Synthesis of Quinolinium Salts from N-Substituted Anilines, Aldehydes, Alkynes, and Acids: Theoretical Understanding of the Mechanism and Regioselectivity

Article abstract of DOI:10.1002/ejoc.202000178

Secondary anilines were first utilized in the four-component coupling of aniline, aldehyde, alkyne, and acid to synthesize a variety of N-substituted quinolinium salts. This method was carried out under mild reaction conditions and exhibited excellent chemo- and regioselectivities. DFT calculation was performed to analyze the cyclization step, where the interaction/distortion model provided better insight into the singular selectivity of terminal/internal alkynes in reaction.

Full text of DOI:10.1002/ejoc.202000178

A Journal of
Accepted Article
Title: Synthesis of Quinolinium Salts from N-Substituted Anilines,
Aldehydes, Alkynes, and Acid: Theoretical Understanding of the
Mechanism and Regioselectivity
Authors: Lin-Chieh Cheng, Wei-Chen Chen, Rajagopal
Santhoshkumar, Tzu-Hsuan Chao, Mu-Jeng Cheng, and
Chien-Hong Cheng
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.202000178
Link to VoR: http://dx.doi.org/10.1002/ejoc.202000178
Supported by

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
Synthesis of Quinolinium Salts from N-Substituted Anilines,
Aldehydes, Alkynes, and Acid: Theoretical Understanding of the
Mechanism and Regioselectivity
Lin-Chieh Cheng‡[a], Wei-Chen Chen‡[a], Rajagopal Santhoshkumar[a], Tzu-Hsuan Chao[b], Mu-Jeng
Cheng*[b], and Chien-Hong Cheng*[a,c]
Abstract: Secondary anilines were first utilized in the four-
component coupling of aniline, aldehyde, alkyne, and acid to
synthesize a variety of N-substituted quinolinium salts. This method
was carried out under mild reaction conditions and exhibited excellent
chemo- and regioselectivities. DFT calculation was performed to
analyze the cyclization step, where the interaction/distortion model
provided better insight into the singular selectivity of terminal/internal
alkynes in reaction.
aromatic aldimines.[12] In this path, the hypothetical mechanism of
[4+2] cyclization reactions have been proposed through a
concerted process or a step-wise manner, but the real mechanism
remained unclear. Though synthesis of quinoline from imines and
alkynes are widely-known, there has been only one report, which
proposed an in situ formed N-substituted iminium ions reacting
with alkynes. In 1998, Katritzky utilized benzotriazole derivatives
as starting materials to synthesize the quinolinium salts (Scheme
1B),[13] but this method needed the prefunctionalization of
secondary anilines and only offered N-alkyl products with low
atom-economy. Based upon this background and our continued
interest in quaternary ammonium salt synthesis,[14] we are highly
interested in developing a rapid and efficient method to furnish N-
aryl and -alkyl quinolinium salts. Herein, we describe a four-
component coupling of aniline, aldehyde, alkyne, and acid to
synthesize N-substituted quinolinium salts. To better explain the
mechanism and regioselectivity, theoretical studies were carried
out for the key cyclization step.
Introduction
N-heteroaromatic cations are essential skeletons found in many
bioactive
molecules,
pharmaceuticals,
and
material
applications.[1] In particular, quinolinium salts are notable due to
their bioactivity in medical researches.[2] The easily convertible
electrophilic 2 and 4 positions of the arene promise quinolinium
salts an useful precursor in the synthesis of N-heterocyclic
derivatives.[3] Due to its strong oxidizing ability at singlet excited
state and long fluorescence lifetimes,[4] quinolinium salts serve as
potent photoredox catalysts, which have been utilized in benzene
C–H functionalizations and benzylic cleavage/cyclization
reactions.[5] Although the basic and nucleophilic nitrogen of
quinolines provides direct access to quinoliniums with
electrophiles,[6] this strategy limits the substrate scopes to N-alkyl
products. In 1950s, Pilyugin first developed a series of cascade
reactions of diarylamine, formaldehyde, acetone, and acid to
access N-aryl quinolinium salts,[7] which addressed the
disadvantages of substitution approach. However, these methods
suffered from harsh reaction conditions and offered poor product
yields. Except for Pilyugin’s works, report of synthesis and
application of N-aryl quinolinium salts is rare.[8]
A) Aniline-aldehyde-alkyne reaction:
H
H
R1
N
N
R1
(a)
H
NH2
LA
R2
LA
R2
H+/LA
1º amine
H/LA
N
O
R1
R1
N
[O]
H
H+/LA
N
R1
step-wise
R2
R1
H
R2
R2
(b)
H+/LA
H
LA= Lewis Acid
R2
R1
H
H
N
concerted
R
B) Previous work:
R2
-
R
N
N
BtBF3
R
N
N
N
-
BtBF3
N
[O]
BF3ꢀOEt2
R3
R3
Benzotriazole
R = Me, Bn
In contrast to lack of synthetic methods for quinolinium salts,
several approaches have been developed to synthesize
quinolines.[9] A well-established route to acquire multi-substituted
quinolines is through Bronsted/Lewis acid activated aniline-
aldehyde-alkyne reaction (A3 reaction)[10] (Scheme 1A). There are
generally two different pathways involved in the reaction. In one
path, a propargylamine generated from nucleophilic addition of
terminal alkyne to imine undergoes cyclization and oxidation to
afford quinoline motif.[11] Another path is a variant of Povarov
reaction with acetylenes used as dienophiles to cyclize with
R2
R2
C) This work:
-
BF4
R
N
H
N
R1/H
O
H
R
Cu(II)/O2
H1/R
R2
R3/H
+
HBF4
+
+
R3/H
2º amine
R = Aryl, Alkyl
R2
[O]
R
N
R
N
R
N
R1/H
R3/H
R1/H
R1/H
R3/H
N-substituted
iminiums
R2
R2
R3
/H
R2
Scheme 1. Strategies for the synthesis of quinolines and quinoliniums
[a] Department of Chemistry, National Tsing Hua University
Hsinchu, 30013, Taiwan
E-mail: chcheng@mx.nthu.edu.tw
http://mx.nthu.edu.tw/~chcheng/
[b] Department of Chemistry, National Cheng Kung University
Tainan, 70101, Taiwan
Results and Discussion
E-mail: mjcheng@mail.ncku.edu.tw
[c] Department of Chemistry, National Sun Yat-sen University,
Kaohsiung, 80424, Taiwan
[‡] Both authors contribute equally.
We commenced our investigation by the reaction of aniline 1a,
phenylacetylene 2a, paraformaldehyde 3a, and HBF4 in
acetonitrile under an oxygen balloon at room temperature for 1 h.
The reaction produced quinolinium salt 4aa in 43% yield and
tertiary aniline 5a in 48% yield (Table 1, entry 1). The formation of
tertiary aniline 5a is consistent with previous research that imines
could act as hydrogen acceptor.[11a, 15] In this case, iminium ion I-
Supporting information for this article is given via a link at the end
of the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
Tol played the role in oxidizing hydroquinoline to form quinolinium
salts. Though isolation of I-Tol was unsuccessful due to the short
quinolinium salts 4aa-ay is consistent with preceding reports.[18]
Phenylacetylenes with substituents at para (2b-2g), meta (2h-2i),
and ortho (2j) positions all underwent the reaction efficiently.
Sterically hindered tri-substituted substrate 2k also participated in
the reaction affording 4ak in 91% yield. Alkynes with thiophene 2l
and naphthyl 2m groups delivered products 4al-am in good
yields. Aliphatic alkynes 2n-o were tolerated well to provide salt
products 4an-ao. Unfortunately, methyl propiolate was incapable
to react in our conditions. Symmetrical alkynes, 3-hexyne 2p and
diphenylacetylenes 2q-s could be used in the reaction but gave
decreased yields. This was probably due to evenly distributed
electronic structure which slower the cyclization step and allowed
side reaction. Unsymmetrical alkynes 2t-y were also examined to
give 3-alkyl quinolinium salts 4at-av. Surprisingly, less
nucleophilic ynone 2w and phenyl propiolates 2x-y could also be
functionalized to afford desired salts 4aw-ay. The structures of
4aw-ay were confirmed by either X-ray crystallographic analysis
or NOE nuclear magnetic resonance spectroscopic analysis (see
supporting information).
lifetime,
fortunately,
we
separated
I-Tol-BrPh[16]
by
recrystallization, which confirmed the iminium ion produced in
situ. In order to prevent depletion of reactive intermediate,
catalysts featuring strong oxidizing efficiency were considered.
Table 1. Optimization studies[a][b]
Entry
1
2
3
4
5
6
7
8
[Cu]
-
CuBF4 6H2O
Cu(OTf)2
Cu(OAc)2
CuSO4
CuCl2
CuCl
Solvent
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3NO2
AcOH
Yield (%)
43
.
52
54
56
69
87
81
49
72
68
80
71
52
CuI
As for aldehydes, the present reaction was not limited to
formaldehyde; it is also suitable for aliphatic and aryl aldehydes.
Valeraldehyde 3b was able to yield salt product 6b. Aromatic
aldehydes 3c-g required higher temperature and longer time to
conquer the steric hindrance in the condensation step.
Disappointingly, these substrates offered quinolinium salts 6c-g
in low yields. Ynal 3h combining alkyne and aldehyde groups in
one reagent directly furnished tricyclic product 6h. N-tethered ynal
3i was also examined, but produced quinoline 7a. This product
might result from salt 6i through elimination reaction of tosyl
group,[19] but the exact mechanism was unclear.
9
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
CuCl2
10
11
12
13[c]
14[d]
CHCl3
DCE
CH3CN
CH3CN
93
[a] Unless otherwise mentioned, all reactions were carried out with aniline 1a
(0.30 mmol), alkyne 2a (0.30 mmol), paraformaldehyde 3a (0.40 mmol), cat.
[Cu] (0.030 mmol), HBF4 (0.40 mmol, 50% in water), and solvent (3.0 mL) at
rt under an O2 balloon. [b] Isolated yields. [c] Reaction under an air balloon.
[d] Reaction with alkyne 2a (0.40 mmol) and CH3CN (2.0 mL). AcOH = acetic
acid, DCE = 1,2-dichloroethane.
Furthermore, with hydrohalic acid and acetic acid, the isolation
of quinolinium salts with these anions was unsuccessful. To our
delight, CF3SO3H provided a good complementary ion and triflate
salt 4aa’ could be isolated in 94% yield.
To elucidate the role of copper catalyst, we carried out several
control experiments. The moderate product yields of internal
alkynes 2t-y under condition without copper catalyst preclude
alkyne complexation by Cu(II) (Scheme 2, condition a). Previously,
CuCl2 have been reported to oxidize N,N-dimethylanilines under
aerobic condition.[17d] To test the possibility, tertiary amine 5a was
treated with 2a in the presence of CuCl2 (Scheme 3a). Only a
trace amount of 4aa was observed in the reaction, indicating 5a
could not be reactivated to iminium ion I-Tol under our conditions.
In addition, stoichiometric CuCl2 was used under condition without
oxygen, and gave good yield (Scheme 3b). This confirmed the
CuCl2 could compete with iminium ions in the oxidation step.
Copper reagent, which has been employed in aerobic
dehydrogenation reaction,[17] was applied to this system. Different
copper salts were tested (Table 1, entries 2‒8), in which CuCl2
provided 4aa in 87% yield (Table 1, entry 6). When the reaction
was performed in other solvents, such as CH3NO2, CH3COOH,
CHCl3, and DCE, there was no improvement in the efficiency
(Table 1, entries 9‒12). The reaction in the presence of an air
balloon was not effective (Table 1, entry 13). Increasing alkyne 2a
to 0.40 mmol in 0.15 M acetonitrile showed the best performance
(Table 1, entry 14).
With the optimized conditions, we explored the scope of the
reaction. The results revealed that a variety of N-substituted
anilines, alkynes, and aldehydes were viable in the transformation
in good to excellent yields (Scheme 2). Different substituted N-
aryl anilines 1a-d underwent tandem cyclization to afford N-aryl
quinolinium salts 4aa-da. The structure of 4aa was
unambiguously confirmed by X-ray crystallographic analysis. It is
noteworthy that unsymmetrical diarylamine 1e furnished product
4ea with a chemo-isomeric ratio of 69:31. The results illustrated
that the electron-rich aryl group favored the reaction. In addition,
N-methyl anilines with electron donating (1g, 1l), halogen (1i-j),
and electron withdrawing (1k) substitution proceeded smoothly to
yield N-alkyl products 4fa-la. N-heterocyclic compounds, indoline
1m and tetrahydroquinoline 1n, participated in the reaction to
build multicyclic quinolinium motifs 4ma-na in good yields. N-
Benzyl aniline 1o is also an effective reagent in the reaction.
(a)
p-Tolyl
p-Tolyl
N
CuCl2 (10 mol%)
HBF4 (1.33 equiv)
-
N
BF4
+
CH3CN
rt, 1hr
O2 balloon
5a
4aa
trace
Ph
X
[O]
p-Tolyl
N
I-Tol
(b)
(c)
p-Tolyl
N
p-Tolyl
NH
CuCl2 (2.2 equiv)
HBF4 (1.33 equiv)
-
BF4
(CH2O)n
+
+
CH3CN
rt, 1hr
N2 balloon
4aa
80%
Ph
p-Tolyl
BF4
p-Tolyl
N
KOH (10 equiv)
- K3[Fe(CN)6] (2.5 equiv)
N
O
H2O
60˚C, 18 hr
4aa
8a
64%
Ph
Ph
Regarding alkyne substrates, both terminal and internal
acetylenes proceeded in the reaction with high efficacy to provide
single regioisomeric products. The regioselectivity of the
Scheme 3. (a) Reaction of tertiary amine with Cu(II). (b) Reaction with
stoichiometric Cu(II) under N2. (c) Synthesis of quinolinone.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
-
BF4
R
N
R
R4
10 mol% CuCl2
1.33 eq. HBF4
O
NH
R2
R3
+
R4
MeCN
O2, rt, 1hr
R1
R3
H
R1
4
1
2
3
R2
Aniline scope:
R’
Aldehyde scope:
p-Tolyl
4aa: R’ = Me, 93% (53%[a]
4ba: R’ = H, 69%
4ca: R’ = tBu, 82%
4da: R’ = Br, 76%
)
-
-
-
BF4
CF3SO3
BF4
N
-
BF4
’R
N
Ph
N
Ph NC
N
Ph
Ph
4aa
4aa’: 94%
4ea: 68%
(69:31)[b]
6b: 77%[e]
R’
4fa: R’ = H, 60%
4ga: R’ = Me, 89%
4ha: R’ = OMe, 63%
4ia: R’ = Cl, 43%
4ja: R’ = Br, 61%
4ka: R’ = CN, 57%
p-Tolyl
N
-
BF4
- N
Ph
- N
Ph
- N
Ph
- N
Ph
- N
Ph
BF4
BF4
BF4
BF4
BF4
R’’’
Ph
4na: 75%
4ma: 69%
4oa: 81%
4la: 91%
6c: R’’’ = 4-Me, 48%[f]
6d: R’’’ = 4-Br, 44%[f]
6e: R’’’= 4-CF3, 50%[f]
6f: R’’’= 3-Br, 37%[f]
6g: R’’’= 2-NO2, 33%[f]
Alkyne scope:
4ab: R’’ = Me, 86%
4ac: R’’= OMe, 72%
4ad: R’’= tBu, 93%
4ae: R’’= F, 86%
R’’
-
-
-
BF4
BF4
BF4
p-Tolyl
N
R’’
p-Tolyl
N
4ah: R’’ = Me, 74% p-Tolyl
4ai: R’’ = Br, 76%
N
4af: R’’= Cl, 76%
4ag: R’’ = COMe, 78%
p-Tolyl
4aj: 80%
N
-
BF4
p-Tolyl
-
-
-
-
BF4
BF4
BF4
BF4
OMe
6h: 94%
R2
p-Tolyl
N
p-Tolyl
N
p-Tolyl
N
p-Tolyl
N
S
p-Tolyl
4ak: 91%
4al: 71%
4am: 82%
4an: R2 = Cy, 80%
4ao: R2 = nPr, 61%
N
-
BF4
NTs
p-Tolyl
6i
-
-
-
BF4
BF4
p-Tolyl
BF4
p-Tolyl
TsH
p-Tolyl
N
N
R’’
N
HBF4
4at: R3 = Me, 79%[d] (52%[a]
4au: R3 = Et, 80%[d]
)
R3
p-Tolyl
4ap: 45%[c]
4aq: R’’ = H, 66%[c]
4ar: R’’ = Me, 60%[c]
4as: R’’ = F, 43%[c]
4av: R3 = Cy, 81%[d] (56%[a]
)
N
4aw: R3 = COMe, 63%[d] (33%[a]
4ax: R3 = CO2Me, 77%[d] (43%[a]
)
)
)
4ax
R’’
N
4ay: R3 = CO2Et, 66%[d] (39%[a]
p-Tolyl
7a: 66%
Scheme 2. Scope of the reaction. Conditions: anilines 1 (0.30 mmol), alkyne 2 (0.40 mmol), paraformaldehyde 3a (0.40 mmol), CuCl2 (0.03 mmol), HBF4 (0.40
mmol, 50% in water) and MeCN (2.0 mL) at rt under O2 balloon for 1 h. Yields of isolated products are given. [a] without CuCl2. [b] Regioisomers were determined
from 1H NMR analysis of crude product. [c] Alkynes 2 (0.60 mmol), paraformaldehyde 3a (0.50 mmol) at 60 °C. [d] Alkynes 2 (0.60 mmol) and paraformaldehyde
3a (0.33 mmol) at rt. [e] Alkyne 2a (0.60 mmol), valeraldehyde 3b (0.40 mmol) at 60 °C. [f] Aldehydes 3c-g (0.40 mmol) at 60 °C for 24 h.
Moreover, quinolinium salts were easily transformed into
corresponding 2-quinolones by oxidation. For example,
quinolinium salt 4aa was treated with K3[Fe(CN)6] in water to give
2-quinolones 8a in 64% yield (Scheme 3c).
CH3 of 2t, was replaced by -H, -C(O)CH3, and -C(O)OCH3 (see
supporting information).
R
O
HBF4
NH
A plausible mechanism for the present reaction is proposed in
Scheme 4. The reaction starts with the formation of iminium ion I-
Ph from aniline 1 and aldehyde 3a in the presence of HBF4. Then,
[4+2] cycloaddition of 2t with I-Ph followed by aromatization
affords intermediate III. Finally, the oxidation of III by Cu(II)
produces the desired salt 4 and Cu(I) (path a). The Cu(I) was
reoxidized to Cu(II) by oxygen for the next oxidation step.
Alternatively, the oxidation of III could be conducted by iminium
ion I-Ph (path b), which is suppressed in the presence of Cu(II).
Density functional theory (DFT, the B3LYP function)[20]
combined with the CPCM implicit solvation model[21] was used to
investigate the [4+2] cycloaddition of iminium intermediate I-Ph
with 2t (methylphenylacetylene) to form II-Ph, the key step in the
proposed mechanism. The reaction is found to proceed through a
concerted and yet asynchronous transition state with one C–C
distance (C1-C2: 2.00 Å for TS-A and C1-C3: 1.89 Å for TS-B,
(Scheme 5a)) that is much shorter than the other (C4-C3: 4.57 Å
for TS-A and C4-C2: 3.18 Å for TS-B, (Scheme 5a)), as confirmed
by the intrinsic reaction coordinate (IRC) calculations. The
ΔH‡/ΔH is 10.8/-22.6 kcal/mol for the formation of II-Ph-A and
19.4/-22.9 kcal/mol for II-Ph-B (Scheme 5b), which is qualitatively
consistent with our experimental results showing that II-Ph-A is
the only product. Similar results were obtained when terminal -
H
H
R
N
3a
BF4
1
H2O
R
R
BF4
N
N
Me
Ph
IV
4
Ph
I-Ph
1/2 O2
H2O
path b
Me
Ph
I-Ph
2t
R
N
R
Cu(I) Cu(II)
N
HBF4
Me
Me H3O
H
path a
III
Ph
II-Ph
Ph
H2O
Scheme 4. A plausible mechanism.
The energy decomposition scheme proposed by Head-Gordon
et al.[22] was used to analyze the transition state to identify the
roles that I-Ph and 2t play in the reaction. This approach has been
utilized by Goddard et al. to characterize the role of metal
complexes in methane C–H activation.[23] From the charge
transfer (CT) term, we find that much more electron density was
transferred from 2t to I-Ph (0.558 e- for TS-A and 0.522 e- for TS-
B) than from I-Ph to 2t (0.006 e- for TS-A and 0.019 e- for TS-B),
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
suggesting that 2t is
a
nucleophile whereas I-Ph is an
In addition to the key step, the energetics for the other steps in
the proposed mechanism were also calculated (Scheme 7). It was
found that all of the kinetic barriers are less than 15.0 kcal/mol
and that most of the reaction energies are downhill, with only two
being slightly uphill (2.1 and 5.9 kcal/mol, colored by red). This
finding demonstrates that the overall reaction is facile and
validates the proposed mechanism (Scheme 4).
electrophile. Moreover, the most significant CT interaction is from
the HOMO of 2t to the LUMO of I-Ph (Scheme 6). The results
support that when the terminal -Me is replaced by more electron-
withdrawing groups, -C(O)CH3 and -C(O)OCH3, ΔH‡ increases
from 10.2 to 11.3 and 13.0 kcal/mol, respectively (see supporting
information).
Ph
N
Ph
H
N
OH
∆ H kcal/mol
0.0
H3O+
H2
O
H2
O
-9.2
Ph
N
-10.4
H
H
Cl
Cu
-21.2
Cl
Ph
N
-23.3
Me
N
H
Ph
N
H3O+
Ph
H
CuCl2
Ph
N
H
H
O
H
OH
Me
-37.9
H
Me
Ph
-43.8
H2
O
Ph
Ph
N
-53.2 CuCl + HCl
-53.7
Ph
N
CuCl2
CuCl2
Ph
N
Me
H
H
H
Ph
Me
Me
Ph
-74.3
Ph
Scheme 7. Calculated ΔH‡ and ΔH for each step in the proposed mechanism.
Conclusion
In summary, we have successfully developed an efficient method
for the synthesis of quinolinium salts from secondary anilines,
alkynes, aldehydes, and acid. The four-component coupling
reaction was combined with Cu-catalyzed aerobic oxidation to
offer a highly atom-economical process. A wide range of
substrates,
including
terminal/internal
alkynes
and
aliphatic/aromatic aldehydes, was converted into quinolinium
salts under ambient temperature. The DFT calculations confirm
that the reaction proceeds through a concerted asynchronous
[4+2] cycloaddition of an iminium ion with alkyne, which occurs in
polar Diels-Alder fashion with the iminium ion acting as the
acceptor and alkyne as the donor. The distortion/interaction
model shows that the regioselectivity of alkynes is controlled by
the distortion energy for easy interaction. Further investigation
into highly atom-economical synthetic methods using Cu(II)/O2 is
underway.
Scheme 5. (a) The optimized structures for all stationary points along the two
pathways. Carbon, nitrogen, and hydrogen are colored by black, blue, and gray,
respectively. (b) The enthalpic reaction profiles for the [4+2] cycloaddition of I-
Ph and 2t. (c) Schematic description of the decomposition of the ΔH‡ into the
distortion energy (ΔHDIS, the energy cost to distort the two isolated reactants into
the corresponding geometries in the transition state, e.g., I-Ph → I-Ph’A and 2t
→ 2t’A) and the interaction energy (ΔHINT, the energy gain from bringing the two
distorted reactants together to form the final transition state structure, e.g., I-
Ph’A + 2t’A → TS-A). The units are kcal/mol for energy and Å for bond length.
To understand the driving force for the regioselectivity, each
ΔH‡s was decomposed into the distortion and interaction energy
(ΔH‡ = ΔHDIS + ΔHINT, Scheme 5c). Our calculations show that
ΔHDIS for Path-A (20.2 kcal/mol) is much smaller than ΔHDIS for
Path-B (32.8 kcal/mol), whereas the ΔHINTs values for the two
pathways are relatively similar (-9.4 and -13.4 kcal/mol for Path-
A and Path-B, respectively). This result means that the lower ΔH‡
for Path-A is due to the lower energy cost to distort the reactants.
Further analysis shows that this is contributed by both fragments
(ΔHDIS, I-Ph, and ΔHDIS, 2t are 10.2 and 10.0 kcal/mol for Path-A
compared with 16.9 and 15.9 kcal/mol for Path-B).
Experimental Section
General procedure for the synthesis of quinolinium salts 4aa-
4oa, 4aa’, 4ab-4ao. A sealed tube fitted with a rubber septum
was charged with CuCl2 (4.0 mg, 0.03 mmol), aniline (0.30 mmol),
alkyne (0.40 mmol) and paraformaldehyde (12 mg, 0.4 mmol),
then, the septum was secured with parafilm. The tube was
evacuated to remove air and O2 balloon inserted. Subsequently,
MeCN (2 mL) and Acid (0.40 mmol) were added to the tube via
syringe. (If aniline or alkyne were liquid, they were added with
syringe following the insertion of MeCN.) The resulting mixture
°
was stirred at 20 C for 1 h. Then, the reaction was diluted with
CH2Cl2 (10 mL), filtered through celite pad, and washed three
times with CH2Cl2 (3×20 mL). The combined filtrate was
concentrated under vacuum. (i) The residue was purified by
chromatography using MeOH and CH2Cl2 as eluent to afford 4aa-
4ha, 4aa’, 4la-4oa, 4ab-4ao. (ii) The residue was dissolved in
minimal CH2Cl2, and Et2O was added dropwise. The precipitate
Scheme 6. Complementary Occupied-Virtual Pair interaction for HOMO of 2t
with LUMO of I-Ph based on the EDA-ALMO scheme. Blue, gray, and white
represent nitrogen, carbon, and hydrogen, respectively.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
was collected and washed with Et2O three times (3×10 mL). The
solid was recrystallized in MeOH and CHCl3 to afford quinolinium
salts 4ia-ka.
119.9 (CH), 35.4 (C), 35.0 (C), 31.0 (3CH3), 30.5 (3CH3) cm-1.
HRMS (FAB, [M]+) for C29H32N calcd 394.2529, found 394.2523.
6-Bromo-1-(4-bromophenyl)-4-phenylquinolin-1-ium
6-Methyl-4-phenyl-1-(p-tolyl)quinolin-1-ium tetrafluoroborate
(4aa). Following the general procedure for the synthesis of
quinolinium salts and purification by chromatography on silica gel
(MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium salts 4aa as
pale yellow solid (110 mg, 93%). mp: 185-187°C. IR (neat): 1616,
1600, 1523, 1508, 1368, 1055 (υ B-F), 846, 823, 763, 704 cm-1. 1H
NMR (500 MHz, CDCl3): δ 9.05 (d, J = 6.0 Hz, 1H), 8.05 (d, J =
6.0 Hz, 1H), 8.00 (s, 1H), 7.78 (d, J = 9.0 Hz, 1 H), 7.65-7.64 (m,
2H), 7.60-7.59 (m, 4H), 7.51 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0
Hz, 2H), 2.53 (s, 3H), 2.49 (s, 3H); 13C NMR (125 MHz, CDCl3): δ
159.5 (C), 147.4 (CH), 142.2 (C), 141.1 (C), 138.4 (C), 137.2 (C),
137.2 (CH), 134.9 (C), 131.1 (2CH), 130.8 (CH), 129.7 (2CH),
129.2 (2CH), 128.3 (C), 127.3 (CH), 126.0 (2CH), 122.8 (CH),
119.9 (CH), 21.7 (CH3), 21.3 (CH3). 11B NMR (160 MHz, CDCl3):
δ -1.21. 19F NMR (470 MHz, CDCl3): δ -152.90, -152.96. HRMS
(FAB, [M]+) for C23H20N calcd 310.1590; found 310.1593.
tetrafluoroborate (4da). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
°
salts 4da as apricot solid (120.mg, 76%). mp: 262-264 C. IR
(neat): 1602, 1513, 1485, 1360, 1057 (υ B-F), 838, 763, 731, 710
1
cm-1. H NMR (500 MHz, (CD3)2CO): δ 9.63 (d, J = 6.0 Hz, 1H),
8.52 (s, 1H), 8.39 (d, J = 6.0 Hz, 1H), 8.33 (d, J = 9.5 Hz, 1H),
8.07 (d, J = 7.5 Hz, 2H), 7.97-7.93 (m, 3H), 7.84-7.83 (m, 2H),
7.78 (m, 3H). 13C NMR (125 MHz, (CD3)2CO): δ 160.5 (C), 150.3
(CH), 140.2 (C), 140.2 (C), 139.2 (CH), 135.6 (C), 134.6 (2CH),
132.1 (CH), 131.1 (CH), 130.8 (2CH), 130.3 (2CH), 130.2 (C),
129.8 (2CH), 126.4 (C), 125.0 (C), 124.4 (CH), 123.5 (CH). HRMS
(FAB, [M]+) for C21H14Br2N calcd 437.9488; found 437.9485.
1-(4-Cyanophenyl)-6-methyl-4-phenylquinolin-1-ium
tetrafluoroborate (4ea). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford products
6-Methyl-4-phenyl-1-(p-tolyl)quinolin-1-ium
°
trifluoromethanesulfonate (4aa’). Following the general
procedure for the synthesis of quinolinium salts and purification
by chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4aa’ as brown solid (130 mg, 94 %). mp:
130-132 °C. IR (neat): 1610, 1600, 1523, 1508, 1369 (υ S=O), 1261,
1224, 1154, 1030 (υ S=O), 824, 762, 734 cm-1. 1H NMR (400 MHz,
CDCl3): δ 9.11 (d, J = 6.0 Hz, 1H), 8.04 (d, J = 6.0 Hz, 1H), 7.99
(s, 1H), 7.79 (dd, J = 8.8, 1.6 Hz, 1H), 7.65-7.58 (m, 6H), 7.52 (d,
J = 8.4 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 2.52 (s, 3H), 2.48 (s, 3H).
13C NMR (100 MHz, CDCl3): δ 159.3 (C), 147.3 (CH), 142.1 (C),
141.0 (C), 138.2 (C), 137.2 (CH), 137.0 (C), 134.6 (C), 131.0
(2CH), 130.6 (CH), 129.5 (2CH), 129.1 (2CH), 128.1 (C), 127.1
(CH), 125.9 (2CH), 122.6 (CH), 120.4 (q, J = 317.8 Hz, CF3),
119.8 (CH), 21.8 (CH3), 21.4 (CH3). 19F NMR (470 MHz, CDCl3):
δ -78.27. HRMS (FD, [M]+) for C23H20N calcd 310.1590; found
310.1592.
4ea+4ea’ as cream yellow solid (83 mg, 68%). mp: 217-219 C.
IR (neat): 1599, 1557, 1524, 1503, 1388, 1304, 1283, 1059 (υ B-
1
F), 852, 823, 788, 764, 705 cm-1. H NMR (500 MHz, CDCl3): δ
9.04 (d, J = 6.0 Hz, 1H), 8.02 (s, 1H), 7.97 (d, J = 6.0 Hz, 1H),
7.93 (d, J = 8.5 Hz, 2H), 7.87 (d, J = 8.5 Hz, 2H), 7.80 (dd, J = 9.0,
1.0 Hz, 1H), 7.66-7.60 (m, 5H), 7.46 (d, J = 9.0, 1H), 2.53 (s, 3H).
13C NMR (125 MHz, CDCl3): δ 160.7 (C), 147.2 (CH), 142.7 (C),
141.4 (C), 137.9 (C), 137.7 (CH), 134.8 (C), 134.5 (2CH), 131.0
(CH), 129.7 (2CH), 129.3 (2CH), 128.4 (C), 128.0 (2CH), 127.7
(CH), 122.7 (CH), 119.2 (CH), 117.0 (C), 115.9 (C), 21.7 (CH3).
HRMS (FAB, [M]+) for C23H17N2 calcd 321.1386; found 321.1388
6-Cyano-4-phenyl-1-(p-tolyl)quinolin-1-ium tetrafluoroborate
(4ea’). Following the general procedure for the synthesis of
quinolinium salts and purification by chromatography on silica gel
(MeOH:CH2Cl2, 0:100 to 4:96) to afford products 4ea+4ea’ as
cream yellow solid (83 mg, 68%). mp: 251-253 °C. IR (neat): 2236
(υ CΞN), 1608, 1564, 1516, 1365, 1307, 1284, 1055 (υ B-F), 830,
787, 763 cm-1. 1H NMR (500 MHz, CDCl3): δ 9.15 (d, J = 6.5 Hz,
1H), 8.55 (s, 1H), 8.13 (d, J = 6.0 Hz, 1H), 8.01 (dd, J = 9.5, 1.0,
1,4-Diphenylquinolin-1-ium tetrafluoroborate (4ba). Following
the general procedure for the synthesis of quinolinium salts and
purification by chromatography on silica gel (MeOH:CH2Cl2, 0:100
to 4:96) to afford quinolinium salts 4ba as olive solid (83 mg, 69%). 1H), 7.79 (d, J = 9.5 Hz, 1H), 7.69-7.61 (m, 5H), 7.54 (d, J = 8.5
mp: 194-196 °C. IR (neat): 1604, 1590, 1525, 1492, 1396, 1308,
1055 (υ B-F), 764, 707 cm-1. 1H NMR (500 MHz, CDCl3): δ 9.06 (d,
J = 6.0 Hz, 1H), 8.24 (d, J = 8.5 Hz, 1H), 8.03 (d, J = 6.0 Hz, 1H),
Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H), 2.50 (s, 3H).13C NMR (125 MHz,
CDCl3): δ 161.3 (C), 150.9 (CH), 142.8 (C), 141.1 (C), 136.8 (C),
135.1 (CH), 134.4 (CH), 133.8 (C), 131.6 (CH), 131.3 (2CH),
130.0 (2CH), 129.6 (2CH), 128.0 (C), 126.1 (2CH), 124.3 (CH),
122.0 (CH), 116.5 (C), 114.0 (C), 21.4 (CH3). HRMS (FAB, [M]+)
for C23H17N2 calcd 321.1386; found 321.1394.
7.96-7.93 (m, 1H), 7.84-7.81 (m, 1H), 7.67-7.54 (m, 11H). 13
C
NMR (125 MHz, CDCl3): δ 160.5 (C), 148.2 (CH), 139.6 (C), 139.5
(C), 135.3 (CH), 134.6 (C), 131.6 (CH), 130.8 (CH), 130.6 (2CH),
130.1 (CH), 129.8 (2CH), 129.1 (2CH), 128.6 (CH), 128.0 (C),
126.3 (2CH), 122.5 (CH), 119.9 (CH). HRMS (FAB, [M]+) for
C21H16N calcd 282.1277; found 282.1287.
1-Methyl-4-phenylquinolin-1-ium tetrafluoroborate (4fa).
Following the general procedure for the synthesis of quinolinium
salts and purification by chromatography on silica gel
(MeOH:CH2Cl2, 0:100 to 6:94) to afford quinolinium salts 4fa as
white solid (56 mg, 60%). mp: 147-149 °C. IR (neat): 1604, 1531,
1448, 1398, 1368, 1056 (υ B-F), 859, 791, 768, 706 cm-1. 1H NMR
(500 MHz, (CD3)2CO): δ 9.51 (d, J = 5.5 Hz, 1H), 8.69 (d,J = 9.0
Hz, 1H), 8.35-8.32 (m, 1H), 8.30 (d, J = 8.5 Hz, 1H), 8.11 (d, J =
5.5 Hz, 1H), 8.07-8.04 (m, 1H), 7.71-7.70 (m, 5H), 4.86 (s, 3H).
13C NMR (125 MHz, (CD3)2CO): δ 159.7 (C), 150.0 (CH), 140.2
(C), 136.2 (CH), 135.9 (C), 131.4 (CH), 131.0 (CH), 130.6 (2CH),
130.0 (2CH), 129.3 (CH), 128.6 (C), 123.1 (CH), 120.2 (CH), 46.3
(CH3). HRMS (FAB, [M]+) for C16H14N calcd 220.1121; found
220.1129.
6-(tert-Butyl)-1-(4-(tert-butyl)phenyl)-4-phenylquinolin-1-ium
tetrafluoroborate (4ca). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4ca as olive solid (119 mg, 82%). mp: 217-219 °C. IR (neat):
1
2965, 1608, 1578, 1517, 1373, 1050 (υ B-F), 843, 764, 705. H
NMR (500 MHz, CDCl3): δ 9.15 (d, J = 6.0 Hz, 1H), 8.22 (d, J =
1.5 Hz, 1H), 8.17 (d, J = 6.0 Hz, 1H), 8.04 (dd, J = 9.0, 1.5 Hz,
1H), 7.70-7.67 (m, 5H), 7.63-7.62 (m, 3H), 7.57 (d, J = 8.5 Hz,
2H), 1.40 (s, 9H), 1.32 (s, 9H). 13C NMR (125 MHz, CDCl3): δ
159.8 (C), 155.1 (C), 153.6 (C), 147.4 (CH), 138.2 (C), 137.0 (C),
134.8 (C), 134.1 (CH), 130.9 (CH), 129.7 (2CH), 129.1 (2CH),
127.9 (C), 127.5 (2CH), 125.8 (2CH), 123.5 (CH), 122.8 (CH),
1,6-Dimethyl-4-phenylquinolin-1-ium tetrafluoroborate (4ga).
Following the general procedure for the synthesis of quinolinium
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
1
salts and purification by chromatography on silica gel
(MeOH:CH2Cl2, 0:100 to 7:93) to afford quinolinium salts 4ga as
white solid (86 mg, 89%). mp: 172-174 °C. IR (neat): 1613, 1536,
1452, 1346, 1234, 1055 (υ B-F), 851, 810, 769, 705 cm-1. 1H NMR
(500 MHz, CDCl3): δ 9.28 (s, 1H), 8.35 (d, J = 8.5 Hz, 1H), 8.00
(d, J = 8.5 Hz, 1H), 7.89 (s, 1H), 7.79 (s, 1H), 7.56-7.55 (m, 3H),
7.50-7.49 (m, 2H), 4.69 (s, 3H), 2.50 (s, 3H). 1H NMR (400 MHz,
(CD3)2SO): δ 9.45 (d, J = 5.2 Hz, 1H), 8.49 (d, J = 8.8 Hz, 1H),
8.15 (d, J = 8.8 Hz, 1H), 8.07 (d, J = 5.2 Hz, 1H), 7.94 (s, 1H),
7.67 (m, 5H), 4.67 (s, 3H), 2.55 (s, 3H). 13C NMR (125 MHz,
CDCl3): δ 158.2 (C), 147.6 (CH), 140.9 (C), 137.7 (CH), 137.5 (C),
134.7 (C), 130.5 (CH), 129.4 (2CH), 129.0 (2CH), 127.9 (C),
127.1 (CH), 122.1 (CH), 118.6 (CH), 45.6 (CH3), 21.5 (CH3).
HRMS (FAB, [M]+) for C17H16N calcd 234.1277; found 234.1287.
704 cm-1. H NMR (400 MHz, (CD3)2CO): δ 9.68 (d, J = 6.0 Hz,
1H), 8.91 (d, J = 9.2 Hz, 1H), 8.80 (d, J = 2.0 Hz, 1H), 8.58 (dd, J
= 9.2, 2.0 Hz, 1H), 8.31 (d, J = 6.0 Hz, 1H), 7.82-7.79 (m, 2H),
7.75-7.72 (m, 3H), 4.93 (s, 3H). 13C NMR (100 MHz, (CD3)2CO):
δ 160.2 (C), 152.4 (CH), 141.4 (C), 136.3 (CH), 135.1 (CH), 135.0
(C), 131.8 (CH), 130.7 (2CH), 130.1 (2CH), 128.2 (C), 124.5 (CH),
122.0 (CH), 117.3 (C), 114.5 (C), 46.7 (CH3). HRMS (FAB, [M]+)
for C17H13N2 calcd 245.1073; found 245.1075.
1,5,7-Trimethyl-4-phenylquinolin-1-ium
tetrafluoroborate
(4la). Following the general procedure for the synthesis of
quinolinium salts and purification by chromatography on silica gel
(MeOH:CH2Cl2, 0:100 to 7:93) to afford quinolinium salts 4la as
golden solid (91 mg, 91%). mp: 176-178 °C. IR (neat): 1621, 1608,
1571, 1456, 1347, 1056 (υ B-F), 855, 771, 708 cm-1. 1H NMR (500
MHz, (CD3)2CO): δ 9.39 (d, J = 6.0 Hz, 1H), 8.40 (s, 1H), 7.90 (d,
J = 6.5 Hz, 1H), 7.73 (s, 1H), 7.62-7.61 (m, 3H), 7.52-7.51 (m, 2H),
4.82 (s, 3H), 2.71 (s, 3H), 2.12 (s, 3H). 13C NMR (125 MHz,
(CD3)2CO): δ 160.4 (C), 148.1 (CH), 147.9 (C), 141.7 (C), 140.7
(C), 139.4 (C), 136.3 (CH), 130.4 (CH), 129.5 (2CH), 129.0 (2CH),
126.8 (C), 124.2 (CH), 117.6 (CH) 46.9 (CH3), 24.4 (CH3), 22.1
(CH3). HRMS (FAB, [M]+) for C18H18N calcd 248.1434; found
248.1443.
6-Methoxy-1-methyl-4-phenylquinolin-1-ium
tetrafluoroborate (4ha). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 7:93) to afford quinolinium
salts 4ha as purple solid (64 mg, 63%). mp: 168-170 °C. IR (neat):
1620, 1532, 1474, 1447, 1383, 1286, 1247, 1054 (υ B-F), 852, 786,
761, 711 cm-1. 1H NMR (500 MHz, (CD3)2CO): δ 9.36 (d, J = 5.5
Hz, 1H), 8.64 (d, J = 9.5 Hz, 1H), 8.07 (d, J = 5.5 Hz, 1H), 7.95
(dd, J = 9.5, 2.5 Hz, 1H), 7.79-7.77 (m, 2H), 7.71-7.70 (m, 3H),
7.61 (d, J = 3.0 Hz, 1H), 4.85 (s, 3H), 3.94 (s, 3H). 13C NMR (125
MHz, (CD3)2CO): 161.0 (C), 157.9 (C), 147.2 (CH), 136.3 (C),
136.0 (C), 131.4 (CH), 130.6 (C), 130.4 (2CH), 130.2 (2CH),
127.9 (CH), 123.5 (CH), 122.0 (CH), 107.1 (CH), 56.5 (CH3), 46.4
(CH3). HRMS (FAB, [M]+) for C17H16NO calcd 250.1226; found
250.1228
8-Methyl-6-phenyl-1,2-dihydropyrrolo[3,2,1-ij]quinolin-3-ium
tetrafluoroborate (4ma). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on alumina (MeOH:CH2Cl2, 0:100 to 3:97) to afford quinolinium
salts 4ma as white solid (66 mg, 69%). mp: 203-205 °C. IR (neat):
1629, 1523, 1438, 1393, 1336, 1222, 1052 (υ B-F), 859, 781, 764,
710 cm-1. 1H NMR (400 MHz, CDCl3): δ 10.08 (d, J = 5.6 Hz, 1H),
7.90 (d, J = 8.4 Hz, 1H), 7.86-7.83 (m, 2H), 7.77-7.73 (m, 1H),
6-Chloro-1-methyl-4-phenylquinolin-1-ium tetrafluoroborate
(4ia). Following the general procedure for the synthesis of
quinolinium salts and purification by recrystallization in
MeOH/CHCl3 (slow evaporation in air) to afford quinolinium salts
4ia as pale yellow solid (44 mg, 43%). mp: 167-169 °C. IR (neat):
1610, 1586, 1523, 1456, 1438, 1368, 1057 (υ B-F), 856, 825, 783,
7.52 (m, 5H), 5.66 (t, J = 6.8 Hz, 2H), 3.83 (t, J = 6.8 Hz, 2H). 13
C
NMR (100 MHz, CDCl3): δ 155.3 (C), 143.6 (CH), 141.8 (C), 136.3
(C), 133.9 (C), 131.6 (CH), 130.6 (CH), 129.1 (2CH), 129.0 (2CH),
128.6 (CH), 125.5 (C), 123.2 (CH), 122.9 (CH), 56.7 (CH2), 27.6
(CH2). HRMS (FAB, [M]+) for C17H14N calcd 232.1121; found
232.1123.
1
761 cm-1. H NMR (500 MHz, (CD3)2CO): δ 9.58 (d, J = 6.0 Hz,
1H), 8.77 (d, J = 9.5 Hz, 1H), 8.34 (dd, J = 9.5, 2.0 Hz, 1H), 8.27
(d, J = 2.5 Hz, 1H), 8.23 (d, J = 6.0 Hz, 1H), 7.78-7.75 (m, 2H),
7.74-7.73 (m, 3H), 4.91 (s, 3H). 13C NMR (125 MHz, (CD3)2CO):
159.1 (C), 150.6 (CH), 139.1 (C), 136.8 (C), 136.3 (CH), 135.6
(C), 131.8 (CH), 130.7 (2CH), 130.2 (2CH), 129.8 (C), 127.9 (CH),
124.3 (CH), 122.7 (CH), 46.6 (CH3). HRMS (FAB, [M]+) for
C16H13ClN calcd 254.0731; found 254.0737.
9-Methyl-7-phenyl-2,3-dihydro-1H-pyrido[3,2,1-ij]quinolin-4-
ium tetrafluoroborate (4na). Following the general procedure for
the synthesis of quinolinium salts and purification by
chromatography on alumina (MeOH:CH2Cl2, 0:100 to 3:97) to
afford quinolinium salts 4na as pale yellow solid (75 mg, 75%).
°
mp: 197-199 C. IR (neat): 1611,1570, 1539, 1450, 1419, 1370,
1274, 1238, 1054 (υ B-F), 859, 821, 770, 714 cm-1. 1H NMR (400
MHz, CDCl3): δ 9.31 (d, J = 6.0 Hz, 1H), 8.04 (d, J = 8.4 Hz, 1H),
7.88-7.86 (m, 2H), 7.76-7.72 (m, 1H), 7.59-7.57 (m, 3H), 7.55-
7.52 (m, 2H), 5.07 (t, J = 5.6 Hz, 2H), 3.36 (t, J = 6.0 Hz, 2H), 2.50
(m, 2H). 13C NMR (100 MHz, CDCl3): 158.8 (C), 147.3 (CH), 136.3
(C), 134.9 (C), 133.7 (CH), 130.5 (CH), 130.1 (C), 129.4 (2CH),
129.2 (CH), 129.1 (2CH), 128.4 (C), 126.5 (CH), 122.0 (CH), 57.3
(CH2), 27.4 (CH2), 20.8 (CH2). HRMS (FAB, [M]+) for C18H16N
calcd 246.1277; found 246.1284.
6-Bromo-1-methyl-4-phenylquinolin-1-ium tetrafluoroborate
(4ja). Following the general procedure for the synthesis of
quinolinium salts and purification by recrystallization in
MeOH/CHCl3 (slow evaporation in air) to afford quinolinium salts
4ja as white solid (71 mg, 61%). mp: 203-205 °C. IR (neat): 1608,
1584, 1520, 1454, 1434, 1365, 1229, 1050 (υ B-F), 839, 782, 762,
727, 710 cm-1. 1H NMR (500 MHz, (CD3)2CO): δ 9.60 (d, J = 5.5
Hz, 1H), 8.69 (d, J = 9.0 Hz, 1H), 8.45 (d, J = 9.0 Hz, 1H), 8.42 (d,
J = 1.5 Hz, 1H), 8.22 (d, J = 5.0 Hz, 1H), 7.77-7.76 (m, 2H), 7.73-
7.72 (m, 3H), 4.90 (s, 3H). 13C NMR (125 MHz, (CD3)2CO): δ
158.9 (C), 150.6 (CH), 139.3 (C), 138.9 (CH), 135.6 (C), 131.7
(CH), 131.2 (CH), 130.7 (2CH), 130.2 (2CH), 130.0 (C), 124.9 (C),
124.3 (CH), 122.6 (CH), 46.6 (CH3). HRMS (FAB, [M]+) for
C16H13BrN calcd 298.0226; found 298.0230.
6-Methyl-1-(4-methylbenzyl)-4-phenylquinolin-1-ium
tetrafluoroborate (4oa). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4oa as pink solid (100 mg, 81%). mp: 122-124 °C. IR (neat):
1606, 1585, 1569, 1529, 1446, 1433, 1375, 1239, 1056 (υ B-F),
820, 786, 763 cm-1. 1H NMR (500 MHz, CDCl3): δ 9.36 (d, J = 6.0
Hz, 1H), 8.36 (d, J = 9.0 Hz, 1H), 7.90-7.85 (m, 3H), 7.57-7.56 (m,
3H), 7.50-7.50 (m, 2H), 7.26 (d, J = 8.0 Hz, 2H), 7.05 (d, J = 8.0
Hz, 2H), 6.11 (s, 2H), 2.44 (s, 3H), 2.17 (s, 3H). 13C NMR (125
6-Cyano-1-methyl-4-phenylquinolin-1-ium tetrafluoroborate
(4ka). Following the general procedure for the synthesis of
quinolinium salts and purification by recrystallization in
MeOH/CHCl3 (slow evaporation in air) to afford quinolinium salts
4ka as yellow solid (56 mg, 57%). mp: 184-186 °C. IR (neat): 1610, MHz, CDCl3): δ 158.7 (C), 147.1 (CH), 140.9 (C), 139.0 (C), 137.6
1587, 1527, 1458, 1441, 1370, 1058 (υ B-F), 854, 835, 787, 765,
(CH), 136.8 (C), 134.7 (C), 130.6 (CH), 129.8 (2CH), 129.4 (2CH),
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
129.4 (C), 129.1 (2CH), 128.4 (C), 127.5 (2CH), 127.3 (CH),
122.2 (CH), 119.1 (CH), 60.8 (CH2), 21.4 (CH3), 20.8 (CH3).
HRMS (FAB, [M]+) for C24H22N calcd 324.1747; found 324.1754.
116.4 (d, J = 22.0 Hz, 2CH), 21.6 (CH3), 21.2 (CH3). 11B NMR (160
MHz, CDCl3): δ -1.29. 19F NMR (470 MHz, CDCl3): δ -108.62, -
152.82, -152.87. HRMS (FAB, [M]+) for C23H19FN calcd 328.1496;
found 328.1504.
6-Methyl-1,4-di-p-tolylquinolin-1-ium tetrafluoroborate (4ab).
Following the general procedure for the synthesis of quinolinium
salts and purification by chromatography on silica gel
(MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium salts 4ab as
4-(4-Chlorophenyl)-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4af). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
brown solid (106 mg, 86%). mp: 196-198 °C. IR (neat): 1598, 1523, on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
1508, 1369, 1056 (υ B-F), 819, 735 cm-1. 1H NMR (500 MHz,
CDCl3): δ 9.02 (d, J = 5.5 Hz, 1H), 8.03-8.01 (m, 2H), 7.78 (d, J =
9.0 Hz, 1H), 7.57 (d, J = 9.0 Hz, 1H), 7.54 (d, J = 7.5 Hz, 2H), 7.48
(d, J = 8.5 Hz, 2H), 7.44 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 7.5 Hz,
2H), 2.52 (s, 3H), 2.46 (s, 3H), 2.45 (s, 3H). 13C NMR (125 MHz,
CDCl3): δ 159.6 (C), 147.1 (CH), 142.1 (C), 141.4 (C), 141.0 (C),
138.3 (C), 137.2 (CH), 137.1 (C), 131.9 (C), 131.1 (2CH), 129.9
(2CH), 129.7 (2CH), 128.1 (C), 127.3 (CH), 125.9 (2CH), 122.4
salts 4af as pale yellow solid (98 mg, 76%). mp: 225-227 C. IR
(neat): 1603, 1592, 1522, 1508, 1368, 1055 (υ B-F), 822, 735 cm-
1. 1H NMR (500 MHz, CDCl3): δ 8.99 (d, J = 6.0 Hz, 1H), 8.01 (d,
J = 6.0 Hz, 1H), 7.92 (s, 1H), 7.77 (d, J = 9.0 Hz, 1H), 7.61 (d, J
= 8.0 Hz, 2H), 7.58-7.99 (m, 3H), 7.50 (d, J = 8.0 Hz, 2H), 7.44 (d,
J = 8.0 Hz, 2H), 2.52 (s, 3H), 2.48 (s, 3H). 13C NMR (125 MHz,
CDCl3): δ 157.9 (C), 147.1 (CH), 142.1 (C), 141.3 (C), 138.3 (C),
137.3 (CH), 137.1 (C), 136.9 (C), 133.2 (C), 131.0 (2CH), 131.0
°
(CH), 119.8 (CH), 21.6 (CH3), 21.3 (CH3), 21.2 (CH3). HRMS (FAB, (2CH), 129.3 (2CH), 128.0 (C), 126.7 (CH), 125.9 (2CH), 122.5
[M]+) for C24H22N calcd 324.1747; found 324.1757.
(CH), 119.8 (CH), 21.5 (CH3), 21.1 (CH3). HRMS (FAB, [M]+) for
C23H19ClN calcd 344.1201; found 344.1202.
4-(4-Methoxyphenyl)-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4ac). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4ac as brown solid (92 mg, 72%). mp: 220-222 °C. IR (neat):
4-(4-Acetylphenyl)-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4ag). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4ag as coffee brown solid (103 mg, 78%). mp: 219-221 °C.
IR (neat): 1684 (υ C=O), 1601, 1523, 1508, 1480, 1365, 1266, 1055
(υ B-F), 823, 733 cm-1. 1H NMR (500 MHz, CDCl3): δ 8.99 (d, J =
6.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 2H), 8.01 (d, J = 5.5 Hz, 1H), 7.85
(s, 1H), 7.78 (d, J = 9.0 Hz, 1H), 7.73 (d, J = 8.0 Hz, 2H), 7.57 (d,
J = 9.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H),
2.63 (s, 3H), 2.49 (s, 3H), 2.45 (s, 3H). 13C NMR (125 MHz,
CDCl3): δ 197.4 (CO), 158.0 (C), 147.3 (CH), 142.1 (C), 141.4 (C),
1391. (C), 138.3 (C), 138.1 (C), 137.4 (CH), 137.1 (C), 131.0
(2CH), 129.9 (2CH), 128.7 (2CH), 128.0 (C), 126.7 (CH), 125.9
(2CH), 122.6 (CH), 119.9 (CH), 26.7 (CH3), 21.5 (CH3), 21.2 (CH3).
HRMS (FD, [M]+) for C25H22NO calcd 352.1696; found 352.1691.
1
1539, 1509, 1368, 1285, 1256, 1182, 1057 (υ B-F), 826 cm-1. H
NMR (500 MHz, CDCl3): δ 8.95 (d, J = 6.0 Hz, 1H), 8.07 (s, 1H),
8.01 (d, J = 6.0 Hz, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.63 (d, J = 8.5
Hz, 2H), 7.55 (d, J = 9.0 Hz, 1H), 7.47-7.43 (m, 4H), 7.10 (d, J =
8.5 Hz, 2H), 3.88 (s, 3H), 2.53 (s, 3H), 2.46 (s, 3H). 13C NMR (125
MHz, CDCl3): δ 161.9 (C), 159.2 (C), 146.8 (CH), 142.1 (C), 140.9
(C), 138.4 (C), 137.1 (C), 137.1 (CH), 131.7 (2CH), 131.1 (2CH),
127.9 (C), 127.4 (CH), 126.9 (C), 126.0 (2CH), 122.2 (CH), 119.7
(CH), 114.8 (2CH), 55.5 (CH3), 21.6 (CH3), 21.2 (CH3). HRMS
(FAB, [M]+) for C24H22NO calcd 340.1696; found 340.1703.
4-(4-(tert-Butyl)phenyl)-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4ad). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
6-Methyl-4-(m-tolyl)-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4ah). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4ah as brown solid (92 mg, 74%). mp: 172-174 °C. IR (neat):
1598, 1523, 1508, 1369, 1057 (υ B-F), 826, 801, 711 cm-1. 1H NMR
(500 MHz, CDCl3): δ 9.07 (d, J = 3.5 Hz, 1H), 8.04 (d, J = 3.5 Hz,
1H), 7.99 (s, 1H), 7.79 (d, J = 9.0 Hz, 1H), 7.59 (d, J = 9.0 Hz, 1H),
7.51-7.40 (m, 8H), 2.52 (s, 3H), 2.47 (s, 3H), 2.44 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 159.7 (C), 147.2 (CH), 142.1 (C), 141.0
(C), 139.1 (C), 138.2 (C), 137.3 (CH), 137.1 (C), 134.7 (C), 131.4
(CH), 131.0 (2CH), 130.1 (CH), 128.9 (CH), 128.2 (C), 127.2 (CH),
126.8 (CH), 126.0 (2CH), 122.6 (CH), 119.8 (CH), 21.6 (CH3),
21.3 (CH3), 21.2 (CH3). HRMS (FAB, [M]+) for C24H22N calcd
324.1747; found 324.1757.
°
salts 4ad as khaki solid (126 mg, 93%). mp: 88-90 C IR (neat):
1
1605, 1597, 1524, 1507, 1368, 1057 (υ B-F), 824, 735 cm-1. H
NMR (500 MHz, CDCl3): δ 9.05 (d, J = 5.5 Hz, 1H), 8.08 (s, 1H),
8.05 (d, J = 5.5 Hz, 1H), 7.78 (d, J = 8.5 Hz, 1H), 7.63-7.59 (m,
4H), 7.58 (d, J = 9.0 Hz, 1H), 7.49 (d, J = 7.5 Hz, 2H), 7.45 (d, J
= 8.0 Hz, 2H), 2.54 (s, 3H), 2.47 (s, 3H), 1.38 (s, 9H). 13C NMR
(125 MHz, CDCl3): δ 159.6 (C), 154.5 (C), 147.2 (CH), 142.1 (C),
141.0 (C), 138.3 (C), 137.2 (CH), 137.2 (C), 131.9 (C), 131.1
(2CH), 129.7 (2CH), 128.1 (C), 127.4 (CH), 126.2 (2CH), 126.0
(2CH), 122.6 (CH), 119.8 (CH), 34.9 (C), 31.1 (3CH3), 21.6 (CH3),
21.2 (CH3). HRMS (FAB, [M]+) for C27H28N calcd 366.2216; found
366.2225.
4-(4-Fluorophenyl)-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4ae). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4ae as pale yellow solid (107 mg, 86%). mp: 219-220 °C. IR
(neat): 1599, 1509, 1368, 1233, 1165, 1057 (υ B-F), 825 cm-1. 1H
NMR (500 MHz, CDCl3): δ 9.00 (d, J = 6.0 Hz, 1H), 8.02 (d, J =
5.5 Hz, 1H), 7.93 (s, 1H), 7.77 (d, J = 9.0 Hz, 1H), 7.68-7.65 (m,
2H), 7.57 (d, J = 9.0 Hz, 1H), 7.49 (d, J = 8.0 Hz, 2H), 7.43 (d, J
= 8.0 Hz, 2H), 7.28-7.24 (m, 2H), 2.52 (s, 3H), 2.47 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 164 (d, J = 252.6 Hz, C), 158.2 (C),
147.2 (CH), 142.1 (C), 141.2 (C), 138.3 (C), 137.3 (CH), 137.2
(C), 131.9 (d, J = 8.7 Hz, 2CH), 131.0 (2CH), 130.9 (d, J = 3.3 Hz,
C), 128.1 (C), 126.9 (CH), 126.0 (2CH), 122.7 (CH), 119.9 (CH),
4-(3-Bromophenyl)-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4ai). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
°
salts 4ai as olive solid (109 mg, 76%). mp: 83-85 C. IR (neat):
1612, 1596, 1556, 1523, 1508, 1369, 1055 (υ B-F), 826, 799, 744
cm-1. 1H NMR (500 MHz, CDCl3): δ 9.01 (d, J = 6.0 Hz, 1H), 7.96
(d, J = 6.0 Hz, 1H), 7.87 (s, 1H), 7.79 (d, J = 9.0 Hz, 1H), 7.74 (s,
1H), 7.71 (d, J = 8.0 Hz, 1H), 7.58 (d, J = 8.5 Hz, 2H), 7.51-7.45
(m, 3H), 7.43 (d, J = 8.0 Hz, 2H), 2.52 (s, 3H), 2.47 (s, 3H). 13C
NMR (125 MHz, CDCl3): δ 157.4 (C), 147.4 (CH), 142.2 (C), 141.4
(C), 138.3 (C), 137.4 (CH), 137.2 (C), 136.8 (C), 133.5 (CH),
131.9 (CH), 131.0 (2CH), 130.7 (CH), 128.4 (CH), 128.1 (C),
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
126.7 (CH), 126.0 (2CH), 123.0 (C), 122.7 (CH), 119.9 (CH), 21.6
(CH3), 21.2 (CH3). HRMS (FAB, [M]+) for C23H19BrN calcd
388.0695; found 388.0704.
142.1 (C), 141.0 (C), 138.7 (C), 137.2 (C), 137.1 (CH), 135.6 (C),
131.1 (2CH), 130.4 (CH), 130.2 (CH), 129.9 (C), 128.4 (C), 128.2
(C), 127.8 (CH), 127.5 (CH), 126.9 (CH), 126.0 (2CH), 122.7 (CH),
120.2 (CH), 119.8 (CH), 105.7 (CH), 55,4 (CH3), 21.6 (CH3), 21.2
(CH3). HRMS (FAB, [M]+) for C28H24NO calcd 390.1852; found
390.1861.
6-Methyl-4-(o-tolyl)-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4aj). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4aj as brown solid (99 mg, 80%). mp: 194-196 °C. IR (neat):
1610, 1521, 1509, 1374, 1055 (υ B-F), 824, 765, 731 cm-1. 1H NMR
(500 MHz, CDCl3): δ 9.08 (d, J = 6.0 Hz, 1H), 7.95 (d, J = 5.5 Hz,
1H), 7.78 (d, J = 8.5 Hz, 1H), 7.60 (d, J = 9.0 Hz, 1H), 7.57-7.51
(m, 3H), 7.47-7.43 (m, 3H), 7.38 (d, J = 7.5 Hz, 1H), 7.34 (t, J =
4-Cyclohexyl-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4an). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4an as brown solid (96 mg, 80%). mp: 198-200 °C. IR (neat):
2932, 2859, 1600, 1528, 1507, 1452, 1367, 1057 (υ B-F), 828 cm-
1. 1H NMR (500 MHz, CDCl3): δ 9.02 (d, J = 6.0 Hz, 1H), 8.19 (s,
1H), 8.12 (d, J = 6.0 Hz, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.54 (d, J
= 9.0 Hz, 1H), 7.45 (d, J = 8.0 Hz, 2H), 7.41 (d, J = 8.5 Hz, 2H),
7.5 Hz, 1H), 7.28(d, J = 7.5 Hz, 1H), 2.47 (s, 6H), 2.10 (s, 3H). 13
C
NMR (125 MHz, CDCl3): δ 160.1 (C), 147.5 (CH), 142.1 (C), 141.3
(C), 137.9 (C), 137.5 (CH), 137.1 (C), 135.5 (C), 134.3 (C), 131.0
(2CH), 130.7 (CH), 130.1 (CH), 129.1 (CH), 128.9 (C), 126.9 (CH), 3.55 (m, 1H), 2.65 (s, 3H), 2.48 (s, 3H), 2.04 (m, 2H), 1.96 (m,
126.1 (CH), 126.0 (CH), 126.0 (CH), 123.2 (CH), 119.9 (CH), 21.5
(CH3), 21.2 (CH3), 19.9 (CH3). HRMS (FAB, [M]+) for C24H22N
calcd 324.1747; found 324.1754.
2H), 1.84 (m, 1H), 1.70 (m, 2H), 1.58 (m, 2H), 1.37 (m, 1H). 13C
NMR (125 MHz, CDCl3): δ 167.1 (C), 147.6 (CH), 142.0 (C), 140.9
(C), 137.3 (C), 137.1 (C), 137.0 (CH), 131.0 (2CH), 128.0 (C),
125.9 (2CH), 123.9 (CH), 120.2 (CH), 119.6 (CH), 40.4 (CH), 32.9
(2CH2), 26.2 (2CH2), 25.5 (CH2), 21.7 (CH3), 21.2 (CH3). HRMS
(FAB, [M]+) for C23H26N calcd 316.2060; found 316.2061.
4-Mesityl-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4ak). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4ak as khaki solid (126 mg, 91%). mp: 278-280 °C. IR (neat):
1611, 1508, 1490, 1374, 1057 (υ B-F), 823, 733 cm-1. 1H NMR (500
MHz, CDCl3): δ 9.12 (d, J = 5.5 Hz, 1H), 7.91 (d, J = 5.5 Hz, 1H),
7.8 (d, J = 9.0 Hz, 1H), 7.63 (d, J = 9.0 Hz, 1H), 7.56 (d, J = 7.0
Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H), 7.44 (s, 1H), 7.02 (s, 2H), 2.47
(s, 6H), 2.37 (s, 3H), 1.89 (s, 6H). 13C NMR (125 MHz, CDCl3): δ
160.9 (C), 148.2 (CH), 142.2 (C), 141.6 (C), 139.6 (C), 137.9 (C),
137.7 (CH), 137.1 (C), 135.2 (2C), 131.1 (2CH), 131.0 (C), 129.2
(C), 128.8 (2CH), 126.2 (CH), 126.1 (2CH), 123.9 (CH), 120.1
(CH) , 21.5 (CH3), 21.2 (CH3), 21.1 (CH3), 20.2 (2CH3). HRMS
(FAB, [M]+) for C26H26N calcd 352.2060; found 352.2069.
6-Methyl-4-propyl-1-(p-tolyl)quinolin-1-ium tetrafluoroborate
(4ao). Following the general procedure for the synthesis of
quinolinium salts and purification by chromatography on silica gel
(MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium salts 4ao as
brown solid (67 mg, 61%). mp: 137-139 °C. IR (neat): 2952, 1608,
1
1526, 1507, 1374, 1050 (υ B-F), 826 cm-1. H NMR (500 MHz,
CDCl3): δ 8.93 (d, J = 5.5 Hz, 1H), 8.14 (s, 1H), 8.02 (d, J = 5.5
Hz, 1H), 7.76 (d, J = 9.0 Hz, 1H), 7.50 (d, J = 9.0 Hz, 1H), 7.42 (d,
J = 8.0 Hz, 2H), 7.38 (d, J = 8.5 Hz, 2H), 3.29 (t, J = 8.0 Hz, 2H),
2.60 (s, 3H), 2.44 (s, 3H), 1.88 (qt, J = 8.0, 7.0 Hz, 2H), 1.07 (t, J
= 7.0 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ 162.7 (C), 147.0
(CH), 142.0 (C), 141.0 (C), 137.2 (C), 137.2 (CH), 136.9 (C),
130.9 (2CH), 128.6 (C), 125.8 (2CH), 124.6 (CH), 122.0 (CH),
119.9 (CH), 35.0 (CH2), 22.9 (CH2), 21.5 (CH3), 21.1 (CH3), 13.9
(CH3). HRMS (FAB, [M]+) for C20H22N calcd 276.1747; found
276.1755.
6-Methyl-4-(thiophen-3-yl)-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4al). Following the general procedure for the
synthesis of quinolinium salts and purification by chromatography
on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium
salts 4al as camel solid (86 mg, 71%). mp: 217-219 °C. IR (neat):
1597, 1563, 1524, 1507, 1056 (υ B-F), 847, 819, 777, 732 cm-1. 1H
NMR (500 MHz, (CD3)2CO): δ 9.37 (d, J = 6.0 Hz, 1H), 8.47 (s,
1H), 8.38 (d, J = 2.0 Hz, 1H), 8.31 (d, J = 6.5 Hz, 1H), 8.07 (d, J
= 9.0 Hz, 1H), 7.94 (dd, J = 4.8, 3.0 Hz, 1H), 7.79 (d, J = 8.5 Hz,
2H), 7.76-7.74 (m, 2H), 7.65 (d, J = 8.5 Hz, 2H), 2.66 (s, 3H), 2.56
(s, 3H). 13C NMR (125 MHz, (CD3)2CO): δ 154.4 (C), 148.5 (CH),
142.9 (C), 142.3 (C), 139.9 (C), 138.9 (C), 138.3 (CH), 136.6 (C),
131.8 (2CH), 131.7 (CH), 129.6 (CH), 129.4 (CH), 128.6 (C),
127.8 (CH), 127.3 (2CH), 122.5 (CH), 121.1 (CH), 21.5 (CH3),
21.2 (CH3). HRMS (FAB, [M]+) for C21H18NS calcd 316.1154;
found 316.1162.
Optimized condition for the synthesis of quinolinium salts
4ap-4as. To a solution of CuCl2 (4.0 mg, 0.03 mmol), di-p-
tolylamine (59.2 mg, 0.30 mmol), alkyne (0.60 mmol) and
paraformaldehyde (15.0 mg, 0.50 mmol) in MeCN (2 mL), HBF4
(0.40 mmol, 50% in water) was added under O2 balloon. The
°
resulting mixture was heated to 60 C and stirred for 1 h. After
cooling, the reaction was diluted with CH2Cl2 (10 mL), filtered
through celite pad, and washed three times with CH2Cl2 (3×20
mL). The combined filtrate was concentrated under vacuum and
the residue was purified by chromatography on using MeOH and
CH2Cl2 as eluent to afford quinolinium salts 4ap-4as.
3,4-Diethyl-6-methyl-1-(p-tolyl)quinolin-1-ium
4-(6-Methoxynaphthalen-2-yl)-6-methyl-1-(p-tolyl)quinolin-1-
ium tetrafluoroborate (4am). Following the general procedure
for the synthesis of quinolinium salts and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4am as brown sticky solid (118 mg, 82%).
mp: 117-119 °C. IR (neat): 1626, 1598, 1524, 1506, 1487, 1392,
1364, 1271, 1222, 1205, 1166, 1057 (υ B-F), 854, 820,733 cm-1. 1H
NMR (500 MHz, CDCl3): δ 9.00 (d, J = 6.0 Hz, 1H), 8.10-8.08 (m,
2H), 8.07 (s, 1H), 7.91 (d, J = 8.5 Hz, 1H), 7.84 (d, J = 9.0 Hz, 1H),
7.76 (dd, J = 9.0, 1.0 Hz, 1H), 7.66 (dd, J = 8.5, 1.0 Hz, 1H), 7.58
(d, J = 9.0 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H), 7.43 (d, J = 8.0 Hz,
2H), 7.21-7.19 (m, 2H), 3.94 (s, 3H), 2.50 (s, 3H), 2.46 (s, 3H);
13C NMR (125 MHz, CDCl3): δ 159.7 (C), 159.4 (C), 147.0 (CH),
tetrafluoroborate (4ap). Following the optimized procedure for
the synthesis of quinolinium salts 4ap-4as and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4ap as brown solid (51 mg, 45%). mp:
138-140 °C. IR (neat): 2982, 2933, 1528, 1509, 1375, 1269, 1053
(υ B-F), 821, 733 cm-1. 1H NMR (400 MHz, CDCl3): δ 8.76 (s, 1H),
8.11 (s, 1H), 7.68 (d, J = 8.8 Hz, 1H), 7.50-7.45 (m, 5H), 3.36 (q,
J = 7.6 Hz, 2H), 3.08 (q¸ J = 7.6 Hz, 2H), 2.63 (s, 3H), 2.49 (s, 3H),
1.44 (t, J = 7.6 Hz, 3H), 1.39 (t, J = 7.6 Hz, 3H). 13C NMR (100
MHz, CDCl3): δ 160.9 (C), 147.3 (CH), 141.9 (C), 140.6 (C), 137.1
(C), 136.4 (C), 136.2 (C), 135.9 (CH), 130.9 (2CH), 128.5 (C),
126.1 (2CH), 124.4 (CH), 120.0 (CH), 23.9 (CH2), 22.7 (CH2), 22.0
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
(CH3), 21.4 (CH3), 14.7 (2CH3). HRMS (FD, [M]+) for C21H24N
calcd 290.1903; found 290.1905.
3,6-Dimethyl-4-phenyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4at). Following the optimized procedure for
the synthesis of quinolinium salts 4at-4ay and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4at as green solid (98 mg, 79%). mp: 88-
90°C. IR (neat): 1526, 1508, 1373, 1340, 1271, 1056 (υ B-F), 822,
6-Methyl-3,4-diphenyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4aq). Following the optimized procedure for
the synthesis of quinolinium salts 4ap-4as and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
1
afford quinolinium salts 4aq as brown solid (93 mg, 66%). mp:
763, 733, 705 cm-1. H NMR (500 MHz, CDCl3): δ 8.89 (s, 1H),
°
237-239 C. IR (neat): 1523, 1509, 1372, 1347, 1269, 1055 (υ
7.65 (d, J = 9.0 Hz, 1H), 7.59-7.56 (m, 5H), 7.49 (d, J = 9.0 Hz,
1H), 7.46-7.45 (m, 3H), 7.38 (d, J = 6.5 Hz, 2H), 2.48 (s, 3H), 2.42
(s, 3H), 2.40 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 158.1 (C),
148.6 (CH), 141.9 (C), 140.4 (C), 137.2 (C), 136.7 (C), 135.9 (CH),
133.7 (C), 131.7 (C), 130.9 (2CH), 129.4 (CH), 129.4 (C), 128.9
(2CH), 128.2 (2CH), 126.9 (CH), 126.1 (2CH), 119.3 (CH), 21.8
(CH3), 21.4 (CH3), 18.1 (CH3). HRMS (FAB, [M]+) for C24H22N
calcd 324.1747; found 324.1745.
B-
F), 820, 784, 732, 703 cm-1. 1H NMR (400 MHz, CDCl3): δ 8.76 (s,
1H), 7.74-7.69 (m, 4H), 7.57 (d, J = 9.6 Hz, 1H), 7.47 (d, J = 8.4
Hz, 2H), 7.42-7.34 (m, 5H), 7.33-7.30 (m, 2H), 7.22-7.18 (m,3H),
2.50 (s, 3H), 2.48 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 157.2
(C), 147.1 (CH), 141.9 (C), 140.8 (C), 137.5 (C), 137.3 (C), 136.8
(CH), 135.0 (C), 133.8 (C), 133.4 (C), 130.9 (2CH), 130.0 (2CH),
129.8 (2CH), 129.6 (C), 129.2 (CH), 128.3 (CH), 128.3 (2CH),
128.3 (2CH), 127.7 (CH), 126.2 (2CH), 119.5 (CH), 21.8 (CH3),
21.4 (CH3). HRMS (FD, [M]+) for C29H24N calcd 386.1903; found
386.1893.
3-Ethyl-6-methyl-4-phenyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4au). Following the optimized procedure for
the synthesis of quinolinium salts 4at-4ay and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4au as green solid (102 mg, 80%). mp:
94-96 °C. IR (neat): 3068, 2928, 1614, 1525, 1509, 1374, 1054 (υ
B-F), 821, 761, 733 cm-1. 1H NMR (500 MHz, CDCl3): δ 8.85 (s, 1H),
7.66 (dd, J = 9.0, 1.5 Hz, 1H), 7.61-7.58 (m, 5H), 7.51 (d, J = 9.0
Hz, 1H), 7.47 (d, J = 8.0 Hz, 2H), 7.41-7.39 (m, 3H), 2.78 (q, J =
6-Methyl-1,3,4-tri-p-tolylquinolin-1-ium
tetrafluoroborate
(4ar). Following the optimized procedure for the synthesis of
quinolinium salts 4ap-4as and purification by chromatography on
silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to afford quinolinium salts
4ar as brown solid (91 mg, 60%). mp: 101-103 °C. IR (neat): 1608,
1510, 1371, 1346, 1269, 1056 (υ B-F), 820, 734 cm-1. 1H NMR (500
MHz, CDCl3): δ 8.73 (s, 1H), 7.74 (s, 1H), 7.71 (d, J = 9.5 Hz, 1H),
7.67 (d, J = 8.0 Hz, 2H), 7.55 (d, J = 8.5 Hz, 1H), 7.47 (d, J = 8.0
Hz, 2H), 7.24-7.17 (m, 6H), 7.02 (d, J = 8.0 Hz, 2H), 2.49 (s, 3H),
2.47 (s, 3H), 2.39 (s, 3H), 2.25 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 157.2 (C), 146.9 (CH), 141.8 (C), 140.6 (C), 139.3 (C),
138.1 (C), 137.3 (C), 137.2 (C), 136.6 (CH), 134.8 (C), 130.9 (C),
130.8 (2CH), 130.3 (C), 129.7 (2CH), 129.7 (2CH), 129.5 (C),
129.0 (2CH), 129.0 (2CH), 127.6 (CH), 126.1 (2CH), 119.4 (CH),
21.7 (CH3), 21.4 (CH3), 21.3 (CH3), 21.1 (CH3). HRMS (FD, [M]+)
for C31H28N calcd 414.2216; found 414.2213.
7.5 Hz, 2H), 2.49 (s, 3H), 2.42 (s, 3H), 1.15 (t, J = 7.5 Hz, 3H). 13
C
NMR (100 MHz, CDCl3): δ 157.7 (C), 147.6 (CH), 141.8 (C), 140.5
(C), 137.2 (C), 136.8 (C), 136.7 (C), 136.1 (CH), 133.3 (C), 130.8
(2CH), 129.6 (C), 129.3 (CH), 128.7 (2CH), 128.2 (2CH), 126.9
(CH), 126.0 (2CH), 119.2 (CH), 24.5 (CH2), 21.7 (CH3), 21.4 (CH3),
14.5 (CH3). HRMS (FAB, [M]+) for C25H24N calcd 338.1903; found
338.1902
3-Cyclohexyl-6-methyl-4-phenyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4av). Following the optimized procedure for
the synthesis of quinolinium salts 4at-4ay and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4av as green solid (116 mg, 81%). mp:
3,4-Bis(4-fluorophenyl)-6-methyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4as). Following the optimized procedure for
the synthesis of quinolinium salts 4ap-4as and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4as as brown solid (66 mg, 43%). mp:
119-121 °C. IR (naet): 1604, 1509, 1371, 1346, 1268, 1228, 1163,
°
74-76 C. IR (neat): 2923, 2853, 2364, 2345, 1525, 1508, 1267,
1
1055 (υ B-F), 818, 767, 733 cm-1. H NMR (500 MHz, CDCl3): δ
8.71 (s, 1H), 7.66 (d, J = 9.0 Hz, 1H), 7.63-7.59 (m, 5H), 7.51-7.49
(m, 3H), 7.41-7.40 (m, 2H), 7.38 (s, 1H), 2.69-2.64 (m, 1H), 2.51
(s, 3H), 2.42 (s, 3H), 1.94-1.91 (m, 2H), 1.74-1.72 (m, 2H), 1.61-
1.58 (m, 1H), 1.49-1.41 (m, 2H), 1.22-1.09 (m, 3H). 13C NMR (100
MHz, CDCl3): δ 157.6 (C), 145.7 (CH), 142.0 (C), 140.5 (C), 139.8
(C), 137.6 (C), 136.8 (C), 136.3 (CH), 133.4 (C), 130.9 (2CH),
129.9 (C), 129.3 (CH), 128.7 (2CH), 128.2 (2CH), 127.3 (CH),
1
1056 (υ B-F), 845, 819, 734 cm-1. H NMR (500 MHz, CDCl3): δ
8.70 (s, 1H), 7.71 (d, J = 9.0 Hz, 1H), 7.67 (d, J = 8.5 Hz, 2H),
7.65 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.43 (d, J = 8.0 Hz, 2H),
7.36-7.30 (m, 4H), 7.07 (t, J = 8.5 Hz, 2H), 6.88 (t, J = 8.5 Hz, 2H),
2.48 (s, 3H), 2.46 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 162.8 (d,
J = 248.3 Hz, C), 162.3 (d, J = 247.1 Hz, C), 156.4 (C), 147.0 (CH), 126.1 (2CH), 119.4 (CH), 39.7 (CH), 33.6 (2CH2), 26.4 (2CH2),
141.9 (C), 140.9 (C), 137.6 (C), 137.3 (C), 136.7 (CH), 134.2 (C),
132.1 (d, J = 8.3 Hz, 2CH), 131.8 (d, J = 8.3 Hz, 2CH), 130.8
(2CH), 129.9 (d, J = 3.4 Hz, C), 129.6 (C), 129.3 (d, J = 3.5 Hz,
C), 127.4 (CH), 126.2 (2CH), 119.5 (CH), 115.7 (d, J = 21.7 Hz,
2CH), 115.4 (d, J = 21.6 Hz, 2CH), 21.8 (CH3), 21.4 (CH3). HRMS
(FAB, [M]+) for C29H22F2N calcd 422.1715; found 422.1719.
25.4 (CH2), 21.8 (CH3), 21.4 (CH3). HRMS (FD, [M]+) for C29H30N
calcd 392.2373; found 392.2375.
3-Acetyl-6-methyl-4-phenyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (4aw). Following the optimized procedure for
the synthesis of quinolinium salts 4at-4ay and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4aw as brown solid (83 mg, 63%). mp:
113-115 °C. IR (neat): 1696 (υ C=O), 1653, 1615, 1507, 1372, 1235,
1057 (υ B-F), 822 cm-1. 1H NMR (400 MHz, CDCl3): δ 8.92 (s, 1H),
7.78 (dd, J = 8.8, 1.6 Hz, 1H), 7.73 (s, 1H), 7.68-7.60 (m, 5H),
7.57-7.55 (m, 3H), 7.47 (d, J = 8.4 Hz, 2H), 2.51 (s, 3H), 2.49 (s,
3H), 2.00 (s, 3H). 13C NMR (100 MHz, CDCl3): δ 198.8 (CO),
156.7 (C), 146.9 (CH), 142.2 (C), 141.4 (C), 138.2 (C), 138.0 (CH),
137.2 (C), 133.5 (C), 133.0 (C), 130.9 (2CH), 130.6 (CH), 129.3
(2CH), 129.2 (C), 129.1 (2CH), 128.2 (CH), 126.1 (2CH), 119.8
(CH), 29.9 (CH3), 21.9 (CH3), 21.5 (CH3). HRMS (FD, [M]+) for
C25H22NO calcd 352.1696; found 352.1696.
Optimized condition for the synthesis of quinolinium salts
4at-4ay. To a solution of CuCl2 (4.0 mg, 0.03 mmol), di-p-
tolylamine (59.2 mg, 0.30 mmol), alkyne (0.60 mmol) and
paraformaldehyde (9.9 mg, 0.33 mmol) in MeCN (2 mL), HBF4
(0.40 mmol, 50% in water) was added under O2 balloon. The
°
resulting mixture was stirred at 20 C for 1 h. Then, the reaction
was diluted with CH2Cl2 (10 mL), filtered through celite pad, and
washed three times with CH2Cl2 (3×20 mL). The combined filtrate
was concentrated under vacuum and the residue was purified by
chromatography using MeOH and CH2Cl2 as eluent to afford
quinolinium salts 4at-4ay.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
Optimized condition for the synthesis of quinolinium salts
6c-g. To a solution of CuCl2 (4.0 mg, 0.03 mmol), di-p-tolylamine
(59.2 mg, 0.30 mmol), phenylacetylene (40.8 mg, 0.40 mmol) and
aldehyde (0.4 mmol) in MeCN (2 mL), HBF4 (0.40 mmol, 50% in
water) was added under O2 balloon. The resulting mixture was
3-(Methoxycarbonyl)-6-methyl-4-phenyl-1-(p-tolyl)quinolin-1-
ium tetrafluoroborate (4ax). Following the optimized procedure
for the synthesis of quinolinium salts 4at-4ay and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4ax as brown solid (106 mg, 77%). mp:
°
heated to 60 C and stirred for 24 h. After cooling, the reaction
233-235 °C. IR (neat): 1747, 1721 (υ C=O), 1617, 1525, 1509, 1438, was diluted with CH2Cl2 (10 mL), filtered through celite pad, and
1379, 1269, 1242, 1208 (υ C-O), 1140, 1054 (υ B-F), 823, 732, 716
cm-1. 1H NMR (500 MHz, CDCl3): δ 9.39 (s, 1H), 7.82 (d, J = 9.0
Hz, 1H), 7.66-7.64 (m, 3H), 7.61-7.56 (m, 4H), 7.50 (d, J = 8.0 Hz,
2H), 7.45 (dd, J = 7.5, 1.0 Hz, 2H), 3.69 (s, 3H), 2.52 (s, 3H), 2.47
(s, 3H). 13C NMR (100 MHz, CDCl3): δ 162.3 (CO), 161.0 (C),
148.2 (CH), 142.3 (C), 141.5 (C), 138.7 (CH), 138.6 (C), 137.2
(C), 133.5 (C), 131.0 (2CH), 130.1 (C), 129.5 (CH), 129.0 (CH),
128.2 (2CH), 128.1 (2CH), 126.1 (2CH), 123.8 (C), 119.8 (CH),
53.3 (CH3), 21.9 (CH3), 21.5 (CH3). HRMS (FAB, [M]+) for
C25H22NO2 calcd 368.1645; found 368.1646.
washed three times with CH2Cl2 (3×20 mL). The combined filtrate
was concentrated under vacuum and the residue was purified by
chromatography on silica gel using MeOH and CH2Cl2 as eluent
to afford quinolinium salts 6c-g.
6-Methyl-4-phenyl-1,2-di-p-tolylquinolin-1-ium
tetrafluoroborate (6c). Following the optimized procedure for the
synthesis of quinolinium salts 6c-g and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 6:94) to
afford quinolinium salts 6c as brown solid (71 mg, 48%). mp: 88-
90 °C. IR (neat): 1610, 1592, 1560, 1509, 1494, 1388, 1365, 1266,
1050 (υ B-F), 821, 769, 736, 704 cm-1. 1H NMR (500 MHz, CDCl3):
δ 7.95 (s, 1H), 7.81 (s, 1H), 7.72-7.69 (m, 3H), 7.59-7.58 (m, 3H),
7.40 (d, J = 9.0Hz, 1H), 7.38 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.0
Hz, 2H), 7.28 (d, J = 8.0 Hz, 2H), 7.08 (d, J = 8.0 Hz, 2H), 2.51 (s,
3H), 2.39 (s, 3H), 2.27 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
158.7 (C), 157.6 (C), 141.0 (C), 140.8 (C), 140.1 (C), 139.6 (C),
136.8 (CH), 135.2 (C), 135.1(C), 130.5 (2CH), 130.3 (CH), 129.9
(C), 129.6 (2CH), 129.5 (2CH), 129.1 (2CH), 128.9 (2CH), 127.8
(2CH), 127.5 (C), 127.1 (CH), 125.2 (CH), 120.4 (CH), 21.7 (CH3),
21.4 (CH3), 21.4 (CH3). HRMS (FAB, [M]+) for C30H26N calcd
400.2060; found 400.2067.
3-(Ethoxycarbonyl)-6-methyl-4-phenyl-1-(p-tolyl)quinolin-1-
ium tetrafluoroborate (4ay). Following the optimized procedure
for the synthesis of quinolinium salts 4at-4ay and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 4:96) to
afford quinolinium salts 4ay as brown solid (93 mg, 66%). mp:
162-164°C. IR (neat): 1741, 1718 (υ C=O), 1616, 1525, 1377, 1268,
1240, 1206 (υ C-O), 1140, 1057 (υ B-F), 824, 733 cm-1.1H NMR (500
MHz, CDCl3): δ 9.35 (s, 1H), 7.82 (dd, J = 9.0, 1.5 Hz, 1H), 7.65
(d, J = 8.0 Hz, 2H), 7.62 (s, 1H), 7.60-7.53 (m, 4H), 7.49 (d, J =
8.5 Hz, 2H), 7.45 (dd, J = 8.0, 1.5 Hz, 2H), 4.10 (q, J = 7.0 Hz,
2H), 2.51 (s, 3H), 2.46 (s, 3H), 0.96 (t, J = 7.0 Hz, 3H). 13C NMR
(100 MHz, CDCl3): δ 162.0 (CO), 160.4 (C), 148.1 (CH), 142.2 (C),
141.5 (C), 138.7 (CH), 138.5 (C), 137.0 (C), 133.7 (C), 130.9
(2CH), 130.0 (C), 129.3 (CH), 128.7 (CH), 128.1 (2CH), 128.0
2-(4-Bromophenyl)-6-methyl-4-phenyl-1-(p-tolyl)quinolin-1-
ium tetrafluoroborate (6d). Following the optimized procedure
(2CH), 126.0 (2CH), 124.1 (C), 119.7 (CH), 62.5 (CH2), 21.8 (CH3), for the synthesis of quinolinium salts 6c-g and purification by
21.4 (CH3), 13.4 (CH3). HRMS (FD, [M]+) for C26H24NO2 calcd
382.1802; found 382.1807.
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 6:94) to
quinolinium salts 6d as brown solid (73 mg, 44%). mp: 111-113 °C.
IR (neat): 1592, 1560, 1507, 1492, 1386, 1365, 1057 (υ B-F), 1011,
1
Optimized condition for the synthesis of quinolinium salts 6b. 818, 769, 733 cm-1. H NMR (400 MHz, CDCl3): δ 7.94 (s, 1H),
To a solution of CuCl2 (4.0 mg, 0.03 mmol), di-p-tolylamine (59.2
mg, 0.30 mmol), phenylacetylene (61.2 mg, 0.60 mmol) and
valeraldehyde (50.4 mg, 0.4 mmol) in MeCN (2 mL), HBF4 (0.40
mmol, 50% in water) was added under O2 balloon. The resulting
mixture was heated to 60 °C and stirred for 1 h. After cooling, the
reaction was diluted with CH2Cl2 (10 mL), filtered through celite
pad, and washed three times with CH2Cl2 (3×20 mL). The
combined filtrate was concentrated under vacuum and the
residue was purified by chromatography gel using MeOH and
CH2Cl2 as eluent to afford quinolinium salts 6b.
7.76 (s, 1H), 7.72-7.67 (m, 3H), 7.57-7.55 (m, 3H), 7.40-7.36 (m,
7H), 7.26 (d, J = 8.0 Hz, 2H), 2.50 (s, 3H), 2.39 (s, 3H). 13C NMR
(100 MHz, CDCl3): δ 159.2 (C), 156.1 (C), 141.2 (C), 140.3 (C),
139.7 (C), 137.0 (CH), 135.0 (C), 135.0 (C), 131.8 (C), 131.5
(2CH), 131.1 (2CH), 130.6 (2CH), 130.3 (CH), 129.6 (2CH), 128.9
(2CH), 127.8 (C), 127.7 (2CH), 127.2 (CH), 125.1 (C), 124.9 (CH),
120.4 (CH), 21.7 (CH3), 21.4 (CH3). HRMS (FD, [M]+) for
C29H23BrN calcd 464.1008; found 464.1003.
6-Methyl-4-phenyl-1-(p-tolyl)-2-(4-
(trifluoromethyl)phenyl)quinolin-1-ium tetrafluoroborate (6e).
Following the optimized procedure for the synthesis of
quinolinium salts 6c-g and purification by chromatography on
silica gel (MeOH:CH2Cl2, 0:100 to 6:94) to quinolinium salts 6e as
brown solid (81 mg, 50%). mp: 110-112 °C. IR (neat): 1591, 1564,
1508, 1324, 1168, 1126, 1066 (υ B-F), 1018, 850, 818, 771 cm-1.
1H NMR (500 MHz, CDCl3): δ 7.95 (s, 1H), 7.76 (s, 1H), 7.72-7.68
(m, 3H), 7.66 (d, J = 8.0 Hz, 2H), 7.59-7.54 (m, 3H), 7.49 (d, J =
7.5 Hz, 2H), 7.41 (d, J = 7.5 Hz, 2H), 7.37 (d, J = 9.0 Hz, 1H), 7.23
(d, J = 6.5 Hz, 2H), 2.49 (s, 3H), 2.35 (s, 3H). 13C NMR (100 MHz,
CDCl3): δ 159.4 (C), 155.5 (C), 141.3 (C), 140.4 (C), 139.7 (C),
137.1 (CH), 136.4 (d, J = 1.3 Hz, C), 135.0 (C), 134.9 (C), 131.8
(q, J = 32.6 Hz, C), 130.6 (2CH), 130.3 (CH), 130.1 (2CH), 129.6
(2CH), 128.8 (2CH), 127.9 (C), 127.7 (2CH), 127.2 (CH), 125.1
(q, J = 3.7 Hz, 2CH), 124.8 (CH), 123.2 (q, J = 270.2 Hz, CF3),
120.4 (CH), 21.7 (CH3), 21.3 (CH3). HRMS (FAB, [M]+) for
C30H23F3N calcd 454.1777; found 454.1786.
2-Butyl-6-methyl-1,4-di-p-tolylquinolin-1-ium
tetrafluoroborate (6b). Following the optimized procedure for the
synthesis of quinolinium salts 6b and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 2:98) to
afford quinolinium salts 6b as black sticky solid (105 mg, 77%).
°
mp: 57-59 C. IR (naet): 2961, 2926, 1598, 1566, 1508, 1457,
1378, 1270, 1056 (υ B-F), 822, 768, 704 cm-1. 1H NMR (500 MHz,
CDCl3): δ 7.87 (s, 1H), 7.79 (s, 1H), 7.68-7.66 (m, 2H), 7.62 (dd,
J = 9.0, 2.0 Hz, 1H), 7.59-7.58 (m, 3H), 7.52 (d, J = 8.0 Hz, 2H),
7.41 (d, J = 8.5 Hz, 2H), 7.17 (d, J = 9.0 Hz, 1H), 2.90 (t, J = 8.0
Hz, 2H), 2.52 (s, 3H), 2.46 (s, 3H), 1.71-1.65 (m, 2H), 1.30-1.23
(m, 2H), 0.77 (t, J = 7.5 Hz, 3H). 13C NMR (125 MHz, CDCl3): δ
162.1 (C), 158.4 (C), 142.0 (C), 139.9 (C), 139.7 (C), 136.4 (CH),
135.1 (C), 134.4 (C), 131.5 (2CH), 130.3 (CH), 129.5 (2CH),
129.0 (2CH), 127.0 (CH), 126.8 (C), 126.6 (2CH), 123.6 (CH),
120.3 (CH), 34.8 (CH2), 30.8 (CH2), 22.4 (CH2), 21.4 (CH3), 21.3
(CH3), 13.3 (CH3). HRMS (FAB, [M]+) for C27H28N calcd 366.2216;
found 366.2214.
2-(3-Bromophenyl)-6-methyl-4-phenyl-1-(p-tolyl)quinolin-1-
ium tetrafluoroborate (6f). Following the optimized procedure
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
for the synthesis of quinolinium salts 6c-g and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 6:94) to
quinolinium salts 6f as brown solid (61 mg, 37%). mp: 101-103 °C.
IR (neat): 2926, 1685, 1568, 1506, 1440, 1418, 1314, 1288, 1262,
of
4-methyl-N-(2-oxoethyl)-N-(3-(p-tolyl)prop-2-yn-1-
yl)benzenesulfonamide 3i (136.6 mg, 0.4 mmol) in MeCN (1.0
mL) and HBF4 (0.4 mmol, 50% in water) were added via syringe
under O2 balloon. The mixture was left stirring at 20 C for 1 h.
Then, the reaction was diluted with CH2Cl2 (10 mL), filtered
through celite pad, and washed three times with CH2Cl2 (3×20
mL). The combined filtrate was concentrated under vacuum. The
residue was purified by chromatography on alumina
(MeOH:CH2Cl2, 0:100 to 2:98) to afford quinoline 7a as purple
°
1
1068 (υ B-F), 814, 748, 707 cm-1. H NMR (500 MHz, CDCl3): δ
7.96 (s, 1H), 7.79 (s,1H), 7.73-7.70 (m, 3H), 7.58-7.57 (m, 3H),
7.55 (s, 1H), 7.51 (d, J = 7.5 Hz, 1H), 7.43 (d, J = 8.5 Hz, 1H),
7.31-7.39 (m, 3H), 7.28 (d, J = 8.5 Hz, 2H), 7.16 (t, J = 7.5 Hz,
1H), 2.51 (s, 3H), 2.39 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ159.4 (C), 155.4 (C), 141.3 (C), 140.4 (C), 139.7 (C), 137.1 (CH),
135.0 (C), 134.9 (C), 134.6 (C), 133.2 (CH), 131.7 (CH), 130.5
(2CH), 130.3 (CH), 130.0 (CH), 129.6 (2CH), 128.9 (2CH), 128.6
(CH), 127.9 (C), 127.7 (2CH), 127.2 (CH), 124.7 (CH), 122.0 (C),
120.4 (CH), 21.8 (CH3), 21.4 (CH3). HRMS (FAB, [M]+) for
C29H23BrN calcd 464.1008; found 464.1016.
°
solid (72 mg, 66 %). mp: 58-60 C. IR (neat): 1605, 1570, 1560,
1509, 1456, 1364, 1252, 1159, 1134, 1020, 813, 732 cm-1. H
1
NMR (400 MHz, CDCl3) δ 7.83 (s, 1H), 7.73 (s,1H), 7.56 (d, J =
8.0 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.42 (d, J = 8.0 Hz, 2H),
7.37-7.35 (m, 3H), 7.15 (d, J = 8.8 Hz, 1H), 6.76 (s, 1H), 2.52 (s,
3H), 2.52 (s, 3H), 2.38 (s, 3H). 13C NMR (100 MHz, CDCl3): δ
148.4 (C), 139.5 (C), 139.2 (C), 137.3 (C), 136.7 (C), 133.8 (CH),
132.1 (C), 131.7 (C), 131.0 (2CH), 130.4 (C), 129.7 (2CH), 129.1
(2CH), 129.0 (CH), 128.1 (CH), 127.3 (2CH), 126.2 (C), 118.8 (C),
115.6 (CH), 109.7 (CH), 21.5 (CH3), 21.4 (CH3), 21.0 (CH3).
HRMS (FD, [M]+) for C26H22N2 calcd 362.1783; found 362.1771.
6-Methyl-2-(2-nitrophenyl)-4-phenyl-1-(p-tolyl)quinolin-1-ium
tetrafluoroborate (6g). Following the optimized procedure for the
synthesis of quinolinium salts 6c-g and purification by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 5:95) to
quinolinium salts 6g as reddish brown solid (51 mg, 33%). mp:
261-263 °C. IR (neat): 1590, 1564, 1527, 1507, 1380, 1366, 1345,
1267, 1056 (υ B-F), 787, 772, 733 cm-1. 1H NMR (500 MHz, CDCl3):
δ 8.13 (d, J = 8.0 Hz, 1H), 8.08 (d, J = 8.5, 1H), 8.01 (s, 1H), 7.76-
7.72 (m, 5H), 7.63 (dd, J = 8.0, 2.0 Hz, 1H), 7.6-7.57 (m, 4H), 7.32
(d, J = 9.0 Hz, 1H), 7.23 (d, J = 9.5 Hz, 1H), 7.16 (d, J = 8.0 Hz,
Synthesis of N,4-dimethyl-N-(p-tolyl)aniline (5a). Following the
general procedure for the synthesis of quinolinium salts, reaction
between di-p-tolylamine (59.2 mg, 0.30 mmol), phenylacetylene
(30.6 mg, 0.30 mmol) and paraformaldehyde (12.0 mg, 0.40
mmol) were performed without copper under N2 balloon.
Purification by chromatography on silica gel (CH2Cl2) to afford 5a
as pale yellow liquid (27 mg, 43%). IR (neat): 1610, 1510, 1336
(υ C-N), 1253 (υ C-N), 1124, 1109, 871, 808, 722 cm-1. 1H NMR (500
MHz, CDCl3) δ 7.06 (d, J = 8.0 Hz, 4H), 6.90 (d, J = 8.5 Hz, 4H),
1H), 7.04 (dd, J = 8.0, 1.5 Hz, 1H), 2.53 (s, 3H), 2.32 (s, 3H). 13
C
NMR (100 MHz, CDCl3): δ 159.4 (C), 154.7 (C), 145.2 (C), 141.6
(C), 140.6 (C), 139.7 (C), 137.1 (CH), 135.0 (CH), 134.7 (C),
134.7 (C), 132.8 (CH), 131.8 (CH), 131.0 (CH), 130.3 (CH), 130.2
(CH), 129.6 (CH), 129.6 (CH), 128.8 (2CH), 128.3 (CH), 127.9 (C), 3.25 (s, 3H), 2.29 (s, 6H). 13C NMR (125 MHz, CDCl3) δ 147.0
127.9 (C), 127.2 (CH), 124.7 (CH), 124.5 (CH), 123.0 (CH), 120.2
(CH), 21.7 (CH3), 21.3 (CH3). HRMS (FAB, [M]+) for C29H23N2O2
calcd 431.1754; found 431.1755.
(2C), 130.4 (2C), 129.6 (4CH), 120.3 (4CH), 40.4 (CH3), 20.5
(2CH3). HRMS (EI, [M]+) for C15H17N calcd 211.1361; found
211.1356.
Synthesis of ynal 6-(p-tolyl)hex-5-ynal 3h and 4-methyl-N-(2-
oxoethyl)-N-(3-(p-tolyl)prop-2-yn-1-yl)benzenesulfonamide 3i can
be found in supporting information.
Synthesis
of
N-(3-Bromobenzylidene)-4-methyl-N-(p-
tolyl)benzenaminium tetrafluoroborate (I-Tol-BrPh). A sealed
tube fitted with a rubber septum was charged with and di-p-
tolylamine (59.2 mg 0.30 mmol) and septum was secured with
parafilm. Subsequently, 3-bromobenzaldehyde (55.5 mg, 0.30
mmol), CHCl3 (0.5 mL), and HBF4 (0.40 mmol, 50% in water) were
added via syringe under an atmosphere of N2. The mixture was
left stirring at 60 °C for 3 h. The organic layer of the crude solution
was collected. The recrystallization was performed with vapor
diffusion of dried Et2O into the crude solution. The precipitate was
washed quickly with Et2O several times to afford I-Tol-BrPh as
moisture sensitive marigold solid (14 mg,13%). mp: 216-218 ºC.
IR (neat): 2364, 2341, 1663, 1617, 1559, 1507, 1285, 1212, 1190,
1068 (υ B-F), 1022, 817, 801, 733 cm-1. 1H NMR (500 MHz,
CD3CN) δ 9.20 (s, 1H), 7.89 (d, J = 7.0 Hz, 1H), 7.56 (s, 1H), 7.50
(d, J = 8.0 Hz, 2H), 7.45-7.41 (m, 6H), 7.37 (d, J = 8.0 Hz, 2H),
2.48 (s, 3H), 2.44 (s, 3H). 13C NMR (125 MHz, CD3CN): δ 170.5
(CH), 144.6 (C), 144.3 (C), 143.5 (C), 140.9 (CH), 138.2 (C),
137.8 (CH), 134.3 (CH), 132.8 (2CH), 132.4 (CH), 131.7 (2CH),
130.7 (C), 126.3 (2CH), 124.6 (2CH), 123.6 (C), 21.5 (CH3), 21.3
(CH3). HRMS (FAB, [M]+) for C21H19BrN calcd 364.0695; found
364.0693.
Synthesis
of
7-Methyl-4,9-di-p-tolyl-2,3-dihydro-1H-
cyclopenta[b]quinolin-4-ium tetrafluoroborate (6h). To
a
solution of CuCl2 (4.0 mg, 0.03 mmol) and di-p-tolylamine (59.2
mg, 0.30 mmol) in MeCN (1.0 mL), solution of 6-(p-tolyl)hex-5-
ynal 3h (74.5 mg, 0.40 mmol) in MeCN (1.0 mL) and HBF4 (0.4
mmol, 50% in water) were added via syringe under O2 balloon.
°
The mixture was left stirring at 20 C for 1 h. Then, the reaction
was diluted with CH2Cl2 (10 mL), filtered through celite pad, and
washed three times with CH2Cl2 (3×20 mL). The combined filtrate
was concentrated under vacuum. The residue was purified by
chromatography on silica gel (MeOH:CH2Cl2, 0:100 to 3:97) as
eluent to afford quinolinium salt 6h as green solid (126.6 mg,
94 %). mp: 102-104 °C. IR (neat): 1597, 1510, 1407, 1054 (υ B-F),
1
813, 733 cm-1. H NMR (400 MHz, CDCl3): δ 7.62 (s, 1H), 7.52
(dd, J = 9.2, 1.0 Hz, 1H), 7.48-7.44 (m, 4H), 7.39 (d, J = 8.4 Hz,
2H), 7.35 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 9.2 Hz, 1H), 3.13 (t, J =
7.2 Hz, 2H), 3.11 (t, J = 7.2 Hz, 2H), 2.49 (s, 3H), 2.46 (s, 3H),
2.41 (s, 3H), 2.24-2.17 (m, 2H). 13C NMR (100 MHz, CDCl3): δ
166.0 (C), 153.0 (C), 141.5 (C), 139.5 (C), 139.0 (C), 138.0 (C),
138.0 (C), 135.0 (CH), 134.6 (C), 131.2 (2CH), 130.7 (C), 129.3
(2CH), 128.5 (2CH), 128.0 (C), 126.7 (CH), 125.7 (2CH), 118.9
(CH), 34.9 (CH2), 31.2 (CH2), 22.6 (CH2), 21.4 (CH3), 21.4 (CH3),
21.3 (CH3). HRMS (FAB, [M]+) for C27H26N calcd 364.2060; found
364.2061.
Synthesis of 6-Methyl-4-phenyl-1-(p-tolyl)quinolin-2(1H)-one
(8a). To an aqueous solution of K3[Fe(CN)6] (469.2 mg 1.4 mmol,
0.2 M) in ice bath, an aqueous solution of KOH (319.8 mg, 5.7
mmol, 0.7 M) was added dropwise. Then, 4aa (227.7 mg, 0.57
mmol) was added in portions to the mixture. The reaction was
allowed to warm to room temperature and left stirring for 1 h. After
that, the suspension was stirred at 60 ºC for 18 h. After cooling to
room temperature, the reaction was partitioned with H2O and
CH2Cl2. The aqueous layer was extracted three times with CH2Cl2
Synthesis
of
7-methyl-4,9-di-p-tolyl-4H-pyrrolo[3,4-
b]quinoline (7a). To a solution of CuCl2 (4.0 mg, 0.03 mmol) and
di-p-tolylamine (59.2 mg, 0.30 mmol) in MeCN (1.0 mL), solution
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
Grozavu, H. B. Hepburn, P. J. Smith, H. K. Potukuchi, P. J. Lindsay-Scott,
T. J. Donohoe, Nat. Chem. 2019, 11, 242-247.
(3×20 mL). The collected organic layer was concentrated under
vacuum. Purification by chromatography on alumina (CH2Cl2) to
afford 8a as pale yellow liquid (120 mg, 64%). IR (neat): 1657 (υ
C=O), 1590, 1559, 1511, 1305 (υ C-N), 874, 815, 776 cm-1. 1H NMR
(400 MHz, CDCl3): δ 7.54-7.41 (m, 5H), 7.40 (d, J = 8.4 Hz, 2H),
7.34 (s, 1H), 7.20 (d, J = 8.4 Hz, 2H), 7.14 (dd, J = 8.4, 1.6 Hz,
1H), 6.73 (s, 1H), 6.67 (d, J = 8.8 Hz, 1H), 2.47 (s, 3H), 2.29 (s,
3H). 13C NMR (100 MHz, CDCl3): δ 161.5 (CO), 151.1 (C), 139.3
(C), 138.4 (C), 136.9 (C), 134.8 (C), 131.3 (C), 131.1 (CH), 130.6
(2CH), 128.5 (2CH), 128.4 (CH), 128.3 (2CH), 128.2 (2CH), 126.6
(CH), 121.4 (CH), 119.7 (C), 116.1 (CH), 21.3 (CH3), 20.7 (CH3).
HRMS (FAB, [M]+) for C23H19NO calcd 325.1467; found 325.1466.
[4] a) U. C. Yoon, S. L. Quillen, P. S. Mariano, R. Swanson, J. L. Stavinoha, E.
Bay, J. Am. Chem. Soc. 1983, 105, 1204-1218; b) H. Kitaguchi, K. Ohkubo,
S. Ogo, S. Fukuzumi, J. Phys. Chem. A 2006, 110, 1718-1725; c) H. Kotani,
K. Ohkubo, S. Fukuzumi, Faraday Discuss. 2012, 155, 89-102.
[5] For selected examples of benzene C-H functionalizations, see: a) V. S.
Kumar, D. L. Aubele, P. E. Floreancig, Org. Lett. 2001, 3, 4123-4125; b) K.
Ohkubo, T. Kobayashi, S. Fukuzumi, Angew. Chem. Int. Ed. 2011, 50,
8652-8655; c) K. Ohkubo, T. Kobayashi, S. Fukuzumi, Opt. Express 2012,
20, A360-A365; d) K. Ohkubo, A. Fujimoto, S. Fukuzumi, J. Phys. Chem. A
2013, 117, 10719-10725; For selected examples of cyclization reactions,
see: e) V. S. Kumar, P. E. Floreancig, J. Am. Chem. Soc. 2001, 123, 3842-
3843; f) D. L. Aubele, P. E. Floreancig, Org. Lett. 2002, 4, 3443-3446.
[6] a) T. Umemoto, Y. Gotoh, Bull. Chem. Soc. Jpn. 1991, 64, 2008-2010; b)
R. Krieg, A. Eitner, W. Günther, K. J. Halbhuber, Biotech. Histochem. 2007,
82, 235-262; c) A. A. Fadda, R. E.-D. El-Mekawy, M. T. AbdelAal,
Phosphorus, Sulfur, Silicon Relat. Elem. 2016, 191, 1148-1154; d) J. R.
Brandt, L. Pospíšil, L. Bednárová, R. C. da Costa, A. J. P. White, T. Mori,
F. Teplý, M. J. Fuchter, Chem. Commun. 2017, 53, 9059-9062.
[7] Contributions of Pilyugin's work were listed in the reviews, see: G. T.
Pilyugin, B. M. Gutsulyak, Russ. Chem. Rev. 1963, 32, 167-188. and
references 13-17 therein cited.
Computational detail:
The geometry optimizations zero-point vibrational energies
(ZPVEs) were calculated using the B3LYP/6-31G** level of theory
combined with the CPCM implicit solvation model to simulate
acetonitrile. Singlet point energy calculations with B3LYP/6-
311++G** were performed on the B3LYP/6-31G** optimized
structures to obtain more accurate electronic energies. The
energy discussed throughout the manuscript is enthalpy
calculated as H = ESCF + ZPVE + Hvib + 4RT. All the calculations
were performed by using Gaussian 09.
[8] a) M. V. Mel'nik, A. V. Turov, Z. L. Novitskii, A. O. Stetskiv, O. V.
Bodnarchuk, N. I. Ganushchak, Russ. J. Gen. Chem. 2006, 76, 634-637; b)
N. E. Shchepina, I. I. Boiko, G. A. Aleksandrova, Pharm. Chem. J. 2011, 45,
159-161.
[9] a) G. A. Ramann, B. J. Cowen, Molecules 2016, 21, 986; b) R. Sharma, P.
Kour, A. Kumar, J. Chem. Sci. 2018, 130, 73.
[10] For applications of A3 reactions, see: a) V. A. Peshkov, O. P. Pereshivko,
E. V. Van der Eycken, Chem. Soc. Rev. 2012, 41, 3790-3807; b) I. Jesin,
G. C. Nandi, Eur. J. Org. Chem. 2019, 2704-2720. For selected examples
of A3 reactions in synthesis of quinolines, see references 11-12.
[11] Generally, the reaction proposed through the formation of acetylide
activated by lewis acid or transition metal, for selected examples, see: a) H.
Z. S. Huma, R. Halder, S. S. Kalra, J. Das, J. Iqbal, Tetrahedron Lett. 2002,
43, 6485-6488; b) K. Cao, F. Zhang, Y. Tu, X. Zhuo, C. Fan, Chem. Eur. J.
2009, 15, 6332-6334; c) H. Huang, H. Jiang, K. Chen, H. Liu, J. Org. Chem.
2009, 74, 5476-5480; d) C. E. Meyet, C. H. Larsen, J. Org. Chem. 2014, 79,
9835-9841; e) K.-M. Jiang, J.-A. Kang, Y. Jin, J. Lin, Org. Chem. Front.
2018, 5, 434-441.
Acknowledgments
We thank the Ministry of Science and Technology of the Republic
of China for the financial support of this research under grant nos.
MOST 105-2633-M-007-003 and 107-2113-M-006-008-MY2.
[12] For selected examples of Povarov reaction with alkynes as dienophiles,
see: a) X. Li, Z. Mao, Y. Wang, W. Chen, X. Lin, Tetrahedron 2011, 67,
3858-3862; b) X. Zhang, X. Xu, L. Yu, Q. Zhao, Asian J. Org. Chem. 2014,
3, 281-284; c) C. Alonso, M. González, F. Palacios, G. Rubiales, J. Org.
Chem. 2017, 82, 6379-6387; d) V. Fasano, J. E. Radcliffe, M. J. Ingleson,
Organometallics 2017, 36, 1623-1629.
Conflict of interest
The authors declare no conflict of interest.
[13] A. R. Katritzky, D. Semenzin, B. Yang, D. P. Pleynet, J. Heterocycl. Chem.
Keywords: aza-Diels-Alder reaction • quinolinium salts •
distortion energy • energy decomposition analysis (EDA)
1998, 35, 467-470.
[14] a) J. Jayakumar, K. Parthasarathy, C.-H. Cheng, Angew. Chem. Int. Ed.
2012, 51, 197-200; b) K. Parthasarathy, N. Senthilkumar, J. Jayakumar, C.-
H. Cheng, Org. Lett. 2012, 14, 3478-3481; c) S. Prakash, K. Muralirajan,
C.-H. Cheng, Angew. Chem. Int. Ed. 2016, 55, 1844-1848; d) P.
Gandeepan, C.-H. Cheng, Chem. Asian J. 2016, 11, 448–460; e) J.
Jayakumar, C.-H. Cheng, J. Chin. Chem. Soc. 2018, 65, 11–23.
[15] J.-D. Yang, J. Xue, J.-P. Cheng, Chem. Soc. Rev. 2019, 48, 2913-2926.
[16] CCDC 1857344 (4aa), 1857342 (4da), 1857343 (4ea'), 1887315 (4ax),
1878890 (4ay), and 1903589 (I-Tol-BrPh) contain the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
[17] a) S. Murata, K. Suzuki, A. Tamatani, M. Miura, M. Nomura, J. Chem. Soc.,
Perkin Trans. 1 1992, 1387-1392; b) E. Boess, D. Sureshkumar, A. Sud, C.
Wirtz, C. Farès, M. Klussmann, J. Am. Chem. Soc. 2011, 133, 8106-8109;
c) L. Huang, T. Niu, J. Wu, Y. Zhang, J. Org. Chem. 2011, 76, 1759-1766;
d) M. Nishino, K. Hirano, T. Satoh, M. Miura, J. Org. Chem. 2011, 76, 6447-
6451; e) G. Zhang, Y. Ma, S. Wang, Y. Zhang, R. Wang, J. Am. Chem. Soc.
2012, 134, 12334-12337; f) T. Wang, M. Schrempp, A. Berndhäuser, O.
Schiemann, D. Menche, Org. Lett. 2015, 17, 3982-3985.
[18] Examples of synthesis of 3,4-disubstituted quinolines with internal alkynes,
see: a) P. Zhao, X. Yan, H. Yin, C. Xi, Org. Lett. 2014, 16, 1120-1123; b)
C.-Z. Luo, P. Gandeepan, Y.-C. Wu, W.-C. Chen, C.-H. Cheng, RSC Adv.
2015, 5, 106012-106018; c) L.-H. Li, Z.-J. Niu, Y.-M. Liang, Chem. Eur. J.
2017, 23, 15300-15304; d) H. Wang, Q. Xu, S. Shen, S. Yu, J. Org. Chem.
2017, 82, 770-775.
[19] S. Ali, H.-T. Zhu, X.-F. Xia, K.-G. Ji, Y.-F. Yang, X.-R. Song, Y.-M. Liang,
Org. Lett. 2011, 13, 2598-2601.
[20] a) A. D. Becke, J. Chem. Phys. 1993, 98, 5648-5652; b) C. Lee, W. Yang,
R. G. Parr, Phys. Rev. B 1988, 37, 785-789; c) A. D. Becke, Phys. Rev. A
1988, 38, 3098-3100.
[1] For selected reciews of natural and bioactive compounds, see: a) W. Sliwa,
Curr. Org. Chem. 2003, 7, 995-1048; b) A. Schmidt, Adv. Heterocycl. Chem.
2003, 85, 67-171; c) L. Grycová., J. Dostál, R. Marek, Phytochemistry 2007,
68, 150-175; d) R. Gaziano, G. Moroni, C. Buè, M. T. Miele, P. Sinibaldi-
Vallebona, F. Pica, World J. Gastrointest. Oncol. 2016, 8, 30-39; For
examples of applications, see: e) J. Fortage, F. Tuyèras, P. Ochsenbein, F.
Puntoriero, F. Nastasi, S. Campagna, S. Griveau, F. Bedioui, I. Ciofini, P.
P. Lainé, Chem. Eur. J. 2010, 16, 11047-11063; f) D. Y. W. Ng, R. Vill, Y.
Wu, K. Koynov, Y. Tokura, W. Liu, S. Sihler, A. Kreyes, S. Ritz, H. Barth, U.
Ziener, T. Weil, Nat. Commun. 2017, 8, 1850; g) K. Xu, Y. Fu, Y. Zhou, F.
Hennersdorf, P. Machata, I. Vincon, J. J. Weigand, A. A. Popov, R. Berger,
X. Feng, Angew. Chem. Int. Ed. 2017, 56, 15876-15881.
[2] a) M. Wainwright, J. E. Kristiansen, Int. J. Antimicrob. Agents 2003, 22, 479-
486; b) S. D. Barchéchath, R. I. Tawatao, M. Corr, D. A. Carson, H. B.
Cottam, Bioorg. Med. Chem. Lett. 2005, 15, 1785-1788; c) R. Sánchez-
Martín, J. M. Campos, A. Conejo-García, O. Cruz-López, M. Báñez-Coronel,
A. Rodríguez-González, M. A. Gallo, J. C. Lacal, A. Espinosa, J. Med.
Chem. 2005, 48, 3354-3363; d) G. Bringmann, K. Thomale, S. Bischof, C.
Schneider, M. Schultheis, T. Schwarz, H. Moll, U. Schurigt, Antimicrob.
Agents Chemother. 2013, 57, 3003-3011; e) P. Singh, R. Kumar, A. K.
Singh, P. Yadav, R. S. Khanna, M. Vinayak, A. K. Tewari, J. Mol. Struct.
2018, 1163, 262-269.
[3] a) N. Baba, K. Nishiyama, J. Oda, Y. Inouye, Agric. Biol. Chem. 1976, 40,
1259-1260; b) F. Diaba, C. Le Houerou, M. Grignon-Dubois, P. Gerval, J.
Org. Chem. 2000, 65, 907-910; c) K. T. Sylvester, K. Wu, A. G. Doyle, J.
Am. Chem. Soc. 2012, 134, 16967-16970; d) Y. Wang, Y. Liu, D. Zhang, H.
Wei, M. Shi, F. Wang, Angew. Chem. Int. Ed. 2016, 55, 3776-3780; e) Y.
Jin, L. Ou, H. Yang, H. Fu, J. Am. Chem. Soc. 2017, 139, 14237-14243; f)
Z. Kang, D. Zhang, W. Hu, Org. Lett. 2017, 19, 3783-3786; g) A. Choi, R.
M. Morley, I. Coldham, Beilstein J. Org. Chem. 2019, 15, 1480-1484; h) A.
[21] a) M. Cossi, N. Rega, G. Scalmani, V. Barone, J. Comput. Chem. 2003, 24,
669-681; b) V. Barone, M. Cossi, J. Phys. Chem. A 1998, 102, 1995-2001.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
[22] R. Z. Khaliullin, E. A. Cobar, R. C. Lochan, A. T. Bell, M. Head-Gordon, J.
Phys. Chem. A 2007, 111, 8753-8765.
[23] D. H. Ess, R. J. Nielsen, W. A. Goddard Iii, R. A. Periana, J. Am. Chem.
Soc. 2009, 131, 11686-11688.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.202000178
European Journal of Organic Chemistry
Full Paper
Entry for the Table of Contents
A3 reaction with secondary
aniline: Secondary anilines
were first utilized in coupling
with aldehydes, and alkynes to
synthesize corresponding N-
substituted quinolinium salts.
DFT calculation was performed
to understand the [4+2]
cycloaddition mechanism and
the singular regioselectivity of
the reaction.
Lin-Chieh Cheng,[a] Wei-Chen Chen,[a] Rajagopal
Santhoshkumar,[a] Tzu-Hsuan Chao,[b] Mu-Jeng
Cheng,[b] and Chien-Hong Cheng[a]*
Page No. – Page No.
Synthesis of Quinolinium Salts from N-
Substituted Anilines, Aldehydes, Alkynes,
and Acid: Theoretical Understanding of the
Mechanism and Regioselectivity
This article is protected by copyright. All rights reserved.