Straightforward Hantzsch four- and three-component condensation in the presence of triphenyl(propyl-3-sulfonyl)phosphoniumtrifluoromethanesulfonate {[TPPSP]OTf} as a reusable and green mild ionic liquid catalyst

Article abstract of DOI:10.1002/aoc.3433

Triphenyl(propyl-3-sulfonyl)phosphoniumtrifluoromethanesulfonate {[TPPSP]OTf} as a reusable, green and benign ionic liquid catalyst has been used in the Hantzsch four-component (synthesis of polyhydroquinolines) and three-component (synthesis of acridines

Full text of DOI:10.1002/aoc.3433

Full paper
Received: 7 November 2015
Revised: 30 November 2015
Accepted: 17 December 2015
Published online in Wiley Online Library: 10 March 2016
(wileyonlinelibrary.com) DOI 10.1002/aoc.3433
Straightforward Hantzsch four- and three-
component condensation in the presence of
triphenyl(propyl-3-sulfonyl)
phosphoniumtrifluoromethanesulfonate
{[TPPSP]OTf} as a reusable and green mild ionic
liquid catalyst
Seyed Mohammad Vahdata*, Mohammad Ali Zolfigolb* and Saeed Bagheryb
Triphenyl(propyl-3-sulfonyl)phosphoniumtrifluoromethanesulfonate {[TPPSP]OTf} as a reusable, green and benign ionic
liquid catalyst has been used in the Hantzsch four-component (synthesis of polyhydroquinolines) and three-
component (synthesis of acridines) condensation reactions of 1,3-diones, β-ketoesters, aldehydes, ammonium acetate
and aniline derivatives in the presence of 0.5 mol% of {[TPPSP]OTf} at room temperature under solvent-free conditions.
1
The new ionic liquid catalyst was fully characterized using infrared, H NMR, 13C NMR, 31P NMR, 19F NMR and mass spec-
troscopies, and thermogravimetric and derivative thermogravimetric analyses. Additionally, the recovered catalyst can
be recycled at least five times in subsequent reactions without significant loss in catalytic activity. The new synthesis
technique presented offers numerous advantages of safety, mild conditions, simplicity, short reaction time, high yields
and easy workup compared to the traditional synthesis method. Twenty products have been reported for the first time.
Copyright © 2016 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: ionic liquid; triphenyl(propyl-3-sulfonyl)phosphoniumtrifluoromethanesulfonate; Hantzsch condensation; polyhydroquinoline;
acridine; solvent-free
Hantzsch products (1,4-dihydropyridine, polyhydroquinoline
and acridine) are a productive source of biologically significant
Introduction
Ionic liquids (ILs) are salts that occur as liquids at low temper-
ature although they are considered among ionic species, cat-
ions and anions. Retaining their ionic nature in bonding, they
have exceptional properties such as non-volatility, high ionic
conductivity and non-flammability as well as a wide liquid
range and wide electrochemical stability.[1] Additionally, the
properties of ILs make a remarkable difference from the con-
ventional organic electrolytes and solvent classifications.[2–5]
ILs have been efficiently employed as solvents and catalysts
for a diversity of reactions,[6–9] which promise prevalent appli-
cations in industry and organic synthesis. Room temperature
ILs are ILs that are liquid at room temperature or to some ex-
tent higher (20–30°C). Use of room temperature ILs has
expanded more and more as green and encouraging solvents
for synthetic chemistry.[10–14] Acidic ILs, including the recognized
chloroaluminate-based ILs and the lately developed Brønsted acidic
ones that contain trifluoromethylsulfuric acid as acidic group,[15]
have been demonstrated to be effective catalysts for a diversity of
reactions. Cautions regarding immobilizing ILs on solid supports
by chemical covalent bonding have previously been reported.[16,17]
molecules having several important pharmacological proper-
ties, such as vasodilator, antihypertensive, bronchodilator,
anti-therosclerotic, hepto-protective, anti-tumour, anti-mutagenic,
geroprotective and anti-diabetic agents.[18–22] In 1882, Hantzsch
described key synthesis of symmetrically substituted 1,4-
dihydropyridines by the one-pot, four-component condensation
of two molecules of aromatic aldehyde, ethyl acetoacetate and
*
Correspondence to: Seyed Mohammad Vahdat, Department of Chemistry,
Ayatollah Amoli Branch, Islamic Azad University, PO Box 678, Amol, Iran. E-mail:
m.vahdat@iauamol.ac.ir
Saeed Baghery, Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali
Sina University, Hamedan 6517838683, Iran. E-mail: zolfi@basu.ac.ir;
mzolfigol@yahoo.com
a Department of Chemistry, Ayatollah Amoli Branch, Islamic Azad University, PO
Box 678, Amol, Iran
b Department of Organic Chemistry, Faculty of Chemistry, Bu-Ali Sina University,
Hamedan 6517838683, Iran
Appl. Organometal. Chem. 2016, 30, 311–317
Copyright © 2016 John Wiley & Sons, Ltd.

S. M. Vahdat et al.
ammonia.[23] Significant rate and yield enhancements were also re-
ported for Hantzsch reactions carried out under microwave
irradiation.[24–26] The utilization of cyclic 1,3-diketone in the
Hantzsch reaction for the synthesis of polyhydroquinoline and acri-
dine has recently been demonstrated using nickel nanoparticles,[27]
1-vinyl-3-ethylimidazolium iodide as an IL catalyst,[28] amberlyst-
15,[29] sulfonated organic heteropolyacid salts,[30] protic pyridinium
IL [2-MPyH]OTf,[31] {[HMIM]C(NO2)3},[32] SnO2 nanoparticles,[33]
[Bsim]Cl,[34] [2-Eim]HSO4,[35] [pyridine–SO3H]Cl[36] and nano-ferrous
ferric oxide (nano-Fe3O4).[37]
Following our attempts to develop a novel room temperature IL
as a catalyst in synthetic methodologies, herein is reported a simple
and green one-pot synthesis of polyhydroquinoline and acridine
derivatives via Hantzsch four- and three-component condensation
reactions in high yields using an acidic IL, triphenyl(propyl-3-sulfo-
nyl)phosphoniumtrifluoromethanesulfonate, as a catalyst for the
first time (1).
Table 1. Solvent effect in the reaction between biphenyl-4-
carbaldehyde, dimedone, ethyl acetoacetate and ammonium acetatea
Solvent
Solvent- H2O C2H5OH CH3CN Toluene Benzene
free
Reaction time (min)
Yield (%)b
8
10
8
15
95
45
71
60
53
97
97 97
a
Reaction conditions: biphenyl-4-carbaldehyde (1 mmol), dimedone
(1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate
(1 mmol), IL catalyst (0.5 mol%), solvent (2 ml).
b
Isolated yield.
The 1H NMR spectrum of {[TPPSP]OTf} (Fig. 2S, supporting infor-
mation) shows a singlet at 9.14 ppm corresponding to OH in the
SO3H group with two doublets at 7.60 and 7.50 ppm and a triplet
at 7.44 ppm related to the aromatic hydrogens. Also, there are
two peaks of a triplet at 2.26 and 2.03 ppm and a multiplet at
1.81 ppm related to the aliphatic hydrogens.
Appearance of 11 signals in the 13C NMR spectrum (Fig. 3S,
supporting information) is in accordance with the IL catalyst
structure. In addition a quartet at 126.7–128.3 ppm in the 13C
NMR spectrum and a singlet at 23.6 ppm in the 31P NMR spectrum
(Fig. 4S, supporting information) and at À77.8 ppm in the 19F NMR
spectrum (Fig. 5S, supporting information) clearly confirm the pro-
tonation of zwitterion via trifluoromethanesulfonic acid.
The mass spectrum of the IL catalyst is in agreement with
the structure of the catalyst and shows the parent peak at
m/z 534 (Fig. 6S, supporting information). The significant peak
of the mass spectrum of the novel IL catalyst is linked to
trifluoromethanesulfonate counter ion which is known at m/z
149 and the peak at m/z 385 is related to triphenyl(propyl-3-
sulfonyl)phosphonium.
TG and DTG analyses of {[TPPSP]OTf} were also conducted.
The results are shown in Figs 7S and 8S of the supporting in-
formation. These analyses clearly reveal that the novel IL cat-
alyst has good stability; there are no clear mass losses before
365°C. The significant weight loss of the catalyst occurred af-
ter 365°C, which means it can be suitable for catalytic usages
Results and Discussion
Characterization of Triphenyl(propyl-3-sulfonyl)
phosphoniumtrifluoromethanesulfonate {[TPPSP]OTf} as
Novel IL Catalyst
A novel room temperature acidic IL is reported as a new catalyst
which has many advantages in comparison with similar catalysts
in the Hantzsch reaction. These advantages include the catalyst be-
ing in the liquid state at room temperature (room temperature IL), a
mild and clean reaction environment without the use of toxic or-
ganic solvents, and easy synthesis, recycling and work-up.
Characterization of the novel IL catalyst was carried out using
several analytical methods, namely infrared (IR), 1H NMR, 13C
NMR, 31P NMR, 19F NMR and mass spectroscopies, and thermogra-
vimetric (TG) and derivative thermogravimetric (DTG) analyses.
In the IR spectrum of {[TPPSP]OTf} the absorption band at 3445
cmÀ1 corresponds to stretching vibration of O–H in the SO3H group
and the two peaks at 1225 and 1166 cmÀ1 are related to vibrational
modes of O–SO2 bonds. The band related to S–O bond vibration
appears at 1029 cmÀ1 (Fig. 1S, supporting information).
Table 2. Optimization reaction between biphenyl-4-carbaldehyde,
dimedone, ethyl acetoacetate and ammonium acetatea
Entry
Amount of
catalyst (mol%)
Temperature
(°C)
Time
(min)
Yield (%)b
1
2
3
4
5
6
7
8
9
10
Catalyst-free
25
100
25
60
60
8
23
25
97
97
97
97
97
97
95
96
Catalyst-free
0.5
0.5
1
100
25
8
8
1
100
25
8
2
8
2
100
25
8
5
10
10
5
100
a
Reaction conditions biphenyl-4-carbaldehyde (1 mmol), dimedone
(1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate (1 mmol);
b
Scheme 1. Hantzsch four- and three-component condensation reactions
catalysed by {[TPPSP]OTf} IL.
Isolated yield.
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 311–317

Hantzsch four- and three-component condensation using {[TPPSP]OTf}
in organic synthesis. The first weight loss around 100°C is at-
tributed to the residual physisorbed water and organic sol-
solvent-free conditions is obviously the best choice. Though,
for this reaction, considering research in the laboratory not
in industry, the best results were obtained by carrying out
the reaction at room temperature in ethanol for 8 min using
0.5 mol% of IL as a catalyst. However, in the present case
solvent-free conditions are preferred to ethanol because
solvent-free conditions are green, safe and cheap in compari-
son with organic solvents.
The reaction between biphenyl-4-carbaldehyde, ethyl acetoa-
cetate, dimedone and ammonium acetate using 0.5, 1, 2 or 5 mol
% catalyst at room temperature or 100°C as a typical study was car-
ried out under solvent-free conditions to determine the optimum
temperature. The results in Table 2 obviously establish that, in the
absence of the catalyst, product is obtained in low yield after 60
vents, which were applied in the catalyst synthesis.
A
significant weight loss occurs in the range 365–500°C, being
attributed to the loss of main {[TPPSP]OTf}.
Application of {[TPPSP]OTf} as Novel IL Catalyst
The effect of solvent on the yield of polyhydroquinoline is
given in Table 1. The reaction between dimedone, biphenyl-
4-carbaldehyde, ethyl acetoacetate and ammonium acetate
was selected as a typical reaction for studying the effect of
solvent. From Table 1 it is evident that this reaction under
Table 3. Synthesis of polyhydroquinoline derivatives using novel IL catalyst under solvent-free conditions
Entry
Aldehyde
R1
R3
Time (min)
Yield (%)
M.p. (°C)
1
4-N,N-Dimethylaminobenzaldehyde
4-Hydroxy-3-methoxybenzaldeyhe
2,5-Dimethoxybenzaldehyde
4-N,N-Dimethylaminobenzaldehyde
4-Hydroxy-3-methoxybenzaldeyhe
2,5-Dimethoxybenzaldehyde
α-Methylcinnamaldehyde
Biphenyl-4-carbaldehyde
Terephthaldehyde
H
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
15
12
8
94
93
96
95
95
97
95
98
95
92
95
96
97
95
96
95
96
96
97
95
97
98
98
95
95
97
96
93
93
92
95
255–257 (253–255)[32]
223–225 (224–226)[32]
237–239 (238–240)[32]
226–228 (228–230)[32]
271–273 (273–275)[32]
197–199 (193–195)[32]
194–196 (193–195)[32]
257–259 (256–258)[32]
345–347 (343–345)[32]
201–203 (197–199)[32]
205–207 (202–204)[38]
209–211 (209–201)[33]
229–231 (229–231)[33]
217–219 (216–218)[33]
229–231 (232–234)[38]
202–204 (201–203)[33]
258–260 (257–259)[38]
265–267 (260–261)[38]
195–197 (191–193)[32]
231–233 (231–233)[33]
175–177 (175–177)[33]
246–248 (244–246)[33]
144–146 (143–145)[33]
204–206 (203–205)[33]
221–223 (218–220)[32]
195–197 (196–198)[32]
247–249 (367–369)[32]
144–146 (145–146)[38]
148–150 (147–148)[38]
164–166 (164–166)[28]
193–195
2
H
3
H
4
Me
Me
Me
Me
Me
Me
H
10
12
6
5
6
7
20
5
8
9
20
10
13
7
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
2,5-Dimethoxybenzaldehyde
Benzaldehyde
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Et
2-Chlorobenzaldehyde
4-Chlorobenzaldehyde
3-Hydroxybenzaldehyde
4-Hydroxybenzaldehyde
3-Methoxybenzaldehyde
4-Methoxybenzaldehyde
4-Methylbenzaldehyde
2,5-Dimethoxybenzaldehyde
4-N,N-Dimethylaminobenzaldehyde
3-Nitrobenzaldehyde
Et
Et
5
Et
12
10
10
8
Et
Et
Et
Et
10
8
Et
Et
10
3
Et
4-Nitrobenzaldehyde
Et
1
4-Cyanobenzaldehyde
Et
2
Cinnamaldehyde
Et
15
25
8
α-Methylcinnamaldehyde
Biphenyl-4-carbaldehyde
Terephthaldehyde
Et
Et
Et
25
17
17
20
10
Propionaldehyde
Et
Butyraldehyde
Et
Pentanal
Et
4-Hydroxy-3-methoxybenzaldehyde
Et
Appl. Organometal. Chem. 2016, 30, 311–317
Copyright © 2016 John Wiley & Sons, Ltd.
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S. M. Vahdat et al.
min, whereas good results are obtained in the presence of 0.5 mol%
of catalyst and 25°C, showing the effect of temperature in terms of
reaction time and obtained yield (Table 2, entry 3). From Table 2
(entries 9 and 10) with respect to the reaction mechanism, it can
be said that an increase in the amount of catalyst protonates the
carbonyl group of 1,3-diketone and β-ketoester compounds and
the nucleophilic properties decrease. Therefore, the products are
obtained in lower yield and also with a longer time.
Table 4. Reusability of catalyst for the synthesis of ethyl 4-(biphenyl-4-
yl)-2,7,7-trimethyl-5-oxo-1,4,5,6,7,8-hexahydroquinoline-3-carboxylate
(Table 3, entry 26)a
Number of experiments
Isolated yield (%)b
Fresh
97
1
2
95
95
3
95
94
4
91
90
96
96
Catalyst recovery (%)
97
a
Reaction conditions: biphenyl-4-carbaldehyde (1 mmol), dimedone
(1 mmol), ethyl acetoacetate (1 mmol), ammonium acetate (1
mmol), IL catalyst (0.5 mol %).
After determining the optimum reaction conditions, the investi-
gation proceeded by performing the reaction between a series of
1,3-diketones, β-ketoesters, aldehydes and ammonium acetate. To
show the common applicability of this method, numerous alde-
hydes were competently reacted under similar conditions. These
results encouraged us to investigate the capacity and the generality
of this new protocol for various aldehydes under optimized condi-
tions. As evident from Table 3, a series of aromatic and aliphatic al-
dehydes undergo electrophilic substitution reactions with a wide
range of polyhydroquinoline derivatives in good to excellent yields.
The nature and electronic properties of the substituents on the
aromatic ring affect the conversion rate, and aromatic aldehydes
containing electron-withdrawing groups on the aromatic ring react
faster than those with electron-releasing groups. Aliphatic alde-
hydes show a slower reaction time, which is most possibly because
of the electron-donating and steric effects of the methyl group.
Also, under these reaction conditions dimedone reacts faster than
1,3-cyclohexanedione. Additionally, under these reaction conditions
methyl acetoacetate reacts faster than ethyl acetoacetate. Also, using
terephthaldehyde as an aldehyde derivative, bisapolyhydroquinoline
products are obtained (Table 3, entries 9 and 27).
In a proposed mechanism (2), we suggest that initially 1,3-dione
(1) is converted to its enol (9) form by the IL catalyst and linked to
activated aldehyde using the IL catalyst to afford intermediate 10.
Also, the activated ethyl acetoacetate using the IL catalyst and am-
monia obtained from ammonium acetate provides enamine 8.
Then, the intermediate 10 and enamine 8 react with each other
to afford intermediate 11. Intermediate 11 is converted to 12 via
tautomerization, and intermediate 12 provides 13 via intramolecu-
lar nucleophilic attack of the NH2 group at the activated carbonyl
group. Finally, polyhydroquinonine derivatives (5) form by remov-
ing one molecule of H2O.[32]
b
Isolated yield.
of the IL catalyst. After completion of the reaction (observed
using TLC), the product was extracted with ethyl acetate
and the catalyst was recovered from the aqueous layer. After
washing the solid products completely with water (IL is more
soluble in water than ethyl acetate), water was evaporated
under reduced pressure and the IL was recovered and
recycled. The recovered catalyst was reused five times without
any loss in activity (Table 4). The deactivation of the catalyst is
low, though coke formation (reactant) was expected. The re-
action was scaled up to 10 mmol of biphenyl-4-carbaldehyde,
dimedone, ethyl acetoacetate and ammonium acetate in the
presence of 5 mol% of catalyst at 25°C. The yield of the reac-
tion is 97% after 8 min and 91% after the fifth run.
In another study, to optimize the reaction conditions, we in-
vestigated the influence of the IL catalyst in the synthesis of
1,8-dioxodecahydroacridines (1). For this, as a model reaction,
the condensation reaction between dimedone, naphthalene-1-
carbaldehyde and ammonium acetate was considered in the
presence of various amounts of the IL catalyst at of 25–
100°C under solvent-free conditions (Table 5). As evident from
Table 5, the best results are obtained when the reaction is
conducted in the presence of 0.5 mol% of IL catalyst at room
temperature (Table 5, entry 3). Increasing the reaction temper-
ature and amount of catalyst does not improve the rate of the
reaction (Table 5, entries 4–11). In the absence of catalyst a
The reusability of the catalyst is an important advantage
and makes it beneficial for commercial applications.[39] For
this purpose, the reaction between dimedone, biphenyl-4-
carbaldehyde, ethyl acetoacetate and ammonium acetate
was selected as a model reaction conducted in the presence
Table 5. Effect of amount of catalyst and temperature in the synthesis
of 1,8-dioxodecahydroacridine under solvent-free conditionsa
Entry
Catalyst
Reaction
Reaction
Yield (%)b
loading (mol%) temperature (°C) time (min)
1
Catalyst-free
r.t.
100
r.t.
60
60
8
21
30
96
96
96
96
96
96
96
96
94
94
2
Catalyst-free
3
0.5
0.5
0.5
0.5
1
4
50
8
5
75
8
5
100
r.t.
8
6
8
7
1
100
r.t.
8
8
2
8
9
2
100
r.t.
8
10
11
5
10
10
5
100
a
Reaction conditions: dimedone (2 mmol), naphthalne-1-
carbaldehyde (1 mmol), ammonium acetate (1 mmol).
b
Scheme 2. Proposed mechanism for the synthesis of polyhydroquinoline
derivatives using {[TPPSP]OTf}.
Isolated yield.
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 311–317

Hantzsch four- and three-component condensation using {[TPPSP]OTf}
Table 6. Three-component Hantzsch synthesis of 1,8-dioxodecahydroacridine derivatives in the presence of 0.5 mol% of {[TPPSP]OTf} as novel IL
catalysta
Entry
Aldehyde
R1
Aniline
NH4OAc
Time (min)
Yield (%)b
M.p. (°C)
1
Biphenyl-4-carbaldehyde
Naphthalene-1-carbaldehyde
Terephthaldehyde
Me
Me
Me
H
5
8
97
96
94
96
95
93
95
94
92
92
91
89
96
95
93
94
93
91
235–237
206–208
2
NH4OAc
3
NH4OAc
18
7
280–282
4
Biphenyl-4-carbaldehyde
Naphthalene-1-carbaldehyde
Terephthaldehyde
NH4OAc
300–302
5
H
NH4OAc
10
20
12
18
33
17
23
38
9
281–283
6
H
NH4OAc
284–286
7
Biphenyl-4-carbaldehyde
Naphthalene-1-carbaldehyde
Terephthaldehyde
Me
Me
Me
H
4-Chloroaniline
4-Chloroaniline
4-Chloroaniline
4-Chloroaniline
4-Chloroaniline
4-Chloroaniline
4-Bromoaniline
4-Bromoaniline
4-Bromoaniline
4-Bromoaniline
4-Bromoaniline
4-Bromoaniline
286–288
8
291–293
293–295 (282)[29]
9
10
11
12
13
14
15
16
17
18
Biphenyl-4-carbaldehyde
Naphthalene-1-carbaldehyde
Terephthaldehyde
221–223
H
221–223
H
280–282
Biphenyl-4-carbaldehyde
Naphthalene-1-carbaldehyde
Terephthaldehyde
Me
Me
Me
H
205–207
13
28
12
18
33
236–238
230–232 (210)[29]
Biphenyl-4-carbaldehyde
Naphthalene-1-carbaldehyde
Terephthaldehyde
218–220
H
217–219
H
271–273
a
Reaction conditions: 1,3-diketones (2 mmol), aldehydes (1 mmol), several anilines or ammonium acetate (1 mmol).
Isolated yield.
b
low yield of the products is obtained after 60 min (Table 5,
are obtained (Table 6, entries 3, 6, 9, 12, 15 and 18). Additionally,
recyclability and reusability of the catalyst were also studied in the
condensation of dimedone, naphthalene-1-carbaldehyde and
entries 1 and 2). To compare the results of solution with
solvent-free conditions, a mixture of dimedone, naphthalene-
1-carbaldehyde and ammonium acetate as a model reaction,
in the presence of 0.5 mol% of IL catalyst in numerous sol-
vents (H2O, CH3CN, C2H5OH, CH2Cl2, CH3CO2Et and toluene),
was studied at room temperature. Solvent-free condition was
the best for this reaction.
In order to confirm this key procedure, we were encouraged
because of the results obtained to produce numerous 1,8-
dioxodecahydroacridines from Hantzsch three-component conden-
sation reactions of various aromatic aldehydes, 1,3-diketone and nu-
merous anilines or ammonium acetate under solvent-free
conditions at room temperature in the presence of a catalytic
amount of {[TPPSP]OTf} as a novel IL catalyst. The results are summa-
rized in Table 6. The effect of substituents on the aromatic ring
shows strong effects in terms of yields under these reaction condi-
tions. All aromatic aldehydes having electron-withdrawing and
electron-releasing substituents on their aromatic ring provide the re-
lated products in high to excellent yields in short reaction time. The
reaction time of aromatic aldehydes bearing electron-withdrawing
groups is rather faster than that for aldehydes bearing electron-
donating groups. Furthermore, under these reaction conditions am-
monium acetate reacts faster than aniline derivatives. Moreover,
dimedone reacts faster than 1,3-cyclohexanedione. Besides, using
terephthaldehyde as an aldehyde derivative, bisacridine products
Scheme 3. The suggested mechanism for the synthesis of acridine
derivatives using {[TPPSP]OTf}.
Appl. Organometal. Chem. 2016, 30, 311–317
Copyright © 2016 John Wiley & Sons, Ltd.
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S. M. Vahdat et al.
Table 7. Comparison of results for condensation reaction of 4-chlorobenzaldehyde, dimedone, ethyl acetoacetate and ammonium acetate catalysed by
{[TPPSP]OTf} with those obtained for other recently reported catalystsa
Entry
Catalyst and amount
Solvent
Temp. (°C)
Time (min)
Yield (%)b
Ref.
[41]
[42]
[43]
[33]
[31]
[44]
[45]
[46]
[47]
[48]
1
L-Proline/10 mol%
C2H5OH/reflux
CH3CN/reflux
H2O
—
—
r.t
360
35
11
9
92
80
96
94
97
92
90
92
93
93
97
2
K7[PW11CoO40]/1 mol%
3
Cu(II) Schiff base complex/1 mol%
SnO2 nanoparticles/1 mol%
[2-MPyH]OTf/1 mol%
4
C2H5OH
r.t
5
H2O
r.t
5
6
γ-Al2O3-nanoparticles/0.2 g
Titanium dioxide nanoparticles/10 mol%
PPA-SiO2/0.03 g
Solvent free
C2H5OH
90
80
80
60
90
r.t
8
7
120
45
180
15
5
8
Solvent free
Perfluorodecalin
Solvent free
Solvent free
9
Hf(NPf2)4/1 mol%
10
11
K5CoW12O40Á3H2O/0.01 mol%
{[TPPSP]OTf}/0.5 mol%
This work
a
Reaction conditions: 4-chlorobenzaldehyde, dimedone, ethyl acetoacetate, ammonium acetate.
Isolated yield.
b
ammonium acetate. Correspondingly, the IL catalyst was separated
and reused for further reaction runs.
Experimental
Materials and Methods
We propose the possible following mechanism for the synthesis
of acridine derivatives (3). The IL catalyst activates the aldehyde (2)
into appropriate electrophile using protonation of the carbonyl
group and then one molecule of 1,3-dione (1) condenses with the
aldehyde to create intermediate 16 (aldol condensation). The active
methylene group of the second molecule of 1,3-dione (2) reacts
with 16 to afford intermediate 17 (Michael addition). Nucleophilic
attack of amine group of ammonium acetate or aniline derivatives
to carbonyl group leads to intermediate 18. In the subsequent step,
cyclization will occur by the nucleophilic attack of amine group to
carbonyl group to achieve intermediate 19. Finally, using the
removal of one water molecule, owing to the driving force of con-
jugation of double bonds with carbonyl groups, the acridine deriv-
atives 6 will be produced.[40]
NMR spectra were obtained with a Fourier transform NMR
Bruker AV-500 spectrometer in DMSO-d6, with shifts mea-
sured relative to tetramethylsilane; coupling constants (J)
were measured in Hz. Melting points were determined with
an Electrothermal 9100. IR spectra were recorded with a
Rayleigh WQF-510 Fourier transform instrument. Commer-
cially available reagents were used without further
purification.
Preparation of Triphenyl(propyl-3-sulfonyl)
phosphoniumtrifluoromethanesulfonate
To compare the efficacy of our catalyst with that of some reported
catalysts for the synthesis of polyhydroquinolines, we present the re-
sults for these catalysts in the condensation of 4-chlorobenzaldehyde,
dimedone, ethyl acetoacetate and ammonium acetate in Table 7. As
evident from Table 7, {[TPPSP]OTf} markedly improves the synthesis
of polyhydroquinolines in terms of various parameters (reaction time,
yield and amount of catalyst).
Triphenylphosphine (3 mmol) and 1,3-propanesultone (3 mmol)
were combined in equimolar quantities in toluene and brought
to reflux for 12 h. Then, a white precipitate formed which was iso-
lated by filtration and dried. Analysis of the solid revealed it to be
the desired zwitterion, formed in quantitative yield. The desired
zwitterion was of sufficient purity to be used without any further
purification. Then trifluoromethanesulfonic acid (3 mmol)
was added slowly over a period of 60 min while stirring
and cooling to maintain the temperature at 0–5°C. Then,
the reaction combination was stirred for an additional pe-
riod of 6 h at room temperature, after which the solvent
was removed by distillation under reduced pressure, and
the product was dried under vacuum at 80°C for 2 h. A yel-
low viscous liquid was formed (1) quantitatively and in high
purity as assessed by physical data (IR, 1H NMR, 13C NMR).
Yield: 98% (1.57 g). IR (nujol, ν, cmÀ1): 3445, 2946, 1715, 1589,
1486, 1287, 1225, 1166, 1029, 725, 690. 1H NMR (400 MHz,
DMSO-d6, δ, ppm): 1.81 (m, 2H, H-C6), 2.03 (t, 2H, J = 6.4 Hz, H-C5),
2.26 (t, 2H, J = 6.2 Hz, H-C7), 7.44 (dd, 6H, J1 = 8.0 Hz, J2 = 7.6 Hz,
H-C3), 7.50 (d, 3H, J = 8.0 Hz, H-C4), 7.60 (d, 6H, J = 7.6 Hz, H-C2),
9.14 (brs, 1H, OH). 13C NMR (100 MHz, DMSO-d6, δ, ppm): 27.1
(C6), 29.5 (C5), 32.7 (C7), 126.7 (C8), 126.9 (C8), 127.6 (C8), 128.3 (C8),
138.1 (C3), 140.6 (C4), 142.9 (C2), 147.2 (C1). 31P NMR (162
MHz, DMSO-d6, δ, ppm): 23.6. 19F NMR (376 MHz, DMSO-d6,
δ, ppm): À77.8, MS: m/z = 534 [M]+, 535 [M + H]+.
Conclusions
In summary, a highly efficient and green process for Hantzsch four-
and three-component condensation reactions has been established.
The procedure was more environmentally friendly and with mild
conditions, little waste and high yield. The novel IL catalyst showed
high activities for the synthesis of polyhydroquinoline and acridine
derivatives. Furthermore, the catalyst offers numerous advantages
including shorter reaction time, mild reaction conditions, high yield
of products, cleaner reactions, large-scale applicability, low cost,
chemical stability, green acid catalyst as well as simple experimental
and isolation procedures, which mean that the novel homogenous
catalyst has great potential for the replacement of heterogeneous
catalysts in green processes. The novel IL catalyst was fully character-
ized using IR, 1H NMR, 13C NMR, 31P NMR, 19F NMR and mass spec-
troscopies, and TG and DTG analyses.
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Copyright © 2016 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2016, 30, 311–317

Hantzsch four- and three-component condensation using {[TPPSP]OTf}
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Acknowledgments
We thank Bu-Ali Sina University, Ayatollah Amoli Branch, Islamic
Azad University, and Iran National Science Foundation (INSF) for fi-
nancial support (grant number: 94002177) of our research group.
Also, the authors are grateful for the facilities provided to carry
out research in the chemistry research laboratory at Ayatollah
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Appl. Organometal. Chem. 2016, 30, 311–317
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