research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 82| Part 6| June 2026| Pages 645-650
https://doi.org/10.1107/S2056989026004810

Midodrine hydro­chloride Form A, C12H19N2O4+·Cl−

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Jacob K. Salazar,a James A. Kaduk,b,c* Anja Dosend and Thomas N. Blantond

aNorth Central College, Department of Chemistry, 131 S. Loomis St., Naperville, IL 60540, USA, bNorth Central College, Department of Physics, 131 S. Loomis St., Naperville, IL 60540, USA, cIllinois Institute of Technology, Department of Chemistry, 3101 S. Dearborn St., Chicago, IL 60616, USA, and dICDD, 12 Campus Blvd., Newtown Square, PA 19073-3273, USA
*Correspondence e-mail: [email protected]

Edited by S.-L. Zheng, Harvard University, USA (Received 23 April 2026; accepted 8 May 2026; online 15 May 2026)

The crystal structure of midodrine hydro­chloride Form A (systematic name: {[2-(2,5-di­meth­oxy­phen­yl)-2-hy­droxy­eth­yl]carbamo­yl}methanaminium chloride, C12H19N2O4+·Cl−) has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional theory techniques. Midodrine hydro­chloride Form A crystallizes in space group P21/c (#14). The crystal structure is characterized by layers perpendicular to the c-axis direction. The Cl anions reside in the center of the layer. Hydrogen bonds are prominent in the structure. Each of the three H on the protonated N acts as a donor – one to the carbonyl group and the other two to the Cl ion. The hydroxyl group and the amide also act as donors to Cl. Considering the classical hydrogen bonds, the Cl ion is four-coordinate.

CCDC references: 2552708; 2552707

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1. Chemical context

Midodrine hydro­chloride (marketed as ProAmatine, among others) is used to treat hypotension (low blood pressure) and urinary incontinence. In particular, midodrine HCl treats symptomatic low blood pressure upon standing from a sitting or laying down position. The systematic name (CAS Registry Number 43218-56-0) is 2-amino-N-[2-(2,5-di­meth­oxy­phen­yl)-2-hy­droxy­eth­yl]acetamide hydro­chloride.

[Scheme 1]

A process for preparing midodrine hydro­chloride has been claimed in US Patent Application US 2022/0144754 A1 (Singh et al., 2022View full citation; Cadila Healthcare Ltd.), and powder diffraction data labeled as Form A are provided but no crystal structure was reported.

This work was carried out as part of a project (Kaduk et al., 2014View full citation) to determine the crystal structures of large-volume commercial pharmaceuticals, and includes high-quality powder diffraction data for them in the Powder Diffraction File (Kabekkodu et al., 2024View full citation).

2. Structural commentary

The synchrotron pattern of midodrine hydro­chloride is similar enough to that reported by Singh et al. (2022View full citation) for Form A (Fig. 1[link]) to conclude that they represent the same material. The patent pattern exhibits small displacement/transparency peak position error, as well as significant preferred orientation.

[Figure 1]
Figure 1
Comparison of the synchrotron pattern from this study of midodrine hydro­chloride (black) to that reported for Form A by Singh et al. (2022View full citation; green). The patent pattern (measured using Cu Kα radiation) was digitized using UN-SCAN-IT (Silk Scientific, 2013View full citation) and converted to the synchrotron wavelength of 0.4687342 Å using JADE Pro (MDI, 2026View full citation). Image generated using JADE Pro (MDI, 2026View full citation).

The root-mean-square deviation of the non-H atoms in the Rietveld-refined and VASP-optimized structures of midodrine hydro­chloride Form A, calculated using the Mercury CSD-Materials/Search/Crystal Packing Similarity tool (Macrae et al., 2020View full citation) is 0.050 Å (Fig. 2[link]); the structures are essentially identical. The root-mean-square Cartesian displacement of the non-H atoms in the refined and optimized structures of the cation, calculated using the Mercury Calculate/Mol­ecule Overlay tool, is 0.042 Å (Fig. 3[link]). The absolute position difference of the Cl is 0.033 Å. The agreements are within the normal range for correct structures (van de Streek & Neumann, 2014View full citation). The asymmetric unit is illustrated in Fig. 4[link]. The remaining discussion will emphasize the VASP-optimized structure.

[Figure 2]
Figure 2
Comparison of the Rietveld-refined (colored by atom type) and VASP-optimized (pale green) structures of midodrine hydro­chloride Form A, calculated using the Mercury CSD-Materials/Search/Crystal Packing Similarity tool. The root-mean-square Cartesian displacement is 0.050 Å. Image generated using Mercury (Macrae et al., 2020View full citation).
[Figure 3]
Figure 3
Comparison of the refined structure of the cation in midodrine hydro­chloride Form A (red) to the VASP-optimized structure (blue). The comparison was generated using the Mercury Calculate/Mol­ecule Overlay tool; the r.m.s. deviation is 0.042 Å. Image generated using Mercury (Macrae et al., 2020View full citation).
[Figure 4]
Figure 4
The asymmetric unit of midodrine hydro­chloride Form A, with the atom numbering. The atoms are represented by 50% probability spheroids/ellipsoids. Image generated using Mercury (Macrae et al., 2020View full citation).

All of the bond distances, bond angles, and torsion angles (Table 1[link]) fall within the normal ranges indicated by a Mercury Mogul Geometry check (Macrae et al., 2020View full citation). Quantum chemical geometry optimization of the isolated midodrine cation (DFT/B3LYP/6-31G*/water) using Spartan '24 (Wavefunction, 2025View full citation) indicated that the observed conformation is 4.4 kcal mol−1 higher in energy than a local minimum, which has an essentially identical conformation (r.m.s. deviation = 0.066 Å). The global minimum-energy conformation (MMFF force field) is 98.1 kcal mol−1 lower in energy, but is unreasonably folded on itself to form intra­molecular hydrogen bonds. Inter­molecular inter­actions are important in determining the solid-state conformation.

Table 1
Selected geometric parameters (Å, °) for midodrine[link]

O1—C7 1.437 (2) C15—O4 1.224 (2)
O1—H26 0.989 (2) C15—N5 1.329 (2)
O2—C10 1.3741 (17) C15—C16 1.5115 (19)
O2—C17 1.427 (3) C16—N6 1.467 (3)
O3—C12 1.3814 (19) C16—C15 1.5115 (19)
O3—C18 1.425 (3) C16—H27 1.085 (3)
O4—C15 1.224 (2) C16—H28 1.125 (3)
N5—C9 1.451 (2) C17—O2 1.427 (3)
N5—C15 1.329 (2) C17—H29 1.060 (3)
N5—H23 1.047 (2) C17—H30 1.115 (3)
N6—C16 1.467 (3) C17—H31 1.100 (3)
N6—H35 1.072 (3) C18—O3 1.425 (3)
N6—H36 1.070 (2) C18—H32 1.142 (3)
N6—H37 1.015 (3) C18—H33 1.067 (3)
C7—O1 1.437 (2) C18—H34 1.089 (3)
C7—C8 1.5181 (10) H19—C7 1.118 (3)
C7—C9 1.519 (3) H20—C9 1.116 (3)
C7—H19 1.118 (3) H21—C9 1.121 (3)
C8—C7 1.5181 (10) H22—C11 1.0811 (19)
C8—C10 1.3914 (18) H23—N5 1.047 (2)
C8—C11 1.4010 (18) H24—C13 1.119 (2)
C9—N5 1.451 (2) H25—C14 1.1036 (19)
C9—C7 1.519 (3) H26—O1 0.989 (2)
C9—H20 1.116 (3) H26—Cl38i 2.1733 (10)
C9—H21 1.121 (3) H27—C16 1.085 (3)
C10—O2 1.3741 (17) H28—C16 1.125 (3)
C10—C8 1.3914 (18) H29—C17 1.060 (3)
C10—C13 1.391 (2) H30—C17 1.115 (3)
C11—C8 1.4010 (18) H31—C17 1.100 (3)
C11—C12 1.3917 (18) H32—C18 1.142 (3)
C11—H22 1.0811 (19) H33—C18 1.067 (3)
C12—O3 1.3814 (19) H34—C18 1.089 (3)
C12—C11 1.3917 (18) H35—N6 1.072 (3)
C12—C14 1.383 (2) H35—Cl38ii 2.1656 (10)
C13—C10 1.391 (2) H36—N6 1.070 (2)
C13—C14 1.378 (2) H36—Cl38iii 2.0529 (10)
C13—H24 1.119 (2) H37—N6 1.015 (3)
C14—C12 1.383 (2) Cl38—H26i 2.1733 (10)
C14—C13 1.378 (2) Cl38—H35ii 2.1656 (10)
C14—H25 1.1036 (19) Cl38—H36iv 2.0529 (10)
       
C7—O1—H26 104.5 (2) C12—C11—H22 122.58 (19)
C10—O2—C17 118.16 (15) O3—C12—C11 123.4 (2)
C12—O3—C18 118.2 (2) O3—C12—C14 116.5 (2)
C9—N5—C15 123.69 (18) C11—C12—C14 120.08 (12)
C9—N5—H23 117.7 (2) C10—C13—C14 120.27 (14)
C15—N5—H23 117.5 (2) C10—C13—H24 120.83 (18)
C16—N6—H35 108.7 (2) C14—C13—H24 118.9 (2)
C16—N6—H36 109.0 (2) C12—C14—C13 120.11 (13)
H35—N6—H36 104.9 (2) C12—C14—H25 119.3 (2)
C16—N6—H37 111.8 (3) C13—C14—H25 120.6 (2)
H35—N6—H37 111.9 (2) O4—C15—N5 124.03 (18)
H36—N6—H37 110.3 (2) O4—C15—C16 120.44 (17)
O1—C7—C8 111.60 (16) N5—C15—C16 115.28 (18)
O1—C7—C9 107.8 (2) N6—C16—C15 110.65 (17)
C8—C7—C9 111.2 (2) N6—C16—H27 107.5 (3)
O1—C7—H19 113.5 (2) C15—C16—H27 113.1 (3)
C8—C7—H19 106.94 (18) N6—C16—H28 109.3 (3)
C9—C7—H19 105.68 (19) C15—C16—H28 109.6 (3)
C7—C8—C10 120.30 (12) H27—C16—H28 106.7 (2)
C7—C8—C11 120.84 (13) O2—C17—H29 112.0 (2)
C10—C8—C11 118.84 (11) O2—C17—H30 111.8 (3)
N5—C9—C7 112.7 (2) H29—C17—H30 111.3 (3)
N5—C9—H20 107.4 (2) O2—C17—H31 112.3 (3)
C7—C9—H20 109.9 (2) H29—C17—H31 106.1 (3)
N5—C9—H21 109.7 (2) H30—C17—H31 102.9 (2)
C7—C9—H21 110.8 (2) O3—C18—H32 109.9 (3)
H20—C9—H21 106.0 (2) O3—C18—H33 107.7 (3)
O2—C10—C8 115.41 (11) H32—C18—H33 108.8 (3)
O2—C10—C13 124.17 (13) O3—C18—H34 111.0 (3)
C8—C10—C13 120.42 (12) H32—C18—H34 106.7 (2)
C8—C11—C12 120.22 (13) H33—C18—H34 112.8 (3)
C8—C11—H22 117.19 (18)    
Symmetry codes: (i) Mathematical equation; (ii) Mathematical equation; (iii) Mathematical equation; (iv) Mathematical equation.

3. Supra­molecular features

The crystal structure (Fig. 5[link]) is characterized by layers perpendicular to the c-axis direction. The Cl anions reside in the center of the layer. The Mercury Aromatics Analyser indicates three moderate inter­actions (d = 5.18, 5.18, and 6.08 Å), which include both slipped stacking and end-face inter­actions. The mean plane of the aromatic rings is approximately (3,4,10).

[Figure 5]
Figure 5
Crystal structure of midodrine hydro­chloride Form A, viewed down the a-axis. Image generated using DIAMOND (Crystal Impact, 2025View full citation).

Analysis of the contributions to the total crystal energy of the structure using the Forcite module of Materials Studio (Dassault Systèmes, 2025View full citation) indicated that the intra­molecular energy is dominated by angle distortion terms. The inter­molecular energy is small and dominated by van der Waals repulsions, which in this force field based analysis include hydrogen bonds. The hydrogen bonds are better discussed using the results of the DFT calculation.

Hydrogen bonds (Table 2[link]) are prominent in the structure. Each of the three H on the protonated N6 acts as a donor – one to the carbonyl group O4 and the other two to Cl38. The energy of the N—H⋯O hydrogen bond was calculated using the correlation of Wheatley & Kaduk (2019View full citation). The hydroxyl group O1—H26 also acts as a donor to Cl38. The energy of the O—H⋯Cl bond was calculated using the correlation of Kaduk (2002View full citation). The amide N5—H23 also acts as a donor to Cl38. Considering the classical hydrogen bonds, the Cl is four-coordinate. These hydrogen bonds result in rings and chains, with graph sets (Etter, 1990View full citation; Bernstein et al., 1995View full citation; Motherwell et al., 2000View full citation) R22(10), C21(7), C21(10), R42(20), and larger features. The result is a complex network of hydrogen bonds in the center of the layers (Fig. 6[link]). C—H⋯Cl and C—H⋯O hydrogen bonds also contribute to the lattice energy.

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A D⋯A D—H⋯A Mulliken overlap H-bond energy
N6—H37⋯O4 1.043 1.807 2.781 153.7 0.063 5.8
N6—H36⋯Cl38 1.054 2.070 3.094 163.2 0.088  
N6—H35⋯Cl38 1.047 2.181 3.159 154.6 0.077  
O1—H26⋯Cl38 0.993 2.159 3.146 172.1 0.064 35.6
N5—H23⋯Cl38 1.025 2.545 3.465 149.0 0.036  
C16—H28⋯Cl38 1.099 2.485 3.422 142.4 0.032  
C11—H22⋯O1 1.090 2.443 2.825 98.9 0.017  
C13—H24⋯O3 1.089 2.656 3.592 143.7 0.012  
C17—H31⋯O3 1.100 2.642 3.637 150.3 0.010  
[Figure 6]
Figure 6
The hydrogen bonding pattern in the layers of midodrine hydro­chloride Form A. Image generated using Mercury (Macrae et al., 2020View full citation).

The volume enclosed by the Hirshfeld surface of midodrine hydro­chloride Form A (Fig. 7[link], Hirshfeld, 1977View full citation, Spackman et al., 2021View full citation) is 343.78 Å3, 97.74% of 1/4 of the unit-cell volume. The packing density is thus typical. The close contacts (red in Fig. 7[link]) involve the hydrogen bonds. The volume/non-hydrogen atom is normal, at 18.5 Å3.

[Figure 7]
Figure 7
The Hirshfeld surface of midodrine hydro­chloride Form A. Inter­molecular contacts longer than the sums of the van der Waals radii are colored blue, and contacts shorter than the sums of the radii are colored red. Contacts equal to the sums of radii are white. Image generated using CrystalExplorer (Spackman et al., 2021View full citation).

The Bravais–Friedel–Donnay–Harker (Bravais, 1866View full citation; Friedel, 1907View full citation; Donnay & Harker, 1937View full citation) algorithm suggests that we might expect platy morphology for midodrine hydro­chloride Form A, with {002} as the major faces. A 2nd-order spherical harmonic model for preferred orientation was included. The texture index was 1.003, indicating that the preferred orientation was negligible in this rotated capillary specimen.

4. Database survey

A reduced cell search in the Cambridge Structural Database (CSD 2026.1.0; Groom et al., 2016View full citation) yielded 16 hits, but no structures of midodrine or its derivatives.

5. Synthesis and crystallization

Midodrine hydro­chloride was a commercial reagent, purchased from TargetMol (Batch #150940), and was used as-received.

6. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 3[link]. The white powder was packed into a 1.5 mm diameter Kapton capillary, and rotated during the measurement at ∼50 Hz. The powder pattern was measured at 295 K at beam line 11-BM (Lee et al., 2008View full citation; Wang et al., 2008View full citation; Antao et al., 2008View full citation) of the Advanced Photon Source at Argonne National Laboratory using a wavelength of 0.4687342 Å from 0.5–50° 2θ with a step size of 0.001° and a counting time of 0.1 sec/step. The high-resolution powder diffraction data were collected using twelve silicon crystal analyzers that allow for high angular resolution, high precision, and accurate peak positions. A mixture of silicon (NIST SRM 640c) and alumina (NIST SRM 676a) standards (ratio Al2O3:Si = 2:1 by weight) was used to calibrate the instrument and refine the monochromatic wavelength used in the experiment.

Table 3
Experimental details

  midodrine
Crystal data
Chemical formula C12H19N2O4+·Cl−
Mr 290.75
Crystal system, space group Monoclinic, P21/c
Temperature (K) 295
a, b, c (Å) 5.17893 (2), 8.25455 (3), 32.95227 (15)
β (°) 87.2465 (3)
V (Å3) 1407.08 (1)
Z 4
Radiation type Synchrotron, λ = 0.46873 Å
μ (mm−1) 0.03
Specimen shape, size (mm) Cylinder, 2.0 × 1.5
 
Data collection
Diffractometer 11-BM, APS
Specimen mounting Kapton capillary
Data collection mode Transmission
Scan method Step
2θ values (°) 2θmin = 0.510, 2θmax = 49.995, 2θstep = 0.001
 
Refinement
R factors and goodness of fit Rp = 0.049, Rwp = 0.061, Rexp = 0.044, R(F2) = 0.03133, χ2 = 2.008
No. of parameters 96
No. of restraints 42
(Δ/σ)max 8.514
Computer programs: GSAS-II (Toby & Von Dreele, 2013View full citation).

The pattern was indexed on a primitive monoclinic unit cell with a = 5.17847, b = 8.25254, c = 32.94869 Å, β = 92.757°, V = 1406.4 Å3, and Z = 4 using N-TREOR as incorporated into EXPO2014 (Altomare et al., 2013View full citation). The suggested space group was P21/c, which was confirmed by the successful solution and refinement of the structure.

The mol­ecular structure of midodrine was downloaded from PubChem (Kim et al., 2023View full citation) as Conformer3D_COMPOUND_CID_4195.sdf. It was converted to a *.mol2 file using Mercury (Macrae et al., 2020View full citation), and to a Fenske–Hall Z-matrix using OpenBabel (O'Boyle et al., 2011View full citation). The structure was solved by parallel tempering techniques as implemented in FOX (Favre-Nicolin & Černý, 2002View full citation) using a midodrine mol­ecule and a Cl atom as fragments, and by Monte Carlo simulated annealing techniques as implemented in EXPO2014 (Altomare et al., 2013View full citation) and DASH (David et al., 2006View full citation). All three programs yielded equivalent structures. The FOX structure was selected for refinement. H37 was added to N6 using Mercury.

Rietveld refinement was carried out using GSAS-II (Toby & Von Dreele, 2013View full citation). Only the 1.5–28.0° portion of the pattern was included in the refinements (dmin = 0.969 Å). All non-H bond distances and angles were subjected to restraints, based on a Mercury/Mogul Geometry Check (Sykes et al., 2011View full citation; Bruno et al., 2004View full citation). The Mogul average and standard deviation for each qu­antity were used as the restraint parameters. The phenyl ring was restrained to be planar. The restraints contributed 1.5% to the overall χ2. The hydrogen atoms were included in calculated positions, which were recalculated during the refinement using Materials Studio (Dassault Systèmes, 2025View full citation). The Uiso of the non-H atoms were grouped by chemical similarity. The Uiso of the H atoms were fixed at 1.2 × the Uiso of the heavy atom to which they are attached. The Cl was refined anisotropically. The peak profiles were described using the generalized microstrain model (Stephens, 1999View full citation). The background was modeled using a six-term shifted Chebyshev polynomial, with peaks at 1.58 and 5.56° to model the scattering from the Kapton capillary and any amorphous component of the sample.

The final refinement of 96 variables using 26,501 observations and 42 restraints yielded the residuals Rwp = 0.06154 and GOF = 1.42. The largest peak (0.77 Å from O3) and hole (0.37 Å from O3) in the difference-Fourier map were 0.17 (4) and −0.17 (4) e Å−3, respectively. The final Rietveld plot is shown in Fig. 8[link]. The largest features in the normalized error plot are in the shapes of some of the strong low-angle peaks.

[Figure 8]
Figure 8
The Rietveld plot for midodrine hydro­chloride Form A. The blue crosses represent the observed data points, and the green line is the calculated pattern. The cyan curve is the normalized error plot, and the red line is the background curve. The blue tick marks indicate the peak positions. The vertical scale has been multiplied by a factor of 10× for 2θ > 11.6°.

The crystal structure of midodrine hydro­chloride Form A was optimized (fixed experimental unit cell) with density functional theory techniques using VASP (Kresse & Furthmüller, 1996View full citation) through the MedeA graphical inter­face (Materials Design, 2024View full citation). The calculation was carried out on 32 cores of a 144-core (768 Gb memory) HPE Superdome Flex 280 Linux server at North Central College. The calculation used the GGA-PBE functional, a plane wave cutoff energy of 400.0 eV, and a k-point spacing of 0.5 Å−1 leading to a 3 × 2 × 1 mesh, and took ∼2.6 h. Single-point density functional theory calculations (fixed experimental cell) and population analysis were carried out using CRYSTAL23 (Erba et al., 2023View full citation) and CRYSTAL17 (Dovesi et al., 2018View full citation). The basis sets for the H, C, N and O atoms in the calculation were those of Gatti et al. (1994View full citation), and that for Cl was from Peintinger et al. (2013View full citation). The calculations were run on a 3.5 GHz PC using 8 k-points and the B3LYP functional, and took ∼1.8 hr. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF®).

Supporting information

CCDC references: 2552708; 2552707

Crystal structure: contains datablocks midodrine, midodrine_midodrine_VASP. DOI: https://doi.org/10.1107/S2056989026004810/oi2037sup1.cif

Supporting information file. DOI: https://doi.org/10.1107/S2056989026004810/oi2037midodrinesup2.cml

checkCIF report


Computing details top

{[2-(2,5-Dimethoxyphenyl)-2-hydroxyethyl]carbamoyl}methanaminium chloride (midodrine) top
Crystal data top
C12H19N2O4+·Cl−V = 1407.08 (1) Å3
Mr = 290.75Z = 4
Monoclinic, P21/cDx = 1.373 Mg m−3
a = 5.17893 (2) ÅSynchrotron radiation, λ = 0.46873 Å
b = 8.25455 (3) ŵ = 0.03 mm−1
c = 32.95227 (15) ÅT = 295 K
β = 87.2465 (3)°cylinder, 2.0 × 1.5 mm
Data collection top
11-BM, APS
diffractometer		Scan method: step
Specimen mounting: Kapton capillary2θmin = 0.510°, 2θmax = 49.995°, 2θstep = 0.001°
Data collection mode: transmission
Refinement top
Least-squares matrix: full96 parameters
Rp = 0.04942 restraints
Rwp = 0.06134 constraints
Rexp = 0.044Weighting scheme based on measured s.u.'s
R(F2) = 0.03133(Δ/σ)max = 8.514
49486 data pointsBackground function: Background function: "chebyschev-1" function with 6 terms: 35.73(7), -4.92(12), -6.39(12), 3.98(12), -3.39(9), -0.15(7), Background peak parameters: pos, int, sig, gam: 1.580(20), 4.39(21)e3, 2.09(13)e3, 0.100, 5.557(6), 4.34(6)e3, 2.74(7)e3, 0.100,
Profile function: Finger-Cox-Jephcoat function parameters U, V, W, X, Y, SH/L: peak variance(Gauss) = Utan(Th)2+Vtan(Th)+W: peak HW(Lorentz) = X/cos(Th)+Ytan(Th); SH/L = S/L+H/L U, V, W in (centideg)2, X & Y in centideg 1.163, -0.126, 0.063, 0.000, 0.000, 0.002,Preferred orientation correction: Simple spherical harmonic correction Order = 2 Coefficients: 0:0:C(2,-2) = -0.0581(18); 0:0:C(2,0) = 0.078(4); 0:0:C(2,2) = -0.0919(24)
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O11.0970 (4)0.7465 (3)0.57295 (6)0.0323 (4)*
O20.6632 (4)0.9002 (2)0.67443 (6)0.0391 (5)*
O31.3249 (4)0.3806 (2)0.68910 (6)0.0391 (5)*
O41.5002 (4)1.0459 (3)0.54902 (6)0.0323 (4)*
N51.0987 (4)1.0938 (3)0.57585 (7)0.0323 (4)*
N61.4661 (5)1.2607 (3)0.48827 (8)0.0323 (4)*
C70.9770 (5)0.8305 (3)0.60708 (6)0.0323 (4)*
C80.9847 (5)0.7310 (3)0.64575 (6)0.0311 (5)*
C91.1161 (5)0.9912 (3)0.61138 (8)0.0323 (4)*
C100.8228 (5)0.7694 (3)0.67930 (6)0.0311 (5)*
C111.1581 (5)0.6018 (3)0.64869 (7)0.0311 (5)*
C121.1601 (5)0.5099 (3)0.68409 (8)0.0311 (5)*
C130.8299 (6)0.6787 (3)0.71481 (7)0.0311 (5)*
C140.9978 (6)0.5498 (3)0.71712 (7)0.0311 (5)*
C151.2919 (5)1.1156 (4)0.54837 (8)0.0323 (4)*
C161.2304 (5)1.2225 (4)0.51286 (9)0.0323 (4)*
C170.4688 (6)0.9328 (4)0.70550 (9)0.0391 (5)*
C181.5119 (6)0.3451 (4)0.65719 (9)0.0391 (5)*
H190.769850.862020.602970.0388 (5)*
H201.325490.969360.615860.0388 (5)*
H211.040321.057890.639090.0388 (5)*
H221.284920.576750.622420.0373 (6)*
H230.938921.171040.574670.0388 (5)*
H240.704770.711200.742230.0373 (6)*
H251.000970.475740.744970.0373 (6)*
H260.989540.648690.569840.0388 (5)*
H271.094801.167530.492870.0388 (5)*
H281.138941.338330.524420.0388 (5)*
H290.354621.034630.698510.0469 (6)*
H300.346230.824260.712430.0469 (6)*
H310.551600.959600.734900.0469 (6)*
H321.410420.316420.628010.0469 (6)*
H331.617460.240850.665950.0469 (6)*
H341.635680.449370.650610.0469 (6)*
H351.607071.308730.507820.0388 (5)*
H361.426301.357680.467950.0388 (5)*
H371.534151.162930.472440.0388 (5)*
Cl380.2652 (2)0.55463 (11)0.44075 (3)0.0394
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Cl380.0457 (9)0.0273 (9)0.0446 (9)0.0127 (16)0.0036 (15)−0.0002 (15)
Geometric parameters (Å, º) top
O1—C71.437 (2)C15—O41.224 (2)
O1—H260.989 (2)C15—N51.329 (2)
O2—C101.3741 (17)C15—C161.5115 (19)
O2—C171.427 (3)C16—N61.467 (3)
O3—C121.3814 (19)C16—C151.5115 (19)
O3—C181.425 (3)C16—H271.085 (3)
O4—C151.224 (2)C16—H281.125 (3)
N5—C91.451 (2)C17—O21.427 (3)
N5—C151.329 (2)C17—H291.060 (3)
N5—H231.047 (2)C17—H301.115 (3)
N6—C161.467 (3)C17—H311.100 (3)
N6—H351.072 (3)C18—O31.425 (3)
N6—H361.070 (2)C18—H321.142 (3)
N6—H371.015 (3)C18—H331.067 (3)
C7—O11.437 (2)C18—H341.089 (3)
C7—C81.5181 (10)H19—C71.118 (3)
C7—C91.519 (3)H20—C91.116 (3)
C7—H191.118 (3)H21—C91.121 (3)
C8—C71.5181 (10)H22—C111.0811 (19)
C8—C101.3914 (18)H23—N51.047 (2)
C8—C111.4010 (18)H24—C131.119 (2)
C9—N51.451 (2)H25—C141.1036 (19)
C9—C71.519 (3)H26—O10.989 (2)
C9—H201.116 (3)H26—Cl38i2.1733 (10)
C9—H211.121 (3)H27—C161.085 (3)
C10—O21.3741 (17)H28—C161.125 (3)
C10—C81.3914 (18)H29—C171.060 (3)
C10—C131.391 (2)H30—C171.115 (3)
C11—C81.4010 (18)H31—C171.100 (3)
C11—C121.3917 (18)H32—C181.142 (3)
C11—H221.0811 (19)H33—C181.067 (3)
C12—O31.3814 (19)H34—C181.089 (3)
C12—C111.3917 (18)H35—N61.072 (3)
C12—C141.383 (2)H35—Cl38ii2.1656 (10)
C13—C101.391 (2)H36—N61.070 (2)
C13—C141.378 (2)H36—Cl38iii2.0529 (10)
C13—H241.119 (2)H37—N61.015 (3)
C14—C121.383 (2)Cl38—H26i2.1733 (10)
C14—C131.378 (2)Cl38—H35ii2.1656 (10)
C14—H251.1036 (19)Cl38—H36iv2.0529 (10)
C7—O1—H26104.5 (2)C12—C11—H22122.58 (19)
C10—O2—C17118.16 (15)O3—C12—C11123.4 (2)
C12—O3—C18118.2 (2)O3—C12—C14116.5 (2)
C9—N5—C15123.69 (18)C11—C12—C14120.08 (12)
C9—N5—H23117.7 (2)C10—C13—C14120.27 (14)
C15—N5—H23117.5 (2)C10—C13—H24120.83 (18)
C16—N6—H35108.7 (2)C14—C13—H24118.9 (2)
C16—N6—H36109.0 (2)C12—C14—C13120.11 (13)
H35—N6—H36104.9 (2)C12—C14—H25119.3 (2)
C16—N6—H37111.8 (3)C13—C14—H25120.6 (2)
H35—N6—H37111.9 (2)O4—C15—N5124.03 (18)
H36—N6—H37110.3 (2)O4—C15—C16120.44 (17)
O1—C7—C8111.60 (16)N5—C15—C16115.28 (18)
O1—C7—C9107.8 (2)N6—C16—C15110.65 (17)
C8—C7—C9111.2 (2)N6—C16—H27107.5 (3)
O1—C7—H19113.5 (2)C15—C16—H27113.1 (3)
C8—C7—H19106.94 (18)N6—C16—H28109.3 (3)
C9—C7—H19105.68 (19)C15—C16—H28109.6 (3)
C7—C8—C10120.30 (12)H27—C16—H28106.7 (2)
C7—C8—C11120.84 (13)O2—C17—H29112.0 (2)
C10—C8—C11118.84 (11)O2—C17—H30111.8 (3)
N5—C9—C7112.7 (2)H29—C17—H30111.3 (3)
N5—C9—H20107.4 (2)O2—C17—H31112.3 (3)
C7—C9—H20109.9 (2)H29—C17—H31106.1 (3)
N5—C9—H21109.7 (2)H30—C17—H31102.9 (2)
C7—C9—H21110.8 (2)O3—C18—H32109.9 (3)
H20—C9—H21106.0 (2)O3—C18—H33107.7 (3)
O2—C10—C8115.41 (11)H32—C18—H33108.8 (3)
O2—C10—C13124.17 (13)O3—C18—H34111.0 (3)
C8—C10—C13120.42 (12)H32—C18—H34106.7 (2)
C8—C11—C12120.22 (13)H33—C18—H34112.8 (3)
C8—C11—H22117.19 (18)
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+2, −y+2, −z+1; (iii) x+1, y+1, z; (iv) x−1, y−1, z.
(midodrine_midodrine_VASP) top
Crystal data top
C12H19ClN2O4c = 32.95150 Å
Mr = 290.75β = 87.25°
Monoclinic, P21/cV = 1406.93 Å3
a = 5.17880 ÅZ = 4
b = 8.25410 Å
Data collection top
h = →l = →
k = →
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzBiso*/Beq
O11.086090.751600.57288
O20.663290.905880.67624
O31.320100.378440.68884
O41.499561.038630.54807
N51.101171.101190.57712
N61.467981.264720.48858
C70.974860.833680.60772
C80.987770.735210.64646
C91.119920.994600.61196
C100.823200.774130.68029
C111.159080.604860.64894
C121.163330.510970.68431
C130.829420.681200.71575
C140.997680.550110.71764
C151.289301.113760.54791
C161.230051.225860.51307
C170.470510.931800.70822
C181.505650.345610.65626
H190.769850.862020.60297
H201.325490.969360.61586
H211.040321.057890.63909
H221.284920.576750.62242
H230.938921.171040.57467
H240.704770.711200.74223
H251.000970.475740.74497
H260.989540.648690.56984
H271.094801.167530.49287
H281.138941.338330.52442
H290.354621.034630.69851
H300.346230.824260.71243
H310.557660.961640.73709
H321.410420.316420.62801
H331.617460.240850.66595
H341.635680.449370.65061
H351.607071.308730.50782
H361.426301.357680.46795
H371.534151.162930.47244
Cl381.260721.554970.44040
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N6—H37···O41.0431.8072.781153.7
N6—H36···Cl381.0542.0703.094163.2
N6—H35···Cl381.0472.1813.159154.6
O1—H26···Cl380.9932.1593.146172.1
N5—H23···Cl381.0252.5453.465149.0
C16—H28···Cl381.0992.4853.422142.4
C11—H22···O11.0902.4432.82598.9
C13—H24···O31.0892.6563.592143.7
C17—H31···O31.1002.6423.637150.3
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···AMulliken overlapH-bond energy
N6—H37···O41.0431.8072.781153.70.0635.8
N6—H36···Cl381.0542.0703.094163.20.088
N6—H35···Cl381.0472.1813.159154.60.077
O1—H26···Cl380.9932.1593.146172.10.06435.6
N5—H23···Cl381.0252.5453.465149.00.036
C16—H28···Cl381.0992.4853.422142.40.032
C11—H22···O11.0902.4432.82598.90.017
C13—H24···O31.0892.6563.592143.70.012
C17—H31···O31.1002.6423.637150.30.010
 

Acknowledgements

Use of the Advanced Photon Source at Argonne National Laboratory was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02–06CH11357. We thank Saul Lapidus for his assistance in the data collection. We also thank the ICDD team – Megan Rost, Steve Trimble, and Dave Bohnenberger – for their contribution to research, sample preparation, and in-house XRD data collection and verification.

Funding information

Funding for this research was provided by: International Centre for Diffraction Data (grant No. 09-03).

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Volume 82| Part 6| June 2026| Pages 645-650
https://doi.org/10.1107/S2056989026004810
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