2—C4—C1216.7 (3)C16—N1—C9—C1460.9 (3)
C5—C6—C7—C852.1 (4)C16—N1—C17—C18176.2 (2)
C5—C13—C14—O477.4 (3)C17—N1—C9—C1061.7 (3)
C5—C13—C14—C842.9 (4)C17—N1—C9—C14171.9 (2)
C5—C13—C14—C9165.5 (2)C17—N1—C16—C15177.1 (2)
C5—C13—C15—C16170.2 (2)C17—C18—C19—C20109.4 (3)
C6—C5—C13—C1285.2 (3)C17—C18—C20—C19108.0 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···Cl1i0.87 (3)2.34 (3)3.102 (3)146 (1)
O3—H3···Cl1ii0.75 (4)2.32 (4)3.066 (3)169 (4)
O4—H4···Cl10.85 (4)2.21 (4)3.054 (2)177 (3)
O5—H5A···O21.00 (6)2.00 (5)2.921 (4)154 (6)
Symmetry codes: (i) x1/2, y+1/2, z+1; (ii) x+1, y+1/2, z+3/2.
(III) 17-(Cyclopropylmethyl)-3,14-dihydroxy-4,5a-epoxymorphinan-6-one hydrochloride 2-methylpropan-2-ol monosolvate top
Crystal data top
C20H24NO4+·ClC4H10OF(000) = 968
Mr = 451.97Dx = 1.259 Mg m3
Monoclinic, P21Cu Kα radiation, λ = 1.54178 Å
a = 8.8487 (4) ÅCell parameters from 9282 reflections
b = 17.3281 (9) Åθ = 3.8–72.0°
c = 15.5702 (8) ŵ = 1.70 mm1
β = 92.702 (2)°T = 173 K
V = 2384.7 (2) Å3Block, colourless
Z = 40.26 × 0.22 × 0.20 mm
Data collection top
Bruker PHOTON-100 CMOS
diffractometer
9642 independent reflections
Radiation source: sealedtube8820 reflections with I > 2σ(I)
φ and ω scansθmax = 74.6°, θmin = 2.8°
Absorption correction: multi-scan
(TWINABS; Bruker, 2012)
h = 1111
k = 2121
9642 measured reflectionsl = 019
Refinement top
Refinement on F2Hydrogen site location: mixed
Least-squares matrix: fullH atoms treated by a mixture of independent and constrained refinement
R[F2 > 2σ(F2)] = 0.033 w = 1/[σ2(Fo2) + (0.0369P)2 + 0.2646P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.079(Δ/σ)max < 0.001
S = 1.04Δρmax = 0.20 e Å3
9642 reflectionsΔρmin = 0.17 e Å3
581 parametersAbsolute structure: Flack x determined using 3828 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
1 restraintAbsolute structure parameter: 0.004 (5)
Primary atom site location: dual
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.

Refinement. Refined as a 2-component twin.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
Cl10.66572 (8)0.25519 (4)0.26921 (4)0.03945 (16)
Cl20.15527 (8)0.59450 (4)0.23882 (4)0.03721 (15)
O1010.4508 (3)0.37330 (15)0.11407 (14)0.0567 (6)
O1020.1647 (3)0.32376 (12)0.09967 (11)0.0398 (5)
O1030.0224 (3)0.44419 (12)0.17614 (12)0.0409 (5)
H1030.077 (5)0.485 (2)0.1889 (6)0.061*
O1040.3849 (2)0.24407 (11)0.15125 (12)0.0363 (4)
H1040.466 (4)0.2502 (3)0.184 (2)0.054*
N1010.1251 (3)0.28034 (14)0.22373 (13)0.0325 (5)
H1010.182 (2)0.2418 (16)0.2306 (3)0.039*
C1010.0057 (4)0.49220 (17)0.05622 (18)0.0392 (7)
H10A0.03980.53150.09320.047*
C1020.0447 (4)0.49543 (17)0.03114 (18)0.0388 (7)
H1020.10840.53610.05200.047*
C1030.0063 (3)0.44113 (16)0.08976 (17)0.0345 (6)
C1040.0958 (3)0.38254 (16)0.05536 (16)0.0340 (6)
C1050.2807 (4)0.29429 (17)0.03854 (17)0.0381 (7)
H1050.29920.23830.04950.046*
C1060.4274 (4)0.34060 (18)0.04789 (18)0.0426 (7)
C1070.5333 (4)0.3442 (2)0.02958 (19)0.0467 (8)
H10B0.61850.37930.01820.056*
H10C0.57530.29230.04210.056*
C1080.4500 (4)0.37357 (18)0.10733 (18)0.0404 (7)
H10D0.52200.37830.15770.049*
H10E0.40670.42520.09460.049*
C1090.2282 (3)0.34699 (16)0.20183 (16)0.0334 (6)
H1090.29880.35610.25290.040*
C1100.1418 (4)0.42301 (17)0.18302 (17)0.0389 (7)
H11A0.05520.42590.22090.047*
H11B0.20990.46690.19780.047*
C1110.0831 (3)0.43183 (16)0.09051 (17)0.0349 (6)
C1120.1276 (3)0.37784 (16)0.03185 (17)0.0318 (6)
C1130.2135 (3)0.30510 (15)0.05051 (16)0.0323 (6)
C1140.3243 (3)0.31769 (16)0.12767 (17)0.0332 (6)
C1150.1007 (3)0.24068 (16)0.07105 (17)0.0364 (6)
H11C0.02760.23370.02150.044*
H11D0.15610.19150.08030.044*
C1160.0155 (3)0.26007 (18)0.15079 (17)0.0371 (6)
H11E0.05340.30410.13850.045*
H11F0.04640.21520.16700.045*
C1170.0460 (3)0.28935 (18)0.30721 (17)0.0365 (6)
H11G0.01900.33580.30370.044*
H11H0.02000.24410.31530.044*
C1180.1548 (4)0.29650 (17)0.38299 (17)0.0382 (6)
H1180.21360.34570.38730.046*
C1190.2336 (4)0.22618 (18)0.41855 (19)0.0466 (8)
H11I0.21210.17630.38950.056*
H11J0.33860.23220.44240.056*
C1200.1099 (5)0.2623 (2)0.46651 (19)0.0528 (9)
H12A0.13850.29070.52000.063*
H12B0.01200.23470.46710.063*
O10.0294 (3)0.47448 (14)0.37422 (13)0.0511 (6)
O20.3248 (2)0.51172 (11)0.40399 (11)0.0368 (4)
O30.5194 (3)0.39454 (13)0.34376 (12)0.0436 (5)
H30.570 (5)0.355 (2)0.3345 (7)0.065*
O40.1098 (2)0.60254 (11)0.64191 (12)0.0358 (4)
H40.036 (4)0.5974 (3)0.675 (2)0.054*
N10.3739 (3)0.56903 (14)0.72755 (13)0.0324 (5)
H10.310 (4)0.6157 (19)0.731 (2)0.039*
C10.5082 (4)0.35396 (17)0.57788 (19)0.0402 (7)
H1A0.54530.31710.61880.048*
C20.5475 (3)0.34791 (18)0.49230 (19)0.0403 (7)
H20.61400.30780.47670.048*
C30.4921 (3)0.39885 (17)0.42884 (17)0.0355 (6)
C40.3974 (3)0.45702 (16)0.45557 (17)0.0326 (6)
C50.2118 (3)0.54665 (16)0.45837 (16)0.0345 (6)
H50.19830.60250.44350.041*
C60.0611 (4)0.50333 (16)0.44294 (18)0.0369 (6)
C70.0406 (4)0.49965 (19)0.51721 (19)0.0422 (7)
H7A0.12570.46410.50300.051*
H7B0.08340.55150.52730.051*
C80.0453 (3)0.47173 (17)0.59927 (18)0.0366 (6)
H8A0.02520.46750.64660.044*
H8B0.08890.42000.58940.044*
C90.2696 (3)0.50184 (16)0.70365 (16)0.0331 (6)
H90.20030.49460.75190.040*
C100.3548 (4)0.42536 (17)0.69254 (17)0.0381 (7)
H10F0.44070.42330.73550.046*
H10G0.28590.38210.70480.046*
C110.4147 (3)0.41385 (16)0.60374 (17)0.0349 (6)
C120.3663 (3)0.46504 (15)0.54039 (16)0.0310 (6)
C130.2796 (3)0.53846 (15)0.55069 (16)0.0310 (6)
C140.1716 (3)0.52858 (15)0.62424 (16)0.0314 (6)
C150.3919 (3)0.60404 (16)0.57368 (16)0.0343 (6)
H15A0.46290.61010.52690.041*
H15B0.33570.65310.57900.041*
C160.4808 (3)0.58751 (18)0.65763 (16)0.0360 (6)
H16A0.54980.54340.64980.043*
H16B0.54290.63310.67450.043*
C170.4593 (3)0.56109 (18)0.81328 (17)0.0376 (6)
H17A0.52500.51490.81200.045*
H17B0.52520.60670.82280.045*
C180.3563 (4)0.55394 (17)0.88672 (17)0.0389 (7)
H180.29910.50440.89050.047*
C190.4090 (4)0.5899 (2)0.97063 (18)0.0524 (8)
H19A0.38630.56241.02420.063*
H19B0.50660.61800.97270.063*
C200.2796 (4)0.62445 (19)0.9190 (2)0.0472 (8)
H20A0.29720.67390.88920.057*
H20B0.17690.61830.94070.057*
O50.4669 (3)0.57652 (18)0.25608 (17)0.0659 (8)
H5A0.4432 (18)0.545 (3)0.297 (3)0.099*
C210.6265 (4)0.5937 (3)0.2645 (2)0.0548 (9)
C220.6449 (5)0.6660 (3)0.2117 (3)0.0857 (16)
H22A0.59980.65790.15370.129*
H22B0.75270.67780.20820.129*
H22C0.59400.70910.23900.129*
C230.7149 (5)0.5272 (3)0.2279 (3)0.0768 (13)
H23A0.69250.47970.25890.115*
H23B0.82340.53820.23440.115*
H23C0.68580.52090.16680.115*
C240.6731 (4)0.6062 (3)0.3577 (2)0.0644 (10)
H24A0.61500.64910.38050.097*
H24B0.78130.61840.36300.097*
H24C0.65340.55920.39040.097*
O60.2828 (3)0.69659 (15)0.32281 (17)0.0634 (7)
H60.33910.66390.30050.095*
C310.1740 (4)0.7253 (2)0.2583 (2)0.0490 (8)
C320.0606 (6)0.7709 (3)0.3054 (3)0.0751 (12)
H32A0.01030.73710.34570.113*
H32B0.01490.79270.26420.113*
H32C0.11210.81280.33730.113*
C330.2538 (5)0.7753 (3)0.1944 (3)0.0766 (13)
H33A0.29900.82010.22420.115*
H33B0.18060.79290.14940.115*
H33C0.33340.74520.16830.115*
C340.1000 (5)0.6567 (3)0.2120 (3)0.0744 (12)
H34A0.17800.62530.18610.112*
H34B0.02810.67520.16680.112*
H34C0.04640.62530.25320.112*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl10.0394 (4)0.0395 (4)0.0390 (4)0.0071 (3)0.0031 (3)0.0032 (3)
Cl20.0407 (4)0.0366 (3)0.0348 (3)0.0083 (3)0.0064 (3)0.0045 (3)
O1010.0668 (16)0.0700 (16)0.0344 (12)0.0128 (13)0.0152 (11)0.0156 (10)
O1020.0554 (13)0.0410 (11)0.0228 (9)0.0142 (10)0.0012 (9)0.0015 (7)
O1030.0544 (14)0.0419 (11)0.0258 (9)0.0102 (10)0.0034 (9)0.0043 (8)
O1040.0388 (11)0.0355 (10)0.0340 (10)0.0020 (9)0.0028 (8)0.0083 (8)
N1010.0380 (13)0.0331 (12)0.0260 (11)0.0001 (10)0.0022 (10)0.0003 (8)
C1010.0500 (19)0.0358 (15)0.0323 (15)0.0072 (13)0.0061 (13)0.0032 (11)
C1020.0448 (17)0.0379 (15)0.0338 (15)0.0090 (13)0.0024 (13)0.0058 (11)
C1030.0398 (16)0.0374 (15)0.0258 (13)0.0011 (12)0.0022 (11)0.0057 (11)
C1040.0417 (16)0.0355 (14)0.0248 (13)0.0023 (12)0.0023 (11)0.0014 (10)
C1050.0515 (18)0.0364 (15)0.0264 (13)0.0147 (14)0.0023 (12)0.0005 (11)
C1060.054 (2)0.0401 (16)0.0348 (16)0.0176 (15)0.0113 (13)0.0051 (12)
C1070.0446 (18)0.055 (2)0.0412 (17)0.0027 (16)0.0067 (14)0.0161 (14)
C1080.0469 (18)0.0418 (16)0.0322 (15)0.0051 (14)0.0023 (13)0.0093 (12)
C1090.0437 (16)0.0331 (14)0.0230 (12)0.0057 (12)0.0020 (11)0.0012 (10)
C1100.0562 (19)0.0344 (15)0.0262 (13)0.0010 (14)0.0019 (13)0.0030 (11)
C1110.0450 (17)0.0334 (14)0.0264 (13)0.0020 (12)0.0042 (11)0.0009 (10)
C1120.0381 (15)0.0315 (14)0.0256 (13)0.0015 (12)0.0014 (11)0.0012 (10)
C1130.0423 (16)0.0328 (14)0.0217 (12)0.0027 (12)0.0001 (11)0.0003 (10)
C1140.0402 (15)0.0325 (14)0.0266 (13)0.0022 (12)0.0017 (11)0.0049 (10)
C1150.0477 (17)0.0328 (14)0.0279 (13)0.0011 (13)0.0067 (12)0.0015 (10)
C1160.0393 (16)0.0397 (15)0.0317 (14)0.0052 (13)0.0054 (12)0.0015 (12)
C1170.0394 (16)0.0413 (15)0.0290 (13)0.0001 (13)0.0039 (12)0.0002 (11)
C1180.0473 (18)0.0406 (16)0.0269 (13)0.0029 (14)0.0031 (12)0.0034 (11)
C1190.060 (2)0.0448 (17)0.0339 (15)0.0020 (15)0.0078 (14)0.0048 (12)
C1200.076 (2)0.056 (2)0.0265 (14)0.0048 (19)0.0075 (15)0.0012 (13)
O10.0558 (14)0.0648 (15)0.0321 (11)0.0027 (12)0.0044 (10)0.0109 (10)
O20.0459 (12)0.0403 (11)0.0246 (9)0.0059 (9)0.0072 (8)0.0036 (7)
O30.0497 (14)0.0495 (13)0.0322 (10)0.0098 (10)0.0088 (9)0.0066 (8)
O40.0384 (11)0.0344 (10)0.0351 (10)0.0009 (9)0.0069 (8)0.0064 (8)
N10.0375 (13)0.0353 (12)0.0247 (11)0.0029 (10)0.0035 (10)0.0029 (9)
C10.0474 (18)0.0362 (15)0.0364 (15)0.0039 (14)0.0036 (13)0.0008 (12)
C20.0425 (17)0.0375 (16)0.0407 (16)0.0060 (14)0.0001 (13)0.0056 (12)
C30.0365 (15)0.0402 (15)0.0299 (14)0.0018 (13)0.0037 (12)0.0067 (11)
C40.0359 (15)0.0328 (14)0.0292 (13)0.0015 (12)0.0027 (11)0.0015 (10)
C50.0442 (16)0.0345 (14)0.0251 (13)0.0067 (12)0.0051 (11)0.0014 (10)
C60.0463 (17)0.0342 (14)0.0298 (14)0.0073 (13)0.0034 (12)0.0025 (11)
C70.0406 (17)0.0491 (18)0.0368 (16)0.0016 (14)0.0003 (13)0.0092 (13)
C80.0396 (16)0.0412 (16)0.0294 (14)0.0074 (13)0.0052 (12)0.0048 (11)
C90.0398 (16)0.0364 (15)0.0236 (12)0.0063 (12)0.0063 (11)0.0017 (10)
C100.0535 (19)0.0359 (15)0.0248 (13)0.0039 (14)0.0010 (12)0.0035 (11)
C110.0412 (16)0.0341 (14)0.0293 (14)0.0001 (13)0.0012 (12)0.0004 (10)
C120.0353 (14)0.0322 (13)0.0257 (13)0.0005 (12)0.0031 (11)0.0018 (10)
C130.0386 (15)0.0292 (13)0.0253 (13)0.0003 (11)0.0034 (11)0.0010 (10)
C140.0369 (15)0.0311 (14)0.0265 (12)0.0017 (12)0.0050 (11)0.0020 (10)
C150.0410 (15)0.0342 (14)0.0284 (12)0.0055 (13)0.0088 (11)0.0002 (11)
C160.0378 (15)0.0404 (15)0.0303 (13)0.0067 (14)0.0065 (11)0.0024 (12)
C170.0417 (17)0.0415 (15)0.0292 (14)0.0017 (13)0.0018 (12)0.0008 (11)
C180.0467 (17)0.0423 (16)0.0273 (14)0.0024 (14)0.0011 (12)0.0038 (11)
C190.070 (2)0.059 (2)0.0279 (14)0.001 (2)0.0000 (14)0.0004 (14)
C200.059 (2)0.0463 (17)0.0377 (16)0.0036 (16)0.0123 (15)0.0032 (13)
O50.0436 (13)0.096 (2)0.0582 (15)0.0102 (14)0.0012 (11)0.0354 (14)
C210.0395 (17)0.075 (2)0.0502 (18)0.0067 (19)0.0057 (14)0.0212 (18)
C220.057 (3)0.104 (4)0.096 (3)0.011 (3)0.003 (2)0.053 (3)
C230.064 (3)0.093 (3)0.075 (3)0.017 (3)0.019 (2)0.006 (2)
C240.056 (2)0.082 (3)0.055 (2)0.008 (2)0.0016 (17)0.0049 (19)
O60.0667 (18)0.0617 (17)0.0604 (16)0.0029 (13)0.0104 (13)0.0094 (12)
C310.0449 (19)0.0504 (19)0.0513 (19)0.0031 (15)0.0002 (15)0.0067 (14)
C320.086 (3)0.073 (3)0.067 (3)0.013 (3)0.013 (2)0.002 (2)
C330.062 (3)0.085 (3)0.082 (3)0.002 (2)0.005 (2)0.034 (2)
C340.058 (3)0.072 (3)0.092 (3)0.000 (2)0.007 (2)0.020 (2)
Geometric parameters (Å, º) top
O101—C1061.203 (4)C2—H20.9500
O102—C1041.387 (3)C2—C31.396 (4)
O102—C1051.459 (3)C3—C41.387 (4)
O103—H1030.87 (4)C4—C121.369 (4)
O103—C1031.358 (3)C5—H51.0000
O104—H1040.87 (4)C5—C61.539 (4)
O104—C1141.425 (3)C5—C131.538 (4)
N101—H1010.84 (3)C6—C71.500 (4)
N101—C1091.520 (4)C7—H7A0.9900
N101—C1161.500 (3)C7—H7B0.9900
N101—C1171.513 (3)C7—C81.534 (4)
C101—H10A0.9500C8—H8A0.9900
C101—C1021.388 (4)C8—H8B0.9900
C101—C1111.399 (4)C8—C141.526 (4)
C102—H1020.9500C9—H91.0000
C102—C1031.400 (4)C9—C101.538 (4)
C103—C1041.380 (4)C9—C141.548 (4)
C104—C1121.376 (4)C10—H10F0.9900
C105—H1051.0000C10—H10G0.9900
C105—C1061.539 (5)C10—C111.517 (4)
C105—C1131.545 (4)C11—C121.380 (4)
C106—C1071.494 (4)C12—C131.498 (4)
C107—H10B0.9900C13—C141.535 (4)
C107—H10C0.9900C13—C151.541 (4)
C107—C1081.533 (4)C15—H15A0.9900
C108—H10D0.9900C15—H15B0.9900
C108—H10E0.9900C15—C161.521 (4)
C108—C1141.520 (4)C16—H16A0.9900
C109—H1091.0000C16—H16B0.9900
C109—C1101.544 (4)C17—H17A0.9900
C109—C1141.551 (4)C17—H17B0.9900
C110—H11A0.9900C17—C181.500 (4)
C110—H11B0.9900C18—H181.0000
C110—C1111.516 (4)C18—C191.502 (4)
C111—C1121.378 (4)C18—C201.496 (4)
C112—C1131.493 (4)C19—H19A0.9900
C113—C1141.530 (4)C19—H19B0.9900
C113—C1151.541 (4)C19—C201.493 (5)
C115—H11C0.9900C20—H20A0.9900
C115—H11D0.9900C20—H20B0.9900
C115—C1161.520 (4)O5—H5A0.87 (5)
C116—H11E0.9900O5—C211.443 (4)
C116—H11F0.9900C21—C221.512 (6)
C117—H11G0.9900C21—C231.518 (6)
C117—H11H0.9900C21—C241.506 (5)
C117—C1181.492 (4)C22—H22A0.9800
C118—H1181.0000C22—H22B0.9800
C118—C1191.497 (4)C22—H22C0.9800
C118—C1201.500 (4)C23—H23A0.9800
C119—H11I0.9900C23—H23B0.9800
C119—H11J0.9900C23—H23C0.9800
C119—C1201.491 (5)C24—H24A0.9800
C120—H12A0.9900C24—H24B0.9800
C120—H12B0.9900C24—H24C0.9800
O1—C61.202 (3)O6—H60.8400
O2—C41.381 (3)O6—C311.447 (4)
O2—C51.471 (3)C31—C321.497 (5)
O3—H30.84 (4)C31—C331.519 (5)
O3—C31.360 (3)C31—C341.522 (5)
O4—H40.86 (4)C32—H32A0.9800
O4—C141.425 (3)C32—H32B0.9800
N1—H10.99 (3)C32—H32C0.9800
N1—C91.521 (4)C33—H33A0.9800
N1—C161.510 (3)C33—H33B0.9800
N1—C171.509 (3)C33—H33C0.9800
C1—H1A0.9500C34—H34A0.9800
C1—C21.397 (4)C34—H34B0.9800
C1—C111.398 (4)C34—H34C0.9800
C104—O102—C105104.2 (2)C13—C5—H5110.0
C103—O103—H103109.5C13—C5—C6113.4 (2)
C114—O104—H104109.5O1—C6—C5120.4 (3)
C109—N101—H101105.7O1—C6—C7123.0 (3)
C116—N101—H101105.7C7—C6—C5116.6 (2)
C116—N101—C109112.4 (2)C6—C7—H7A109.4
C116—N101—C117111.4 (2)C6—C7—H7B109.4
C117—N101—H101105.7C6—C7—C8111.3 (2)
C117—N101—C109114.9 (2)H7A—C7—H7B108.0
C102—C101—H10A119.6C8—C7—H7A109.4
C102—C101—C111120.9 (3)C8—C7—H7B109.4
C111—C101—H10A119.6C7—C8—H8A109.7
C101—C102—H102118.7C7—C8—H8B109.7
C101—C102—C103122.6 (3)H8A—C8—H8B108.2
C103—C102—H102118.7C14—C8—C7109.7 (2)
O103—C103—C102124.6 (2)C14—C8—H8A109.7
O103—C103—C104119.4 (3)C14—C8—H8B109.7
C104—C103—C102116.0 (2)N1—C9—H9107.3
C103—C104—O102127.2 (2)N1—C9—C10113.1 (2)
C112—C104—O102111.9 (2)N1—C9—C14106.1 (2)
C112—C104—C103120.9 (3)C10—C9—H9107.3
O102—C105—H105110.1C10—C9—C14115.3 (2)
O102—C105—C106109.1 (2)C14—C9—H9107.3
O102—C105—C113104.7 (2)C9—C10—H10F108.7
C106—C105—H105110.1C9—C10—H10G108.7
C106—C105—C113112.5 (2)H10F—C10—H10G107.6
C113—C105—H105110.1C11—C10—C9114.2 (2)
O101—C106—C105120.5 (3)C11—C10—H10F108.7
O101—C106—C107123.0 (3)C11—C10—H10G108.7
C107—C106—C105116.5 (2)C1—C11—C10126.7 (3)
C106—C107—H10B109.6C12—C11—C1116.1 (2)
C106—C107—H10C109.6C12—C11—C10117.2 (3)
C106—C107—C108110.2 (3)C4—C12—C11123.7 (3)
H10B—C107—H10C108.1C4—C12—C13108.5 (2)
C108—C107—H10B109.6C11—C12—C13127.8 (2)
C108—C107—H10C109.6C5—C13—C15111.6 (2)
C107—C108—H10D109.7C12—C13—C599.1 (2)
C107—C108—H10E109.7C12—C13—C14109.0 (2)
H10D—C108—H10E108.2C12—C13—C15108.9 (2)
C114—C108—C107109.7 (3)C14—C13—C5118.6 (2)
C114—C108—H10D109.7C14—C13—C15109.1 (2)
C114—C108—H10E109.7O4—C14—C8110.3 (2)
N101—C109—H109107.5O4—C14—C9108.7 (2)
N101—C109—C110113.2 (2)O4—C14—C13107.5 (2)
N101—C109—C114105.9 (2)C8—C14—C9112.7 (2)
C110—C109—H109107.5C8—C14—C13110.9 (2)
C110—C109—C114114.9 (2)C13—C14—C9106.5 (2)
C114—C109—H109107.5C13—C15—H15A109.4
C109—C110—H11A108.7C13—C15—H15B109.4
C109—C110—H11B108.7H15A—C15—H15B108.0
H11A—C110—H11B107.6C16—C15—C13111.3 (2)
C111—C110—C109114.3 (2)C16—C15—H15A109.4
C111—C110—H11A108.7C16—C15—H15B109.4
C111—C110—H11B108.7N1—C16—C15110.1 (2)
C101—C111—C110126.8 (2)N1—C16—H16A109.6
C112—C111—C101115.3 (2)N1—C16—H16B109.6
C112—C111—C110117.7 (3)C15—C16—H16A109.6
C104—C112—C111124.2 (3)C15—C16—H16B109.6
C104—C112—C113108.7 (2)H16A—C16—H16B108.2
C111—C112—C113127.1 (2)N1—C17—H17A109.1
C112—C113—C10598.1 (2)N1—C17—H17B109.1
C112—C113—C114109.5 (2)H17A—C17—H17B107.8
C112—C113—C115108.9 (2)C18—C17—N1112.6 (2)
C114—C113—C105117.6 (3)C18—C17—H17A109.1
C114—C113—C115109.7 (2)C18—C17—H17B109.1
C115—C113—C105112.2 (2)C17—C18—H18116.3
O104—C114—C108110.7 (2)C17—C18—C19117.0 (3)
O104—C114—C109108.3 (2)C19—C18—H18116.3
O104—C114—C113107.1 (2)C20—C18—C17119.3 (3)
C108—C114—C109112.3 (2)C20—C18—H18116.3
C108—C114—C113112.1 (2)C20—C18—C1959.7 (2)
C113—C114—C109106.2 (2)C18—C19—H19A117.8
C113—C115—H11C109.4C18—C19—H19B117.8
C113—C115—H11D109.4H19A—C19—H19B114.9
H11C—C115—H11D108.0C20—C19—C1859.9 (2)
C116—C115—C113111.1 (2)C20—C19—H19A117.8
C116—C115—H11C109.4C20—C19—H19B117.8
C116—C115—H11D109.4C18—C20—H20A117.7
N101—C116—C115110.0 (2)C18—C20—H20B117.7
N101—C116—H11E109.7C19—C20—C1860.3 (2)
N101—C116—H11F109.7C19—C20—H20A117.7
C115—C116—H11E109.7C19—C20—H20B117.7
C115—C116—H11F109.7H20A—C20—H20B114.9
H11E—C116—H11F108.2C21—O5—H5A109.5
N101—C117—H11G109.1O5—C21—C22104.5 (3)
N101—C117—H11H109.1O5—C21—C23109.2 (4)
H11G—C117—H11H107.9O5—C21—C24109.8 (3)
C118—C117—N101112.4 (2)C22—C21—C23110.7 (3)
C118—C117—H11G109.1C24—C21—C22112.0 (4)
C118—C117—H11H109.1C24—C21—C23110.4 (3)
C117—C118—H118116.0C21—C22—H22A109.5
C117—C118—C119119.8 (3)C21—C22—H22B109.5
C117—C118—C120117.7 (3)C21—C22—H22C109.5
C119—C118—H118116.0H22A—C22—H22B109.5
C119—C118—C12059.7 (2)H22A—C22—H22C109.5
C120—C118—H118116.0H22B—C22—H22C109.5
C118—C119—H11I117.7C21—C23—H23A109.5
C118—C119—H11J117.7C21—C23—H23B109.5
H11I—C119—H11J114.9C21—C23—H23C109.5
C120—C119—C11860.3 (2)H23A—C23—H23B109.5
C120—C119—H11I117.7H23A—C23—H23C109.5
C120—C119—H11J117.7H23B—C23—H23C109.5
C118—C120—H12A117.8C21—C24—H24A109.5
C118—C120—H12B117.8C21—C24—H24B109.5
C119—C120—C11860.1 (2)C21—C24—H24C109.5
C119—C120—H12A117.8H24A—C24—H24B109.5
C119—C120—H12B117.8H24A—C24—H24C109.5
H12A—C120—H12B114.9H24B—C24—H24C109.5
C4—O2—C5104.94 (19)C31—O6—H6109.5
C3—O3—H3109.5O6—C31—C32106.3 (3)
C14—O4—H4109.5O6—C31—C33109.7 (3)
C9—N1—H1107.4 (19)O6—C31—C34108.5 (3)
C16—N1—H1104.0 (18)C32—C31—C33111.3 (3)
C16—N1—C9112.3 (2)C32—C31—C34111.2 (3)
C17—N1—H1106.9 (18)C33—C31—C34109.8 (4)
C17—N1—C9114.8 (2)C31—C32—H32A109.5
C17—N1—C16110.7 (2)C31—C32—H32B109.5
C2—C1—H1A119.8C31—C32—H32C109.5
C2—C1—C11120.5 (3)H32A—C32—H32B109.5
C11—C1—H1A119.8H32A—C32—H32C109.5
C1—C2—H2118.9H32B—C32—H32C109.5
C3—C2—C1122.2 (3)C31—C33—H33A109.5
C3—C2—H2118.9C31—C33—H33B109.5
O3—C3—C2125.6 (3)C31—C33—H33C109.5
O3—C3—C4118.0 (2)H33A—C33—H33B109.5
C4—C3—C2116.3 (2)H33A—C33—H33C109.5
O2—C4—C3126.5 (2)H33B—C33—H33C109.5
C12—C4—O2112.5 (2)C31—C34—H34A109.5
C12—C4—C3121.0 (3)C31—C34—H34B109.5
O2—C5—H5110.0C31—C34—H34C109.5
O2—C5—C6108.5 (2)H34A—C34—H34B109.5
O2—C5—C13104.7 (2)H34A—C34—H34C109.5
C6—C5—H5110.0H34B—C34—H34C109.5
O101—C106—C107—C108124.1 (3)O1—C6—C7—C8129.6 (3)
O102—C104—C112—C111175.1 (3)O2—C4—C12—C11174.5 (3)
O102—C104—C112—C1136.0 (3)O2—C4—C12—C137.9 (3)
O102—C105—C106—O10123.8 (4)O2—C5—C6—O130.2 (4)
O102—C105—C106—C107154.2 (2)O2—C5—C6—C7149.9 (2)
O102—C105—C113—C11233.9 (3)O2—C5—C13—C1231.2 (3)
O102—C105—C113—C114151.0 (2)O2—C5—C13—C14148.7 (2)
O102—C105—C113—C11580.3 (3)O2—C5—C13—C1583.3 (3)
O103—C103—C104—O1020.6 (5)O3—C3—C4—O20.8 (4)
O103—C103—C104—C112179.8 (3)O3—C3—C4—C12179.4 (3)
N101—C109—C110—C11186.3 (3)N1—C9—C10—C1185.1 (3)
N101—C109—C114—O10448.8 (3)N1—C9—C14—O449.5 (3)
N101—C109—C114—C108171.4 (2)N1—C9—C14—C8172.1 (2)
N101—C109—C114—C11365.9 (2)N1—C9—C14—C1366.1 (3)
N101—C117—C118—C11976.9 (3)N1—C17—C18—C19145.7 (3)
N101—C117—C118—C120146.1 (3)N1—C17—C18—C2076.9 (4)
C101—C102—C103—O103176.5 (3)C1—C2—C3—O3176.7 (3)
C101—C102—C103—C1041.4 (5)C1—C2—C3—C41.0 (4)
C101—C111—C112—C1043.0 (5)C1—C11—C12—C44.0 (4)
C101—C111—C112—C113175.6 (3)C1—C11—C12—C13173.1 (3)
C102—C101—C111—C110176.2 (3)C2—C1—C11—C10176.1 (3)
C102—C101—C111—C1120.3 (5)C2—C1—C11—C120.2 (4)
C102—C103—C104—O102177.4 (3)C2—C3—C4—O2177.2 (3)
C102—C103—C104—C1121.8 (4)C2—C3—C4—C122.6 (4)
C103—C104—C112—C1114.2 (5)C3—C4—C12—C115.4 (5)
C103—C104—C112—C113174.6 (3)C3—C4—C12—C13172.3 (3)
C104—O102—C105—C10688.5 (3)C4—O2—C5—C693.1 (2)
C104—O102—C105—C11332.1 (3)C4—O2—C5—C1328.3 (3)
C104—C112—C113—C10524.4 (3)C4—C12—C13—C524.1 (3)
C104—C112—C113—C114147.5 (2)C4—C12—C13—C14148.6 (2)
C104—C112—C113—C11592.5 (3)C4—C12—C13—C1592.5 (3)
C105—O102—C104—C103162.4 (3)C5—O2—C4—C3166.5 (3)
C105—O102—C104—C11216.9 (3)C5—O2—C4—C1213.3 (3)
C105—C106—C107—C10853.9 (3)C5—C6—C7—C850.4 (3)
C105—C113—C114—O10478.5 (3)C5—C13—C14—O477.4 (3)
C105—C113—C114—C10843.1 (3)C5—C13—C14—C843.3 (3)
C105—C113—C114—C109166.0 (2)C5—C13—C14—C9166.2 (2)
C105—C113—C115—C116169.7 (2)C5—C13—C15—C16169.0 (2)
C106—C105—C113—C11284.4 (3)C6—C5—C13—C1286.9 (3)
C106—C105—C113—C11432.6 (3)C6—C5—C13—C1430.6 (3)
C106—C105—C113—C115161.3 (2)C6—C5—C13—C15158.6 (2)
C106—C107—C108—C11462.1 (3)C6—C7—C8—C1462.0 (3)
C107—C108—C114—O10462.9 (3)C7—C8—C14—O461.7 (3)
C107—C108—C114—C109176.0 (2)C7—C8—C14—C9176.6 (2)
C107—C108—C114—C11356.6 (3)C7—C8—C14—C1357.4 (3)
C109—N101—C116—C11557.1 (3)C9—N1—C16—C1556.5 (3)
C109—N101—C117—C11860.2 (3)C9—N1—C17—C1859.8 (3)
C109—C110—C111—C101176.2 (3)C9—C10—C11—C1173.3 (3)
C109—C110—C111—C1128.0 (4)C9—C10—C11—C1210.4 (4)
C110—C109—C114—O104174.6 (2)C10—C9—C14—O4175.5 (2)
C110—C109—C114—C10862.9 (3)C10—C9—C14—C861.9 (3)
C110—C109—C114—C11359.8 (3)C10—C9—C14—C1359.9 (3)
C110—C111—C112—C104173.4 (3)C10—C11—C12—C4172.6 (3)
C110—C111—C112—C1138.0 (5)C10—C11—C12—C1310.2 (4)
C111—C101—C102—C1032.4 (5)C11—C1—C2—C32.2 (5)
C111—C112—C113—C105156.8 (3)C11—C12—C13—C5158.4 (3)
C111—C112—C113—C11433.7 (4)C11—C12—C13—C1433.9 (4)
C111—C112—C113—C11586.3 (3)C11—C12—C13—C1585.0 (3)
C112—C113—C114—O104170.8 (2)C12—C13—C14—O4170.5 (2)
C112—C113—C114—C10867.6 (3)C12—C13—C14—C868.8 (3)
C112—C113—C114—C10955.3 (3)C12—C13—C14—C954.1 (3)
C112—C113—C115—C11662.2 (3)C12—C13—C15—C1660.7 (3)
C113—C105—C106—O101139.6 (3)C13—C5—C6—O1146.1 (3)
C113—C105—C106—C10738.5 (3)C13—C5—C6—C734.0 (3)
C113—C115—C116—N10152.1 (3)C13—C15—C16—N152.5 (3)
C114—C109—C110—C11135.6 (4)C14—C9—C10—C1137.2 (4)
C114—C113—C115—C11657.6 (3)C14—C13—C15—C1658.1 (3)
C115—C113—C114—O10451.4 (3)C15—C13—C14—O451.8 (3)
C115—C113—C114—C108173.0 (2)C15—C13—C14—C8172.4 (2)
C115—C113—C114—C10964.1 (3)C15—C13—C14—C964.6 (3)
C116—N101—C109—C11062.6 (3)C16—N1—C9—C1063.9 (3)
C116—N101—C109—C11464.2 (3)C16—N1—C9—C1463.4 (3)
C116—N101—C117—C118170.5 (2)C16—N1—C17—C18171.8 (2)
C117—N101—C109—C11066.3 (3)C17—N1—C9—C1063.6 (3)
C117—N101—C109—C114166.9 (2)C17—N1—C9—C14169.1 (2)
C117—N101—C116—C115172.2 (2)C17—N1—C16—C15173.8 (2)
C117—C118—C119—C120106.7 (3)C17—C18—C19—C20109.8 (3)
C117—C118—C120—C119110.0 (3)C17—C18—C20—C19106.0 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···Cl1i0.99 (3)2.43 (3)3.245 (3)140 (3)
O3—H3···Cl10.84 (4)2.20 (3)2.999 (2)162 (2)
O4—H4···Cl2ii0.86 (3)2.21 (3)3.063 (2)175 (1)
O5—H5A···O20.87 (5)2.09 (3)2.902 (3)154 (4)
O6—H6···O50.842.032.867 (4)174
N101—H101···Cl2iii0.84 (2)2.57 (2)3.239 (3)138 (2)
O103—H103···Cl20.87 (4)2.15 (3)3.002 (2)164 (3)
O104—H104···Cl10.87 (3)2.16 (3)3.026 (2)175 (1)
Symmetry codes: (i) x+1, y+1/2, z+1; (ii) x, y, z+1; (iii) x, y1/2, z.
Ring puckering analysis (Å, °) of five- and six-membered rings top
Ring A dihydrofuran (atoms O2/C4/C12/C13/C5), ring B piperidine (atoms N1/C9/C14/C13/C15/C16), ring C cyclohexanone (atoms C5/C6/C7/C8/C13/C14) and ring D cyclohexene (atoms C9/C10/C11/C12/C13/C14).
Ringparameter(I)(II)(III) cation 1(III) cation 2
AQ0.341 (2)0.340 (3)0.313 (3)0.341 (3)
φ314.5 (4)314.3 (5)310.6 (5)314.4 (5)
BQ0.637 (2)0.624 (3)0.637 (3)0.636 (3)
θ11.28 (18)10.9 (3)9.3 (3)9.6 (3)
φ101.0 (9)110.8 (14)102.1 (15)97.6 (15)
CQ0.546 (3)0.509 (3)0.509 (3)0.516 (3)
θ157.3 (2)157.7 (3)155.8 (3)158.5 (3)
φ322.5 (7)343.9 (10)349.1 (9)340.4 (10)
DQ0.495 (2)0.502 (3)0.499 (3)0.508 (3)
θ131.6 (2)134.1 (3)134.2 (3)132.1 (3)
φ121.2 (3)122.7 (5)123.7 (5)122.4 (4)
 

Acknowledgements

Financial support from the State University of New York for acquisition and maintenance of the X-ray diffractometer is gratefully acknowledged.

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