Imino- and aminomethylphenylboronic acids: Stabilizing effect of hydrogen bonds

Article abstract of DOI:10.1016/j.tet.2012.02.072

ortho-Iminomethylphenylboronic acids were synthesized from the reaction of 2-formyl-phenylboronic acid with primary aromatic amines. Reduction of these compounds yielded the corresponding aminomethylphenylboronic acids. For both types of the compounds, th

Full text of DOI:10.1016/j.tet.2012.02.072

Tetrahedron 68 (2012) 3761e3767
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Imino- and aminomethylphenylboronic acids: stabilizing effect of hydrogen bonds
a
b
b
a
ꢀ
ꢀ
Agnieszka Adamczyk-Wozniak , Micha1 K. Cyranski , Beata T. Fra˛czak , Agnieszka Lewandowska ,
a
a,
*
ꢀ
Izabela D. Madura , Andrzej Sporzynski
a Faculty of Chemistry, Warsaw University of Technology, Noakowskiego 3, 00-664 Warsaw, Poland
b Faculty of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland
a r t i c l e i n f o
a b s t r a c t
Article history:
ortho-Iminomethylphenylboronic acids were synthesized from the reaction of 2-formylephenylboronic
acid with primary aromatic amines. Reduction of these compounds yielded the corresponding amino-
methylphenylboronic acids. For both types of the compounds, the crystal structure was determined by
single crystal X-ray diffraction method. Hydrogen-bonded dimers with an additional intramolecular
BeOeH.N hydrogen bond have been observed. Calculations at MP2/6e31þG** level proved that the
most stable form is that with the above-mentioned intramolecular hydrogen bond while the form with
dative N/B bond is less favoured. Since the calculated energy difference is small, the competition
between possible forms was analyzed in terms of substituent effect stabilization energy (SESE). In the
case of p-iminomethylphenylboronic acid, both hydroxyl groups are engaged in intermolecular OeH.O
interactions resulting in a supramolecular ribbon motif.
Received 2 December 2011
Received in revised form 10 February 2012
Accepted 27 February 2012
Available online 9 March 2012
Keywords:
Boronic acids
Hydrogen bond
BꢀN bond
Schiff bases
Mannich bases
MP2/6-31þG**
SESE
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
formylphenylboronic acids with primary amines, can be further
functionalized due to the presence of the C]N bond. For instance,
Arylboronic acids are systems that attract increasing scientific
interest due to their new applications in organic synthesis, cataly-
sis, supramolecular chemistry, biology, medicine and material en-
gineering.1 Hydrogen bond plays the key role in the supramolecular
assemblies formed by boronic acids.2 In addition to strong in-
termolecular hydrogen bonds in typical dimeric units and lateral
hydrogen bonds connecting them,3 there are many examples of
inter- and intramolecular bond formation, which together with the
intermolecular interactions tune the crystal architecture.4 The
special case is the presence of the ortho substituent able to form
a hydrogen bond with the BeOeH group. Intramolecular hydrogen
bonds are formed in this way with alkoxy,5 polyoxaalkyl,6 fluorine,7
or formyl8 groups. However, an intramolecular hydrogen bond is
not formed in case of the compounds with acetyl9 or methox-
ycarbonyl10 group at the ortho position.
boronic acids with the aminophosphonate group have been syn-
thesized from the reaction of Schiff bases with tris(trimethylsilyl)
phosphite.12
There are several examples of crystal structures, in which an
intramolecular BeOeH.N hydrogen bond is formed.8,13e20 In the
case of phenylboronic acid possessing both fluorine and amino-
methyl groups at ortho positions, an intramolecular hydrogen
bond is formed with the nitrogen atom but not with the fluorine
one.14
Esterification of the boronic group precludes the formation of
hydrogen bonds. Instead, formation of intramolecular N/B bond is
observed for many systems. The majority of open and cyclic boronic
esters with secondary and tertiary aminomethyl group form crys-
tals, in which such a bond is formed.18,21e31 Another example of an
intramolecular N/B bond is the pinacol ester of naphthylboronic
acid with an amino substituent.32 A similar structure was also ob-
served for the ester of 1,8-bis(dimethyl-amino)-9-boronoanth-
racene.33,34 The exceptions are the compounds with bulky sub-
stituents at nitrogen,35e39 where intramolecular N/B bond is not
formed due to steric hindrance. The N/B interaction is also not
present in compounds with eCH]NeNHe groups, in which E
configuration of the double bond and an anti arrangement of boron
and imine nitrogen atoms is observed.40e42
The compounds with aminomethyl substituent at the ortho
position of phenylboronic acids play a special role due to their wide
applications. Compounds with tertiary aminomethyl groups are
applied in a variety of sugars’ receptor systems.11 Iminomethyl
compounds (Schiff bases), which can be obtained in the reaction of
* Corresponding author. Tel.: þ48 22 2345737; fax: þ48 22 6282741; e-mail
ꢀ
address: spor@ch.pw.edu.pl (A. Sporzynski).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.072

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3762
The presence of an oxygen atom in the system makes the for-
For the typical reaction conditions applied in the synthesis of
Schiff bases (reflux in ethanol), the product contains various
amounts of ester II (path b). Moreover, elevated temperature and
azeotropic distillation of water promotes the formation of the
boroxin III (path c). It is possible to hydrolyze both products to the
desired boronic acid during the crystallization from water, but the
product may be contaminated by the products of hydrolysis of the
Schiff base fragment. Comparison of the results of the reactions
conducted in various solvents (ethanol, dichloromethane) and
temperatures allowed us to find the optimal conditions, described
for the synthesis of the compound 1a. The Mannich base 2b was
obtained by the reduction of the corresponding Schiff base with
sodium borohydride.51 For comparison, para-substituted Schiff
base 3 was synthesized. The reaction scheme and the structures of
the synthesized compounds are shown in Scheme 2.
mation of the structures with intramolecular BeOeH.O bond
possible. For instance, in phenylboronic acids with amido groups at
the ortho position, the O/B bond is observed instead of the N/B
one.13,29 Zwitterionic structures with methanol molecules, in which
the BꢀeO(Me).HeNþ intramolecular hydrogen bond was formed,
were obtained for several esters of boronic acids.18,19,43
In boroxins, similarly to the boronic esters, there are no hydroxyl
groups at boron able to form hydrogen bonds. Hence, the amino-
methyl substituents can interact with the boron centre with the
formation of the N/B bond. There are examples of crystals with
one,44 two,18,28,45,46 or three32 intramolecular N/B bonds
depending on the substituents on the nitrogen atoms. Structures of
unsymmetrical boroxins with one aminomethylphenyl group were
also described.47
The results of a computational investigation of the nitrogen-
boron interaction in o-(N,N-dialkylaminomethyl)arylboronate sys-
tems have been recently reported.48
2.2. Structures
Contrary to the numerous examples of phenylboronic acids with
CH2eNR2 groups at the ortho position, there are only a few exam-
ples of structures with CH2eNHR groups (Mannich bases)16 and
one with the CH]NR group (Schiff base).8 For such Mannich bases,
there is a possibility of three types of intramolecular interaction:
N/B, BeOeH.N or BeO.HeN. The aim of the present work was
to determine crystal and molecular structures of this type of
compounds and to compare the energy of possible structures with
various intramolecular interactions to determine the most stable
form.
The molecular structures of Schiff and Mannich bases,1a and 2b,
respectively, are shown in Fig. 1.
The molecules of 1a and 2b both crystallize in the monoclinic
system with one molecule in the asymmetric unit (Table S1,
Supplementary data). In both 1a and 2b molecules the boronic
moiety, B(OH)2, shows similar geometry with syn and anti confor-
mation of OH groups (Fig. 1). The CH2N group of the ortho sub-
stituents is situated in such a way that the B.N distances are
ꢁ
3.196(2) and 3.287(2) A in 1a and 2b, respectively. These distances
are almost twice as long as those observed for the N/B dative
bonds.18,21e31 Moreover, in both cases the boronic group is planar
with the boron atom being out of the plane defined by O1O2C1
2. Results and discussion
2.1. Synthesis
ꢁ
atoms by only 0.018(1) and 0.015(1) A for 1a and 2b, respectively.
Hence, the N/B dative bonds are not observed. Instead, in both
cases the nitrogen atoms interact with the syn hydroxyl group
through intramolecular OeH.N hydrogen bond forming a seven-
membered ring (Fig. 1). The formation of the H-bonded ring cau-
ses the boronic group to be tilted in such a way that the B1C1C2
angle increases to 129.2(6)ꢁ and 126.6(2)ꢁ in 1a and 2b, re-
spectively. In 1a, the dihedral angle between the boronic group’s
plane and the phenyl ring is only 6.56(6)ꢁ. Both the C7 and N1
atoms show the geometry in accordance with a sp2 hybridization
and hence the H-bonded seven-membered ring is almost flat with
In the reaction of aldehydes possessing a boronic group with
amines, several products can be formed (Scheme 1).
ꢁ
the highest deviation from planarity being less than 0.043(1) A. In
case of 2b the twist of the boronic group towards the phenyl ring is
significantly higher and amounts to 26.61(9)ꢁ. This, and the sp3
geometry of both C7 and N1 atoms, causes the H-bonded seven-
membered ring to be undulated and its geometry can be best de-
scribed as an envelope with O1, H1 and N1 atoms lying at the same
side of the plane formed by B1C1C2C7 atoms (see torsion angles in
Table S2, Supplementary data).
Further, the second hydroxyl group (anti) is a donor in an in-
termolecular OeH.O hydrogen bond while the acceptor is the syn
oriented hydroxyl group’s oxygen atom in the molecule related by
the inversion centre. Hence, compounds 1a and 2b exist in the
crystalline state as hydrogen-bonded centrosymmetric dimers
(Fig. 1). The OeH.O bridges are relatively strong, with O.O dis-
ꢁ
tances 2.761(1) and 2.772(1) A for 1a and 2b, respectively (Table 1).
It should be noted that in 1a the dimers are generally flat and the
only deviation from planarity is caused by the twist of the phenyl
groups of the iminomethyl substituents (the dihedral angle is
29.34(3)ꢁ). In 2b the whole aminomethyl group is almost perpen-
dicularly oriented towards the boronic acid dimeric [B(OH)2]2 unit
(the dihedral angle equals to 83.02(3)ꢁ). These differences influence
the secondary supramolecular structure in 1a and 2b (Fig. 2), al-
though in both cases the most significant CeH.O hydrogen bonds
are formed between the same pair of atoms (C5eH5 group is
a donor while O2 atom is an acceptor). In the case of 1a these
Scheme 1. Possible products of the reaction of o-formylphenylboronic acid with
amines.
In addition to the desired product I, ester II can be formed, when
the reaction is conducted in alcohol. Dehydration leads to the for-
mation of the boroxin III. Moreover, benzoxaboroles IV can also be
formed, especially for secondary amines.49,50

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A. Adamczyk-Wozniak et al. / Tetrahedron 68 (2012) 3761e3767
3763
Scheme 2. Synthesis of the compounds described in this work.
secondary H-bonds leads to 2-D layer structure on (100) plane,
while in 2b they form a ribbon propagating along [010] direction
(Fig. 2).
molecules (denoted as A and B in Fig. 3) in the asymmetric unit. The
geometry of molecules A and B is comparable and the slight dif-
ference is only in the twist of the iminomethyl substituent (see
torsion angles in Table S2). The boronic group orientation shows
syneanti conformation and the geometry of the phenylboronic
moiety is very close to that observed in the ortho derivative (Table
S2). The BC1C2 and B1C2C6 angles in 3 are close to 120ꢁ showing
symmetrical orientation of the boronic group, which is one of the
consequences of the lack of an ortho substituent. The most impor-
tant difference connected with the absence of the nitrogen atom at
the ortho position is the inability of the formation of the N/B
dative bond as well as OeH.N intramolecular interaction. As
mentioned above, the molecules of 1a are almost planar with only
a slight twist of the boronic unit towards phenyl ring. In case of 3
the B(OH)2 moiety is twisted by approx. 30ꢁ. Thus the geometry
resembles more the Mannich base derivative 2b than 1a.
These ribbons are further joined by weak CeH.p interactions,
while planes in 1a are joined by weaker CeH.O interactions. The
interesting feature of Mannich base derivative 2b is the fact that NH
group is not engaged in any intermolecular interactions as a hy-
drogen bond donor. It is worth to compare the above described
structures with the crystal structure of the phenylboronic acid with
para-substituted Schiff base (3). The molecules of 3 crystallize
in triclinic system with two crystallographically independent
1a
i
N1
i
O2
O1
O1
Table 1
C5
C6
B1
The geometry of intra- and intermolecular interactions in crystals of 1a, 2b and 3
C4
C3
C1
a
ꢁ
ꢁ
i
(A,
)
B1
C2
C7
i
O2
H.A
D.A
DeH.A
N1
1a
C9
C8
C13
O1eH1.N1
O2eH2.O1b
C5eH5.O2c
C4eH4.Cg2d
2b
1.67(2)
1.85(2)
2.48(2)
2.87(2)
2.616(2)
2.761(1)
3.449(2)
3.774(2)
166(2)
177(2)
166(1)
154(1)
C10
C11
C12
O1eH1.N1
O2eH2.O1e
C5eH5.O2f
C4 eH4.Cg2g
C14eH14B.Cg1h
3
1.84(2)
1.85(2)
2.60(1)
2.83(2)
2.77(2)
2.744(2)
2.772(1)
3.512(2)
3.689(2)
3.565(2)
162(2)
172(2)
153(1)
146(1)
137(1)
iv
N1
2b
iv
O1
O2
B1
C7
C5
C6
C1
C2
iv
B1
O2AeH20A.O1Ai
O2BeH20B.O1Bj
O1AeH1A.O2Bk
O1BeH1B.O2A
1.87(2)
1.83(2)
2.00(2)
1.95(2)
2.754(2)
2.738(2)
2.759(2)
2.764(2)
175(2)
175(2)
152(2)
153(2)
C3
C4
O1
iv
O2
N1
C8
C14
a
C13
Cg(1) and Cg(2) denote the centroids of the phenyl ring of the phenylboronic
moiety and the imino/aminomethyl substituent, respectively.
C12
b
Symmetry codes: 1/2ꢀx, 5/2ꢀy, 1ꢀz.
C9
c
Symmetry codes: 1/2ꢀx, ꢀ1/2þy, 1/2ꢀz.
d
C11
Symmetry codes: x, 1ꢀy, ꢀ1/2þz.
e
Symmetry codes: ꢀx, 2ꢀy, ꢀz.
C10
f
Symmetry codes: ꢀx, 1ꢀy, ꢀz.
g
Symmetry codes: x, ꢀ1þy, z.
h
Fig. 1. Basic centrosymmetric dimers in crystals of 1a and 2b with the atom num-
bering scheme. Thermal ellipsoids are drawn with 50% probability level. The intra-
molecular OeH/N hydrogen bonds are denoted with dots while intermolecular
OeH/O bonds with dashes.
Symmetry codes: 1ꢀx, 1/2þy, 1/2ꢀz.
i
Symmetry codes: 2ꢀx, 1ꢀy, 1ꢀz.
j
Symmetry codes: 2ꢀx, 2ꢀy, 1ꢀz
k
Symmetry codes: x, 1þy, z.

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A. Adamczyk-Wozniak et al. / Tetrahedron 68 (2012) 3761e3767
3764
alternately joined by O1eH1 donors and O2 acceptors forming
second type of eight-membered H-bonded rings. It is noteworthy
that all O.O separations in 3 are shorter than those observed for
OeH.O bonds in 1a and 2b (Table S2). The ribbons are further
connected through weak CH.O interactions into layers enclosed
with the iminomethyl substituents. Therefore the 3-D structure is
achieved by weak CH.p interactions. The nitrogen atom in 3 is not
engaged in any significant intermolecular interactions as an
acceptor.
2.3. Calculations
Starting from experimental geometries, a conformational anal-
ysis has been performed (in the case of 2b the methyl group has
been omitted for simplicity). Two forms of 1 were found: (a) sta-
bilized by H-bond (1A) or (b) stabilized by N/B donoreacceptor
interaction (1B) (Fig. 4). Although the lowest energy molecule is the
system existing in the crystal lattice, the difference in energy be-
tween both forms is very small (ca. 3.3 kcal/mol), so the N/B
donoreacceptor interaction may efficiently compete with an
intramolecular H-bond in solution or gas phase. Therefore, the
possibility of formation of the polymorph stabilized by the dative
bond cannot be excluded. In the case of 2, a system with N/B
donoreacceptor interaction and two forms of H-bond stabilized
structures where OH or NH groups may play a role of hydrogen
bond donors, were analyzed. Both systems stabilized by intra-
molecular hydrogen bond differ in energy by 6.5 kcal/mol, whereas
a system with a dative bond is placed in the middle. Similarly to the
Fig. 2. Secondary supramolecular structure formed by CeH.O hydrogen bonds: (a) 2-
D layer on (100) plane in crystals of 1a; (b) 1-D ribbon motif along [100] direction in
crystals of 2b. In both cases the hydrogen atoms not involved in H-bonds are omitted
for clarity.
Fig. 3. (a) Molecular structure of molecules A and B in crystals of 3 with the atom numbering scheme. Thermal ellipsoids are drawn with 50% probability level; (b) Basic su-
pramolecular ribbon motif along [010] direction. The intermolecular OeH.O hydrogen bonds are denoted with dashes.
Another consequence of the absence of the intramolecular hy-
drogen bond is a completely different basic supramolecular motif
observed in crystals of 3 (Fig. 3b). In this case it is a ribbon motif
formed by OeH.O hydrogen bonds, oriented along [010] direction.
In the ribbon, molecules A are bonded through two OeH.O
bridges with molecules A related by an inversion centre forming
eight-membered dimers (Table S2). The B molecules form the
analogous motif (Table S2). The A and B dimers are further
Schiff base (1), it is less stable by 3.3 kcal/mol as compared with the
most stable conformer (2C). Interestingly, due to much higher
flexibility of the aminomethyl group, the distance between boron
ꢁ
and nitrogen atoms is much smaller in the Mannich base (1.798 A,
ꢁ
2A), compared to the Schiff base (2.458 A, 1A). However, the OH.N
distance is the reverse: it is longer in the Mannich base (H.N
ꢁ
distance equal to 1.808 A, 2C) and shorter in the Schiff base (H.N
ꢁ
distance equal to 1.683 A, 1B). The latter observation is in line with

ꢀ
A. Adamczyk-Wozniak et al. / Tetrahedron 68 (2012) 3761e3767
3765
Fig. 4. Possible conformations of 1 and 2. The relative energies in respect to the lower energy conformer given in kcal/mol. The data in brackets refer to the molecules with
hydrogen atom replacing the phenyl ring bonded to nitrogen atom.
Table 2
the experimentally determined geometries. Replacing the phenyl
The SESE values for Schiff and Mannich bases. para and meta position is given in
respect to the boronic group. The values given in kcal/mol
ring at nitrogen by a hydrogen atom essentially does not change the
relative stability of the systems, they agree within 1 kcal/mol. No-
ꢁ
System/substituent
H
m-NH2
p-NH2
m-NO2
p-NO2
tably, the B.N distance is shorter in the Mannich base (1.723 A),
approaching a covalent single bond,53 whereas in the Schiff base it is
H
O
ꢁ
even longer as compared with the methylene derivative (2.579 A).
HO
B
NH
Although the stabilities of the above forms are comparable, in-
troduction of a substituent at the phenyl ring and/or at the nitrogen
may influence the relative energies and favour one of the struc-
tures. This point may be analyzed in terms of substituent effect
stabilization energy (SESE),54e56 which is the measure of the in-
crease/decrease in the stability of a system due to interactions
between the substituents at the ortho position. The SESE may be
accounted for by the following homodesmotic reaction (Scheme 3).
3.0
4.7
3.3
3.0
3.1
3.2
Y
HO
OH
B
NH
4.6
4.7
5.1
4.5
Y
HO
OH
HO
OH
B
N(H)R
+
B
N(H)R
H
O H
HO
B
NH
+
ꢀ0.3
ꢀ1.0
ꢀ0.5
da
ꢀ0.5
Y
Y
Y
Y
Y
where Y = NH2 or NO2
Scheme 3. Homodesmotic reaction.
7.4
7.5
8.0
7.2
7.6
7.7
8.0
7.9
8.0
The resulting energies lead both to information about the extent
of each interaction and the influence of substituents at the meta- or
para-position. The boronic group is a weakly electron accepting
group (sm¼ꢀ0.01, sp¼0.12).57 Similarly to the CH¼NPh group
(
sm¼0.35, sp¼0.42)57 or CH]NH, it should be stabilized by electron
7.9
donating substituents both in para or meta position in the phenyl
ring, whereas the CH2eNH2
(
sm¼ꢀ0.03, sp¼ꢀ0.11)57 or
eCH2eNHePh fragment should be stabilized in the reverse way.
Strong electron donating (NH2, sm¼ꢀ0.16, sp¼ꢀ06)57 or electron
accepting (NO2, sm¼0.71, sp¼0.78)57 groups have been chosen to
analyze the subtle interplay between substituents with and
through the phenyl ring to find whether they can support dative
bond or hydrogen bond formation. The results are given in Table 2.
As expected, the highest stabilization of both systems is always
due to hydrogen bond formation between the boronic group,
where hydroxyl group plays a role of hydrogen donor, and the ni-
a
one of the component of the reaction did not converge.
crucial,58 the influence of intramolecular factors that stimulate
esterification is more important than the intramolecular effects due
to substitution.59,60
trogen at
b position in ortho substituent is an acceptor. The dative
bond is only a little less favourable, but the differences are small
enough to be easily formed. The most striking observation is,
however, that the substituents in the ring practically do not in-
fluence the preference of hydrogen bond or dative bond formation.
They modify the strength of the interaction between B(OH)2 and
CH2eNH2 or CH]NH only in a very subtle way. The most important
factor that results in dative N/B bond formation seems to be the
esterification of the hydroxy groups. In the absence of hydrogen
atoms at oxygen atoms, the boronic group turns by ca. 90ꢁ to form
a donoreacceptor interaction, which is very significant and stabi-
lizes the system. Since obviously the environment of this process is
3. Conclusion
Both aminomethyl- and iminomethylphenylboronic acids are
stabilized by intramolecular hydrogen bonds involving hydroxyl
fragment at boronic group and nitrogen atom in
substituent at ortho position. Due to small difference in energy
between possible forms, the structures with dative bond N/B may
exist in solution, gas phase, and although we were not able to detect
other polymorphs, they possibly may also exist in the solid state.
Notably, the substituents at the phenyl ring practically do not in-
fluence the preference of hydrogen bond or dative bond formation.
b position of the

ꢀ
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4. Experimental
4.3. Calculations
4.1. Synthesis
All systems were fully optimised at MP2/6e31þG** level of
theory. The systems with hydrogen atoms replacing the phenyl ring
at nitrogen (see Fig. 4) corresponded to real minima at the potential
energy surface as checked by frequency calculations at the same
level of theory (MP2/6e31þG*). Their energies were corrected for
Zero Point Energy correction (ZPE). The molecules used for esti-
mation of aromatic stabilization energies were calculated in their
most stable conformations, except the case where dative bonds
were considered. Here phenylboronic acid, aminophenylboronic
acid or nitrophenylboronic acid had boronic group perpendicular to
the phenyl ring, to avoid the correction due to effect of rotation of
the group. These compounds had negative frequencies due to ro-
tation of the group. The differences between planar and nonplanar
phenylboronic acid, p-aminophenylboronic acid m-amino-
phenylboronic acid, p-nitrophenylboronic acid or m-nitro-
phenylboronic acid were 2.7 kcal/mol, 3.5 kcal/mol, 3.5 kcal/mol,
2.5 kcal/mol or 1.9 kcal/mol, respectively. The calculations were
carried out using Gaussian03 program.66
4.1.1. 2-(Phenyliminomethyl)phenylboronic
(0.84 g, 9.00 mmol) was added to
acid
(1a). Aniline
a solution of o-for-
mylphenylboronic acid (0.90 g, 6.00 mmol) in dichloromethane
(18 mL). The clear yellow solution was stirred at room temper-
ature for 0.5 h and refluxed for 9 h in the flask fitted with
a DeaneStark water separator. The reaction mixture was stored at
ꢀ4 ꢁC overnight. Crystalline precipitate was filtered and vacuum-
dried to give 1a (1.14 g, 84.4%), yellowish crystals, mp
234e238 ꢁC; Anal. Calcd for C13H12BNO2: C 69.38%, H 5.37%, N
6.22%; Found: C 69.30%, H 5.37%, N 6.25%. 11B NMR (128.3 MHz,
acetone-d6): d: 27.6 ppm.
4.1.2. 2-(o-Tolyliminomethyl)phenylboronic acid (1b). This com-
pound was synthesized in the same way from o-toluidine and o-
formylphenylboronic acid. Yield: 86.0%, yellowish crystals, mp
220e224 ꢁC; Anal. Calcd for C14H14BNO2: C 70.33%, H 5.90%, N
5.86%, Found: C 70.44%, H 5.93%, N 5.95%. 11B NMR (128.3 MHz,
acetone-d6): d: 27.5 ppm.
Acknowledgements
This work was supported by the Ministry of Science and Higher
Education (grant N204 01932/0614). B.T.F. acknowledges the
120000-501/68-BW-1681/17/05 grant for financial support of the
X-ray study and Interdisciplinary Centre for Mathematical and
Computational Modeling (Warsaw) for computational facilities.
A.A.-W., I.D.M. and A.S. acknowledge the financial support from
Warsaw University of Technology.
4.1.3. 4-(p-Tolyliminomethyl)phenylboronic acid (3). This com-
pound was synthesized in the same way from p-toluidine and p-
formylphenylboronic acid. Yield: 80.9%, yellowish crystals, mp
204e230 (dec); Anal. Calcd for C14H14BNO2: C 70.33%, H 5.90%, N
5.86%; Found: C 69.19%, H 5.83%, N 5.89%. 11B NMR (128.3 MHz,
acetone-d6): d: 27.7 ppm.
4.1.4. 2-(o-Tolylaminomethyl)phenylboronic acid (2b). Sodium bo-
rohydride (0.52 g, 13.8 mmol) was added slowly to 0.66 g,
(2.76 mmol) of 2-(o-tolyliminomethyl)phenylboronic acid (1b) in
anhydrous methanol (33 mL). The reaction was stirred at room
temperature for 2 h and then poured into iceewater (15 mL).
Hydrochloric acid (1 M, 7 ml) was added slowly and the mixture
stirred for 30 min. Crystalline precipitate was filtered and dried in
air to give 2b (0.54 g, 80.6%), yellowish crystals, mp 138e146 ꢁC;
Anal. Calcd for C14H16BNO2: C 69.75%, H 6.69%, N 5.81%; Found: C
Supplementary data
Crystal data and selected geometrical parameters for the com-
pounds 1a, 2b, and 3. Supplementary data associated with this
article can be found in the online version, at doi:10.1016/
j.tet.2012.02.072. These data include MOL files and InChiKeys of the
most important compounds described in this article.
69.38%, H 6.49%, N 5.18%. 11B NMR (128.3 MHz, acetone-d6):
d:
References and notes
29.4 ppm.
1. Boronic Acids. Preparation, Applications in Organic Synthesis and Medicine; Hall,
D. G., Ed.; Wiley-VCH: Weinheim, 2005.
2. Nishiyabu, R.; Kubo, Y.; James, T. D.; Fossey, J. S. Chem. Commun. 2011,1124e1150.
4.2. X-ray diffraction
ꢀ
ꢀ
3. Cyranski, M. K.; Jezierska, A.; Klimentowska, P.; Panek, J. J.; Sporzynski, A. J.
Phys. Org. Chem. 2008, 21, 472e482.
Crystal data and details of structure refinement for compounds
1a, 2b and 3 are specified in Table 1. X-ray diffraction data were
collected on a KUMA CCD k-axis diffractometer with graphite-
ꢀ
4. Sporzynski, A. Pol. J. Chem. 2007, 81, 757e766.
5. Davies, C. J.; Gregory, A.; Griffith, P.; Perkins, T.; Singh, K.; Solan, G. A. Tetra-
hedron 2008, 64, 9857e9864.
ꢀ
ꢀ
_
6. Adamczyk-Wozniak, A.; Cyranski, M. K.; Da˛browska, A.; Gierczyk, B.; Kli-
ꢁ
monochromated Mo-K
a
radiation (0.71073 A). The crystals were
ꢀ
mentowska, P.; Schroeder, G.; Zubrowska, A.; Sporzynski, A. J. Mol. Struct. 2009,
920, 430e435.
7. Rodriguez-Cuamatzi, P.; Tlahuext, H.; Hopfl, H. Acta Crystallogr. E 2009, 65,
positioned at 62.3 mm from the KM4CCD camera. Data collection
and reduction were performed with CrysAlis CCD and CrysAlis RED
programs, respectively.61 The data were corrected for Lorentz and
polarization effects but no absorption correction was applied. The
structures were solved by direct methods and refined with the full-
matrix least-squares technique using the SHELXS97 and SHELXL97
programs, respectively.62 The positions of H atoms were refined
freely. The presented figures were generated using ORTEP-3 for
Windows v.1.08 program63 and DIAMOND,64 while the geometric
calculations were done by PLATON package.65 Crystallographic data
for the structure have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication No. CCDC
854576 (1a), 854577 (2b) and 854578 (3). Copies of the data can be
obtained on application to CCDC, 12 Union Road, Cambridge CB2
1EZ, UK (email: deposit@ccdc.cam.ac.uk). Crystal data for the
compounds 1a, 2b and 3 are collected in Table S2 (Supplementary
data).
€
o44eo45.
8. Scouten, W. H.; Liu, X.-C.; Khangin, N.; Mullica, D. F.; Sappenfield, E. L. J. Chem.
Crystallogr. 1994, 24, 621e626.
9. Ganguly, A.; Meyers, C. Y.; Robinson, P. D. Acta Crystallogr.
o759eo761.
E 2003, 59,
10. Lulinski, S.; Serwatowski, J. Acta Crystallogr. C 2006, 62, o301eo303.
11. James, T. D.; Phillips, M. D.; Shinkai, S. Boronic Acids in Saccharide Recognition;
RSC Publishing: Cambridge, 2006.
12. M1ynarz, P.; Rydzewska, A.; Pok1adek, Z. J. Organomet. Chem. 2011, 696,
457e460.
13. Coghlan, S. W.; Giles, R. L.; Howard, J. A. K.; Patrick, L. G. F.; Probert, M. R.;
Smith, G. E.; Whiting, A. J. Organomet. Chem. 2005, 690, 4784e4793.
14. Arnold, K.; Batsanov, A. S.; Davies, B.; Whiting, A. Green Chem. 2008, 10,124e134.
ꢀ
ꢀ
ꢀ
ꢀ
15. Adamczyk-Wozniak, A.; Brzozka, Z.; Cyranski, M. K.; Filipowicz-Szymanska, A.;
_
_
ꢀ
Klimentowska, P.; Zubrowska, A.; Zukowski, K.; Sporzynski, A. Appl. Organomet.
Chem. 2008, 22, 427e432.
16. Zhao, J.; Davidson, M. G.; Mahon, M. F.; Kociok-Kohn, G.; James, T. D. J. Am.
€
Chem. Soc. 2004, 126, 16179e16186.
17. Blacquiere, J. M.; Sicora, O.; Vogels, C. M.; Cupertovic-Culf, M.; Decken, A.;
ꢂ
ꢀ
Ouellette, R. J.; Westcott, S. A. Can. J. Chem. 2005, 83, 2052e2059.

ꢀ
A. Adamczyk-Wozniak et al. / Tetrahedron 68 (2012) 3761e3767
3767
18. Zhu, L.; Shabbir, S. H.; Gray, M.; Lynch, V. M.; Sorey, S.; Anslyn, E. V. J. Am.
Chem. Soc. 2006, 122, 1222e1232.
44. Bosch, L. I.; Mahon, M. F.; James, T. D. Tetrahedron Lett. 2004, 45, 2859e2862.
45. Robinson, P. D.; Groziak, M. P.; Yi, L. Acta Crystallogr. C 1996, 52, 2826e2830.
46. Blatch, A. J.; Chetina, O. V.; Howard, J. A. K.; Patrick, L. G. F.; Smethurst, C. A.;
Whiting, A. Org. Biomol. Chem. 2006, 4, 3297e3302.
47. Iovine, P. M.; Gyselbrecht, C. R.; Perttu, E. K.; Klick, C.; Neuwelt, A.; Loera, J.;
DiPasquale, A. G.; Rheingold, A. L.; Kua, J. Dalton Trans. 2008, 3791e3794.
48. Larkin, J. D.; Fossey, J. S.; James, T. D.; Brooks, B. R.; Bock, C. W. J. Phys. Chem. A
2010, 114, 12531e12539.
19. Zhang, L.; Kerszulis, J. A.; Clark, R. J.; Ye, T.; Zhu, L. Chem. Commun. 2009, 2151e2153.
_
ꢀ
ꢀ
20. Adamczyk-Wozniak, A.; Madura, I.; Pawe1ko, A.; Sporzynski, A.; Zubrowska, A.;
_
Zy1a, J. Cent. Eur. J. Chem. 2011, 9, 199e205.
21. Wiskur, S. L.; Lavigne, J. J.; Metzger, A.; Tobey, S. L.; Lynch, V. Chem.dEur. J. 2004,
310, 792e3804.
22. Wiskur, S. L.; Lavigne, J. J.; Ait-Haddou, H.; Lynch, V.; Chiu, Y. H.; Canary, J. W.;
ꢀ
ꢀ
Anslyn, E. V. Org. Lett. 2001, 3, 1311e1314.
49. Sporzynski, A.; Lewandowski, M.; Rogowska, P.; Cyranski, M. K. Appl. Organo-
met. Chem. 2005, 19, 1202e1203.
23. Irving, A. M.; Vogels, C. M.; Nikolcheva, L. G.; Edwards, J. P.; He, X.-F.; Hamilton,
M. G.; Baerlocher, M. O.; Baerlocher, F. J.; Decken, A.; Westcott, S. A. New J.
Chem. 2003, 27, 1419e1424.
24. Toyota, S.; Oki, M. Bull. Chem. Soc. Jpn. 1992, 65, 1832e1840.
25. Toyota, S.; Asakura, M.; Futawaka, T.; Oki, M. Bull. Chem. Soc. Jpn. 1999, 72,
1879e1885.
26. Toyota, S.; Futawaka, T.; Ikeda, H.; Oki, M. J. Chem. Soc., Chem. Commun. 1995,
2499e2500.
27. Toyota, S.; Futawaka, T.; Asakura, M.; Ikeda, H.; Oki, M. Organometallics 1998, 17,
4155e4163.
ꢀ
ꢀ
50. Adamczyk-Wozniak, A.; Madura, I.; Velders, A. H.; Sporzynski, A. Tetrahedron
Lett. 2010, 51, 6181e6185.
51. Recently, the efficient methods of the syntheses of aliphatic20 and aromatic52
ortho-aminomethylphenylboronic acids via reductive amination have been
described
ꢀ
ꢀ
52. Adamczyk-Wozniak, A.; Fratila, R. M.; Madura, I. D.; Pawe1ko, A.; Sporzynski, A.;
Tumanowicz, M.; Velders, A. H.; Zy1a, J. Tetrahedron Lett. 2011, 52, 6639e6642.
53. Madura, I.; Krygowski, T. M.; Cyranski, M. K. Tetrahedron 1998, 54, 14913e14918.
_
ꢀ
54. Pross, A.; Radom, L.; Taft, R. W. J. Org. Chem. 1980, 45, 818e826.
55. Hehre, W. J.; Radom, L.; Schleyer, P. R.; Pople, J. A. Ab Initio Molecular Orbital
Theory; Wiley: Chichester, 1986; p 364.
28. Norrild, J. C.; Sotofte, I. J. Chem. Soc., Perkin Trans. 2 2002, 303e311.
29. Liu, X.-C.; Hubbard, J. L.; Scouten, W. C. J. Organomet. Chem. 1995, 493, 91e94.
€
ꢀ
30. Galbraith, E.; Kelly, A. M.; Fossey, J. S.; Kociok-Kohn, G.; Davidson, M. G.; Bull, S.
56. Krygowski, T. M.; Ste˛pien, B. T. Chem. Rev. 2005, 105, 3482e3512.
D.; James, T. D. New J. Chem. 2009, 33, 181e185.
31. Kim, K. T.; Cornelissen, J. J. L. M.; Nolte, R. J. M.; van Hest, J. C. M. J. Am. Chem.
Soc. 2009, 131, 13908e13909.
32. Giles, R. L.; Howard, J. A. K.; Patrick, L. G. F.; Probert, M. R.; Smith, G. E.; Whiting,
A. J. Organomet. Chem. 2003, 680, 257e262.
57. Hansch, C.; Leo, A.; Taft, R. W. Chem. Rev. 1991, 91, 165e195.
58. Kuivila, H. G.; Keough, A. H.; Soboczenski, E. J. J. Org. Chem. 1954, 19, 780e783.
59. Lorand, J. P.; Edwards, J. O. J. Org. Chem. 1959, 24, 769e774.
60. International Tables for Crystallography, Wilson, A. J. C., Ed.; Kluwer, Dordrecht,
1992, vol. C.
33. Yamashita, M.; Kamura, K.; Yamamoto, Y.; Akiba, K. Chem.dEur. J. 2002, 8,
2976e2979.
61. KUMA Diffraction Instruments GmbH, CrysAlis RED, Version 1.163; 2000.
62. Sheldrick, G. M. Acta Crystallogr. A 2008, 64, 112e122.
34. Yamashita, M.; Yamamoto, Y.; Akiba, K.; Hashizume, D.; Iwasaki, F.; Takagi, N.;
63. Farrugia, L. J. J. Appl. Crystallogr. 1997, 30, 565.
Nagase, S. J. Am. Chem. Soc. 2006, 128, 12424e12425.
64. Diamond ver. 3.2g, Crystal Impact GbR, Bonn, Germany.
35. Spencer, J.; Burd, A. P.; Goodwin, C. A.; Merette, S. A. M.; Scully, M. F.; Adatia, T.;
Deadman, J. J. Tetrahedron 2002, 58, 1551e1556.
36. Barkhuizen, D. A.; Howie, R. A.; Maguire, G. E. M.; Rademeyer, M. Acta Crys-
65. Spek, A. L. Heteroat. Chem. 2003, 36, 7e13.
66. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Montgomery, J. A.; 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,: Wallingford CT, 2004.
tallogr. E 2004, 60, o571eo573.
37. Hutin, M.; Bernardinelli, G.; Nitschke, J. R. Chem.dEur. J. 2008, 14, 4585e4593.
38. Scrafton, D. K.; Taylor, J. E.; Mahon, M. F.; Fossey, J. S.; James, T. D. J. Org. Chem.
2008, 73, 2871e2874.
39. Appoh, F. E.; Wheaton, S. L.; Vogels, C. M.; Baerlocher, F. J.; Decken, A.; Westcott,
S. A. Heteroat. Chem. 2009, 20, 56e63.
40. Groziak, M. P.; Robinson, P. D. Collect. Czech. Chem. Commun. 2002, 67,1084e1095.
41. Charkoudian, L. K.; Pham, D. M.; Franz, K. J. J. Am. Chem. Soc. 2006, 128,
12424e12425.
42. Charkoudian, L. K.; Pham, D. M.; Kwon, A. M.; Vangeloff, A. D.; Franz, K. J. Dalton
Trans. 2007, 5031e5042.
43. Collins, B. E.; Sorey, S.; Hargrove, A. E.; Shabbir, S. H.; Lynch, V. M.; Anslyn, E. V.
J. Org. Chem. 2009, 74, 4055e4060.