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IR Spectra of Paracetamol and Phenacetin. 1. Theoretical and Experimental

Studies

Article  in  Journal of Structural Chemistry · January 2004

DOI: 10.1023/B:JORY.0000041502.85584.d5

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Journal of Structural Chemistry. Vol. 45, No. 1, pp. 64-73, 2004
Original Russian Text Copyright © 2004 by E. B. Burgina, V. P. Baltakhinov, E. V. Boldyreva, and T. P. Shakhtschneider

IR SPECTRA OF PARACETAMOL AND PHENACETIN.

1. THEORETICAL AND EXPERIMENTAL STUDIES

E. B. Burgina,1 V. P. Baltakhinov,3 E. V. Boldyreva,2 UDC 539.2+543.42

and T. P. Shakhtschneider2

IR spectra of paracetamol and phenacetin have been measured for powder crystals of these compounds and
for their solutions in chloroform and dimethylsulfoxide. Ab initio calculations of their equilibrium geometry
and vibrational spectra were carried out for spectrum interpretation. Differences between the experimental
IR spectra of solutions and crystalline samples have been analyzed. Variations of molecular structure from
the isolated state to molecular crystal were estimated based on the difference between the optimized
molecular parameters of free molecules and the experimental bond lengths and angles evaluated for the
crystal forms of the title compounds. The role of hydrogen bonds in the structure of molecular crystals of
paracetamol and phenacetin is investigated, and spectral ranges with maximal intermolecular interactions
are determined.
Key words: pharmaceuticals, ab initio calculation, molecular crystals, hydrogen bond, intermolecular
interaction.

Paracetamol (para-acetaminophenol) and phenacetin (para-acetophenitidine) are widespread pharmaceuticals with

analgesic and anti-fever activities. As is known, the biological activity and the pharmaceutical properties of drugs are strongly
dependent on their structure. The structural formulas and some physicochemical properties of these compounds have been
known for decades. Detailed investigations of their crystal forms, however, were started in recent years [1-13]. For
paracetamol, three polymorphic modifications were described [2, 3, 5, 6]. Low-temperature [5, 8-11] and high-pressure [12,
13] diffraction experiments indicate that an important role in crystal structure formation for paracetamol modifications is
played by the OH…O and NH…O intermolecular hydrogen bonds [2-13].
Molecular spectroscopy methods, in particular, experimental IR spectroscopy, have long been successfully
employed for structure investigations of complex molecular compounds. These techniques are especially effective when used
in combination with direct methods of structural analysis in hydrogen bond investigations.
At present, few works reporting the IR spectra of paracetamol are available. Thus IR spectra have been published for
three of its crystal modifications, and an assignment of the most intense bands has been suggested [6]. The first and, to the
best of our knowledge, the single spectroscopic work with full quantum-chemical calculation of the structure and vibrational
spectrum of paracetamol appeared in 1998 [14]. The vibrational spectrum calculated with a good (HF/6-31G) basis set and
with appropriate scaling of frequencies was successfully correlated with the experimental IR spectrum of a deuterochloroform
solution of paracetamol. Full spectrum assignment was made based on the calculation using the shapes of normal vibrations

1
G. K. Boreskov Institute of Catalysis, Siberian Branch, Russian Academy of Sciences, Novosibirsk;
burgina@ngs.ru. 2Institute of Solid State Chemistry and Mechanochemistry, Siberian Branch, Russian Academy of Sciences,
Novosibirsk. 3MDEBT Research and Educational Center, Novosibirsk State University. Translated from Zhurnal Strukturnoi
Khimii, Vol. 45, No. 1, pp. 67-76, January-February, 2004. Original article submitted December 2, 2002.

64 0022-4766/04/4501-0064 © 2004 Springer Science+Business Media, Inc.

in accordance with the potential energy distribution over internal coordinates. We do not know of any publications analyzing
the vibrational spectrum of phenacetin.
The aim of the present work is theoretical and experimental spectroscopic investigation of free molecules and
molecular crystals of paracetamol and phenacetin to gain insight into the structure and role of hydrogen bonds in their
molecular crystals.

EXPERIMENTAL

Paracetamol and phenacetin (commercial samples, Kursk Drug Plant) were purified by recrystallization from an
ethanol solution. The orthorhombic modification of paracetamol was obtained from a melt according to the procedure
described in [15].
IR spectra were recorded on a Bomem MB-102 Fourier spectrometer (resolution 4 cm–1) for KBr pellets (2 mg
sample with 500 mg KBr) and solutions (at first, the spectrum of the solvent was recorded and then the spectrum of the
solution was measured in the same cell with subsequent subtraction of the spectrum of the solvent). The solvents used include
chloroform, deuterochloroform, and dimethylsulfoxide. Saturated solutions of paracetamol and phenacetin were prepared,
then their IR spectra were recorded and processed, and the solutions were successively diluted until the spectrum of the solute
completely vanished. Attempts were made to monitor the intermolecular interactions in solutions according to changes in the
spectra. As paracetamol has much lower solubility in chloroform and deuterochloroform compared to phenacetin, for
spectrum measurements in solution we used a NaCl cell 1.0 mm thick for paracetamol and a KBr cell 0.3 mm thick for
phenacetin. In each case, the spectrum of the solvent in a cell of appropriate thickness was subtracted.
For spectrum measurements in the near IR range (4000 cm–1 -10000 cm–1), an Interspec 2010 Fourier spectrometer
was used. Diffuse scattering spectra of paracetamol and phenacetin powders were recorded, which were subsequently
converted into absorption spectra.
Ab initio calculation of equilibrium geometry and normal vibration frequencies for paracetamol and phenacetin
molecules was carried out using the Gaussian-94/DFT program.

RESULTS AND DISCUSSION

Ab initio quantum-chemical calculation of the structure and vibrational spectra of paracetamol and phenacetin
molecules was carried out in a density functional theory (DFT) approximation using hybrid (B3LYP) potentials [16]. The
DFT method provides the best agreement with experiment for vibrational frequencies and is considered to be the most
suitable technique for spectrum calculations of moderately large molecules [17]. The standard 6-31G* basis set was used.
For geometry optimization for paracetamol, the Cartesian atomic coordinates obtained from structure determination
of the monoclinic modification were specified as initial data [3]. The optimized geometry of paracetamol with the OH group
replaced by the ethyl fragment was given as the initial structure for geometry optimization of phenacetin.
Frequency assignment for normal vibrations was fulfilled by analyzing atomic displacements in Cartesian
coordinates, by calculating the potential energy distribution over internal coordinates (bond lengths and angles, dihedral
angles, and coordinates of bond departure from the molecular plane), and by calculating the potential and kinetic energy
distribution over the molecular fragments –CH3, –C=O, –NH, –C6H4, and –O–H (for paracetamol) or –CH2CH3 (for
phenacetin), or over larger fragments: phenyl, amide, and –O–H or –CH2CH3.
Optimization gave planar conformations (with the phenyl and amide fragments lying in the same plane) for both
molecules (Fig. 1). The calculated normal vibration frequencies and their assignment are given in Table 1.
Theoretical spectra of paracetamol and phenacetin. The X–H high-frequency vibrations above 2900 cm–1 (Table 1)
are completely localized on the corresponding molecular fragments of paracetamol and phenacetin, namely, on –OH, –NH,
–C4H6, –CH3, and –CH2CH3. Judging from the splitting of the stretching frequencies of the amide methyl fragment, the sym-

65
 TABLE 1. Normal Vibration Frequencies and Their Assignment

Paracetamol Phenacetin
Ȟ, theor form Ȟ, Ȟ, mon Ȟ, orth Ȟ, theor form Ȟ, Ȟ, cryst
CDCl3 CDCl3
1 2 3 4 5 6 7 8 9

3661 QOH 3600 3161 3205

3517 QNH 3438 3327 3327 3515 QNH 3436 3283
3167 QPhH 3164 QPhH
3134 QPhH 3147 QPhH 3069 3072
3108 QPhH 3145 QPhH
3093 QPhH 3026 3032 3041 3097 QPhH 3044
3096 Q CH 2
3092 Q CH3 3093 Q CH3 amid
3092 Q CH3 + Q CH 2
3090 Q CH3 2964 3091 Q CH3 amid
3005 Q CH 2 + Q CH3 2983 2981
3000 Q CH3 2927 2926 2940 3001 Q CH3 amid 2930 2927
2956 Q CH3 2900
2920 Q CH3 2882 2884
1779 QC=O + GCNH 1683 1653 1667,1655 1777 QC=O + GCNH 1679 1659,1646
1682 QPh 1624 1610 1622,1610 1677 QPh 1599 1605
1642 QPh + GCNH 1605 1634 QPh + GCNH 1556 1556
1559 GCNH + QPh 1560 1565 1559 1552 GCNH + QPh 1538 1538
1529 GCNH + QPh 1513 1516,1506 1513 1531 GCNH + QPh 1510 1509
1482 G CH 2 + G CH3 1478 1482
1466 G CH3 + QPh 1448 1442 1454 1463 QPh + G CH3 1447 1447
1457 QPh + G CH3 1413 1412
1450 G CH3 + QPh 1438 1451 G CH3 amid
1428 GCOH + QPh 1423 1424 1442 G CH 2 + G CH3
1423 G CH3 1367 1371 1375 1422 G CH3 amid
1412 QPh + G CH3 1394 1393
1391 QPh + G CH3 1370 1369
1355 G CH3 1327 1327 1326 1356 G CH3 amid 1324
1335 QCO + GCNH 1351 G CH 2 + G CH3 1300 1306
1323 G CH3 + QCN 1266
1291 GPhH + QCN 1260 1260 1280 1279 GPhH + QCN 1240 1245
1243 1262 G CH 2 + G CH3 1223
1259 GPhH + QCC 1227 1220 1259 GPhH + QCC
1237 GPhH + QCC 1239 GPhH + QCC
1171 GPhH + GCOH 1170 1172 1169 1154 GPhH 1173 1174
1155 GPhH 1152 G CH 2 + G CH3 1152
1137 QCO + GPh
1103 GPhH + G CH3 1116 1116

66
 TABLE 1 (Continued)
1 2 3 4 5 6 7 8 9
1095 GPhH + G CH3 1102 1107 1106 1099 GPhH + QCO 1107
1015 GCOH + GPhH 1015 1015 1015 GPhH + QCC 1048
1006 GPhH + QCC 1023 1006 GPhH + QCC 1020 1020
984 GPhH + QCN 984 GPhH + QCN 1013 1013
969 GPhH + QCN 968 966 968 GPhH + QCN 968
952 ȤPhH 924 939 GPhH + G CH3 951
937 ȤPhH 923
872 GPh + QCC 890 ȤPhH
855 ȤPhH 856 861 864 GPh + Gamid
830 ȤPhH 837 837 830 ȤPhH 838
799 GPh + Gamid 810,795 797 803 ȤPhH 826
793 GPh + Gamid 785
765 ȤPhH 730 727 783 ȤPhH 744
699 ȤCNH + ȤPhH 715,668 710 705 ȤCNH + ȤPhH
645 GPh + Gamid 650 670 643 GPh + Gamid 646
621 ȤPh + Ȥamid 624 625 630 GPh + Gamid 631
613 ȤPh + Ȥamid 604 608 617 ȤPh + Ȥamid 605
545 b(Ph-amid) 545 b(Ph-amid) 542 546
511 b(Ph-amid) 520 513 535 Gin-plane 520 523
516 b(Ph-amid)
490 b(Ph-amid) 504 508 441 Gin-plane 456
415 Gin-plane 413 415 b(Ph-amid) 417
412 b(Ph-amid) 390 Gin-plane
390 b(Ph-amid) 392 388 382 b(Ph-amid) 398
Note: Q are stretching vibrations; G, deformation vibrations; F, out-of-plane vibrations (deviation of atoms from the
plane of the molecule); b, vibrations corresponding to alteration of the dihedral angle between the planes.

Fig. 1. Ab initio DFT structures of paracetamol (a) and phenacetin (b) molecules.

67
metry of the fragment corresponds to C3v symmetry of the free methyl group in both molecules. The nearly free rotation of
the methyl group noted [9] for the monoclinic modification of crystalline paracetamol is evidently also due to the minor
changes in the parameters of the methyl fragment in the molecular crystal compared to the free methyl group. The vibrations
of the methyl fragment of the ethyl group of phenacetin are partially mixed with the vibrations of the –CH2 fragment.
The 1779 cm–1 (1777 cm–1 in phenacetin) vibrations are localized on the amide fragment. According to the potential
energy distribution over the internal coordinates (more than 57% of which is on the C=O bond), these vibrations may be
assigned to the band that is interpreted in experimental spectroscopy as the first band of the amide group. The potential
energy of these vibrations also has contributions from the variation of the NCH bond angle and of the bond lengths and
angles of the amide methyl group.
The frequencies in the range 1682 cm–1 -1530 cm–1 are due to the stretching vibrations of the phenyl ring; the highest
frequency is completely localized on the phenyl ring in both molecules, and the other frequencies are mixed with the
vibrations of the amide fragment. The largest contribution to the potential energy of these mixed vibrations is from the
variation of the NCH bond angle in the plane of the molecule. For lower frequencies from this range, the contributions from
the amide and phenyl fragments are approximately the same. Based on the potential energy distribution over the internal
coordinates, these vibrations are in a certain sense attributable to the band that is interpreted in experimental spectroscopy as
the second band of the amide group. It should be noted, however, that none of the vibrations in this range is localized on the
amide fragment.
In the range 1500 cm–1 -1300 cm–1, the C–C stretching vibrations of the phenyl group are mixed with the
deformation vibrations of the amide methyl fragment; in phenacetin, they are also mixed with the deformation vibrations of
the ethyl group. The potential energy of the low frequencies of this range has a contribution from the variation of the CO and
CN bonds, but this contribution is too low (20%) to assign any of these frequencies to the stretching vibrations.
The vibrations in the range 1291 cm–1 -950 cm–1 are in-plane deformation vibrations of the C–H bonds of the phenyl
ring, which are mixed [except the 1155 (1154) cm–1 frequencies] with the stretching and deformation vibrations of the amide
fragment (and also with the deformation vibrations of the ethyl group in the case of phenacetin).
Starting from 952 cm–1 for paracetamol and 937 cm–1 for phenacetin, one can observe the out-of-plane deformation
vibrations of the phenyl C–H bonds; these are mixed with the deformation vibrations of the C–C bonds accompanied by the
departure of the carbon atoms from the plane of the phenyl ring. Some of these are completely localized on the phenyl
fragment, while the others are mixed with the deformation and out-of-plane vibrations of the amide group. The frequencies
below 600 cm–1 correspond to the in-plane and out-of-plane (alteration of the dihedral angles between the planes of the
phenyl and amide groups) vibrations of molecules and are not localized on any fragments.
Thus our calculations enabled us to assign the calculated frequencies within the framework of the group frequency
concept, which is conveniently used for interpreting the experimental data.
Experimental spectra of paracetamol and phenacetin. In nonpolar solvents (chloroform and deuterochloroform),
the spectra of paracetamol and phenacetin are not changed by dilution, indicating that no solute–solvent and solute–solute
interactions take place in solution. Figures 2 and 3 show the spectra of the CDCl3 solutions of paracetamol and phenacetin;
Table 1 lists the frequencies. The calculated frequencies of free paracetamol and phenacetin molecules are similar to the
frequencies in the experimental spectra of diluted chloroform and deuterochloroform solutions of these compounds.
Therefore, one can conclude that the calculated molecular parameters (bond lengths and angles, dihedral angles, and force
constants) are similar to the corresponding parameters of free molecules.
Our DFT calculation is slightly better in reproducing the experimental frequencies of paracetamol than the
calculation of [14]. The maximal divergence of the unscaled frequencies is 435 cm–1 in [14] and 96 cm–1 in our calculation. It
seemed useful to give our assignment of the calculated normal vibration frequencies for paracetamol (Table 1), although it
does not differ fundamentally from [14].

68
 Fig. 2. IR spectra of paracetamol and phenacetin in the region of XH vibrations:
1) CDCl3 solution of paracetamol; 2) CDCl3 solution of phenacetin; 3) monoclinic
modification of paracetamol; 4) orthorhombic modification of paracetamol;
5) crystalline phenacetin.

Fig. 3. IR spectra of paracetamol and phenacetin in the range 2000 cm–1 -

400 cm–1: 1) CDCl3 solution of paracetamol; 2) CDCl3 solution of
phenacetin; 3) monoclinic modification of paracetamol; 4) orthorhombic
modification of paracetamol; 5) crystalline phenacetin.

For the spectra of solutions, the assignment of the experimental 3600 cm–1 and 3438 cm–1 absorption bands (ABs) to
the OH and NH stretching vibrations in paracetamol and of the 3436 cm–1 band to the NH stretching vibrations in phenacetin
does not raise any doubt. The weak ABs above 3000 cm–1 are also unambiguously assigned to the C–H stretching vibrations
of the phenyl ring, and the stronger bands above 2800 cm–1 are attributed to the stretching vibrations of the methyl and ethyl
groups (Fig. 2, 1, 2; Table 1).

69
 Fig. 4. Near IR spectra of monoclinic paracetamol (1)
and crystalline phenacetin (2).

In the case of the crystal modifications of the compounds (Fig. 2, 3-5), this range is much more difficult to interpret.
The spectra of crystalline powders differ significantly from the spectra of solutions. First, the intermolecular interactions are
most conspicuous in this spectral region because of the displacement and broadening of the absorption bands caused by
hydrogen bonding. Second, interpreting the spectral region above 2500 cm–1 is complicated by the presence of overtones and
composite frequencies. In view of the Fermi resonance, the intensity of these bands may be anomalously high. The presence
of anharmonic frequencies in great numbers in the spectra of paracetamol and phenacetin is also confirmed by the
experimental spectra of the crystalline powders in the near IR region (Fig. 4).
According to our calculation, the intense 1683 cm–1 band of a paracetamol solution and the 1679 cm–1 band of a
phenacetin solution (nonpolar solvents in both cases) correspond to the first band of the amide group, more than 57% of their
potential energy reflecting the state of the C=O bond. In the spectra of the two crystal modifications of paracetamol and
crystalline phenacetin, the frequency of this vibration is 20 cm–1 -30 cm–1 lower than that in the spectra of the molecular
forms. For the monoclinic modification of paracetamol, this is a single vibration band (1654 cm–1); for the orthorhombic
modification, there are two bands (1667 cm–1 and 1656 cm–1). In the spectrum of crystalline phenacetin, this is the 1659 cm–1
band with a shoulder at 1646 cm–1.
In the range 1625 cm–1 -1000 cm–1, the spectra of the solutions and crystal forms of paracetamol (Fig. 3, 1, 3, 4) and
phenacetin (Fig. 3, 2, 5) differ mainly in the relative intensity and in the number of absorption bands, while the position of the
fundamental bands changes insignificantly and the experimental spectra are rather close to the theoretical spectra (Table 1).
Below 1000 cm–1, the spectra of solutions could not be obtained for any of the two compounds because of solvent
absorption and the narrow spectral ranges of solvent transparency, leading to unreliable spectrum subtraction. Therefore in
the range 1000 cm–1 -400 cm–1, Fig. 3 shows only the spectra of the crystal forms of the compounds. The assignment of the
relevant absorption bands in the spectra of the crystalline samples based on the assignments in the theoretical spectra seems to
be quite correct because of good agreement between the theoretical and experimental frequencies (Table 1).
Spectral features indicative of intermolecular interactions. The molecular crystals of paracetamol and phenacetin
are suitable model systems for investigating intermolecular interactions. The paracetamol molecule includes two potential
donor (N–H and O–H) and two acceptor (C=O and H–O) groups, while the phenacetin molecule has one donor (N–H) and
one acceptor (C=O) groups, which can be involved in hydrogen bonding in molecular crystals. The OH group is both proton
donor and acceptor (–NH…OH…O=C–), while the NH group is a proton donor alone.
The difference between the optimized parameters of the free paracetamol and phenacetin molecules (Fig. 1) and the
experimental bond lengths and angles of their crystal forms is associated with the presence of hydrogen bond systems in the
crystals of these compounds [2-13, 20]. The paracetamol molecule is planar in the free state, but not in molecular crystals,
where the angle between the planes of the amide and phenyl fragments is about 22q. This may be due to the fact that both OH

70
and NH groups form hydrogen bonds of varying strength [14, 18]. In the phenacetin molecule, there are no OH groups, NH
being the only group involved in hydrogen bonding. This molecule is planar in the free state and in molecular crystal [20].
According to neutron diffraction data obtained in precision experiments [11], intermolecular hydrogen bonding leads
to lengthening of OH and NH bonds in the crystal forms of paracetamol (Fig. 1).
The difference between the spectra of crystalline powders and those of diluted solutions of paracetamol and
phenacetin, which is especially conspicuous in the region of the X–H stretching vibrations, is a spectral indication to the
presence of a system of hydrogen bonds in paracetamol and phenacetin crystals.
Based on the data of [2-13] about the presence of a system of hydrogen bonds (–NH…OH…O=C–) in molecular
crystals of paracetamol and using the results of spectral studies at elevated hydrostatic pressures and reduced temperatures
[18, 19], we suggest the following assignment of experimental frequencies in the spectra of the crystal modifications of
paracetamol and phenacetin. The narrow 3324 cm–1 and 3327 cm–1 bands in the monoclinic and orthorhombic modifications
of paracetamol, respectively, and the 3283 cm–1 band in the spectrum of phenacetin are assigned with confidence to the QNH
stretching vibrations. The broader bands with maxima at 3161 cm–1 and 3205 cm–1 in the monoclinic and orthorhombic
modifications of paracetamol are attributed to the QOH mode.
The large shifts of these frequencies compared to the spectra of solutions, as well as the complex shape of the
absorption contours, point to the presence of a system of strong hydrogen bonds (NH…O and OH…O) in the molecular
crystals of both modifications of paracetamol and NH…O in the molecular crystals of phenacetin. This agrees with the results
of diffraction studies [2-5, 7-13] including studies at reduced temperatures and elevated pressures.
The lowering of the QXH frequency due to hydrogen bonding compared to the spectrum of the free molecule is a
direct measure of hydrogen bond strength. Therefore, one can assume that in the monoclinic modification of paracetamol, the
–O–H…O hydrogen bonds ('QOH = 440 cm–1) are slightly stronger than those in the orthorhombic modification ('QOH =
400 cm–1). This agrees with the conclusions based on the diffraction analysis of the geometrical parameters of hydrogen
bonds [13, 18].
Similarly, from the shifts of the QNH frequencies ('QNH = 110 cm–1) one can assume that in both crystal modifications
of paracetamol, the –N–H…O hydrogen bonds are approximately equal in stability and are less stable than the N–H…O
hydrogen bonds in phenacetin crystals ('QNH = 153 cm–1). As intermolecular hydrogen bonding in the latter is only possible to
NH groups, one would expect that the NH stretching vibration frequency will decrease more drastically compared to the
spectrum of the free molecule. Indeed, in the crystal forms of paracetamol, the QNH frequency has a 44 cm–1 smaller shift than
in phenacetin crystals relative to the position of this frequency in the molecular state that is free from hydrogen bonds.
The C=O bond length was calculated to be 1.226 Å (Fig. 1) for the optimized structure of free paracetamol and
phenacetin molecules, 1.235 Å for monoclinic paracetamol, and 1.241 Å for crystalline phenacetin. The larger C=O bond
length and the correspondingly decreased QC=O frequency unambiguously indicate that hydrogen bonding leads to a
redistribution of electron density.
In the spectra of both crystalline modifications of paracetamol and crystalline phenacetin, the frequencies in the
range 1660 cm–1 -1640 cm–1, reflecting the state of the C=O bond (denoted for simplicity QC=O), are 20 cm–1 -30 cm–1 lower
than in the spectra of the molecular form. This is another indication to strong intermolecular interactions involving the C=O
bond in crystals.
We traced the effect of intermolecular interactions on the QC=O frequency in the spectra of DMSO solutions of
paracetamol and phenacetin. The QC=O frequency was slightly shifted in both paracetamol and phenacetin solutions depending
on the solution concentration; it was roughly the same — around 1670 cm–1, which is lower than in the molecular form and
higher than in crystal forms. Probably, the formation of hydrogen bonds between the S=O group of DMSO and the NH and
OH groups of paracetamol, as well as the NH group of phenacetin, also leads to an electron density redistribution on the C=O
bond, which is manifested as the decreased QC=O frequency.

71
 The larger shift of QC=O in the monoclinic form of paracetamol versus the orthorhombic form relative to the same
frequency in a molecule that is free from hydrogen bonds also points to stronger hydrogen bonds in the monoclinic
modification of paracetamol.
The spectral features responsible for hydrogen bonding in the crystals of the two polymorphic modifications of
paracetamol and phenacetin recorded at low temperatures and elevated pressures will be discussed in our next communication
[19].

CONCLUSIONS

Ab initio quantum-chemical calculations of the geometry and vibrational spectra of para-acetaminophenol

(paracetamol) and para-acetylphenitidine (phenacetin) have been carried out.
Based on the similarity between the frequencies in the calculated spectra of free paracetamol and phenacetin
molecules and the frequencies in the experimental spectra of solutions of these compounds in nonpolar solvents, it is
concluded that the calculated molecular parameters (bond lengths and bond and dihedral angles) agree with the corresponding
parameters of free molecules.
The calculated distributions of the potential and kinetic energies over fragments of the two molecules (–CH3, –C=O,
–NH, C6H4, CO, and OH for paracetamol and CH2CH3 for phenacetin) permitted us to determine the spectral ranges
in the experimental spectra corresponding to the vibrations of these fragments.
The spectra of the solutions differ significantly from the spectra of the crystalline powders, especially in the range
2800 cm -3600 cm–1 corresponding to the OH, NH, and CH stretching vibrations of paracetamol and NH and CH stretching
–1

vibrations of phenacetin. This spectral region contains overtones. In the range 400 cm–1 -10000 cm–1 for crystalline powders, a
spectrum of anharmonic frequencies has been recorded.
The effect of hydrogen bonds on the frequencies has been investigated. It has been shown that the intermolecular
hydrogen bonds formed by the OH…O and NH…O groups of paracetamol and NH…O=C of phenacetin play an
essential role in molecular crystals of these compounds.
Comparison of the calculated structural parameters of free molecules of paracetamol and phenacetin and comparison
of these values with bond lengths and bond and dihedral angles in crystal forms have made it possible to evaluate structural
changes due to intermolecular interactions.
This work was supported by CRDF and RF Ministry of Education grant REC-008, by DLR grant RUS-131-98, and
by RF Ministry of Education (Integration Program) grants 274, Ch0069, and E-00-5.0-81.

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