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Charge density and computational study of benzhydrol and benzhydrol-d10
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Journal of Molecular Structure 875 (2008) 173–182 www.elsevier.com/locate/molstruc
Charge density and computational study of benzhydrol and benzhydrol-d10 Chong Zheng *, Heike Hofstetter *, Oliver Hofstetter Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA Received 12 October 2006; received in revised form 17 April 2007; accepted 18 April 2007 Available online 29 April 2007
Abstract The structures and charge distribution of benzhydrol (C13H12O) and its deuterated equivalent benzhydrol-d10 (C13D10H2O) were studied by X-ray diffraction. Raman and IR spectra obtained for the compounds and ab initio calculations help to understand the structural features of these molecules. 2007 Elsevier B.V. All rights reserved. Keywords: Benzhydrol; Diphenylmethanol; Charge density; Vibrational frequencies
1. Introduction Benzhydrol (i.e., diphenylmethanol), C13H12O, is an important molecule in chemistry and biology whose structure has been reported previously by Ferguson and coworkers [1]. It has been used as a model target in many metal-catalyzed hydrogenation reactions [2]. Its analogs have shown strong biological inhibitory activity in the dopamine transporter and, thus, are potential therapeutic agents for treatment of cocaine addiction [3]. Recent results suggest that suitably raised antibodies can distinguish between benzhydrol and its deuterated analog [4]. Because deuterium isotope effects on noncovalent interactions in chemical and biological systems are based on the electronic and, in turn, the molecular volume, polarity and vibrational features of the isotopic molecules [5], it is important to understand their structural and electronic details. Lately, it has been shown that substitution of hydrogen atoms by deuterium affects the basicity and stereochemical properties of amines [6], changes the enzymatic activity of tyrosine hydroxylase [7,8] and phenylalanine hydroxylase [9], shifts *
Corresponding authors. Tel.: +1 815 753 6871; fax: +1 815 753 4802. E-mail addresses: [email protected] (C. Zheng), [email protected] (H. Hofstetter). 0022-2860/$ - see front matter 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2007.04.034
the ESR proton hyperfine coupling constants [10], and alters the hydrogen bond strength in the base pairs in DNA and RNA [11]. The deuterium isotope effects can be enhanced under high pressure [12], and the effect on structural configurations can be predicted from computational studies [13]. Effects on molecular structures have also been observed. For example, deuteration can result in a smaller unit cell volume [14]. In this contribution, we report X-ray charge density, IR and Raman spectroscopy as well as computational studies of benzhydrol and its deuterated analog, benzhydrol-d10. More detailed structural information promises to further better understanding of the chemical and biological properties of these compounds. 2. Experimental section 2.1. Preparation Benzhydrol (powder, Alfa Aesar, 99%), 1, and its deuterated equivalent benzhydrol-d10, 2, were crystallized by the liquid diffusion method. Compound 2 was prepared as follows: benzophenone-d10 was synthesized according to the procedure by Makino et al. [15]. In short, benzoylchloride-d5 was dissolved in benzene-d6 (99% deuterated) and treated with trifluoromethanesulfonic acid (all chemicals
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were purchased from Sigma, St. Louis, MO). The reaction was carried out at 80 C for 18 h under reflux. After cooling, the reaction mixture was washed several times with water and the white product was crystallized from benzene. Reduction of benzophenone-d10 was then carried out in anhydrous ethanol with NaBH4. The temperature was maintained at <35 C and the mixture was allowed to react for 17 h. The product benzhydrol-d10 was precipitated on ice using 10% HCl and recrystallized from hexane. The compounds have two rotational angles /1 and /2 associated with the two phenyl rings. These angles are important in determining the conformation of the compounds.
φ1
OH φ 2 C H
OH C H D D
D D D
D D
D
1
D
2
D
Approximately 2 mL of the saturated solutions of compounds 1 and 2, respectively, in methylene chloride (CH2Cl2) were pipetted into glass tubes of ca. 3 mm in diameter. An equal amount of cyclohexane (C6H12) was
Table 1 Data collection strategy Run#
2h ()
x ()
/ ()
# of Frames
Exposure time (s)
0 1 2 3 4 5 6 7 8 9 10 11 12
25 25 25 25 50 50 50 50 75 75 75 75 25
25 25 25 25 50 50 50 50 75 75 75 75 25
0 90 180 270 0 90 180 270 0 90 180 270 0
606 606 606 606 606 606 606 606 606 606 606 606 50
15 15 15 15 30 30 30 30 45 45 45 45 15
The scan axis is x with frame width = 0.3, v = 54.77. The sample-to-detector distance was 4.943 cm. Run #12 was used for crystal decay estimate. No decay was detected.
Table 2 Crystal data and structure refinement for benzhydrol (H10) and benzhydrol-d10 (D10) Compound/refinement
H10/CV
D10/CV
H10/CD
D10/CD
Empirical formula Formula weight Temperature (K) ˚) Wavelength (A Crystal system Space group ˚) Unit cell dimensions (A a b c ˚ 3) Volume (A Z Density (calculated) (Mg/m3) Absorption coefficient (mm1) Index ranges Reflections collected Independent reflections Completeness to theta () Absorption correction Refinement method Final R indices [I > 2sigma(I)]
C13 H12 O 184.23
C13 H2 D10 O 194.29 203 (2) 0.71073 Orthorhombic P22121 (No. 18)
C13 H12 O 184.23
C13 H2 D10 O 194.29
5.0945 18.784 21.181 2027.0
5.0772 (3) 5.0945 18.6499 (9) 18.784 21.032 (1) 21.181 1991.5 (2) 2027.0 8 1.296 1.207 0.076 0.075 6 h 6, 22 k 22, 25 l 25 30810 34462 3474 [R(int) = 0.0418] 99.9%
1.207 0.075
(7) (2) (3) (4)
34462 3554 [R(int) = 0.0263] 25.00 Semi-empirical from equivalents Full-matrix least-squares on F2 R1 = 0.0317 0.0398 wR2 = 0.0828 0.1028
Refinement type: CV, conventional; CD, multipole charge density refinement.
(7) (2) (3) (4)
5.0772 (3) 18.6499 (9) 21.032 (1) 1991.5 (2) 1.296 0.076 30810
Multipole with lmax = 5 0.0253 0.0324 0.0462 0.0723
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then gently added to the tubes. The nonpolar cyclohexane solvent in the sealed tubes was allowed to slowly diffuse into the polar methylene chloride solution resulting in a reduced solubility of the polar compounds. After one week, needle crystals of ca. 5 mm in length were obtained. 2.2. Charge density study Several crystals of the compounds were indexed on a Bruker SMART CCD diffractometer using 40 frames with an exposure time of 20 s per frame. All crystals exhibited the same orthorhombic lattice. One crystal with good reflection quality from each compound was chosen for data collection. A total of 7322 frames were collected for each compound to ensure adequate data redundancy. The experimental parameters used for the charge density study are listed in Table 1. An empirical absorption correction using the program SADABS [16] was applied to all reflections. The structure was solved with direct methods using the SIR97 program [17]. A full matrix least-square refinement on F2 was carried out using the SHELXTL program [18]. The multipole refinement for the charge density study was carried out using the XD program [19]. The unit cell information and refinement details are reported in Table 2. The atomic positions and equivalent isotropic displacement parameters are listed in Table 3. 2.3. Spectroscopy Raman spectra were recorded for the same single crystals used for the X-ray data collection on a Renishaw System 2000 microfocus Raman spectrometer (Renishaw, System 2000, UK). The IR spectra were obtained on a Bruker Vector 22 instrument (Bruker, Billerica, MA). 2.4. Computational study The energy levels, total energy and vibrational modes of the molecules were calculated using the ab initio Gaussian03 package [20]. The RHF/6-31G* model was used for all calculations. The deformation density and Laplacian of the electron density were calculated with the program MOLDEN [21]. 3. Results and discussion 3.1. Crystal structure The structure of benzhydrol is shown in Fig. 1. The deuterated benzhydrol-d10 has the same structure. The average atomic RMS difference between the benzhydrol structure ˚ . The unit and the benzhydrol-d10 molecule is only 0.04 A cell volumes of them, however, are slightly different with ˚ 3 for benzhydrol and 1991.5(2) A ˚ 3 for benzhy2027.0(4) A drol-d10. The 2% volume decrease can be a result of larger polarity of the deuterated compound producing a tighter hydrogen bond network, since it is known that deuteration
175
Table 3 ˚ · 104) and equivalent isotropic displacement Atomic coordinates (A ˚ 2 · 103) for benzhydrol and benzhydrol-d10 parameters (A x
y
z
U(eq)
Benzhydrol O (1) C (11) C (111) C (112) C (113) C (114) C (115) C (116) C (121) C (122) C (123) C (124) C (125) C (126) O (2) C (21) C (211) C (212) C (213) C (214) C (215) C (216) C (221) C (222) C (223) C (224) C (225) C (226)
6334 6599 4538 3333 1501 866 2079 3898 6396 4428 4263 6055 8017 8191 1289 1406 734 2118 3999 4522 3152 1268 1230 702 799 971 2866 3002
(2) (3) (3) (4) (4) (4) (4) (3) (3) (4) (4) (4) (4) (4) (2) (3) (3) (3) (4) (4) (4) (3) (3) (4) (4) (4) (4) (3)
8288 8075 8476 9088 9456 9223 8622 8250 7269 6884 6152 5787 6159 6895 8297 8061 8447 9023 9380 9171 8602 8244 7251 6875 6134 5764 6131 6872
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
311 340 727 492 855 1460 1699 1335 407 99 160 537 845 778 899 1548 1921 1670 2025 2644 2902 2545 1592 1265 1305 1673 2003 1961
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
39 32 32 41 51 46 43 39 32 40 48 49 49 40 38 32 31 36 42 44 45 39 32 42 51 51 50 40
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
Benzhydrol-d10 O (1) C (11) C (111) C (112) C (113) C (114) C (115) C (116) C (121) C (122) C (123) C (124) C (125) C (126) O (2) C (21) C (211) C (212) C (213) C (214) C (215) C (216) C (221) C (222) C (223) C (224) C (225) C (226)
3657 3412 5469 6672 8513 9136 7931 6098 3597 5578 5734 3950 1982 1805 8704 8598 10723 12106 13993 14514 13146 11264 8769 10694 10808 9026 7126 6985
(3) (4) (4) (5) (5) (5) (5) (4) (4) (4) (5) (5) (5) (4) (3) (4) (4) (4) (4) (5) (5) (4) (4) (5) (5) (5) (5) (4)
1709 1924 1521 911 543 775 1377 1750 2729 3114 3848 4215 3841 3103 1700 1937 1551 974 619 829 1398 1758 2747 3126 3867 4237 3869 3128
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
9688 10342 10729 10491 10855 11461 11703 11339 10407 10100 10159 10534 10842 10777 9101 8451 8076 8329 7970 7354 7095 7452 8407 8734 8697 8323 7995 8038
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
45 39 38 48 58 53 50 44 39 46 53 55 55 46 45 39 38 44 48 50 51 46 38 49 56 57 56 47
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
of hydrocarbons will generally result in a more polar and thus less lipophilic molecule [5]. This effect has been
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Fig. 1. Ellipsoid (50% probability) plot of the structure of benzhydrol. There are two molecules in the asymmetric unit. Molecule 1 is on the left side and molecule 2 on the right.
observed previously in the tetracyanoanthraquinodimethane (TCAQ) structure [14]. Using the reported average lattice constants for TCAQ and TCAQ-d8, the volumes ˚ 3, respectively. The are calculated to be 741.8 and 737.8 A difference corresponds to approximately 1% decrease in unit cell volume upon deuteration. For the benzhydrol structure, there are two molecules in the asymmetric unit. A hydrogen bond is formed between the hydroxyl groups of the two molecules. This hydrogen bond donor is also shared with an acceptor of another molecule in the next unit cell. In this fashion, the hydrogen bond propagates along the a-axis as demonstrated in Fig. 2. The two molecules in the asymmetric unit differ in the dihedral angles associated to the phenyl groups as depicted in Fig. 3. The O1–C11–C111–C112 angle is 18.4(2) in molecule 1, but the corresponding angle O2–
Fig. 2. Crystal packing of benzhydrol. Extended hydrogen bonds (green) are formed between molecules along the a-axis. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
C21–C211–C212 is 11.2(2) in molecule 2. Similarly, the dihedral angle of the second phenyl ring in molecule 1, O1–C11–C121–C122, is 45.8(2), while the related angle O2–C21–C221–C222 of molecule 2 is 48.2(2). These two conformations correspond to points 1 and 2 on the ab initio potential surface in Fig. 4. They are related by a pseudo inversion center. This surface was calculated using the rigid molecule approximation, keeping other degrees of freedom frozen while varying the two dihedral angles /1 and /2 which are defined in drawing 1. The structural difference between these two molecules is likely due to the crystal packing, because the ab initio optimized structure of an isolated benzhydrol molecule would have the O1– C11–C111–C112 and O2–C21–C221–C222 angles equal to 5.42 and 54.96, respectively. Because of their structural difference, the energies of the two molecules differ slightly, with molecule 2 being more stable by ca. 0.2 eV according to our ab initio calculation with optimization on all degrees of freedom minus the two angles. The stabilization comes from a better hyperconjugation interaction of the C21–O2 bond with the p orbitals of the second phenyl ring. The interaction would be even better if the O2–C21–C221–C222 dihedral angle were 90, but this configuration would diminish another hyperconjugation interaction between the C21–H21 bond and the p system of the first phenyl ring with the dihedral angle H21–C21–C211–C212 equal to 104.6. The optimized structure has the best compromise between these two types of hyperconjugation interaction with the two angles at 55.0 and 123.4, respectively. As a consequence the optimized structure is about 2.9 eV more stable than molecule 2 of benzhydrol. Because of the rotations from their idealized angle of 0 or 90, the two phenyl rings on molecule 1 or 2 are not related by a symmetry operation. This makes the molecule similar to a chiral one. The initial refinement of the benzhydrol-d10 data results in a Flack parameter of 0.6 ± 1.4 sug-
Fig. 3. Overlay comparison of molecule 1 (blue) and molecule 2 (red) of benzhydrol. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
C. Zheng et al. / Journal of Molecular Structure 875 (2008) 173–182
Fig. 4. Potential energy surface of benzhydrol calculated by the ab initio method. /1 and /2 are the two phenyl rotation angles defined in drawing 1. Points 1 and 2 correspond to the conformations of molecules 1 and 2 in the unit cell.
gesting the wrong absolute configuration. Because of the large uncertainty of the parameter, the determination is not conclusive. However, the charge density study in the following section also revealed signs of wrong absolute configuration. Therefore, the initial structure was inverted and Table 3 presents the coordinates of the inverted structure. For benzhydrol, the Flack parameter is 0.09 and the absolute configuration is unambiguous. 3.2. Charge density The static deformation densities Dq(r) of benzhydrol and benzhydrol-d10 are shown in Fig. 5. For clarity, only the regions around the first phenyl group and the hydroxyl group are plotted. The deformation density around the second phenyl group is similar. The static deformation density is defined as the difference in electron densities between a molecule and the sum of its corresponding spherical atoms [22]: X DqðrÞ ¼ qmol ðrÞ qk ðr rk Þ k
Therefore, the maxima of Dq(r) usually correspond to bonding regions. As seen in the top left in Fig. 5, the Dq(r) of benzhydrol shows maxima along the phenyl ring indicating bonding interaction. The top right of the figure illustrates the Dq(r) for benzhydrol-d10 structure of the initial refinement. There is a sign of an inverted phase compared to that of benzhydrol. After a structure inversion under which molecule 1 is mapped to molecule 2, the phase follows that of benzhydrol as shown at the center of Fig. 5. The bottom of the figure depicts the calculated Dq(r)’s for the two molecules using the ab initio method. These two Dq(r)’s are identical as expected. In general, the experimental Dq(r) of
177
benzhydrol-d10 reveals more polar features than that of benzhydrol. The Dq(r) of benzhydrol is more uniform along the C–C bonds of the phenyl ring. The variation in the experimental Dq(r)’s of the two compounds may come from differences in crystal quality and/or polarity due to isotope effect [5]. It is also interesting to note that near the center carbon C1, the C1–O1 bond is much more polar as predicted by the theoretical calculations. The Laplacian of the electron densities, $2q(r), of the two molecules are plotted in Fig. 6. The Laplacian represents local concentrations, with $2q(rc) < 0 indicating shared interactions and $2q(rc) > 0 closed shell interaction at an electron density critical point rc [23]. Fig. 6 reveals a more continuous delocalized p interaction on the phenyl ring for benzhydrol. The topological features and phases of $2q(r) of the two molecules also support the conclusion that the inverted benzhydrol-d10 structure has the correct absolute configuration. Beside this, the main topological features of $2q(r) of the two molecules are very similar as expected. 3.3. IR spectrum The IR spectra for benzhydrol and benzhydrol-d10 are shown in Fig. 7. The main difference between the spectra of these two compounds is the shift of the aromatic C–H stretching frequencies. In benzhydrol the frequencies are around 3026–3084 cm1. The corresponding peaks are shifted to 2276 cm1 for benzhydrol-d10. The down shift is as expected from the square p root of the mass ratio of hydrogen versus deuterium (H/D) = 0.707. Our ab initio calculation confirms that these peaks are indeed the aromatic C–H and C–D stretching modes. Table 4 lists the calculated IR frequencies, assignments and relative intensities of the two compounds in their experimental conformations. It is well-known that ab initio HF methods usually overestimate the frequency by 10–15% [24]. In addition, the experimental crystal structures are usually not at the potential minima of the corresponding gas phase configuration, resulting in an additional overestimate of frequencies. Therefore, it is customary to scale the calculated frequencies by a factor normally set to 0.89 [24]. The frequencies in Table 4 are the unscaled values. In Table 4, most of the aromatic C–H p frequencies in benzhydrol are down shifted by the (H/D) factor in benzhydrol-d10. However, because of the low symmetry of the molecule, the C–H stretching modes are also coupled to the collective motions of the phenyl C atoms. Therefore p the down shift factor is usually slightly less than the (H/D) value of p 0.707 or the reduced mass scaling (lCH/lCD) of 0.734 as the 3084 cm1 peak in benzhydrol attests. 3.4. Raman spectrum Fig. 8 is the Raman shift of benzhydrol taken at different rotation angles of the needle crystal with respect to the
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C. Zheng et al. / Journal of Molecular Structure 875 (2008) 173–182
Fig. 5. Deformation density Dq(r) of benzhydrol (top left) and benzhydrol-d10 (top right) at the first phenyl group and the hydroxyl group. The center shows Dq(r) of benzhydrol-d10 after a structural inversion in the refinement. Positive regions are in blue and negative in red. Contours of negative Dq(r) are ˚ 3 intervals starting at 0.02 e/A ˚ 3. Contours of positive Dq(r) are in logarithmic scale starting at 0.001 e/A ˚ 3 with increment of 2 at each drawn at 0.001 e/A interval. The bottom two drawings are theoretical Dq(r)’s calculated using the ab initio method. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Raman polarization vector. Because of the low symmetry of the molecule, the Raman intensity is less sensitive to
the rotational angle as compared to other molecules of higher symmetry. The most pronounced change of inten-
C. Zheng et al. / Journal of Molecular Structure 875 (2008) 173–182
179
Fig. 6. $2q(r) of Benzhydrol (top left) and benzhydrol-d10 (top right) at the first phenyl group and the hydroxyl group. Positive regions are in blue and ˚3 negative in red. The center shows $2q(r) of benzhydrol-d10 after a structural inversion in the refinement. Contours of negative $2q(r) are drawn at 0.2 e/A 5 2 5 ˚ ˚ intervals starting at 4.0 ending at 0.1 e/A . Contours of positive $ q(r) are in logarithmic scale starting at 0.1 e/A with increment of 2 at each interval. The bottom two drawings are theoretical $2q(r)’s calculated using the ab initio method. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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C. Zheng et al. / Journal of Molecular Structure 875 (2008) 173–182
IR Spectrum of Benzhydrol (H10) and Benzhydrol-d10 (D10) 0.8
H10 D10
Transmittance (%)
0.7
Benzhydrol
0.6
0.5 3084 3059 3026 C-H
0.4
0.3 3389 O-H
0.2 2276 C-D
0.1 4000
3500
3000
Table 4 Calculated IR frequencies and relative intensities (RI) of benzhydrol and benzhydrol-d10
2500
2000
1500
1000
500
-1
Wavenumber (cm ) Fig. 7. IR spectrum of benzhydrol (black line) and benzhydrol-d10 (red line). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
sity is observed for the two peaks at 1000 and 1022 cm1. Their ratio changes from 17 to 5 when the rotation angle moves from 90 to 0. In other words, the 1000 cm1 peak decreases while the one at 1022 cm1 increases with decreasing angle. The highest peak at 1000 cm1 corresponds to the calculated Raman peak with the largest relative intensity of 48 at 1092 cm1 in Table 5. Its vibrational mode is depicted on the left panel in Fig. 9. This mode involves a collective motion of the first phenyl ring, and its dipole derivative vector is approximately parallel to the C1–O bond. Since the crystal needle is parallel to the a-axis along which the extended hydrogen bonds propagate, this dipole derivative vector is approximately perpendicular to the needle axis. Thus the corresponding Raman intensity is highest when the polarization vector is perpendicular to the crystal needle axis. The next calculated peak is at 1098 cm1. Its mode is shown on the right side of Fig. 9. It is a collective motion in the second phenyl ring coupled to the H–C1–C scissoring motion around the center C1 atom. The dipole derivative vector is approximately parallel to the phenyl rings, thus perpendicular to that of the 1092 cm1 mode. The Raman intensity is therefore highest when the polarization vector is parallel to the crystal needle axis. Because both peaks involve collective motion of the phenyl rings, isotope down shifts are expected for them in benzhydrol-d10. Indeed the shifts shown in Fig. 10 are most pronounced at these frequencies. The highest peak at 1000 cm1 in benzhydrol is down shifted to 957 cm1, which equals a decrease by a factor of 0.96. As this mode is a collection motion involving both C and H atoms in the first phenyl ring, the down p shift factor is not quite as large as the mass ratio (H/D) or p (lCH/lCD) dictates.
Benzhydrol-d10
Frequency (cm1)
Mode
RI
Frequency (cm1)
Mode
RI
672 702 745 764 797 809 855 908 941 980 987 1014 1034 1085 1092 1098 1110 1153 1158 1192 1290 1309 1480 1499 1540 1545 1723 1743 4187 4235 4271 4299 4506 4519 4526 4568 4584 4912 5429
/ / H–C–C / / / / H–C–C / / + H–C1–C H–C–C / / H–C1–C / H–C1–C H–C1–C H–C–C H–C–C O–C1–H C1–C C1–C C–C C–C C–C C–C C–C C–C C–H C1–H C–H C–H C–H C–H C-H C–H C–H C–H O–H
3 2 5 6 13 1 2 9 18 11 8 4 2 15 7 12 40 5 2 8 23 22 4 18 3 4 5 2 8 22 7 14 4 5 11 3 8 4 84
653 690 725 729 739 753 781 786 792 848 885 901 953 1002 1059 1078 1107 1165 1243 1280 1302 1450 1464 1534 1739 1754 1756 2916 2986 3008 3118 3263 3269 3418 3449 4345 5231
/ D–C–C / / D–C–C / / / / / D–C–C / + H–C1–C / / + H–C1–O / H–C1–C O–C1 H–O–C1 C–C C–C C1–C C–C C–C C–C + C1–C C–C C–C C–C C–D C–D C–D C–D C–D C–D C–D C–D C1–H O–H
5 2 1 1 9 6 3 4 13 5 2 2 9 5 3 24 56 10 2 19 19 12 5 2 5 1 1 8 4 9 8 5 4 3 4 20 88
Vibrational mode assignment: /, phenyl ring collective motion; H–C–C, scissoring motion involving the H and C atoms in the phenyl ring; H–C1– C, scissoring motion involving the H and center C1 and phenyl C atoms; / + H–C1–C, phenyl collective motion plus H–C1–C scissoring motion; C–C, bond stretching motion in the phenyl ring; etc. Frequencies with relative intensity less than 1 are omitted.
4. Conclusions The crystal structures and charge distribution of benzhydrol and benzhydrol-d10 have been investigated by Xray diffraction techniques. The structures and topological features of electron densities of these two molecules are similar. Spectroscopic and computational study revealed that the 3026–3084 cm1 IR peaks are associated with aromatic C–H stretching and thus demonstrate strongest iso-
C. Zheng et al. / Journal of Molecular Structure 875 (2008) 173–182
Table 5 Calculated Raman frequencies and relative intensities (RI) of benzhydrol and benzhydrol-d10
Raman Spectrum of Benzhydrol 1000
160000
Intensity (Arbitrary Unit)
140000 120000 100000 80000
Benzhydrol
o
Rotation ( ) 90 67.5 45 22.5 0 1022
60000 40000 20000 0 -20000 500
1000
1500
2000
-1
Raman Shift (cm ) Fig. 8. Raman spectrum of benzhydrol taken at different rotation angle between the needle crystal and the Raman polarization vector.
Raman Spectrum of Benzhydrol (H10) and Benzhydrol-d 10 (D10)
Intensity (Arbitrary Unit)
160000
H10 at 90 degree D10 at 90 degree
140000 1000
120000 957
100000 80000 60000 40000 20000 0 -20000
500
181
1000
1500
2000
-1
Raman Shift (cm )
Benzhydrol-d10
Frequency (cm1)
Mode
RI
Frequency (cm1)
Mode
RI
236 288 300 331 360 452 568 615 764 809 817 941 980 987 1014 1034 1085 1092 1098 1110 1153 1158 1192 1223 1290 1309 1718 1723 1737 1743
/ / / / / / H–C–C H–C–C + H–O–C1 / / / / / + H–C1–C H–C–C / / H–C1–C / H–C1–C H–C1–C H–C–C H–C–C O–C1–H C–C C1–C C1–C C–C C-C C–C C–C
4 4 3 3 6 4 3 6 2 6 3 6 9 8 7 10 6 48 5 4 2 3 16 3 7 5 4 10 9 23
165 236 309 362 489 622 629 739 753 781 786 792 885 901 953 1002 1054 1059 1078 1107 1165 1255 1280 1302 1735 1739 1754 1756 2916 2986 3008 3057 3118
/ H-C1-O / / / / + H–C1–O / + H–C1–C D–C–C / / / / D–C–C / + H–C1–C / / + H–C1–O / / H–C1–C O–C1 H–O–C1 C–C C–C C1–C C–C C–C C–C C–C C–D C–D C–D C–D C–D
3 2 4 3 2 2 2 3 3 7 5 3 10 8 3 8 33 16 8 4 19 2 9 4 4 7 22 11 33 19 41 18 44
Vibrational mode assignment: /, phenyl ring collective motion; H–C–C, scissoring motion involving the H and C atoms in the phenyl ring; H–C1– C, scissoring motion involving the H and center C1 and phenyl C atoms; / + H–C1–C, phenyl collective motion plus H–C1–C scissoring motion; C–C, bond stretching motion in the phenyl ring; etc. Frequencies with relative intensity less than 2 are omitted.
Fig. 9. Raman spectrum of benzhydrol (H10, black line) and benzhydrold10 (D10, red line) with the needle crystals perpendicular to the Raman polarization vector. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 10. Calculated vibrational modes at 1092 cm1 (left) and 1098 cm1 (right). The atomic vibration vectors are indicated by the blue arrows and the dipole derivative vector is represented by the yellow arrow for each mode. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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tope effect. Similarly, the 1000 cm1 peak in the Raman spectrum is due to a collective motion in the first phenyl ring of benzhydrol and shows strong polarization as well as isotopic effects. Acknowledgment Parts of this work was supported by the Research Corporation (Research Innovation Award No. RI0715). References [1] G. Ferguson, C.D. Carroll, C. Glidewell, C.M. Zakaria, A.J. Lough, Acta Crystallogr. B 51 (1995) 367. [2] G. Venkatachalam, R. Ramesh, S.M. Mobin, J. Organomet. Chem. 690 (2005) 937. [3] D. Simoni, M. Rossi, V. Bertolasi, M. Roberti, D. Pizzirani, R. Rondanin, R. Baruchello, F.P. Invidiata, M. Tolomeo, S. Grimaudo, S. Merighi, K. Varani, S. Gessi, P.A. Borea, S. Marino, S. Cavallini, C. Bianchi, A. Siniscalchi, J. Med. Chem. 48 (2005) 3337. [4] H. Hofstetter,O. Hofstetter, unpublished results. [5] D. Wade, Chem. Biol. Int. 117 (1999) 191. [6] C.L. Perrin, B.K. Ohta, J. Kuperman, J. Am. Chem. Soc. 125 (2003) 15008. [7] P.A. Frantom, R. Pongdee, G.A. Sulikowski, P.F. Fitzpatrick, J. Am. Chem. Soc. 124 (2002) 4202. [8] P.A. Frantom, P.F. Fitzpatrick, J. Am. Chem. Soc. 125 (2003) 16190. [9] J.A. Pavon, P.F. Fitzpatrick, J. Am. Chem. Soc. 127 (2005) 16414. [10] M. Shiotani, N. Isamoto, M. Hayashi, T. Fa¨ngstro¨m, S. Lunell, J. Am. Chem. Soc. 122 (2000) 12281. [11] I. Vakonakis, A.C. LiWang, J. Am. Chem. Soc. 126 (2004) 5688. [12] D.B. Northrop, J. Am. Chem. Soc. 121 (1999) 3521. [13] X. Huang, L.M. Johnson, J.M. Bowman, A.B. McCoy, J. Am. Chem. Soc. 128 (2006) 3478. [14] N.E. Hemer, D.L. Mattern, J. Am. Chem. Soc. 115 (1993) 2217.
[15] T. Makino, M. Orfanopoulos, T.P. You, B. Wu, C.W. Mosher, H.S. Mosher, J. Org. Chem. 50 (1985) 5357. [16] G.M. Sheldrick, SADABS. Program for Empirical Absorption Correction of Area Detector Data, University of Go¨ttingen, Germany, 2005. [17] A. Altomare, M.C. Burla, M. Camalli, G.L. Cascarano, C. Giacovazzo, A. Guagliardi, A.G.G. Moliterni, G. Polidori, R. Spagna, J. Appl. Cryst. 32 (1999) 115. [18] G.M. Sheldrick, SHELXTL. Version 6.10, Bruker Analytical X-ray Systems, Madison, Wisconsin, USA, 2005. [19] T. Koritsanszky, S. Howard, P.R. Mallinson, Z. Su, T. Richter, N.K. Hansen, XD: A Computer Program Package for Multipole Refinement and Analysis of Electron Densities from Diffraction Data, Freie Universita¨t Berlin, Germany, 1995. [20] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, J.R.C.M.A. Robb, J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A. Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox, H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O. Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K. Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S. Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K. Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J. Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L. Martin, D.J. Fox, T. Keith, M.A. AlLaham, C.Y. Peng, A. Nanayakkara, M. Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A. Pople, Gaussian 03W, Version 6.0, Gaussian, Inc., Pittsburgh PA, USA, 2003. [21] G. Schaftenaar, J.H. Noordik, J. Comput. Aided Mol. Des. 14 (2000) 123. [22] M. Roux, S. Besnainou, R. Daudel, J. Chim. Phys. 53 (1956) 218. [23] Z. Shi, R.J. Boyd, J. Phys. Chem. 95 (1993) 9614. [24] B. Foresman, Æ. Frisch, Exploring Chemistry with Electronic Structure Methods, second ed., Gaussian, Inc., Pittsburgh, PA, 1996.
Journal of Molecular Structure 875 (2008) 173–182 www.elsevier.com/locate/molstruc
Charge density and computational study of benzhydrol and benzhydrol-d10 Chong Zheng *, Heike Hofstetter *, Oliver Hofstetter Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb, IL 60115, USA Received 12 October 2006; received in revised form 17 April 2007; accepted 18 April 2007 Available online 29 April 2007
Abstract The structures and charge distribution of benzhydrol (C13H12O) and its deuterated equivalent benzhydrol-d10 (C13D10H2O) were studied by X-ray diffraction. Raman and IR spectra obtained for the compounds and ab initio calculations help to understand the structural features of these molecules. 2007 Elsevier B.V. All rights reserved. Keywords: Benzhydrol; Diphenylmethanol; Charge density; Vibrational frequencies
1. Introduction Benzhydrol (i.e., diphenylmethanol), C13H12O, is an important molecule in chemistry and biology whose structure has been reported previously by Ferguson and coworkers [1]. It has been used as a model target in many metal-catalyzed hydrogenation reactions [2]. Its analogs have shown strong biological inhibitory activity in the dopamine transporter and, thus, are potential therapeutic agents for treatment of cocaine addiction [3]. Recent results suggest that suitably raised antibodies can distinguish between benzhydrol and its deuterated analog [4]. Because deuterium isotope effects on noncovalent interactions in chemical and biological systems are based on the electronic and, in turn, the molecular volume, polarity and vibrational features of the isotopic molecules [5], it is important to understand their structural and electronic details. Lately, it has been shown that substitution of hydrogen atoms by deuterium affects the basicity and stereochemical properties of amines [6], changes the enzymatic activity of tyrosine hydroxylase [7,8] and phenylalanine hydroxylase [9], shifts *
Corresponding authors. Tel.: +1 815 753 6871; fax: +1 815 753 4802. E-mail addresses: [email protected] (C. Zheng), [email protected] (H. Hofstetter). 0022-2860/$ - see front matter 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.molstruc.2007.04.034
the ESR proton hyperfine coupling constants [10], and alters the hydrogen bond strength in the base pairs in DNA and RNA [11]. The deuterium isotope effects can be enhanced under high pressure [12], and the effect on structural configurations can be predicted from computational studies [13]. Effects on molecular structures have also been observed. For example, deuteration can result in a smaller unit cell volume [14]. In this contribution, we report X-ray charge density, IR and Raman spectroscopy as well as computational studies of benzhydrol and its deuterated analog, benzhydrol-d10. More detailed structural information promises to further better understanding of the chemical and biological properties of these compounds. 2. Experimental section 2.1. Preparation Benzhydrol (powder, Alfa Aesar, 99%), 1, and its deuterated equivalent benzhydrol-d10, 2, were crystallized by the liquid diffusion method. Compound 2 was prepared as follows: benzophenone-d10 was synthesized according to the procedure by Makino et al. [15]. In short, benzoylchloride-d5 was dissolved in benzene-d6 (99% deuterated) and treated with trifluoromethanesulfonic acid (all chemicals
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were purchased from Sigma, St. Louis, MO). The reaction was carried out at 80 C for 18 h under reflux. After cooling, the reaction mixture was washed several times with water and the white product was crystallized from benzene. Reduction of benzophenone-d10 was then carried out in anhydrous ethanol with NaBH4. The temperature was maintained at <35 C and the mixture was allowed to react for 17 h. The product benzhydrol-d10 was precipitated on ice using 10% HCl and recrystallized from hexane. The compounds have two rotational angles /1 and /2 associated with the two phenyl rings. These angles are important in determining the conformation of the compounds.
φ1
OH φ 2 C H
OH C H D D
D D D
D D
D
1
D
2
D
Approximately 2 mL of the saturated solutions of compounds 1 and 2, respectively, in methylene chloride (CH2Cl2) were pipetted into glass tubes of ca. 3 mm in diameter. An equal amount of cyclohexane (C6H12) was
Table 1 Data collection strategy Run#
2h ()
x ()
/ ()
# of Frames
Exposure time (s)
0 1 2 3 4 5 6 7 8 9 10 11 12
25 25 25 25 50 50 50 50 75 75 75 75 25
25 25 25 25 50 50 50 50 75 75 75 75 25
0 90 180 270 0 90 180 270 0 90 180 270 0
606 606 606 606 606 606 606 606 606 606 606 606 50
15 15 15 15 30 30 30 30 45 45 45 45 15
The scan axis is x with frame width = 0.3, v = 54.77. The sample-to-detector distance was 4.943 cm. Run #12 was used for crystal decay estimate. No decay was detected.
Table 2 Crystal data and structure refinement for benzhydrol (H10) and benzhydrol-d10 (D10) Compound/refinement
H10/CV
D10/CV
H10/CD
D10/CD
Empirical formula Formula weight Temperature (K) ˚) Wavelength (A Crystal system Space group ˚) Unit cell dimensions (A a b c ˚ 3) Volume (A Z Density (calculated) (Mg/m3) Absorption coefficient (mm1) Index ranges Reflections collected Independent reflections Completeness to theta () Absorption correction Refinement method Final R indices [I > 2sigma(I)]
C13 H12 O 184.23
C13 H2 D10 O 194.29 203 (2) 0.71073 Orthorhombic P22121 (No. 18)
C13 H12 O 184.23
C13 H2 D10 O 194.29
5.0945 18.784 21.181 2027.0
5.0772 (3) 5.0945 18.6499 (9) 18.784 21.032 (1) 21.181 1991.5 (2) 2027.0 8 1.296 1.207 0.076 0.075 6 h 6, 22 k 22, 25 l 25 30810 34462 3474 [R(int) = 0.0418] 99.9%
1.207 0.075
(7) (2) (3) (4)
34462 3554 [R(int) = 0.0263] 25.00 Semi-empirical from equivalents Full-matrix least-squares on F2 R1 = 0.0317 0.0398 wR2 = 0.0828 0.1028
Refinement type: CV, conventional; CD, multipole charge density refinement.
(7) (2) (3) (4)
5.0772 (3) 18.6499 (9) 21.032 (1) 1991.5 (2) 1.296 0.076 30810
Multipole with lmax = 5 0.0253 0.0324 0.0462 0.0723
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then gently added to the tubes. The nonpolar cyclohexane solvent in the sealed tubes was allowed to slowly diffuse into the polar methylene chloride solution resulting in a reduced solubility of the polar compounds. After one week, needle crystals of ca. 5 mm in length were obtained. 2.2. Charge density study Several crystals of the compounds were indexed on a Bruker SMART CCD diffractometer using 40 frames with an exposure time of 20 s per frame. All crystals exhibited the same orthorhombic lattice. One crystal with good reflection quality from each compound was chosen for data collection. A total of 7322 frames were collected for each compound to ensure adequate data redundancy. The experimental parameters used for the charge density study are listed in Table 1. An empirical absorption correction using the program SADABS [16] was applied to all reflections. The structure was solved with direct methods using the SIR97 program [17]. A full matrix least-square refinement on F2 was carried out using the SHELXTL program [18]. The multipole refinement for the charge density study was carried out using the XD program [19]. The unit cell information and refinement details are reported in Table 2. The atomic positions and equivalent isotropic displacement parameters are listed in Table 3. 2.3. Spectroscopy Raman spectra were recorded for the same single crystals used for the X-ray data collection on a Renishaw System 2000 microfocus Raman spectrometer (Renishaw, System 2000, UK). The IR spectra were obtained on a Bruker Vector 22 instrument (Bruker, Billerica, MA). 2.4. Computational study The energy levels, total energy and vibrational modes of the molecules were calculated using the ab initio Gaussian03 package [20]. The RHF/6-31G* model was used for all calculations. The deformation density and Laplacian of the electron density were calculated with the program MOLDEN [21]. 3. Results and discussion 3.1. Crystal structure The structure of benzhydrol is shown in Fig. 1. The deuterated benzhydrol-d10 has the same structure. The average atomic RMS difference between the benzhydrol structure ˚ . The unit and the benzhydrol-d10 molecule is only 0.04 A cell volumes of them, however, are slightly different with ˚ 3 for benzhydrol and 1991.5(2) A ˚ 3 for benzhy2027.0(4) A drol-d10. The 2% volume decrease can be a result of larger polarity of the deuterated compound producing a tighter hydrogen bond network, since it is known that deuteration
175
Table 3 ˚ · 104) and equivalent isotropic displacement Atomic coordinates (A ˚ 2 · 103) for benzhydrol and benzhydrol-d10 parameters (A x
y
z
U(eq)
Benzhydrol O (1) C (11) C (111) C (112) C (113) C (114) C (115) C (116) C (121) C (122) C (123) C (124) C (125) C (126) O (2) C (21) C (211) C (212) C (213) C (214) C (215) C (216) C (221) C (222) C (223) C (224) C (225) C (226)
6334 6599 4538 3333 1501 866 2079 3898 6396 4428 4263 6055 8017 8191 1289 1406 734 2118 3999 4522 3152 1268 1230 702 799 971 2866 3002
(2) (3) (3) (4) (4) (4) (4) (3) (3) (4) (4) (4) (4) (4) (2) (3) (3) (3) (4) (4) (4) (3) (3) (4) (4) (4) (4) (3)
8288 8075 8476 9088 9456 9223 8622 8250 7269 6884 6152 5787 6159 6895 8297 8061 8447 9023 9380 9171 8602 8244 7251 6875 6134 5764 6131 6872
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
311 340 727 492 855 1460 1699 1335 407 99 160 537 845 778 899 1548 1921 1670 2025 2644 2902 2545 1592 1265 1305 1673 2003 1961
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
39 32 32 41 51 46 43 39 32 40 48 49 49 40 38 32 31 36 42 44 45 39 32 42 51 51 50 40
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
Benzhydrol-d10 O (1) C (11) C (111) C (112) C (113) C (114) C (115) C (116) C (121) C (122) C (123) C (124) C (125) C (126) O (2) C (21) C (211) C (212) C (213) C (214) C (215) C (216) C (221) C (222) C (223) C (224) C (225) C (226)
3657 3412 5469 6672 8513 9136 7931 6098 3597 5578 5734 3950 1982 1805 8704 8598 10723 12106 13993 14514 13146 11264 8769 10694 10808 9026 7126 6985
(3) (4) (4) (5) (5) (5) (5) (4) (4) (4) (5) (5) (5) (4) (3) (4) (4) (4) (4) (5) (5) (4) (4) (5) (5) (5) (5) (4)
1709 1924 1521 911 543 775 1377 1750 2729 3114 3848 4215 3841 3103 1700 1937 1551 974 619 829 1398 1758 2747 3126 3867 4237 3869 3128
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
9688 10342 10729 10491 10855 11461 11703 11339 10407 10100 10159 10534 10842 10777 9101 8451 8076 8329 7970 7354 7095 7452 8407 8734 8697 8323 7995 8038
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
45 39 38 48 58 53 50 44 39 46 53 55 55 46 45 39 38 44 48 50 51 46 38 49 56 57 56 47
(1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1) (1)
U(eq) is defined as one third of the trace of the orthogonalized Uij tensor.
of hydrocarbons will generally result in a more polar and thus less lipophilic molecule [5]. This effect has been
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Fig. 1. Ellipsoid (50% probability) plot of the structure of benzhydrol. There are two molecules in the asymmetric unit. Molecule 1 is on the left side and molecule 2 on the right.
observed previously in the tetracyanoanthraquinodimethane (TCAQ) structure [14]. Using the reported average lattice constants for TCAQ and TCAQ-d8, the volumes ˚ 3, respectively. The are calculated to be 741.8 and 737.8 A difference corresponds to approximately 1% decrease in unit cell volume upon deuteration. For the benzhydrol structure, there are two molecules in the asymmetric unit. A hydrogen bond is formed between the hydroxyl groups of the two molecules. This hydrogen bond donor is also shared with an acceptor of another molecule in the next unit cell. In this fashion, the hydrogen bond propagates along the a-axis as demonstrated in Fig. 2. The two molecules in the asymmetric unit differ in the dihedral angles associated to the phenyl groups as depicted in Fig. 3. The O1–C11–C111–C112 angle is 18.4(2) in molecule 1, but the corresponding angle O2–
Fig. 2. Crystal packing of benzhydrol. Extended hydrogen bonds (green) are formed between molecules along the a-axis. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
C21–C211–C212 is 11.2(2) in molecule 2. Similarly, the dihedral angle of the second phenyl ring in molecule 1, O1–C11–C121–C122, is 45.8(2), while the related angle O2–C21–C221–C222 of molecule 2 is 48.2(2). These two conformations correspond to points 1 and 2 on the ab initio potential surface in Fig. 4. They are related by a pseudo inversion center. This surface was calculated using the rigid molecule approximation, keeping other degrees of freedom frozen while varying the two dihedral angles /1 and /2 which are defined in drawing 1. The structural difference between these two molecules is likely due to the crystal packing, because the ab initio optimized structure of an isolated benzhydrol molecule would have the O1– C11–C111–C112 and O2–C21–C221–C222 angles equal to 5.42 and 54.96, respectively. Because of their structural difference, the energies of the two molecules differ slightly, with molecule 2 being more stable by ca. 0.2 eV according to our ab initio calculation with optimization on all degrees of freedom minus the two angles. The stabilization comes from a better hyperconjugation interaction of the C21–O2 bond with the p orbitals of the second phenyl ring. The interaction would be even better if the O2–C21–C221–C222 dihedral angle were 90, but this configuration would diminish another hyperconjugation interaction between the C21–H21 bond and the p system of the first phenyl ring with the dihedral angle H21–C21–C211–C212 equal to 104.6. The optimized structure has the best compromise between these two types of hyperconjugation interaction with the two angles at 55.0 and 123.4, respectively. As a consequence the optimized structure is about 2.9 eV more stable than molecule 2 of benzhydrol. Because of the rotations from their idealized angle of 0 or 90, the two phenyl rings on molecule 1 or 2 are not related by a symmetry operation. This makes the molecule similar to a chiral one. The initial refinement of the benzhydrol-d10 data results in a Flack parameter of 0.6 ± 1.4 sug-
Fig. 3. Overlay comparison of molecule 1 (blue) and molecule 2 (red) of benzhydrol. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
C. Zheng et al. / Journal of Molecular Structure 875 (2008) 173–182
Fig. 4. Potential energy surface of benzhydrol calculated by the ab initio method. /1 and /2 are the two phenyl rotation angles defined in drawing 1. Points 1 and 2 correspond to the conformations of molecules 1 and 2 in the unit cell.
gesting the wrong absolute configuration. Because of the large uncertainty of the parameter, the determination is not conclusive. However, the charge density study in the following section also revealed signs of wrong absolute configuration. Therefore, the initial structure was inverted and Table 3 presents the coordinates of the inverted structure. For benzhydrol, the Flack parameter is 0.09 and the absolute configuration is unambiguous. 3.2. Charge density The static deformation densities Dq(r) of benzhydrol and benzhydrol-d10 are shown in Fig. 5. For clarity, only the regions around the first phenyl group and the hydroxyl group are plotted. The deformation density around the second phenyl group is similar. The static deformation density is defined as the difference in electron densities between a molecule and the sum of its corresponding spherical atoms [22]: X DqðrÞ ¼ qmol ðrÞ qk ðr rk Þ k
Therefore, the maxima of Dq(r) usually correspond to bonding regions. As seen in the top left in Fig. 5, the Dq(r) of benzhydrol shows maxima along the phenyl ring indicating bonding interaction. The top right of the figure illustrates the Dq(r) for benzhydrol-d10 structure of the initial refinement. There is a sign of an inverted phase compared to that of benzhydrol. After a structure inversion under which molecule 1 is mapped to molecule 2, the phase follows that of benzhydrol as shown at the center of Fig. 5. The bottom of the figure depicts the calculated Dq(r)’s for the two molecules using the ab initio method. These two Dq(r)’s are identical as expected. In general, the experimental Dq(r) of
177
benzhydrol-d10 reveals more polar features than that of benzhydrol. The Dq(r) of benzhydrol is more uniform along the C–C bonds of the phenyl ring. The variation in the experimental Dq(r)’s of the two compounds may come from differences in crystal quality and/or polarity due to isotope effect [5]. It is also interesting to note that near the center carbon C1, the C1–O1 bond is much more polar as predicted by the theoretical calculations. The Laplacian of the electron densities, $2q(r), of the two molecules are plotted in Fig. 6. The Laplacian represents local concentrations, with $2q(rc) < 0 indicating shared interactions and $2q(rc) > 0 closed shell interaction at an electron density critical point rc [23]. Fig. 6 reveals a more continuous delocalized p interaction on the phenyl ring for benzhydrol. The topological features and phases of $2q(r) of the two molecules also support the conclusion that the inverted benzhydrol-d10 structure has the correct absolute configuration. Beside this, the main topological features of $2q(r) of the two molecules are very similar as expected. 3.3. IR spectrum The IR spectra for benzhydrol and benzhydrol-d10 are shown in Fig. 7. The main difference between the spectra of these two compounds is the shift of the aromatic C–H stretching frequencies. In benzhydrol the frequencies are around 3026–3084 cm1. The corresponding peaks are shifted to 2276 cm1 for benzhydrol-d10. The down shift is as expected from the square p root of the mass ratio of hydrogen versus deuterium (H/D) = 0.707. Our ab initio calculation confirms that these peaks are indeed the aromatic C–H and C–D stretching modes. Table 4 lists the calculated IR frequencies, assignments and relative intensities of the two compounds in their experimental conformations. It is well-known that ab initio HF methods usually overestimate the frequency by 10–15% [24]. In addition, the experimental crystal structures are usually not at the potential minima of the corresponding gas phase configuration, resulting in an additional overestimate of frequencies. Therefore, it is customary to scale the calculated frequencies by a factor normally set to 0.89 [24]. The frequencies in Table 4 are the unscaled values. In Table 4, most of the aromatic C–H p frequencies in benzhydrol are down shifted by the (H/D) factor in benzhydrol-d10. However, because of the low symmetry of the molecule, the C–H stretching modes are also coupled to the collective motions of the phenyl C atoms. Therefore p the down shift factor is usually slightly less than the (H/D) value of p 0.707 or the reduced mass scaling (lCH/lCD) of 0.734 as the 3084 cm1 peak in benzhydrol attests. 3.4. Raman spectrum Fig. 8 is the Raman shift of benzhydrol taken at different rotation angles of the needle crystal with respect to the
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Fig. 5. Deformation density Dq(r) of benzhydrol (top left) and benzhydrol-d10 (top right) at the first phenyl group and the hydroxyl group. The center shows Dq(r) of benzhydrol-d10 after a structural inversion in the refinement. Positive regions are in blue and negative in red. Contours of negative Dq(r) are ˚ 3 intervals starting at 0.02 e/A ˚ 3. Contours of positive Dq(r) are in logarithmic scale starting at 0.001 e/A ˚ 3 with increment of 2 at each drawn at 0.001 e/A interval. The bottom two drawings are theoretical Dq(r)’s calculated using the ab initio method. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Raman polarization vector. Because of the low symmetry of the molecule, the Raman intensity is less sensitive to
the rotational angle as compared to other molecules of higher symmetry. The most pronounced change of inten-
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Fig. 6. $2q(r) of Benzhydrol (top left) and benzhydrol-d10 (top right) at the first phenyl group and the hydroxyl group. Positive regions are in blue and ˚3 negative in red. The center shows $2q(r) of benzhydrol-d10 after a structural inversion in the refinement. Contours of negative $2q(r) are drawn at 0.2 e/A 5 2 5 ˚ ˚ intervals starting at 4.0 ending at 0.1 e/A . Contours of positive $ q(r) are in logarithmic scale starting at 0.1 e/A with increment of 2 at each interval. The bottom two drawings are theoretical $2q(r)’s calculated using the ab initio method. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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IR Spectrum of Benzhydrol (H10) and Benzhydrol-d10 (D10) 0.8
H10 D10
Transmittance (%)
0.7
Benzhydrol
0.6
0.5 3084 3059 3026 C-H
0.4
0.3 3389 O-H
0.2 2276 C-D
0.1 4000
3500
3000
Table 4 Calculated IR frequencies and relative intensities (RI) of benzhydrol and benzhydrol-d10
2500
2000
1500
1000
500
-1
Wavenumber (cm ) Fig. 7. IR spectrum of benzhydrol (black line) and benzhydrol-d10 (red line). (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
sity is observed for the two peaks at 1000 and 1022 cm1. Their ratio changes from 17 to 5 when the rotation angle moves from 90 to 0. In other words, the 1000 cm1 peak decreases while the one at 1022 cm1 increases with decreasing angle. The highest peak at 1000 cm1 corresponds to the calculated Raman peak with the largest relative intensity of 48 at 1092 cm1 in Table 5. Its vibrational mode is depicted on the left panel in Fig. 9. This mode involves a collective motion of the first phenyl ring, and its dipole derivative vector is approximately parallel to the C1–O bond. Since the crystal needle is parallel to the a-axis along which the extended hydrogen bonds propagate, this dipole derivative vector is approximately perpendicular to the needle axis. Thus the corresponding Raman intensity is highest when the polarization vector is perpendicular to the crystal needle axis. The next calculated peak is at 1098 cm1. Its mode is shown on the right side of Fig. 9. It is a collective motion in the second phenyl ring coupled to the H–C1–C scissoring motion around the center C1 atom. The dipole derivative vector is approximately parallel to the phenyl rings, thus perpendicular to that of the 1092 cm1 mode. The Raman intensity is therefore highest when the polarization vector is parallel to the crystal needle axis. Because both peaks involve collective motion of the phenyl rings, isotope down shifts are expected for them in benzhydrol-d10. Indeed the shifts shown in Fig. 10 are most pronounced at these frequencies. The highest peak at 1000 cm1 in benzhydrol is down shifted to 957 cm1, which equals a decrease by a factor of 0.96. As this mode is a collection motion involving both C and H atoms in the first phenyl ring, the down p shift factor is not quite as large as the mass ratio (H/D) or p (lCH/lCD) dictates.
Benzhydrol-d10
Frequency (cm1)
Mode
RI
Frequency (cm1)
Mode
RI
672 702 745 764 797 809 855 908 941 980 987 1014 1034 1085 1092 1098 1110 1153 1158 1192 1290 1309 1480 1499 1540 1545 1723 1743 4187 4235 4271 4299 4506 4519 4526 4568 4584 4912 5429
/ / H–C–C / / / / H–C–C / / + H–C1–C H–C–C / / H–C1–C / H–C1–C H–C1–C H–C–C H–C–C O–C1–H C1–C C1–C C–C C–C C–C C–C C–C C–C C–H C1–H C–H C–H C–H C–H C-H C–H C–H C–H O–H
3 2 5 6 13 1 2 9 18 11 8 4 2 15 7 12 40 5 2 8 23 22 4 18 3 4 5 2 8 22 7 14 4 5 11 3 8 4 84
653 690 725 729 739 753 781 786 792 848 885 901 953 1002 1059 1078 1107 1165 1243 1280 1302 1450 1464 1534 1739 1754 1756 2916 2986 3008 3118 3263 3269 3418 3449 4345 5231
/ D–C–C / / D–C–C / / / / / D–C–C / + H–C1–C / / + H–C1–O / H–C1–C O–C1 H–O–C1 C–C C–C C1–C C–C C–C C–C + C1–C C–C C–C C–C C–D C–D C–D C–D C–D C–D C–D C–D C1–H O–H
5 2 1 1 9 6 3 4 13 5 2 2 9 5 3 24 56 10 2 19 19 12 5 2 5 1 1 8 4 9 8 5 4 3 4 20 88
Vibrational mode assignment: /, phenyl ring collective motion; H–C–C, scissoring motion involving the H and C atoms in the phenyl ring; H–C1– C, scissoring motion involving the H and center C1 and phenyl C atoms; / + H–C1–C, phenyl collective motion plus H–C1–C scissoring motion; C–C, bond stretching motion in the phenyl ring; etc. Frequencies with relative intensity less than 1 are omitted.
4. Conclusions The crystal structures and charge distribution of benzhydrol and benzhydrol-d10 have been investigated by Xray diffraction techniques. The structures and topological features of electron densities of these two molecules are similar. Spectroscopic and computational study revealed that the 3026–3084 cm1 IR peaks are associated with aromatic C–H stretching and thus demonstrate strongest iso-
C. Zheng et al. / Journal of Molecular Structure 875 (2008) 173–182
Table 5 Calculated Raman frequencies and relative intensities (RI) of benzhydrol and benzhydrol-d10
Raman Spectrum of Benzhydrol 1000
160000
Intensity (Arbitrary Unit)
140000 120000 100000 80000
Benzhydrol
o
Rotation ( ) 90 67.5 45 22.5 0 1022
60000 40000 20000 0 -20000 500
1000
1500
2000
-1
Raman Shift (cm ) Fig. 8. Raman spectrum of benzhydrol taken at different rotation angle between the needle crystal and the Raman polarization vector.
Raman Spectrum of Benzhydrol (H10) and Benzhydrol-d 10 (D10)
Intensity (Arbitrary Unit)
160000
H10 at 90 degree D10 at 90 degree
140000 1000
120000 957
100000 80000 60000 40000 20000 0 -20000
500
181
1000
1500
2000
-1
Raman Shift (cm )
Benzhydrol-d10
Frequency (cm1)
Mode
RI
Frequency (cm1)
Mode
RI
236 288 300 331 360 452 568 615 764 809 817 941 980 987 1014 1034 1085 1092 1098 1110 1153 1158 1192 1223 1290 1309 1718 1723 1737 1743
/ / / / / / H–C–C H–C–C + H–O–C1 / / / / / + H–C1–C H–C–C / / H–C1–C / H–C1–C H–C1–C H–C–C H–C–C O–C1–H C–C C1–C C1–C C–C C-C C–C C–C
4 4 3 3 6 4 3 6 2 6 3 6 9 8 7 10 6 48 5 4 2 3 16 3 7 5 4 10 9 23
165 236 309 362 489 622 629 739 753 781 786 792 885 901 953 1002 1054 1059 1078 1107 1165 1255 1280 1302 1735 1739 1754 1756 2916 2986 3008 3057 3118
/ H-C1-O / / / / + H–C1–O / + H–C1–C D–C–C / / / / D–C–C / + H–C1–C / / + H–C1–O / / H–C1–C O–C1 H–O–C1 C–C C–C C1–C C–C C–C C–C C–C C–D C–D C–D C–D C–D
3 2 4 3 2 2 2 3 3 7 5 3 10 8 3 8 33 16 8 4 19 2 9 4 4 7 22 11 33 19 41 18 44
Vibrational mode assignment: /, phenyl ring collective motion; H–C–C, scissoring motion involving the H and C atoms in the phenyl ring; H–C1– C, scissoring motion involving the H and center C1 and phenyl C atoms; / + H–C1–C, phenyl collective motion plus H–C1–C scissoring motion; C–C, bond stretching motion in the phenyl ring; etc. Frequencies with relative intensity less than 2 are omitted.
Fig. 9. Raman spectrum of benzhydrol (H10, black line) and benzhydrold10 (D10, red line) with the needle crystals perpendicular to the Raman polarization vector. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
Fig. 10. Calculated vibrational modes at 1092 cm1 (left) and 1098 cm1 (right). The atomic vibration vectors are indicated by the blue arrows and the dipole derivative vector is represented by the yellow arrow for each mode. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article.)
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