Literature DB >> 21587506

Trihexyphenidyl hydro-chloride: a powder diffraction study.

Elisabetta Maccaroni, Luciana Malpezzi, Norberto Masciocchi.   

Abstract

IN THE CATION OF THE TITLE COMPOUND [SYSTEMATIC NAME: 1-(3-cyclo-hexyl-3-hy-droxy-3-phenyl-prop-yl)piperidinium chloride], C(20)H(32)NO(+)·Cl(-), the cyclo-hexyl and piperidine rings are in chair conformations. In the crystal structure, cations and anions are linked into chains along the c-axis direction via O-H⋯Cl and N-H⋯Cl hydrogen bonds. Weak inter-molecular C-H⋯Cl inter-actions link further these chains into layers parallel to the bc plane. The salt, obtained from a racemic solution, was found to crystallize in the chiral P2(1)2(1)2 space group, indicating that, in the absence of any evident chirality-inducing process, the polycrystalline powders consist of an equivalent mixture of R and S enanti-omers, forming a racemic conglomerate.

Entities:  

Year:  2010        PMID： 21587506      PMCID： PMC2983296          DOI： 10.1107/S1600536810035294

Source DB:  PubMed          Journal:  Acta Crystallogr Sect E Struct Rep Online        ISSN： 1600-5368


Related literature

For characterization of related structures, see Camerman & Camerman (1971a ▶, 1972a ▶); Codding (1986 ▶); Marubayashi et al. (1999 ▶). For structure–activity relationships, see Camerman & Camerman (1970 ▶, 1971a ▶,b ▶, 1972a ▶,b ▶, 1981 ▶). For the profile function, see: Cheary & Coelho (1992 ▶) and for the March–Dollase orientation correction, see: Dollase (1986 ▶).

Experimental

Crystal data

C20H32NO+·Cl− M = 337.93 Orthorhombic, a = 30.0265 (8) Å b = 11.2297 (4) Å c = 5.8931 (2) Å V = 1987.08 (12) Å3 Z = 4 Cu Kα radiation, λ = 1.540562, 1.544390 Å T = 298 K Flat sheet, 15 × 20 mm

Data collection

Bruker D8 Advance diffractometer Specimen mounting: packed powder Data collection mode: reflection Scan method: step 2θmin = 5°, 2θmax = 104.86°, 2θstep = 0.02°

Refinement

R p = 0.051 R wp = 0.075 R exp = 0.008 R Bragg = 0.023 χ2 = 91.317 4994 data points 100 parameters 46 restraints H-atom parameters constrained Data collection: D8 Software (Bruker, 2005 ▶); cell refinement: TOPAS-R (Coelho, 2005 ▶); data reduction: TOPAS-R; program(s) used to solve structure: TOPAS-R; program(s) used to refine structure: TOPAS-R; molecular graphics: SHELXTL/NT (Sheldrick, 2008 ▶); software used to prepare material for publication: enCIFer (Allen et al., 2004 ▶). Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810035294/cv2721sup1.cif Rietveld powder data: contains datablocks I. DOI: 10.1107/S1600536810035294/cv2721Isup2.rtv Additional supplementary materials: crystallographic information; 3D view; checkCIF report
C20H32NO+·Cl−F(000) = 736
Mr = 337.93Dx = 1.130 Mg m−3
Orthorhombic, P21212Cu Kα radiation, λ = 1.540562, 1.544390 Å
a = 30.0265 (8) ÅT = 298 K
b = 11.2297 (4) ÅParticle morphology: no specific habit
c = 5.8931 (2) Åwhite
V = 1987.08 (12) Å3flat sheet, 15 × 20 mm
Z = 4Specimen preparation: Prepared at 298 K and 101.325 kPa
Bruker AXS D8 Advance diffractometerData collection mode: reflection
Radiation source: sealed X-ray tubeScan method: step
Ni filter2θmin = 5°, 2θmax = 104.86°, 2θstep = 0.02°
Specimen mounting: packed powder
Refinement on InetProfile function: fundamental parameters (Cheary & Coelho, 1992)
Least-squares matrix: full with fixed elements per cycle100 parameters
Rp = 0.05146 restraints
Rwp = 0.075H-atom parameters constrained
Rexp = 0.008w = 1/σ(Yobs)2
RBragg = 0.023(Δ/σ)max = 0.01
χ2 = 91.317Background function: Chebyshev polynomial
4994 data pointsPreferred orientation correction: March–Dollase (Dollase, 1986); direction of preferred orientation 100, texture parameter r = 0.763).
Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All e.s.d.'s are estimated from the variances of the (full) variance-covariance matrix. The cell e.s.d.'s are taken into account in the estimation of distances, angles and torsion angles
xyzUiso*/Ueq
O1−0.1539 (3)0.9849 (13)−0.521 (2)0.0703 (16)*
N1−0.2407 (2)1.0155 (11)−0.0092 (18)0.0703 (16)*
C1−0.1953 (3)1.0772 (12)−0.079 (3)0.0703 (16)*
C2−0.1630 (3)0.9800 (12)−0.118 (2)0.0703 (16)*
C3−0.1306 (3)0.9977 (10)−0.3049 (17)0.0703 (16)*
C4−0.0896 (3)0.9088 (8)−0.3708 (19)0.0703 (16)*
C5−0.1053 (3)0.7793 (9)−0.349 (2)0.0703 (16)*
C6−0.0643 (3)0.6928 (9)−0.3714 (19)0.0703 (16)*
C7−0.0458 (3)0.7068 (9)−0.6064 (19)0.0703 (16)*
C8−0.0271 (3)0.8346 (9)−0.617 (2)0.0703 (16)*
C9−0.0682 (3)0.9211 (9)−0.612 (2)0.0703 (16)*
C10−0.1089 (3)1.1202 (8)−0.2851 (17)0.0703 (16)*
C11−0.1119 (4)1.2011 (9)−0.4647 (19)0.0703 (16)*
C12−0.0882 (3)1.3065 (10)−0.4550 (18)0.0703 (16)*
C13−0.0620 (4)1.3275 (10)−0.2593 (16)0.0703 (16)*
C14−0.0603 (4)1.2490 (9)−0.0726 (18)0.0703 (16)*
C15−0.0837 (4)1.1401 (9)−0.0896 (18)0.0703 (16)*
C16−0.2651 (3)1.0901 (10)0.1634 (19)0.0703 (16)*
C17−0.3081 (3)1.0375 (12)0.2536 (16)0.0703 (16)*
C18−0.3374 (3)1.0063 (13)0.051 (2)0.0703 (16)*
C19−0.3122 (3)0.9158 (10)−0.091 (2)0.0703 (16)*
C20−0.2705 (3)0.9634 (13)−0.1905 (16)0.0703 (16)*
Cl−0.22190 (13)0.8068 (5)−0.6675 (10)0.0703 (16)*
H1−0.231870.950670.071640.0703*
H1A−0.199141.12387−0.216480.0703*
H1B−0.184911.129410.040690.0703*
H2−0.172340.92801−0.560390.0703*
H2A−0.179520.90757−0.148640.0703*
H2B−0.146410.967520.021160.0703*
H4−0.065860.92116−0.258920.0703*
H5A−0.126880.76178−0.466480.0703*
H5B−0.119510.76773−0.202720.0703*
H6A−0.041840.71266−0.259460.0703*
H6B−0.073680.61116−0.346740.0703*
H7A−0.068950.69573−0.719080.0703*
H7B−0.022340.64909−0.633620.0703*
H8A−0.010160.84599−0.755760.0703*
H8B−0.007720.84971−0.488820.0703*
H9A−0.058721.00254−0.638160.0703*
H9B−0.089560.89932−0.728250.0703*
H11−0.129671.18414−0.589780.0703*
H12−0.089331.36158−0.572730.0703*
H13−0.045061.39670−0.253390.0703*
H14−0.044321.268220.057460.0703*
H15−0.082301.083560.025510.0703*
H16A−0.271761.166750.095540.0703*
H16B−0.245301.104230.290600.0703*
H17A−0.323131.094680.350330.0703*
H17B−0.301880.966620.342160.0703*
H18A−0.365470.973020.101710.0703*
H18B−0.343571.07706−0.038430.0703*
H19A−0.305050.847570.003040.0703*
H19B−0.331370.88837−0.212980.0703*
H20A−0.277641.02447−0.301030.0703*
H20B−0.254770.89994−0.268420.0703*
O1—C31.460 (15)C2—H2A0.9696
O1—H20.8767C2—H2B0.9696
N1—C11.584 (13)C4—H40.9808
N1—C201.511 (14)C5—H5A0.9684
N1—C161.508 (15)C5—H5B0.9705
N1—H10.9096C6—H6A0.9694
C1—C21.478 (17)C6—H6B0.9700
C2—C31.483 (14)C7—H7A0.9693
C3—C41.632 (14)C7—H7B0.9704
C3—C101.527 (14)C8—H8A0.9714
C4—C51.534 (13)C8—H8B0.9685
C4—C91.566 (16)C9—H9A0.9701
C5—C61.574 (13)C9—H9B0.9697
C6—C71.500 (15)C11—H110.9297
C7—C81.542 (14)C12—H120.9301
C8—C91.571 (13)C13—H130.9294
C10—C111.398 (14)C14—H140.9297
C10—C151.396 (15)C15—H150.9301
C11—C121.382 (15)C16—H16A0.9700
C12—C131.416 (15)C16—H16B0.9698
C13—C141.411 (15)C17—H17A0.9700
C14—C151.414 (15)C17—H17B0.9700
C16—C171.516 (14)C18—H18A0.9693
C17—C181.524 (15)C18—H18B0.9713
C18—C191.518 (17)C19—H19A0.9697
C19—C201.482 (14)C19—H19B0.9710
C1—H1A0.9718C20—H20A0.9698
C1—H1B0.9688C20—H20B0.9704
Cl···C203.623 (12)H2B···C152.7799
Cl···O12.986 (13)H2B···H12.5900
Cl···N1i3.141 (13)H2B···H9Biii2.3837
Cl···C16i3.577 (12)H2B···H152.3248
Cl···H20B2.7567H4···C152.7069
Cl···H16Aii2.9787H4···H6A2.4500
Cl···H5A3.1305H4···H8B2.3510
Cl···H17Bi2.9986H4···H152.5257
Cl···H1i2.2501H5A···Cl3.1305
Cl···H22.1132H5A···H9B2.4538
O1···Cl2.986 (13)H5A···H17Aiv2.4986
O1···H9B2.4795H5A···H7A2.4065
O1···H112.3874H5A···O12.6532
O1···H2Bi2.7145H5A···H22.3779
O1···H5A2.6532H5B···H2A2.4113
O1···H1A2.7389H5B···C22.7635
N1···Cliii3.141 (13)H6A···H42.4500
C1···C153.425 (15)H6A···H8B2.2902
C9···C113.516 (15)H7A···H5A2.4065
C11···C93.516 (15)H7A···H9B2.3691
C15···C13.425 (15)H8A···H14vii2.3521
C16···Cliii3.577 (12)H8A···C14vii3.0168
C17···C20iii3.564 (14)H8B···H42.3510
C20···Cl3.623 (12)H8B···H6A2.2902
C20···C17i3.564 (14)H9A···C112.9269
C1···H19Aiv3.0690H9A···C102.8888
C2···H5B2.7635H9A···H15i2.2929
C2···H20B3.0310H9B···H5A2.4538
C2···H152.8176H9B···H7A2.3691
C4···H153.0584H9B···O12.4795
C5···H22.8970H9B···H2Bi2.3837
C5···H17Aiv2.9860H9B···H15i2.5364
C5···H2A2.9043H11···O12.3874
C9···H15i2.8409H14···H8Avi2.3521
C10···H9A2.8888H15···C43.0584
C10···H1A2.7400H15···C9iii2.8409
C10···H1B2.9842H15···H2B2.3248
C11···H9A2.9269H15···H42.5257
C13···H18Av2.8767H15···H9Aiii2.2929
C14···H8Avi3.0168H15···H9Biii2.5364
C15···H42.7069H15···C22.8176
C15···H2B2.7799H16A···Clviii2.9787
C17···H20Aiii2.7832H16A···H18B2.5072
C20···H17Bi2.9110H16B···H1B2.3531
C20···H2A2.8138H17A···H5Av2.4986
H1···H2B2.5900H17A···C5v2.9860
H1···H19A2.5165H17A···H20Aiii2.5901
H1···H2A2.0953H17B···Cliii2.9986
H1···Cliii2.2501H17B···C20iii2.9110
H1A···O12.7389H17B···H19A2.4063
H1A···C102.7400H17B···H20Aiii2.3180
H1B···C102.9842H18A···C13iv2.8767
H1B···H19Av2.4818H18B···H20A2.5811
H1B···H16B2.3531H18B···H16A2.5072
H2···C52.8970H19A···C1iv3.0690
H2···Cl2.1132H19A···H12.5165
H2···H2A2.4468H19A···H17B2.4063
H2···H5A2.3779H19A···H1Biv2.4818
H2A···C52.9043H20A···H17Bi2.3180
H2A···H5B2.4113H20A···H18B2.5811
H2A···H20B2.3689H20A···C17i2.7832
H2A···C202.8138H20A···H17Ai2.5901
H2A···H12.0953H20B···Cl2.7567
H2A···H22.4468H20B···C23.0310
H2B···O1iii2.7145H20B···H2A2.3689
C3—O1—H2127.25C5—C6—H6B110.09
C1—N1—C16110.5 (10)C7—C6—H6A110.27
C16—N1—C20113.8 (7)C7—C6—H6B110.17
C1—N1—C20119.7 (10)H6A—C6—H6B108.52
C20—N1—H1103.47C6—C7—H7A110.70
C1—N1—H1103.61C6—C7—H7B110.57
C16—N1—H1103.48C8—C7—H7A110.65
N1—C1—C2106.4 (10)C8—C7—H7B110.52
C1—C2—C3116.5 (11)H7A—C7—H7B108.76
O1—C3—C495.4 (8)C7—C8—H8A110.32
O1—C3—C10111.1 (9)C7—C8—H8B110.50
C2—C3—C4126.1 (9)C9—C8—H8A110.22
C2—C3—C10110.1 (9)C9—C8—H8B110.43
O1—C3—C2108.7 (8)H8A—C8—H8B108.60
C4—C3—C10104.3 (7)C4—C9—H9A110.35
C3—C4—C5109.2 (7)C4—C9—H9B110.34
C3—C4—C9118.1 (8)C8—C9—H9A110.45
C5—C4—C9106.6 (8)C8—C9—H9B110.51
C4—C5—C6109.7 (7)H9A—C9—H9B108.63
C5—C6—C7107.6 (8)C10—C11—H11120.28
C6—C7—C8105.6 (9)C12—C11—H11120.24
C7—C8—C9106.8 (7)C11—C12—H12121.32
C4—C9—C8106.5 (8)C13—C12—H12121.14
C11—C10—C15123.8 (9)C12—C13—H13118.29
C3—C10—C11120.0 (9)C14—C13—H13118.26
C3—C10—C15116.0 (8)C13—C14—H14121.10
C10—C11—C12119.5 (10)C15—C14—H14121.04
C11—C12—C13117.5 (10)C10—C15—H15121.13
C12—C13—C14123.5 (10)C14—C15—H15121.09
C13—C14—C15117.9 (10)N1—C16—H16A108.37
C10—C15—C14117.8 (9)N1—C16—H16B108.33
N1—C16—C17115.7 (9)C17—C16—H16A108.34
C16—C17—C18107.9 (8)C17—C16—H16B108.35
C17—C18—C19107.3 (8)H16A—C16—H16B107.45
C18—C19—C20113.4 (10)C16—C17—H17A110.15
N1—C20—C19111.1 (8)C16—C17—H17B110.15
N1—C1—H1A110.51C18—C17—H17A110.12
N1—C1—H1B110.66C18—C17—H17B110.12
C2—C1—H1A110.28H17A—C17—H17B108.46
C2—C1—H1B110.41C17—C18—H18A110.43
H1A—C1—H1B108.59C17—C18—H18B110.31
C1—C2—H2A108.23C19—C18—H18A110.20
C1—C2—H2B108.19C19—C18—H18B110.09
C3—C2—H2A108.04H18A—C18—H18B108.47
C3—C2—H2B108.10C18—C19—H19A108.92
H2A—C2—H2B107.39C18—C19—H19B108.96
C3—C4—H4107.56C20—C19—H19A108.91
C5—C4—H4107.53C20—C19—H19B108.80
C9—C4—H4107.42H19A—C19—H19B107.67
C4—C5—H5A109.77N1—C20—H20A109.39
C4—C5—H5B109.65N1—C20—H20B109.31
C6—C5—H5A109.75C19—C20—H20A109.50
C6—C5—H5B109.62C19—C20—H20B109.48
H5A—C5—H5B108.29H20A—C20—H20B108.00
C5—C6—H6A110.19
C16—N1—C1—C2144.9 (11)C2—C3—C10—C11−122.4 (10)
C20—N1—C1—C2−79.8 (14)C3—C4—C5—C6−170.5 (8)
C1—N1—C16—C17−176.9 (9)C3—C4—C9—C8174.3 (8)
C20—N1—C16—C1745.0 (14)C5—C4—C9—C8−62.5 (9)
C1—N1—C20—C19−177.0 (10)C9—C4—C5—C660.9 (10)
C16—N1—C20—C19−43.2 (14)C4—C5—C6—C7−64.1 (11)
N1—C1—C2—C3143.5 (10)C5—C6—C7—C866.4 (9)
C1—C2—C3—O1−72.9 (14)C6—C7—C8—C9−69.6 (10)
C1—C2—C3—C4175.4 (10)C7—C8—C9—C467.6 (10)
C1—C2—C3—C1049.0 (12)C3—C10—C11—C12−173.1 (9)
O1—C3—C4—C5−77.8 (10)C15—C10—C11—C121.4 (16)
C2—C3—C10—C1562.7 (11)C3—C10—C15—C14175.3 (9)
C4—C3—C10—C1199.8 (10)C11—C10—C15—C140.6 (16)
C4—C3—C10—C15−75.2 (11)C10—C11—C12—C13−0.5 (15)
C10—C3—C4—C5168.8 (8)C11—C12—C13—C14−2.4 (16)
C10—C3—C4—C9−69.3 (10)C12—C13—C14—C154.4 (17)
O1—C3—C10—C11−1.9 (13)C13—C14—C15—C10−3.4 (16)
O1—C3—C10—C15−176.8 (9)N1—C16—C17—C18−53.6 (13)
O1—C3—C4—C944.1 (11)C16—C17—C18—C1960.4 (13)
C2—C3—C4—C540.0 (13)C17—C18—C19—C20−64.4 (12)
C2—C3—C4—C9161.9 (9)C18—C19—C20—N154.5 (13)
D—H···AD—HH···AD···AD—H···A
N1—H1···Cliii0.912.253.141 (13)166
O1—H2···Cl0.882.112.986 (13)173
C11—H11···O10.932.392.756 (17)103
C20—H20B···Cl0.972.763.623 (12)149
Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯AD—HH⋯AD⋯AD—H⋯A
N1—H1⋯Cli0.912.253.141 (13)166
O1—H2⋯Cl0.882.112.986 (13)173
C20—H20B⋯Cl0.972.763.623 (12)149

Symmetry code: (i) .

  5 in total

1.  A short history of SHELX.

Authors:  George M Sheldrick
Journal:  Acta Crystallogr A       Date:  2007-12-21       Impact factor: 2.290

2.  The stereochemical basis of anticonvulsant drug action. IV. The crystal and molecular structure of trihexyphenidyl.

Authors:  N Camerman; A Camerman
Journal:  J Am Chem Soc       Date:  1972-11-29       Impact factor: 15.419

3.  The stereochemical basis of anticonvulsant drug action. 3. The structure of procyclidine hydrochloride.

Authors:  N Camerman; A Camerman
Journal:  Mol Pharmacol       Date:  1971-07       Impact factor: 4.436

4.  Diphenylhydantoin and diazepam: molecular structure similarities and steric basis of anticonvulsant activity.

Authors:  A Camerman; N Camerman
Journal:  Science       Date:  1970-06-19       Impact factor: 47.728

5.  Stereochemical basis of anticonvulsant drug action. II. Molecular structure of diazepam.

Authors:  A Camerman; N Camerman
Journal:  J Am Chem Soc       Date:  1972-01-12       Impact factor: 15.419
  5 in total

北京卡尤迪生物科技股份有限公司 © 2022-2023.