Glutaconaldehyde as an Alternative Reagent to the Zincke Salt for the Transformation of Primary Amines into Pyridinium Salts

Article abstract of DOI:10.1021/acs.joc.9b02538

In the presence of amines, the degradation of glutaconaldehyde in acidic medium can be prevented. By exploitation of this behavior, primary amines are transformed into their corresponding pyridinium salts, including those substrates that remain unreactive toward the Zincke salt, which is the reagent typically used to perform this transformation. The use of glutaconaldehyde also allows control of the nature of the counterion of the pyridinium with no need for additional salt metathesis reaction.

Full text of DOI:10.1021/acs.joc.9b02538

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pubs.acs.org/joc
Cite This: J. Org. Chem. XXXX, XXX, XXX−XXX
Glutaconaldehyde as an Alternative Reagent to the Zincke Salt for
the Transformation of Primary Amines into Pyridinium Salts
Ghada Asskar, Michael Rivard,* and Thierry Martens
́
ICMPE (UMR 7182), CNRS, UPEC, Universite Paris Est, 94320 Thiais, France
S
* Supporting Information
ABSTRACT: In the presence of amines, the degradation of
glutaconaldehyde in acidic medium can be prevented. By
exploitation of this behavior, primary amines are transformed
into their corresponding pyridinium salts, including those
substrates that remain unreactive toward the Zincke salt, which
is the reagent typically used to perform this transformation.
The use of glutaconaldehyde also allows control of the nature
of the counterion of the pyridinium with no need for
additional salt metathesis reaction.
he transformation of primary amines 1 into pyridiniums 2
follows a multistep SN(ANRORC) process that includes
the formation of open-chain intermediates of type 3 (Scheme
1). This transformation is typically performed either with
salt, further steps of salt metathesis are necessary.23,24 The
same limitation occurs with pyrylium salts.
T
In our search for an alternative reagent to 4·Cl, we based our
idea on Marazano’s findings showing the accelerated trans-
formation of primary amines by a Zincke salt in the presence of
diethylamine.25 This result, explained by the in situ formation
Scheme 1. Transformation of Primary Amines into
Pyridinium Salts
+
of intermediate aminopentadiene-imium (3, X = NEt2 ),
logically suggested using a reagent that easily generates open-
chain species of type 3. Considering that aminopentadienals
(3, X = O) lead to pyridiniums after cyclization,26
glutaconaldehyde salt 5 (Scheme 1) appeared as a promising
substitute for the Zincke salt 4·Cl. It is noteworthy that,
although glutaconaldehyde derivatives have already been
employed for the quaternization of primary amines, their
advantageous use as reagents instead of 4·Cl has not been
demonstrated to date.27,28
Recently, we showed that the transformation of weakly
nucleophilic anilines (typically those with a pKa of conjugated
acid less than 2.75) requires 12 equiv of substrate to fully
convert the Zincke salt 4·Cl, despite microwave (MW)
irradiation at 150 °C and prolonged heating times (60−75
min).22 In the present study, weakly nucleophilic anilines 1a−e
(0.5 mmol, 1.0 equiv) were engaged with 5 (1.5−2.0 equiv) in
an aqueous alcoholic (EtOH or tBuOH) solvent and in the
presence of HCl. Following these conditions, expected salts
2a−e·Cl were quantitatively obtained under MW at 130 °C
after only 15 min of reaction (Table 1, entries 1−5, method 1).
To compare the efficacy of in situ generated glutaconalde-
hyde vs 4·Cl, anilines 1a−e (1.5−2.0 equiv) were treated with
Zincke salt 4·Cl (1.0 equiv) under MW at 130 °C for 15 min.
This returned no or negligible conversions (Table 1, entries 1−
5, method 2). In the case of the anilines 1a−d, unreacted
materials were found to be unchanged by 1H NMR and in the
pyryliums,1−4 thiopyryliums,5,6 or with reagents resulting from
the electrophilic activation of pyridines. A common method for
the latter is the one originally described by Zincke7 and using
the Zincke salt 4·Cl (Scheme 1).8 The quaternization of
primary amines by 4·Cl or its derivatives is commonly used in
materials science,9 supramolecular chemistry,10,11 and also for
the synthesis of compounds of natural origin12,13 or biological
interest.14,15 Viologens, compounds also valuable in materials
science16,17 and supramolecular chemistry,18−20 are typically
prepared according to the Zincke procedure.
Despite its frequent use, the Zincke salt 4·Cl is associated
with various limitations. Using this reagent in excess results in
a mixture of salts 4·Cl and 2·Cl, inseparable according to
traditional chromatographic methods.21 Consequently, weakly
nucleophilic amines need to be engaged in large excess to fully
convert the reagent. Even so, reaction times may be long,
especially under conventional activation. SNAr side reactions
leading to unwanted diarylamines may also occur with anilines
carrying adjacent functions with labile hydrogen.22 Addition-
ally, to obtain any anion different to the one from the Zincke
Received: September 18, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.9b02538
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
and examples of transformations with other Zincke salts are
scarce.29,30 Consequently, the quaternization of sterically
hindered substrates was tested with 2,6-disubstituted anilines
1o−q (Table 1, entries 15−17). Complete conversions were
obtained with in situ generated glutaconaldehyde (method 1),
while 4·Cl provided no or negligible conversions, systemati-
cally associated with a partial loss of substrate (method 2).
Challenging substrates with a 2,6-disubstitution and bearing
an adjacent function with labile hydrogen were also subjected
to quaternization (Table 1, entries 18 and 19). Treating
anthranilic acid derivatives 1r and 1s with in situ generated
glutaconaldehyde yielded the corresponding salts 2r·Cl and 2s·
Cl with a conversion of 100 and 72%, respectively (method 1),
whereas 4·Cl did not bring about the expected salts (method
2).
To ensure that the acidic medium required to in situ
generate glutaconaldehyde from 5 does not prevent the
transformation of basic primary amines, p-toluidine 1t and
benzylamine 1u were submitted to quaternization (Table 1,
entries 20 and 21). In both cases, quantitative conversions
were observed with in situ generated glutaconaldehyde
(method 1). The conversions with 4·Cl were similar or
lower (method 2).
The quaternization of primary heteroarylamines was
exemplified with 3-aminopyridine 1v and 2-aminopyrazine
1w (Table 1, entries 22 and 23). The use of in situ generated
glutaconaldehyde returned quantitative conversions, whereas
employing 4·Cl resulted in low or almost no conversion.
Reactions described above proceeded cleanly in an aqueous-
alcoholic mixture, typically in an EtOH/H2O binary solvent.
However, when side reactions were likely to occur, they were
alternatively conducted in a tBuOH/H2O mixture (e.g., with
substrates prone to esterify 1i−n, 1r, and 1s). Pyridinium salts
2a−w·Cl prepared according to method 1 were purified by
reversed phase chromatography with nonaqueous eluents.
Except in the case of salts deriving from aminobenzamides 1l−
n or from 2-aminopyrazine 1w, expected pyridinium salts were
isolated in good to excellent yields (60−100%).
It is established that reactions using 4·Cl may require
prolonged heating times to reach completion when conducted
under conventional activation. Trabolsi also demonstrated that
the morphology of materials prepared by Zincke reaction may
vary depending on the nature of the activation mode
employed.31 Consequently, the transformation of weakly
nucleophilic anilines (Table 2, entries 1−3), anilines carrying
adjacent functions with labile hydrogen (entries 4−6), and/or
sterically hindered (entries 7−11) was carried out in the
presence of in situ generated glutaconaldehyde and under
conventional activation. Substrates 1 (0.5 mmol) were
quantitatively transformed in the presence of 5 (2 equiv)
and HCl (3 equiv) at 90 °C after only 1 h of reaction, except
for anthranilic acid derivatives 1r and 1s. For the latter two, a
slightly higher amount of HCl (5 equiv) improved the
conversions; in the case of compound 1s, even dramatically
so (entries 10 and 11). Because the conventional heating
allows scaling up chemical processes, a reaction with 5 was
tested on a multigram scale. Sterically hindered 2,6-dichlorani-
line 1q (10 g) was quaternized at 90 °C after 3 h of reaction.
The corresponding salt 2q·Cl was isolated in 97% yield after
purification by reversed phase chromatography.
Table 1. Scope of in Situ Generated Glutaconaldehyde and
Comparison with Zincke Salt 4-Cl
a
conversion (%)
b
c d
,
entry
substrate
R1
2-CN
4-CN
4-Ac
2-Cl
2-CF3
2-OH
3-OH
R2
method 1
100 (90)
method 2
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
1h
1i
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
iPr
Cl
Cl
CF3
H
n.r.
n.r.
3
100 (100)
100 (61)
100 (97)
100 (100)
100 (98)
100 (100)
100 (97)
100 (85)
100 (61)
100 (60)
n.r.
f
n.r.
g
8
g
12
4-OH
42
9
2-CO2H
3-CO2H
4-CO2H
2-CONH2
3-CONH2
4-CONH2
2-Me
2-iPr
2-Cl
2-CO2H
2-CO2H
4-Me
n.r.
g
10
11
12
13
14
15
16
17
18
19
20
21
22
23
1j
1k
1l
9
n.r.
2
e
100 (38)
1m
1n
1o
1p
1q
1r
1s
1t
100 (55)
100 (54)
100 (91)
100 (100)
100 (95)
100 (86)
72 (65)
24
8
f
n.r.
f
2
f
n.r.
n.r.
n.r.
100
83
45
1
100 (89)
100 (83)
100 (80)
100 (55)
1u
1v
1w
benzylamine
3-aminopyridine
2-aminopyrazine
a
b
1
Measured by H NMR. Method 1: 1 (0.50 mmol, 1.0 equiv), 5
(0.75−1.00 mmol, 1.5−2.0 equiv), HCl (2.0−5.0 equiv), EtOH/H2O
or tBuOH/H2O (see the Experimental Section), MW, 130 °C, 15
c
min. Isolated yields are given in brackets. Method 2: 1 (0.75−1.00
mmol, 1.5−2.0 equiv), 4·Cl (0.50 mmol, 1.0 equiv), EtOH/H2O,
d
e
MW, 130 °C, 15 min. n.r. = no reaction. Presence of 25% of 2i·Cl in
f
the crude (1H NMR estimation). Partial loss of substrate 1 observed
by H NMR. Salt 2·Cl obtained in complex mixture.
g
1
ratio as expected. This result suggests that, compared with
Zincke salt 4·Cl, in situ generated glutaconaldehyde exhibits a
significantly higher electrophilicity and provides easier access
to intermediates of type 3. In the case of o-trifluoromethyl
1
aniline 1e, the analysis of the crude by H NMR revealed that
the absence of the expected salt was associated with a partial
loss of substrate, relative to 4·Cl (entry 5).
Substrates prone to produce SNAr side reactions with 4·Cl
were also subjected to quaternization. Aminophenols 1f−h
(Table 1, entries 6−8), aminobenzoic acids 1i−k (entries 9−
11), and aminobenzamides 1l−n (entries 12−14) were treated
with 5 in the presence of HCl. This quantitatively led to the
expected salts 2f−n·Cl (method 1) except in the case of 2l·Cl,
which partially hydrolyzed during the reaction. Substrates 1f−
n treated with 4·Cl (method 2) did not react or returned
transformation with low conversion not exceeding 42%. In
some cases, method 2 also provided the expected pyridinum
salts in complex mixtures (entries 6, 7, and 10).
Using 5 also enabled the control of the counterion by simply
varying the nature of the acid present in the reaction mixture.
For demonstration purposes, p-toluidine 1t (0.5 mmol, 1
To our knowledge, there are no descriptions of any
transformation of 2,6-disubstituted anilines with 4·Cl to date,
B
DOI: 10.1021/acs.joc.9b02538
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Note
of glutaconaldehyde, which is known to readily polymerize.32,33
It has been reported that this compound remains stable for ca.
30 min at −70 °C in a relatively concentrated methanolic
solution,34 and its half-life in Et2O does not exceed 10 min at
room temperature.35 The propensity of glutaconaldehyde
derivatives to dimerize is also well documented.36 The results
presented here therefore suggest that the reaction leading to
the formation of intermediates of type 3 is significantly faster
than the degradation of 5 in the acidic reaction mixture, even
with weakly nucleophilic or sterically hindered substrates.
Reagent 5 is classically obtained after basic treatment of
activated pyridines.37,38 For this study, a straightforward access
to 5 was developed from the commercially available dianil salt
6 (Scheme 2). Treating 6 (20 g) with a cyclic secondary amine
such as pyrrolidine led to the transamination product, which
was hydrolyzed under basic conditions. The resulting amino-
pentadienal 7 was then treated with KOH as previously
described. This procedure allowed the obtaining of 5 on
multigram scale in only two steps and with an overall yield of
91% from 6.
Table 2. Use of in Situ Generated Glutaconaldehyde under
Conventional Activation
a
b
entry
substrate
R1
2-CN
2-Cl
2-CF3
R2
conversion (%)
1
2
3
4
5
6
7
1a
1d
1e
1f
1i
1l
1o
1p
1q
1r
1s
H
H
H
H
H
H
Me
iPr
Cl
Cl
CF3
100
100
100
100
100
2-OH
2-CO2H
2-CONH2
2-Me
c
100
100
100
100
8
2-iPr
9
10
11
2-Cl
2-CO2H
2-CO2H
d
94 (100)
16 (75)
d
In summary, glutaconaldehyde salt 5 in the presence of acid
appears as the reagent of choice as a substitute for the Zincke
salt to perform the efficient transformation of primary amines
into pyridinium salts. Reagent 5 allowed to reverse the
stoichiometric ratio in favor of the substrate but also to
significantly reduce the excess of material involved when the
substrate is a weak nucleophile. Unlike 4·Cl, it prevented SNAr
side reactions and allowed control of the counterion of the
pyridinium with no need for additional steps of salt metathesis.
All in all, using 5 in the presence of acid allowed overcoming
the limitations associated with 4·Cl and broadening the scope
of the pyridinium salts accessible by quaternization of primary
amines. Importantly, all of these advantages have been
established in an acidic medium that should induce (according
to literature) the fast decomposition of the glutaconaldehyde.
As demonstrated in this study, this degradation is prevented in
the presence of amines, and this behavior can be used to
perform the transformation of primary amines into their
corresponding pyridinium salts from milli- to multigram scale.
a
Conditions: 1 (0.50 mmol, 1 equiv), solvent used identical as for
b
c
method 1 (Table 1). Measured by 1H NMR. Presence of 30% of 2i-
d
Cl in the crude (1H NMR estimation). HCl (5 equiv).
equiv) was treated with 5 (2 equiv) in the presence of various
acids under MW activation at 130 °C for 15 min (Table 3,
entries 1−5). In the presence of, respectively, CF3CO2H,
TfOH, HNO3, HBF4, and HPF6, pyridinium salts 2t·CF3CO2,
2t·TfO, 2t·NO3, 2t·BF4, and 2t·PF6 were quantitatively
obtained.
a
Table 3. Variation of the Counterion
c
entry
X
m
n
2t-X (%)
1
2
3
4
5
CF3CO2
CF3SO3
NO3
BF4
PF6
2
2
2
3
3
5
5
3
5
5
65
65
84
60
50
EXPERIMENTAL SECTION
■
General Information. All chemicals and solvents were purchased
from commercial suppliers (glutaconaldehyde dianil hydrochloride 6
was purchased from TCI) and were used as received; H2O used as
solvent was distillated. Zincke salt 4·Cl was prepared according to the
reported procedure.21 MW-assisted reactions were carried out with an
Anton Paar Monowave 300 reactor, provided with an IR temperature
sensor. The automated purification of pyridinum salts was performed
on a C18 reversed-phase instrument (40 g cartridges). NMR spectra
a
Conditions: 1t (0.50 mmol, 1 equiv), 5 (1.0−1.5 mmol, 2−3 equiv),
EtOH/H2O or tBuOH/H2O (see the Experimental Section), MW,
b
c
130 °C, 15 min. Measured by 1H NMR. Isolated yields after
reversed phase chromatography.
Again, reactions were conducted in an EtOH/H2O mixture
or alternatively in a tBuOH/H2O mixture when side reactions
involving the anion were likely to occur. Reversed phase
chromatography produced the expected pyridinum salts in
satisfactory yields ranging between 50 and 84%.
It is noteworthy that the generally good conversions
observed in this study were obtained despite the instability
1
were recorded at 20 °C at 400 MHz for the H NMR spectra, 100
MHz for 13C NMR spectra, and 376 MHz for 19F spectra. Chemical
shifts (δ) are reported in part per million (ppm) relative to the
residual nondeuterated solvent signal: δ1H(CD3OD) = 3.31 ppm,
δ13C(CD3OD) = 49.00 ppm, δ1H(CDCl3) = 7.26 ppm, δ1H(DMSO-
d6) = 2.50 ppm, δ13C(DMSO-d6) = 39.52 ppm. Coupling constant
values (J) are given in hertz (Hz) and refer to apparent multiplicities
Scheme 2. Preparation of Reagent 5
C
DOI: 10.1021/acs.joc.9b02538
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The Journal of Organic Chemistry
Note
indicated as follows: s (singlet), d (doublet), t (triplet), q
(quadruplet), hept (heptuplet), m (multiplet), dd (doublet of
doublets), td (triplet of doublets), tt (triplet of triplets). IR spectra
were recorded on a spectrometer equipped with a diamond ATR unit
between 400 and 4000 cm−1. Wavenumbers (ν) are expressed in cm−1
at their maximum intensity. LC-MS analyses were performed with a
reversed-phase chromatographic system (MeOH was used as eluent
in isocratic mode) coupled with a single-quadrupole mass
spectrometer (ESI+ mode, 50 V, 400 °C). CHN analyses were
performed by the elemental analysis service of the “Institut de Chimie
des Substances Naturelles”, Gif-sur-Yvette (France). HRMS spectra
were measured in ESI+ mode by the mass spectrometry service of the
1-(2-Cyanophenyl)pyridin-1-ium Chloride (2a-Cl).22 The reaction
was performed on a mixture of 1a (59.1 mg) and 5 (102 mg, 0.75
mmol, 1.5 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL of
EtOH. Purification of the crude according to Method P1 gave 2a-Cl
as a light brown powder (98 mg, 90%).
1-(4-Cyanophenyl)pyridin-1-ium Chloride (2b·Cl).22 The reaction
was performed on a mixture of 1b (59.1 mg) and 5 (136 mg, 1.00
mmol, 2.0 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL of
EtOH. Purification of the crude according to Method P1 gave 2b-Cl
as a beige powder (108 mg, 100%).
1-(4-Acetylphenyl)pyridin-1-ium Chloride (2c·Cl).22 The reaction
was performed on a mixture of 1c (67.6 mg) and 5 (136 mg, 1.00
mmol, 2.0 equiv) in 0.6 mL of S2 (3.0 equiv of HCl) and 1.4 mL of
tBuOH/H2O (50/50). Purification of the crude according to Method
P1 gave 2c·Cl as a brown solid (72 mg, 62%).
́
“Institut de Chimie Organique et Analytique”, Orleans (France).
Preparation of Pyridinum Salts 2a−w·Cl by Action of
Glutaconaldehyde Salt 5. Prior to being used in the reaction, a
stock-solution of HCl (2.5 N) was prepared either in H2O or in a
tBuOH/H2O mixture. Aqueous solution S1 was prepared by diluting
2.08 mL of HClaq (12 N) in 7.92 mL of H2O; aqueous-alcoholic
solution S2 was prepared by diluting 2.08 mL of HClaq (12 N) in 7.92
mL of a tBuOH/H2O (50/50) mixture.
1-(2-Chlorophenyl)pyridin-1-ium Chloride (2d·Cl).22 The reaction
was performed on a mixture of 1d (63.8 mg) and 5 (136 mg, 1.00
mmol, 2.0 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL of
EtOH. Purification of the crude according to Method P1 gave 2d·Cl
as a very hygroscopic brown solid (110 mg, 97%).
1-(2-(Trifluoromethyl)phenyl)pyridin-1-ium Chloride (2e·Cl).22
The reaction was performed on a mixture of 1e (80.6 mg) and 5
(136 mg, 1.00 mmol, 2.0 equiv) in 1.0 mL of S1 (5.0 equiv of HCl)
and 1.0 mL of EtOH. Purification of the crude according to Method
P1 gave 2e·Cl as a very hygroscopic brown solid (130 mg, 100%).
1-(2-Hydroxyphenyl)pyridin-1-ium Chloride (2f·Cl).22 The reac-
tion was performed on a mixture of 1f (54.6 mg) and 5 (102 mg, 0.75
mmol, 1.5 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL of
EtOH. Purification of the crude according to Method P1 gave 2f·Cl as
a light brown powder (102 mg, 98%).
Preparation under MW Activation (General Procedure A). Into a
MW vial (10 mL) equipped with a stirring bar were successively
added the potassium salt 5 (0.75−1.00 mmol, 1.5−2.0 equiv), the
aniline derivative 1a−w (0.50 mmol, 1.0 equiv), and the specified
acidic aqueous alcoholic solvent (2 mL). The reaction was performed
at 130 °C in a closed vial for 15 min. After completion of the reaction,
the solvent was removed under reduced pressure. After addition of
MeCN (90 mL), the resulting mixture was sonicated (2 min) and
then filtrated over Celite. The salt was obtained after concentration
under reduced pressure and purification by reversed phase
chromatography according to the specified method (see general
procedure B).
Preparation under Conventional Activation. Into a Schlenk tube
(10 mL) equipped with a stirring bar were successively added the
potassium salt 5 (1.00 mmol, 2.0 equiv), the aniline derivative 1 (0.50
mmol, 1.0 equiv), and the acidic aqueous alcoholic solvent (2 mL).
The solvent system used was the same as for the corresponding
transformation performed under MW, and it was prepared as follows:
0.6 mL (3.0 equiv of HCl) of S1 (alternatively, S2) and 1.4 mL of
EtOH (alternatively, of a tBuOH/H2O (50/50) mixture).
Preparation of Pyridinum Salts 2a−w·Cl by Action of Zincke
Salt 4·Cl. Into a MW vial (10 mL) equipped with a stirring bar, were
successively added Zincke salt 4·Cl (141 mg, 0.5 mmol, 1.0 equiv)
and the aniline derivative 1a−w (0.75−1.00 mmol, 1.5−2.0 equiv).
For this set of experiments, the aniline was introduced in such amount
so that the molar ratio of 1/4·Cl equaled the molar ratio of 5/1 used
for the equivalent transformation engaged with 5 under MW. The
solvent (2 mL) consisted of an EtOH/H2O (60/40) mixture, except
in the case of the aniline derivative 1e, where an EtOH/H2O (80/20)
mixture was used. The reaction was performed at 130 °C in a closed
vial, for 15 min.
Purification of Pyridinium Salts (General Procedure B). The
purification was performed by reversed phase chromatography using a
CyH/EtOAc/EtOH ternary system as an eluent. The elution gradient
was obtained by adding an increasing proportion of EtOH to a
solution S3 consisting of a CyH/EtOAc (50/50) mixture.
Method P1. Impurities were eluted with EtOH/S3 (10/90) for 4
column-volume (CV), and the salt was eluted with EtOH/S3 (50/50,
5 CV).
Method P2. Impurities were eluted with EtOH/S3 (5/95, 4 CV),
and the salt was eluted with EtOH/S3 (50/50, 5 CV).
Method P3. Impurities were eluted with EtOH/S3 (10/90, 4 CV
and then 30/70, 4 CV), and the salt was eluted with EtOH/S3 (50/
50, 5 CV).
1-(3-Hydroxyphenyl)pyridin-1-ium Chloride (2g·Cl).22 The re-
action was performed on a mixture of 1g (54.6 mg) and 5 (102 mg,
0.75 mmol, 1.5 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL
of EtOH. Purification of the crude according to Method P1 gave 2g·
Cl as a beige powder (103 mg, 99%).
1-(4-Hydroxyphenyl)pyridin-1-ium Chloride (2h·Cl).22 The re-
action was performed on a mixture of 1h (54.6 mg) and 5 (136 mg,
1.00 mmol, 2.0 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL
of EtOH. Purification of the crude according to Method P1 gave 2h·
Cl as a brown powder (101 mg, 97%).
1-(2-Carboxyphenyl)pyridin-1-ium Chloride (2i·Cl). The reaction
was performed on a mixture of 1i (68.6 mg) and 5 (102 mg, 0.75
mmol, 1.5 equiv) in 1.0 mL of S2 (5.0 equiv of HCl) and 1.0 mL of
tBuOH/H2O (50/50). The purification according to Method P1 gave
2c·Cl as an orange-brown solid (100 mg, 85%). 1H NMR (400 MHz,
CD3OD) δ 9.14 (d, J = 7.0 Hz, 2H), 8.81 (t, J = 7.0 Hz, 1H), 8.37 (d,
J = 7.5 Hz, 1H), 8.24 (t, J = 7.0 Hz, 2H), 8.01−7.82 (m, 2H), 7.77 (d,
J = 7.5 Hz, 1H). 13C{1H} NMR (100 MHz, CD3OD) δ 165.9, 148.4,
147.6, 143.8, 135.5, 133.8, 133.3, 128.8, 128.7, 127.2. IR (neat) ν
3370, 2988, 1690, 1626, 1603, 1486, 1394, 1248, 773. LC-MS m/z
(%) 200 (100), 201 (14). HRMS (ESI-TOF) m/z: [M]+ Calcd for
C12H10NO2 200.0706; Found 200.0702.
1-(3-Carboxyphenyl)pyridin-1-ium Chloride (2j·Cl).22 The reac-
tion was performed on a mixture of 1j (68.6 mg) and 5 (136 mg, 1.00
mmol, 2.0 equiv) in 0.5 mL of S2 (2.5 equiv of HCl) and 1.5 mL of
tBuOH/H2O (50/50). Purification of the crude according to Method
P1 gave 2j·Cl as a light-brown powder (72 mg, 61%).
1-(4-Carboxyphenyl)pyridin-1-ium Chloride (2k·Cl).22 The reac-
tion was performed on a mixture of 1k (68.6 mg) and 5 (136 mg, 1.00
mmol, 2.0 equiv) in 1.0 mL of S2 (5.0 equiv of HCl) and 1.0 mL of
tBuOH/H2O (50/50). Purification of the crude according to Method
P1 gave 2k·Cl as an orange powder (71 mg, 60%).
1-(2-Carbamoylphenyl)pyridin-1-ium Chloride (2l·Cl). The re-
action was performed on a mixture of 1l (68.1 mg) and 5 (136 mg,
1.00 mmol, 2.0 equiv) in 1.0 mL of S2 (5.0 equiv of HCl) and 1.0 mL
of tBuOH/H2O (50/50). Purification of the crude according to
Synthesis and Characterization of Pyridinium Salts. Unless
specified, the synthesis of pyridinium salts 2a−w·Cl described
hereafter followed the general procedure A. The indicated purification
method refers to one of the methods described in the general
procedure B. 1H and 13C NMR spectra of compounds already
described were in accordance with data previously reported.
1
Method P3 gave 2l·Cl as a yellow viscous liquid (45 mg, 38%). H
NMR (400 MHz, CD3OD) δ 9.10 (d, J = 7.0 Hz, 2H), 8.79 (t, J =
7.0z Hz, 1H), 8.24 (t, J = 7.0 Hz, 2H), 8.05−7.96 (m, 1H), 7.86 (m,
2H), 7.79 (m, 1H). 13C{1H} NMR (100 MHz, CD3OD) δ 169.1,
D
DOI: 10.1021/acs.joc.9b02538
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The Journal of Organic Chemistry
Note
148.3, 147.4, 142.5, 133.7, 133.2, 132.1, 130.7, 128.8, 128.4. IR (neat)
ν 3369, 3067, 1669, 1621, 1575, 1471, 1209, 767. LC-MS m/z (%)
199 (100), 200 (17). HRMS (ESI-TOF) m/z: [M]+ Calcd for
C12H11N2O 199.0866; Found 199.0862.
13C{1H} NMR (100 MHz, CD3OD) δ 165.0, 149.6, 148.1, 140.4,
136.1, 134.4, 132.5, 132.4, 129.8, 129.6. IR (neat) ν 3369, 3024, 2946,
1697, 1631, 1591, 1471, 1356, 1238, 898, 777, 722. LC-MS m/z (%)
234 (100), 235 (15), 236 (37). HRMS (ESI-TOF) m/z [M]+ Calcd
for C12H9ClNO2 234.0316; Found 234.0314.
1-(3-Carbamoylphenyl)pyridin-1-ium Chloride (2m·Cl).22 The
reaction was performed on a mixture of 1m (68.1 mg) and 5 (136
mg, 1.00 mmol, 2.0 equiv) in 0.5 mL of S2 (2.5 equiv of HCl) and 1.5
mL of tBuOH/H2O (50/50). Purification of the crude according to
Method P1 gave 2m·Cl as a brown powder (65 mg, 55%).
1-(2-Carboxy-6-(trifluoromethyl)phenyl)pyridin-1-ium Chloride
(2s·Cl). The reaction was performed on a mixture of 1s (102.6 mg)
and 5 (136 mg, 1.00 mmol, 2.0 equiv) in 1.0 mL of S2 (5.0 equiv of
HCl) and 1.0 mL of tBuOH/H2O (50/50). Purification of the crude
according to Method P3 gave 2s·Cl as a light-brown solid (99 mg,
65%). 1H NMR (400 MHz, CD3OD) δ 9.30 (d, J = 7.0 Hz, 2H), 8.91
(t, J = 7.0 Hz, 1H), 8.64 (d, J = 7.9 Hz, 1H), 8.32 (m, 3H), 8.11 (t, J
= 7.9 Hz, 1H). 13C{1H} NMR (100 MHz, CD3OD) δ 164.7, 150.1,
148.8, 140.0, 137.8, 134.3, 132.8, 129.8, 128.9, 127.7 (q, J = 32.1 Hz),
123.6 (q, J = 273.8 Hz). 19F{1H} NMR (376 MHz, CD3OD) δ
−59.85. IR (neat) ν 3369, 2978, 1713, 1628, 1607, 1477, 1385, 1314,
1185, 1125, 793, 692. LC-MS m/z (%) 268 (100), 269 (14), 535 (8).
HRMS (ESI-TOF) m/z: [M]+ Calcd for C13H9F3NO2 268.0580;
Found 268.0576.
1-(4-Carbamoylphenyl)pyridin-1-ium Chloride (2n·Cl).22 The
reaction was performed on a mixture of 1n (68.1 mg) and 5 (136
mg, 1.00 mmol, 2.0 equiv) in 0.6 mL of S2 (3.0 equiv of HCl) and 1.4
mL of tBuOH/H2O (50/50). Purification of the crude according to
Method P1 gave 2n·Cl as a light-brown powder (49 mg, 42%).
1-(2,6-Dimethylphenyl)pyridin-1-ium Chloride (2o·Cl). The re-
action was performed on a mixture of 1o (60.6 mg) and 5 (102 mg,
0.75 mmol, 1.5 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL
of EtOH. Purification of the crude according to Method P1 gave 2o·
1
Cl as a light-brown powder (100 mg, 91%). H NMR (400 MHz,
CD3OD) δ 9.09 (d, J = 6.9 Hz, 2H), 8.89 (t, J = 6.9 Hz, 1H), 8.39 (t,
J = 6.9 Hz, 2H), 7.53 (t, J = 7.7 Hz, 1H), 7.41 (d, J = 7.7 Hz, 2H),
2.08 (s, 6H). 13C{1H} NMR (100 MHz, CD3OD) δ 148.7, 147.6,
143.2, 134.3, 132.6, 130.7, 130.5, 17.1. IR (neat) ν 3349, 3029, 1621,
1468, 1388, 1338, 783, 761. LC-MS m/z (%) 184 (100), 185 (39),
403 (18). HRMS (ESI-TOF) m/z: [M]+ Calcd for C13H14N
184.1121; Found 184.1118.
1-(2,6-Diisopropylphenyl)pyridin-1-ium Chloride (2p·Cl). The
reaction was performed on a mixture of 1p (88.6 mg) and 5 (136
mg, 1.00 mmol, 2.0 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0
mL of EtOH. Purification of the crude according to Method P2 gave
2p·Cl as a brown solid (138 mg, 100%). 1H NMR (400 MHz,
CD3OD) δ 9.22 (d, J = 6.8 Hz, 2H), 8.92 (t, J = 6.8 Hz, 1H), 8.39 (t,
J = 6.8 Hz, 2H), 7.71 (t, J = 7.9 Hz, 1H), 7.54 (d, J = 7.9 Hz, 2H),
2.12 (hept, J = 6.8 Hz, 2H), 1.21 (d, J = 6.8 Hz, 12H). 13C{1H} NMR
(100 MHz, CD3OD) δ 149.0, 148.0, 144.7, 140.3, 133.5, 130.2 126.3,
29.9, 24.2. IR (neat) ν 3362, 3107, 3064, 2934, 2908, 1621, 1464,
789, 695. LC-MS m/z (%) 240 (100), 241 (39), 242 (3). Anal. calcd
for C17H22ClN.2H2O: C, 65.48; H, 8.40; N, 4.49; Found C, 65.34; H,
8.31; N, 4.32. HRMS (ESI-TOF) m/z: [M]+ Calcd for C17H22N
240.1747; Found 240.1747.
1-(2,6-Dichlorophenyl)pyridin-1-ium Chloride (2q·Cl). The re-
action was performed on a mixture of 1q (81.0 mg) and 5 (102 mg,
0.75 mmol, 1.5 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL
of EtOH. Purification of the crude according to Method P1 gave 2q·
Cl as a brown powder (124 mg, 95%). The multigram scale
preparation of 2q·Cl was performed in a one-neck round-bottom flask
(500 mL) equipped with a stirring bar and containing aniline 1q (10.0
g, 61.7 mmol, 1.0 equiv) in EtOH (120 mL). Potassium salt 5 (12.6 g,
92.6 mmol, 1.5 equiv) and HClaq (2.5 N, 123.4 mL, 5.0 equiv) were
successively added to this solution. After the flask was capped with a
rubber septum, the mixture was heated and kept at 90 °C for 3 h and
then concentrated under reduced pressure. The resulting solid was
taken up with MeCN (450 mL), and KCl was removed by filtration
on a fritted glass. After concentration of the mother liquor, the
resulting slurry was purified according to Method P1 (15.65 g,
97%). 1H NMR (400 MHz, CD3OD) δ 9.29 (d, J = 7.0 Hz, 2H), 9.01
(t, J = 7.0 Hz, 1H), 8.48 (t, J = 7.0 Hz, 2H), 7.86 (d, J = 7.1 Hz, 2H),
7.83−7.76 (m, 1H). 13C{1H} NMR (100 MHz, CD3OD) δ 150.6,
148.2, 138.7, 135.2, 132.5, 131.1, 130.6. IR (neat) ν 3382, 3007, 1620,
1577, 1471, 1446, 780, 729, 691. LC-MS m/z (%) 224 (100), 225
(23), 226 (95). Anal. calcd for C11H8Cl3N.H2O: C, 47.43; H, 3.62 N,
5.03; Found C, 47.22; H, 3.57; N, 4.94. HRMS (ESI-TOF) m/z:
[M]+ Calcd for C11H8Cl2N 224.0028; Found 224.0029.
1-(p-Tolyl)pyridin-1-ium Chloride (2t·Cl).22 The reaction was
performed on a mixture of 1t (53.6 mg) and 5 (136 mg, 1.00 mmol,
2.0 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL of EtOH.
Purification of the crude according to Method P1 gave 2t·Cl as a red-
brown powder (92 mg, 89%).
1-Benzylpyridin-1-ium Chloride (2u·Cl).39 The reaction was
performed on a mixture of 1u (53.6 mg) and 5 (102 mg, 0.75
mmol, 1.5 equiv) in 0.4 mL of S1 (2.0 equiv of HCl) and 1.6 mL of
EtOH. Purification of the crude according to Method P1 gave 2u·Cl
as a brown viscous liquid (85 mg, 83%).
[1,3′-Bipyridin]-1-ium Chloride (2v·Cl). The reaction was
performed on a mixture of 1v (47.1 mg) and 5 (102 mg, 0.75
mmol, 1.5 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL of
EtOH. Purification of the crude according to Method P1 gave 2v·Cl
as a yellow viscous liquid (77 mg, 80%). 1H NMR (400 MHz,
CD3OD) δ 9.34 (d, J = 7.2 Hz, 2H), 9.11 (s, 1H), 8.96 (d, J = 4.9 Hz,
1H), 8.87 (t, J = 7.2 Hz, 1H), 8.44−8.39 (m, 1H), 8.36 (t, J = 7.2 Hz,
2H), 7.86 (dd, J = 8.4, 4.9 Hz, 1H). 13C{1H} NMR (100 MHz,
CD3OD) δ 152.7, 148.8, 146.4, 145.8, 141.5, 135.1, 129.8, 126.7. IR
(neat) ν 3364, 3040, 1626, 1470, 777, 679. LC-MS m/z (%) 157
(100), 158 (12). Anal. calcd for C10H9ClN2.3/8H2O: C, 49.90; H,
6.00; N, 11.64; Found C, 50.06; H, 5.60; N, 11.44. HRMS (ESI-
TOF) m/z: [M]+ Calcd for C10H9N2 157.0760; Found 157.0759.
1-(Pyrazin-2-yl)pyridin-1-ium Chloride (2w·Cl). The reaction was
performed on a mixture of 1w (47.6 mg) and 5 (136 mg, 1.00 mmol,
2.0 equiv) in 1.0 mL of S1 (5.0 equiv of HCl) and 1.0 mL of EtOH.
Purification of the crude according to Method P1 gave 2w·Cl as a
1
light-brown powder (53 mg, 55%). H NMR (400 MHz, CD3OD) δ
9.69 (d, J = 7.0 Hz, 2H), 9.44 (s, 1H), 9.07 (d, J = 1.9 Hz, 1H), 8.92
(t, J = 7.0 Hz, 1H), 8.85 (d, J = 1.9 Hz, 1H), 8.40 (t, J = 7.0 Hz,
2H).13C{1H} NMR (100 MHz, CD3OD) δ 150.2 (overlap of two
signals), 149.1, 145.1, 144.2, 140.5, 129.7. IR (neat) ν 3420, 3029,
1621, 1612, 1484, 797, 679. LC-MS m/z (%) 158 (100), 159 (12).
HRMS (ESI-TOF) m/z: [M]+ Calcd for C9H8N3 158.0713; Found
158.0711.
1-(p-Tolyl)pyridin-1-ium 2,2,2-trifluoroacetate (2t·CF3CO2). The
reaction was performed in a closed MW vial (10 mL) equipped with a
stirring bar and containing 1t (53.6 mg, 0.50 mmol, 1.0 equiv), 5 (136
mg, 1.00 mmol, 2.0 equiv), 1.0 mL (5 equiv) of CF3CO2H (2.5 N) in
H2O and 1.0 mL of EtOH. After 15 min of reaction at 130 °C, the
solvent was removed under reduced pressure. EtOAc (90 mL) was
added to the crude, and the resulting solution was successively
sonicated (2 min), filtrated over Celite, and concentrated under
reduced pressure. Purification by reversed phase chromatography
according to Method P2 gave 2t·CF3CO2 as a brown viscous liquid
(92 mg, 65%). 1H NMR (400 MHz, CD3OD) δ 9.22 (d, J = 7.1 Hz,
2H), 8.77 (t, J = 7.1 Hz, 1H), 8.27 (t, J = 7.1 Hz, 2H), 7.70 (d, J = 8.1
Hz, 2H), 7.56 (d, J = 8.1 Hz, 2H), 2.51 (s, 3H). 13C{1H} NMR (100
MHz, CD3OD) δ 162.6 (q, J = 34.0 Hz), 147.62, 145.0, 143.7, 142.2,
132.2, 129.5, 125.2, 118.0 (q, J = 292.3 Hz), 21.1. 19F{1H} NMR (376
MHz, CD3OD) δ −76.86. IR (neat) ν 3427, 3070, 1672, 1629, 1509,
1-(2-Carboxy-6-chlorophenyl)pyridin-1-ium Chloride (2r·Cl). The
reaction was performed on a mixture of 1r (85.8 mg) and 5 (136 mg,
1.00 mmol, 2.0 equiv) in 1.0 mL of S2 (5.0 equiv of HCl) and 1.0 mL
of tBuOH/H2O (50/50). Purification of the crude according to
1
Method P3 gave 2r·Cl as a brown powder (116 mg, 86%). H NMR
(400 MHz, CD3OD) δ 9.20 (d, J = 6.8 Hz, 2H), 8.92 (t, J = 6.8 Hz,
1H), 8.36 (m, 3H), 8.09 (d, J = 8.2 Hz, 1H), 7.91 (t, J = 8.2 Hz, 1H).
E
DOI: 10.1021/acs.joc.9b02538
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The Journal of Organic Chemistry
Note
1476, 1415, 1198, 1171, 1120, 799. LC-MS m/z (%) 170 (100), 171
(13). HRMS (ESI-TOF) m/z: [M]+ Calcd for C12H12N 170.0964;
Found 170.0962.
(d, J = 7.1 Hz, 2H), 8.77 (t, J = 7.1 Hz, 1H), 8.27 (t, J = 7.1 Hz, 2H),
7.70 (d, J = 8.1 Hz, 2H), 7.56 (d, J = 8.1 Hz, 2H), 2.51 (s, 3H).
13C{1H} NMR (100 MHz, CD3OD) δ 147.6, 146.0, 143.8, 142.2,
1-(p-Tolyl)pyridin-1-ium Trifluoromethanesulfonate (2t·CF3SO3).
The reaction was performed in a closed MW vial (10 mL) equipped
with a stirring bar and containing 1t (53.6 mg, 0.50 mmol, 1.0 equiv),
5 (136 mg, 1.00 mmol, 2.0 equiv), 1.0 mL (5 equiv) of CF3SO3H (2.5
N) in EtOH and 1.0 mL of H2O. After 15 min of reaction at 130 °C,
the solvent was removed under reduced pressure. EtOAc (90 mL)
was added to the crude, and the resulting solution was successively
sonicated (2 min), filtrated over Celite, and concentrated under
reduced pressure. Purification by reversed phase chromatography
according to Method P2 gave 2t·CF3SO3 as a brown viscous liquid
(104 mg, 65%). 1H NMR (400 MHz, CD3OD) δ 9.21 (d, J = 7.0 Hz,
2H), 8.76 (t, J = 7.0 Hz, 1H), 8.26 (t, J = 7.0 Hz, 2H), 7.69 (d, J = 8.0
Hz, 2H), 7.56 (d, J = 8.0 Hz, 2H), 2.51 (s, 3H). 13C{1H} NMR (100
MHz, CD3OD) δ 147.5, 145.8, 143.6, 142.1, 132.1, 129.5, 125.1,
121.75 (q, J = 318.7 Hz), 21.1. 19F{1H} NMR (376 MHz, CD3OD) δ
−79.94. IR (neat) ν 3444, 3075, 1630, 1509, 1476, 1447, 1155, 1027,
778. LC-MS m/z (%) 170 (100), 171 (15), 489 (6). Anal. calcd for
C13H12F3NO3S: C, 48.90; H, 3.79; N, 4.39; Found C, 48.74; H, 3.75;
N, 4.05. HRMS (ESI-TOF) m/z: [M]+ Calcd for C12H12N 170.0964;
Found 170.0961.
132.2, 129.5, 125.2, 21.1. IR (neat) ν 3288, 2940, 2874, 1634, 1524,
1455, 882. ν LC-MS m/z (%) 170 (100), 171 (14). HRMS (ESI-
TOF) m/z: [M]+ Calcd for C12H12N 170.0964; Found 170.0960.
Preparation of Glutaconaldehyde Salt 5. (2E,4E)-5-(Pyrroli-
din-1-yl)penta-2,4-dienal (7). A solution of pyrrolidine (12.1 mL,
147.4 mmol, 2.1 equiv) in MeOH (250 mL) was prepared in a one-
neck round-bottom flask (500 mL) equipped with a stirring bar and
cooled at 0 °C. Glutaconaldehyde dianil hydrochloride 6 (20 g, 70.2
mmol, 1.0 equiv) was added portionwise to the solution, and the
mixture was maintained at 0 °C under agitation. After 45 min, the
solvent was removed under reduced pressure. To the resulting solid,
THF (200 mL) was added. After trituration, the mixture was filtrated
on a fritted glass, and the solid was first washed with THF (3 × 100
mL), then with Et2O (200 mL). After dissolution of the solid in H2O
(300 mL), the resulting aqueous solution was washed with Et2O (4 ×
100 mL) and then poured in an Erlenmeyer (1 L) equipped with a
stirring bar. Under stirring, the aqueous solution was cooled down to
0 °C and then basified by adding NaOH (56 g, 1.4 mol, 20.0 equiv).
CH2Cl2 (400 mL) was added to this solution, and the biphasic
mixture was stirred for a further 60 min at room temperature. After
separation, the organic layer was dried over Na2SO4, filtrated, and
concentrated under reduced pressure. Aminopentadienal 7 was
obtained as a brown solid (10.2 g) and engaged in the next step
without further purification. 1H NMR (400 MHz, CDCl3) δ 9.27 (d, J
= 8.5 Hz, 1H), 7.09 (t, J = 14.0 Hz, 1H), 7.01 (d, J = 12.5 Hz, 1H),
5.83 (dd, J = 14.0, 8.5 Hz, 1H), 5.24 (t, J = 12.5 Hz, 1H), 3.53- 3.04
(m, 4H), 2.07−1.81 (m, 4H).
1-(p-Tolyl)pyridin-1-ium Nitrate (2t·NO3). The reaction was
performed in a closed MW vial (10 mL) equipped with a stirring
bar and containing 1t (53.6 mg, 0.50 mmol, 1.0 equiv), 5 (136 mg,
1.00 mmol, 2.0 equiv), 0.6 mL (3 equiv) of HNO3 (2.5 N) in
tBuOH/H2O (50/50) and 1.4 mL of tBuOH/H2O (50/50). After 15
min of reaction at 130 °C, the solvent was removed under reduced
pressure. EtOH (90 mL) was added to the crude, and the resulting
solution was successively sonicated (2 min), filtrated over Celite, and
concentrated under reduced pressure. Purification by reversed phase
chromatography according to Method P1 gave 2t·NO3 as a brown
Glutaconaldehyde Potassium Salt (5).40 In a one-neck round-
bottom flask (500 mL) equipped with a stirring bar, KOH (99.98%
purity, 3.77 g, 67.4 mmol, 1.0 equiv) was dissolved in MeOH (18
mL). After addition of THF (160 mL) and aminopentadienal 7 (10.2
g, 67.4 mmol, 1.0 equiv), the mixture was refluxed for 5 h. The
mixture was cooled to 0 °C, and the expected salt was precipitated by
addition of Et2O (300 mL). After filtration on a fritted glass, the solid
was washed with CH2Cl2 (70 mL) and then dissolved in a MeOH/
EtOH (90/10) mixture (880 mL). The alcoholic solution was filtered
over a pad of Celite and concentrated under reduced pressure.
Glutaconaldehyde potassium salt 5 was obtained as a brown powder,
stored in a desiccator, and used without further purification (8.7 g,
91% from dianil hydrochloride 6).
1
viscous liquid (98 mg, 84%). H NMR (400 MHz, CD3OD) δ 9.22
(d, J = 7.0 Hz, 2H), 8.76 (t, J = 7.0 Hz, 1H), 8.26 (t, J = 7.0 Hz, 2H),
7.70 (d, J = 8.2 Hz, 2H), 7.56 (d, J = 8.2 Hz, 2H), 2.51 (s, 3H).
13C{1H} NMR (100 MHz, CD3OD) δ 147.6, 146.0, 143.7, 142.2,
132.1, 129.5, 125.2, 21.1. IR (neat) ν 3119, 3062, 1629, 1511, 1475,
1339, 827. LC-MS m/z (%) 170 (100), 171 (13). HRMS (ESI-TOF)
m/z: [M]+ Calcd for C12H12N 170.0964; Found 170.0959.
1-(p-Tolyl)pyridin-1-ium Tetrafluoroborate (2t·BF4). The reaction
was performed in a closed MW vial (10 mL) equipped with a stirring
bar and containing 1t (53.6 mg, 0.50 mmol, 1.0 equiv), 5 (204 mg,
1.50 mmol, 3.0 equiv), 1.0 mL (5 equiv) of HBF4 (2.5 N) in tBuOH/
H2O (50/50) and 1.0 mL of tBuOH/H2O (50/50). After 15 min of
reaction at 130 °C, the solvent was removed under reduced pressure.
EtOH (90 mL) was added to the crude, and the resulting solution was
successively sonicated (2 min), filtrated over Celite, and concentrated
under reduced pressure. Purification by reversed phase chromatog-
raphy according to Method P2 gave 2t·BF4 as an orange powder (77
mg, 60%). 1H NMR (400 MHz, CD3OD) δ 9.19 (d, J = 6.9 Hz, 2H),
8.76 (t, J = 6.9 Hz, 1H), 8.26 (t, J = 6.9 Hz, 2H), 7.70 (d, J = 8.2 Hz,
2H), 7.56 (d, J = 8.2 Hz, 2H), 2.51 (s, 3H). 13C{1H} NMR (100
MHz, CD3OD) δ 147.6 (s), 146.0, 143.7, 142.2, 132.1, 129.5, 125.2,
21.1. 19F{1H} NMR (376 MHz, CD3OD) δ −154.2. IR (neat) ν
3132, 3082, 1633, 1515, 1488, 1415, 781. LC-MS m/z (%) 170 (100),
171 (14). Anal. calcd for C12H12BF4N.1/4H2O: C, 55.11; H, 4.82; N,
5.36; Found C, 55.45; H, 4.64; N, 5.29. HRMS (ESI-TOF) m/z:
[M]+ Calcd for C12H12N 170.0964; Found 170.0963.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.9b02538.
NMR and IR spectra of purified compounds (PDF)
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: rivard@icmpe.cnrs.fr.
ORCID
Michael Rivard: 0000-0002-5487-1595
1-(p-Tolyl)pyridin-1-ium Hexafluorophosphate (2t·PF6). The
reaction was performed in a closed MW vial (10 mL) equipped
with a stirring bar and containing 1t (53.6 mg, 0.50 mmol, 1.0 equiv),
5 (204 mg, 1.50 mmol, 3.0 equiv), 1.0 mL (5 equiv) of HPF6 (2.5 N)
in tBuOH/H2O (50/50) and 1.0 mL of tBuOH/H2O (50/50). After
15 min of reaction at 130 °C, the solvent was removed under reduced
pressure. EtOH (90 mL) was added to the crude, and the resulting
solution was successively sonicated (2 min), filtrated over Celite, and
concentrated under reduced pressure. Purification by reversed phase
chromatography according to Method P2 gave 2t·PF6 as a brown
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
G.A. thanks the MENESR and the Ecole Doctorale SIE
(Universite Paris Est) for a PhD fellowship. G.A. also thanks
́
̀
̀
the team “Systemes Polymeres Complexes” for financial
support. Tanya Farthing is gratefully acknowledged for
proofreading this article.
1
viscous liquid (55 mg, 35%). H NMR (400 MHz, CD3OD) δ 9.22
F
DOI: 10.1021/acs.joc.9b02538
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(18) Yazaki, K.; Sei, Y.; Akita, M.; Yoshizawa, M. A polyaromatic
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DEDICATION
■
In memory of Dr. Christian Marazano, who passed away on
November 12, 2008.
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