Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536802019840/na6176sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536802019840/na61761sup2.hkl |
CCDC reference: 202320
Key indicators
- Single-crystal X-ray study
- T = 150 K
- Mean (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
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.
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.
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.
C8H9NO2·H2O | F(000) = 360 |
Mr = 169.18 | Dx = 1.397 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2yn | Cell parameters from 1700 reflections |
a = 4.5039 (6) Å | θ = 2.2–26.4° |
b = 10.5391 (14) Å | µ = 0.11 mm−1 |
c = 17.048 (2) Å | T = 150 K |
β = 96.399 (3)° | Needle, colourless |
V = 804.18 (19) Å3 | 0.45 × 0.07 × 0.06 mm |
Z = 4 |
Bruker SMART APEX CCD area-detector diffractometer | 1650 independent reflections |
Radiation source: fine-focus sealed tube | 1232 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.052 |
ϕ and ω scans | θmax = 26.4°, θmin = 2.3° |
Absorption correction: multi-scan SADABS (Sheldrick, 1997), based on a procedure given by Blessing (1995) | h = −5→5 |
Tmin = 0.864, Tmax = 0.962 | k = −13→13 |
4516 measured reflections | l = −18→21 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.062 | Hydrogen site location: geom + difmap |
wR(F2) = 0.153 | H 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 parameters | Δρmax = 0.35 e Å−3 |
0 restraints | Δρmin = −0.28 e Å−3 |
C8H9NO2·H2O | V = 804.18 (19) Å3 |
Mr = 169.18 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 4.5039 (6) Å | µ = 0.11 mm−1 |
b = 10.5391 (14) Å | T = 150 K |
c = 17.048 (2) Å | 0.45 × 0.07 × 0.06 mm |
β = 96.399 (3)° |
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 = 0.962 | Rint = 0.052 |
4516 measured reflections |
R[F2 > 2σ(F2)] = 0.062 | 0 restraints |
wR(F2) = 0.153 | H atoms treated by a mixture of independent and constrained refinement |
S = 0.97 | Δρmax = 0.35 e Å−3 |
1650 reflections | Δρmin = −0.28 e Å−3 |
126 parameters |
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. |
x | y | z | Uiso*/Ueq | ||
C1 | 0.5762 (5) | 0.6687 (2) | 0.15652 (13) | 0.0203 (5) | |
C2 | 0.6405 (5) | 0.5890 (2) | 0.09617 (14) | 0.0228 (6) | |
H2 | 0.5360 | 0.5979 | 0.0449 | 0.027* | |
C3 | 0.8575 (5) | 0.4962 (2) | 0.11063 (14) | 0.0227 (6) | |
H3 | 0.9020 | 0.4418 | 0.0691 | 0.027* | |
C4 | 1.0105 (5) | 0.4823 (2) | 0.18545 (14) | 0.0201 (5) | |
O4 | 1.2257 (4) | 0.39115 (15) | 0.20327 (10) | 0.0237 (4) | |
H4 | 1.256 (6) | 0.344 (3) | 0.1589 (17) | 0.032 (7)* | |
C5 | 0.9479 (5) | 0.5626 (2) | 0.24524 (14) | 0.0231 (6) | |
H5 | 1.0530 | 0.5541 | 0.2965 | 0.028* | |
C6 | 0.7335 (5) | 0.6550 (2) | 0.23077 (14) | 0.0228 (6) | |
H6 | 0.6924 | 0.7104 | 0.2722 | 0.027* | |
N7 | 0.3541 (5) | 0.76490 (18) | 0.14821 (12) | 0.0210 (5) | |
H7 | 0.317 (5) | 0.802 (2) | 0.1921 (15) | 0.017 (6)* | |
C8 | 0.1973 (5) | 0.8114 (2) | 0.08327 (13) | 0.0197 (5) | |
O8 | 0.2264 (4) | 0.77490 (15) | 0.01541 (9) | 0.0256 (4) | |
C9 | −0.0181 (6) | 0.9152 (2) | 0.09736 (15) | 0.0251 (6) | |
H9A | 0.0620 | 0.9968 | 0.0819 | 0.038* | |
H9B | −0.0470 | 0.9175 | 0.1535 | 0.038* | |
H9C | −0.2101 | 0.8991 | 0.0659 | 0.038* | |
O1W | 0.1960 (5) | 0.73246 (17) | 0.41504 (11) | 0.0283 (5) | |
H1W | 0.363 (9) | 0.725 (3) | 0.452 (2) | 0.062 (11)* | |
H2W | 0.045 (9) | 0.739 (3) | 0.446 (2) | 0.060 (10)* |
U11 | U22 | U33 | U12 | U13 | U23 | |
C1 | 0.0202 (13) | 0.0170 (11) | 0.0232 (13) | −0.0018 (9) | −0.0003 (9) | 0.0017 (9) |
C2 | 0.0266 (14) | 0.0190 (11) | 0.0210 (13) | −0.0012 (10) | −0.0051 (9) | 0.0017 (9) |
C3 | 0.0269 (14) | 0.0182 (11) | 0.0226 (13) | −0.0013 (10) | 0.0005 (10) | −0.0032 (10) |
C4 | 0.0168 (13) | 0.0183 (11) | 0.0244 (13) | −0.0013 (9) | −0.0014 (9) | 0.0044 (10) |
O4 | 0.0286 (10) | 0.0211 (9) | 0.0204 (10) | 0.0044 (7) | −0.0020 (7) | 0.0001 (7) |
C5 | 0.0244 (14) | 0.0219 (12) | 0.0214 (13) | −0.0027 (10) | −0.0046 (9) | 0.0027 (10) |
C6 | 0.0257 (14) | 0.0213 (11) | 0.0204 (13) | −0.0012 (10) | −0.0012 (9) | −0.0043 (10) |
N7 | 0.0251 (12) | 0.0192 (10) | 0.0181 (11) | 0.0001 (8) | −0.0006 (8) | −0.0029 (8) |
C8 | 0.0212 (13) | 0.0172 (11) | 0.0198 (12) | −0.0040 (9) | −0.0015 (9) | −0.0012 (9) |
O8 | 0.0265 (10) | 0.0274 (9) | 0.0214 (10) | 0.0038 (7) | −0.0032 (7) | −0.0023 (7) |
C9 | 0.0268 (14) | 0.0219 (12) | 0.0250 (13) | −0.0001 (10) | −0.0034 (10) | 0.0005 (10) |
O1W | 0.0301 (11) | 0.0299 (10) | 0.0237 (10) | −0.0025 (8) | −0.0019 (8) | 0.0016 (8) |
C1—C2 | 1.384 (3) | C5—H5 | 0.9500 |
C1—C6 | 1.387 (3) | C6—H6 | 0.9500 |
C1—N7 | 1.420 (3) | N7—C8 | 1.338 (3) |
C2—C3 | 1.386 (3) | N7—H7 | 0.88 (3) |
C2—H2 | 0.9500 | C8—O8 | 1.240 (3) |
C3—C4 | 1.388 (3) | C8—C9 | 1.499 (3) |
C3—H3 | 0.9500 | C9—H9A | 0.9800 |
C4—O4 | 1.374 (3) | C9—H9B | 0.9800 |
C4—C5 | 1.378 (3) | C9—H9C | 0.9800 |
O4—H4 | 0.93 (3) | O1W—H1W | 0.93 (4) |
C5—C6 | 1.375 (3) | O1W—H2W | 0.90 (4) |
C2—C1—C6 | 119.2 (2) | C5—C6—C1 | 121.0 (2) |
C2—C1—N7 | 124.2 (2) | C5—C6—H6 | 119.5 |
C6—C1—N7 | 116.6 (2) | C1—C6—H6 | 119.5 |
C1—C2—C3 | 119.9 (2) | C8—N7—C1 | 130.2 (2) |
C1—C2—H2 | 120.1 | C8—N7—H7 | 114.1 (16) |
C3—C2—H2 | 120.1 | C1—N7—H7 | 115.6 (16) |
C2—C3—C4 | 120.4 (2) | O8—C8—N7 | 123.9 (2) |
C2—C3—H3 | 119.8 | O8—C8—C9 | 120.9 (2) |
C4—C3—H3 | 119.8 | N7—C8—C9 | 115.23 (19) |
O4—C4—C5 | 117.6 (2) | C8—C9—H9A | 109.5 |
O4—C4—C3 | 122.9 (2) | C8—C9—H9B | 109.5 |
C5—C4—C3 | 119.6 (2) | H9A—C9—H9B | 109.5 |
C4—O4—H4 | 110.9 (18) | C8—C9—H9C | 109.5 |
C6—C5—C4 | 120.0 (2) | H9A—C9—H9C | 109.5 |
C6—C5—H5 | 120.0 | H9B—C9—H9C | 109.5 |
C4—C5—H5 | 120.0 | H1W—O1W—H2W | 102 (3) |
D—H···A | D—H | H···A | D···A | D—H···A |
N7—H7···O4i | 0.88 (3) | 2.04 (3) | 2.918 (3) | 174 (2) |
O4—H4···O1Wii | 0.93 (3) | 1.76 (3) | 2.673 (2) | 170 (2) |
O1W—H1W···O8iii | 0.93 (4) | 1.85 (4) | 2.780 (3) | 171 (3) |
O1W—H2W···O8iv | 0.90 (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, y−1/2, −z+1/2; (iii) x+1/2, −y+3/2, z+1/2; (iv) x−1/2, −y+3/2, z+1/2. |
Experimental details
Crystal data | |
Chemical formula | C8H9NO2·H2O |
Mr | 169.18 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 150 |
a, b, c (Å) | 4.5039 (6), 10.5391 (14), 17.048 (2) |
β (°) | 96.399 (3) |
V (Å3) | 804.18 (19) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.11 |
Crystal size (mm) | 0.45 × 0.07 × 0.06 |
Data collection | |
Diffractometer | Bruker SMART APEX CCD area-detector diffractometer |
Absorption correction | Multi-scan SADABS (Sheldrick, 1997), based on a procedure given by Blessing (1995) |
Tmin, Tmax | 0.864, 0.962 |
No. of measured, independent and observed [I > 2σ(I)] reflections | 4516, 1650, 1232 |
Rint | 0.052 |
(sin θ/λ)max (Å−1) | 0.626 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.062, 0.153, 0.97 |
No. of reflections | 1650 |
No. of parameters | 126 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.35, −0.28 |
Computer programs: SMART (Bruker, 2001), SAINT (Bruker, 2002), SAINT, SHELXTL (Sheldrick, 1997), SHELXTL and CAMERON (Watkin et al., 1993).
D—H···A | D—H | H···A | D···A | D—H···A |
N7—H7···O4i | 0.88 (3) | 2.04 (3) | 2.918 (3) | 174 (2) |
O4—H4···O1Wii | 0.93 (3) | 1.76 (3) | 2.673 (2) | 170 (2) |
O1W—H1W···O8iii | 0.93 (4) | 1.85 (4) | 2.780 (3) | 171 (3) |
O1W—H2W···O8iv | 0.90 (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, y−1/2, −z+1/2; (iii) x+1/2, −y+3/2, z+1/2; (iv) x−1/2, −y+3/2, z+1/2. |
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.