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organic compounds
Bupropion hydrobromide propanol hemisolvate
aChemistry Department, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China, and bCenter of Analysis and Measurement, Zhejiang University, Hangzhou, Zhejiang 310028, People's Republic of China
*Correspondence e-mail: huxiurong@yahoo.com.cn
The title compound {systematic name: N-[1-(3-chlorophenyl)-1-oxopropan-2-yl]-tert-butanaminium bromide propanol hemisolvate}, C13H19ClNO+·Br−·0.5C3H8O, crystallizes with two independent bupropion hydrobromide ion pairs and a solvent 1-propanol molecule in the In both molecules, the expected proton transfer from HBr to the amino group of the bupropion molecule is observed, and intra- and intermolecular N—H⋯Br hydrogen-bond interactions are formed. These interactions link the molecules into hydrogen-bond dimers. The side chains of the two cations have slightly different orientations. The 1-propanol solvent molecule is linked to a bromide ion by an O—H⋯Br hydrogen bond.
Related literature
For applications of bupropion in the medicine field, see: Fryer et al. (1999); Stewart et al. (2001
); Fang et al. (2000
). For the related structures of an ethanol hemi-solvate bupropion derivative and bupropion hydrochloride, see: Froimowitz et al. (1998
); Maccaroni et al. (2009
).
Experimental
Crystal data
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Data collection: PROCESS-AUTO (Rigaku, 2006); cell PROCESS-AUTO; data reduction: CrystalStructure (Rigaku, 2007
); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008
); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008
); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997
); software used to prepare material for publication: WinGX (Farrugia, 1999
).
Supporting information
https://doi.org/10.1107/S1600536811037093/bx2372sup1.cif
contains datablocks global, I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S1600536811037093/bx2372Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S1600536811037093/bx2372Isup3.cml
The crude product is supplied by Zhejiang Apeloa Pharmaceutical Co.,LTD. It was recrystallized from 1-propanol solution, giving colorless crystals of (1) suitable for X-ray diffraction.
The residual electron density to indicate the presence of a possible H atom on the atoms N1A and N1B, showing that a proton transfer from HBr to amino group of bupropion molecule. These H atoms were placed in calculated positions with N—H = 0.90Å and refined as riding with Uiso(H) = 1.2Ueq(N). All other H atoms were placed in calculated positions with C—H = 0.93–0.99Å and included in the
in riding model, with Uiso(H) = 1.2Ueq or 1.5Ueq(carrier atom). Temperature factor of atom O21, C21, C22 and C23 from solvent molecule were restrained with effective standard deviations so that their Uij components approximate to isotropic behavior; however the corresponding isotropic U is free to vary.The title compound, bupropion hydrobromide, 1-(3-chlorophenyl)-2-[(1,1- dimethylethyl)amino]-1-propanone hydrobromide, belongs to the class of antidepressants known as aminoketones and it is known also with the drug name Aplenzin. It is a second generation antidepressant approved in US and in some European countries, its mechanism of action, both as an antidepressant and as an aids to smoking cessation, is thought to involve nicotinic acetylcholine receptors that are linked to dopamine and norepinephrine release (Fryer et al. 1999 & Stewart et al., 2001). Pure bupropion enantiomers were successfully synthesized but they give rise to a rapid
(Fang et al., 2000). In literature, of an ethanol hemi-solvate bupropion derivative and bupropion hydrochloride, obtained from single-crystal X-ray analysis and powder diffraction, were reported (Froimowitz et al., 1998 & Maccaroni et al., 2009). Here, we reported of bupropion hydrobromide propanol solvate. The consists of two bupropion cations, two bromide anions and one 1-propanol molecule (Fig.1). Expected proton transfer from HBr to amino group of bupropion is observed, intramolecular and intermolecular hydrogen bond interactions are formed (Table 1).These interactions result in hydrogen-bond dimers in the two polymorphic forms, in which two Br- ions bridge the NH2—NH2 contact (above 4.2 Å), similar to that of BUP hydrochloride (Maccaroni et al., 2009). Solvent molecule 1-propanol is linked to bupropion hydrobromide by intramolecular hydrogen bond O21—H21···Br1A. The side chains of the two molecules have slightly different orientations, as seen by the torsion angles of C6—C5—C7—C8, C5—C7—C8—N1, C7—C8—N1—C10 and O1—C7—C5—C6. Carbonyl groups in the two molecules are not coplanar with phenyl ring plane, atom O1A and O1B deviated from the least-squares plane of phenyl ring (C1A/C6A and C1B/C6B) 0.238Å and 0.139 Å, respectively.For applications of bupropion in the medicine field, see: Fryer et al. (1999); Stewart et al. (2001); Fang et al. (2000). For the related structures of an ethanol
hemi-solvate bupropion derivative and bupropion hydrochloride, see: Froimowitz et al. (1998); Maccaroni et al. (2009).
Data collection: PROCESS-AUTO (Rigaku, 2006); cell
PROCESS-AUTO (Rigaku, 2006); data reduction: CrystalStructure (Rigaku, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999). ![]() | Fig. 1. Molecular structure of the title compound (1) showing atom-labelling scheme and displacement ellipsoids at 40% probability level. H atoms are shown as small circles of arbitrary radii. |
C13H19ClNO+·Br−·0.5C3H8O | Z = 2 |
Mr = 350.70 | F(000) = 362 |
Triclinic, P1 | Dx = 1.361 Mg m−3 |
Hall symbol: P 1 | Mo Kα radiation, λ = 0.71073 Å |
a = 7.8614 (4) Å | Cell parameters from 5965 reflections |
b = 9.4100 (6) Å | θ = 3.4–27.4° |
c = 11.8477 (7) Å | µ = 2.56 mm−1 |
α = 85.783 (2)° | T = 296 K |
β = 78.159 (2)° | Chunk, colorless |
γ = 89.450 (2)° | 0.46 × 0.28 × 0.14 mm |
V = 855.46 (9) Å3 |
Rigaku R-AXIS RAPID diffractometer | 6355 independent reflections |
Radiation source: rolling anode | 4179 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.031 |
Detector resolution: 10.00 pixels mm-1 | θmax = 27.5°, θmin = 3.4° |
ω scans | h = −10→8 |
Absorption correction: multi-scan (ABSCOR; Higashi, 1995) | k = −12→12 |
Tmin = 0.361, Tmax = 0.647 | l = −15→15 |
8456 measured reflections |
Refinement on F2 | Hydrogen site location: inferred from neighbouring sites |
Least-squares matrix: full | H-atom parameters constrained |
R[F2 > 2σ(F2)] = 0.043 | w = 1/[σ2(Fo2) + (0.0295P)2 + 2.750P] where P = (Fo2 + 2Fc2)/3 |
wR(F2) = 0.138 | (Δ/σ)max = 0.002 |
S = 1.00 | Δρmax = 0.74 e Å−3 |
6355 reflections | Δρmin = −0.97 e Å−3 |
354 parameters | Extinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
77 restraints | Extinction coefficient: 0.038 (2) |
Primary atom site location: structure-invariant direct methods | Absolute structure: Flack (1983), 2490 Friedel pairs |
Secondary atom site location: difference Fourier map | Absolute structure parameter: 0.34 (3) |
C13H19ClNO+·Br−·0.5C3H8O | γ = 89.450 (2)° |
Mr = 350.70 | V = 855.46 (9) Å3 |
Triclinic, P1 | Z = 2 |
a = 7.8614 (4) Å | Mo Kα radiation |
b = 9.4100 (6) Å | µ = 2.56 mm−1 |
c = 11.8477 (7) Å | T = 296 K |
α = 85.783 (2)° | 0.46 × 0.28 × 0.14 mm |
β = 78.159 (2)° |
Rigaku R-AXIS RAPID diffractometer | 6355 independent reflections |
Absorption correction: multi-scan (ABSCOR; Higashi, 1995) | 4179 reflections with I > 2σ(I) |
Tmin = 0.361, Tmax = 0.647 | Rint = 0.031 |
8456 measured reflections |
R[F2 > 2σ(F2)] = 0.043 | H-atom parameters constrained |
wR(F2) = 0.138 | Δρmax = 0.74 e Å−3 |
S = 1.00 | Δρmin = −0.97 e Å−3 |
6355 reflections | Absolute structure: Flack (1983), 2490 Friedel pairs |
354 parameters | Absolute structure parameter: 0.34 (3) |
77 restraints |
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. |
x | y | z | Uiso*/Ueq | ||
Br1A | 0.2817 (5) | 0.0940 (4) | 0.4424 (3) | 0.0574 (4) | |
Br1B | 0.8907 (5) | 0.3667 (4) | 0.2779 (3) | 0.0577 (4) | |
Cl1A | 0.5787 (10) | 1.0426 (6) | −0.1054 (6) | 0.096 (2) | |
Cl1B | 0.5901 (10) | 0.4189 (6) | 0.8270 (6) | 0.099 (2) | |
N1A | 0.2948 (10) | 0.4307 (9) | 0.3266 (6) | 0.044 (3) | |
H1A1 | 0.2916 | 0.3381 | 0.3520 | 0.053* | |
H1A2 | 0.1945 | 0.4498 | 0.3032 | 0.053* | |
O1A | 0.2393 (18) | 0.6111 (14) | 0.1487 (11) | 0.073 (4) | |
C5B | 0.6396 (10) | 0.7943 (10) | 0.6451 (12) | 0.049 (3) | |
N1B | 0.8848 (10) | 1.0271 (9) | 0.3887 (6) | 0.041 (3) | |
H1B1 | 0.8891 | 1.1197 | 0.3632 | 0.049* | |
H1B2 | 0.9870 | 1.0066 | 0.4091 | 0.049* | |
C7A | 0.398 (2) | 0.5823 (16) | 0.1472 (13) | 0.055 (4) | |
C8A | 0.4388 (13) | 0.4504 (9) | 0.2238 (8) | 0.045 (3) | |
H8A | 0.5518 | 0.4593 | 0.2455 | 0.054* | |
O1B | 0.9229 (17) | 0.8444 (14) | 0.5699 (13) | 0.080 (4) | |
C10B | 0.8749 (8) | 0.9430 (6) | 0.2890 (6) | 0.050 (4) | |
C6B | 0.670 (2) | 0.6656 (11) | 0.7018 (12) | 0.053 (4) | |
H6B | 0.7841 | 0.6344 | 0.6958 | 0.063* | |
C13A | 0.4498 (12) | 0.4659 (13) | 0.4839 (11) | 0.062 (4) | |
H13A | 0.5548 | 0.4633 | 0.4260 | 0.092* | |
H13B | 0.4246 | 0.3723 | 0.5214 | 0.092* | |
H13C | 0.4645 | 0.5308 | 0.5401 | 0.092* | |
C1A | 0.6250 (10) | 0.8758 (9) | −0.0469 (12) | 0.064 (5) | |
C10A | 0.2985 (8) | 0.5161 (6) | 0.4266 (6) | 0.051 (4) | |
C8B | 0.7476 (14) | 1.0115 (9) | 0.4957 (8) | 0.049 (3) | |
H8B | 0.6371 | 0.9965 | 0.4721 | 0.059* | |
C6A | 0.500 (2) | 0.7921 (12) | 0.0245 (13) | 0.059 (4) | |
H6A | 0.3846 | 0.8209 | 0.0386 | 0.071* | |
C4B | 0.4675 (9) | 0.8365 (11) | 0.6632 (12) | 0.069 (4) | |
H4B | 0.4410 | 0.9225 | 0.6268 | 0.083* | |
C4A | 0.7179 (8) | 0.6209 (11) | 0.0595 (12) | 0.058 (4) | |
H4A | 0.7482 | 0.5365 | 0.0963 | 0.070* | |
C11B | 0.846 (2) | 0.7831 (7) | 0.3252 (16) | 0.071 (5) | |
H11A | 0.8494 | 0.7317 | 0.2577 | 0.106* | |
H11B | 0.7354 | 0.7690 | 0.3766 | 0.106* | |
H11C | 0.9365 | 0.7489 | 0.3638 | 0.106* | |
C5A | 0.5463 (9) | 0.6643 (11) | 0.0754 (12) | 0.048 (3) | |
C11A | 0.321 (2) | 0.6762 (8) | 0.3895 (15) | 0.070 (5) | |
H11D | 0.4355 | 0.6937 | 0.3436 | 0.105* | |
H11E | 0.3054 | 0.7295 | 0.4569 | 0.105* | |
H11F | 0.2361 | 0.7054 | 0.3448 | 0.105* | |
C12B | 1.0499 (12) | 0.9757 (14) | 0.2054 (10) | 0.061 (4) | |
H12A | 1.0684 | 1.0769 | 0.1948 | 0.091* | |
H12B | 1.0482 | 0.9388 | 0.1322 | 0.091* | |
H12C | 1.1422 | 0.9317 | 0.2370 | 0.091* | |
C12A | 0.1247 (13) | 0.4992 (16) | 0.5144 (11) | 0.074 (5) | |
H12D | 0.1256 | 0.5583 | 0.5770 | 0.112* | |
H12E | 0.1089 | 0.4015 | 0.5440 | 0.112* | |
H12F | 0.0310 | 0.5274 | 0.4770 | 0.112* | |
C13B | 0.7260 (13) | 1.0021 (17) | 0.2329 (11) | 0.071 (5) | |
H13D | 0.7401 | 1.1032 | 0.2168 | 0.107* | |
H13E | 0.6168 | 0.9820 | 0.2849 | 0.107* | |
H13F | 0.7284 | 0.9578 | 0.1622 | 0.107* | |
C2B | 0.3677 (10) | 0.6293 (11) | 0.7882 (13) | 0.070 (5) | |
H2B | 0.2803 | 0.5765 | 0.8381 | 0.084* | |
C7B | 0.7805 (18) | 0.8790 (15) | 0.5713 (13) | 0.049 (4) | |
C9A | 0.433 (2) | 0.3227 (11) | 0.1505 (11) | 0.057 (4) | |
H9A1 | 0.4510 | 0.2362 | 0.1946 | 0.085* | |
H9A2 | 0.5222 | 0.3333 | 0.0818 | 0.085* | |
H9A3 | 0.3214 | 0.3189 | 0.1295 | 0.085* | |
C1B | 0.5383 (12) | 0.5830 (9) | 0.7665 (12) | 0.067 (5) | |
C2A | 0.7974 (10) | 0.8344 (13) | −0.0634 (13) | 0.082 (6) | |
H2A | 0.8830 | 0.8932 | −0.1090 | 0.098* | |
C3B | 0.3327 (15) | 0.7575 (12) | 0.7325 (11) | 0.074 (5) | |
H3B | 0.2191 | 0.7904 | 0.7415 | 0.088* | |
C9B | 0.728 (3) | 1.1461 (12) | 0.5637 (12) | 0.072 (5) | |
H9B1 | 0.6318 | 1.1337 | 0.6283 | 0.108* | |
H9B2 | 0.7072 | 1.2269 | 0.5140 | 0.108* | |
H9B3 | 0.8325 | 1.1615 | 0.5911 | 0.108* | |
C3A | 0.8433 (17) | 0.7064 (12) | −0.0127 (14) | 0.089 (6) | |
H3A | 0.9588 | 0.6777 | −0.0271 | 0.106* | |
O21 | 0.0850 (16) | 0.0562 (11) | 0.7350 (9) | 0.140 (3) | |
H21 | 0.0956 | 0.0584 | 0.6646 | 0.211* | |
C23 | 0.016 (3) | 0.3261 (16) | 0.9379 (14) | 0.167 (5) | |
H23A | 0.0930 | 0.3666 | 0.9807 | 0.250* | |
H23B | −0.0973 | 0.3139 | 0.9861 | 0.250* | |
H23C | 0.0098 | 0.3888 | 0.8713 | 0.250* | |
C21 | 0.142 (3) | 0.1909 (14) | 0.7667 (10) | 0.152 (4) | |
H21A | 0.0864 | 0.2703 | 0.7323 | 0.183* | |
H21B | 0.2673 | 0.2019 | 0.7426 | 0.183* | |
C22 | 0.086 (3) | 0.1810 (15) | 0.8990 (10) | 0.158 (4) | |
H22A | 0.1850 | 0.1546 | 0.9336 | 0.190* | |
H22B | −0.0030 | 0.1086 | 0.9240 | 0.190* |
U11 | U22 | U33 | U12 | U13 | U23 | |
Br1A | 0.0472 (9) | 0.0500 (9) | 0.0750 (11) | −0.0012 (7) | −0.0172 (8) | 0.0093 (8) |
Br1B | 0.0486 (9) | 0.0505 (9) | 0.0743 (11) | −0.0007 (7) | −0.0185 (8) | 0.0109 (8) |
Cl1A | 0.138 (6) | 0.060 (3) | 0.082 (4) | −0.010 (3) | −0.018 (4) | 0.024 (3) |
Cl1B | 0.150 (7) | 0.058 (3) | 0.088 (4) | −0.022 (3) | −0.031 (4) | 0.027 (3) |
N1A | 0.039 (6) | 0.041 (6) | 0.053 (7) | 0.006 (5) | −0.013 (5) | 0.003 (5) |
O1A | 0.058 (8) | 0.069 (7) | 0.084 (8) | −0.004 (6) | −0.011 (6) | 0.031 (6) |
C5B | 0.047 (7) | 0.047 (8) | 0.051 (8) | 0.005 (6) | −0.010 (6) | −0.002 (6) |
N1B | 0.033 (6) | 0.042 (6) | 0.046 (6) | −0.004 (5) | −0.006 (5) | 0.006 (5) |
C7A | 0.059 (9) | 0.060 (9) | 0.053 (8) | 0.017 (7) | −0.031 (7) | 0.000 (7) |
C8A | 0.039 (6) | 0.044 (7) | 0.046 (7) | 0.002 (5) | 0.001 (5) | 0.012 (6) |
O1B | 0.041 (7) | 0.075 (8) | 0.120 (10) | −0.003 (6) | −0.021 (7) | 0.038 (8) |
C10B | 0.050 (9) | 0.051 (8) | 0.052 (8) | 0.010 (7) | −0.017 (7) | −0.011 (7) |
C6B | 0.073 (11) | 0.039 (7) | 0.046 (7) | −0.007 (7) | −0.017 (7) | 0.013 (6) |
C13A | 0.077 (11) | 0.046 (7) | 0.073 (10) | 0.017 (7) | −0.039 (9) | −0.014 (7) |
C1A | 0.080 (13) | 0.056 (9) | 0.052 (9) | −0.006 (9) | −0.004 (9) | −0.003 (8) |
C10A | 0.043 (9) | 0.047 (8) | 0.059 (8) | −0.008 (7) | −0.005 (7) | −0.002 (7) |
C8B | 0.035 (6) | 0.048 (7) | 0.066 (9) | 0.004 (5) | −0.018 (6) | 0.002 (6) |
C6A | 0.056 (10) | 0.060 (9) | 0.057 (8) | −0.005 (8) | −0.003 (7) | −0.005 (7) |
C4B | 0.096 (11) | 0.045 (7) | 0.066 (9) | −0.025 (7) | −0.016 (8) | 0.010 (6) |
C4A | 0.029 (5) | 0.070 (8) | 0.066 (8) | 0.016 (5) | 0.007 (5) | 0.000 (7) |
C11B | 0.078 (12) | 0.046 (8) | 0.095 (12) | 0.025 (7) | −0.029 (9) | −0.014 (8) |
C5A | 0.050 (7) | 0.047 (7) | 0.049 (8) | −0.004 (6) | −0.021 (6) | 0.003 (6) |
C11A | 0.066 (10) | 0.047 (8) | 0.091 (11) | −0.021 (7) | −0.002 (9) | −0.006 (8) |
C12B | 0.059 (8) | 0.067 (7) | 0.045 (6) | 0.034 (6) | 0.017 (6) | −0.011 (6) |
C12A | 0.070 (9) | 0.066 (8) | 0.093 (10) | −0.024 (7) | −0.034 (8) | 0.008 (7) |
C13B | 0.048 (9) | 0.112 (13) | 0.058 (9) | 0.005 (8) | −0.019 (7) | −0.015 (9) |
C2B | 0.089 (13) | 0.061 (10) | 0.059 (9) | −0.024 (9) | −0.011 (8) | −0.001 (8) |
C7B | 0.032 (7) | 0.046 (7) | 0.061 (8) | −0.018 (6) | 0.004 (6) | 0.014 (6) |
C9A | 0.064 (9) | 0.040 (6) | 0.059 (8) | −0.002 (6) | 0.000 (7) | 0.011 (6) |
C1B | 0.109 (16) | 0.043 (8) | 0.045 (8) | −0.021 (9) | −0.011 (9) | 0.013 (7) |
C2A | 0.090 (15) | 0.069 (11) | 0.067 (10) | −0.020 (10) | 0.030 (9) | 0.001 (9) |
C3B | 0.049 (9) | 0.091 (13) | 0.074 (11) | −0.011 (9) | 0.008 (8) | −0.019 (9) |
C9B | 0.097 (14) | 0.066 (9) | 0.048 (7) | 0.014 (9) | −0.004 (8) | −0.007 (7) |
C3A | 0.075 (13) | 0.062 (10) | 0.107 (14) | −0.004 (9) | 0.028 (10) | 0.010 (10) |
O21 | 0.176 (9) | 0.144 (8) | 0.092 (6) | 0.003 (7) | −0.009 (6) | −0.006 (5) |
C23 | 0.241 (12) | 0.138 (11) | 0.104 (8) | 0.023 (11) | 0.000 (9) | 0.007 (8) |
C21 | 0.218 (10) | 0.127 (9) | 0.100 (7) | 0.019 (9) | −0.009 (7) | 0.006 (6) |
C22 | 0.234 (10) | 0.133 (10) | 0.097 (7) | 0.018 (9) | −0.013 (8) | −0.005 (6) |
Cl1A—C1A | 1.735 (11) | C4A—H4A | 0.9300 |
Cl1B—C1B | 1.735 (11) | C11B—H11A | 0.9601 |
N1A—C8A | 1.485 (12) | C11B—H11B | 0.9601 |
N1A—C10A | 1.485 (10) | C11B—H11C | 0.9601 |
N1A—H1A1 | 0.9000 | C11A—H11D | 0.9601 |
N1A—H1A2 | 0.9000 | C11A—H11E | 0.9601 |
O1A—C7A | 1.271 (19) | C11A—H11F | 0.9601 |
C5B—C4B | 1.385 (12) | C12B—H12A | 0.9600 |
C5B—C6B | 1.384 (16) | C12B—H12B | 0.9600 |
C5B—C7B | 1.464 (15) | C12B—H12C | 0.9600 |
N1B—C10B | 1.485 (10) | C12A—H12D | 0.9600 |
N1B—C8B | 1.485 (12) | C12A—H12E | 0.9600 |
N1B—H1B1 | 0.9000 | C12A—H12F | 0.9600 |
N1B—H1B2 | 0.9000 | C13B—H13D | 0.9600 |
C7A—C5A | 1.481 (19) | C13B—H13E | 0.9600 |
C7A—C8A | 1.553 (17) | C13B—H13F | 0.9600 |
C8A—C9A | 1.540 (14) | C2B—C3B | 1.385 (16) |
C8A—H8A | 0.9800 | C2B—C1B | 1.385 (13) |
O1B—C7B | 1.160 (18) | C2B—H2B | 0.9300 |
C10B—C13B | 1.541 (13) | C9A—H9A1 | 0.9600 |
C10B—C11B | 1.540 (10) | C9A—H9A2 | 0.9600 |
C10B—C12B | 1.540 (12) | C9A—H9A3 | 0.9600 |
C6B—C1B | 1.367 (17) | C2A—C3A | 1.385 (17) |
C6B—H6B | 0.9300 | C2A—H2A | 0.9300 |
C13A—C10A | 1.540 (12) | C3B—H3B | 0.9300 |
C13A—H13A | 0.9600 | C9B—H9B1 | 0.9600 |
C13A—H13B | 0.9600 | C9B—H9B2 | 0.9600 |
C13A—H13C | 0.9600 | C9B—H9B3 | 0.9600 |
C1A—C6A | 1.370 (16) | C3A—H3A | 0.9300 |
C1A—C2A | 1.385 (12) | O21—C21 | 1.449 (18) |
C10A—C11A | 1.540 (11) | O21—H21 | 0.8200 |
C10A—C12A | 1.540 (12) | C23—C22 | 1.530 (19) |
C8B—C7B | 1.532 (17) | C23—H23A | 0.9600 |
C8B—C9B | 1.540 (15) | C23—H23B | 0.9600 |
C8B—H8B | 0.9800 | C23—H23C | 0.9600 |
C6A—C5A | 1.385 (17) | C21—C22 | 1.535 (17) |
C6A—H6A | 0.9300 | C21—H21A | 0.9700 |
C4B—C3B | 1.385 (16) | C21—H21B | 0.9700 |
C4B—H4B | 0.9300 | C22—H22A | 0.9700 |
C4A—C3A | 1.385 (17) | C22—H22B | 0.9700 |
C4A—C5A | 1.385 (11) | ||
C8A—N1A—C10A | 118.2 (8) | C10A—C11A—H11E | 109.5 |
C8A—N1A—H1A1 | 107.8 | H11D—C11A—H11E | 109.5 |
C10A—N1A—H1A1 | 107.8 | C10A—C11A—H11F | 109.5 |
C8A—N1A—H1A2 | 107.8 | H11D—C11A—H11F | 109.5 |
C10A—N1A—H1A2 | 107.8 | H11E—C11A—H11F | 109.5 |
H1A1—N1A—H1A2 | 107.1 | C10B—C12B—H12A | 109.5 |
C4B—C5B—C6B | 115.4 (11) | C10B—C12B—H12B | 109.5 |
C4B—C5B—C7B | 122.8 (10) | H12A—C12B—H12B | 109.5 |
C6B—C5B—C7B | 121.9 (10) | C10B—C12B—H12C | 109.5 |
C10B—N1B—C8B | 120.2 (8) | H12A—C12B—H12C | 109.5 |
C10B—N1B—H1B1 | 107.3 | H12B—C12B—H12C | 109.5 |
C8B—N1B—H1B1 | 107.3 | C10A—C12A—H12D | 109.5 |
C10B—N1B—H1B2 | 107.3 | C10A—C12A—H12E | 109.5 |
C8B—N1B—H1B2 | 107.3 | H12D—C12A—H12E | 109.5 |
H1B1—N1B—H1B2 | 106.9 | C10A—C12A—H12F | 109.5 |
O1A—C7A—C5A | 124.3 (12) | H12D—C12A—H12F | 109.5 |
O1A—C7A—C8A | 117.8 (13) | H12E—C12A—H12F | 109.5 |
C5A—C7A—C8A | 117.9 (11) | C10B—C13B—H13D | 109.5 |
N1A—C8A—C9A | 107.1 (9) | C10B—C13B—H13E | 109.5 |
N1A—C8A—C7A | 108.5 (10) | H13D—C13B—H13E | 109.5 |
C9A—C8A—C7A | 105.0 (10) | C10B—C13B—H13F | 109.4 |
N1A—C8A—H8A | 112.0 | H13D—C13B—H13F | 109.5 |
C9A—C8A—H8A | 111.9 | H13E—C13B—H13F | 109.5 |
C7A—C8A—H8A | 112.0 | C3B—C2B—C1B | 117.2 (10) |
N1B—C10B—C13B | 108.6 (8) | C3B—C2B—H2B | 121.4 |
N1B—C10B—C11B | 112.0 (9) | C1B—C2B—H2B | 121.4 |
C13B—C10B—C11B | 110.3 (10) | O1B—C7B—C5B | 118.7 (13) |
N1B—C10B—C12B | 103.2 (7) | O1B—C7B—C8B | 118.6 (11) |
C13B—C10B—C12B | 109.3 (9) | C5B—C7B—C8B | 122.7 (11) |
C11B—C10B—C12B | 113.1 (10) | C8A—C9A—H9A1 | 109.5 |
C1B—C6B—C5B | 122.1 (12) | C8A—C9A—H9A2 | 109.5 |
C1B—C6B—H6B | 119.0 | H9A1—C9A—H9A2 | 109.5 |
C5B—C6B—H6B | 119.0 | C8A—C9A—H9A3 | 109.5 |
C10A—C13A—H13A | 109.5 | H9A1—C9A—H9A3 | 109.5 |
C10A—C13A—H13B | 109.5 | H9A2—C9A—H9A3 | 109.5 |
H13A—C13A—H13B | 109.5 | C6B—C1B—C2B | 121.9 (8) |
C10A—C13A—H13C | 109.5 | C6B—C1B—Cl1B | 118.3 (8) |
H13A—C13A—H13C | 109.5 | C2B—C1B—Cl1B | 119.8 (8) |
H13B—C13A—H13C | 109.5 | C1A—C2A—C3A | 120.6 (11) |
C6A—C1A—C2A | 119.5 (8) | C1A—C2A—H2A | 119.7 |
C6A—C1A—Cl1A | 122.1 (7) | C3A—C2A—H2A | 119.7 |
C2A—C1A—Cl1A | 118.0 (8) | C2B—C3B—C4B | 119.7 (12) |
N1A—C10A—C11A | 111.6 (9) | C2B—C3B—H3B | 120.1 |
N1A—C10A—C12A | 109.8 (7) | C4B—C3B—H3B | 120.1 |
C11A—C10A—C12A | 106.6 (9) | C8B—C9B—H9B1 | 109.5 |
N1A—C10A—C13A | 109.4 (8) | C8B—C9B—H9B2 | 109.5 |
C11A—C10A—C13A | 109.1 (10) | H9B1—C9B—H9B2 | 109.5 |
C12A—C10A—C13A | 110.3 (9) | C8B—C9B—H9B3 | 109.5 |
N1B—C8B—C7B | 110.4 (9) | H9B1—C9B—H9B3 | 109.5 |
N1B—C8B—C9B | 112.6 (9) | H9B2—C9B—H9B3 | 109.5 |
C7B—C8B—C9B | 111.6 (11) | C4A—C3A—C2A | 120.3 (13) |
N1B—C8B—H8B | 107.3 | C4A—C3A—H3A | 119.9 |
C7B—C8B—H8B | 107.3 | C2A—C3A—H3A | 119.9 |
C9B—C8B—H8B | 107.3 | C21—O21—H21 | 109.5 |
C1A—C6A—C5A | 119.7 (12) | C22—C23—H23A | 109.5 |
C1A—C6A—H6A | 120.1 | C22—C23—H23B | 109.5 |
C5A—C6A—H6A | 120.1 | H23A—C23—H23B | 109.5 |
C5B—C4B—C3B | 123.5 (11) | C22—C23—H23C | 109.5 |
C5B—C4B—H4B | 118.3 | H23A—C23—H23C | 109.5 |
C3B—C4B—H4B | 118.3 | H23B—C23—H23C | 109.5 |
C3A—C4A—C5A | 118.3 (12) | O21—C21—C22 | 103.6 (11) |
C3A—C4A—H4A | 120.9 | O21—C21—H21A | 111.1 |
C5A—C4A—H4A | 120.9 | C22—C21—H21A | 111.0 |
C10B—C11B—H11A | 109.5 | O21—C21—H21B | 111.0 |
C10B—C11B—H11B | 109.5 | C22—C21—H21B | 111.0 |
H11A—C11B—H11B | 109.5 | H21A—C21—H21B | 109.0 |
C10B—C11B—H11C | 109.5 | C21—C22—C23 | 109.0 (11) |
H11A—C11B—H11C | 109.5 | C21—C22—H22A | 109.9 |
H11B—C11B—H11C | 109.5 | C23—C22—H22A | 109.9 |
C6A—C5A—C4A | 121.5 (11) | C21—C22—H22B | 109.9 |
C6A—C5A—C7A | 114.1 (10) | C23—C22—H22B | 109.9 |
C4A—C5A—C7A | 124.4 (10) | H22A—C22—H22B | 108.3 |
C10A—C11A—H11D | 109.5 | ||
C10A—N1A—C8A—C9A | 163.9 (10) | O1A—C7A—C5A—C6A | 11 (2) |
C10A—N1A—C8A—C7A | −83.3 (12) | C8A—C7A—C5A—C6A | −170.2 (13) |
O1A—C7A—C8A—N1A | −30.1 (17) | O1A—C7A—C5A—C4A | −169.4 (16) |
C5A—C7A—C8A—N1A | 151.2 (12) | C8A—C7A—C5A—C4A | 9 (2) |
O1A—C7A—C8A—C9A | 84.1 (16) | C4B—C5B—C7B—O1B | 172.1 (16) |
C5A—C7A—C8A—C9A | −94.6 (14) | C6B—C5B—C7B—O1B | −8 (2) |
C8B—N1B—C10B—C13B | 71.2 (11) | C4B—C5B—C7B—C8B | −8 (2) |
C8B—N1B—C10B—C11B | −50.9 (13) | C6B—C5B—C7B—C8B | 171.9 (13) |
C8B—N1B—C10B—C12B | −172.9 (10) | N1B—C8B—C7B—O1B | 31.9 (19) |
C4B—C5B—C6B—C1B | 3 (2) | C9B—C8B—C7B—O1B | −94.2 (18) |
C7B—C5B—C6B—C1B | −176.9 (16) | N1B—C8B—C7B—C5B | −148.0 (13) |
C8A—N1A—C10A—C11A | 52.4 (12) | C9B—C8B—C7B—C5B | 85.9 (17) |
C8A—N1A—C10A—C12A | 170.4 (10) | C5B—C6B—C1B—C2B | −6 (3) |
C8A—N1A—C10A—C13A | −68.4 (11) | C5B—C6B—C1B—Cl1B | 176.3 (12) |
C10B—N1B—C8B—C7B | 81.1 (13) | C3B—C2B—C1B—C6B | 6 (3) |
C10B—N1B—C8B—C9B | −153.4 (11) | C3B—C2B—C1B—Cl1B | −176.5 (12) |
C2A—C1A—C6A—C5A | −3 (3) | C6A—C1A—C2A—C3A | 3 (3) |
Cl1A—C1A—C6A—C5A | −175.4 (12) | Cl1A—C1A—C2A—C3A | 176.0 (14) |
C6B—C5B—C4B—C3B | 0 (2) | C1B—C2B—C3B—C4B | −3 (2) |
C7B—C5B—C4B—C3B | 179.8 (15) | C5B—C4B—C3B—C2B | 0 (2) |
C1A—C6A—C5A—C4A | 2 (2) | C5A—C4A—C3A—C2A | 3 (3) |
C1A—C6A—C5A—C7A | −178.1 (15) | C1A—C2A—C3A—C4A | −3 (3) |
C3A—C4A—C5A—C6A | −2 (2) | O21—C21—C22—C23 | −140.0 (16) |
C3A—C4A—C5A—C7A | 178.3 (16) |
D—H···A | D—H | H···A | D···A | D—H···A |
N1A—H1A1···Br1A | 0.90 | 2.46 | 3.353 (9) | 174 |
N1A—H1A2···Br1Bi | 0.90 | 2.60 | 3.410 (9) | 150 |
N1B—H1B1···Br1Bii | 0.90 | 2.46 | 3.362 (9) | 175 |
N1B—H1B2···Br1Aiii | 0.90 | 2.58 | 3.383 (9) | 149 |
O21—H21···Br1A | 0.82 | 2.73 | 3.487 (10) | 153 |
Symmetry codes: (i) x−1, y, z; (ii) x, y+1, z; (iii) x+1, y+1, z. |
Experimental details
Crystal data | |
Chemical formula | C13H19ClNO+·Br−·0.5C3H8O |
Mr | 350.70 |
Crystal system, space group | Triclinic, P1 |
Temperature (K) | 296 |
a, b, c (Å) | 7.8614 (4), 9.4100 (6), 11.8477 (7) |
α, β, γ (°) | 85.783 (2), 78.159 (2), 89.450 (2) |
V (Å3) | 855.46 (9) |
Z | 2 |
Radiation type | Mo Kα |
µ (mm−1) | 2.56 |
Crystal size (mm) | 0.46 × 0.28 × 0.14 |
Data collection | |
Diffractometer | Rigaku R-AXIS RAPID |
Absorption correction | Multi-scan (ABSCOR; Higashi, 1995) |
Tmin, Tmax | 0.361, 0.647 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 8456, 6355, 4179 |
Rint | 0.031 |
(sin θ/λ)max (Å−1) | 0.649 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.043, 0.138, 1.00 |
No. of reflections | 6355 |
No. of parameters | 354 |
No. of restraints | 77 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.74, −0.97 |
Absolute structure | Flack (1983), 2490 Friedel pairs |
Absolute structure parameter | 0.34 (3) |
Computer programs: PROCESS-AUTO (Rigaku, 2006), CrystalStructure (Rigaku, 2007), SHELXS97 (Sheldrick, 2008), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997), WinGX (Farrugia, 1999).
D—H···A | D—H | H···A | D···A | D—H···A |
N1A—H1A1···Br1A | 0.90 | 2.46 | 3.353 (9) | 173.7 |
N1A—H1A2···Br1Bi | 0.90 | 2.60 | 3.410 (9) | 149.8 |
N1B—H1B1···Br1Bii | 0.90 | 2.46 | 3.362 (9) | 174.7 |
N1B—H1B2···Br1Aiii | 0.90 | 2.58 | 3.383 (9) | 148.9 |
O21—H21···Br1A | 0.82 | 2.73 | 3.487 (10) | 153.4 |
Symmetry codes: (i) x−1, y, z; (ii) x, y+1, z; (iii) x+1, y+1, z. |
Acknowledgements
The project was supported by the Zhejiang Provincial Natural Science Foundation of China (J200801).
References
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The title compound, bupropion hydrobromide, 1-(3-chlorophenyl)-2-[(1,1- dimethylethyl)amino]-1-propanone hydrobromide, belongs to the class of antidepressants known as aminoketones and it is known also with the drug name Aplenzin. It is a second generation antidepressant approved in US and in some European countries, its mechanism of action, both as an antidepressant and as an aids to smoking cessation, is thought to involve nicotinic acetylcholine receptors that are linked to dopamine and norepinephrine release (Fryer et al. 1999 & Stewart et al., 2001). Pure bupropion enantiomers were successfully synthesized but they give rise to a rapid racemization (Fang et al., 2000). In literature, crystal structure of an ethanol hemi-solvate bupropion derivative and bupropion hydrochloride, obtained from single-crystal X-ray analysis and powder diffraction, were reported (Froimowitz et al., 1998 & Maccaroni et al., 2009). Here, we reported crystal structure of bupropion hydrobromide propanol solvate. The asymmetric unit consists of two bupropion cations, two bromide anions and one 1-propanol molecule (Fig.1). Expected proton transfer from HBr to amino group of bupropion is observed, intramolecular and intermolecular hydrogen bond interactions are formed (Table 1).These interactions result in hydrogen-bond dimers in the two polymorphic forms, in which two Br- ions bridge the NH2—NH2 contact (above 4.2 Å), similar to that of BUP hydrochloride (Maccaroni et al., 2009). Solvent molecule 1-propanol is linked to bupropion hydrobromide by intramolecular hydrogen bond O21—H21···Br1A. The side chains of the two molecules have slightly different orientations, as seen by the torsion angles of C6—C5—C7—C8, C5—C7—C8—N1, C7—C8—N1—C10 and O1—C7—C5—C6. Carbonyl groups in the two molecules are not coplanar with phenyl ring plane, atom O1A and O1B deviated from the least-squares plane of phenyl ring (C1A/C6A and C1B/C6B) 0.238Å and 0.139 Å, respectively.