A triclinic polymorph of (-)-(S)-N-benzyl-2-[(R)-6-fluoro-chroman-2-yl]-2-hy-droxy-ethanaminium bromide.

The title salt, C18H21FNO2 (+)·Br(-), determined at 115 K, crystallizes in the triclinic space group P1. The previously reported polymorph occurs in the monoclinic space group P21 and has two independent mol-ecules in the asymmetric unit [Peeters et al. (1993 ▶). Acta Cryst. C49, 2157-2160]. In the title molecule, the pyran rings adopt half-chair conformations. The absolute configuration is S for the hy-droxy-bearing C atom and R for the asymmetric C atom in the di-hydro-pyran unit. In the crystal, the components are linked by N-H⋯Br and O-H⋯Br hydrogen bonds, forming chains along the c-axis direction. The crystal studied was refined as an inversion twin.

Related literature

For the synthesis of the enanti­opure title product, see: Jas et al. (2011 ▶). For studies of related isomers, see: Cini et al. (1990 ▶); Tuchalski et al. (2006 ▶, 2008 ▶); Rousselin et al. (2012 ▶). for the monoclinic polymorph, see: Peeters et al. (1993 ▶). The title compound is a key inter­mediate in the synthesis of the beta blocker dl-nebivolol [systematic name: 1-(6-fluoro­chroman-2-yl)-{[2-(6-fluoro­chroman-2-yl)-2-hy­droxy-eth­yl]amino}­ethanol. For the pharmacological properties of nebivolol, see: Van Lommen et al. (1990 ▶). For puckering parameters, see: Cremer & Pople (1975 ▶). For background to polymorphism, see: Bernstein (2002 ▶).

Experimental

Crystal data

C18H21FNO2 +·Br−

M = 382.27

Triclinic,

a = 4.9248 (2) Å

b = 5.5117 (2) Å

c = 16.3894 (7) Å

α = 83.721 (2)°

β = 89.038 (2)°

γ = 86.765 (2)°

V = 441.48 (3) Å3

Z = 1

Mo Kα1 radiation

μ = 2.35 mm−1

T = 115 K

0.25 × 0.2 × 0.2 mm

Data collection

Nonius KappaCCD diffractometer with APEXII detector

Absorption correction: multi-scan (SADABS; Bruker, 2012 ▶) T min = 0.61, T max = 0.74

10328 measured reflections

3903 independent reflections

3886 reflections with I > 2σ(I)

R int = 0.020

Refinement

R[F 2 > 2σ(F 2)] = 0.021

wR(F 2) = 0.052

S = 1.11

3903 reflections

210 parameters

3 restraints

H-atom parameters constrained

Δρmax = 0.37 e Å−3

Δρmin = −0.18 e Å−3

Absolute structure: Flack (1983 ▶); refined as an inversion twin

Absolute structure parameter: 0.013 (7)

Data collection: APEX2 (Bruker, 2012 ▶); cell refinement: SAINT (Bruker, 2012 ▶); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: OLEX2 (Dolomanov et al., 2009 ▶); software used to prepare material for publication: OLEX2.

Crystal structure: contains datablock(s) I. DOI: 10.1107/S1600536813030377/gw2140sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813030377/gw2140Isup2.hkl

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536813030377/gw2140Isup3.cdx

Click here for additional data file.

Supplementary material file. DOI: 10.1107/S1600536813030377/gw2140Isup4.cml

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

C18H21FNO2+·Br−	V = 441.48 (3) Å3
Mr = 382.27	Z = 1
Triclinic, P1	F(000) = 196
a = 4.9248 (2) Å	Dx = 1.438 Mg m−3
b = 5.5117 (2) Å	Mo Kα1 radiation, λ = 0.71073 Å
c = 16.3894 (7) Å	µ = 2.35 mm−1
α = 83.721 (2)°	T = 115 K
β = 89.038 (2)°	Prism, clear light colourless
γ = 86.765 (2)°	0.25 × 0.2 × 0.2 mm

Nonius KappaCCD diffractometer with APEXII detector	3903 independent reflections
Radiation source: X-ray tube, Siemens KFF Mo 2K-180	3886 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.020
Detector resolution: 9 pixels mm-1	θmax = 27.6°, θmin = 3.7°
CCD rotation images, thick slices scans	h = −6→6
Absorption correction: multi-scan (SADABS; Bruker, 2012)	k = −7→6
Tmin = 0.61, Tmax = 0.74	l = −21→21
10328 measured reflections

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.021	w = 1/[σ2(Fo2) + (0.0317P)2 + 0.0488P] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.052	(Δ/σ)max < 0.001
S = 1.11	Δρmax = 0.37 e Å−3
3903 reflections	Δρmin = −0.18 e Å−3
210 parameters	Absolute structure: Flack (1983); refined as an inversion twin
3 restraints	Absolute structure parameter: 0.013 (7)
0 constraints

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. Refined as a 2-component inversion twin.

	x	y	z	Uiso*/Ueq
C1	−0.0450 (9)	0.1145 (8)	0.4454 (2)	0.0432 (10)
C2	0.1300 (8)	0.3000 (9)	0.4294 (2)	0.0438 (11)
H2	0.1974	0.3810	0.4725	0.053*
C3	0.2056 (7)	0.3656 (7)	0.3481 (2)	0.0336 (7)
H3	0.3260	0.4932	0.3348	0.040*
C4	0.1030 (6)	0.2425 (5)	0.28630 (16)	0.0208 (5)
C5	−0.0712 (6)	0.0542 (6)	0.30396 (17)	0.0229 (6)
C6	−0.1462 (7)	−0.0085 (7)	0.3862 (2)	0.0350 (8)
H6	−0.2666	−0.1356	0.4003	0.042*
C7	−0.1764 (6)	−0.0806 (7)	0.2368 (2)	0.0220 (6)
H7A	−0.3673	−0.0241	0.2246	0.026*
H7B	−0.1721	−0.2580	0.2551	0.026*
C8	−0.0012 (6)	−0.0345 (6)	0.15966 (19)	0.0155 (6)
H8A	0.1775	−0.1248	0.1676	0.019*
H8B	−0.0911	−0.0932	0.1125	0.019*
C9	0.0379 (5)	0.2363 (5)	0.14248 (15)	0.0135 (5)
H9	−0.1448	0.3254	0.1390	0.016*
C10	0.2004 (5)	0.3138 (5)	0.06472 (15)	0.0142 (5)
H10	0.2312	0.4917	0.0642	0.017*
C11	0.0363 (5)	0.2836 (6)	−0.01119 (18)	0.0122 (6)
H11A	−0.0166	0.1125	−0.0092	0.015*
H11B	−0.1318	0.3911	−0.0120	0.015*
C12	0.0371 (6)	0.3492 (6)	−0.1649 (2)	0.0174 (7)
H12A	−0.0300	0.1845	−0.1681	0.021*
H12B	−0.1225	0.4662	−0.1633	0.021*
C13	0.2086 (6)	0.4206 (5)	−0.23948 (16)	0.0186 (5)
C14	0.4109 (6)	0.2578 (6)	−0.26486 (18)	0.0263 (6)
H14	0.4397	0.1012	−0.2349	0.032*
C15	0.5715 (8)	0.3220 (8)	−0.3336 (2)	0.0394 (8)
H15	0.7117	0.2107	−0.3494	0.047*
C16	0.5283 (9)	0.5446 (9)	−0.3784 (2)	0.0438 (10)
H16	0.6358	0.5868	−0.4260	0.053*
C17	0.3274 (12)	0.7082 (9)	−0.3541 (2)	0.0481 (13)
H17	0.2989	0.8634	−0.3851	0.058*
C18	0.1655 (10)	0.6482 (8)	−0.2847 (2)	0.0332 (10)
H18	0.0277	0.7615	−0.2685	0.040*
N1	0.2011 (4)	0.3481 (4)	−0.08768 (13)	0.0128 (4)
H1A	0.3584	0.2287	−0.0893	0.015*
H1B	0.2725	0.5118	−0.0859	0.015*
O1	0.1885 (4)	0.3208 (4)	0.20789 (11)	0.0191 (4)
O2	0.4597 (3)	0.1871 (4)	0.06423 (12)	0.0191 (4)
H2A	0.4477	0.0574	0.0423	0.029*
F1	−0.1223 (7)	0.0501 (6)	0.52531 (13)	0.0673 (9)
Br1	0.56053 (2)	0.82061 (2)	0.92529 (2)	0.02213 (8)

	U11	U22	U33	U12	U13	U23
C1	0.055 (2)	0.058 (3)	0.0135 (14)	0.0171 (19)	0.0071 (14)	−0.0006 (14)
C2	0.058 (3)	0.055 (3)	0.0186 (15)	0.016 (2)	−0.0064 (19)	−0.0170 (16)
C3	0.0379 (18)	0.042 (2)	0.0223 (15)	0.0058 (15)	−0.0052 (13)	−0.0137 (14)
C4	0.0202 (13)	0.0257 (14)	0.0158 (12)	0.0085 (10)	−0.0025 (10)	−0.0045 (10)
C5	0.0190 (13)	0.0303 (15)	0.0173 (13)	0.0093 (11)	0.0031 (10)	0.0012 (11)
C6	0.0363 (18)	0.043 (2)	0.0228 (15)	0.0080 (15)	0.0072 (13)	0.0047 (14)
C7	0.0181 (13)	0.0259 (16)	0.0207 (16)	−0.0041 (11)	0.0036 (12)	0.0049 (13)
C8	0.0139 (13)	0.0169 (15)	0.0157 (14)	−0.0014 (10)	−0.0005 (11)	−0.0009 (12)
C9	0.0117 (11)	0.0151 (12)	0.0142 (11)	0.0001 (9)	−0.0005 (9)	−0.0038 (9)
C10	0.0106 (11)	0.0166 (12)	0.0161 (12)	−0.0021 (9)	0.0005 (9)	−0.0042 (9)
C11	0.0065 (11)	0.0168 (13)	0.0135 (14)	−0.0025 (9)	0.0012 (10)	−0.0017 (11)
C12	0.0136 (13)	0.0244 (15)	0.0152 (14)	−0.0036 (11)	−0.0040 (11)	−0.0055 (12)
C13	0.0214 (13)	0.0216 (14)	0.0140 (12)	−0.0088 (10)	−0.0044 (10)	−0.0022 (10)
C14	0.0285 (15)	0.0325 (16)	0.0190 (13)	−0.0058 (12)	0.0027 (11)	−0.0060 (12)
C15	0.0361 (18)	0.063 (3)	0.0220 (15)	−0.0132 (17)	0.0078 (13)	−0.0121 (16)
C16	0.050 (2)	0.067 (3)	0.0170 (14)	−0.034 (2)	0.0022 (14)	−0.0008 (16)
C17	0.082 (3)	0.037 (2)	0.025 (2)	−0.030 (2)	−0.016 (2)	0.0138 (18)
C18	0.047 (2)	0.027 (2)	0.0249 (19)	−0.0061 (16)	−0.0111 (16)	0.0009 (15)
N1	0.0104 (10)	0.0143 (10)	0.0140 (10)	−0.0030 (8)	0.0001 (8)	−0.0017 (8)
O1	0.0196 (9)	0.0250 (10)	0.0139 (8)	−0.0045 (7)	−0.0015 (7)	−0.0060 (7)
O2	0.0065 (8)	0.0321 (11)	0.0197 (9)	0.0000 (7)	−0.0006 (7)	−0.0073 (8)
F1	0.101 (2)	0.082 (2)	0.0154 (10)	0.0127 (17)	0.0165 (12)	−0.0005 (11)
Br1	0.01948 (11)	0.01430 (11)	0.03333 (14)	−0.00276 (7)	−0.00045 (8)	−0.00482 (8)

C1—C2	1.375 (7)	C10—O2	1.421 (3)
C1—C6	1.360 (6)	C11—H11A	0.9900
C1—F1	1.372 (4)	C11—H11B	0.9900
C2—H2	0.9500	C11—N1	1.502 (3)
C2—C3	1.392 (6)	C12—H12A	0.9900
C3—H3	0.9500	C12—H12B	0.9900
C3—C4	1.396 (4)	C12—C13	1.503 (4)
C4—C5	1.387 (5)	C12—N1	1.513 (4)
C4—O1	1.377 (3)	C13—C14	1.392 (4)
C5—C6	1.403 (4)	C13—C18	1.393 (5)
C5—C7	1.508 (5)	C14—H14	0.9500
C6—H6	0.9500	C14—C15	1.390 (4)
C7—H7A	0.9900	C15—H15	0.9500
C7—H7B	0.9900	C15—C16	1.367 (6)
C7—C8	1.525 (4)	C16—H16	0.9500
C8—H8A	0.9900	C16—C17	1.384 (7)
C8—H8B	0.9900	C17—H17	0.9500
C8—C9	1.511 (4)	C17—C18	1.399 (7)
C9—H9	1.0000	C18—H18	0.9500
C9—C10	1.527 (3)	N1—H1A	0.9900
C9—O1	1.446 (3)	N1—H1B	0.9900
C10—H10	1.0000	O2—H2A	0.8400
C10—C11	1.524 (4)
C6—C1—C2	123.4 (3)	O2—C10—H10	107.5
C6—C1—F1	118.2 (4)	O2—C10—C11	112.2 (2)
F1—C1—C2	118.4 (4)	C10—C11—H11A	109.6
C1—C2—H2	121.0	C10—C11—H11B	109.6
C1—C2—C3	118.1 (4)	H11A—C11—H11B	108.1
C3—C2—H2	121.0	N1—C11—C10	110.3 (2)
C2—C3—H3	120.3	N1—C11—H11A	109.6
C2—C3—C4	119.4 (4)	N1—C11—H11B	109.6
C4—C3—H3	120.3	H12A—C12—H12B	108.1
C5—C4—C3	121.5 (3)	C13—C12—H12A	109.6
O1—C4—C3	115.2 (3)	C13—C12—H12B	109.6
O1—C4—C5	123.2 (3)	C13—C12—N1	110.4 (2)
C4—C5—C6	118.2 (3)	N1—C12—H12A	109.6
C4—C5—C7	121.0 (2)	N1—C12—H12B	109.6
C6—C5—C7	120.8 (3)	C14—C13—C12	120.2 (3)
C1—C6—C5	119.4 (4)	C14—C13—C18	119.1 (3)
C1—C6—H6	120.3	C18—C13—C12	120.7 (3)
C5—C6—H6	120.3	C13—C14—H14	119.6
C5—C7—H7A	109.7	C15—C14—C13	120.7 (3)
C5—C7—H7B	109.7	C15—C14—H14	119.6
C5—C7—C8	109.8 (3)	C14—C15—H15	119.9
H7A—C7—H7B	108.2	C16—C15—C14	120.3 (4)
C8—C7—H7A	109.7	C16—C15—H15	119.9
C8—C7—H7B	109.7	C15—C16—H16	120.2
C7—C8—H8A	109.9	C15—C16—C17	119.7 (3)
C7—C8—H8B	109.9	C17—C16—H16	120.2
H8A—C8—H8B	108.3	C16—C17—H17	119.5
C9—C8—C7	109.1 (3)	C16—C17—C18	120.9 (4)
C9—C8—H8A	109.9	C18—C17—H17	119.5
C9—C8—H8B	109.9	C13—C18—C17	119.3 (4)
C8—C9—H9	108.7	C13—C18—H18	120.4
C8—C9—C10	115.5 (2)	C17—C18—H18	120.4
C10—C9—H9	108.7	C11—N1—C12	112.5 (2)
O1—C9—C8	110.5 (2)	C11—N1—H1A	109.1
O1—C9—H9	108.7	C11—N1—H1B	109.1
O1—C9—C10	104.45 (19)	C12—N1—H1A	109.1
C9—C10—H10	107.5	C12—N1—H1B	109.1
C11—C10—C9	110.3 (2)	H1A—N1—H1B	107.8
C11—C10—H10	107.5	C4—O1—C9	115.5 (2)
O2—C10—C9	111.7 (2)	C10—O2—H2A	109.5
C1—C2—C3—C4	−0.1 (5)	C10—C9—O1—C4	−171.2 (2)
C2—C1—C6—C5	−0.1 (6)	C10—C11—N1—C12	−173.5 (2)
C2—C3—C4—C5	−0.6 (5)	C12—C13—C14—C15	−179.8 (3)
C2—C3—C4—O1	179.8 (3)	C12—C13—C18—C17	−179.5 (4)
C3—C4—C5—C6	0.9 (4)	C13—C12—N1—C11	178.6 (2)
C3—C4—C5—C7	−178.8 (3)	C13—C14—C15—C16	−1.5 (5)
C3—C4—O1—C9	−166.3 (2)	C14—C13—C18—C17	−0.4 (5)
C4—C5—C6—C1	−0.6 (5)	C14—C15—C16—C17	1.3 (6)
C4—C5—C7—C8	17.2 (4)	C15—C16—C17—C18	−0.6 (6)
C5—C4—O1—C9	14.1 (4)	C16—C17—C18—C13	0.1 (7)
C5—C7—C8—C9	−47.7 (3)	C18—C13—C14—C15	1.0 (5)
C6—C1—C2—C3	0.4 (6)	N1—C12—C13—C14	72.8 (3)
C6—C5—C7—C8	−162.5 (3)	N1—C12—C13—C18	−108.0 (3)
C7—C5—C6—C1	179.1 (3)	O1—C4—C5—C6	−179.5 (3)
C7—C8—C9—C10	−177.6 (2)	O1—C4—C5—C7	0.8 (4)
C7—C8—C9—O1	64.1 (3)	O1—C9—C10—C11	−168.4 (2)
C8—C9—C10—C11	70.0 (3)	O1—C9—C10—O2	66.1 (2)
C8—C9—C10—O2	−55.4 (3)	O2—C10—C11—N1	−52.0 (3)
C8—C9—O1—C4	−46.4 (3)	F1—C1—C2—C3	−179.5 (3)
C9—C10—C11—N1	−177.2 (2)	F1—C1—C6—C5	179.8 (3)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···Br1i	0.99	2.40	3.306 (2)	152
N1—H1B···Br1ii	0.99	2.30	3.258 (2)	162
O2—H2A···Br1i	0.84	2.47	3.2198 (19)	149

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯Br1i	0.99	2.40	3.306 (2)	152
N1—H1B⋯Br1ii	0.99	2.30	3.258 (2)	162
O2—H2A⋯Br1i	0.84	2.47	3.2198 (19)	149

Symmetry codes: (i) ; (ii) .