Succinimidinium hydrogensulfate ([H-Suc]HSO4) as a new, green and efficient ionic liquid catalyst for the synthesis of tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-one, 1-(benzothiazolylamino)phenylmethyl-2-naphthol, 1, 8-dioxo-octahydroxanthen

Article abstract of DOI:10.1007/s13738-016-0822-1

In this work, succinimidinium hydrogensulfate ([H-Suc]HSO₄), a newly reported Br?nsted acidic ionic liquid, is used as an efficient and reusable catalyst in the synthesis of tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-ones, 1-(benzothiazolylam

Full text of DOI:10.1007/s13738-016-0822-1

J IRAN CHEM SOC
DOI 10.1007/s13738-016-0822-1
ORIGINAL PAPER
Succinimidinium hydrogensulfate ([H‑Suc]HSO4) as a new,
green and efficient ionic liquid catalyst for the synthesis
of tetrahydrobenzimidazo[2,1‑b]quinazolin‑1(2H)‑one,
1‑(benzothiazolylamino)phenylmethyl‑2‑naphthol, 1,
8‑dioxo‑octahydroxanthene and bis(indolyl)methane derivatives
Omid Goli‑Jolodar1 · Farhad Shirini1
Received: 4 November 2015 / Accepted: 19 January 2016
© Iranian Chemical Society 2016
Abstract In this work, succinimidinium hydrogensulfate
([H-Suc]HSO4), a newly reported Brönsted acidic ionic liq-
uid, is used as an efficient and reusable catalyst in the syn-
thesis of tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-
ones, 1-(benzothiazolylamino)phenylmethyl-2-naphthols,
1,8-dioxo-octahydroxanthenes and bis(indolyl)methanes.
All reactions were performed during relatively short reac-
tion times with excellent yields. The structures of the prod-
ucts were characterized by IR, 1H NMR and 13C NMR spec-
troscopy and confirmed by comparison authentic samples.
synthesis of heterocyclic compounds has always been a sub-
ject of great interest due to their wide applicability in indus-
try such as pharmaceutical industry (drugs), catalysts in
petroleum processing, catalysts and reagents in fine chemical
synthesis, dyes, agrochemicals, health-care consumables and
additives in polymer manufacturing [4–13].
In recent decades, preparation and use of ionic liquids
(ILs) in organic transformations became one of the remark-
able and important branches in catalyst science because of
their unique properties such as negligible volatility, non-
flammability, good thermal stability, high conductivity and
great chemical and electro-chemical stability [14]. Also,
ILs being accepted as environmentally benign media and
have been widely applied in many reactions as catalysts or
dual catalyst-solvent due to their defined properties.
In this media Brönsted acidic ionic liquids, which com-
bine the advantages of solid acids (e.g., non-volatility and
recyclability) and those of liquid acids (e.g., greater effec-
tive surface area and potential activity of liquid phase),
have been designed and used as dual solvent-catalysts for
many famous organic reactions [15]. Among these types
of compounds Brönsted-acidic ionic liquids having a func-
tional group into cations or anions of ionic liquids, espe-
cially SO3H and SO4H functional groups, obviously show
enhancement in their acidities and water solubility [16, 17].
Furthermore, their polar nature makes them useful for use
under solvent-free conditions [18].
Keywords Multi-component reactions · Brönsted acidic
ionic liquids · Tetrahydrobenzimidazo[2, 1-b]quinazolin-
1(2H)-ones · 1-(Benzothiazolylamino)phenylmethyl-2-
naphthols · 1,8-Dioxo-octahydroxanthenes ·
Bis(indolyl)methanes
Introduction
Nowadays, selectivity atom economy, time saving, environ-
mental friendliness, cost effectiveness and the reconciliation
of molecular complexity with experimental simplicity are
the most important pieces of the puzzle needing to be assem-
bled by modern academic and industrial synthetic chemists
to reach the maximum of efficiency [1–3]. Attention to these
constraints has resulted in the tremendous development of
new concepts and new methodologies able to produce valu-
able elaborated compounds [3]. Among of these compounds
Experimental
General
* Farhad Shirini
shirini@guilan.ac.ir
1
Chemicals were purchased from Fluka, Merck, Aldrich
and Southern Clay Products Chemical Companies. Yields
Department of Chemistry, College of Science, University
of Guilan, Rasht 41335, Islamic Republic of Iran
1 3

J IRAN CHEM SOC
refer to isolated products. The products were character-
ized by their physical constants, comparison with authentic
samples, FT-IR and NMR spectroscopy. The purity deter-
mination of the substrate and reaction monitoring were
accomplished by TLC on silica-gel polygram SILG/UV
254 plates.
product and the separated product was washed twice with
water (2 × 5 mL). The crude products were purified by
recrystallization from EtOH and water.
General procedure for the synthesis of 1‑(benzothia‑
zolylamino)phenylmethyl‑2‑naphthols
Instrumentation
A mixture of the aldehyde (1 mmol), 2-aminobenzothiazole
(1 mmol), 2-naphthol (1 mmol) and [H-Suc]HSO4 (30 mg,
15 mol %) was heated at 80 °C under solvent-free condi-
tions for the appropriate time as identified by TLC (n-Hex-
ane: EtOAc, 70:30). After completion of the reaction, it was
cooled to room temperature and 3 mL of water was added
to the mixture. The ionic liquid was dissolved in water and
filtered for separation of the crude product and the sepa-
rated product was washed twice with water (2 × 5 mL).
The crude products were purified by recrystallization from
ethyl acetate.
The FT-IR spectra were run on a Perkin-Elmer bio-spec-
trometer and Bruker Vector 22. The HNMR (400 MHz)
1
and 13CNMR (100 MHz) were run on a Bruker AVANCE
III-400 spectrometer using TMS as an internal reference (δ
in ppm). Microanalyses were performed on a Perkin-Elmer
240-B microanalyzer. Melting points were recorded on a
Büchi B-545 apparatus in open capillary tubes.
General procedure for the preparation of the succinimi‑
dinium hydrogensulfate ([H‑Suc]HSO4) [19]
Synthesis of 1,8‑dioxo‑octahydro‑xanthenes
In a round-bottomed flask, 0.53 mL sulfuric acid (98 %,
d = 1.84) was added drop wise to a succinimide (0.99 g,
10 mmol) in 25 mL of dichloromethane on an ice bath.
The reaction mixture was stirred at room temperature for
30 min, and then the solvent was evaporated under reduced
pressure. The solid residue was washed with Et2O and dried
under vacuum. [H-Suc]HSO4 was obtained as a cream
solid (1.94 g, 97 %) (M.P. 78 °C); FT-IR (neat) ν = 3128,
A mixture of [H-Suc]HSO4 (10 mg, 5 mol %), aldehyde
(1 mmol) and dimedone (2.1 mmol) was stirred in an oil-
bath at 90 °C under solvent-free conditions. After comple-
tion of the reaction [monitored by TLC:n-hexane–EtOAc
(2:8)], the reaction mixture was cooled, H2O (5 mL)
was added and filtered to separate the catalyst. Then the
product was recrystallized from EtOH to give the pure
product.
1
1693, 1404, 1295, 1180, 1071, 1007, 883, 579 cm−1; H
NMR (400 MHz, DMSO-d6): d = 2.55 (s, 4H, CH2CH2),
7.31 (s, 2H, NH2), 10.93 (br s, 1H, HSO4) ppm; 13C NMR
(100 MHz, DMSO-d6): d = 29.76 (CH2CH2), 180.14
(C=O) ppm. Also and to determine the acidity of the pre-
pared reagent, to 25 mL of an aqueous solution of NaCl
(1 M) with a primary pH 5.2, [H-Suc]HSO4 (0.5 g) was
added and the resulting mixture was stirred for 2 h at room
temperature. The pH of the solution decreased to 1.7. This
is equal to a loading of 1.23 mmol H+ per gram of the
catalyst.
Synthesis of bis‑indolylmethanes
A mixture of [H-Suc]HSO4 (10 mg, 5 mol %), aldehyde
(1 mmol) and indole (2 mmol) under solvent-free condition
was heated at 80 °C. After completion of the reaction, as
monitored by TLC, using n-hexane:EtOAc (1:4) as the elu-
ent, the crude product was filtered off, washed with water,
and recrystallized from ethanol to give the pure compound.
Spectral (1H and 13C NMR) data of new compounds are
presented below:
General procedure for the synthesis
of tetrahydrobenzimidazo[2,1‑b]quinazolin‑1(2H)‑one
derivatives
3,3‑dimethyl‑12‑(4‑thiomethyl‑phenyl)‑3,4,5,12‑tetrahy‑
drobenzimidazo [2,1‑b]quinazolin‑1(2H)‑one (M1)
A mixture of the requested aldehyde (1 mmol), 2-amin-
obenzimidazole (1 mmol), dimedone (1 mmol), [H-Suc]
HSO4 (20 mg, 10 mol %) was heated at 90 °C under sol-
vent-free conditions for the appropriate time. After comple-
tion of the reaction [monitored by TLC (n-Hexane: EtOAc,
70:30)], it was cooled to room temperature and 3 mL of
water was added to the mixture. The ionic liquid was dis-
solved in water and filtered for separation of the crude
FT-IR (neat) ν = 3418, 3148, 2954, 1671, 1568, 1375,
1262, 744 cm−1; 1H NMR (DMSO-d6, 400 MHz): δ = 1.07
(6H, s, CH3), 2.15 (4H, s, CH2), 2.40 (3H, s, SCH3), 6.12
(1H, s), 6.93 (2H, d, J = 8.0 Hz), 7.03 (2H, d, J = 7.6 Hz),
7.07–7.11 (2H, m), 7.25–7.28 (2H, m), 7.65 (1H, s, NH)
ppm; 13C NMR (DMSO-d6, 100 Mz): δ = 15.8, 28.8, 30.3,
31.6, 48.8, 111.8, 114.8, 122.1, 126.1, 128.1, 132.7, 133,1,
142.8, 152.5 ppm.
1 3

J IRAN CHEM SOC
Scheme 1 Synthesis of tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-one derivatives catalyzed by [H-Suc]HSO4
3,3‑dimethyl‑12‑(4‑cyano‑phenyl)‑3,4,5,12‑tetrahydrobe
nzimidazo[2,1‑b]quinazolin‑1(2H)‑one (N1):
1‑((benzo[d]thiazol‑2‑ylamino)(pyridin‑2‑yl)methyl)
naphthalen‑2‑ol (O2)
1
FT-IR (neat) ν = 3425, 3045, 2962, 2227,1567, 1448,1358,
1264, 748 cm−1; 1H NMR (DMSO-d6, 400 MHz): δ = 0.92
(3H, s, CH3), 1.07 (3H, s,CH3), 2.07 (1H, d, J = 16.0 Hz),
2.28 (1H, d, J = 16.0 Hz), 2.67–2.69 (2H, m), 6.56 (1H,
s), 6.98 (1H, td, J1 = 8.0 Hz, J2 = 0.8 Hz), 7.08 (1H,
td, J1 = 8.2 Hz, J2 = 0.8 Hz), 7.41 (1H, d, J = 8.0 Hz),
7.24 (1H, d, J = 8.0 Hz), 7.54 (2H, dd, J1 = 5.0 Hz,
J2 = 1.6 Hz), 7.75 (2H, dd, J1 = 5.0 Hz, J2 = 1.6 Hz),
11.26 (1H, s, NH) ppm. 13C NMR (DMSO-d6, 100 Mz):
Sample solubility was too low for 13C NMR.
FT-IR (neat) ν = 3310, 1599, 1545, 1510, 1449 cm−1; H
NMR (DMSO-d6, 400 MHz): δ = 7.00 (s, 1H), 7.02–7.80
(m, 15H), 8.80 (s, 1H), 10.28 (br, 1H) ppm; 13C NMR
(DMSO-d6, 100 MHz): δ = 21.7, 119.3, 121.4, 121.4,
122.9, 123.7, 123.7, 125.9, 126.0, 126.8, 126.9, 127.1,
127.4, 127.5, 128.4, 128.5, 129.1, 130.0, 131.2, 132.6,
137.5, 143.0, 152.6, 153.6, 166.8 ppm.
Results and discussion
3,3‑dimethyl‑12‑(2‑naphthyl)‑3,4,5,12‑tetrahyd‑
robenzo[4,5]imidazo[2,1‑b]quinazolin‑1(2H)‑one (P1)
Very recently and in continuation of our previous reports on
the preparation and use of ionic liquids in different types of
organic transformations [20–23], we have reported the prepa-
ration of succinimidinium hydrogen sulfate ([H-Suc]HSO4)
and its applicability in the acceleration of the N-Boc protection
of amines. On the basis of these results we were interested in
investigating the applicability of [H-Suc]HSO4 in the accelera-
tion of the synthesis of some of the heterocyclic compounds.
Tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-ones,
one of the most important class of quinazolines, are very
interesting heterocycles as they serve as building blocks in
numerous natural and synthetic products that exhibit a wide
spectrum of biological and pharmacological activities.
Because of these important activities various types of cata-
lysts were used for the promotion of the synthesis of these
compounds via the three-component reaction between an
aldehyde, 2-aminobenzimidazole and dimedone (5,5-dime-
thyl-1,3-cyclohexanedione) [24–27]. Although these
methods are useful, but introduction of more efficient
and green catalysts for the promotion of the preparation
of tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-one is
under considerable attention yet.
FT-IR (neat) ν = 3443, 3050, 2964,1575, 1370, 1261,
746 cm−1; 1H NMR (DMSO-d6, 400 MHz): δ = 0.94 (3H,
s, CH3), 1.08 (3H, s, CH3), 2.04 (1H, d, J = 16.0 Hz), 2.29
(1H, d, J = 16.0 Hz), 2.67- 274 (2H, m), 6.60 (1H, s), 6.93
(1H, t, J = 7.6 Hz), 7.03 (1H, t, J = 7.6 Hz), 7.31 (2H,
m), 7.38 (1H, d, J = 8.0 Hz), 7.49 (2H, m), 7.80 (2H, t,
J = 7.6 Hz), 7.92 (1H, d, J = 7.6), 8.04 (1H, s), 11.19 (1H,
s, NH) ppm; 13C NMR (DMSO-d6, 100 Mz): sample solu-
bility was too low for 13C NMR.
12‑(2‑fluorenyl)‑3,3‑dimethyl‑3,4,5,12‑tetrahyd‑
robenzo[4,5]imidazo[2,1‑b]quinazolin‑1(2H)‑one (Q1)
FT-IR (neat) ν = 3431, 3047, 3229, 2908, 1575, 1372,
1264, 741 cm-1; 1H NMR (DMSO-d6, 400 MHz): δ = 0.96
(3H, s, CH3), 1.08 (3H, s, CH3), 2.07 (1H, d, J = 16.0 Hz),
2.28 (1H, d, J = 16.0 Hz), 2.65–2.69 (2H, m), 3.85 (2H, s,
CH2), 6.50 (1H, s), 6.96 (1H, td, J1 = 7.2 Hz, J2 = 1.2 Hz),
7.05 (1H, td, J1 = 7.2 Hz, J2 = 1.2 Hz), 7.28 (1H, td,
J1 = 7.2 Hz, J2 = 1.2 Hz), 7.31 (2H, d, J = 7.6 Hz), 7.38
(2H, d, J = 7.6 Hz), 7.54 (1H, d, J = 7.2 Hz), 7.54 (1H, s),
7.78 (1H, d, J = 7.6 Hz), 7.81 (1H, d, J = 7.2 Hz), 11.1
(1H, s, NH) ppm; 13C NMR (DMSO-d6, 100 Mz): sample
solubility was too low for 13C NMR.
To optimize the amount of the catalyst and the reaction
temperature in the synthesis of tetrahydrobenzimidazo[2,1-
b]quinazolin-1(2H)-ones, the condensation of 2-aminoben-
zimidazole, benzaldehyde and dimedone under thermal
solvent-free conditions was selected as a model reaction.
1 3

J IRAN CHEM SOC
Table 1 Preparation of
tetrahydrobenzimidazo[2,1-b]
quinazolin-1(2H)-one
derivatives using [H-Suc]HSO4
as the catalyst
Melꢀng point (°C)
Time
(min)
Yield
(%)a,b
Reported
Entry
A1
Aldehyde
Product
Found
[References]
CHO
O
O
16
28
92
87
>350
359-363 [28]
N
N
N
H
Cl
CHO
Cl
B1
C1
D1
E1
340-342
>300 [29]
>300 [29]
>300 [29]
>300 [29]
N
N
N
H
Br
CHO
O
O
20
45
14
91
88
90
334-336
334-336
340-342
N
Br
N
N
H
H
3C
CHO
CH3
N
N
N
H
Cl
CHO
CHO
CHO
O
O
O
N
Cl
N
N
H
H
3CO
F1
23
18
91
92
320-322
335-337
>300 [30]
>300 [29]
N
OMe
NO2
N
N
H
O2N
G1
N
N
N
N
N
H
Cl
CHO
O
O
H1
14
14
94
92
>350
>350
>300 [28]
>300 [28]
Cl
N
N
H
Br
CHO
I1
Br
N
N
H
1 3

J IRAN CHEM SOC
Table 1 continued
OCH3
CHO
O
J1
K1
L1
30
10
1h
15
15
14
93
94
91
87
92
92
340-342
344-346
332-334
342-344
340-342
340-342
>300 [28]
MeO
O2N
HO
N
N
N
N
N
N
N
N
N
N
N
N
N
H
NO2
CHO
O
O
O
O
O
>300 [28]
N
H
OH
CHO
CHO
CHO
CHO
330-332 [28]
N
H
SMe
M1
N1
O1
-
MeS
N
H
CN
-
NC
N
H
CH3
>300 [30]
H
3C
N
H
CHO
O
P1
20
89
344-346
-
N
N
N
H
CHO
Q1
30
89
347-349
-
O
N
N
N
H
a
Isolated yields
b
Products were characterized by their physical constants and comparison with authentic samples (Refs. [28–30])
1 3

J IRAN CHEM SOC
Table 2 Comparison of
Entry Catalyst (amount)
Conditions
Time (min) Yield (%)a References
the result obtained from the
synthesis of 3,3-dimethyl-
12-(4-nitro-phenyl)-3,4,5,12-
tetrahydrobenzimidazo[2,1-b]
quinazolin-1(2H)-one (Table 1,
entry K1) using [H-Suc]HSO4
with other reported methods
1
2
3
4
5
6
7
8
H6P2W18O62.18H2O (1 mol %) Reflux/CH3CN
10
–
99
–
[28]
–
110 °C/solvent-free
Reflux/DMF
[29]
–
–
–
[30]
NH2SO3H (50 mol %)
I2 (10 mol %)
SiO2 (10 mol %)
p-TSA (15 mol %)
[H-Suc]HSO4 (10 mol %)
Reflux/CH3CN
Reflux/CH3CN
MW/120 °C
18
10
5
95
69
95
98
94
[31]
[24]
[25]
50 °C/CH3CN
90 °C/solvent-free
20
10
[26]
This work
a
Isolated yields
Scheme 2 [H-Suc]HSO4 catalyzed the synthesis of 1-(benzothiazolylamino)-phenylmethyl-2-naphthols derivatives
This study showed that the best results can be obtained
using 20 mg [H-Suc]HSO4 at 90 °C under solvent-free con-
ditions (Scheme 1). To explore the general applicability of
this reaction, a variety of tetrahydrobenzimidazo [2,1-b]
quinazolin-1(2H)-one were prepared under the optimized
reaction conditions. As it is clear from Table 1, under the
selected conditions various aldehydes with different elec-
tron-donating and electron-withdrawing groups were well
tolerated and yields are almost quantitative in all cases.
To highlight the merits of our newly developed
procedure, we compared the obtained results for the
synthesis of 3,3-dimethyl-12-(4-nitro-phenyl)-3,4,5,12-
tetrahydrobenzimidazo[2,1-b]quinazolin-1(2H)-one
(Table 1, entry K1) using the [H-Suc]HSO4 as the catalyst
with the other results reported in the literature for the same
transformations. As shown in Table 2, the newly developed
method avoids some of the disadvantages associated with
the other procedures such as long reaction times, large
excesses of the reagents, use of organic solvents, reflux
conditions, toxic reagents and low yields of the products.
Benzothiazole derivatives are important classes of heter-
ocyclic compounds that occur significantly in pharmaceuti-
cal industry. Compounds containing 2-aminobenzothiazole
motif have attracted an interest because they demonstrate a
wide range of biological activities such as anti-tumor, anti-
inflammatory, analgesic, anti-microbial, anti-leishmanial,
anti-convulsant, anti-malarial and anti-HIV activities [32].
The preparation of 1-(benzothiazolylamino)phenylme-
thyl-2-naphthols is establish the three-component con-
densation reaction of an aldehyde, 2-aminobenzothiazole
and 2-naphthol. For this aim several catalysts including
LiCl [33], sodium dodecyl sulfate (SDS) [34], HPA [35],
NaHSO4.H2O [36], trichloroisocyanuric acid (TCCA) [37],
3-methyl-1-(4-sulfonic acid)propylimidazolium hydrogen
sulfate ([(CH2)3SO3HMIM][HSO4]) [38], have been used
to facilitate this reaction that suffers from prolonged reac-
tion times, low yields, difficulties in work-up, use of stoi-
chiometric amounts of the catalysts and often expensive
catalysts.
Aimed at the synthesis of the 1-(benzothiazolylamino)
phenylmethyl-2-naphthols derivatives in the presence of
[H-Suc]HSO4 as catalyst, at first and for optimization of
the reaction conditions, the reaction of 4-chloro benzalde-
hyde, 2-aminobenzothiazole and 2-naphthol was selected
as a model reaction in various conditions. For choosing the
reaction media, different solvents and solvent free condi-
tions were used by various amounts of the [H-Suc]HSO4
at several temperatures. The chosen optimized condition is
shown in Scheme 2. It should be noticed that any further
increase of the catalyst or temperature did not improve the
reaction time and yield. Also to illustrate the efficiency of
[H-Suc]HSO4 in these reactions, the model reaction was
carried out in the absence of the catalyst and the reaction
was not proceeded at all that indicated the catalyst is neces-
sary to produce the products.
After the optimization of the reaction conditions, we
explored the protocol with a variety of aromatic, aliphatic
and heterocyclic aldehydes under the optimal conditions.
The results are presented in Table 3. It was observed that
under similar conditions, a wide range of aromatic alde-
hydes containing electron-withdrawing as well as electron-
donating groups such as Cl, Br, CH3, OCH3, and NO2 in
1 3

J IRAN CHEM SOC
Table 3 Preparation of
1-(benzothiazolylamino)
phenylmethyl-2-naphthol
derivatives catalyzed by
[H-Suc]HSO4 under solvent-
free conditions
Melꢀng point (°C)
Time
(min)
Yield
Entry
A2
Aldehyde
Product
Reported
[References]
(%)a,b
Found
S
H
N
CHO
N
OH
6
7
93
89
201-203
188-190
202-204 [41]
Cl
S
H
CHO
Cl
N
N
B2
C2
D2
187-189 [41]
168-170 [41]
215-216 [41]
OH
OMe
S
H
CHO
OMe
N
N
5
7
90
90
170-172
218-220
OH
NO2
S
H
CHO
NO2
N
N
OH
Br
CHO
CHO
CHO
CHO
S
H
N
E2
F2
G2
5
7
7
93
92
92
203-205
184-186
190-192
203-205 [41]
184-186 [41]
191-194 [37]
N
OH
Br
OMe
NO2
CH3
S
H
N
N
OH
OMe
NO2
CH3
S
H
N
N
OH
S
H
N
H2
I2
7
5
93
92
187-188
208-210
189-191 [35]
209-210 [36]
N
OH
Cl
S
H
N
CHO
N
OH
Cl
1 3

J IRAN CHEM SOC
Br
Table 3 continued
S
H
N
CHO
CHO
CHO
N
J2
K2
L2
5
6
6
91
93
91
211-213
172-174
186-188
200-202 [41]
OH
Br
MeO
S
H
N
N
172-173 [40]
187-189 [41]
OH
MeO
O2N
O2N
S
H
N
N
OH
S
CHO
H
N
M2
6
6
94
90
197-199
194-196
197-199 [35]
N
OH
CHO
S
H
N
N2
195-197 [35]
N
OH
N
S
H
N
N
CHO
N
O2
P2
Q2
11
91
92
89
191-193
187-188
209-211
-
OH
N
S
H
N
CHO
CHO
N
N
N
7
189-190 [41]
210-212 [41]
OH
N
S
H
N
N
6
OH
HO
N
CHO
N
S
H
N
H
S
R2
7
87
214-216
215-217 [35]
N
OHC
OH
a
Isolated yields
b
Products were characterized by their physical constants and comparison with authentic samples (Refs. [32–34, 37,
38])
1 3

J IRAN CHEM SOC
Table 4 Comparison of
the results of the reaction
between 3-nitro benzaldehyde,
2-aminobenzothiazole and
2-naphthol catalyzed by
[H-Suc]HSO4 with those
obtained by some of the
reported catalysts
Entry Catalyst (amount)
Reaction conditions Time (min) Yield (%)a References
1
2
3
4
5
6
LiCl (710 mol %)
HPA (3 mol %)
90 °C/H2O
60 °C/neat
100 °C/neat
80 °C/neat
6 h
5.2 h
30
91
86
59
90
55
92
[23]
[25]
NaHSO4.H2O (10 mol %)
TCCA (10 mol %)
[26]
40
[27]
[(CH2)3SO3HMIM]HSO4 (10 mol %) 100 °C/neat
[H-Suc]HSO4 (15 mol %) 80 °C/neat
30
[28]
7
This work
a
Isolated yields
Scheme 3 Synthesis of 3,4,6,7-tetrahydro-3,3,6,6-tetramethyl-9-phenyl-2H-xanthene-1,8(5H,9H)-dione catalyzed by [H-Suc]HSO4
the ortho, meta, and para positions of the benzene ring
easily converted to the corresponding products in short
reaction times with high isolated yields (Table 3, entries
A2–L2). Polycyclic aromatic aldehydes such as 2-naphthal-
dehyde and fluorene-3-carbaldehyde were also provided the
desired products in very good yields (Table 3, entries M2–
N2). Pyridine-2-carbaldehyde, Pyridine-3-carbaldehyde
and pyridine-4-carbaldehyde as the heterocyclic aldehydes
were also used as substrates under the selected conditions
and the desired products were successfully obtained with
high yields (Table 3, entries O2–Q2).
conditions, the interaction of benzaldehyde (1 mmol) and
dimedone (2.1 mmol) was studied using [H-Suc]HSO4 as
the catalyst. These studies revealed that the best results can
be obtained under solvent-free conditions at 90 °C using
10 mg of [H-Suc]HSO4 (Scheme 3). After determination
of the optimized reaction conditions the same reaction was
performed on different types of aromatic aldehydes. The
obtained results are presented in Table 5. On the basis of
the obtained results, it can be concluded that the electron
property of the substituent, on the aromatic ring of the alde-
hydes has a little effect on the reaction times.
To show the efficiency of the present method, we have
compared our result obtained from the reaction of 3-nitro
benzaldehyde, 2-aminobenzothiazole and 2-naphthol cata-
lyzed by [H-Suc]HSO4 with the other results reported in
the literature (Table 4). It is clear that the present method is
superior in terms of the reaction times and yields.
In the next step we focused our attentions on the synthe-
sis of 3, 3, 6, 6-tetramethyl-1, 8-dioxo-octahydroxanthenes
as an important derivative of xanthenes that exhibit a broad
spectrum of applications in pharmacology, dyes, pH-sensi-
tive fluorescent materials for visualization of biomolecular
assemblies and in laser technologies [39]. These derivatives
of xanthenes can be prepared via the reaction of aromatic
aldehydes and dimedone in the presence of different types
of catalysts.
After determination of the optimized reaction condi-
tions the same reaction was performed on different types
of aromatic aldehydes. The obtained results are presented
in Table 5. On the basis of the obtained results, it can be
concluded that the electron property of the substituent, on
the aromatic ring of the aldehydes has a little effect on the
reaction times.
The advantages of [H-Suc]HSO4 over some of the other
catalysts for the synthesis of 3, 3, 6, 6-tetramethyl-1,8-di-
oxo-octahydroxanthene derivative of 4-chlorobenzaldehyde
are shown in Table 6. This Table clearly shows that the
other methods require harsh reaction conditions and longer
reaction times.
Furthermore, bis(indolyl)methanes (BIMs) derivatives
are the subject of considerable levels of interest because
of their numerous applications in pharmaceutical and bio-
logical research, where they show antitumor, antileishma-
nial, antihyperlipidemic, and anticancer [50] activities.
The preparation of BIMs via the reaction of aldehyde and
indole accelerated using different types of catalysts such
In this regards and to extension of the applications
of [H-Suc]HSO4 in the organic reactions, the synthesis
of 3, 3, 6, 6-tetramethyl-1,8-dioxo-octahydroxanthenes
(DOXs) in the presence of this reagent was investigated.
At the first step and for the optimization of the reaction
1 3

J IRAN CHEM SOC
Table 5 Solvent-free synthesis
of DOXs in the presence of
[H-Suc]HSO4
Melꢀng point (°C)
Time
(min)
Yield (%)
Entry
A3
Aldehyde
Product
a, b
Reported
[References]
Found
O
O
O
O
O
O
O
O
O
O
CHO
15
10
92
90
202-204
231-232
203-205 [43]
O
Cl
CHO
B3
230-232 [43]
Cl
O
Br
CHO
C3
15
97
240-241
240-241 [43]
Br
O
F
CHO
D3
10
20
94
89
223-224
243-244
223-224 [43]
241-243 [44]
F
O
OCH3
CHO
E3
O
MeO
O
NO2
CHO
O
F3
20
93
219-220
221-223 [44]
O2N
O
as, N-sulfonic acid poly(4-vinylpyridinium) chloride [51],
sulfonated rice husk ash (RHA-SO3H) [52], I2 [53], sul-
famic acid [54], benzyltriphenylphosphonium tribromide
[55], ceric ammonium nitrate [56], [hmim]HSO4 acidic
ionic liquid [57], ZrOCl2.8H2O and camphor sulphonic
acid [58], PEG-SO3H [59]. In spite of the potential utility
1 3

J IRAN CHEM SOC
Br
O
Table 5 continued
CHO
CHO
O
O
G3
H3
I3
20
15
20
20
97
96
90
95
192-193
166-167
163-165
227-228
190-192 [44]
167-168 [44]
162-164 [45]
Br
O
O
NO2
O
NO2
OCH3
O
CHO
O
O
OMe
O
O
Cl
O
CHO
Cl
J3
225-227 [46]
a
Isolated yield
b
Products were characterized by their physical constants and comparison with authentic samples (Refs. [40–43])
Table 6 Comparison of the results obtained from the reaction of 4-chlorobenzaldehyde and dimedone using various catalysts
Entry
Catalyst (amount)
Conditions
Time (min)
Yield (%)a
References
1
2
3
4
5
6
7
8
TBAHS (10 mol %)
1,4-dioxane/water, reflux
Solvent-free, 80 °C
Solvent-free, 80 °C
Solvent-free, 80 °C
Solvent-free, 110 °C.
CH3CN/DMF, reflux
Solvent-free, 100 °C
Solvent-free, 90 °C
180
150
210
270
300
480
160
10
92
93
95
75
94
74.3
95
90
[43]
[Hmim]TFA (100 mg)
[bmim]HSO4 (10 mg)
SiO2-R-SO3H (10 mol %)
Cellulose sulfonic acid (10 mol %)
TMSCl (50 mol %)
[44]
[45]
[46]
[47]
[48]
FeCl3-RiH (20 mol %)
[H-Suc]HSO4 (5 mol %)
[49]
This work
a
Isolated yields
Scheme 4 Preparation of
3-((1H-indol-3-yl)(phenyl)
methyl)-1H-indole in the pres-
ence of [H-Suc]HSO4
1 3

J IRAN CHEM SOC
Table 7 Preparation of
bis(indolyl)methanes in the
presence of [H-Suc]HSO4
Melꢀng point (°C)
Time
(min)
Yield
(%)a,b
Entry
A4
Aldehyde
Product
Reported
[References]
Found
CHO
5
5
90
92
127–128
76-78
128–130 [53]
HN
HN
HN
NH
NH
NH
Cl
CHO
B4
78-80 [53]
Cl
OMe
CHO
CHO
C4
30
93
187-188
185-186 [53]
MeO
O2N
HO
NO2
D4
E4
F4
10
25
10
91
87
90
220-223
121-123
94-96
222-224 [53]
122-124 [53]
93-94 [63]
HN
HN
HN
NH
OH
CHO
CHO
NH
CH3
H
3C
NH
NO2
CHO
G4
H4
20
30
95
90
220-222
77-79
221-224 [64]
78-80 [53]
NO2
HN
HN
NH
Cl
CHO
Cl
NH
of the above routes for the synthesis of BIMs, most of them
suffer from several disadvantages such as long times, poor
yields of the products, use of toxic solvents and catalysts,
use of expensive reagents and catalysts and harsh reaction
conditions. Therefore, it is important to find more conveni-
ent methods for the synthesis of these types of compounds.
After the above mentioned studies, investigation on the
effect of [H-Suc]HSO4 in the acceleration of the synthesis
of bis(indolyl)methane via the reaction of aldehydes with
indoles became the other part of our research program. This
study was also started by the optimization of the reaction
conditions using the reaction of benzaldehyde and indole in
1 3

J IRAN CHEM SOC
Table 7 continued
CHO
I4
7
97
210-212
212-214 [53]
HN
NH
CHO
J4
K4
L4
15
88
94
91
99-101
244-246
235-237
98-99 [63]
244-246 [53]
242-244 [53]
HN
NH
CHO
8
HN
NH
Cl
CHO
CHO
6
Cl
HN
HN
HN
NH
NH
NH
NO2
M4
N4
9
94
87
245-247
214-217
240-242 [65]
O2N
OH
CHO
18
237-239 [66]
HO
a
Isolated yield
b
Products were characterized by their physical constants and comparison with authentic samples (Refs. [50, 60–63])
Table 8 Comparison of the
results obtained from the
condensation of benzaldehyde
and indole using various
catalysts
Entry
Catalyst (amount)
Conditions
Time (min)
Yield (%)a
References
1
2
3
4
5
6
7
FeCl3-RiH (0.15 g)
I2 (20 mol %)
EtOH, 80 °C
Solvent-free,r.t.
r.t.
15
10
92
72
90
98
89
96
90
[49]
[53]
[bmim]BF4 (2 mL)
FeCl3·6H2O (20 mol %)
Mg(HSO4)2 (100 mol %)
NH4Cl (50 mol %)
270
90
[64]
Solvent-free,r.t.
EtOH, r.t.
[65]
360
120
5
[66]
Solvent-free, 90 °C
EtOH, 80 °C
[67]
[H-Suc]HSO4 (5 mol %)
This work
a
Isolated yield
1 3

J IRAN CHEM SOC
Scheme 5 Plausible mechanisms for the synthesis of prepare compounds in the presence of [H-Suc]HSO4
the presence of [H-Suc]HSO4. The obtained results showed
that the best results can be obtained at 80 °C in the presence
of 10 mg of [H-Suc]HSO4 under solvent-free conditions
(Scheme 4). After optimization of the reaction conditions
a series of aromatic aldehydes bearing electron with-
drawing or donating groups underwent the same reaction
with indole and 2-methyl indole, to afford the requested
bis(indolyl)methanes in good to excellent yields (Table 7).
Table 8 shows that this procedure is superior, compared
to the previously reported methods, with respect to the cat-
alyst, solvent and eco-friendliness.
reaction conditions. When the reactions completed, water was
added and the precipitated mixtures were filtered off for sepa-
ration of crude products. After washing the solid products
with water completely, the water containing ionic liquid (IL
is soluble in water) was evaporated under reduced pressure
and the ionic liquid was recovered and reused (Table 9). The
recovered catalyst was reused for five runs without any con-
siderable loss of its activity. FT-IR spectroscopy they showed
that reused ionic liquid was not consumed or degraded.
The suggested mechanism for the preparation of benzo[4,5]
imidazo[1,2-a]pyrimidine, 1-(benzothiazolylamino)-phenyl-
methyl-2-naphthols, xanthenedione and bis(indolyl)meth-
anes derivatives using [H-Suc]HSO4 as the catalyst is shown
in Scheme 5. On the basis of this mechanism and in the first
step, the catalyst activates the carbonyl group of the aldehyde,
which then reacts with dimedone, 2-naphthol or indole to
produce the adduct products.
Conclusions
In summary, we have developed an environmentally
friendly, high yielding and mild condition protocol for
the three-component synthesis of benzo[4,5]imidazo[1,2-
a]pyrimidine,
1-(benzothiazolylamino)-phenylmethyl-
2-naphthol, xanthenedione and bis(indolyl)methanes
derivatives using [H-Suc]HSO4 as the catalyst. These
methods offer several advantages, compared to those
reported in literature, i.e., (1) mild and highly efficient
catalyst activity, (2) cost efficiency of the catalyst, (3)
The reusability of the catalyst was also checked in four
types of the above mentioned reactions. For this purpose,
the model reactions were studied again under the optimized
1 3

J IRAN CHEM SOC
Table 9 Reusability of the
Run 1
Run 2
Run 3
Run 4
catalyst
Compounds
Time
(min)
Time
(min)
Time
(min)
Time
(min)
Yield
(%)a
Yield (%)a
Yield (%)a
Yield (%)a
O
18
92
16
92
16
91
17
92
N
N
N
H
S
H
N
N
OH
6
93
6
92
7
92
7
90
O
O
15
92
90
16
92
92
16
92
92
16
92
91
O
5
6
6
6
HN
NH
a
Isolated yield
9. M.F. Branã, M.J. Pérez De Vega, D. Perron, D. Conlon, P.F.
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1 3