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The crystal structure of a new monohydrate of paracetamol (4-hydroxy­acetanilide), C8H9NO2·H2O, is reported at 150 K. It consists of paracetamol and water mol­ecules bound by hydrogen bonding into columns; further hydrogen bonds between paracetamol mol­ecules connect the columns to form a three-dimensional array.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536802019840/na6176sup1.cif
Contains datablocks global, 1

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536802019840/na61761sup2.hkl
Contains datablock 1

CCDC reference: 202320

Key indicators

  • Single-crystal X-ray study
  • T = 150 K
  • Mean [sigma](C-C) = 0.003 Å
  • R factor = 0.062
  • wR factor = 0.153
  • Data-to-parameter ratio = 13.1

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry








Comment top

Paracetamol is an important drug molecule with two structurally characterized phases (monoclinic phase I and orthorhombic phase II, Nichols & Frampton, 1998) and an elusive phase III (Di Martino et al., 1997). Solvates of paracetamol have also recently been studied in some detail, with the structural elucidation of a trihydrate (McGregor et al., 2002) and the publication of a series of cocrystals with organic hydrogen-bond acceptors (Oswald et al., 2002). We report here the crystal structure of a monohydrate, (1), of paracetamol.

The habit of the crystals is needle-like and distinctly different from the hexagonal blocks of the monoclinic anhydrous phase I and the rectangular blocks of the orthorhombic anhydrous phase II, making optical identification simple. Under ambient conditions, the crystals are unstable with respect to loss of water and dehydrate within five minutes on exposure to air, giving monoclinic paracetamol (identified by X-ray powder diffraction).

The crystal structure of the monohydrate shows that the paracetamol molecule is not completely planar, with a dihedral angle of 10.29 (14)° between the phenolic and amide fragments. This dihedral angle is highly variable (Oswald et al., 2002); for example, values of 20.5 and 17.7° are observed in the monoclinic and orthorhombic forms of anhydrous paracetamol, respectively (Nichols & Frampton, 1998), and a value 45.9° is observed in the trihydrate (McGregor et al., 2002).

The paracetamol molecules are stacked along the a axis and linked by interleaving water molecules, which act as hydrogen-bond donors to the carbonyl-O atoms above and below. This forms a C12(4) chain at the binary level (Bernstein et al., 1995). Related to this by the inversion centre at (1/2, 1/2, 0) is a second stack, and this is linked to the first by hydrogen bonds between the phenolic OH (donor) and the water O (acceptor) (Figs. 2a and 2 b). This scheme satisfies all the hydrogen-bonding potential of the water, with the exception of the second acceptor functionality of the oxygen. This motif is far from uncommon (Jeffrey, 1997).

The remaining donor and acceptor capacity of the paracetamol molecules comprises an amidic NH (donor) and a phenolic O atom (acceptor). Interactions between these moieties link the water-bound stacks together. This interaction, which is the longest hydrogen bond in the structure, is the only direct link between paracetamol molecules. It acts to build-up C(7) chains. These linkages are depicted in Fig. 3, in which different water-bound stacks are colour-coded.

Experimental top

Paracetamol (0.108 g, 0.714 mmol; Sigma–Aldrich) and disodium terephthalate (0.180 g, 0.857 mmol; Sigma-Aldrich) were dissolved in deionized water (3.25 ml) by warming to 333 K. The solution was cooled rapidly to 273 K, at which point, colourless crystals were produced. Prior to data collection, it was necessary to mount the crystals quickly under perfluoropolyether oil in order to minimize dehydration.

Refinement top

H atoms bound to carbon were placed in calculated positions and refined as riding or rotating groups. The amide, hydroxyl and water H atoms were located in a difference map and freely refined, giving an N—H bond length of 0.88 (3) Å and O—H bond lengths of between 0.90 (4) and 0.93 (4) Å.

Computing details top

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2002); data reduction: SAINT; program(s) used to solve structure: SHELXTL (Sheldrick, 1997); program(s) used to refine structure: SHELXTL; molecular graphics: SHELXTL and CAMERON (Watkin et al., 1993); software used to prepare material for publication: SHELXTL.

Figures top
[Figure 1] Fig. 1. A view of paracetamol monohydrate with the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] Fig. 2. (a) View of the water-bound stack along the a axis. The b and c axes, respectively, lie vertically and horizontally in this figure. Colour scheme: C green, N blue, O red, and H grey. The stack forms an R44(22) ring. (b) The same stack as (a), with the a axis vertical.
[Figure 3] Fig. 3. Packing in the crystal structure of paracetamol monohydrate. The stacks shown in Fig. 2 are shown here in different colours, although the colour scheme used in Fig. 2 is retained in the case of the stack in the bottom right. In addition to the small R44(22) rings of the water-bound stacks, larger R88(30) patterns are observed between four of these stacks.
4-hydroxyacetanilide hydrate top
Crystal data top
C8H9NO2·H2OF(000) = 360
Mr = 169.18Dx = 1.397 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 1700 reflections
a = 4.5039 (6) Åθ = 2.2–26.4°
b = 10.5391 (14) ŵ = 0.11 mm1
c = 17.048 (2) ÅT = 150 K
β = 96.399 (3)°Needle, colourless
V = 804.18 (19) Å30.45 × 0.07 × 0.06 mm
Z = 4
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
1650 independent reflections
Radiation source: fine-focus sealed tube1232 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.052
ϕ and ω scansθmax = 26.4°, θmin = 2.3°
Absorption correction: multi-scan
SADABS (Sheldrick, 1997), based on a procedure given by Blessing (1995)
h = 55
Tmin = 0.864, Tmax = 0.962k = 1313
4516 measured reflectionsl = 1821
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.062Hydrogen site location: geom + difmap
wR(F2) = 0.153H atoms treated by a mixture of independent and constrained refinement
S = 0.97 w = 1/[σ2(Fo2) + (0.0834P)2]
where P = (Fo2 + 2Fc2)/3
1650 reflections(Δ/σ)max < 0.001
126 parametersΔρmax = 0.35 e Å3
0 restraintsΔρmin = 0.28 e Å3
Crystal data top
C8H9NO2·H2OV = 804.18 (19) Å3
Mr = 169.18Z = 4
Monoclinic, P21/nMo Kα radiation
a = 4.5039 (6) ŵ = 0.11 mm1
b = 10.5391 (14) ÅT = 150 K
c = 17.048 (2) Å0.45 × 0.07 × 0.06 mm
β = 96.399 (3)°
Data collection top
Bruker SMART APEX CCD area-detector
diffractometer
1650 independent reflections
Absorption correction: multi-scan
SADABS (Sheldrick, 1997), based on a procedure given by Blessing (1995)
1232 reflections with I > 2σ(I)
Tmin = 0.864, Tmax = 0.962Rint = 0.052
4516 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0620 restraints
wR(F2) = 0.153H atoms treated by a mixture of independent and constrained refinement
S = 0.97Δρmax = 0.35 e Å3
1650 reflectionsΔρmin = 0.28 e Å3
126 parameters
Special details top

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.5762 (5)0.6687 (2)0.15652 (13)0.0203 (5)
C20.6405 (5)0.5890 (2)0.09617 (14)0.0228 (6)
H20.53600.59790.04490.027*
C30.8575 (5)0.4962 (2)0.11063 (14)0.0227 (6)
H30.90200.44180.06910.027*
C41.0105 (5)0.4823 (2)0.18545 (14)0.0201 (5)
O41.2257 (4)0.39115 (15)0.20327 (10)0.0237 (4)
H41.256 (6)0.344 (3)0.1589 (17)0.032 (7)*
C50.9479 (5)0.5626 (2)0.24524 (14)0.0231 (6)
H51.05300.55410.29650.028*
C60.7335 (5)0.6550 (2)0.23077 (14)0.0228 (6)
H60.69240.71040.27220.027*
N70.3541 (5)0.76490 (18)0.14821 (12)0.0210 (5)
H70.317 (5)0.802 (2)0.1921 (15)0.017 (6)*
C80.1973 (5)0.8114 (2)0.08327 (13)0.0197 (5)
O80.2264 (4)0.77490 (15)0.01541 (9)0.0256 (4)
C90.0181 (6)0.9152 (2)0.09736 (15)0.0251 (6)
H9A0.06200.99680.08190.038*
H9B0.04700.91750.15350.038*
H9C0.21010.89910.06590.038*
O1W0.1960 (5)0.73246 (17)0.41504 (11)0.0283 (5)
H1W0.363 (9)0.725 (3)0.452 (2)0.062 (11)*
H2W0.045 (9)0.739 (3)0.446 (2)0.060 (10)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0202 (13)0.0170 (11)0.0232 (13)0.0018 (9)0.0003 (9)0.0017 (9)
C20.0266 (14)0.0190 (11)0.0210 (13)0.0012 (10)0.0051 (9)0.0017 (9)
C30.0269 (14)0.0182 (11)0.0226 (13)0.0013 (10)0.0005 (10)0.0032 (10)
C40.0168 (13)0.0183 (11)0.0244 (13)0.0013 (9)0.0014 (9)0.0044 (10)
O40.0286 (10)0.0211 (9)0.0204 (10)0.0044 (7)0.0020 (7)0.0001 (7)
C50.0244 (14)0.0219 (12)0.0214 (13)0.0027 (10)0.0046 (9)0.0027 (10)
C60.0257 (14)0.0213 (11)0.0204 (13)0.0012 (10)0.0012 (9)0.0043 (10)
N70.0251 (12)0.0192 (10)0.0181 (11)0.0001 (8)0.0006 (8)0.0029 (8)
C80.0212 (13)0.0172 (11)0.0198 (12)0.0040 (9)0.0015 (9)0.0012 (9)
O80.0265 (10)0.0274 (9)0.0214 (10)0.0038 (7)0.0032 (7)0.0023 (7)
C90.0268 (14)0.0219 (12)0.0250 (13)0.0001 (10)0.0034 (10)0.0005 (10)
O1W0.0301 (11)0.0299 (10)0.0237 (10)0.0025 (8)0.0019 (8)0.0016 (8)
Geometric parameters (Å, º) top
C1—C21.384 (3)C5—H50.9500
C1—C61.387 (3)C6—H60.9500
C1—N71.420 (3)N7—C81.338 (3)
C2—C31.386 (3)N7—H70.88 (3)
C2—H20.9500C8—O81.240 (3)
C3—C41.388 (3)C8—C91.499 (3)
C3—H30.9500C9—H9A0.9800
C4—O41.374 (3)C9—H9B0.9800
C4—C51.378 (3)C9—H9C0.9800
O4—H40.93 (3)O1W—H1W0.93 (4)
C5—C61.375 (3)O1W—H2W0.90 (4)
C2—C1—C6119.2 (2)C5—C6—C1121.0 (2)
C2—C1—N7124.2 (2)C5—C6—H6119.5
C6—C1—N7116.6 (2)C1—C6—H6119.5
C1—C2—C3119.9 (2)C8—N7—C1130.2 (2)
C1—C2—H2120.1C8—N7—H7114.1 (16)
C3—C2—H2120.1C1—N7—H7115.6 (16)
C2—C3—C4120.4 (2)O8—C8—N7123.9 (2)
C2—C3—H3119.8O8—C8—C9120.9 (2)
C4—C3—H3119.8N7—C8—C9115.23 (19)
O4—C4—C5117.6 (2)C8—C9—H9A109.5
O4—C4—C3122.9 (2)C8—C9—H9B109.5
C5—C4—C3119.6 (2)H9A—C9—H9B109.5
C4—O4—H4110.9 (18)C8—C9—H9C109.5
C6—C5—C4120.0 (2)H9A—C9—H9C109.5
C6—C5—H5120.0H9B—C9—H9C109.5
C4—C5—H5120.0H1W—O1W—H2W102 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N7—H7···O4i0.88 (3)2.04 (3)2.918 (3)174 (2)
O4—H4···O1Wii0.93 (3)1.76 (3)2.673 (2)170 (2)
O1W—H1W···O8iii0.93 (4)1.85 (4)2.780 (3)171 (3)
O1W—H2W···O8iv0.90 (4)1.97 (4)2.866 (3)171 (3)
Symmetry codes: (i) x+3/2, y+1/2, z+1/2; (ii) x+3/2, y1/2, z+1/2; (iii) x+1/2, y+3/2, z+1/2; (iv) x1/2, y+3/2, z+1/2.

Experimental details

Crystal data
Chemical formulaC8H9NO2·H2O
Mr169.18
Crystal system, space groupMonoclinic, P21/n
Temperature (K)150
a, b, c (Å)4.5039 (6), 10.5391 (14), 17.048 (2)
β (°) 96.399 (3)
V3)804.18 (19)
Z4
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.45 × 0.07 × 0.06
Data collection
DiffractometerBruker SMART APEX CCD area-detector
diffractometer
Absorption correctionMulti-scan
SADABS (Sheldrick, 1997), based on a procedure given by Blessing (1995)
Tmin, Tmax0.864, 0.962
No. of measured, independent and
observed [I > 2σ(I)] reflections
4516, 1650, 1232
Rint0.052
(sin θ/λ)max1)0.626
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.062, 0.153, 0.97
No. of reflections1650
No. of parameters126
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.35, 0.28

Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2002), SAINT, SHELXTL (Sheldrick, 1997), SHELXTL and CAMERON (Watkin et al., 1993).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N7—H7···O4i0.88 (3)2.04 (3)2.918 (3)174 (2)
O4—H4···O1Wii0.93 (3)1.76 (3)2.673 (2)170 (2)
O1W—H1W···O8iii0.93 (4)1.85 (4)2.780 (3)171 (3)
O1W—H2W···O8iv0.90 (4)1.97 (4)2.866 (3)171 (3)
Symmetry codes: (i) x+3/2, y+1/2, z+1/2; (ii) x+3/2, y1/2, z+1/2; (iii) x+1/2, y+3/2, z+1/2; (iv) x1/2, y+3/2, z+1/2.
 

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