Venlafaxine hydrochloride, [(
)-
N,N-dimethyl-2-(1-hydroxycyclohex-1-yl)-2-(4-methoxyphenyl) ethylamine hydrochloride, C
17H
28ClNO
2] is found to crystallize in both orthorhombic and monoclinic crystal systems. The molecular structures in the two polymorphs differ in the conformations of the substituents at the ethylamine group. In the monoclinic crystal structure, the molecules translated along the
a axis are linked by Cl
− ions through O—H
Cl and N—H
Cl hydrogen bonds to form infinite one-dimensional chains.
Supporting information
CCDC reference: 198947
Key indicators
- Single-crystal X-ray study
- T = 298 K
- Mean (C-C) = 0.007 Å
- R factor = 0.068
- wR factor = 0.068
- Data-to-parameter ratio = 9.1
checkCIF results
No syntax errors found
Structure: II
-------------
ADDSYM reports no extra symmetry
Alert Level C:
REFNR_01 Alert C Ratio of reflections to parameters is < 10 for a
centrosymmetric structure
sine(theta)/lambda 0.6098
Proportion of unique data used 0.5496
Ratio reflections to parameters 9.1256
PLAT_031 Alert C Refined Extinction parameter within range .... 3.14 Sigma
General Notes
ABSTM_02 When printed, the submitted absorption T values will be replaced
by the scaled T values. Since the ratio of scaled T's is
identical to the ratio of reported T values, the scaling does
not imply a change to the absorption corrections used in the
study.
Ratio of Tmax expected/reported 0.825
Tmax scaled 0.821 Tmin scaled 0.695
0 Alert Level A = Potentially serious problem
0 Alert Level B = Potential problem
2 Alert Level C = Please check
Crystals of form II of venlafaxine hydrochloride suitable for X-ray diffraction were grown from a mixture of methanol and ethyl acetate (1:1).
Data collection: MSC/AFC Diffractometer Control Software (Molecular Structure Corporation, 1994); cell refinement: MSC/AFC Diffractometer Control Software; data reduction: TEXSAN (Molecular Structure Corporation, 1995); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: TEXSAN; molecular graphics: TEXSAN; software used to prepare material for publication: TEXSAN.
(±)–
N,
N–dimethyl–2–(1–hydroxycyclohex–1–yl)–2–(4–methoxyphenyl) ethylamine hydrochloride(±)–1–[2–(Dimethylamino)–1–(4–methoxyphenyl)ethyl] cyclohexanol hydrochloride1-(2-(1-Hydroxycyclohexyl)-2-(4-methoxyphenyl)ethyl)dimethylammonium chloride
top
Crystal data top
C17H28NO2+·Cl− | F(000) = 680.00 |
Mr = 313.87 | Dx = 1.197 Mg m−3 |
Monoclinic, P21/n | Cu Kα radiation, λ = 1.5418 Å |
Hall symbol: -P 2yn | Cell parameters from 24 reflections |
a = 5.797 (6) Å | θ = 6.4–23.7° |
b = 26.074 (7) Å | µ = 1.97 mm−1 |
c = 11.722 (3) Å | T = 298 K |
β = 100.72 (5)° | Needle, colourless |
V = 1741 (2) Å3 | 0.40 × 0.10 × 0.10 mm |
Z = 4 | |
Data collection top
Rigaku AFC7S diffractometer | 3304 reflections with I > 1.30s(I) |
Radiation source: X-ray tube | Rint = 0.078 |
Graphite monochromator | θmax = 70.1°, θmin = 3.4° |
ω–2θ scans | h = 0→6 |
Absorption correction: ψ scan (North, Phillips & Mathews, 1968) | k = 0→31 |
Tmin = 0.843, Tmax = 0.996 | l = −14→14 |
3564 measured reflections | 4 standard reflections every 150 reflections |
3304 independent reflections | intensity decay: −0.3% |
Refinement top
Refinement on F | 78 constraints |
Least-squares matrix: full | H atoms treated by a mixture of independent and constrained refinement |
R[F2 > 2σ(F2)] = 0.068 | Weighting scheme based on measured s.u.'s w = 1/[σ2(Fo) + 0.00016|Fo|2] |
wR(F2) = 0.068 | (Δ/σ)max = 0.001 |
S = 1.29 | Δρmax = 0.40 e Å−3 |
1816 reflections | Δρmin = −0.33 e Å−3 |
199 parameters | Extinction correction: Zachariasen (1967), equ(3) Acta Cryst.(1968) A24, p213. |
0 restraints | Extinction coefficient: 0.0000022 (7) |
Crystal data top
C17H28NO2+·Cl− | V = 1741 (2) Å3 |
Mr = 313.87 | Z = 4 |
Monoclinic, P21/n | Cu Kα radiation |
a = 5.797 (6) Å | µ = 1.97 mm−1 |
b = 26.074 (7) Å | T = 298 K |
c = 11.722 (3) Å | 0.40 × 0.10 × 0.10 mm |
β = 100.72 (5)° | |
Data collection top
Rigaku AFC7S diffractometer | 3304 reflections with I > 1.30s(I) |
Absorption correction: ψ scan (North, Phillips & Mathews, 1968) | Rint = 0.078 |
Tmin = 0.843, Tmax = 0.996 | 4 standard reflections every 150 reflections |
3564 measured reflections | intensity decay: −0.3% |
3304 independent reflections | |
Refinement top
R[F2 > 2σ(F2)] = 0.068 | 0 restraints |
wR(F2) = 0.068 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.29 | Δρmax = 0.40 e Å−3 |
1816 reflections | Δρmin = −0.33 e Å−3 |
199 parameters | |
Special details top
Experimental. The scan width was (0.94 + 0.14tanθ)° with an ω scan speed of 16° per minute (up to 5 scans to achieve I/σ(I) > 15). Stationary background counts were recorded at each end of the scan, and the scan time:background time ratio was 2:1. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
Cl1 | 0.3864 (2) | 0.77716 (5) | 0.75684 (10) | 0.0628 (4) | |
O1 | 0.4899 (6) | 0.93560 (14) | 0.0837 (3) | 0.0686 (11) | |
O2 | 1.1462 (5) | 0.86870 (12) | 0.5932 (3) | 0.0526 (11) | |
N1 | 0.6144 (7) | 0.75613 (14) | 0.5480 (3) | 0.0505 (12) | |
C1 | 0.6672 (7) | 0.87054 (16) | 0.4127 (3) | 0.0451 (12) | |
C2 | 0.4611 (8) | 0.89845 (18) | 0.3773 (4) | 0.0543 (17) | |
C3 | 0.4079 (8) | 0.91970 (18) | 0.2679 (4) | 0.0577 (17) | |
C4 | 0.5583 (8) | 0.91298 (18) | 0.1894 (4) | 0.0520 (16) | |
C5 | 0.7582 (8) | 0.88458 (17) | 0.2224 (4) | 0.0543 (17) | |
C6 | 0.8127 (8) | 0.86362 (17) | 0.3321 (4) | 0.0524 (17) | |
C7 | 0.7290 (7) | 0.84980 (16) | 0.5355 (3) | 0.0430 (12) | |
C8 | 0.9178 (7) | 0.88243 (15) | 0.6157 (3) | 0.0438 (12) | |
C9 | 0.8885 (9) | 0.93963 (17) | 0.5908 (4) | 0.0587 (17) | |
C10 | 1.0629 (10) | 0.97210 (19) | 0.6748 (5) | 0.0746 (19) | |
C11 | 1.0499 (12) | 0.96105 (19) | 0.7997 (5) | 0.078 (2) | |
C12 | 1.0831 (9) | 0.90406 (18) | 0.8256 (4) | 0.0625 (18) | |
C13 | 0.9062 (8) | 0.87267 (16) | 0.7432 (3) | 0.0509 (14) | |
C14 | 0.8064 (7) | 0.79359 (15) | 0.5410 (4) | 0.0458 (12) | |
C15 | 0.7138 (10) | 0.70360 (19) | 0.5658 (5) | 0.077 (2) | |
C16 | 0.4212 (9) | 0.7576 (2) | 0.4450 (5) | 0.077 (2) | |
C17 | 0.6411 (10) | 0.9296 (2) | 0.0016 (4) | 0.074 (2) | |
H1 | 0.35503 | 0.90279 | 0.42930 | 0.0650* | |
H2 | 0.26802 | 0.93914 | 0.24605 | 0.0704* | |
H3 | 0.86077 | 0.87922 | 0.16910 | 0.0651* | |
H4 | 0.95257 | 0.84412 | 0.35301 | 0.0632* | |
H5 | 0.59009 | 0.85138 | 0.56748 | 0.0525* | |
H6 | 0.91105 | 0.94607 | 0.51387 | 0.0707* | |
H7 | 0.73381 | 0.94937 | 0.59778 | 0.0707* | |
H8 | 1.21703 | 0.96500 | 0.66231 | 0.0895* | |
H9 | 1.02784 | 1.00730 | 0.65941 | 0.0895* | |
H10 | 1.17141 | 0.97945 | 0.84836 | 0.0939* | |
H11 | 0.90194 | 0.97174 | 0.81492 | 0.0939* | |
H12 | 1.23688 | 0.89420 | 0.81729 | 0.0744* | |
H13 | 1.06323 | 0.89771 | 0.90296 | 0.0744* | |
H14 | 0.75313 | 0.88097 | 0.75543 | 0.0608* | |
H15 | 0.93669 | 0.83739 | 0.75969 | 0.0608* | |
H16 | 0.92585 | 0.78920 | 0.60774 | 0.0547* | |
H17 | 0.86819 | 0.78619 | 0.47328 | 0.0547* | |
H18 | 0.59481 | 0.68050 | 0.57907 | 0.0933* | |
H19 | 0.77182 | 0.69318 | 0.49881 | 0.0933* | |
H20 | 0.83837 | 0.70354 | 0.63117 | 0.0933* | |
H21 | 0.35386 | 0.79094 | 0.43811 | 0.0913* | |
H22 | 0.48217 | 0.74988 | 0.37721 | 0.0913* | |
H23 | 0.30425 | 0.73315 | 0.45389 | 0.0913* | |
H24 | 0.65662 | 0.89413 | −0.01422 | 0.0890* | |
H25 | 0.57583 | 0.94697 | −0.06811 | 0.0890* | |
H26 | 0.79113 | 0.94352 | 0.03239 | 0.0890* | |
H27 | 1.226 (9) | 0.848 (2) | 0.649 (4) | 0.070 (13)* | |
H28 | 0.565 (10) | 0.763 (2) | 0.617 (5) | 0.101 (13)* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
Cl1 | 0.0613 (7) | 0.0738 (8) | 0.0592 (6) | 0.0130 (6) | 0.0269 (5) | 0.0163 (7) |
O1 | 0.071 (2) | 0.082 (2) | 0.0544 (19) | 0.0120 (18) | 0.0158 (16) | 0.0130 (19) |
O2 | 0.0431 (17) | 0.063 (2) | 0.0573 (19) | −0.0043 (16) | 0.0239 (15) | 0.0022 (15) |
N1 | 0.057 (2) | 0.042 (2) | 0.058 (2) | −0.0084 (17) | 0.0253 (19) | −0.0041 (17) |
C1 | 0.044 (2) | 0.045 (2) | 0.049 (2) | 0.004 (2) | 0.0157 (19) | −0.0002 (19) |
C2 | 0.052 (3) | 0.054 (3) | 0.061 (3) | 0.012 (2) | 0.021 (2) | 0.010 (2) |
C3 | 0.049 (3) | 0.062 (3) | 0.063 (3) | 0.017 (2) | 0.013 (2) | 0.011 (2) |
C4 | 0.057 (3) | 0.053 (3) | 0.047 (2) | 0.002 (2) | 0.012 (2) | 0.004 (2) |
C5 | 0.060 (3) | 0.058 (3) | 0.049 (3) | 0.003 (2) | 0.021 (2) | −0.005 (2) |
C6 | 0.050 (3) | 0.055 (3) | 0.056 (3) | 0.015 (2) | 0.020 (2) | 0.002 (2) |
C7 | 0.040 (2) | 0.044 (2) | 0.049 (2) | 0.0025 (18) | 0.0186 (18) | 0.0053 (18) |
C8 | 0.050 (2) | 0.039 (2) | 0.046 (2) | 0.0025 (17) | 0.0181 (19) | 0.0027 (18) |
C9 | 0.076 (3) | 0.048 (3) | 0.055 (3) | −0.003 (2) | 0.020 (2) | 0.006 (2) |
C10 | 0.112 (4) | 0.044 (3) | 0.070 (3) | −0.014 (3) | 0.023 (3) | 0.001 (3) |
C11 | 0.116 (5) | 0.052 (3) | 0.067 (3) | −0.007 (3) | 0.017 (3) | −0.009 (3) |
C12 | 0.084 (4) | 0.058 (3) | 0.047 (2) | 0.005 (2) | 0.016 (2) | −0.001 (3) |
C13 | 0.064 (3) | 0.047 (2) | 0.047 (2) | 0.007 (2) | 0.024 (2) | 0.008 (2) |
C14 | 0.049 (2) | 0.038 (2) | 0.052 (2) | −0.0002 (19) | 0.0139 (19) | 0.0014 (18) |
C15 | 0.087 (4) | 0.046 (3) | 0.109 (4) | −0.002 (3) | 0.043 (3) | 0.001 (3) |
C16 | 0.056 (3) | 0.088 (4) | 0.086 (4) | −0.016 (3) | 0.014 (3) | −0.026 (3) |
C17 | 0.092 (4) | 0.085 (4) | 0.047 (3) | 0.000 (3) | 0.016 (3) | 0.006 (3) |
Geometric parameters (Å, º) top
O1—C4 | 1.363 (6) | C5—H3 | 0.95 |
O1—C17 | 1.426 (7) | C6—H4 | 0.95 |
O2—C8 | 1.442 (5) | C7—H5 | 0.95 |
O2—H27 | 0.91 (5) | C9—H6 | 0.95 |
N1—C15 | 1.486 (6) | C9—H7 | 0.95 |
N1—C16 | 1.487 (7) | C10—H8 | 0.95 |
N1—C14 | 1.495 (6) | C10—H9 | 0.95 |
N1—H28 | 0.92 (6) | C11—H10 | 0.95 |
C1—C7 | 1.517 (5) | C11—H11 | 0.95 |
C1—C6 | 1.390 (6) | C12—H12 | 0.95 |
C1—C2 | 1.395 (6) | C12—H13 | 0.95 |
C2—C3 | 1.378 (7) | C13—H14 | 0.95 |
C3—C4 | 1.391 (7) | C13—H15 | 0.95 |
C4—C5 | 1.369 (7) | C14—H16 | 0.95 |
C5—C6 | 1.379 (7) | C14—H17 | 0.95 |
C7—C8 | 1.557 (6) | C15—H18 | 0.95 |
C7—C14 | 1.531 (6) | C15—H19 | 0.95 |
C8—C13 | 1.530 (5) | C15—H20 | 0.95 |
C8—C9 | 1.523 (6) | C16—H21 | 0.95 |
C9—C10 | 1.529 (7) | C16—H22 | 0.95 |
C10—C11 | 1.508 (8) | C16—H23 | 0.95 |
C11—C12 | 1.522 (7) | C17—H24 | 0.95 |
C12—C13 | 1.512 (7) | C17—H25 | 0.95 |
C2—H1 | 0.95 | C17—H26 | 0.95 |
C3—H2 | 0.95 | | |
| | | |
Cl1···O2i | 3.213 (5) | H6···C2 | 3.0585 |
Cl1···N1 | 3.040 (5) | H6···C6 | 3.0058 |
Cl1···C16ii | 3.571 (7) | H6···C10viii | 3.0969 |
Cl1···H15i | 3.0489 | H6···H9viii | 2.4489 |
Cl1···H27i | 2.33 (5) | H7···C1 | 2.9612 |
Cl1···H28 | 2.13 (6) | H7···C2 | 3.0694 |
Cl1···H16i | 2.9232 | H7···H14 | 2.5556 |
Cl1···H17iii | 3.0457 | H8···O2 | 2.6469 |
Cl1···H19iii | 3.1281 | H8···H12 | 2.5775 |
Cl1···H22iii | 3.0347 | H9···H6viii | 2.4489 |
Cl1···H23ii | 3.0321 | H10···H25v | 2.5136 |
O2···Cl1iv | 3.213 (5) | H10···C17viii | 3.0310 |
O2···C6 | 3.305 (7) | H10···H26viii | 2.4336 |
O2···H1iv | 2.6100 | H11···C17xii | 3.0843 |
O2···H4 | 2.9021 | H11···H14 | 2.5706 |
O2···H5iv | 2.6842 | H11···H2x | 2.5728 |
O2···H8 | 2.6469 | H12···O2 | 2.6655 |
O2···H12 | 2.6655 | H12···C17v | 3.0211 |
O2···H16 | 2.4573 | H12···H8 | 2.5775 |
O2···H17 | 2.8912 | H12···H25v | 2.5645 |
N1···Cl1 | 3.040 (5) | H12···H27 | 2.3022 |
C1···C16 | 3.324 (7) | H13···C17xii | 3.0115 |
C2···C9 | 3.354 (8) | H14···H5 | 2.3596 |
C6···C9 | 3.581 (7) | H14···H7 | 2.5556 |
C6···O2 | 3.305 (7) | H14···H11 | 2.5706 |
C9···C6 | 3.581 (7) | H15···Cl1iv | 3.0489 |
C9···C2 | 3.354 (8) | H15···C14 | 2.7795 |
C12···C17v | 3.561 (8) | H15···H16 | 2.1711 |
C16···C1 | 3.324 (7) | H15···H27 | 2.3200 |
C16···Cl1vi | 3.571 (7) | H16···Cl1iv | 2.9232 |
C17···C12vii | 3.561 (8) | H16···O2 | 2.4573 |
C1···H7 | 2.9612 | H16···C13 | 2.7089 |
C1···H6 | 2.5806 | H16···H15 | 2.1711 |
C1···H21 | 2.8102 | H16···H20 | 2.3180 |
C2···H21 | 2.9862 | H16···H27 | 2.3019 |
C2···H7 | 3.0694 | H17···O2 | 2.8912 |
C2···H6 | 3.0585 | H17···C6 | 2.5923 |
C5···H26 | 2.7418 | H17···H4 | 2.1829 |
C5···H24 | 2.7376 | H17···H19 | 2.5190 |
C6···H6 | 3.0058 | H17···H22 | 2.4969 |
C6···H17 | 2.5923 | H17···Cl1xi | 3.0457 |
C7···H21 | 2.7321 | H18···H23 | 2.4404 |
C10···H6viii | 3.0969 | H18···H3iii | 2.4314 |
C12···H27 | 2.78 (5) | H19···H17 | 2.5190 |
C13···H16 | 2.7089 | H19···H22 | 2.4792 |
C14···H15 | 2.7795 | H19···Cl1xi | 3.1281 |
C14···H27 | 2.90 (5) | H20···H16 | 2.3180 |
C14···H4 | 2.8292 | H21···C1 | 2.8102 |
C16···H5 | 2.9114 | H21···C2 | 2.9862 |
C17···H3 | 2.5044 | H21···C7 | 2.7321 |
C17···H11ix | 3.0843 | H21···H5 | 2.4261 |
C17···H12vii | 3.0211 | H22···H17 | 2.4969 |
C17···H13ix | 3.0115 | H22···H19 | 2.4792 |
C17···H10viii | 3.0310 | H22···Cl1xi | 3.0347 |
H1···O2i | 2.6100 | H23···H18 | 2.4404 |
H1···H5 | 2.3358 | H23···Cl1vi | 3.0321 |
H2···H11x | 2.5728 | H24···C5 | 2.7376 |
H3···C17 | 2.5044 | H24···H3 | 2.2855 |
H3···H24 | 2.2855 | H25···H10vii | 2.5136 |
H3···H26 | 2.3024 | H25···H12vii | 2.5645 |
H3···H18xi | 2.4314 | H26···C5 | 2.7418 |
H4···O2 | 2.9021 | H26···H3 | 2.3024 |
H4···C14 | 2.8292 | H26···H10viii | 2.4336 |
H4···H17 | 2.1829 | H27···Cl1iv | 2.33 (5) |
H5···O2i | 2.6842 | H27···C12 | 2.78 (5) |
H5···C16 | 2.9114 | H27···C14 | 2.90 (5) |
H5···H1 | 2.3358 | H27···H5iv | 2.4751 |
H5···H14 | 2.3596 | H27···H12 | 2.3022 |
H5···H21 | 2.4261 | H27···H15 | 2.3200 |
H5···H27i | 2.4751 | H27···H16 | 2.3019 |
H5···H28 | 2.3874 | H28···Cl1 | 2.13 (6) |
H6···C1 | 2.5806 | H28···H5 | 2.3874 |
| | | |
C4—O1—C17 | 117.0 (4) | C10—C9—H6 | 108.79 |
C8—O2—H27 | 112 (3) | C10—C9—H7 | 108.55 |
C14—N1—C16 | 113.3 (4) | H6—C9—H7 | 109.47 |
C15—N1—C16 | 110.6 (4) | C9—C10—H8 | 108.72 |
C14—N1—C15 | 109.7 (4) | C9—C10—H9 | 108.67 |
C14—N1—H28 | 106 (3) | C11—C10—H8 | 109.31 |
C15—N1—H28 | 103 (3) | C11—C10—H9 | 108.75 |
C16—N1—H28 | 113 (4) | H8—C10—H9 | 109.46 |
C2—C1—C7 | 120.4 (4) | C10—C11—H10 | 108.73 |
C6—C1—C7 | 122.2 (4) | C10—C11—H11 | 109.65 |
C2—C1—C6 | 117.4 (4) | C12—C11—H10 | 108.74 |
C1—C2—C3 | 121.2 (4) | C12—C11—H11 | 109.52 |
C2—C3—C4 | 120.4 (4) | H10—C11—H11 | 109.49 |
O1—C4—C3 | 115.8 (4) | C11—C12—H12 | 109.27 |
C3—C4—C5 | 118.9 (4) | C11—C12—H13 | 109.11 |
O1—C4—C5 | 125.4 (4) | C13—C12—H12 | 109.02 |
C4—C5—C6 | 120.9 (4) | C13—C12—H13 | 109.11 |
C1—C6—C5 | 121.3 (4) | H12—C12—H13 | 109.48 |
C8—C7—C14 | 109.3 (3) | C8—C13—H14 | 108.76 |
C1—C7—C8 | 113.2 (3) | C8—C13—H15 | 108.64 |
C1—C7—C14 | 113.4 (3) | C12—C13—H14 | 108.78 |
O2—C8—C9 | 106.3 (3) | C12—C13—H15 | 108.41 |
O2—C8—C13 | 110.2 (3) | H14—C13—H15 | 109.49 |
C7—C8—C9 | 112.3 (3) | N1—C14—H16 | 108.19 |
C7—C8—C13 | 110.2 (3) | N1—C14—H17 | 108.28 |
O2—C8—C7 | 108.7 (3) | C7—C14—H16 | 108.24 |
C9—C8—C13 | 109.1 (3) | C7—C14—H17 | 108.22 |
C8—C9—C10 | 112.5 (4) | H16—C14—H17 | 109.47 |
C9—C10—C11 | 111.9 (5) | N1—C15—H18 | 109.45 |
C10—C11—C12 | 110.7 (4) | N1—C15—H19 | 109.60 |
C11—C12—C13 | 110.8 (4) | N1—C15—H20 | 109.36 |
C8—C13—C12 | 112.7 (4) | H18—C15—H19 | 109.49 |
N1—C14—C7 | 114.4 (3) | H18—C15—H20 | 109.45 |
C1—C2—H1 | 119.50 | H19—C15—H20 | 109.48 |
C3—C2—H1 | 119.33 | N1—C16—H21 | 109.15 |
C2—C3—H2 | 119.82 | N1—C16—H22 | 109.44 |
C4—C3—H2 | 119.82 | N1—C16—H23 | 109.79 |
C4—C5—H3 | 119.63 | H21—C16—H22 | 109.50 |
C6—C5—H3 | 119.50 | H21—C16—H23 | 109.44 |
C1—C6—H4 | 119.39 | H22—C16—H23 | 109.50 |
C5—C6—H4 | 119.30 | O1—C17—H24 | 109.31 |
C1—C7—H5 | 106.92 | O1—C17—H25 | 109.39 |
C8—C7—H5 | 106.88 | O1—C17—H26 | 109.64 |
C14—C7—H5 | 106.75 | H24—C17—H25 | 109.47 |
C8—C9—H6 | 108.96 | H24—C17—H26 | 109.43 |
C8—C9—H7 | 108.58 | H25—C17—H26 | 109.58 |
| | | |
C17—O1—C4—C3 | 179.7 (4) | C1—C7—C8—O2 | −80.2 (4) |
C17—O1—C4—C5 | −0.8 (7) | C1—C7—C8—C9 | 37.1 (5) |
C16—N1—C14—C7 | 62.0 (5) | C1—C7—C8—C13 | 158.9 (3) |
C15—N1—C14—C7 | −173.9 (4) | C14—C7—C8—O2 | 47.2 (4) |
C6—C1—C2—C3 | −2.0 (7) | C14—C7—C8—C9 | 164.5 (4) |
C7—C1—C2—C3 | 176.8 (4) | C14—C7—C8—C13 | −73.7 (4) |
C2—C1—C6—C5 | 1.5 (6) | C1—C7—C14—N1 | −95.1 (4) |
C7—C1—C6—C5 | −177.3 (4) | C8—C7—C14—N1 | 137.6 (4) |
C2—C1—C7—C8 | −101.8 (5) | O2—C8—C9—C10 | −65.2 (5) |
C2—C1—C7—C14 | 133.0 (4) | C7—C8—C9—C10 | 176.1 (4) |
C6—C1—C7—C8 | 77.0 (5) | C13—C8—C9—C10 | 53.7 (5) |
C6—C1—C7—C14 | −48.3 (5) | O2—C8—C13—C12 | 61.0 (4) |
C1—C2—C3—C4 | 1.0 (7) | C7—C8—C13—C12 | −179.0 (4) |
C2—C3—C4—O1 | −179.9 (4) | C9—C8—C13—C12 | −55.4 (5) |
C2—C3—C4—C5 | 0.6 (7) | C8—C9—C10—C11 | −55.0 (6) |
O1—C4—C5—C6 | 179.4 (5) | C9—C10—C11—C12 | 54.8 (6) |
C3—C4—C5—C6 | −1.1 (7) | C10—C11—C12—C13 | −55.8 (6) |
C4—C5—C6—C1 | 0.0 (7) | C11—C12—C13—C8 | 57.1 (5) |
Symmetry codes: (i) x−1, y, z; (ii) x+1/2, −y+3/2, z+1/2; (iii) x−1/2, −y+3/2, z+1/2; (iv) x+1, y, z; (v) x+1, y, z+1; (vi) x−1/2, −y+3/2, z−1/2; (vii) x−1, y, z−1; (viii) −x+2, −y+2, −z+1; (ix) x, y, z−1; (x) −x+1, −y+2, −z+1; (xi) x+1/2, −y+3/2, z−1/2; (xii) x, y, z+1. |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H27···Cl1iv | 0.91 (5) | 2.33 (5) | 3.213 (5) | 164 (4) |
N1—H28···Cl1 | 0.92 (6) | 2.13 (6) | 3.040 (5) | 169 (5) |
Symmetry code: (iv) x+1, y, z. |
Experimental details
Crystal data |
Chemical formula | C17H28NO2+·Cl− |
Mr | 313.87 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 298 |
a, b, c (Å) | 5.797 (6), 26.074 (7), 11.722 (3) |
β (°) | 100.72 (5) |
V (Å3) | 1741 (2) |
Z | 4 |
Radiation type | Cu Kα |
µ (mm−1) | 1.97 |
Crystal size (mm) | 0.40 × 0.10 × 0.10 |
|
Data collection |
Diffractometer | Rigaku AFC7S diffractometer |
Absorption correction | ψ scan (North, Phillips & Mathews, 1968) |
Tmin, Tmax | 0.843, 0.996 |
No. of measured, independent and observed [I > 1.30s(I)] reflections | 3564, 3304, 3304 |
Rint | 0.078 |
(sin θ/λ)max (Å−1) | 0.610 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.068, 0.068, 1.29 |
No. of reflections | 1816 |
No. of parameters | 199 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.40, −0.33 |
Selected geometric parameters (Å, º) topO1—C4 | 1.363 (6) | N1—C15 | 1.486 (6) |
O1—C17 | 1.426 (7) | N1—C16 | 1.487 (7) |
O2—C8 | 1.442 (5) | N1—C14 | 1.495 (6) |
| | | |
C4—O1—C17 | 117.0 (4) | O1—C4—C5 | 125.4 (4) |
C14—N1—C16 | 113.3 (4) | O2—C8—C9 | 106.3 (3) |
C15—N1—C16 | 110.6 (4) | O2—C8—C13 | 110.2 (3) |
C14—N1—C15 | 109.7 (4) | O2—C8—C7 | 108.7 (3) |
O1—C4—C3 | 115.8 (4) | N1—C14—C7 | 114.4 (3) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O2—H27···Cl1i | 0.91 (5) | 2.33 (5) | 3.213 (5) | 164 (4) |
N1—H28···Cl1 | 0.92 (6) | 2.13 (6) | 3.040 (5) | 169 (5) |
Symmetry code: (i) x+1, y, z. |
Comparision of some torsion angles (°) in Form-I and Form-II topangle | Form-I | Form-II |
| | |
C16-N1-C14-C7 | 58.8 (5) | 62.0 (5) |
C15-N1-C14-C7 | -177.0 (4) | -173.9 (4) |
C2-C1-C7-C8 | -107.3 (4) | -101.8 (5) |
C2-C1-C7-C14 | 129.1 (4) | 133.0 (4) |
C6-C1-C7-C8 | 71.7 (5) | 77.0 (5) |
C6-C1-C7-C14 | -51.9 (5) | -48.3 (5) |
C1-C7-C14-N1 | -88.9 (4) | -95.1 (4) |
C8-C7-C14-N1 | 144.7 (3) | 137.6 (4) |
Venlafaxine hydrochloride, [(±)-N,N-dimethyl-2-(1-hydroxycyclohex-1-yl)-2-(4-methoxyphenyl) ethylamine hydrochloride, C17H28ClNO2] is used as an antidepressant and an anxiolytic. Recrystallization of the compound for purification yielded crystals of two different morphologies, viz. blocks (form I) and needles (form II), as observed under the microscope. They were separated manually and characterized by different solid-state techniques such as differential scanning calorimetry, infrared spectroscopy, powder X-ray diffraction and single-crystal X-ray diffraction. These polymorphic forms were patented along with their characteristic physicochemical data (Mahender Rao et al., 1999; Mahender Rao et al., 2002). Recently, the crystal structure of form I has been reported in the orthorhombic space group Pca21 by Vega et al. (2000). In this paper we report the structure of form II and compare it with that of form I.
Form II of venlafaxine hydrochloride is found to crystallize in the monoclinic space group P21/n. The structure of the molecule in the monoclinic form is shown in Fig. 1. A l l the bond lengths show normal values (Allen et al., 1987) and match well with the corresponding values observed for the orthorhombic polymorph (Vega et al., 2000). In both polymorphs, the cyclohexane ring adopts a chair conformation. An intermolecular hydrogen bond links the nitrogen atom of the dimethylammonium group of the venlafaxine cation to the chloride anion. The chloride ion is also involved in another hydrogen bond, with the oxygen atom of the hydroxyl group of the cation translated one unit along the a axis. These hydrogen bonds (Table 2), which stabilize the crystal lattice (Fig. 2), lead to chains of molecules along the short a (= 5.797 Å) axis. An identical hydrogen-bonding scheme constitutes the molecular chain in the orthorhombic polymorph, along the short b (=5.881 Å) axis (Vega et al., 2000). Hence the two polymorphic modifications have the same lattice stabilization mechanism. However, careful comparison of the torsion angles (Table 3) reveals that the molecules differ by 3 to 6° in the rotations about the bonds N1—C14, C1—C7 and C7—C14. Hence these two forms of venlafaxine hydrochloride are conformational polymorphs (Bilton et al., 1999).