Bupropion hydro­bromide propanol hemisolvate

Min Liu; Xiu-Rong Hu; Jian-Ming Gu; Gu-Ping Tang

doi:10.1107/S1600536811037093

. 2011 Sep 30;67(Pt 10):o2772. doi: 10.1107/S1600536811037093

Bupropion hydrobromide propanol hemisolvate

Min Liu ^a, Xiu-Rong Hu ^a,^*, Jian-Ming Gu ^b, Gu-Ping Tang ^a

PMCID: PMC3201450 PMID: 22064727

Abstract

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 asymmetric unit. 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

C₁₃H₁₉ClNO⁺·Br⁻·0.5C₃H₈O
M _r = 350.70
Triclinic,
a = 7.8614 (4) Å
b = 9.4100 (6) Å
c = 11.8477 (7) Å
α = 85.783 (2)°
β = 78.159 (2)°
γ = 89.450 (2)°
V = 855.46 (9) Å³
Z = 2
Mo Kα radiation
μ = 2.56 mm⁻¹
T = 296 K
0.46 × 0.28 × 0.14 mm

Data collection

Rigaku R-AXIS RAPID diffractometer
Absorption correction: multi-scan (ABSCOR; Higashi, 1995 ▶) T _min = 0.361, T _max = 0.647
8456 measured reflections
6355 independent reflections
4179 reflections with I > 2σ(I)
R _int = 0.031

Refinement

R[F ² > 2σ(F ²)] = 0.043
wR(F ²) = 0.138
S = 1.00
6355 reflections
354 parameters
77 restraints
H-atom parameters constrained
Δρ_max = 0.74 e Å⁻³
Δρ_min = −0.97 e Å⁻³
Absolute structure: Flack (1983 ▶), 2490 Friedel pairs
Flack parameter: 0.34 (3)

Data collection: PROCESS-AUTO (Rigaku, 2006 ▶); cell refinement: 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 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536811037093/bx2372sup1.cif

e-67-o2772-sup1.cif^{(26.5KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536811037093/bx2372Isup2.hkl

e-67-o2772-Isup2.hkl^{(304.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811037093/bx2372Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

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

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

The project was supported by the Zhejiang Provincial Natural Science Foundation of China (J200801).

supplementary crystallographic information

Comment

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.

Experimental

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.