Divergent reaction pathways for one-pot, three-component synthesis of novel 4H-pyrano[3,2-h]quinolines under ultrasound irradiation

Article abstract of DOI:10.1016/j.ultsonch.2013.03.003

The present paper deal with the multi-component condensation of 8-hydroxy quinoline, aromatic aldehydes, and sulfone derivatives catalyzed by p-toluenesulfonic acid for the synthesis of a series of 4H-pyrano[3,2-h] quinoline derivatives in ethanol under u

Full text of DOI:10.1016/j.ultsonch.2013.03.003

Ultrasonics Sonochemistry 20 (2013) 1194–1202
Contents lists available at SciVerse ScienceDirect
Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultson
Divergent reaction pathways for one-pot, three-component synthesis of novel
4H-pyrano[3,2-h]quinolines under ultrasound irradiation
a,b
Abdullah S. Al-Bogami a, Tamer S. Saleh a,b, , Ehab M. Zayed
⇑
a Chemistry Department, Faculty of Science, King Abdulaziz University, North Jeddah, P.O. Box 80203, Jeddah 21589, Saudi Arabia
b Green Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
The present paper deal with the multi-component condensation of 8-hydroxy quinoline, aromatic
aldehydes, and sulfone derivatives catalyzed by p-toluenesulfonic acid for the synthesis of a series of
4H-pyrano[3,2-h]quinoline derivatives in ethanol under ultrasonic irradiations. We provide a series of
quinoline derivatives containing sulfone moiety interesting for biological screening tests. The reactions
were carried out under both conventional and ultrasonic irradiation conditions. In general, improvement
in rates and yields were observed when reactions were carried out under sonication compared with clas-
sical silent conditions. Also, also, sonochemical reaction give different reaction pathway other than silent
reaction. These remarkable effects appeared in sonicated reactions can be reasonably interpreted in terms
of acoustic cavitation phenomenon. Structures of the products were established on analytical and spec-
tral data.
Received 7 December 2012
Received in revised form 19 February 2013
Accepted 16 March 2013
Available online 28 March 2013
Keywords:
Ultrasound irradiation
p-Toluenesulfonic acid
Pyranoquinoline derivatives
b-Ketosulfone
Ó 2013 Elsevier B.V. All rights reserved.
Multicomponent reaction (MCR)
1. Introduction
Although a variety of methods are used to prepare the heterocyclic
compounds contain sulfone moiety, the synthetic access to poly-
Quinolines have amazing intrinsic pharmacological and biologi-
cal activities such as antimalaria, antiflammatory, antiasthmatic,
antibacterial and antihypersensitive activities [1]. In addition, quin-
olines are valuable synthons used for the preparation of
nanostructures and polymers that combine enhanced electronic,
optoelectronic or non-linear optical properties with excellent
mechanical properties [2]. In spite of their importance from
pharmacological, industrial and synthetic points of view, relatively
few methods for their synthesis of its derivatives have been
reported. Although compounds possessing this ring system have
wide applications as drugs and pharmaceuticals [3,4]. In addition
to, strategically positioned sulfone group in heterocyclic com-
pounds plays an important roles in medicine. Recently, heteroaryl
substituents have been attached to the sulfone, for example, pyrrol-
yl aryl sulfone (PASs) have been reported by Silvestri et al. [5] and
Artico et al. [6–8] as a new class of human immunodeficiency virus
type 1 (HIV-1) RT inhibitors acting at the non-nucleoside binding
site of this enzyme. Therefore, a considerable efforts have been di-
rected towards the preparation and synthetic manipulation of no-
vel heterocyclic compounds contain sulfone moiety [9–12].
substituted-polyfunctionalized derivatives remains a serious
challenge [13]. Multistep sequences are widespread in the litera-
ture, but even in these cases the preparation of some substitution
patterns and functional group combinations is particularly difficult.
Multi-component reactions (MCRs) play an important role in
combinatorial chemistry because of its ability to synthesize small
drug-like molecules with several degrees of structural diversity.
MCRs are defined as three or more different starting materials that
react to form a product, where most, if not all of the atoms are
incorporated in the final product. This reaction tool allows com-
pounds to be synthesized in a few steps and usually in a one-pot
operation [14]. Another typical benefit from these reactions is sim-
plified purification, because all of the reagents are incorporated
into the final product. In other words the recent introduction of
MCRs into field of synthesis has brought interesting features typi-
cal of the ideal reaction, such as atom- and step economy, conver-
gence, and exploratory power, together with new avenues in
connectivity, leading to the straightforward synthesis of previously
unobtainable scaffolds [15].
In the last few years the application of ultrasound in synthetic
organic chemistry became more and more interesting ‘‘Sonochem-
istry’’ is a new trend in organic chemistry, offering a versatile and
facile pathway for a large variety of syntheses. Thus, a large
number of organic reactions can be carried out under ultrasonic
irradiation in high yields, short reaction times and mild conditions
[16–23].
⇑
Corresponding author. Current address: Chemistry Department, Faculty of
Science, King Abdulaziz University-North Jeddah. Permanent address: Green
Chemistry Department, National Research Centre, Dokki, Cairo 12622, Egypt. Tel.:
+20 01001978724.
E-mail address: tamsaid@yahoo.com (T.S. Saleh).
1350-4177/$ - see front matter Ó 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.ultsonch.2013.03.003

A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
1195
Table 1
Motivated by the afore-mentioned findings, and in a continua-
Optimization of the conditions for the three component reaction.
tion of our interest, in synthesis of a wide range of heterocyclic
systems, for biological screening programme in our laboratory
[24–32], and as a part of our growing interest in sonochemistry
[33–37]. We describe here an environmentally benign protocol
for facile sonochemical synthesis of novel 4H-pyrano[3,2-h]quino-
line derivatives contains sulfone moiety through MCRs using
p-toluene sulfonic acid as a catalyst. The structure of the products
was established on different analytical and spectroscopic data.
Entry Catalyst
Ultrasonic irradiation
Silent condition
Time
Yield (%)
Time (h) Yield (%)
(min.)
(4a) (5a)
(4a) (5a)
1
2
3
4
None
120
45
45
68
0
8
0
85
82
80
12
6
8
0
91
88
85
0
Piperidine
Basic alumina
Acidic
Trace
Trace
Trace
45
14
8
alumina
p-TsOH
5
30
0
95
5
39
56
2. Result and discussion
A wide variety of catalysts were scanned in an attempt to
prepare 4H-pyrano[3,2-h]quinoline derivatives contains sulfone
moiety in a multicomponent one-pot fashion, in which the 8-
hydroxy quinoline (1), benzaldehyde (2a) were allowed to react
with 2-(phenylsulfonyl)- acetonitrile (3), in ethanol under ultra-
sonic irradiation at 70 °C as a model reaction. (Scheme 1, Table 1).
Some catalysts, namely, piperidine, basic alumina, acidic alu-
mina, and p-toluene sulphonic acid (p-TsOH) were selected. This
group of catalysts except piperidine has the advantage low impact
in the environment.
It is important to mention here that, although using of piperi-
dine as catalyst for the above mentioned reaction give good yield
under ultrasonic irradiation but it has some limitation in which
not applicable for all aldehyde derivatives (such as 4-flurobenzal-
dehyde) it give rapidly a product identified as 4-(piperidin-1-yl)
benzaldehyde as in Fig. 1 [39]. In addition to its hazardous effect
on environment.
It is noteworthy to mention that we optimize first the reaction
conditions for the formation of 4H-pyrano[3,2-h]quinoline deriva-
tive as in Table 2, to select the appropriate p-TsOH amounts neces-
sary to perform these three-components one pot reaction under
ultrasound irradiation, different amounts of p-TsOH (mol/mol)
ratios were tested.
To find the specific effect of ultrasound on this reaction, the
above mentioned reaction was carried out under the same condi-
tions in the absence of ultrasound irradiation (Table 1).
It is clear from results cited in Table 1 that, under silent method
even after 12 h, no reaction occurs in absence of a catalyst. In addi-
tion, only Knoevenagal product 4a was obtained after 2 h under
ultrasound irradiation in moderate yield in absence of a catalyst
(entry 1). in case of using piperidine, basic alumina and acidic alu-
mina as a catalyst only the Knoevenagel product 4a was obtained
with a trace amount of expected 4H-pyrano[3,2-h]quinoline deriv-
ative 5a, under silent condition but under ultrasonic irradiation the
Knoevenagel product 4a was obtained as minor product and the
major product is the expected 4H-pyrano[3,2-h]quinoline deriva-
tive 5a (Table 1, entries 3 and 4), and the desired product 5a
obtained only as one isolable product with best yield (95%) using
p-toluene sulphonic acid and good yield (85%) using piperidine
under ultrasonic irradiations, Obviously, the Knoevenagel product
obtained 4a is reluctant to undergo Michael addition reaction with
8-hydroxy quinoline (1) under silent condition may be need more
and more time. Therefore, it was found that the ultrasound irradia-
tions enable this reaction to occur which could not be carried out
under silent condition. This may be attributed to the fact that ultra-
sonic irradiation give the reactants sufficient energy to exceed en-
ergy barrier of the reaction and so 4H-pyrano[3,2-h]quinoline
derivative 5a formed. This sufficient energy can be reasonably
interpreted in terms of the physical phenomenon called acoustic
cavitation, that is, formation, growth, and collapse of micrometer-
sized bubbles when a pressure wave of enough intensity propagates
through a liquid. Acoustic cavitation is also accompanied by
mechanical effects [23]. Also, the intensity of cavitations increase
depending on type of solvent and frequency used in which we
use in the above mentioned reaction ethanol and Cavities are more
readily formed when using a solvent with a high vapor pressure low
viscosity, and low surface tension [38,18].
Table 2 represents the effect of p-TsOH on the % yield of com-
pound 5a From the results cited in Table 2, it is clear that 0.3 mo-
l equiv of p-TsOH furnishes the respective product in a quantitative
yield (Table 2, entry 3).
The isolated product 5a gave satisfactory elemental analyses
and spectroscopic data (IR, 1H NMR, 13C NMR, MS) consistent with
their assigned structure. Their IR spectra of the product showed
C@N absorption band at 1621 cmÀ1 and presence of two bands
due to sulfone group 1135, 1363 cmÀ1 in addition to two bands
due to amino group at 3313, 3422 cmÀ1. The mass spectra of the
isolated product 5a showed, a peak corresponding to the molecular
ion at 414, its 1H NMR spectrum revealed a D2O exchangeable sin-
glet signal at d 4.39 due to NH2 protons, singlet signal at d 5.10 due
to H-4pyran proton in addition to aromatic multiplet and H-8quinoline
proton at d 7.06–7.71, and two doublet signals at 8.30, 8.91 due to
H-7quinoline proton and H-9quinoline proton respectively.
To our knowledge, there are no established mechanisms for the
formation of 4H-pyrano[3,2-h]quinoline utilizing p-TsOH; a rea-
sonable possibility for The formation of 4H-pyrano[3,2-h]quinoline
derivative from MCRs [the reaction of 8-hydroxy quinoline,
aldehyde derivatives and 2-(phenylsulfonyl)-acetonitrile (3)] is
shown in Scheme 2.
The reaction presumably proceeds first as the Knoevenagel
reaction occurs in the presence of p-TsOH catalyst via an initial for-
mation of Knoevenagel product 4a by the condensation of proton-
ated aldehydes 2a and sulfone derivatives 3. Then, Micheal
addition of intermediate 4a with 8-hydroxy quinoline (1) followed
by cyclization and rearrangement provides desired product 5a.
6
7
8
O
S
5
O
S
CHO
9
Ph
CN
Ph
CN
4
N
+
3
1O
Catalyst
O
+
+
2
O
PhO2S
))) or Reflux
Ethanol
N
NH2
5a
OH
1
2a
3
4a
Scheme 1. Optimization of the conditions for the three component reaction.

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A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
Table 3
Synthesis of 4H-pyrano[3,2-h]quinoline derivatives 5b,c under ultrasonic irradiation.
Compound
Time (min.)
30
Yield (%)
92
Fig. 1. Structure of 4-(piperidin-1-yl)benzaldehyde.
Table 2
5b
Effect of p-TsOH on the % yield of compound 5a under ultrasonic irradiations.
Entry
p-TsOH ratio
Solvent
Yield 5a (%)
Time (min.)
1
2
3
4
5
0
EtOH
EtOH
EtOH
EtOH
EtOH
0
86
92
95
95
90
45
30
30
30
5b
0.1
0.2
0.3
0.4
45
95
5c
It is noteworthy to mention here that the Micheal addition step
of 4a which could not be fully consumed under adopted reaction
condition (p-TsOH) in classical silent conditions even after 18 h,
but consumed completely under ultrasonic irradiation to afford
only one isolable product in excellent yield 5a confirm the will
established theory of effect of ultrasonic on organic reactions spe-
cially the previously mentioned about the ability of ultrasonic irra-
5c
diation to produce the sufficient energy via the acoustic cavitation
phenomenon.
Scheme 2. Suggested mechanism for synthesis of 5a.
Scheme 3. p-TsOH catalysed synthesis of 4H-pyrano[3,2-h]quinoline derivatives 5b,c under ultrasonic irradiation.

A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
1197
The scope and generality of this protocol was tested by various
derivatives of aldehydes 2b,c as shown in the Scheme 3 under the
optimized reaction conditions and corresponding 4H-pyrano[3,2-
h]quinoline derivatives 5b,c were obtained in excellent yields
(Table 3). The reaction worked-up was very well with all products.
Again, ultrasonic irradiation showed beneficial effect on MCRs
reaction in terms of reaction time and percentage yields (92–95%).
The observed increase in rates of reaction can be attributed to
the fact that ultrasound plays a dual role in creating higher inter-
facial area as well as facilitating the process of interfacial transport.
[40]
Also, this mechanism was supported via reaction of equimolar
amount of 1,3-diphenyl-2-(phenylsulfonyl)prop-2-en-1-one (Kno-
evenagl product which obtained from reaction of benzaldehyde 2a
with 1-phenyl-2-(phenylsulfonyl)ethanone 6a [37]) and 8-hydroxy
quinoline (1) in ethanol in presence of p-TsOH under ultrasonic irra-
diation the corresponding pure 2,4-diphenyl-3-(phenylsulfonyl)-
4H-pyrano[3,2-h]quinoline derivatives (7a) has been obtained in a
87% yield (Scheme 5).
Also, the beneficial effect of ultrasonic irradiation on the syn-
thesis of 2,4-diaryl-3-(phenylsulfonyl)-4H-pyrano[3,2-h]quino-
lines in comparing the silent condition may be attributed to The
ultrasonic cavitation induced shear forces and the jets produced
near the surface of the vessel and the catalyst may activate the pas-
sive 8-hydroxy quinoline through sonolysis of the O–H bond. The
We extended our study to find out the reactivity of b-ketosulf-
one 6a–c towards 8-hydroxy quinoline (1) and aldehyde deriva-
tives 2a–c in MCRs fashion using p-TsOH as catalyst under both
ultrasonic irradiation and silent conditions.
reaction between the activated 8-hydroxy quinoline and the a,b-
The reaction of 8-hydroxy quinoline (1) with the aldehyde
derivatives 2a–c and 1-Aryl-2-(phenylsulfonyl)ethanone 6a–c in
ethanol as solvent under ultrasonic irradiation at 70 °C afforded
one product in each case (as evidenced by TLC) (Scheme 4). IR spec-
tra of the latter products revealed absorption bands of C@N func-
tion in the region 1590–1623 cmÀ1 and two absorption bands
due to sulfone group. Their 1H NMR spectra exhibited singlet signal
in region of 5.35–5.49 due to H-4Pyran in addition to aromatic mul-
tiplet and quinoline protons signals in region 6.99–8.92 The latter
spectroscopic data of the reaction products and their satisfactory
elemental analyses supported the structure 2,4-diaryl-3-(phenyl-
sulfonyl)-4H-pyrano[3,2-h]quinoline 7a–i.
unsaturated carbonyl intermediate 8 may facilitate the formation
of the corresponding intermediate 9 under sonic condition, and
this intermediate 9 followed by cyclization to give desired product
7a–i with the removal of a molecule of water as shown in Scheme
5.
Finally, the improvement induced by ultrasound can be attrib-
uted to the well established theory of ultrasonic irradiation in
which it differs from traditional energy sources (such as heat) in
duration, pressure, and energy per molecule. Because of the im-
mense temperatures and pressures and the extraordinary heating
rate generated by cavitation bubble collapse, ultrasound provides
an unusual mechanism [23,41,42] so reaction time decreases
clearly and high yield obtained.
In addition, according to sonochemical reactions classification
of Luche [43–45] and the recent fruitful highlights about forcing
and controlling chemical reactions with ultrasound [23], we have
both types false and true sonochemistry, in which some of the
above mentioned reactions are considered true sonochemistry
type which occur due to the effects derived directly from the ‘‘hot-
spots’’ of cavitational collapse energy, which cause in our case
what is called ‘‘sonochemical switching’’ means the products
obtained under conventional conditions are different from those
obtained under the influence of ultrasound [23,45] and the other
mentioned reactions considered false sonochemistry type in which
cavitation effect provides the mechanical energy for all subsequent
chemical reactions, including bond scission induced by viscous
frictional forces and same products produced under both silent
and ultrasonic conditions, and the other mentioned reactions.
The above reaction was also carried out under silent condition
to study the effect of ultrasound; the results of which are given
in Table 4.
It was observed that from the results cited in Table 4, the
reaction of b-ketosulfone 6a–c towards 8-hydroxy quinoline (1)
and aldehyde derivatives 2a–c in MCRs using p-TsOH as catalyst
under silent conditions have different behavior than the 2-
(phenylsulfonyl)-acetonitrile (3), in which only the isolable prod-
uct obtained is the desired product 7a–i as in Scheme 4, also it
was observed that the reaction time increased considerably and
yield of the products decreased under silent condition. Therefore,
ultrasound was found to have beneficial effect on the synthesis
of 2,4-diaryl-3-(phenylsulfonyl)-4H-pyrano[3,2-h]quinoline deriv-
atives in which decrease time of above reactions from 8 to 13 h
in conventional (silent) procedure to less than 1 h, also, a notice-
able improvement in yields of reactions under ultrasonic
irradiations.
The results obtained in Table 4 led us to assumption the plausible
mechanism for the formation of 2,4-diaryl-3-(phenylsulfonyl)-4H-
pyrano[3,2-h]quinoline derivatives 7a–i in the presence of p-TsOH
(Scheme 5). Taking compound 7a as example the reaction starts
with intermolecular condensation between benzaldehyde 2a and
3. Conclusion
A novel and efficient green protocol three-components conden-
sation reaction of 8-hydroxy quinoline, aldehydes and sulfone
derivative has been developed for the synthesis of 4H-pyrano
[3,2-h]quinoline derivatives contains sulfone moiety under ultra-
sonic irradiation via utilization of p-TsOH as a catalyst. The simple
one-pot nature of the reaction makes it an interesting alternative
to other multi-step approaches. In general, improvements in rates
and yield of reactions are observed when reactions were carried
1-phenyl-2-(phenylsulfonyl)ethanone 6a to form a,b-unsaturated
carbonyl intermediate 8 then via an initial Michael addition of the
the quinolinyl C-7 to the activated double bond in 8 to yield the
corresponding acyclic non-isolable intermediates 9 followed by
cyclization to afford the final product 7a (Scheme 5).
Scheme 4. p-TsOH catalysed synthesis of 4H-pyrano[3,2-h]quinoline derivatives 7a-i under ultrasonic irradiation.

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A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
Table 4
Synthesis of 2,4-diaryl-3-(phenylsulfonyl)-4H-pyrano[3,2-h]quinoline 7a–i.
Entry
Product
Ultrasonic Irradiation
Time (min.)
Silent condition
Time (h)
Yield (%)
91
Yield (%)
69
1
45
8
7a
2
45
93
8
70
7b
3
45
93
8
69
7c
4
45
90
10
62
7d
5
45
90
10
65
7e

A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
1199
Table 4 (continued)
Entry
Product
Ultrasonic Irradiation
Silent condition
Time (h)
Time (min.)
Yield (%)
91
Yield (%)
6
45
10
62
7f
7
45
90
10
62
7g
8
45
88
13
58
7h
9
45
85
12
58
7i
out under sonication compared with classical condition, due to the
mechanical shocks resulting from the cavitational collapse which
could provide what we have seen of chemical consequences. More-
over, the present work evidences an example to that sometimes
ultrasound irradiations enable some reactions to occur which
could not be carried out under silent condition.
by means of UV light at 254 and 360 nm. All melting points were
measured on a Stuart melting point apparatus and are uncorrected.
IR spectra were recorded in IR spectra were recorded in The Smart
iTR which is an ultra-high-performance, versatile Attenuated Total
Reflectance (ATR) sampling accessory on The Nicolet iS10 FT-IR
spectrometer. The NMR spectra were recorded on
a Varian
Mercury VX-300 NMR spectrometer. 1H spectra were run at
300 MHz and 13C spectra were run at 75.46 MHz in dimethyl
sulphoxide (DMSO-d6). Chemical shifts were related to that of
the solvent. Mass spectra were recorded on the Thermo Scientific
ITQ 1100™ mass spectrometer. Elemental analyses were carried
out on EuroVector instrument C, H, N, S analyzer EA3000 Series.
Sonication was performed by Techno-gaz sonicator (with a
frequency of 37 kHz and ultrasonic peak max 320 W).
2-(phenylsulfonyl)acetonitrile (3) [46] and 1-aryl-2-(phenylsul-
fonyl) ethanone 6a–c [47] were prepared according to the reported
literature.
4. Experimental
4.1. General
All organic solvents were purchased from commercial sources
and used as received or dried using standard procedures, unless
otherwise stated. All chemicals were purchased from Merck,
Aldrich or Acros and used without further purification, thin-layer
chromatography (TLC) was performed on precoated Merck 60
GF254 silica gel plates with a fluorescent indicator, and detection

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A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
Scheme 5. Suggested Mechanism for synthesis of 7a.
4.2. Typical procedure for synthesis of 4-aryl-3-(phenylsulfonyl)-4H-
pyrano[3,2-h]quinolin-2-amine 5a-c
put in ethanol under reflux for suitable time (cf. Table 1) until
the starting materials were no longer detectable by TLC. The prod-
ucts were obtained and purified as described above in sonicated
reaction.
4.2.1. Sonicated reactions
In an Erlenmeyer flask, a mixture of 8-hydroxy quinoline
(1 mmol) (1), aldehyde (1 mmol) (2a–c) and 2-(phenylsulfo-
nyl)acetonitrile (1 mmol) (3) in ethanol (20 ml) in the presence
of 0.3 (mol/mol) ratio p-TsOH as catalyst subjected to ultrasonic
irradiations for appropriate time (cf. Tables 1 and 3). All The reac-
tions were kept at 70–80 °C (the temperature inside reaction vessel
was 70–75 °C and the reaction flask was put in the mid of sonicator
bath to achieve effective cavitations). The sonochemical reactions
were continued until the starting materials were no longer detect-
able by TLC. The precipitate formed was collected by filtration then
washed with water (2 Â 20 ml), dried and purified by recrystalliza-
tion from chloroform.
Physical and spectral data of the compounds 4a and 5a–c are
listed below:
4.2.2.1. 3-Phenyl-2-(phenylsulfonyl)acrylonitrile (4a) [48]
. IR (KBr):
2194 (C„N), 1129, 1347 (SO2) cmÀ1 1H NMR (300 MHz, CDCl3)
;
d: 7.11–7.72 (m, 10H, ArH’s), 8.16 (s, 1H, @CH); 13C NMR
(75.46 MHz, CDCl3) d: 110.25, 118.43, 125.87, 126.81, 126.82,
127.00, 127.01, 127.58, 128.55, 128.56, 130.11, 132.79, 138.65,
148.72. MS (m/z): 269 (M+). (Found: C, 67.16; H, 4.02; N, 5.10; S,
11.83. C15H11NO2S requires C, 66.89; H, 4.12; N, 5.20; S, 11.90.)
4.2.2.2. 2-Amino-4-phenyl-3-(phenylsulfonyl)-4H-pyrano[3,2-h]quin-
The above reaction was studied also by using various catalysts
(i) in presence of 4 drops (0.5 ml) of piperidine, this process was
performed on the same scale described above and only one product
obtained identified as 5a in 85% yield (cf. Table 1) the product was
purified as described above. (ii) In presence of 0.5 g of basic alu-
mina or acidic alumina, also, these processes were performed on
the same scale described above and the progress of the reaction
was monitored by TLC, the same two products were formed in each
case (cf. Table 1) in different percent yield, After completion of the
reaction, the reaction mixture was filtered and the filtrate was con-
centrated in vacuo and the residual solid was taken in ethanol and
boiled to separate the first fraction [identified as compound 4a
(soluble in ethanol)] and the second fraction recrystallised from
chloroform to afford compound identified as 5a as pure product).
(iii) The reaction was also performed on the same scale described
above without any catalyst to afford only one isolable product
identified as 4a in 68% yield recrystalized from ethanol.
oline (5a). Mp = 251 °C; IR (KBr): 3422, 3313 (NH2), 1135, 1363
(SO2), 1621 (C@N) cmÀ1 1H NMR (300 MHz, DMSO-d6) d: 4.39 (s,
;
2H, NH2, D2O-exchangeable), 5.10 (s, 1H, pyran-H), 7.06–7.71 (m,
13H, ArH’s and H-8), 8.30 (d, J = 7.8 Hz, 1H, H-7), 8.91 (dd, J = 5.4
and 2.4 Hz, 1H, H-9); 13C NMR (75.46 MHz, DMSO-d6) d: 24.54,
81.01, 114.28, 115.12, 115.98, 121.13, 125.63, 126.54, 126.55,
127.45, 127.46, 128.00, 128.01, 129.12, 131.19, 133.42, 135.48,
140.00, 141.01, 146.85, 150.00, 153.12. MS (m/z): 414 (M+).
(Found: C, 69.84; H, 4.26; N, 6.60; S, 7.64. C24H18N2O3S requires
C, 69.55; H, 4.38; N, 6.67; S, 7.74.)
4.2.2.3. 2-Amino-4-(4-flurophenyl)-3-(phenylsulfonyl)-4H-pyrano[3,
2-h] quinoline (5b). Mp = 265 °C; IR (KBr): 3409, 3366 (NH2),
1143, 1283 (SO2), 1611 (CN) cmÀ1 1H NMR (300 MHz, DMSO-d6)
;
d: 4.22 (s, 2H, NH2, D2O-exchangeable), 5.06 (s, 1H, Pyran-H),
7.14–7.82 (m, 12H, ArH’s and H-8), 8.28 (d, J = 7.8 Hz, 1H, H-7),
8.89 (dd, J = 5.7 and 2.4 Hz, 1H, H-9); 13C NMR (75.46 MHz,
DMSO-d6) d: 23.99, 83.81, 111.47, 111.48, 116.91, 118.07, 120.00,
122.47, 124.51, 124.52, 126.25, 126.26, 128.98, 128.99, 129.46,
129.47, 130.12, 131.19, 135.48, 140.78, 145.45, 151.80, 154.12,
4.2.2. Silent reactions
These processes were performed on the same scale described
above for sonicated reaction. Here the reactant and catalyst were

A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
1201
158.17. MS (m/z): 432 (M+). (Found: C, 66.97; H, 3.84; N, 6.37; S,
7.32. C24H17FN2O3S requires C, 66.65; H, 3.96; N, 6.48; S, 7.41.)
ano[3,2-h]quinoline (7c). Mp = >300 °C; IR (KBr): 1599 (C = N),
1159, 1318 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-d6) d: 5.22 (s,
;
1H, pyran-H), 6.98–7.88 (m, 17H, ArH’s+H-8), 8.47 (d, J = 8.2 Hz,
1H, H-7), 8.79 (d, J = 4.2 Hz, 1H, H-9); 13C NMR (75.46 MHz,
DMSO-d6) d: 25.66, 98.25, 116.16, 116.98, 117.55, 123.78, 125.12,
126.88, 126.89, 127.87, 127.88, 127.98, 128.09, 128.10, 130.11,
130.61, 132.55, 136.00, 138.11, 141.58, 149.11, 150.02, 151.85.
MS (m/z): 554 (M+). (Found: C, 65.29; H, 3.57; N, 2.40; S, 5.68. C30-
H20BrNO3S requires C, 64.99; H, 3.64; N, 2.53; S, 5.78.)
4.2.2.4.
4H-pyrano[3,2-h quinoline (5c). Mp = 281–282 °C; IR (KBr): 3392,
3320 (NH2), 1128, 1318 (SO2), 1612 (C@N) cmÀ1 1H NMR
2-Amino-3-(phenylsulfonyl)4-(4-(trifluoromethyl)phenyl)-
;
(300 MHz, DMSO-d6) d: 4.19 (s, 2H, NH2, D2O-exchangeable), 5.26
(s, 1H, Pyran-H), 6.83–8.22 (m, 13H, ArH’s, H-8and H-7), 8.79
(dd, J = 5.4 and 2.4 Hz 1H, H-9); 13C NMR (75.46 MHz, DMSO-d6)
d: 23.05, 80.25, 115.22, 115.91, 118.31, 120.10, 121.62, 121.63,
125.63, 127.34, 127.35, 127.45, 127.97, 127.98, 128.01, 129.87,
131.17, 133.09, 136.14, 139.45, 142.88, 148.85, 151.04, 155.49.
MS (m/z): 482 (M+). (Found: C, 62.46; H, 3.48; N, 5.80; S, 658. C25-
H17F3N2O3S requires C, 62.23; H, 3.55; N, 5.81; S, 6.65.)
4.3.2.4.
ano[3,2-h]quinoline (7d). Mp = 290 °C; IR (KBr): 1591 (C@N),
1152, 1233 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-d6) d: 5.59 (s,
4-(4-Fluorophenyl)-2-phenyl-3-(phenylsulfonyl)-4H-pyr-
;
1H, pyran-H), 7.09–7.84 (m, 17H, ArH’s+H-8), 8.19 (d, J = 8.2 Hz,
1H, H-7), 8.65 (dd, J = 4.5 and 1.5 Hz, 1H, H-9); 13C NMR
(75.46 MHz, DMSO-d6) d: 24.94, 100.02, 116.04, 116.05, 119.54,
119.87, 120.08, 124.58, 125.87, 125.88, 126.14, 126.15, 126.98,
127.11, 127.12, 128.00, 128.01, 128.99, 130.32, 133.89, 134.54,
136.00, 139.11, 145.05, 150.29, 152.33, 159.07. MS (m/z): 493
(M+). (Found: C, 73.32; H, 3.96; N, 2.72; S, 6.42. C30H20FNO3S re-
quires C, 73.01; H, 4.08; N, 2.84; S, 6.50.)
4.3. Typical procedure for synthesis of 2,4-diaryl-3-(phenylsulfonyl)-
4H-pyrano[3,2-h]quinoline derivatives 7a-i
4.3.1. Sonicated reactions
In an Erlenmeyer flask, a mixture of 8-hydroxy quinoline
(1 mmol) (1), aldehyde (1 mmol) 2a–c 1-aryl-2-(phenylsulfo-
nyl)ethanone (1 mmol) 6a–c, and p-TsOH 0.3 (mol/mol) ratio as
catalyst were taken in ethanol (20 ml) and subjected to ultrasonic
irradiatios for appropriate time (cf. Table 4). All the reactions were
kept at 70–80 °C (the temperature inside reaction vessel was 70–
75 °C and the reaction flask was put in the mid of sonicator bath
to achieve effective cavitations). After completion of the reaction
as indicated by TLC (EtOAc/n-hexane, 1:2), the reaction mixture
was allowed to cool. The solvent was removed by evaporation
and the residue was washed with H2O (2 Â 20 ml). The solid prod-
ucts were purified by recrystallization from chloroform.
4.3.2.5. 4-(4-Fluorophenyl)-3-(phenylsulfonyl)-2-(4-methylphenyl)-
4H-pyrano[3,2-h]quinoline (7e). Mp = >300 °C; IR (KBr): 1606
(C@N), 1195, 1366 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-d6) d:
;
2.45 (s, 3H, CH3), 5.46 (s, 1H, pyran-H), 6.89–7.88 (m, 16H,
ArH’s+H-8), 8.52 (d, J = 8.2 Hz, 1H, H-7), 8.79 (dd, J = 4.5 and
1.8 Hz, 1H, H-9); 13C NMR (75.46 MHz, DMSO-d6) d: 21.26, 25.36,
99.63, 115.42, 115.43, 119.10, 119.54, 120.03, 125.36, 125.89,
125.98, 125.99, 126.80, 126.81, 127.00, 127.12, 127.13, 128.00,
128.01, 128.19, 128.20, 130.02, 131.89, 135.65, 138.11, 147.08,
149.14, 158.00. MS (m/z): 507 (M+). (Found: C, 73.58; H, 4.32; N,
2.68; S, 6.23. C31H22FNO3S requires C, 73.36; H, 4.37; N, 2.76; S,
6.32.)
4.3.2. Silent reactions
These processes were performed on the same scale described
above for sonicated reactions. Here the reactant and catalyst were
put in ethanol under reflux for suitable time (cf. Table 4) until the
starting materials were no longer detectable by TLC. The products
were obtained and purified as described above in sonicated
reaction.
4.3.2.6.
4H-pyrano[3,2-h]quinoline (7f). Mp = 292 °C; IR (KBr): 1606
(C@N), 1199, 1328 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-d6) d:
2-(4-Bromophenyl)-4-(4-fluorophenyl)-3-(phenylsulfonyl)-
;
5.09 (s, 1H, pyran-H), 6.95–7.83 (m, 16H, ArH’s+H-8), 8.25 (d, 1H,
J = 8.40 Hz, H-7), 8.71 (d, J = 4.2 Hz 1H, H-9); 13C NMR (75.46
MHz, DMSO-d6) d: 26.11, 98.94, 116.01, 116.02, 118.11, 118.59,
118.97, 125.47, 125.89, 125.90, 126.08, 126.97, 126.98, 127.00,
130.12, 130.13, 131.54, 132.33, 135.88, 135.96, 138.11, 148.32,
148.89, 150.01, 160.31. MS (m/z): 572 (M+). (Found: C, 63.22; H,
3.21; N, 2.36; S, 5.55. C30H19BrFNO3S requires C, 62.94; H, 3.35;
N, 2.45; S, 5.60.)
The synthesized compounds with their physical data are listed
below.
4.3.2.1. 2,4-Diphenyl-3-(phenylsulfonyl)-4H-pyrano[3,2-h]quinoline
(7a). Mp = 272 °C; IR (KBr): 1611 (C@N), 1158, 1325 (SO2) cmÀ1
;
1H NMR (300 MHz, DMSO-d6) d: 5.02 (s, 1H, pyran-H), 6.87–8.12
(m, 18H, ArH’s+H-8), 8.29 (d, J = 7.8 Hz, 1H, H-7), 8.42 (d,
J = 4.2 Hz, 1H, H-9); 13C NMR (75.46 MHz, DMSO-d6) d: 24.54,
97.23, 116.35, 116.89, 118.00, 124.56, 125.12, 126.32, 126.33,
127.11, 127.12, 127.58, 127.59, 128.00, 128.56, 128.99, 129.01,
129.58, 131.47, 132.55, 134.25, 139.00, 147.11, 147.19, 152.06.
MS (m/z): 475 (M+). (Found: C, 76.02; H, 4.34; N, 2.89; S, 6.66. C30-
H21NO3S requires C, 75.77; H, 4.45; N, 2.95; S, 6.74.)
4.3.2.7. 2-Phenyl-3-(phenylsulfonyl)-4-(4-(trifluoromethyl)phenyl)-
4H-pyrano[3,2-h]quinoline (7g). Mp = >300 °C; IR (KBr): 1621
(C@N), 1149, 1305 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-d6) d:
;
5.19 (s, 1H, pyran-H), 7.06–7.84 (m, 17H, ArH’s+H-8), 8.43 (d,
J = 7.8 Hz, 1H, H-7), 8.79 (dd, J = 4.5 and 1.8 Hz 1H, H-9); 13C
NMR (75.46 MHz, DMSO-d6) d: 25.98, 99.58, 118.16, 118.89,
123.55, 124.56, 124.57, 126.32, 126.98, 126.99, 127.55, 127.56,
128.00, 128.59, 128.60, 129.11, 129.12, 129.88, 129.89, 131.54,
132.60, 133.05, 135.69, 140.11, 143.12, 148.10, 148.98, 152.09.
MS (m/z): 543 (M+). (Found: C, 68.76; H, 3.60; N, 2.49; S, 5.84.
4.3.2.2.
ano[3,2-h] quinoline (7b). Mp = 284 °C; IR (KBr): 1606 (C@N),
1149, 1299 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-d6) d: 2.39 (s,
4-Phenyl-3-(phenylsulfonyl)-2-(4-methylphenyl)-4H-pyr-
;
3H, CH3), 5.19 (s, 1H, pyran-H), 6.92–7.95 (m, 17H, ArH’s+H-8),
8.41 (d, J = 7.8 Hz, 1H, H-7), 8.89 (d, J = 4.5 Hz 1H, H-9); 13C NMR
(75.46 MHz, DMSO-d6) d: 19.58, 24.98, 99.89, 115.23, 115.98,
116.25, 121.36, 124.58, 126.21, 126.22, 126.69, 127.00, 127.01,
127.58, 127.97, 128.45, 128.46, 128.98, 128.99, 130.14, 132.54,
133.47, 133.98, 140.11, 140.78, 147.58, 151.32. MS (m/z): 489
(M+). (Found: C, 76.34; H, 4.64; N, 2.76; S, 6.46. C31H23NO3S re-
quires C, 76.05; H, 4.74; N, 2.86; S, 6.55.)
C31H20F3NO3S requires C, 68.50; H, 3.71; N, 2.58; S, 5.90.)
4.3.2.8. 3-(Phenylsulfonyl)-2-(4-methylphenyl)-4-(4-(trifluoromethyl)
phenyl)-4H-pyrano[3,2-h]quinoline (7 h). Mp = >300 °C; IR (KBr):
1616 (C@N), 1159, 1298 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-
;
d6) d: 2.21 (s, 3H, CH3), 5.22 (s, 1H, pyran-H), 7.13–7.91 (m, 16H,
ArH’s+H-8), 8.19 (d, J = 8.2 Hz, 1H, H-7), 8.59 (dd, J = 4.5 and
1.5 Hz, 1H, H-9); 13C NMR (75.46 MHz, DMSO-d6) d: 22.12, 25.65,
98.29, 118.54, 118.78, 118.99, 123.45, 124.11, 124.12, 125.00,
4.3.2.3.
2-(4-Bromophenyl)-4-phenyl-3-(phenylsulfonyl)-4H-pyr-

1202
A.S. Al-Bogami et al. / Ultrasonics Sonochemistry 20 (2013) 1194–1202
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125.65, 125.66, 125.85, 126.01, 126.02, 127.02, 127.03, 127.41,
127.50, 127.51, 128.00, 128.01, 131.20, 131.92, 133.40, 135.66,
139.11, 140.01, 148.23, 148.85, 152.00. MS (m/z): 557 (M+).
(Found: C, 69.22; H, 3.84; N, 2.43; S, 5.68. C32H22F3NO3S requires
C, 68.93; H, 3.98; N, 2.51; S, 5.75.)
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4.3.2.9. 2-(4-Bromophenyl)-3-(phenylsulfonyl)-4-(4-(trifluoromethyl)
phenyl)-4H-pyrano[3,2-h]quinoline(7i). Mp = >300 °C; IR (KBr):
1614 (C@N), 1149, 1284 (SO2) cmÀ1 1H NMR (300 MHz, DMSO-
;
d6) d: 5.50 (s, 1H, pyran-H), 7.20–8.01 (m, 16H, ArH’s+H-8), 8.25
(d, J = 7.8 Hz, 1H, H-7), 8.63 (dd, J = 4.2 and 1.5 Hz, 1H, H-9); 13C
NMR (75.46 MHz, DMSO-d6) d: 25.95, 99.13, 119.15, 119.89,
120.11, 122.36, 123.15, 125.44, 126.45, 126.46, 127.11, 127.56,
127.57, 128.11, 128.12, 128.98, 129.14, 129.15, 130.00, 130.01,
131.64, 132.14, 136.21, 138.79, 141.08, 149.17, 149.82, 152.34.
MS (m/z): 622 (M+). (Found: C, 60.15; H, 2.96; N, 2.14; S, 5.05. C31-
H19BrF3NO3S requires C, 59.82; H, 3.08; N, 2.25; S, 5.15.)
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Orient. J. Chem. 28 (2012) 619.
This work was funded by the Deanship of Scientific Research
(DSR), King Abdulaziz University, Jeddah, under Grant No. (15-
965-D1432). The authors, therefore, acknowledge with thanks
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