Acid assisted proton transfer in 4-[(4-R-phenylimino)methyl]pyridin-3-ols: NMR spectroscopy in solution and solid state. X-ray and UV studies and DFT calculations

Article abstract of DOI:10.1002/poc.1217

The behaviour of Schiff bases of 3-hydroxy-4-pyridincarboxaldehyde and 4-R-anilines (R=H, CH₃, OCH₃, Br, Cl, NO₂) in acid media has been described. ¹H, ¹³C, ¹⁵N-NMR chemical shifts allow to

Full text of DOI:10.1002/poc.1217

JOURNAL OF PHYSICAL ORGANIC CHEMISTRY
J. Phys. Org. Chem. 2007; 20: 610–623
Published online 31 May 2007 in Wiley InterScience
(
www.interscience.wiley.com) DOI: 10.1002/poc.1217
Acid assisted proton transfer in
-[(4-R-phenylimino)methyl]pyridin-3-ols: NMR
4
spectroscopy in solution and solid state,
X-ray and UV studies and DFT calculations
1
1
1
2
2
Almudena Perona, * Dionisia Sanz, * Rosa M. Claramunt, Elena Pinilla, M. Rosario Torres
and Jos e´ Elguero
3
1
Departamento de Qu ´ı mica Org a´ nica y Bio-Org a´ nica, Facultad de Ciencias, UNED, Senda del Rey 9, E-28040 Madrid, Spain
Departamento de Qu ´ı mica Inorg a´ nica, Laboratorio de Difracci o´ n de Rayos-X, Facultad de Ciencias Qu ı´ micas,
2
UCM, E-28040 Madrid, Spain
3
Instituto de Qu ´ı mica M e´ dica, CSIC, Juan de la Cierva, 3, E-28006 Madrid, Spain
Received 5 March 2007; accepted 18 April 2007
—
ABSTRACT: The behaviour of Schiff bases of 3-hydroxy-4-pyridincarboxaldehyde and 4-R-anilines (R—H, CH ,
3
1
OCH , Br, Cl, NO ) in acid media has been described. H, C, N-NMR chemical shifts allow to establish the
13
15
3
2
protonation site and its influence on the hydroxyimino/oxoenamino tautomerism. DFT calculations, electronic spectra
and X-ray diffraction are in agreement with the NMR conclusions. Copyright # 2007 John Wiley & Sons, Ltd.
KEYWORDS: Schiff bases; acid media; tautomerism; hydrogen bonds; NMR spectroscopy; density functional
calculations; X-ray; electronic spectra
INTRODUCTION
The present paper analyses the proton transfer due to
the effect of substituents and to the presence of acids on
the 3-hydroxypyridine-4-carboxaldehyde aromatic Schiff
bases (8–13) depicted in Scheme 1. H, C and N-NMR
spectroscopy have proved to be the best technique to
evaluate the tautomeric equilibrium. The conclusions
based on NMR studies (both in solution and in the solid
state) are supported by computational calculations and
UV–Visible studies as well as by one X-ray structure
determination.
Transfer of a proton is the basic step in numerous
chemical reactions and in many enzymatic processes it
1
13
15
1
becomes the rate-determining step. Double proton
transfer among DNA bases has been proposed as a
2
mechanism for DNA mutation. The importance of such
phenomenon in biochemical processes has lead to the
study of many tautomeric equilibria.
Aromatic Schiff bases of o-hydroxyaldehydes are an
interesting kind of molecules because of their tautomeric
In previous publications we demonstrated the existence
of the intramolecular hydrogen bonded structure present
—
in 4-[(4-R-phenylimino)methyl]pyridin-3-ols (R—
3
properties related to proton transfer; in general the
4–6
hydroxyimino tautomer is the only observed form.
However, the tautomeric equilibrium depends on the
H, CH , OCH , Br, Cl, NO ) (8–13), prepared from
3
3
2
7
solvent, temperature, substituents pattern, physical
8
8,9
3-hydroxypyridine-4-carboxaldehyde (1) and an equi-
molar amount of the corresponding 4-R-anilines, and
confirmed that these compounds exist as hydroxyimino
8
state of the compound and added hosts (i.e. cyclodex-
10
trins).
6
One of the most important Schiff base is the cofactor of
0
tautomers with (E)-configuration.
the vitamin B , pyridoxal-5 -phosphate PLP, involved in
6
the transformation of aminoacids. In the first step of the
catalytic cycle the proton transfer occurs in the
intramolecular O—HꢀꢀꢀN hydrogen bond, assisted by
RESULTS AND DISCUSSION
NMR spectroscopy
11
protonation of the pyridine ring.
*
Correspondence to: A. Perona, D. Sanz, Departamento de Qu ´ı mica
Org a´ nica y Bio-Org a´ nica, Facultad de Ciencias, UNED, Senda del Rey
, E-28040 Madrid, Spain.
In order to study the protonation site and how this affects
the acid-base characteristics of the hydrogen bond,
9
E-mail: aperona@bec.uned.es; dsanz@ccia.uned.es
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623

ACID ASSISTED PROTON TRANSFER
611
1
13
15
In acid media, the H, C and N-NMR data support
the coexistence of both hydroxyimino and oxoenamino
tautomers in compounds 8–13, as we will discuss later on.
1
The H-NMR chemical shifts of compounds 8–13 in
neutral and acid media are shown in Table 2. The
chemical shift protonation effects on protons H2, H5 and
—
CH—N of the pyridine moiety are significant in imines
–12, the most important of ꢁ0.95 ppm for H5 and
8
ꢁ
—
0.65 ppm for CH—N. Moreover, the J
coupling
,6
5
12
constant increases 1 Hz due to protonation. In com-
pound 13, all protons are only slightly affected save the
—
CH—N that is shifted downfield 0.35 ppm and the H5
shifted downfield 0.77 ppm. Finally, the chemical shifts
values of the phenyl group protons close to the tautomeric
0
0
imine centre, H2 /H6 , increase in all cases on protonation
Fig. 1).
(
13
The C-NMR chemical shifts of compounds 8–13 in
neutral and acid media are gathered in Tables 3 and 4.
Scheme 1. 4-[(4-R-Phenylimino)-methyl]-pyridin-3-ol
8–13), hydroxyimino/oxoenamino forms
The assignments of all signals in CDCl and TFA at 300 K
3
(
are based on gs-HMQC and gs-HMBC experiments and
the coupling constants values. We already reported
that the hydroxyimino and oxoenamino forms can be
13
1
0–20 mg of each imine (8–13) were dissolved in
distinguished by C-NMR, the most affected carbon
atom when the tautomeric equilibrium changes is that
bonded to the oxygen, the corresponding chemical shifts
values for other carbons do not significantly vary
trifluoroacetic acid (TFA, pK ¼ 0.2) and the NMR
a
spectra recorded. In all cases, protonation takes place
on the pyridine nitrogen, making these molecules highly
sensitive to hydrolysis with partial decomposition into
their precursors (Scheme 2). The less stable imines in acid
media are those bearing electron-withdrawing substitu-
ents and Table 1 shows the relative percentages of
compounds in TFA solution after time evolution.
13
when the tautomeric form changes. The results found
for Schiff bases 8–13 in acid media are very similar: C6
0
and C1 chemical shifts decrease around 12 ppm, C2
diminishes about 6 ppm and C5 increases in 6 ppm.
These changes can be explained as the result of the
þ
þ
Scheme 2. 4-[(4-R-Phenylimino)methyl]pyridinium-3-ols trifluoroacetates (8H –13H )
Table 1. Relative percentages in TFA solution
Comp.
Imine
H
CH3
OCH3
Br
Cl
52
24
24
NO2
Freshly prepared solution
75
12.5
12.5
72
14
14
80
10
10
58
21
21
43
28.5
28.5
Aldehyde
Amine
5
days
Imine
Aldehyde
Amine
46
27
27
50
25
25
44
28
28
48
26
26
47
26.5
26.5
33.3
33.3
33.3
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

6
12
A. PERONA ET AL.
1
Table 2. H-NMR chemical shifts (d in ppm) and coupling constants (J in Hz) of 8–13 in neutral and acid media
—
Comp.
Solvent
CDCl3
TFA
CH—N
8.65(s)
9.30(s)
H2
OH
12.76(sbr)
—
H5
H6
H2’/H6’
7.33(m)
7.61(m)
H3’/H5’
7.46(m)
7.51(m)
R4’
8
8.52(s)
8.75(s)
7.28(d)
8.27(d)
J5,6 ¼ 4.8 a
8.10
J5,6 ¼ 6.0
ꢂ0.17
8.25(dbr)
7.35(m)
7.51(m)
HR
8.17
a
8
Dd
CDCl3
0.65
8.64(sbr)
0.23
8.50(sbr)
0.89
7.25(m)
0.28
7.25(m)
0.05
7.25(m)
0.16
2.40(s)
9
9
12.90(sbr)
—
J5,6 ¼ 4.6 a
8.17
HR
TFA
9.29(s)
8.82(sbr)
8.21
a
7.56(m)
7.35(m)
2.35(s)
J5,6 ¼ 5.7
Dd
CDCl3
0.65
8.55(s)
0.32
8.42(s)
0.96
7.17(d)
ꢂ0.08
0.31
7.26(m)
0.10
6.90(m)
ꢂ0.05
1
1
0
12.87(s)
—
8.17(d)
J5,6 ¼ 4.8 a
8.20
3.78(s)
0HR
TFA
9.18(s)
8.84(s)
8.21
a
7.70(m)
7.08(m)
3.86
J5,6 ¼ 6.1
Dd
CDCl3
0.63
8.63(s)
0.42
8.52(s)
1.04
7.28(d)
0.03
8.28(d)
0.44
7.20(m)
0.18
7.59(m)
0.08
—
1
1
1
12.50(sbr)
—
J5,6 ¼ 4.9 a
8.11
1HR
TFA
9.25(s)
8.71(s)
8.13
a
7.65(m)
7.48(m)
—
J5,6 ¼ 6.0
Dd
CDCl3
0.66
8.60(s)
0.23
8.50(s)
0.89
7.24(d)
ꢂ0.13
0.45
7.25(m)
ꢂ0.11
1
1
2
12.50(sbr)
—
8.26(d)
J5,6 ¼ 4.9 a
8.12
7.41(m)
—
—
2HR
TFA
9.24(s)
8.71(s)
8.14
a
7.58(m)
7.48(m)
J5,6 ¼ 6.0
Dd
CDCl3
0.64
8.67(s)
0.21
8.57(s)
0.90
7.34(d)
ꢂ0.12
0.33
7.37(m)
0.07
8.35(m)
1
1
3
12.06(sbr)
—
8.33(d)
—
—
J5,6 ¼ 5.0
3HR
TFA
9.02(s)
0.35
8.51(s)
8.11(d)
0.77
8.26(d)
7.57(m)
0.20
8.33(m)
J5,6 ¼ 5.9
ꢂ0.07
Dd
ꢂ0.06
ꢂ0.02
1
a
1
These protons show an AB system, the assignments are based on gs-HMQC experiments and on the coupling constant values JC5H5 < JC6H6
.
pyridine nitrogen protonation that leads in solution to the
coexistence of the two tautomeric protonated forms in
equilibrium. The phenyl moiety, due to intrinsic R
substituent effects, is not useful for equilibrium studies
(
Fig. 2).
15
Similarly, Table 5 reports the N chemical shifts of N1
and N2 for compounds 8–13 in neutral and acid media,
the assignments are based on gs-HMBC spectra (Fig. 3).
In the case of N1, the Dd values (ꢂ120 to ꢂ130 ppm) are
14
characteristic of pyridine protonation. The values of N2
obtained in TFA for 8–12 are intermediate between the
typical chemical shifts of hydroxyimino (approximately
ꢂ55.5 ppm) and oxoenamino (approximately ꢂ285 ppm)
8,13–15
nitrogen atoms,
pointing out to a rapid proton
exchange between the two tautomers (Fig. 4). On
the other hand, the chemical shifts of N2 of 4-(4-
nitrophenylimino)methyl]pyridin-3-ol (13) in neutral and
acid media are very close (Dd ¼ ꢂ0.8 ppm), indicating
that the hydroxyimino form is the predominant one in
both media (>99%) for such derivative. The reason for
such behaviour can be explained as due to the p-nitro
group effect that diminishes the electron density on the
imino nitrogen.
1
Figure 1. Protonation effects in the H-NMR chemical shifts
Dd(TFA-CDCl )] of compounds 8–12. This figure is available
in colour online at www.interscience.wiley.com/journal/poc
[
3
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

ACID ASSISTED PROTON TRANSFER
613
1
3
Table 3. C-NMR chemical shifts (d in ppm) and coupling constants (J in Hz) for the pyridine moiety of 8–13
—
CH—N
Comp.
Solvent
CDCl3
C2
C3
C4
C5
C6
8
160.9
J ¼ 163.6
141.2
J ¼ 180.8
155.1
123.6
123.6
J ¼ 161.0
140.3
J ¼ 179.9
1
1
1
1
1
1
1
1
3
3
3
3
J ¼ 6.2
J ¼ 10.3
J ¼ 9.2
J ¼ 11.0
þ
8
H
TFA
158.3
135.0
J ¼ 193.3
162.3
125.7
130.6
J ¼ 174.6
127.9
J ¼ 183.5
J ¼ 198.0
3
3
3
J ¼ 6.1
J ¼ 5.9
J ¼ 5.0
Dd
CDCl3
ꢂ2.6
ꢂ6.2
7.2
155.1
J ¼ J ¼ J ¼ 7.3
2.1
123.6
7.0
123.4
ꢂ12.4
9
9
159.6
140.9
J ¼ 180.8
140.2
1
1
1
3
3
2
1
1
1
J ¼ 163.4
J ¼ 161.0
J ¼ 181.5
3
3
3
3
J ¼ 6.3
J ¼ 11.1
J ¼ 9.2
J ¼ 11.4
þ
H
TFA
156.2
134.6(br)
157.5
J ¼ 3.1
126.3(br)
130.5
J ¼ 175.9
128.6
1
2
1
J ¼ 184.4
J ¼ 191.6
J ¼ 194.7
3
3
J ¼ 6.1
J ¼ 8.0
Dd
CDCl3
ꢂ3.4
ꢂ6.3
2.4
155.1
2.7
123.8
7.1
123.4
ꢂ11.6
1
1
1
1
0
158.2
J ¼ 163.1
141.1
J ¼ 181.0
140.4
J ¼ 182.3
1
1
1
1
1
1
1
1
1
1
1
1
1
J ¼ 160.7
3
3
3
3
3
J ¼ 6.2
J ¼ J ¼ 9.3
J ¼ 9.0
J ¼ 11.9
þ
þ
0H
TFA
153.1
J ¼ 185.8
ꢂ5.1
133.9
J ¼ 193.4
160.8
126.8
130.0
J ¼ 174.8
6.6
129.2
J ¼ 198.2
ꢂ11.2
1
Dd
CDCl3
ꢂ7.2
5.7
154.9
3.0
123.3
1
161.3
141.2
J ¼ 181.8
123.6
J ¼ 161.0
140.4
1
J ¼ 163.6
J ¼ 182.0
3
3
3
3
J ¼ 6.2
J ¼ 10.3
J ¼ 10.1
J ¼ 10.7
1H
TFA
158.2
134.7
J ¼ 195.0
162.4
127.2
129.9
J ¼ 173.8
127.8
1
J ¼ 181.5
J ¼ 195.1
3
J ¼ 5.3
Dd
CDCl3
ꢂ3.1
ꢂ6.5
7.5
154.8
3.9
123.2
6.3
123.5
ꢂ12.6
1
2
161.1
141.0
J ¼ 181.1
140.3
1
1
1
1
J ¼ 163.7
J ¼ 161.1
J ¼ 182.6
3
3
3
3
J ¼ 6.2
J ¼ 10.7
J ¼ 9.1
J ¼ 12.5
3
J ¼ 5.8
þ
þ
1
1
1
2H
TFA
158.2
J ¼ 180.9
ꢂ2.9
134.7
J ¼ 192.0
162.4
126.9
129.9
J ¼ 173.9
6.4
127.8
J ¼ 196.4
ꢂ12.5
1
1
1
1
1
1
1
1
1
1
Dd
CD CN
ꢂ6.3
7.6
155.9
J ¼ J ¼ 4.9
3.9
124.6
3
166.8
141.8
J ¼ 181.7
125.8
J ¼ 163.6
141.7
3
1
3
3
J ¼ 168.2
J ¼ 182.0
3
3
3
3
J ¼ 5.9
J ¼ 10.2
J ¼ 9.9
J ¼ 10.1
3H
TFA
161.2
132.7
J ¼ 191.8
159.5
J ¼ 6.1
130.2
5.6
128.7
J ¼ 175.6
130.0
1
3
J ¼ 174.8
J ¼ 197.0
3
J ¼ 6.0
Dd
ꢂ5.6
ꢂ9.1
3.6
2.9
ꢂ11.7
To verify that TFA, which modifies the acidity of the
are observed and no evolution with time was observed.
Similarly occurs in DMSO-d solution, the minor species
media and the polarity around the hydrogen bonds,
stabilizes the oxoenamino versus the hydroxyimino
tautomer, we decided to prepare the tetrafluoroborate
6
evolving towards the major one after 12 h; the OH
chemical shift was detected only in DMSO-d as a very
6
R
S
R
S
salts 10H BF , 11H BF plus the complex 11ꢀPicric
broad signal at 9.70 ppm. In CD OD addition of the
3
4
4
acid to study them in solid state comparatively to solution
by NMR spectroscopy. The CPMAS NMR spectroscopy
has been already used to elucidate Schiff bases
solvent to the double imino bond occurs, the imino proton
shifts upfield from 9.12 to 5.90 ppm (Experimental Part).
1
3
R
S
4
R
S
4
The C-NMR data for salts 10H BF , 11H BF and
15–17
structure.
In the solid state, where the signals are
11ꢀPicric acid are shown in Table 6 (gs-HMQC and
not averaged by solvent effects or by rapid exchange
processes often present in solution, the change in the
nitrogen chemical shifts caused by complete protonation
can be of the order of 50–100 ppm, allowing a more
gs-HMBC spectra were used for the assignments). For
tetrafluoroborate salts 10H BF , 11H BF no signifi-
R
S
4
R
S
4
cant differences between neutral imines and their salts
appear, and the signals used to be very broad in solid state
18–20
15
(e.g. in Fig. 5). The N-NMR chemical shifts show that
accurate study.
1
From the H-NMR data, these salts exist in the
the pyridine nitrogen is protonated and only the
hydroxyimino form is present (Table 7, Fig. 6). In
hydroxyimino form. In THF-d two different salt species
8
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

6
14
A. PERONA ET AL.
1
3
Table 4. C-NMR chemical shifts (d in ppm) and coupling constants (J in Hz) for the phenyl moiety of 8–13
0
0
0
0
C4
Comp.
Solvent
CDCl3
C1
C2
C3
R
8
147.6
121.2
J ¼ 160.4
129.5
J ¼ 161.8
128.0
—
3
3
3
1
1
1
1
1
1
J ¼ J ¼ J ¼ 8.7
J ¼ 163.0
3
3
3
3
3
J ¼ 6.2
J ¼ 8.0
J ¼ J ¼ 7.6
4
J ¼ 5.5
þ
8
H
TFA
134.7
120.4
J ¼ 164.1
129.9
J ¼ 167.0
132.9
1
J ¼ 165.3
3
3
3
3
J ¼ J ¼ 6.0
ꢂ0.8
J ¼ 7.7
J ¼ J ¼ 7.1
Dd
CDCl3
ꢂ12.9
0.4
130.1
4.9
138.3
9
144.8
121.1
J ¼ 159.6
21.0
1
3
3
3
1
3J
2
J ¼ J ¼ J ¼ 7.3
J ¼ 158.3
¼ J
¼ 6:3
J ¼ 126.6
ðH20=H60Þ
ðH20=H60Þ
ðCH3Þ
ðCH3Þ
3
3J
3
3
J ¼ 4.1
¼ 5:0
J ¼ J ¼ 3.6
ðCH3Þ
3
J ¼ 5.0
þ
9
H
0
TFA
131.9
120.4
J ¼ 162.0
130.7
J ¼ 161.3
140.8
¼ 6:3
19.0
1
1
1
3J
¼ J
2
J ¼ 127.8
3
3
J ¼ 4.6
J ¼ 4.0
Dd
CDCl3
ꢂ12.9
ꢂ0.7
0.6
114.8
2.5
159.8
ꢂ2
1
140.36
122.7
J ¼ 159.3
55.6
1
1
1
J ¼ 160.3
J ¼ 144.1
3
3
J ¼ 6.2
J ¼ 5.2
þ
1
0H
TFA
1
27.8
122.9
115.6
J ¼ 165.6
164.0
54.5
J ¼ 146.2
1
1
1
J ¼ 163.5
3
3
J ¼ 5.5
J ¼ 4.7
Dd
CDCl3
ꢂ12.6
0.2
122.8
0.8
132.6
4.2
121.7
J ¼ J ¼ 9.8
ꢂ1.2
1
1
146.5
—
3
3
3
1
1
1
3
3
J ¼ J ¼ J ¼ 8.3
J ¼ 161.6
J ¼ 167.2
3
3
J ¼ 5.8
J ¼ 6.0
þ
þ
þ
1
1H
TFA
135.5
121.8
J ¼ 165.9
133.2
J ¼ 172.1
127.0
—
1
3
3
J ¼ 5.0
J ¼ 5.5
Dd
CDCl3
ꢂ11
ꢂ1
0.6
129.5
5.3
133.6
1
1
2
145.8
122.4
J ¼ 163.2
—
—
3
3
3
1
1
1
3
3
J ¼ J ¼ J ¼ 8.8
J ¼ 167.6
J ¼ J ¼ 10.1
3
3
2
2
J ¼ 5.8
J ¼ 5.4
J ¼ J ¼ 3.2
2H
TFA
135.0
121.7
J ¼ 165.3
130.1
J ¼ 170.9
139.4
1
3
3
J ¼ 5.5
J ¼ 5.2
Dd
CD CN
ꢂ10.8
ꢂ0.7
0.6
126.2
5.8
147.8
1
1
3
154.5
123.6
J ¼ 166.4
—
—
3
3
1
1
1
J ¼ 8.1
J ¼ 169.9
3
3
J ¼ 5.7
J ¼ 4.6
3H
TFA
147.0
121.7
J ¼ 167.1
124.7
J ¼ 171.5
149.2
1.4
1
3
3
J ¼ 5.6
J ¼ 5.1
Dd
ꢂ7.5
ꢂ1.9
ꢂ1.5
1
5
R
S
1
1ꢀPicric acid the acidity of picric acid (2,4,6-
N CPMAS NMR spectrum of 11H BF suggests the
4
trinitrophenol, pK ¼ 0.4) is not strong enough to
existence either of different conformations or poly-
morphs.
a
protonate the pyridine nitrogen, as we can observe in
the N1 chemical shift of Table 7; possibly this nitrogen
atom is coordinated through hydrogen bonding to the OH
of the picric acid, thus the compound is not a picrate but a
X-Ray crystallographic studies
21
13
picric acid complex. The C chemical shift values of
0
0
00
00
the picric acid, C1 , C2 and C4 in the Experimental
Part, also indicate that the hydroxyl proton is transferred
in some amount towards the pyridine nitrogen. The
presence of different signals for N1 and N2 in the
The molecular structure of a compound being dependent
on its physical state, different tautomeric forms can be
found in solution, in the crystal and in the gas phase.
Concerning the present work, X-ray diffraction studies
2
2
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

ACID ASSISTED PROTON TRANSFER
615
N2ꢀꢀꢀH1B-O1, which locks the imine group into the
planar configuration even in the presence of the water
23
molecule, where O2A binds the pyridine nitrogen
through H1A-N1. The hydrogen atoms of the water
molecule were not observed in the difference maps and
˚
are not shown, but OꢀꢀꢀBr [mean value of 3.65(2) A] and
˚
OꢀꢀꢀF [in the range 2.63(3)–2.91(3) A] distances are
consistent with hydrogen-bonding formation between the
heteroatoms.
The N1-H1AꢀꢀꢀO2A and BrꢀꢀO hydrogen bonds lead to
the formation of dimers in the packing, which also
present p–p stacking interactions between the phenyl
and pyridinium rings. The distance between the ring
˚
centroids is 3.79 A and the angle between the ring normal
and the vector between the ring centroids is of 21.23,
˚
since one ring is slipped 1.38 A relative to the opposite
2
4
molecule. Additionally the OꢀꢀꢀF(BF ) hydrogen bonds
4
give rise to undulated layers parallel to (100) as depicted
in Fig. 8.
1
3
Figure 2. Protonation effects in the C-NMR chemical
shifts [Dd(TFA-CDCl )] of compounds 8–13. This figure is
3
available in colour online at www.interscience.wiley.com/
journal/poc
Theoretical calculations
ꢃꢃ
25,26
The hybrid DFT B3LYP/6-31G method
was used to
carry out the optimisation of the structures and no
restrictions were imposed, save the initial angle C4CHN
that was set to 08 in order to form the intramolecular
showthat (E)-4-[(4-bromophenylimino)methyl]-3-hydro-
R
S
xypyridinium tetrafluoroborate (11H BF ) exists exclu-
4
—
sively in the hydroxyimino form in the crystal at room
temperature, in agreement with the CPMAS NMR data.
—OHꢀꢀꢀN—C< hydrogen bond. After each geometry
optimisation, the vibrational frequencies were computed
in order to ensure that the calculated geometry
corresponds to a minimum and not to a saddle point
on the energy hypersurface.
R
S
4
Attempts to get good quality crystals of 10H BF and
1
unsuccessful.
1ꢀPicric acid for X-ray diffraction analysis proved to be
R
The structure of the cation 11H showing the atomic
numbering is shown in Fig. 7 and selected distances and
angles are listed in Table 8. The driving force for the
observed planarity is the intramolecular hydrogen bond
At the same theoretical level we had already
established that in neutral imines the hydroxyimino
6
tautomer with E configuration is the most stable. Taking
this structure as the starting point, the Schiff bases 8–13
present three different positions to be protonated by TFA
(N1, N2 and OH). The results on the geometry
optimisation of the different structures point out that
protonation are clearly favoured at the pyridine nitrogen
1
5
Table 5. N-NMR chemical shifts (d in ppm) of 8–13
Compound
Solvent
N1
N2
(N1) over protonation at the other sites. According to
calculations, in the gas phase, the protonated oxoenamino
form is only 3–7 kJ mol higher in energy than the
protonated hydroxyimino one (Table 9). Therefore,
theoretical results would predict that in solution or in
solid state the two protonated forms can be present.
In hydrogen bonds the heavy atoms are separated by
less than the sum of their van der Waals radii, that is, for
8
8
CDCl3
TFA
Dd
CDCl3
TFA
Dd
CDCl3
TFA
Dd
CDCl3
TFA
Dd
ꢂ56.6
ꢂ178.1
ꢂ121.5
ꢂ57.7
ꢂ67.5
ꢂ166.4
ꢂ98.9
ꢂ69.1
ꢂ167.7
ꢂ98.6
ꢂ70.5
ꢂ168.7
ꢂ98.2
ꢂ71.4
ꢂ149.2
ꢂ77.8
ꢂ70.6
ꢂ149.2
ꢂ78.6
ꢂ75.5
ꢂ76.3
ꢂ0.8
HR
ꢂ1
9
9
HR
ꢂ176.0
ꢂ118.3
ꢂ57.5
1
1
0
0H
R
ꢂ178.1
ꢂ120.6
ꢂ55.0
1
1
˚
weak HBs, NꢀꢀꢀHꢀꢀꢀO ꢄ 2.7 A, whereas in strong HBs the
R
R
R
1
1H
ꢂ179.6
ꢂ124.6
ꢂ55.8
27
˚
separation is 2.5–2.6 A for NꢀꢀꢀHꢀꢀꢀO. When the proton
moves towards the centre of the hydrogen bond, a
contraction of the NꢀꢀꢀO distance is observed. The HB
distances summarised in Table 10 show a shorter value for
the protonated form, therefore the hydrogen bond
becomes stronger, with the nitrogen atom and the proton
closer making the proton transfer easier.
1
2
CDCl3
TFA
Dd
1
2H
ꢂ179.6
ꢂ123.8
ꢂ50.5
1
3
CD CN
3
TFA
Dd
1
3H
ꢂ181.2
ꢂ131.2
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

6
16
A. PERONA ET AL.
(
a)
CH=N
(b)
H2
H5/H6
CH=N
H6
H2’/H6’
H2
-
88
-
192
184
-
80
-
N1
N2
70.5
-
178.1
-
72
64
56
-
-176
-168
-160
-152
N2
-
-168.7
N1
-
-57.5
-48
8
.4
8.0
7.2
6.8
6.4
9
.2
8.8
8.4
8.0
7.6
1
5
Figure 3. N-NMR of 10 in solution: (a) CDCl , (b) in CF COOH
3
3
(
a)
(b)
3
50
300
50
00
50
00
R
R
2
2
1
N -90.4 TFA
OH
NH
1
O
50
0
N
N
H
-121.8
Ph
NH2
Me OMe Br
NH/CH=N
Cl NO2
CH=N
H
1
5
Figure 4. (a) Protonation effects in the N-NMR chemical shift [Dd(TFA-CDCl )] of
3
compounds 8–12, (b) Chemical shift values (ꢂd in ppm) of N2 for 8–13 oxoenamino/
hydroxyimino forms (red), hydroxyimino forms (green) and the anilines 2–7 (blue)
Electronic spectra
tion band in 0.1 M TFA in CH CN are shown in Table 11.
3
These absorptions mainly represent the pyridine chro-
6
mophore. Figure 9 shows the electronic spectra in neutral
and acid media of 3-hydroxypyridine-4-carboxaldehyde
(1) and two of the Schiff bases studied, the
The wavelength absorption bands (lmax in nm) in the
electronic spectra of the Schiff bases 8–13 in acetonitrile
(
absorption at <190 nm) and the corresponding absorp-
1
3
R
R
S
4
Table 6. C-NMR chemical shifts (d in ppm) and coupling constants (J in Hz) for the pyridine moiety of 10H BF , 11H BF
4
and 11ꢀPicric acid
—
CH—N
Compound
Solvent
C2
133.2
C3
C4
C5
125.9
C6
þ
1
1
0H BFS4
DMSO-d6
155.2
156.3
J ¼ 4.6
J ¼ 7.1
132.0
133.5
J ¼ 191.3
1
1
3
3
1
1
J ¼ 172.3
J ¼ 188.6
J ¼ 171.7
3
3
3
3
J ¼ 5.3
J ¼ 8.1
J ¼ 6.0
J ¼ 7.2
2
2
J ¼ 2.4
J ¼ 4.2
a
THF-d8
CP-MAS
THF-d8
157.5
157.6
153.9
133.6
135.0
132.1
158.8
157.6
157.6
135.0
134.9
130.3
128.7
127.8
130.0
134.1
134.8
132.1
b
127.4
123.7
1H BFS4
þ
162.8
1
a
135.5
135.2
133.4
1c58.4
128.2
128.2
130.6
125.2
c135.8
b
c
61.5
157.7
158.0
CP-MAS
DMSO-d6
158.6
155.7
130.0
124.3
133.4
134.4
J ¼ 186.5
1
1ꢀPicric acid
134.7
1
1
1
J ¼ 171.6
J ¼ 186.5
a
Major product.
Minor product.
Not observed.
b
c
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

ACID ASSISTED PROTON TRANSFER
617
+
-
1
1
0H BF
4
C
2’/C6’
2
C and C1’
C
4
C
4’
C
3
C
5
3’ 5’
C /C
C
6
CH=N
0
170
160
150
140
130
120
110
100
1
3
Figure 5. C CPMAS NMR of (E)-4-[(4-methoxyphenylimino)methyl]-3-
hydroxypyridine (10) and its tetrafluoro-
R
S
4
borate salt 10H BF
1
5
R
S
4
Table 7. N-NMR chemical shifts (d in ppm) of 10H BF ,
R
S
1
1H BF and 11ꢀPicric acid
4
Compound
Solvent
N1
N2
þ
1
0H BFS4
DMSO-d6
THF-d8
ꢂ157.1
ꢂ154.0
ꢂ177.3
ꢂ58.7
ꢂ68.0
ꢂ66.0
ꢂ70.7
ꢂ68.3
ꢂ71.2
ꢂ72.1
ꢂ72.8
a
b
CP-MAS
THF-d8
CP-MAS
ꢂ180.0
1H BFS4
þ
c
1
ꢂ177.5
ꢂ178.3
ꢂ179.9
ꢂ181.2
ꢂ137.6
d
1
1ꢀPicric acid
Major product.
Minor product.
Not observed.
DMSO-d6
ꢂ54.8
a
b
c
d
15
15
Figure 6. gs-HMBC N-NMR of (E)-4-[(4-methoxypheny-
limino)methyl]-3-hydroxypyridinium tetrafluoroborate
Picric acid N-NMR d (ppm): ꢂ12.6 (NO
2
), ꢂ9.5 (NO
2
).
R
S
(
10H BF ) in DMSO-d
4
6
4
-[(4-methoxyphenylimino)methyl]pyridin-3-ol (10) and
chemical shifts indicate the expected equilibrium
1
between the two tautomeric forms: H-NMR d: 9.06 (s,
the 4-[(4-nitrophenylimino)methyl]pyridin-3-ol (13).
Comparing the two spectra we notice that in the aldehyde
the protonation of the pyridine nitrogen red-shifted the
absorption band of the pyridine chromophore (Fig. 9a),
but in the Schiff bases the longer wavelength absorption
bands are blue-shifted (Fig. 9b) suggesting the presence
of the oxoenamino tautomer in equilibrium with the
3
—
CH—N), 8.43 (s, H2), 8.13 (d, H6, J ¼ 5.97 Hz), 8.05 (d,
0
0
0
0
H5), 7.63 (m, H2 /H6 ), 7.07 (m, H3 /H5 ), 3.84 (s,
13
—
OCH3); C-NMR d: 157.9 (CH—N), 134.9 (C2), 131.3
0
0
0
(C5), 130.8 (C6), 126.0 (C4), 125.6 (C2 /C6 ), 117.0 (C3 /
15
0
C5 ), 56.9 (OCH ); N-NMR d: ꢂ109.7 (N2), ꢂ180.0
3
(N1). Only in the 4-[(4-nitrophenylimino)methyl] pyr-
idin-3-ol (13) such blue-shift was not observed (Fig. 9c),
indicating that there was no proton transfer between the
28
hydroxyimino. To confirm our proposal we recorded the
1
13 15
H, C and N-NMR in 0.5M TFA in CD CN of 10, the
3
Figure 7. ORTEP plot of (E)-4-[(4-bromophenylimino)methyl]-3-hydroxypyr-
R
S
idinium tetrafluoroborate (11H BF ) with thermal ellipsoids at 30% prob-
4
ability. The BF anion is omitted for clarity purposes
4
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

6
18
A. PERONA ET AL.
R
S
4
˚
Table 8. Selected bond lengths [A] and angles [8] including hydrogen bonds for 11H BF
Br-C10
N2-C7
N2-C6
C5-C6
C1-O1
N1-C2
N1-C3
O1-H1B
N1-H1A
1.884(8)
1.435(9)
1.259(9)
1.46(1)
1.337(8)
1.34(1)
1.31(1)
1.1025
0.8645
2.563(8)
2.68(2)
2.77(2)
1.64
C11-C10-Br
C9-C10-Br
C6-N2-C7
N2-C6-C5
C1-C5-C6
O1-C1-C5
C2-C1-O1
C3-N1-C2
C1-O1-H1B
C3-N1-H1A
C2-N1-H1A
119.7(7)
120.3(6)
122.7(7)
121.3(7)
120.3(7)
121.8(7)
119.6(7)
122.0(7)
107.7
118.9
117.8
138.0
170.5
162.2
.
. .
O1 N2
a
N1 O2A
.
. .
.
. .
a
. . .
N1 O2B
H1B N2
O1-H1B N2
a
.
. .
. . .
N1-H1A O2A
a
N1-H1A O2B
.
H1A O2B
. .
a
a
. . .
1.94
1.83
.
. .
H1A O2A
a
Oxygen atom of water molecule with 0.5/0.5 occupancy.
Figure 8. Crystal packing of (E)-4-[(4-bromophenylimino)methyl]-3-hydro-
R
S
4
xypyridinium tetrafluoroborate (11H BF ) along a. The fluorine atoms and
the water oxygen are represented only in one of the two disordered positions
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

ACID ASSISTED PROTON TRANSFER
619
ꢂ1
R
R
Table 9. Absolute energies (hartrees) and relative energies (kJ mol ) of structures 8H –13H
Compound
Hydroxyimino
Oxoenamino
þ
—
H (R—H)
8
9
1
1
1
1
ꢂ648.42433 (0.0)
ꢂ648.21482 (0.0)
ꢂ687.74823 (0.0)
ꢂ687.51132 (0.0)
ꢂ762.95747 (0.0)
ꢂ762.71511 (0.0)
ꢂ3221.70012 (0.0)
ꢂ3221.50081 (0.0)
ꢂ1108.01520 (0.0)
ꢂ1107.81540 (0.0)
ꢂ852.91163 (0.0)
ꢂ852.69953 (0.0)
2.99
4.00
3.52
3.84
6.25
6.67
5.38
5.93
5.59
6.23
5.91
5.89
þZPE
þZPE
þZPE
þZPE
þZPE
þZPE
þ
—
H (R—CH )
3
þ
—
0H (R—OCH )
3
þ
—
1H (R—Br)
þ
—
2H (R—Cl)
þ
—
3H (R—NO )
2
—
(R—H, CH , OCH , Br, Cl, NO ), in acid solution has
3 3 2
imino nitrogen and the OH group and that the
oxoenamino form is not present. The overall results
agree with those obtained by NMR spectroscopy in TFA.
The electronic spectra of the tetrafluoroborate salts of
imines 10 and 11 were also registered, the wavelength
been determined showing that the transfer of the bridging
proton of the intramolecular O—HꢀꢀꢀN hydrogen bond
from the hydroxyl oxygen to the imino proton is assisted
by protonation of the pyridine ring. A comparison of the
solution results with the data obtained for the tetrafluor-
oborate salts in solid state by CPMAS NMR and X-ray
analysis has demonstrated that protonation takes place on
the pyridine nitrogen but the compounds still exist in the
hydroxyimino form in solid state.
absorption bands in acetonitrile [l
in nm, (loge)]
being: 10H BF 385.0 (4.17), 11H BF 359.5 (4.12)
max
R
R
S
S
4
4
and Dl(10H BF S4 ꢂ10) ¼ 30 nm, Dl(11H BF4
R
R
S
ꢂ11) ¼ 30 nm.
An increase in the solvent acidity changes the polarity
around the hydrogen bond and shifts the equilibrium from
hydroxyimino towards oxoenamino tautomers. The
magnitude of the effect is related to the solvent capacity
CONCLUSIONS
1
13
A set of novel H, C and N-NMR data of aromatic
15
29
Schiff bases, 4-[(4-R-phenylimino)methyl]pyridin-3-ols
to protonate the pyridine ring.
Table 10. Hydrogen bond distances rN H=rN O
2
2
þ
Compound
Hydroxyimino
HydroxyiminoH
Dr
˚
˚
˚
˚
˚
˚
˚
1.653 A/2.572 A
˚ ˚
˚
8
9
0
1
1.747 A/2.638 A
0.094/0.066
0.092/0.065
0.088/0.063
0.096/0.068
1.745 A/2.637 A
1.653 A/2.572 A
˚
˚ ˚
1.656 A/2.575 A
1
1
1.744 A/2.638 A
˚
1.755 A/2.643 A
˚ ˚
1.659 A/2.575 A
´
˚
˚
1.754 A/2.642 A
˚
˚
1.661 A /2.576 A
1
1
2
3
0.093/0.066
0.089/0.065
´
˚ ˚
˚
1.766 A/2.649 A
˚
1.677 A /2.584 A
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

6
20
A. PERONA ET AL.
Table 11. The wavelength absorption bands in the electronic spectra of 1, 8–13, lmax in nm, (loge)
Compound
CH CN
3
0.1 M TFA in CH CN
3
~l
1
8
9
0
1
2
3
332.5 (3.63)
338.5 (3.94)
342.5 (4.10)
355.0 (4.19)
328.5 (4.07)
329.5 (4.03)
329.0 (3.96)
320.5 (3.79)
354.0 (4.05)
365.5 (4.21)
394.0 (4.27)
361.0 (4.20)
360.5 (4.14)
322.0 (4.04)
ꢂ12
15.5
23
1
1
1
1
39
32.5
31
ꢂ7
Figure 9. Electronic spectra in CH CN (blue) and 0.1M TFA in CH CN (red) of compounds: (a) 1, (b) 10, (c) 13
3
3
EXPERIMENTAL PART
General procedures
pling; the FIDS were multiplied by an exponential
weighting (lb ¼ 2 Hz) before Fourier transformation. 2D
inverse proton detected heteronuclear shift correlation
1
13
1
13
spectra, ( H– C) gs-HMQC, ( H– C) gs-HMBC and
1
15
Melting points were determined by DSC on a SEIKO
DSC 220C connected to a Model SSC5200H Disk
Station. Thermograms (sample size 0.003–0.010 g) were
( H– N) gs-HMBC, were acquired and processed using
standard Bruker NMR software and in non-phase-sensitive
mode. Gradient selection was achieved through a 5% sine
truncated shaped pulse gradient of 1 ms. Selected
ꢂ1
recorded at the scanning rate of 2.0 8C min .
1
13
parameters for ( H– C) gs-HMQC and gs-HMBC spectra
1
were spectral width 2500–8000Hz for H and 12.0 kHz for
NMR spectroscopy
1
3
C, 1024 ꢅ 256 data set, number of scans 2 (gs-HMQC) or
Solution NMR spectra were recorded on a Bruker DRX
4
4 (gs-HMBC) and relaxation delay 1 s. The FIDs were
processed using zero filling in the F1 domain and a
sine-bell window function in both dimensions was applied
prior to Fourier transformation. In the gs-HMQC
1 13
00 (9.4 T, 400.13 MHz for H, 100.62 MHz for C and
15
4
detection H—X probe equipped with a z-gradient coil, at
0.56 MHz for N) spectrometer with a 5-mm inverse-
30
13
3
internal solvent, CDCl 7.26 for H and 77.0 for
00 K. Chemical shifts (d in ppm) are given from
1
experiments GARP modulation of C was used for
1
decoupling. Selected parameters for ( H- N) gs-HMBC
15
3
1
3
1
C, DMSO-d 2.49 for H and 39.5 for C, THF-d8
13
1
spectra were spectral width 2500–3500Hz for H and
6
1
.58 for H and 67.6 for C, CD CN 1.94 for H and
13
1
15
3
1
12.5 kHz for N, 1024 ꢅ 512 data set, number of scans
3
13
15
18.7 for C and for N-NMR nitromethane (0.0) was
4–16, relaxation delay 1 s, 37–150 ms delay for the
15
1
used as external standard. The spectra done in TFA
solution was recorded with a lock capillary with
evolution of the N- H long-range coupling. The FIDs
were processed using zero filling in the F1 domain and a
sine-bell window function in both dimensions was applied
prior to Fourier transformation.
1
DMSO-d6 2.49 for H and 39.5 for C. Typical
13
1
parameters for H-NMR spectra were spectral width
13
15
7
0
000 Hz and pulse width 7.5 ms at an attenuation level of
dB and resolution 0.15–0.25 Hz per point. Typical
Solid state C (100.73 MHz) and N (40.60MHz)
CPMAS NMR spectra have been obtained on a Bruker WB
400 spectrometer at 300 K using a 4 mm DVT probehead.
Samples were carefully packed in a 4-mm diameter
cylindrical zirconia rotor with Kel-F end-caps. Operating
13
parameters for C-NMR spectra were spectral width
1 kHz, pulse width 10.6 ms at an attenuation level of
ꢂ6 dB, resolution 0.6 Hz per point and relaxation delay
s; WALTZ-16 was used for broadband proton decou-
2
1
2
conditions involved 3.2 ms 90 H pulses and decoupling
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

ACID ASSISTED PROTON TRANSFER
621
1
3
0
3
3
3
1
—
field strength of 78.1 kHz by TPPM sequence. C spectra
were originally referenced to a glycine sample and then the
chemical shifts were recalculated to the Me Si [for the
(C1 , J ¼ J ¼ J ¼ 8.7 Hz) 155.2, (CH—N, J ¼ 172.3,
3
3
3
0
J ¼ 5.3), 156.3 (C3, J ¼ 4.6, J ¼ 7.1) and 160.2 (C4 ).
1
H-NMR (THF-d ), we observed two species a, 66%,
4
8
15
0 0
b, 34%. a, d: 3.85 (s, 3H, OCH ), 7.05 (m, 2H, H3 /H5 ),
3
carbonyl atom d (glycine)¼ 176.1 ppm] and N spectra to
15
0
0
NH Cl and then converted to nitromethane scale using
4
7.60 (m, 2H, H2 /H6 ), 8.11 (d, 1H, J ¼ 5.8 Hz, H5), 8.47
(d, 1H, J ¼ 5.8 Hz, H6), 8.57 (s, 1H, H2) and 9.14 (s, 1H,
15
15
the relationship: d N(MeNO )¼ d N(NH Cl) ꢂ338.1 ppm.
2
4
13
0 0
—
CH—N); b, d: 3.80 (s, 3H, OCH ), 7.05 (m, 2H, H3 /H5 ),
3
Typical acquisition parameters for C CPMAS were:
spectral width, 40 kHz; recycle delay, 5–30 s; acquisition
time, 30 ms; contact time, 2–4 ms; and spin rate, 12 kHz. In
order to distinguish protonated and unprotonated carbon
atoms, the Non-Quaternary Suppression (NQS) exper-
iment by conventional cross-polarization was recorded;
before the acquisition the decoupler is switched off for a
0
0
7.57 (m, 2H, H2 /H6 ), 7.92 (d, 1H, J ¼ 5.9 Hz, H5), 8.30
(d, 1H, J ¼ 5.9 Hz, H6), 8.43 (s, 1H, H2) and 9.05 (s, 1H,
—
CH—N).
1
3
0
C-NMR (THF-d ) a, d: 56.1 (OCH ), 115.9 (C3 /
8
3
0
0
0
C5 ), 125.0 (C2 /C6 ), 128.7 (C5), 133.6 (C2), 134.1 (C6),
—
0
135.0 (C4), 140.3 (C1 ), 157.5 (CH—N), 158.8 (C3) and
31,32
0 0 0
162.4 (C4 ); b, d: 56.0 (OCH ), 116.0 (C3 /C5 ), 124.6
3
very short time of 25 ms.
Typical acquisition para-
meters for N CPMAS were: spectral width, 40 kHz;
recycle delay, 5–30 s; acquisition time, 35ms; contact time,
15
0 0
(C2 /C6 ), 127.7 (C5), 135.0 (C2), 134.8 (C6), 134.9 (C4),
0
0
—
140.5 (C1 ), 157.6 (CH—N, C3) and 161.1 (C4 ).
1
4
ms; and spin rate, 6 kHz.
H-NMR (CD OD), we observed two species:
3
R
S
0
0H BF , d: 3.88 (s, 3H, OCH ), 7.08 (m, 2H, H3 /
4
3
1
0
0
0
DFT calculations
H5 ), 7.60 (m, 2H, H2 /H6 ), 8.15 (d, 1H, J ¼ 5.8 Hz, H5),
8
.37 (d, 1H, J ¼ 5.8 Hz, H6), 8.55 (s, 1H, H2) and 9.12 (s,
—
1H, CH—N); and the addition product, d: 3.83 (s, 3H,
The optimisation of the structures of all compounds
discussed in this paper was carried out at the hybrid
B3LYP/6-31G level with basis sets of Gaussian
type functions using Spartan ’02 for Windows.
0
OCH ), 5.90 (s, 1H, —CH—NH—), 7.06 (m, 2H, H3 /
3
ꢃꢃ
25,26
0
0
0
H5 ), 7.31 (m, 2H, H2 /H6 ), 8.07 (d, 1H, J ¼ 5.8 Hz, H5),
33
8.34 (d, 1H, J ¼ 5.8 Hz, H6) and 8.26 (s, 1H, H2).
(
E)-4-[(4-bromophenylimino)methyl]-3-hydroxypyr-
Electronic spectra
R
S
idinium tetrafluoroborate (11H BF ). Equimolar
amounts of imine 11 (116 mg, 0.42 mmol) and tetraflour-
oboric acid 54 wt% solution in diethyl ether (68.6 mg,
0.42 mmol) were mixed in CHCl (25ml) and stirred with a
4
UV–Visible spectra were measured on Shimadzu
UV-250rPC UV–Visible spectrometer.
3
magnetic bar at room temperature. Instantly a strong orange
solid precipitates in the media solution. After filtration, the
solid was washed twice with CHCl to remove possible rests
Syntheses
3
Compounds (8–13) have been prepared by refluxing
in toluene equimolar amounts of 3-hydroxypyridine-
of starting materials. The crystals were purified by crystal-
lisation (THF/CHCl ); mp 216.1 8C with a lost at 139.1 8C,
3
4
(
-carboxaldehyde (1) and the corresponding anilines
6
2–7) in toluene with quantitative yields.
and 227.7 decomposes (DSC).
1
H-NMR (THF-d ), we observed two species a, 70%,
8
0
0
0
b, 30%. a, d: 7.53 (m, 2H, H3 /H5 ), 7.55 (m, 2H, H2 /
0
(E)-4-[(4-methoxyphenylimino)methyl]-3-hydroxy-
R
S
H6 ), 8.31 (d, 1H, J ¼ 5.8 Hz, H5), 8.53 (d, 1H, J ¼ 5.8 Hz,
pyridinium tetrafluoroborate (10H BF ). Equimolar
amounts of imine 10 (158 mg, 0.69 mmol) and tetra-
4
—
H6), 8.66 (s, 1H, H2) and 9.23 (s, 1H, CH—N); b, d: 7.49
0
0
0
0
(
m, 2H, H3 /H5 ), 7.54 (m, 2H, H2 /H6 ), 8.01 (d, 1H,
fluoroboric acid 54 wt% solution in diethyl ether
(
J ¼ 5.8 Hz, H5), 8.33 (d, 1H, J ¼ 5.8 Hz, H6), 8.47 (s, 1H,
112.69 mg, 0.69 mmol) were mixed in CHCl (25 ml)
3
—
H2) and 9.10 (s, 1H, CH—N).
and stirred with a magnetic bar at room temperature.
Immediately a red solid precipitates in the media. After
filtration, the solid was washed twice with CHCl to
remove possible rests of starting materials. The crystals
were purified by crystallisation (THF/CHCl ); mp
13
0
C-NMR (THF-d ) a/b, d: 123.7 (C4), 125.0 (C2 /
8
0
0
0
C6 ), 128.2 (C5), 133.9 (C3 /C5 ), 135.5/135.2 (C2),
0
3
1
(
35.8 (C6), 158.4 (C3), 147.4 (C1 ) and 162.8/161.5
0
0
—
CH—N); CP-MAS d: 119.2 (C2 /C6 ), 130.0 (C4), 130.6
3
0
0
0
0
(C3 /C5 , C5), 132.0 (C4 ), 133.4 (C6, C2), 143.1 (C1 )
157.7 (CH—N) and 158.6 (C3).
1
2
81.9 8C, and 189.2 8C (DSC) with a lost at 153.9 8C.
—
1
H-NMR (DMSO-d ), d: 3.82 (s, 3H, OCH ), 7.08 (m,
0
6
3
0
0
0
H, H3 /H5 ), 7.57 (m, 2H, H2 /H6 ), 8.08 (d, 1H,
Complex (E)-4-[(4-bromophenylimino)methyl]-3-
hydroxypyridine picric acid (11ꢀPicric acid). Equi-
molar amounts of imine 11 (20 mg, 0.07 mmol) and picric
J ¼ 5.6 Hz, H5), 8.40 (d, 1H, J ¼ 5.6 Hz, H6), 8.59 (s, 1H,
—
H2) and 9.12 (s, 1H, CH—N).
1
3
1
C-NMR (DMSO-d ), d: 55.6 (OCH , J ¼ 145.0 Hz),
acid (16.6 mg, 0.07 mmol) were mixed in CHCl at room
3
6
3
0
0
1
3
0
1
14.9 (C3 /C5 , J ¼ 161.4 Hz, J ¼ 4.8 Hz), 123.8 (C2 /
temperature. The solution was extracted three times with
water, and the solvent was evaporated under reduce
pressure giving a yellow solid of 11ꢀPicric acid
(quantitative yield).
0
1
3
1
C6 , J ¼ 160.9 Hz, J ¼ 6.2 Hz), 125.9 (C5, J ¼ 171.7,
3
3
2
1
J ¼ 6.0, J ¼ 2.4), 132.0 (C4), 133.2 (C2, J ¼ 188.6,
1
3
2
J ¼ 8.1), 133.5 (C6, J ¼ 191.3, J ¼ 7.2, J ¼ 4.2), 139.8
Copyright # 2007 John Wiley & Sons, Ltd.
J. Phys. Org. Chem. 2007; 20: 610–623
DOI: 10.1002/poc

6
22
A. PERONA ET AL.
1
0
0
H-NMR (DMSO-d ), d: 7.44 (m, 2H, H3 /H5 ), 7.69
6
solved by direct methods and conventional Fourier
techniques. The refinement was done by full-matrix
0
0
(
m, 2H, H2 /H6 ), 8.04 (d, 1H, J ¼ 5.4 Hz, H5), 8.37 (d,
0
0
2
34
1
H5 ) and 9.04 (s, 1H, CH—N).
H, J ¼ 5.4 Hz, H6), 8.54 (s, 1H, H2), 8.58 (s, 2H, H3 /
least-squares on F (SHELXS-97). In the last cycles of
refinement a residual electronic density was assigned to a
disordered water molecule in two positions with 0.5/0.5
occupancy. Anisotropic parameters were used in the last
cycles of refinement for all non-hydrogen atoms with
0
0
—
13
0
0
0
C-NMR (DMSO-d ), d: 121.2 (C4 ), 123.9 (C2 /C6 ,
6
1
3
J ¼ 162.4 Hz, J ¼ 5.9 Hz), 124.3 (C4), 125.2 (C5 and
0
0
00
1
3
0
0
C3 /C5 , J ¼ 167.6 Hz, J ¼ 5.8 Hz), 132.4 (C3 /C5 ,
1
3
1
J ¼ 167.3 Hz, J ¼ 5.6 Hz), 134.4 (C6, J ¼ 186.5 Hz),
some exceptions. The fluorine atoms of the BF anion are
4
1
00
1
00
0
1
34.7 (C2, J ¼ 186.5 Hz), 141.8 (C2 /C6 ), 147.4 (C1
disordered over two positions which were refined
isotropically with an occupancy of 0.5/0.5. Hydrogen
atoms bonded to N1 and O1 atoms have been located in a
Fourier synthesis, included and refined as riding on their
respective bonded atoms. The hydrogen atoms for the
water molecule were not observed in the difference maps
and were not included in the model. The remaining
hydrogen atoms were included in calculated positions and
refined as riding on their respective carbon atoms. Largest
peaks and holes in the final difference map were 0.763
00
—
and C4 ), 155.7 (C3), 158.0 (CH—N, J ¼ 171.6 Hz) and
00
1
60.8 (C1 ).
X-Ray data collection and structure refinement. Light-
yellow needles single crystals of (11H BF ) suitable for
X-ray diffraction experiments were obtained by crystal-
lization from THF/CHCl . Data collection were carried
3
out at room temperature on a Bruker Smart CCD
diffractometer using graphite-monochromated Mo-Ka
R
S
4
ꢂ3
˚
˚
radiation (l ¼ 0.71073 A) operating at 50 kV and 30 mA.
and ꢂ1.170 eA . Final R(Rw) values were 0.0666
(0.2204). These values can be somewhat high since the
crystal diffracted poorly partly due to its needle shape that
gave rise to a low ratio: observed/unique reflections.
CCDC-637109 contains the supplementary crystal-
lographic data for this paper. These data can be obtained
free charge via www.ccdc.cam.ac.uk/conts/retrieving.
html (or from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
(þ44) 1223-336033; or www.deposit@ccde.cam.uk).
The data were collected over a hemisphere of the
reciprocal space by combination of three exposure sets.
Each exposure of 30 s covered 0.3 in v. The first 100
frames were recollected at the end of the data collection to
monitor crystal decay. No appreciable drop in the
intensities of standard reflections was observed. The cell
parameters were determined and refined by
least-squares fit of all reflections.
A summary of the fundamental crystal and refinement
a
R
S
data of 11H BF4 is given in Table 12. The structure was
Table 12. Crystal and refinement data for 2-(E)-4-[(4-bro-
mophenylimino)methyl]-3-hydroxypyridinium tetrafluorobo-
R
S
Acknowledgements
rate (11H BF )
4
CCDC number
Empirical formula
Formula weight
Crystal system
Space group
637109
C H BrN O.BF O
This work was supported by DGES/MEyC
(BQU2003-00976 and CTQ2006-02586) of Spain. One
of us (A.P.) is indebted to the MCyT of Spain for an FPI
grant.
1
2
10
2
380.94
4
Monoclinic
P2 /c
1
˚
a (A)
9.278(1)
7.345(1)
22.346(3)
97.632(2)
1509.3(3)
4
296(2)
752
1.685
˚
b (A)
˚
c (A)
b (8)
V (A )
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DOI: 10.1002/poc