Influence of the substituents on the structure and properties of benzoxaboroles

Article abstract of DOI:10.1021/jp9086283

Benzoxaboroles possessing aryl substituents in the oxaborole ring were synthesized, and their structures were detennined by single-crystal X-ray diffraction. Structures in the solid state are centrosymmetric dimers with two intermolecular hydrogen bonds. These compounds were investigated using a combination of the spectroscopic and the computational approach, comparing their properties with the unsubstituted compound. Investigated compounds were characterized by ¹H, ¹³C, and ¹¹B NMR spectroscopy in solution. Assignment of ¹H and ¹³C signals was made on the basis of HSQC and HMBC spectra. The molecular structure of 1,3dihydro-1-hydroxy-3-phenyl-2,1-benzoxaborole was calculated by the density functional (B3LYP) method with the extended 6-311++G(d,p) basis set. The calculated geometrical parameters were compared with experimental X-ray data, and the differences between experimental and calculated values were found to be of the order of experiment standard deviation, confirming a good description by this level of theory. The harmonic frequencies, potential energy distribution (PED), and IR intensities of this compound and its deuterated analogue were calculated with the B3LYP method. The assignment of the experimental spectra was made on the basis of the calculated PED. The consequence of dimer formation is the splitting of the vibrational modes into symmetric and antisymmetric vibrations. The structure modification resulting from the hydrogen bonded dimers formation is presented.

Full text of DOI:10.1021/jp9086283

2324
J. Phys. Chem. A 2010, 114, 2324–2330
Influence of the Substituents on the Structure and Properties of Benzoxaboroles
Agnieszka Adamczyk-Woz´niak,† Michał K. Cyran´ski,‡ Michał Jakubczyk,†
Paulina Klimentowska,‡ Aleksander Koll,§ Jerzy Kołodziejczak,§ Grzegorz Pojmaj,†
†
†
,†
˙
˙
Anna Zubrowska, Graz˙yna Z. Zukowska, and Andrzej Sporzyn´ski*
Warsaw UniVersity of Technology, Faculty of Chemistry, Noakowskiego 3, 00-664 Warsaw, Poland, UniVersity
of Warsaw, Faculty of Chemistry, Pasteura 1, 02-093 Warsaw, Poland, and UniVersity of Wrocław,
Faculty of Chemistry, Joliot-Curie 14, 50-383 Wrocław, Poland
ReceiVed: September 7, 2009; ReVised Manuscript ReceiVed: January 5, 2010
Benzoxaboroles possessing aryl substituents in the oxaborole ring were synthesized, and their structures were
determined by single-crystal X-ray diffraction. Structures in the solid state are centrosymmetric dimers with
two intermolecular hydrogen bonds. These compounds were investigated using a combination of the
spectroscopic and the computational approach, comparing their properties with the unsubstituted compound.
Investigated compounds were characterized by 1H, 13C, and 11B NMR spectroscopy in solution. Assignment
1
of H and 13C signals was made on the basis of HSQC and HMBC spectra. The molecular structure of 1,3-
dihydro-1-hydroxy-3-phenyl-2,1-benzoxaborole was calculated by the density functional (B3LYP) method
with the extended 6-311++G(d,p) basis set. The calculated geometrical parameters were compared with
experimental X-ray data, and the differences between experimental and calculated values were found to be
of the order of experiment standard deviation, confirming a good description by this level of theory. The
harmonic frequencies, potential energy distribution (PED), and IR intensities of this compound and its deuterated
analogue were calculated with the B3LYP method. The assignment of the experimental spectra was made on
the basis of the calculated PED. The consequence of dimer formation is the splitting of the vibrational modes
into symmetric and antisymmetric vibrations. The structure modification resulting from the hydrogen bonded
dimers formation is presented.
Introduction
in medicine. 5-Fluoro-1,3-dihydro-1-hydroxy-2,1-benzoxaborole,
AN2690, is a broad-spectrum antifungal drug that easily transits
Boronic acids, RB(OH)2, are objects of increasing interest
because of their new applications in organic synthesis, catalysis,
supramolecular chemistry, biology, and medicine.1 Following
the research on molecular recognition, phenylboronic acids have
also recently been employed as promising building blocks in
crystal engineering to achieve predictably organized crystal
materials.2 Supramolecular assemblies of various types have
been generated in this manner.3–5 The reversibility of their
interactions with diols is widely exploited in the construction
of molecular receptors6 and makes them ideal candidates for
the design of self-assembled molecular structures.7,8
through the nail plate.10,11 After the discovery of its antifungal
properties,12–14 systematic investigations of biological activity of
substituted benzoxaboroles were carried out.15,16 Recently, 5-chloro-
substituted benzoxaborole, AN2718, is being developed for topical
treatment of tinea pedis.15 Benzoxaborole with cyanophenoxy
substituents in five-position reveals anti-inflammatory activity
against psoriasis, a common skin disease characterized by chronic
inflammation. On the basis of structure-activity relationship
studies, it was found to be the most active compound and is
currently in clinical trials.15,17,18 Determination of the structure of
the complexes with leucyl-tRNA synthetase was the basis for the
rational design of antifungal benzoxaboroles.19 Benzoxaboroxoles
were also tested for the treatment of periodontal disease.20
Although the possibility of ester formation by benzoxaboroles
with monohydroxy compounds was reported as early as 1982 by
Wulff,21 their surprisingly high activity toward polyols was only
recently reported. Formation of the cyclic esters by boronic acids
with diols is the basis of boronic acids’ action as sugar molecular
receptors.6 In that case, cyclic esters are formed by both hydroxy
groups in the boronic group. Similar cyclic esters can be formed
by the anionic form of the benzoxaboroles in neutral or slightly
alkaline media.22,23
Benzoxaboroles I are internal hemiesters of phenylboronic
acids. They reveal a very high chemical stability of both
oxaborole ring and boron-carbon bond toward hydrolysis
compared with corresponding boronic acids.9 Only recently has
great attention been paid to a new application of these compounds
Another important application of benzoxaboroles is their use
in Suzuki coupling to yield ortho-substituted benzyl alcohols.24
Substituted benzoxaborole was used, for example, in the total
synthesis of vancomycin.25
Only a few crystal structures of benzoxaboroles are known to
date.26 Similarly to phenylboronic acids, the basic structural motive
is a dimer with two intermolecular hydrogen bonds. Importantly,
* To whom correspondence should be addressed. E-mail: spor@
ch.pw.edu.pl. Fax: +48-22-6282741.
† Warsaw University of Technology.
‡ University of Warsaw.
§ University of Wrocław.
10.1021/jp9086283  2010 American Chemical Society
Published on Web 01/21/2010

Structure and Properties of Benzoxaboroles
J. Phys. Chem. A, Vol. 114, No. 6, 2010 2325
TABLE 1: Selected Crystal Data and Structure Refinement
for Compounds 1-3
obtained by recrystallization from acetonitrile and of 3 crystal-
lized from the reaction mixture dissolved in hexane. The X-ray
measurement of 1, 2, and 3 was performed at 100(2) K on a
KUMA CCD k axis diffractometer with graphite-monochro-
mated Mo KR radiation (0.71073 Å). The crystal was positioned
at 62.25 mm from the KM4CCD camera; 750 frames were
measured at 0.5° intervals on a counting time of 20 s, 748 frames
were measured at 0.8° intervals on a counting time of 10 s, and
4000 frames were measured at 0.3° intervals on a counting time
of 20 s, respectively for 1-3. Data reduction and analysis were
carried out with the KUMA diffraction programs. The data were
corrected for Lorentz and polarization effects, but no absorption
correction was applied. Data reduction and analysis were carried
out with the Kuma diffraction (Wrocław, Poland) programs.32
The structure was solved by direct methods33 and refined by
using SHELXL.34 The refinement was based on F2 for all
reflections except for those with negative F2. The weighted R
factor, wR, and all goodness-of-fit S values are based on F2.
The nonhydrogen atoms were refined anisotropically. The
hydrogen atoms were located from a difference map and were
refined isotropically. The atomic scattering factors were taken
from the international tables.35 Selected crystal structure and
structural refinement are specified in Table 1. (See the Sup-
porting Information for more details.) Selected bond lengths,
bond angles, and torsion angles are given in Table 2. Crystal-
lographic data for the structure have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCDC 744739 (1), 744740 (2), and 744741 (3).
Copies of the data can be obtained on application to CCDC, 12
Union Road, Cambridge CB2 1.EZ, U.K. (e-mail: deposit@ccdc.
cam.ac.uk).
compound
1
2
3
empirical formula
space group
unit cell dimensions
a [Å]
b [Å]
c [Å]
2C7H7BO2
P21
C13H11BO2
C2/c
C15H16NBO2
P1
j
4.536(1)
24.292(4)
6.144(1)
16.663(1)
6.247(1)
21.040(2)
6.897(1)
9.838(1)
10.578(1)
68.399(6)
78.575(6)
78.580(6)
647.90(8)
2
R [°]
ꢀ [°]
102.73(1)
104.712(7)
γ [°]
volume V [Å3]
Z [molecules/cell]
final R indices
(I > 2σ)
660.5(2)
4
R ) 0.0423
2118.3(3)
8
R ) 0.0324
R ) 0.0350
wR2 ) 0.0881 wR2 ) 0.0876 wR2 ) 0.0969
only one hydroxy group at the boron atom is present, and hence
there is no possibility of lateral hydrogen bond formation to form
infinite 2D or 3D networks, as observed in the case of phenylbo-
ronic acids.27 The boron center is always trigonal, but unlike in
phenylboronic acids, the BOO fragment is coplanar with the phenyl
fragment. Substitution at phenyl ring and/or on methylene carbon
of oxaborole fragment can influence the molecular interactions both
by steric and electronic effects, so more complicated patterns are
also observed.28–30 Recently, the influence of amino substituent on
the intermolecular hydrogen bond was investigated using a
combination of the spectroscopic and the computational approach.31
The aim of the present work is the comparison of the parent
compound, unsubstituted benzoxaborole (1), of which the crystal
structure was redetermined, with the newly synthesized com-
pounds (2, 3) with different substituents in the oxaborole ring.
Nuclear Magnetic Resonance Measurements. The 1H
NMR, 13C NMR, and 2D spectra were recorded on Varian
INOVA 500 spectrometer operating at frequency 500 and 125.1
MHz at ambient temperature. The 11B spectra were recorded
on Varian UnityPlus 200 spectrometer at frequency 64 MHz.
Infrared Measurements. Infrared absorption spectra were
recorded on a computer interfaced Perkin-Elmer 2000 FT-IR
system with a wavenumber resolution of 1 cm-1. The spectra
were obtained for samples dispersed in KBr pellets.
Experimental Section
X-ray Crystallography. The crystals of 1 were obtained from
an acidic aqueous-methanol solution. The crystals of 2 were
TABLE 2: Selected Bond Lengths (angstroms), Bond Angles (degrees), and Torsion Angles (degrees) for Compounds 1-3a
1
2
3
compound/parameter
A
B
B(1)-O(12)
1.351(5)
1.401(5)
1.550(6)
1.455(4)
0.89(5)
1.398(5)
1.406(4)
121.9(4)
130.1(3)
108.0(3)
111.0(3)
105.0(3)
136.2(3)
104.7(3)
179.7(3)
0.7(4)
1.347(5)
1.405(5)
1.560(6)
1.453(4)
0.84(4)
1.398(5)
1.399(5)
122.3(4)
129.9(4)
107.8(3)
110.3(3)
105.7(3)
135.4(3)
106.0(3)
179.2(3)
0.1(4)
1.3452(14)
1.3936(13)
1.5488(15)
1.4501(12)
0.881(16)
1.3970(14)
1.3977(14)
121.90(9)
129.97(9)
108.10(9)
111.19(8)
105.21(9)
135.21(10)
104.60(8)
179.21(9)
0.92(11)
1.3466(15)
1.3842(15)
1.5538(17)
1.4694(13)
0.905(19)
1.3986(16)
1.3977(16)
122.44(10)
129.37(11)
108.19(10)
111.30(9)
105.09(10)
135.25(11)
103.91(9)
177.67(10)
2.20(12)
B(1)-O(11)
B(1)-C(1)
O(11)-C(7)
O(12)-H(12)
C(1)-C(6)
C(1)-C(2)
O(12)-B(1)-O(11)
O(12)-B(1)-C(1)
O(11)-B(1)-C(1)
B(1)-O(11)-C(7)
C(2)-C(1)-B(1)
C(6)-C(1)-B(1)
O(11)-C(7)-C(2)
O(11)-B(1)-O(12)-C(7)
C(1)-B(1)-O(11)-C(7)
C(1)-C(2)-C(7)-O(11)
1.6(4)
-0.7(4)
0.30(10)
3.90(12)
a A and B denote two independent molecules of 1.

2326 J. Phys. Chem. A, Vol. 114, No. 6, 2010
Adamczyk-Woz´niak et al.
SCHEME 1: Synthesis of the Investigated Compounds
Computational Details
Density function theory (DFT)36 with the hybrid functionals
(B3LYP)37,38 and basis set 6-311++G(d,p) was applied to
calculate vibrational frequencies and their IR intensities. Normal
coordinate analysis method was used to obtain the potential
energy distribution (PED).39 Calculations were made using the
Gaussian03 program.40
The comparison between the experimental structures of 2 and
3 and the calculated at B3LYP/6-311++G(d,p) level was
performed (Table S3 in the Supporting Information). The
differences between experimental and theoretical values are of
the order of experiment standard deviations.
Figure 2. Dimeric interaction in 2. The molecules are related by an
inversion center (i: 1/2-x, 3/2-y, -z). The intermolecular hydrogen bonds
are marked as dotted lines. The displacement parameters are drawn at
50% probability level.
by Zhdankin et al.41 The system crystallizes in P1 triclinic space
j
group where an asymmetric part of the unit cell consists of the
two independent molecules. They form two kinds of planar
centrosymmetric dimers, which are situated almost perpendicu-
larly to each other. The angle between the best planes calculated
for all atoms of the dimers is 73.7°.41 In the present article,
another polymorph of this compound is reported. Polymorph II
crystallizes in monoclinic P21 space group and, similarly to the
case of polymorph I, an asymmetric part of the unit cell is also
formed by two molecules of benzoxaborole. In this case,
however, two independent molecules form only one kind of
dimer, which is also planar. (See Figure 1.) Despite this
difference, the two-screw axis leads to almost perpendicular
positioning of the neighboring dimers, and as in polymorph I,41
the angle between the best planes calculated for all atoms of
the dimers is 75.2°. The hydrogen bonds in the dimer are rather
strong: the O(12A)-H(12A) · · ·O(11B) and O(12B)-H(12B)· · ·
O(11A) distances are 1.88(5) and 1.91(4) Å, respectively (the
Results and Discussion
Synthesis. Compounds 1-3 were synthesized according to
Scheme 1. Unsubstituted compound 1 was obtained by the
reduction of 2-formylphenylboronic acid and spontaneous
dehydration of the formed benzylic compound. Phenyl-
substituted compound (2) was synthesized according to the
literature method with small modifications.24 Compound 3 was
obtained as an unexpected product of the reaction of 2-formylphe-
nylboronic acid with N-ethylaniline. The full description of the
syntheses and characterization of the products are given in the
Supporting Information.
Crystal Structures. The structure of the parent 1,3-dihydro-
1-hydroxy-2,1-benzoxaborole (1) was published 10 years ago
Figure 1. Dimeric interactions in 1,3-dihydro-1-hydroxy-2,1-benzoxaborole (polymorph II) (1). The intermolecular hydrogen bonds are marked as
dotted lines. The displacement parameters are drawn at 50% probability level.

Structure and Properties of Benzoxaboroles
J. Phys. Chem. A, Vol. 114, No. 6, 2010 2327
Figure 3. Dimeric interaction in 3. The molecules are related by an inversion center (i: -x, 1-y, 1-z). The intermolecular hydrogen bonds are
marked as dotted lines. The displacement parameters are drawn at 50% probability level.
O · · · O distances are 2.767(3) and 2.757(3) Å, respectively),
which is comparable to the strength of the hydrogen bonds
forming the dimers in polymorph I. (The O · · ·O distances are
in the range of 2.752 to 2.757 Å.) For polymorph I, it has been
observed that the geometries of the benzoxaborole molecules
differ significantly.41,42 For instance, the endocyclic C-B or
exocyclic BO(H) bond lengths differ by 0.046 or 0.021 Å,
respectively. Such big discrepancies have been attributed to both
the different environment of van der Waals interactions in the
crystal lattice and the quality of the refinement.42 Despite many
attempts, we were unable to obtain a good quality crystal of
polymorph I following the original procedure given in ref 41;
therefore, it is difficult to argue with the latter factor. Impor-
tantly, in the case of polymorph II, the differences in geometries
of two independent molecules are fairly small and statistically
insignificant. (See Table 2.)
Both benzoxaborole derivatives 2 and 3 crystallize as
centrosymmetric planar dimers with one molecule in the
asymmetric part of the unit cell. The strength of the interactions
in dimers is comparable to that of the parent system (1), albeit
the O · · ·O distances are slightly smaller (2.737 and 2.712 Å,
respectively, for 2 and 3). The structure of 3 is additionally
stabilized by a hydrogen bond between amino group and oxygen
of hydroxy group (Figure 3), with the O · · ·HN distance equal
to 2.142 Å (O · · ·N distance 3.001 Å). In both cases, the
substituting phenyl ring is twisted in respect to oxaborole moiety
by 65.9 and 83.2° for 2 and 3, respectively.
of the oxaborole ring. For instance, O(11)-C(7) bond length
increases to 1.469(1) Å in 3 from 1.450(1) Å in 2 or
1.453(4)-1.455(4) Å in 1. Also, B(1)-O(11) shortens to
1.384(2) Å in 3 as compared with 1.401(5)-1.405(5) Å in 1.
This is solely an intramolecular effect because the ethylamino
group is involved in an intermolecular hydrogen bond with
O(12) (Figure 3), but despite this, the B(1)-O(12) bond is not
perturbed appreciably. (The B-O distance is 1.347(2) versus
1.347(5)-1.351(5) Å, respectively, for 3 and 1.) This strongly
supports a view that an oxaborole fragment is highly sensitive
to the structural modifications arising from substitution.42
Nuclear Magnetic Resonance Spectroscopy. The assign-
1
ment of all of the signals in H and 13C spectra of 1, 2, and 3
1
was made on the basis of H-1H COSY (correlated spectros-
copy), HSQC (heteronuclear single quantum coherence), and
HMBC (heteronuclear multiple bond correlation) spectra of the
solutions in deuterated acetone. The 13C NMR spectra of all of
the investigated boronic acids displayed the characteristic lack
of the signal of carbon atom adjacent to boron atom.1 The
B-OH proton signals were observed as singlets at 8.04 (1),
8.25 (2), and 8.07 ppm (3), respectively. The deshielding effect
of B-OH group44 results in the 6-H (ꢀ to the B-OH) signal
being the most shifted and similar for all compounds (7.74 for
1, 7.78 for 2, and 7.75 ppm for 3). Substitution at the
benzoxaborole ring in 2 and 3 results in shifting of the
corresponding proton signals (7-H) from 5.01 ppm for 1 to 6.18
(2) and 6.06 (3). The most deshielded carbon signals correspond
to C-2 and appear at 155.35 for 1, 158.48 for 2, and 159.10 for
3, showing no correlation in HSQC spectra. All of the observed
1H and 13C signals of 1, 2, and 3 as well as correlations are
given in Tables 3-5.
The phenyl ring is known as a weakly interacting substitu-
ent,43 and its impact on molecular geometry is usually small.
Indeed, in the case of 2, the geometry of the benzoxaborole
fragment is similar to that of 1 (Figure 2). However, small
modification of the phenyl ring by substitution in para position
by ethylamino substituent noticeably influences the geometry
Infrared Spectroscopy. The harmonic frequencies, PED, and
IR intensities of the compound 2 were calculated with the

2328 J. Phys. Chem. A, Vol. 114, No. 6, 2010
Adamczyk-Woz´niak et al.
1
TABLE 3: 1H and 13C NMR Signals and H,13C Correlations of Compound 1a
a * indicates signals of low intensity.
1
TABLE 4: 1H and 13C NMR Signals and H,13C Correlations of Compound 2a,b
a #
indicates 5-H, 9-H, 10-H, 11-H, 12-H, and 13-H signals overlap, and it is not possible to make the assignment, b * indicates signals of
low intensity.
1
TABLE 5: 1H and 13C NMR Signals and H,13C Correlations of Compound 3a
a * indicates signal of low intensity.
B3LYP method. Experimental and calculated IR frequencies
of this compound as well as their assignment together with PED
values calculated by normal coordinate analysis are presented
in the Supporting Information (Table S2). For the calculated
frequencies, the scaling factor of 0.9940 was applied,45 which
slightly improves the agreement between these series of values.
Experimental and calculated IR spectrum of compound 2 as
well as its deuterated analog is shown in Figure 4. The spectrum
of the deuterated compound was measured to facilitate bands
assignment. Appropriate calculations were also performed for
samples deuterated at OH position. Definitions of symmetry
coordinates are presented at the end of Table S2 in the
Supporting Information, which describes the character of
particular modes. In these assignments, no specification of
vibrations of particular bonds is given, so, for example, the
r(C-H) marks the stretching of the C-H bond, regardless of
the numbers of atoms forming the particular C-H bonds.
The force field of the dimer consists of 156 normal modes.
The interpretation of the spectra requires, however, such a
tedious procedure, because the formation of hydrogen bonds in
dimers leads to remarkable structural changes in interacting
molecules. Because of the performed calculations within

Structure and Properties of Benzoxaboroles
J. Phys. Chem. A, Vol. 114, No. 6, 2010 2329
and deuterated samples, which is 1.34 in molecule 2. For νBO
and νB-O(H) frequencies, the splitting is 5 and 7 cm-1
respectively.
,
Conclusions
The introduction of a phenyl substituent at the methylene
group of oxaborole ring has a small influence on the structure.
However, a small modification of the phenyl ring by the
introduction of an ethylamine group results not only in the
formation of N · · ·H-O hydrogen bond, but also in a change
of the angles between oxaborole and substituting phenyl rings
as well as the change of the O-C and B-O distances.
The geometrical parameters calculated by the DFT method
with the B3LYP/6-311++G(d,p) basis set are in good agree-
ment with the experimental values. The obtained results confirm
the good description of experimental spectra by this level of
theory. Performing calculations in internal coordinates, we were
able to discuss the effects of hydrogen bond formation on the
force field of monomers taking part in interactions. The results
demonstrate that it is necessary to describe the dimer as one
unit in calculations. It was also possible to describe the mutual
interactions in the complex by the band splitting parameters.
Crystallographic data also show that in molecules 1 and 3, the
hydrogen bonds are of similar strength, as one can judge from
the length of studied hydrogen bonds.
Figure 4. Experimental IR spectrum of solid 2 (b), its deuterated analog
(c), and calculated spectrum (a).
TABLE 6: Force Constants in Internal Coordinates [N/m]
Acknowledgment. This work was supported by the Ministry
of Science and Higher Education (grant N204 01932/0614). We
want to acknowledge the help of Professor Alfred Karpfen in
performing the calculation of the structure and force field on
advanced level of DFT theory. Possibilities of using the
computing facilities of WCSS (Wrocław Centre for Networking
and Supercomputing) are also acknowledged.
monomer
dimer
rOH
rBO(H)
rBO
827
662
582
425
427
656
5.9
699
757
523
412
436
662
6.1
RCO
rCC(O)
rCC(B)
γOH
Supporting Information Available: Description of the
syntheses of the investigated compounds, full crystal structure,
and structural refinement information, detailed description of
all NMR signals assignments as well as copies of 1H, 13C, HH
COSY, HMBC, and HSQC spectra for compounds 1-3, and
comparison of experimental and calculated molecular parameters
of compound 2 and 3. This material is available free of charge
via the Internet at http://pubs.acs.org.
ꢀBOH
52
149
approximation of internal coordinates, we are able to
demonstrate those changes in force constants of the most
important bonds in the formation of dimers. The results are
presented in Table 6.
The formation of a cyclic dimer leads to weakening of the
O-H bond force constant, from 827 to 699 N/m, which is
typical for hydrogen bonding. The difference in the behavior
of B-O bonds is interesting. The B-O(H) bond becomes
stronger after formation of the hydrogen bond, whereas the B-O
bond, participating in a five-member ring, becomes weaker. In
the first case, the force constant increases from 662 to 757,
whereas for the B-O bond, it decreases from 582 to 523 N/m.
Simultaneously, the strength of the C-O bond being a member
of a five-atom ring decreases, the force constant changes from
425 to 412 N/m. Additional increase in the bending frequencies
is observed. The formation of dimers of hydrogen bonds leads
to substantial reorganization of electron clouds in the five-
member ring.
References and Notes
(1) Boronic Acids: Preparation, Applications in Organic Synthesis and
Medicine; Hall, D. G., Ed.; Wiley-VCH: Weinheim, Germany, 2005.
(2) Maly, K. E.; Malek, N.; Fournier, J.-H.; Rodriguez-Cuamatzi, P.;
Maris, T.; Wuest, J. D. Pure Appl. Chem. 2006, 78, 1305.
(3) Rodriguez-Cuamatzi, P.; Vargas-Diaz, G.; Ho¨pfl, H. Angew. Chem.,
Int. Ed. 2004, 43, 3041.
(4) Rogowska, P.; Cyran´ski, M. K.; Sporzyn´ski, A.; Ciesielski, A.
Tetrahedron Lett. 2006, 47, 1389.
(5) Shimpi, M. R.; SeethaLekshmi, N.; Pedireddi, V. R. Cryst. Growth
Des. 2007, 7, 1958.
(6) James, T. D.; Phillips, M. D.; Shinkai, S. Boronic Acids in
Saccharide Recognition; RSC Publishing: Cambridge, U.K., 2006.
(7) Fujita, N.; Shinkai, S.; James, T. D. Chem. Asian J. 2008, 3, 1076.
(8) Severin, K. Dalton Trans. 2009, 5254.
(9) Haynes, R. R.; Snyder, H. R. J. Org. Chem. 1964, 29, 3229.
(10) Baker, S. J.; Hui, X.; Maibach, H. I. Annu. Rep. Med. Chem. 2005,
40, 323.
(11) Hui, X.; Baker, S. J.; Wester, R. C.; Barbadillo, S.; Cashmore, A. K.;
Sanders, V.; Hold, K. M.; Akama, T.; Zhang, Y.-K.; Plattner, J. J.; Maibach,
H. I. J. Pharm. Sci. 2007, 96, 2622.
(12) Baker, S. J.; Zhang, Y.-K.; Akama, T.; Lau, A.; Zhou, H.;
Hernandez, V.; Mao, W.; Alley, M. R. K.; Sanders, V.; Plattner, J. J. J. Med.
Chem. 2006, 49, 4447.
The consequence of the formation of dimers with the
symmetry center is the splitting of the vibrational modes into
symmetric and antisymmetric vibrations. In experimental IR,
as a rule, only in-phase vibration is observed. Running the
quantum chemical calculations, one can establish the effect of
the splitting. For the νOH stretching vibrations, it is 30 cm-1
,
which demonstrates rather weak interactions in the hydrogen
bonds forming dimers.
A similar conclusion follows from the experimental value of
ISR (isotopic spectral ratio) for the frequency of nondeuterated
(13) Rock, F. L.; Mao, W.; Yaremchuk, A.; Tukalo, M.; Crepin, T.;
Zhou, H.; Zhang, Y.-K.; Hernandez, V.; Akama, T.; Baker, S. J.; Plattner,

2330 J. Phys. Chem. A, Vol. 114, No. 6, 2010
Adamczyk-Woz´niak et al.
J. J.; Shapiro, L.; Martinis, S. A.; Benkovic, S. J.; Cusack, S.; Alley, M. R. K.
Science 2007, 316, 1759.
(14) Alley, M. R. K.; Baker, S. J.; Beutner, K. R.; Plattner, J. Expert
Opin. InVest. Drugs 2007, 16, 157.
(15) Anacor Pharmaceuticals, CA. http://www.anacor.com/conference_
posters.php.
(34) Sheldrick, G. M. SHELXL93: Program for the Refinement of Crystal
Structures; University of Go¨ttingen: Go¨ttingen, Germany, 1993.
(35) International Tables for Crystallography; Wilson, A. J. C., Ed.;
Kluwer: Dordrecht, The Netherlands, 1992; Vol. C.
(36) Modern Density Functional Theory: A Tool for Chemistry; Semi-
nario, J. M., Politzer, P., Eds.; Elsevier: Amsterdam, 1995; Vol. 2.
(37) Becke, A. D. J. Chem. Phys. 1993, 98, 5648.
(38) Lee, C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785.
(39) Martin, J. M. L.; Van Alsenoy, C. GAR2PED, University of
Antwerp: Antwerp, Belgium, 1995.
(40) Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb,
M. A.; Cheeseman, J. R.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.;
Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.;
Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.;
Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.;
Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li,
X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Adamo, C.; Jaramillo, J.;
Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.;
Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels,
A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.;
Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.;
Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.;
Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson,
B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03,
revision C.02; Gaussian, Inc.: Wallingford, CT, 2004.
(16) Baker, S. J.; Zhang, Y.-K.; Akama, T.; Wheeler, C.; Plattner, J. J.;
Rosser, R. M.; Reid, R. P.; Nixon, N. S. J. Labelled Compd. Radiopharm.
2007, 50, 245.
(17) Expert ReV. Clin. Immunol. 2008, 4, 309.
(18) Akama, T.; Baker, S. J.; Zhang, Y.-K.; Hernandez, V.; Zhou, H.;
Sanders, V.; Freund, Y.; Kimura, R.; Maples, K. R.; Plattner, J. J. Bioorg.
Med. Chem. 2009, 19, 2129.
(19) Seiradake, E.; Mao, W.; Hernandez, V.; Baker, S. J.; Plattner, J. J.;
Alley, M. R. K.; Cusack, S. J. Mol. Biol. 2009, 390, 196.
(20) Sanders, V.; Maples, K. R.; Plattner, J. J.; Bellinger-Kawahara, C.
PCT Int. Appl. WO-2007-146965, 2007.
(21) Wulff, G. Pure Appl. Chem. 1982, 54, 2093.
(22) Dowlut, M.; Hall, D. G. J. Am. Chem. Soc. 2006, 128, 4226.
(23) Be´rube´, M.; Dowlut, M.; Hall, D. G. J. Org. Chem. 2008, 73, 6471.
(24) Gunasekera, D. S.; Gerold, D. J.; Aalderks, N. S.; Chandra, J. S.;
Maanu, C. A.; Kiprof, P.; Zhdankin, V. V.; Reddy, M. V. R. Tetrahedron
2007, 63, 9401.
(25) Nicolaou, K. C.; Li, H.; Boddy, C. N. C.; Ramanjulu, J. M.; Yue,
T.-Y.; Natarajan, S.; Chu, X-J; Bra¨se, S.; Ru¨bsam, F. Chem.sEur. J. 1999,
5, 2584.
(26) Cambridge Structural Database, see: Allen, F. H. Acta Crystallogr.,
Sect. B: Struct. Sci. 2002, 58, 380.
(41) Zhdankin, V. V.; Persichini, P. J.; Zhang, L.; Fix, S.; Kiprof, P.
Tetrahedron Lett. 1999, 40, 6705.
(27) Cyran´ski, M. K.; Jezierska, A.; Klimentowska, P.; Panek, J. J.;
Sporzyn´ski, A. J. Phys. Org. Chem. 2008, 21, 472.
(28) Da¸browski, M.; Kurach, P.; Lulin´ski, S.; Serwatowski, J. Appl.
Organometal. Chem. 2007, 21, 234.
˙
(42) Adamczyk-Woz´niak, A.; Cyran´ski, M. K.; Zubrowska, A.; Sporzyn´-
ski, A. J. Organomet. Chem. 2009, 694, 3533.
(43) See, for example: (a) Hansch, C.; Leo, A.; Taft, R. W Chem. ReV.
1991, 91, 165. (b) Krygowski, T. M.; Ste¸pien´, B. T. Chem. ReV. 2005,
105, 3482. (c) Krygowski, T. M.; Ejsmont, K.; Ste¸pien´, B. T.; Cyran´ski,
M. K.; Poater, J.; Sola, M. J. Org. Chem. 2004, 69, 6634. (d) Dobrowolski,
M. A.; Kaniewski, J.; Krygowski, T. M.; Cyran´ski, M. K. Collect. Czech.
Chem. Commun. 2009, 74, 115.
(29) Lulin´ski, S.; Serwatowski, J. J. Organomet. Chem. 2007, 692, 2924.
(30) Arcus, V. L.; Main, L.; Nicholson, B. K. J. Organomet. Chem.
1993, 460, 139.
˙
(31) Jezierska, A.; Panek, J. J.; Zukowska, G. Z.; Sporzyn´ski, A. J. Phys.
Org. Chem., published online Nov 13, 2009, http://dx.doi.org/10.1002/
poc.1625.
(32) Oxford Diffraction CrysAlis CCD and CrysAlis RED; Oxford
Diffraction Poland: Wrocław, Poland, 2001.
(33) Sheldrick, G. M. Acta Crystallogr., Sect. A: Found. Crystallogr.
1990, 46, 467.
(44) Yamamoto, Y.; Moritani, I. J. Org. Chem. 1975, 40, 3434.
(45) Takahashi, M.; Ishikawa, Y.; Nishizawa, J.; Ito, H. Chem. Phys.
Lett. 2005, 401, 475.
JP9086283