N-{(2RS)-2-Hydr­oxy-3-[2-(3-phenyl­propano­yl)phen­oxy]prop­yl}propanaminium chloride

The title compound, propafenone hydro­chloride, C₂₁H₂₈NO₃⁺·Cl^-, is a potent anti­arrhythmic drug, which acts by blocking channels for sodium transport across cell borders. The crystal packing is essentially controlled by a system of hydrogen bonds involving the quaternary N atom, the (disordered) hydr­oxy group and the chloride ion.

Key indicators

• Single-crystal X-ray study
• T = 170 K
• Mean [sigma](C-C) = 0.005 Å
• Disorder in main residue
• R factor = 0.048
• wR factor = 0.123
• Data-to-parameter ratio = 10.8

checkCIF/PLATON results

No syntax errors found



Alert level A
PLAT027_ALERT_3_A _diffrn_reflns_theta_full (too) Low ............      58.04 Deg.

Author Response: 'see _publ_section_exptl_refinement'

Alert level B
THETM01_ALERT_3_B  The value of sine(theta_max)/wavelength is less than 0.575
            Calculated sin(theta_max)/wavelength =    0.5503
PLAT023_ALERT_3_B Resolution (too) Low [sin(th)/Lambda < 0.6].....      58.04 Deg.

Alert level C
PLAT029_ALERT_3_C _diffrn_measured_fraction_theta_full Low .......       0.97
PLAT062_ALERT_4_C Rescale T(min) & T(max) by .....................       0.74
PLAT063_ALERT_3_C Crystal Probably too Large for Beam Size .......       0.80 mm
PLAT125_ALERT_4_C No _symmetry_space_group_name_Hall Given .......          ?
PLAT128_ALERT_4_C Non-standard setting of Space group P21/c   ....    P21/a
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for        C11
PLAT301_ALERT_3_C Main Residue  Disorder .........................       4.00 Perc.
PLAT340_ALERT_3_C Low Bond Precision on C-C bonds (x 1000) Ang ...          5
PLAT415_ALERT_2_C Short Inter D-H..H-X       H91    ..  H32O    ..       2.10 Ang.
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          1
              C21 H28 N O3
PLAT790_ALERT_4_C Centre of Gravity not Within Unit Cell: Resd.  #          2
              Cl

Alert level G
ABSTM02_ALERT_3_G  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      0.735
            Tmax scaled      0.687 Tmin scaled      0.491

   1 ALERT level A = In general: serious problem
   2 ALERT level B = Potentially serious problem
  11 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   8 ALERT type 3 Indicator that the structure quality may be low
   5 ALERT type 4 Improvement, methodology, query or suggestion

---

Computing details

Data collection: CrysAlis CCD (Oxford Diffraction, 2006); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2006); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

N-{(2RS)-2-Hydroxy-3-[2-(3-phenylpropanoyl)phenoxy]propyl}propanaminium chloride

Crystal data

C21H28NO3^+·Cl^−	F(000) = 808
Mr = 377.89	Dx = 1.275 Mg m^−3
Monoclinic, P21/a	Cu Kα radiation, λ = 1.54180 Å
a = 7.709 (1) Å	Cell parameters from 6206 reflections
b = 15.959 (2) Å	θ = 6.3–36.4°
c = 16.007 (2) Å	µ = 1.88 mm^−1
β = 90.49 (1)°	T = 170 K
V = 1969.2 (4) Å^3	Elongated prism, colorless
Z = 4	0.80 × 0.40 × 0.20 mm

Data collection

Oxford Diffraction Excalibur PX Ultra CCD diffractometer	2676 independent reflections
Radiation source: fine-focus sealed tube	1528 reflections with I > 2σ(I)
Oxford Diffraction, Enhance ULTRA assembly monochromator	Rint = 0.043
ω scans	θmax = 58.0°, θmin = 5.5°
Absorption correction: multi-scan (ABSPACK; Oxford Diffraction, 2006)	h = −8→7
Tmin = 0.668, Tmax = 0.935	k = −17→17
15256 measured reflections	l = −17→17

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.048	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.123	H-atom parameters constrained
S = 0.92	w = 1/[σ^2(Fo^2) + (0.0706P)^2] where P = (Fo^2 + 2Fc^2)/3
2676 reflections	(Δ/σ)max < 0.001
247 parameters	Δρmax = 0.24 e Å^−3
2 restraints	Δρmin = −0.23 e Å^−3

Special details

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq	Occ. (<1)
Cl	0.14472 (12)	−0.14653 (5)	0.15687 (6)	0.0526 (3)
C1	−0.1743 (5)	0.0774 (2)	0.4875 (2)	0.0456 (9)
O1	−0.1069 (4)	0.13979 (14)	0.51885 (14)	0.0670 (8)
C2	−0.1807 (4)	0.06884 (18)	0.39419 (18)	0.0412 (9)
H21	−0.2987	0.0510	0.3769	0.049*
H22	−0.0985	0.0246	0.3770	0.049*
C3	−0.1356 (5)	0.14993 (19)	0.34933 (19)	0.0496 (10)
H31	−0.2103	0.1953	0.3710	0.060*
H32	−0.0138	0.1647	0.3628	0.060*
C4	−0.2479 (4)	0.01229 (18)	0.5442 (2)	0.0393 (9)
C5	−0.2999 (4)	−0.0686 (2)	0.5205 (2)	0.0446 (10)
C6	−0.3649 (5)	−0.1243 (2)	0.5791 (2)	0.0565 (11)
H61	−0.3998	−0.1789	0.5625	0.068*
C7	−0.3788 (5)	−0.1002 (2)	0.6615 (2)	0.0583 (11)
H71	−0.4233	−0.1385	0.7014	0.070*
C8	−0.3285 (5)	−0.0209 (2)	0.6868 (2)	0.0538 (10)
H81	−0.3374	−0.0045	0.7436	0.065*
C9	−0.2656 (4)	0.0335 (2)	0.6283 (2)	0.0480 (10)
H91	−0.2326	0.0882	0.6457	0.058*
O2	−0.2794 (3)	−0.09010 (12)	0.43818 (14)	0.0510 (7)
C10	−0.3088 (6)	−0.17571 (19)	0.4150 (2)	0.0732 (14)
H101	−0.4347	−0.1880	0.4153	0.088*
H102	−0.2507	−0.2135	0.4555	0.088*
C11	−0.2375 (8)	−0.1900 (2)	0.3290 (3)	0.0764 (15)
H11A	−0.2690	−0.2492	0.3153	0.092*	0.534 (6)
H11B	−0.1248	−0.1593	0.3339	0.092*	0.466 (6)
O31	−0.0742 (7)	−0.1908 (3)	0.3376 (3)	0.065 (2)	0.534 (6)
H31O	−0.0290	−0.2098	0.2940	0.098*	0.534 (6)
O32	−0.1796 (7)	−0.2672 (2)	0.3041 (3)	0.055 (2)	0.466 (6)
H32O	−0.2645	−0.2970	0.2898	0.083*	0.466 (6)
C12	−0.3268 (5)	−0.1384 (2)	0.2625 (2)	0.0485 (10)
H121	−0.4536	−0.1479	0.2651	0.058*
H122	−0.3049	−0.0782	0.2732	0.058*
N	−0.2636 (4)	−0.16059 (15)	0.17814 (17)	0.0468 (8)
H1N	−0.2856	−0.2164	0.1684	0.056*
H2N	−0.1454	−0.1530	0.1767	0.056*
C13	−0.3467 (5)	−0.10944 (19)	0.1097 (2)	0.0467 (10)
H131	−0.3176	−0.0495	0.1177	0.056*
H132	−0.4744	−0.1154	0.1123	0.056*
C14	−0.2838 (5)	−0.1382 (2)	0.0255 (2)	0.0547 (10)
H141	−0.3262	−0.1958	0.0148	0.066*
H142	−0.1554	−0.1398	0.0261	0.066*
C15	−0.3460 (5)	−0.0807 (2)	−0.0449 (2)	0.0627 (11)
H151	−0.4729	−0.0774	−0.0444	0.094*
H152	−0.3079	−0.1031	−0.0986	0.094*
H153	−0.2970	−0.0245	−0.0367	0.094*
C16	−0.1568 (5)	0.14588 (19)	0.2558 (2)	0.0433 (9)
C17	−0.0728 (5)	0.0860 (2)	0.2080 (2)	0.0490 (10)
H171	−0.0014	0.0453	0.2347	0.059*
C18	−0.0915 (5)	0.0847 (2)	0.1218 (2)	0.0533 (10)
H181	−0.0312	0.0438	0.0901	0.064*
C19	−0.1969 (5)	0.1422 (2)	0.0814 (2)	0.0568 (11)
H191	−0.2098	0.1411	0.0224	0.068*
C20	−0.2824 (5)	0.2008 (2)	0.1282 (3)	0.0597 (11)
H201	−0.3554	0.2406	0.1012	0.072*
C21	−0.2639 (5)	0.2027 (2)	0.2145 (2)	0.0529 (10)
H211	−0.3254	0.2434	0.2458	0.064*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Cl	0.0551 (7)	0.0381 (5)	0.0646 (7)	0.0011 (5)	0.0033 (5)	0.0073 (4)
C1	0.049 (3)	0.035 (2)	0.053 (2)	0.0028 (19)	0.0035 (19)	−0.0068 (18)
O1	0.092 (2)	0.0538 (15)	0.0546 (17)	−0.0246 (16)	−0.0015 (15)	−0.0109 (13)
C2	0.047 (2)	0.0339 (18)	0.043 (2)	0.0020 (17)	0.0040 (18)	−0.0042 (16)
C3	0.062 (3)	0.0352 (19)	0.051 (2)	−0.0101 (19)	0.001 (2)	0.0007 (18)
C4	0.041 (2)	0.0343 (19)	0.042 (2)	0.0058 (17)	−0.0035 (18)	−0.0047 (17)
C5	0.050 (3)	0.039 (2)	0.045 (2)	0.0101 (18)	−0.0088 (19)	−0.0025 (19)
C6	0.070 (3)	0.041 (2)	0.059 (3)	−0.002 (2)	−0.004 (2)	0.009 (2)
C7	0.053 (3)	0.061 (3)	0.061 (3)	0.007 (2)	0.002 (2)	0.020 (2)
C8	0.055 (3)	0.060 (3)	0.047 (2)	0.016 (2)	0.005 (2)	0.001 (2)
C9	0.048 (3)	0.042 (2)	0.054 (3)	0.0088 (19)	−0.003 (2)	−0.005 (2)
O2	0.0755 (19)	0.0280 (12)	0.0493 (16)	0.0036 (12)	−0.0041 (13)	−0.0035 (11)
C10	0.132 (4)	0.026 (2)	0.061 (3)	−0.004 (2)	−0.028 (3)	−0.0021 (19)
C11	0.138 (5)	0.034 (2)	0.057 (3)	0.025 (3)	−0.027 (3)	−0.018 (2)
O31	0.061 (4)	0.084 (4)	0.052 (3)	0.026 (3)	0.004 (3)	−0.022 (3)
O32	0.075 (5)	0.028 (3)	0.062 (4)	0.004 (3)	−0.010 (3)	−0.003 (2)
C12	0.053 (3)	0.043 (2)	0.049 (2)	0.0002 (19)	−0.001 (2)	0.0015 (18)
N	0.046 (2)	0.0335 (16)	0.061 (2)	0.0044 (14)	−0.0010 (16)	−0.0080 (14)
C13	0.049 (2)	0.0329 (18)	0.058 (2)	0.0019 (18)	−0.002 (2)	−0.0004 (18)
C14	0.061 (3)	0.051 (2)	0.053 (2)	0.002 (2)	0.003 (2)	−0.0092 (19)
C15	0.061 (3)	0.064 (2)	0.063 (3)	0.002 (2)	−0.002 (2)	−0.004 (2)
C16	0.050 (2)	0.0324 (19)	0.048 (2)	−0.0061 (19)	0.0037 (19)	0.0006 (19)
C17	0.050 (3)	0.044 (2)	0.052 (2)	−0.004 (2)	−0.005 (2)	0.0067 (19)
C18	0.051 (3)	0.050 (2)	0.059 (3)	−0.009 (2)	0.007 (2)	−0.005 (2)
C19	0.062 (3)	0.061 (3)	0.047 (2)	−0.018 (2)	−0.001 (2)	0.005 (2)
C20	0.060 (3)	0.052 (2)	0.067 (3)	−0.008 (2)	−0.005 (2)	0.018 (2)
C21	0.056 (3)	0.037 (2)	0.065 (3)	−0.008 (2)	0.008 (2)	0.0051 (19)

Geometric parameters (Å, º)

C1—O1	1.228 (3)	O31—H31O	0.8400
C1—C4	1.495 (4)	O32—H32O	0.8400
C1—C2	1.500 (4)	C12—N	1.483 (4)
C2—C3	1.522 (4)	C12—H121	0.9900
C2—H21	0.9900	C12—H122	0.9900
C2—H22	0.9900	N—C13	1.505 (4)
C3—C16	1.505 (4)	N—H1N	0.9200
C3—H31	0.9900	N—H2N	0.9200
C3—H32	0.9900	C13—C14	1.508 (4)
C4—C9	1.396 (4)	C13—H131	0.9900
C4—C5	1.404 (4)	C13—H132	0.9900
C5—O2	1.372 (4)	C14—C15	1.527 (4)
C5—C6	1.388 (5)	C14—H141	0.9900
C6—C7	1.379 (5)	C14—H142	0.9900
C6—H61	0.9500	C15—H151	0.9800
C7—C8	1.383 (5)	C15—H152	0.9800
C7—H71	0.9500	C15—H153	0.9800
C8—C9	1.368 (4)	C16—C17	1.389 (4)
C8—H81	0.9500	C16—C21	1.390 (4)
C9—H91	0.9500	C17—C18	1.385 (4)
O2—C10	1.433 (3)	C17—H171	0.9500
C10—C11	1.504 (5)	C18—C19	1.383 (4)
C10—H101	0.9900	C18—H181	0.9500
C10—H102	0.9900	C19—C20	1.370 (5)
C11—O31	1.265 (5)	C19—H191	0.9500
C11—O32	1.371 (5)	C20—C21	1.388 (4)
C11—C12	1.507 (5)	C20—H201	0.9500
C11—H11A	1.0000	C21—H211	0.9500
C11—H11B	1.0000
O1—C1—C4	118.5 (3)	H11A—C11—H11B	133.6
O1—C1—C2	119.4 (3)	C11—O31—H31O	109.5
C4—C1—C2	122.1 (3)	C11—O32—H32O	109.5
C1—C2—C3	112.7 (3)	N—C12—C11	111.1 (3)
C1—C2—H21	109.0	N—C12—H121	109.4
C3—C2—H21	109.0	C11—C12—H121	109.4
C1—C2—H22	109.0	N—C12—H122	109.4
C3—C2—H22	109.0	C11—C12—H122	109.4
H21—C2—H22	107.8	H121—C12—H122	108.0
C16—C3—C2	114.2 (3)	C12—N—C13	113.1 (2)
C16—C3—H31	108.7	C12—N—H1N	109.0
C2—C3—H31	108.7	C13—N—H1N	109.0
C16—C3—H32	108.7	C12—N—H2N	109.0
C2—C3—H32	108.7	C13—N—H2N	109.0
H31—C3—H32	107.6	H1N—N—H2N	107.8
C9—C4—C5	117.0 (3)	N—C13—C14	110.3 (3)
C9—C4—C1	117.3 (3)	N—C13—H131	109.6
C5—C4—C1	125.8 (3)	C14—C13—H131	109.6
O2—C5—C6	122.3 (3)	N—C13—H132	109.6
O2—C5—C4	117.0 (3)	C14—C13—H132	109.6
C6—C5—C4	120.7 (3)	H131—C13—H132	108.1
C7—C6—C5	120.0 (3)	C13—C14—C15	112.0 (3)
C7—C6—H61	120.0	C13—C14—H141	109.2
C5—C6—H61	120.0	C15—C14—H141	109.2
C6—C7—C8	120.7 (4)	C13—C14—H142	109.2
C6—C7—H71	119.6	C15—C14—H142	109.2
C8—C7—H71	119.6	H141—C14—H142	107.9
C9—C8—C7	118.7 (3)	C14—C15—H151	109.5
C9—C8—H81	120.7	C14—C15—H152	109.5
C7—C8—H81	120.7	H151—C15—H152	109.5
C8—C9—C4	123.0 (3)	C14—C15—H153	109.5
C8—C9—H91	118.5	H151—C15—H153	109.5
C4—C9—H91	118.5	H152—C15—H153	109.5
C5—O2—C10	117.9 (3)	C17—C16—C21	117.7 (3)
O2—C10—C11	108.9 (3)	C17—C16—C3	122.1 (3)
O2—C10—H101	109.9	C21—C16—C3	120.3 (3)
C11—C10—H101	109.9	C18—C17—C16	121.0 (3)
O2—C10—H102	109.9	C18—C17—H171	119.5
C11—C10—H102	109.9	C16—C17—H171	119.5
H101—C10—H102	108.3	C19—C18—C17	120.7 (4)
O31—C11—C10	105.9 (4)	C19—C18—H181	119.6
O32—C11—C10	121.6 (4)	C17—C18—H181	119.6
O31—C11—C12	122.0 (5)	C20—C19—C18	118.8 (4)
O32—C11—C12	115.7 (4)	C20—C19—H191	120.6
C10—C11—C12	113.3 (4)	C18—C19—H191	120.6
O31—C11—H11A	104.7	C19—C20—C21	120.9 (4)
C10—C11—H11A	104.7	C19—C20—H201	119.6
C12—C11—H11A	104.7	C21—C20—H201	119.6
O32—C11—H11B	100.3	C20—C21—C16	121.0 (4)
C10—C11—H11B	100.3	C20—C21—H211	119.5
C12—C11—H11B	100.3	C16—C21—H211	119.5
O1—C1—C2—C3	−12.6 (5)	C5—O2—C10—C11	−166.0 (3)
C4—C1—C2—C3	167.2 (3)	O2—C10—C11—O31	73.3 (4)
C1—C2—C3—C16	−174.6 (3)	O2—C10—C11—O32	152.0 (5)
O1—C1—C4—C9	12.0 (5)	O2—C10—C11—C12	−62.9 (5)
C2—C1—C4—C9	−167.8 (3)	O31—C11—C12—N	57.2 (5)
O1—C1—C4—C5	−167.6 (3)	O32—C11—C12—N	−27.3 (6)
C2—C1—C4—C5	12.5 (5)	C10—C11—C12—N	−174.6 (3)
C9—C4—C5—O2	−178.8 (3)	C11—C12—N—C13	−178.9 (3)
C1—C4—C5—O2	0.8 (5)	C12—N—C13—C14	−177.1 (3)
C9—C4—C5—C6	−0.4 (5)	N—C13—C14—C15	−172.4 (3)
C1—C4—C5—C6	179.3 (3)	C2—C3—C16—C17	−56.0 (4)
O2—C5—C6—C7	178.3 (3)	C2—C3—C16—C21	123.5 (3)
C4—C5—C6—C7	0.0 (5)	C21—C16—C17—C18	1.8 (5)
C5—C6—C7—C8	0.0 (6)	C3—C16—C17—C18	−178.6 (3)
C6—C7—C8—C9	0.4 (5)	C16—C17—C18—C19	−1.1 (5)
C7—C8—C9—C4	−0.8 (5)	C17—C18—C19—C20	0.1 (5)
C5—C4—C9—C8	0.8 (5)	C18—C19—C20—C21	0.1 (5)
C1—C4—C9—C8	−178.9 (3)	C19—C20—C21—C16	0.7 (5)
C6—C5—O2—C10	−6.9 (5)	C17—C16—C21—C20	−1.6 (5)
C4—C5—O2—C10	171.5 (3)	C3—C16—C21—C20	178.8 (3)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O31—H31O···Cl	0.84	2.77	3.435 (5)	137
O32—H32O···Cl^i	0.84	2.41	3.038 (5)	132
N—H2N···Cl	0.92	2.26	3.177 (3)	172
N—H1N···Cl^i	0.92	2.26	3.176 (3)	174

Symmetry code: (i) x−1/2, −y−1/2, z.