Microwave promoted one-pot synthesis of some novel N-aryl isoquinoline derivatives

Article abstract of DOI:10.1002/jhet.1105

Homophthalic anhydride 1 reacts with different aromatic amines to produce N-substituted homophthalimides 2 under microwave irradiation. A rapid microwave-assisted chemical synthesis of condensed 4-substituted furo[2,3-c]isoquinoline-1,5(2H,4H)-diones 3 an

Full text of DOI:10.1002/jhet.1105

8
28
Microwave Promoted One-Pot Synthesis of Some Novel N-Aryl
Isoquinoline Derivatives
Vol 50
Freddy H. Havaldar,* Ganesh B. Mule, and Bhushan V. Dabholkar
Department of Chemistry, Nadkarni-Sacasa Research Laboratory, St. Xavier’s College, Mumbai 400001, India
*
E-mail: ganeshmule76@rediffmail.com
Received March 28, 2011
DOI 10.1002/jhet.1105
Published online 27 June 2013 in Wiley Online Library (wileyonlinelibrary.com).
Homophthalic anhydride 1 reacts with different aromatic amines to produce N-substituted homophthalimides
under microwave irradiation. A rapid microwave-assisted chemical synthesis of condensed 4-substituted furo
2
[
2,3-c]isoquinoline-1,5(2H,4H)-diones 3 and 5-substituted-2,3-dihydro-1H-pyrano[2,3-c]isoquinoline-1,6(5H)-
diones 4 involving the condensation of a variety of alkanoyl chlorides with 2-arylisoquinoline-1,3-diones 2 in
the presence of base and aprotic solvent is described for the first time. By contrast, the facile ring opening reac-
tion of furo[2,3-c]isoquinoline-1,5(2H,4H)-dione 3 with Vilsmeier–Haack reagent under microwave irradiation
yielded the a-b unsaturated carboxyaldehyde 5. This novel and clean one-pot methodology, which is character-
ized by very short reaction time and easy workup procedure, can be exploited to generate some novel condensed
isoquinoline derivatives.
J. Heterocyclic Chem., 50, 828 (2013).
INTRODUCTION
used for the construction of various types of compounds
such as isoquinolinones [1], isocoumarins [2], phthalazines
[3], and peri-hydroxy polycyclic aromatic compounds [4],
leading to alkaloids, antibiotics, and pharmacologically
important compounds. A great number of substituted isoqui-
noline-1,3(2H,4H)-dione derivatives have been published as
Homophthalic anhydrides 1 are very important intermedi-
ates in organic synthesis because they have two active sites
towards nucleophiles (C and C positions) and another ac-
1
3
tive site towards electrophiles (C position). They have been
4
©
2013 HeteroCorporation

June 2013
Microwave Promoted One-Pot Synthesis of Some Novel N-Aryl Isoquinoline Derivatives
829
HIV-1 reverse transcriptase (RT) polymerase, HIV-1 RT
ribonuclease H (RNase H) inhibitors and were reported as a
novel class of potent inhibitors that selectively inhibit CDK4
over CDK2 and CDK1 activities [5]. Furoisoquinolines [6]
and condensed pyranoisoquinolines [7] have a long and
distinguished history on their numerous biological and me-
dicinal applications. The synthesis and biological evaluation
homophthalic anhydride with different aromatic amines
under microwave irradiation (MWI). The purpose of this in-
vestigation was to provide novel derivatives of 4-substituted
furo[2,3-c]isoquinoline-1,5(2H,4H)-diones and 5-aryl-2,3-
dihydro-1H-pyrano[2,3-c]isoquinoline-1,6(5H)-diones in-
volving the condensation of variety of alkanoyl chlorides
with 2-arylisoquinoline-1,3-diones in the presence of
sodium hydride as a base with the use of tetrahydrofuran
as a solvent by conventional method as well as MWI, and
a comparison of both methods has been carried out. This
obtained product furo[2,3-c]isoquinoline-1,5(2H,4H)-diones
undergoes Vilsmeier–Haack formylation reactions under
MWI affords the a-b unsaturated carboxyaldehyde.
[8] of potentially bioactive condensed isoquinolines, appro-
priately functionalized, especially at the C position, have
3
attracted considerable attention of medicinal chemists world-
wide. Therefore, the synthesis of condensed isoquinolines
has been a very important process, subject to improve-
ment, from time to time. Prior art synthetic methodologies
involve annulation of the isoquinoline ring that resulted
in substituted carbocycles and heterocycles [9]. Of these,
the most popularly used synthetic methodology is the
In this paper, we present a full account of the aforemen-
tioned chemistry that includes complete experimental
details and a detailed characterization of all products.
“Principal Isoquinoline Synthesis”, which involves mainly
the cyclocondensation of homophthalic anhydride substrates
with reagents such as aldehydes, ketones [10], and imines
RESULTS AND DISCUSSION
[
11], giving rise to products of different heterocyclic
The isoquinolines were synthesized by a direct one-pot
process under thermal and microwave conditions. In the
thermal conditions, a mixture of homophthalic anhydride
and substituted aromatic amines was fused at 150–170 C
for 2–4 h yielded (65–78%) tetrahydroisoquinoline-1,3-diones
families. Alternatively, use of alkanoyl chlorides for
cyclocondensation with homophthalic anhydride substrate
is less exploited and is reported under basic conditions
ꢀ
[12]. The direct use of alkanoyl chlorides in these cyclocon-
densation is attractive as it offers more flexibility and
generates a variety of 4- and 5-substituents in the resultant
condensed isoquinolines. The direct use of the electrophilic
properties of alkanoyl chlorides in such synthesis, although
previously reported [13], has received only scant attention.
Benzoylation of 1 can be accomplished by treatment with
benzoyl chloride in the presence of base pyridine as a solvent
[
18] 2a–e (Scheme 1) in a one-pot process. In the microwave
conditions, the synthetic procedure involved homophthalic
anhydride with substituted aromatic amines in 1,2-dichloro-
benzene solution exposed under MWI at 150 C at (initial
power 200 W) for 20–25 min in a self-tuning single-mode
CEM Discover synthesizer (CEM Corporation, Matthews,
ꢀ
TM
NC). This procedure is highly comparable with others
reported in the literature [18], having the advantages such as
higher yields and shortened reaction times. The comparison
data of 2-substituted isoquinoline-1,3-diones 2a–e synthe-
sized under microwave as well as conventional conditions
are presented in Table 1.
We envisaged the construction of furan ring on 3,4 bond
of the isoquinoline-1,3(2H,4H)-diones 2 by utilizing the re-
activity of active methylene group at C-4 position, which is
highly reactive because it is located between two electron
withdrawing groups; on one side, there is a carbonyl and
on other side the benzene ring. This makes the protons
of the methylene group highly acidic; because of this, it
readily loses the proton in the presence of a suitable base
as a result of which carbanion is generated and the adjacent
enolizable carbonyl group is obtained, which is further
stabilized by resonance.
Compound 2 is efficiently acylated by reaction with an
alkanoyl chloride when conducted in pyridine. It appears
that pyridine undergoes a reaction with the acid chloride
to generate an intermediate N-acylpyridinium cation that
is more reactive than the starting acid chloride. As a part
of this work, we have found that prolonged heating of reac-
tion mixture 2 with an alkanoyl chloride in the presence of
[14]. Acetylation of 1 can be accomplished by treatment with
acetyl chloride in the presence of pyridine as a base and sol-
vent [15], but similar preparations of higher alkanoyl
derivatives have not been reported.
Reactions that are adaptable for high speed throughout
the synthesis have become an important component of
the modern medicinal chemist’s armory, as a great number
of compounds can be produced through such rapid parallel
synthetic programs [16]. Synthetic methods that enable the
rapid production of an array of heterocycles, useful for
the identification of new lead structures, are of critical
importance from the point of new drug discovery. More-
over, isoquinolines have been extensively studied as build-
ing blocks for a wide range of important biologically active
heterocyclic compounds such as furoisoquinolines and
pyranoisoquinolines and show a significant pharmacologi-
cal activity against a variety of molecular targets [17].
Therefore, these studies represent a simple introduction
of a plethora of substituent into the structures of these
substituted isoquinolines, which still constitutes a chal-
lenge for the scientific community.
In the present manuscript, we report on the synthesis
of N-substituted homophthalimides by the reaction of
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F. H. Havaldar, G. B. Mule, and B. V. Dabholkar
Vol 50
Scheme 1
Table 1
Physical data and comparison between conventional and microwave synthesis of 2-substituted isoquinoline-1,3-diones (2a–e).
R1
O
N
O
2
a-e
a
b
Conventional method
Microwave-assisted method
ꢀ
ꢀ
R
1
Yield (%)
mp ( C)
Time (h)
Yield (%)
mp ( C)
Time (min)
–
H
66
76
70
68
75
184–185 2a
154–156 2b
179–180 2c
171–172 2d
198–200 2e
2–3
2–3
2–4
2–3
2–4
78
80
80
75
80
184–185
154–156
178–180
173–174
198–200
20
15
25
20
18
–
–
–
–
CH
3
OCH
Cl
3
F
ꢀ
ꢀ
ꢀ
ꢀ
2
a Reported mp 184–185 C [18]. 2b Reported mp 154–156 C [18]. 2c Reported mp 179–180 C [18]. 2d Reported mp 171–172 C [18]. 2e Reported mp
ꢀ
1
98–200 C [18].
a
ꢀ
Heated at 150–170 C for 2–4 h.
Irradiation at 200 W for 15–25 min.
b
triethylamine or excess of pyridine is refluxed and
produced only traces of the desired alkanoyl derivative.
Unfortunately, this method is not suitable for the prepara-
tion of nucleophile-sensitive compounds such as 3a–e
basic condition in dry polar aprotic solvent tetrahydrofuran
at 0–5 C for 5–6 h and heated on a water bath for 1–2 h,
ꢀ
obtained with an overall yield of 65–80%. Similarly, reac-
tion of sodium derivative 2-substituted isoquinoline-1,3
(2H,4H)-diones 2a–e with 3-chloropropionyl chloride gave
the corresponding 5-aryl-2,3-dihydro-1H-pyrano[2,3-c]
isoquinoline-1,6(5H)-diones 4a–e. This particular reaction
(Scheme 2).
We started the experiments by using different alkanoyl
chlorides such as chloroacetyl chloride and 3-chloropro-
pionyl chloride. The conventional methods for the syn-
thesis of the target condensed 4-substituted furo[2,3-c]
isoquinoline-1,5(2H,4H)-diones 3a–e are through the
cyclization of appropriate 2-substituted isoquinoline-1,3
ꢀ
mixture is stirred continuously at 0–5 C for 7–8 h and then
heated on a water bath for 2–3 h, obtained with an overall
yield of 68–80%.
Interestingly, these same reactions under MWI at 150 W
were accomplished by the use of tetrahydrofuran as a
(2H,4H)-diones 2a–e with these alkanoyl chlorides under
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Microwave Promoted One-Pot Synthesis of Some Novel N-Aryl Isoquinoline Derivatives
831
Scheme 2
solvent and 60% sodium hydride as a base in very short
periods. The physical data for the 4-substituted furo[2,3-c]
isoquinoline-1,5(2H,4H)-diones 3a–e and 5-substituted
pyrano[2,3-c]isoquinolines-1,6(5H)-diones 4a–e synthe-
sized under MWI is presented in Table 2. The reaction time
varied depending upon the type of alkanoyl chlorides used.
The reactions with chloroacetyl chloride were completed in
NMR predicted value for the all-carbonyl tautomer is d
76.30 for all compounds 3a–e. It gave a positive DNP test,
and chlorine was found to be absent. This compound
contained furo[2,3-c]isoquinoline-1,5(2H,4H)-dione 3a,
and its mass spectrum (ESI mode) showed molecular ion
+
peak at 278 M .
1
H NMR spectra of 4a–e taken in anhydrous CDCl3
3
0–40 min to obtain the condensed 4-substituted furo[2,3-
(ÀOH) resonance was not observed. It shows the presence
of two triplet of two protons d 2.82 and d 4.58 attributed to
O–CH –CH –CO– of the pyranone moiety. It gave a pos-
c]isoquinoline-1,5(2H,4H)-diones 3a–e with isolated yields
ranging from 72% to 90%. Similarly, reactions with 3-
chloropropionyl chloride were completed in 35–45 min
and afforded the condensed 5-substituted-2,3-dihydro-1H-
pyrano[2,3-c]isoquinoline-1,6(5H)-diones 4a–e in 75–
2
2
itive DNP test, and chlorine was found to be absent. This
compound contained pyrano[2,3-c]isoquinoline-1,6(5H)-
dione 4a, and its mass spectrum (ESI mode) showed
+
9
0% yields (Scheme 2). Thus, in all the aforementioned
molecular ion peak at 292 M .
cases, there is considerable reduction in the reaction times,
when conventional heating is replaced by microwave-
assisted heating, that is, from 8–14 h to 30–45 min, respec-
tively. Considerable improvement in yields was also
observed.
In contrast to the facile nucleophile-mediated furan ring
opening reaction of 3, the ring system of 3 is stable under
electrophilic conditions. The methylene group in the furan
ring of compound 3 is sufficiently active. We therefore
decided to introduce Vilsmeier–Haack formylation at the
active methylene group. Vilsmeier–Haack reagent was pre-
pared by dropwise addition of phosphorus oxychloride to
an ice-cold solution of dimethylformamide. The reaction
1
Thus, the H NMR spectra of 3a–e taken in anhydrous
CDCl do not show the –OH resonance form. It showed
3
a singlet of two protons at d 4.70 attributed to –O–CH2–
CO– of the furanone moiety. The structure is such in furo
ꢀ
mixture was warmed on water bath at 80 C for 3–4 h and
then poured into ice-cold water, which resulted in the
13
[
2,3-c]isoquinoline-1,5(2H,4H)-dione agreement by
C
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F. H. Havaldar, G. B. Mule, and B. V. Dabholkar
Vol 50
Table 2
Physical data of other 4-substituted isoquinoline-1,5-diones (3a–e) and 5-substituted isoquinoline-1,6-diones (4a–e).
R1
R1
O
O
N
N
&
O
O
O
O
3
a-e
4
a-e
a
b
Conventional method
Microwave-assisted method
ꢀ
ꢀ
R
1
Yield (%)
mp ( C)
Time (h)
Yield (%)
mp ( C)
Time (min)
3
a
b
c
–H
–CH
–OCH
–Cl
–F
66
76
80
70
68
75
80
68
80
70
225–226
274–276
258–259
248–249
195–196
212–213
230–231
199–200
214–215
194–195
8–10
9–10
8–10
8–9
8–10
12–14
14–15
13–14
12–14
12–13
72
89
90
82
75
85
88
75
85
82
225–226
274–276
258–259
248–249
195–196
212–213
230–231
199–200
214–215
194–195
25
35
25
40
30
35
40
30
40
30
3
3
3
3
4
4
4
4
4
3
3
d
e
a
b
c
–H
–CH
3
–OCH
–Cl
–F
3
d
e
a
ꢀ
ꢀ
Stirred for 5–6 h at 0–5 C and then refluxed for 1–2 h (3a–e); stirred for 7–8 h at 0–5 C and refluxed for 2–3 h (4a–e).
b
Irradiation at 150 W for 30–40 min (3a–e); irradiation at 150 W for 35–45 min (4a–e).
formation of the desired compound 1-chloro-5-oxo-4-substi-
tuted-4,5-dihydrofuro[2,3-c]isoquinoline-2-carbaldehyde 5a–
e with overall yield (66–80%). Classically, this reaction
was completed in 3–4 h, so we thought that the same reac-
tion can be carried out under MWI to reduce the reaction
2-substituted isoquinoline-1,3-diones 2a–e in the presence
of sodium hydride as a base and variety of alkanoyl chlorides
in tetrahydrofuran as a solvent was performed by MWI
in a controlled temperature with simultaneous cooling
system in open vessel with the use of the CEM Discover
synthesizer. This novel synthesis involving chlorides as
building blocks, under MWI for these condensed 4-
substituted furoisoquinoline-1,5-diones and 5-substituted
pyranoisoquinoline-1,6-diones, requires only 20–45 min as
compared with the conventional heating protocols that
require 6–14h, thereby showing a significant acceleration
in reaction rates (Table 2). Varying the reaction condition
of furo[2,3-c]isoquinoline-1,5(2H,4H)-diones 3a–e with
Vilsmeier–Haack reagent exposed under MWI 10–15min
yielded the a-b unsaturated carboxyaldehyde 5a–e (Table 3).
Coupled with simple workup procedures and superior yields,
the methodology is eminently suitable for the generation of
diverse libraries.
time. Dimethylformamide was added dropwise to the ice-
ꢀ
cold solution of POCl at 0 C with constant stirring. To
3
this, 3 was added, and the reaction mixture was exposed
ꢀ
to MWI at 80 C (initial power 120 W) for 10–15 min in a
self-tuning single-mode CEM Discover synthesizer, which
resulted in the formation of the desired compound with
overall yield (70–90%) 5a–e. The comparison between
conventional and microwave methodologies has been
shown in Table 3. Although there was an increase in yield
compared with that in the classical method, there was
remarkable reduction in reaction time.
CONCLUSION
An experimental procedure to obtain N-substituted
homophthalimides under MWI from homophthalic
anhydride that reacts with different aromatic amines and
EXPERIMENTAL
Microwave reactions were conducted with the use of a CEM
Discover Synthesis unit (CEM Corp. Matthews, NC). The ma-
chine consists of a continuous focused microwave power delivery
system with operator selectable power output from 0 to 300 W
reactions were performed in open vessel and glass vessels
(capacity 10 mL) sealed with a septum. The pressure is controlled
1,2-dichlorobenzene as a solvent is described in Table 1.
A novel one-pot microwave-assisted synthesis of the
condensed 4-substituted furoisoquinoline-1,5-diones 3a–e
and 5-substituted pyranoisoquinoline 1,6-diones 4a–e from
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Microwave Promoted One-Pot Synthesis of Some Novel N-Aryl Isoquinoline Derivatives
833
Table 3
A comparison between conventional and microwave synthesis of 1-chloro-5-oxo-4-substituted-4,5-dihydrofuro[2,3-c]isoquinoline-2-carbaldehyde (5a–e).
R1
O
N
O
Cl
a-e
O
5
a
b
Conventional method
Microwave-assisted method
ꢀ
ꢀ
R
1
Yield (%)
mp ( C)
Time (h)
Yield (%)
mp ( C)
Time (min)
5
5
5
5
5
a
b
c
d
e
–H
–CH
–OCH
–Cl
66
76
80
70
68
250–252
245–247
268–270
255–257
260–262
3–4
2–3
2–4
2–3
2–4
70
89
90
82
75
250–252
245–247
268–270
255–257
260–262
10
15
12
15
12
3
3
–F
a
ꢀ
Heated at 80 C for 3–4 h.
b
Irradiation at 120 W for 10–15 min.
by a load cell connected to the vessel via a 14-gauge needle,
which penetrates just below the septum surface. The temperature
of the contents of the vessel was monitored with the use of a
calibrated IR temperature control mounted under the reaction
vessel. All experiments were performed with the use of a stirring
option whereby the contents of the vessel are stirred by means of
a rotating magnetic plate located below the floor of the micro-
wave cavity and a Teflon-coated magnetic stir bar in the vessel.
Tetrahydrofuran was distilled from benzophenone ketyl immedi-
ately before use. All reactions were conducted under a nitrogen
atmosphere. The melting points were determined in open capil-
lary on Veego (VMP-D) electronic apparatus and are uncorrected.
The IR spectra of synthesized compounds were recorded on
Perkin Elmer BX2 FT-IR Spectrophotometer in KBr and reported
acetic acid and yielded the appropriate condensed 2-
substituted isoquinoline-1,3(2H,4H)-diones 2a–e.
Microwave method (B). A mixture of the appropriate
aromatic amine substrates (0.001 mol), homophthalic
anhydride 1 (0.001 mol), and 5 mL 1,2 dichlorobenzene
ꢀ
was exposed to MWI at 150 C (initial power 200 W) for
2
0–25 min in a self-tuning single-mode CEM Discover
synthesizer. The progress of reaction was monitored by
(using TLC) after 5-min intervals. The resulting reaction
mixture was allowed to cool at room temperature
and poured into ice water. The resulting precipitated
solid was collected by filtration, washed with chilled
water, and dried. The crude product on recrystallization
from methanol yielded the condensed 2-substituted
isoquinoline-1,3(2H,4H)-diones 2a–e.
À1
1
in cm . H NMR spectra were measured on a Varian Mercury
YH-400 FT NMR spectrometer in CDCl , DMSO-d with chem-
3
6
ical shifts (d) given in ppm relative to TMS as internal standard.
Thin-layer chromatography was performed on precoated silica
plates (Merck Silica gel F 254) with the use of hexane–ethyl
acetate (4.5 mL : 0.5 mL) and chloroform–methanol (4.5 mL : 0.5
mL) as the solvent systems, and the spots were visualized by
exposure to iodine vapors or under UV light.
2
-Phenylisoquinoline-1,3(2H,4H)-dione (2a). mp 184–
ꢀ
À1
1
1
85 C; IR (KBr, v, cm ): –CO 1683, 1729; H NMR
(
CDCl ): d (ppm) 4.23 (s, 2H, –CH ), 7.21 (d, 2H, Ar–H),
3
2
7.35 (d, 1H, Ar–H), 7.43–7.49 (m, 4H, Ar–H), 7.61 (t, 1H,
Ar–H), 8.22 (d, 1H, Ar–H); MS (APCI, m/z): 238.21
+
[
M+ H] . Anal. Calcd for C H NO : C, 75.94; H, 4.67;
15 12 2
General procedure: Reaction of homophthalic anhydride 1
with aromatic amines
N, 5.90. Found: C, 75.92; H, 4.68; N, 5.91.
-p-Tolylisoquinoline-1,3(2H,4H)-dione (2b). This compound
was obtained according to the aforementioned general
2
Conventional method (A).
A mixture of homophthalic
anhydride 1 (0.01mol) and substituted aromatic amines
ꢀ
À1
procedure; mp 154–156 C; IR (KBr, v, cm ): –CO 1671,
1
(
1
0.01 mol) was fused in an oil bath for 2–4 h at 150–
70 C. A clear thick solution was obtained, which on
1
713; H NMR (CDCl ): d (ppm) 2.42 (s, 3H, –CH ), 4.22
3 3
ꢀ
(
s, 2H, –CH ), 7.09 (d, 2H, Ar–H), 7.30 (m, 3H, Ar–H),
2
cooling at room temperature gave the gray hard solid. This
solid was then refluxed with acetic acid (20 mL) in the
same flask for 20min. The resulted solution on cooling
gave crystallized solid. The product was recrystallized from
7
.46 (t, 1H, Ar–H), 7.62 (t,1H, Ar–H), 8.23 (d, 1H, Ar–H);
+
MS (APCI, m/z): 252.10 [M + H] . Anal. Calcd for
C H NO : C, 76.48; H, 5.21; N, 5.57. Found: C, 76.46;
16
14
2
H, 5.20; N, 5.59.
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F. H. Havaldar, G. B. Mule, and B. V. Dabholkar
Vol 50
ꢀ
2
-(4-Methoxyphenyl)isoquinoline-1,3(2H,4H)-dione (2c). This
exposed to MWI at 45 C (initial power 150 W) for
30–40 min in a self-tuning single-mode CEM Discover
synthesizer. After cooling, dry methanol (10 mL) was
added to quench the excess of sodium hydride. The
reaction mixture was then concentrated under reduced
pressure and filtered, and the product was washed with
water. Recrystallization from methanol yielded the appro-
priate condensed 4-substituted furo[2,3-c]isoquinoline-1,5
compound was obtained according to the aforementioned
general procedure; mp 179–180 C; IR (KBr, v, cm ): –CO
659, 1740; H NMR (CDCl ): d (ppm) 3.85 (s, 3H,
OCH ), 4.22 (s, 2H, –CH ), 7.02 (d, 2H, Ar–H),
.12 (d, 2H, Ar–H), 7.34 (d, 1H, Ar–H), 7.48 (t, 1H, Ar–H),
.64 (t, 1H, Ar–H), 8.24 (d, 1H, Ar–H); MS (APCI, m/z):
68.23 [M + H] . Anal. Calcd for C H NO : C, 71.90; H,
ꢀ
À1
1
1
–
7
7
2
4
3
3
2
+
16
14
3
(2H,4H)-diones 3a–e.
.90; N, 5.24. Found: C, 71.94; H, 4.92; N, 5.21.
-(4-Chlorophenyl)isoquinoline-1,3(2H,4H)-dione (2d). This
compound was obtained according to the aforementioned
2
4-Phenylfuro[2,3-c]isoquinoline-1,5(2H,4H)-dione (3a). mp
225–226 C; IR (KBr, v, cm ): –CO 1619, 1675; H NMR
(CDCl ): d (ppm) 4.75 (s, 2H, –CH ), 7.38 (d, 2H, Ar–H),
7.47 (t, 1H, Ar–H), 7.56–7.60 (m, 3H, Ar–H), 7.74 (d, 1H,
Ar–H), 8.31 (d, 1H, Ar–H), 8.41 (d, 1H, Ar–H); C NMR
(CDCl ): d (ppm) 76.45, 94.29, 121.40, 122.68, 126.23,
28.10, 129.0, 129.54, 129.71, 131.06, 132.50, 134.54,
162.46, 172.96, 190.98; MS (ESI, m/z): 278.39 [M + H] .
Anal. Calcd for C H NO : C, 73.64; H, 4.00; N, 5.05.
Found: C, 73.60; H, 3.98; N, 5.01.
-(4-Methylphenyl)furo[2,3-c]isoquinoline-1,5(2H,4H)-dione
3b). This compound was obtained according to the
aforementioned general procedure; mp 258–259 C; IR
KBr, v, cm ): –CO 1625, 1667; H NMR (CDCl ): d
ppm) 2.48 (s, 3H, –CH ), 4.76 (s, 2H, –CH ), 7.26 (d, 2H,
Ar–H), 7.39–7.47 (m, 3H, Ar–H), 7.75 (t, 1H, Ar–H), 8.32
d, 1H, Ar–H), 8.42 (d, 1H, Ar–H); C NMR (CDCl ): d
(ppm) 21.52, 94.55, 121.72, 122.99, 126.40, 128.04, 129.30,
ꢀ
À1
1
ꢀ
À1
general procedure; mp 173–175 C; IR (KBr, v, cm ): –CO
635, 1750; H NMR (CDCl ): d (ppm) 4.23 (s, 2H,
CH ), 7.15 (d, 2H, Ar–H), 7.32 (d, 1H, Ar–H), 7.46 (m,
H, Ar–H), 7.64 (t, 1H, Ar–H), 8.24 (d, 1H, Ar–H); MS
3
2
1
1
–
3
3
13
2
3
+
(
APCI, m/z): 272.20 [M + H] . Anal. Calcd for
1
+
C H ClNO : C, 66.31; H, 3.71; N, 5.16. Found: C, 66.32;
15
11
2
H, 3.74; N, 5.17.
-(4-Fluorophenyl)isoquinoline-1,3(2H,4H)-dione (2e). This
compound was obtained according to the aforementioned
17
11
3
2
4
ꢀ
À1
general procedure; mp 198–200 C; IR (KBr, v, cm ): –CO
675, 1730; H NMR (CDCl ): d (ppm) 4.23 (s, 2H, –CH ),
.18–7.20 (m, 4H, Ar–H), 7.36 (d, 1H, Ar–H), 7.49 (t, 1H,
Ar–H), 7.66 (t, 1H, Ar–H), 8.24 (d, 1H, Ar–H); MS (APCI,
m/z): 256.19 [M + H] . Anal. Calcd for C H FNO : C,
0.58; H, 3.95; N, 5.49. Found: C, 70.60; H, 3.97; N, 5.51.
General procedure: Reaction of 2-arylisoquinoline-1,3
2H,4H)-diones 2a–e with chloroacetyl chloride
Conventional method (A). A solution of 2-arylisoquinoline-
,3(2H,4H)-diones 2a–e (0.01 mol) in tetrahydrofuran
25 mL) is mixed with a suspension of 60% sodium
hydride (0.02mol) in tetrahydrofuran (20 mL), and the
mixture was stirred under nitrogen atmosphere for 1 h.
After being cooled at 0 C, chloroacetyl chloride (0.02mol)
was added dropwise for a period of 20 min with continuous
stirring for 5–6 h at 0 C. The reaction was then heated on
a water bath for 1–2 h. The completion of the reaction
mixture was checked by TLC. Further, dry methanol
10 mL) was added to quench the excess of sodium
hydride. The reaction mixture was then concentrated under
reduced pressure and filtered, and the product was washed
with water. The crude product on recrystallization from
methanol yielded the appropriate condensed 4-substituted
furo[2,3-c]isoquinoline-1,5(2H,4H)-diones 3a–e.
Microwave method (B). To a solution of 2-arylisoquinoline-
,3(2H,4H)-diones 2a–e (0.01mol) in tetrahydrofuran
(
1
1
7
ꢀ
3
2
1
1
(
3
(
3
2
+
15
11
2
13
7
(
3
(
1
1
30.08, 130.50, 131.34, 134.78, 140.23, 162.91, 173.38,
91.24; MS (ESI, m/z): 292.35 [M + H] . Anal. Calcd for
C H NO : C, 74.22; H, 4.50; N, 4.81. Found: C, 74.26; H,
+
1
(
18
13
3
4
.48; N, 4.84.
4
-(4-Methoxyphenyl)furo[2,3-c]isoquinoline-1,5(2H,4H)-dione
3c). This compound was obtained according to the
aforementioned general procedure; mp 274–275 C; IR
KBr, v, cm ): –CO 1623, 1656; H NMR (CDCl ): d
ppm) 3.86 (s, 3H, –OCH ), 4.87 (s, 2H, –CH ), 7.10
d, 2H, Ar–H), 7.41–7.48 (m, 3H, Ar–H), 7.81 (t, 1H,
Ar–H), 8.18 (d, 1H, Ar–H), 8.33 (d, 1H, Ar–H);
NMR (CDCl ): d (ppm) 55.87, 94.58, 115.10, 121.73,
23.02, 125.17, 126.50, 129.33, 129.41, 129.51, 131.38,
34.80, 160.60, 163.07, 173.57, 191.27; MS (ESI, m/z):
08.31 [M + H] . Anal. Calcd for C H NO : C, 70.34;
H, 4.26; N, 4.56. Found: C, 70.30; H, 4.30; N, 4.58.
-(4-Chlorophenyl)furo[2,3-c]isoquinoline-1,5(2H,4H)-dione
3d). This compound was obtained according to the
aforementioned general procedure; mp 248–249 C; IR
KBr, v, cm ): –CO 1627, 1675; H NMR (CDCl ): d
ppm) 4.75 (s, 2H, –CH ), 7.33 (m, 2H, Ar–H), 7.46 (t,
H, Ar–H), 7.55–7.57 (m, 2H, Ar–H), 7.77 (m, 1H, Ar–H),
.30 (d, 1H, Ar–H), 8.41 (d, 1H, Ar–H); C NMR
): d (ppm) 76.77, 94.72, 121.59, 123.09, 126.69,
129.35, 129.79, 130.10, 131.17, 131.31, 135.02, 136.11,
162.62, 172.96, 191.13; MS (ESI, m/z): 312.31 [M + H] .
H10ClNO : C, 65.50; H, 3.23; N,
3
11.37. Found: C, 65.55; H, 3.26; N, 11.40.
(
ꢀ
ꢀ
À1
1
(
ꢀ
3
(
3
2
(
1
3
C
(
3
1
1
3
+
18 13
4
4
(
1
(
ꢀ
25 mL), a suspension of 60% sodium hydride (0.02 mol) in
À1
1
(
(
tetrahydrofuran (20 mL) was charged in a round-bottom
glass flask containing a magnetic stirring bar and fitted
with a reflux condenser, which was attached to a water
aspirator. The flask was placed in a CEM Discover
Focused Microwave Synthesis System, which is designed
to house a round-bottom flask (50 mL). Reaction mixture
was stirred under nitrogen atmosphere, and chloroacetyl
chloride (0.02 mol) diluted in tetrahydrofuran (20 mL) was
3
2
1
8
13
(CDCl
3
+
Anal. Calcd for C17
ꢀ
added dropwise at 0 C. The reaction mixture was
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

June 2013
Microwave Promoted One-Pot Synthesis of Some Novel N-Aryl Isoquinoline Derivatives
835
4
-(4-Fluorophenyl)furo[2,3-c]isoquinoline-1,5(2H,4H)-dione
7
1
.51–7.56 (m, 3H, Ar–H), 7.75 (d, 1H, Ar–H), 8.32 (m,
(
3e). This compound was obtained according to the
aforementioned general procedure; mp 195–196 C; IR
KBr, v, cm ): –CO 1623, 1669; H NMR (CDCl ): d
ppm) 4.74 (s, 2H, –CH ), 7.24 (m, 2H, Ar–H), 7.29–7.46
m, 3H, Ar–H), 7.74 (d, 1H, Ar–H), 8.27 (d, 1H, Ar–H),
.40 (d, 1H, Ar–H); C NMR (CDCl ): d (ppm) 76.39,
4.26, 116.44, 121.14, 122.53, 126.18, 128.18, 128.86,
29.94, 130.03, 130.91, 134.52, 162.36, 164.05, 172.95,
13
H, Ar–H), 9.25 (d, 1H, Ar–H); C NMR (CDCl ): d
3
ꢀ
(ppm) 37.2, 68.6, 95.8, 122.1, 125.5, 125.9, 128.1, 128.4,
À1
1
(
(
(
8
9
1
1
3
129.1, 129.5, 134.2, 134.3, 135.0, 161.4, 162.4, 188.6; MS
(APCI, m/z): 292.16 [M + H] . Anal. Calcd for
C H NO : C, 74.22; H, 4.50; N, 4.81. Found: C, 74.25;
H, 4.48; N, 4.85.
+
2
18
13
3
1
3
3
5-(4-Methylphenyl)-2,3-dihydro-1H-pyrano[2,3-c]isoquinoline-
1,6(5H)-dione (4b). This compound was obtained according
to the aforementioned general procedure; mp 199.0–199.2 C;
IR (KBr, v, cm ): –CO 1651, 1674; H NMR (CDCl ): d
+
ꢀ
90.85; MS (ESI, m/z): 296.25 [M + H] . Anal. Calcd for
À1
1
C H FNO : C, 69.15; H, 3.41; N, 4.74. Found: C, 69.12;
1
7
10
3
3
H, 3.45; N, 4.70.
(ppm) 2.46 (s, 3H, –CH ), 2.80 (t, 2H, –CH ), 4.57 (t, 2H,
3 2
–
CH ), 7.15 (d, 2H, Ar–H), 7.34–7.42 (m, 3H, Ar–H), 7.70
Reaction of 2-arylisoquinoline-1,3(2H,4H)-diones with 3-
2
chloropropionyl chloride
Conventional method (A). A solution of 2-arylisoquinoline-
(q, 1H, Ar–H), 8.32 (d, 1H, Ar–H), 9.23 (d, 1H, Ar–H);
13
C NMR (CDCl ): d (ppm) 21.4, 37.2, 68.6, 95.8, 122.0,
3
1
,3(2H,4H)-diones (0.01mol) in tetrahydrofuran (25 mL)
125.4, 125.8, 128.1, 130.2, 132.3, 134.2, 139.1, 161.5,
162.4, 188.7; MS (ESI, m/z): 306.40 [M + H] . Anal. Calcd
+
was added to a suspension of sodium hydride (0.02 mol) in
tetrahydrofuran (20 mL), and the mixture was stirred under
for C19H15NO : C, 74.74; H, 4.95; N, 4.59. Found: C,
3
ꢀ
nitrogen atmosphere for 1 h. After being cooled at 0 C,
-chloropropionyl chloride (0.02 mol) was added dropwise
74.71; H, 4.92; N, 4.56.
5-(4-Methoxyphenyl)-2,3-dihydro-1H-pyrano[2,3-c]isoquinoline-
3
1
,6(5H)-dione (4c). This compound was obtained according
for a period of 20 min with continuous stirring for 7–8 h at
0
2
checked by TLC. Further, dry methanol (10 mL) was
added to quench the excess of sodium hydride. The reaction
mixture was then concentrated under reduced pressure and
filtered, and the product was washed with water. The crude
product on recrystallization from methanol yielded the
condensed 5-(4-substituted)-2,3-dihydro-1H-pyrano[2,3-c]
ꢀ
ꢀ
to the aforementioned general procedure; mp 230–231 C;
IR (KBr, v, cm ): –CO 1645, 1682; H NMR (CDCl ): d
C. The reaction was then heated on a water bath for
À1
1
3
–3 h. The completion of the reaction mixture was
(
ppm) 2.80 (t, 2H, –CH ), 3.85 (s, 3H, –OCH ), 4.57 (t, 2H,
2 3
–
CH ), 7.01 (t, 2H, Ar–H), 7.14 (q, 2H, Ar–H), 7.39 (m,
2
1
H, Ar–H), 7.69 (m, 1H, Ar–H), 8.31 (d, 1H, Ar–H), 9.23
13
(d, 1H, Ar–H); C NMR (CDCl ): d (ppm) 37.1, 55.5,
3
6
1
3
4
8.6, 95.8, 114.7, 122.0, 125.4, 125.8, 127.3, 128.1, 129.3,
34.1, 134.2, 159.8, 161.7, 162.5, 188.6; MS (ESI, m/z):
+
22.31 [M + H] . Anal. Calcd for C H NO : C, 71.02; H,
19
15
4
isoquinoline-1,6(5H)-diones 4a–e.
.71; N, 4.36. Found: C, 71.05; H, 4.68; N, 4.38.
Microwave method (B). To a solution of 2-arylisoquinoline-
5-(4-Chlorophenyl)-2,3-dihydro-1H-pyrano[2,3-c]isoquinoline-
1
,3(2H,4H)-diones (0.01 mol) in tetrahydrofuran (25 mL),
1,6(5H)-dione (4d). This compound was obtained according
ꢀ
to the aforementioned general procedure; mp 214.0–215 C;
a suspension of 60% sodium hydride (0.02mol) in
tetrahydrofuran (20 mL) was charged in a round-bottom
glass flask containing a magnetic stirring bar and fitted with
a reflux condenser, which was attached to a water aspirator.
The flask was placed in a CEM Discover Focused
Microwave Synthesis system, which is designed to house a
round-bottom flask (50 mL). Reaction mixture was stirred
under nitrogen atmosphere, in which 3-chloropropionyl
chloride (0.02 mol) diluted in tetrahydrofuran (20 mL) was
À1
1
IR (KBr, v, cm ): –CO 1650, 1674; H NMR (CDCl ): d
3
(ppm) 2.77 (t, 2H, –CH ), 4.63 (t, 2H, –CH ), 7.41 (t, 3H,
2
2
Ar–H), 7.59 (d, 2H, Ar–H), 7.77 (t, 1H, Ar–H), 8.20 (d,
13
1H, Ar–H), 9.20 (d, 1H, Ar–H); C NMR (CDCl ): d
3
(ppm) 37.33, 68.83, 96.11, 122.10, 125.72, 126.20, 128.29,
129.90, 129.98, 133.55, 134.23, 134.65, 135.27, 161.21,
+
162.33, 188.61; MS (ESI, m/z): 326.65 [M + H] . Anal.
Calcd for C H ClNO : C, 66.37; H, 3.71; N, 4.30.
18
12
3
ꢀ
added dropwise at 0 C. The reaction mixture was exposed
to MWI at 45 C (initial power 150 W) for 35–45min in a
Found: C, 66.38; H, 3.72; N, 4.28.
ꢀ
5-(4-Fluorophenyl)-2,3-dihydro-1H-pyrano[2,3-c]isoquinoline-
1,6(5H)-dione (4e). This compound was obtained according to
self-tuning single-mode CEM Discover synthesizer. After
cooling, dry methanol (10 mL) was added to quench the
excess of sodium hydride. Further, the reaction mixture
was concentrated under reduced pressure. The filtered
product washed with water recrystallization from methanol
yielded the condensed 5-(4-substituted)-2,3-dihydro-1H-
pyrano[2,3-c]isoquinoline-1,6(5H)-diones 4a–e.
ꢀ
the aforementioned general procedure; mp 194.3–194.6 C;
À1
1
IR (KBr, v, cm ): –CO 1661, 1685; H NMR (CDCl ): d
3
(ppm) 2.75 (t, 2H, –CH ), 4.52 (t, 2H, –CH ), 7.12–7.19
2
2
(m, 4H, Ar–H), 7.35 (t, 1H, Ar–H), 7.65 (t, 1H, Ar–H), 8.23
13
(m, 1H, Ar–H), 9.15 (d, 1H, Ar–H); C NMR (CDCl ) :d
3
(ppm) 36.8, 68.4, 95.6, 116.1, 116.3, 121.6, 125.2, 125.6,
5
-Phenyl-2,3-dihydro-1H-pyrano[2,3-c]isoquinoline-1,6(5H)-
127.7, 129.9, 130.0, 130.4, 133.8, 134.1 161.0, 162.0, 163.5,
188.2; MS (ESI, m/z): 310.18 [M + H] . Anal. Calcd for
ꢀ
À1
+
dione (4a). mp 212–213 C; IR (KBr, v, cm ): –CO 1647,
672; H NMR (CDCl ): d (ppm) 2.81 (t, 2H, –CH ), 4.56
1
1
C H FNO : C, 69.90; H, 3.91; N, 4.53. Found: C, 69.92;
3
2
18 12
3
(
t, 2H, –CH ), 7.27 (m, 2H, Ar–H), 7.43 (q, 1H, Ar–H),
H, 3.90; N, 4.50.
2
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

8
36
F. H. Havaldar, G. B. Mule, and B. V. Dabholkar
Vol 50
General procedure: Vilsmeier–Haack formylation of 4-
substituted furo[2,3-c]isoquinoline-1,5(2H,4H)-diones 3a–e
Conventional method (A). Dimethylformamide (0.01 mol)
obtained according to the aforementioned general
ꢀ
À1
procedure; mp 268–270 C; IR (KBr, v, cm ): –CHO
1
1
614, –CO 1660; H NMR (CDCl ): d (ppm) 3.8 (s, 3H, –
3
was added dropwise to the ice-cold solution of POCl3
OCH ), 7.07 (d, 2H, Ar–H), 7.30 (d, 2H, Ar–H), 7.6 (t,
3
ꢀ
(
0.03 mol) at 0 C with constant stirring. The complex thus
1
1
1
1
H, Ar–H), 7.82 (t, 1H, Ar–H), 8.3 (d, 2H, Ar–H), 9.70 (s,
formed was further stirred for 45 min, and 4-arylfuro[2,3-c]
isoquinoline-1,5(2H,4H)-diones 3a–e (0.01 mol) was added
to this. Then, the reaction mixture was heated on a water
13
H, –CHO); C NMR (CDCl ): d (ppm) 55.80, 100.42,
3
15.41, 122.51, 124.56, 125.16, 127.75, 129.29, 130.27,
30.42, 134.15, 142.5, 151.80, 160.64, 161.17, 173.80;
ꢀ
bath at 80 C for 4–5 h, cooled to room temperature, and
+
MS (APCI, m/z): 354.22 [M + H] . Anal. Calcd for
poured in an ice-water mixture (50–75 mL). The reaction
C H ClNO : C, 64.51; H, 3.42; N, 3.96. Found: C,
19
12
4
mixture was neutralized with saturated NaHCO solution.
3
6
4.53; H, 3.43; N, 3.94.
The separated solid was collected by filtration, washed with
water, dried, and recrystallized from appropriate solvent.
Microwave method (B). Dimethylformamide (0.01 mol)
was charged in a round-bottom glass flask containing a
magnetic stirring bar fitted with a reflux condenser, which
1
-Chloro-4-(4-chlorophenyl)-5-oxo-4,5-dihydrofuro[2,3-c]
isoquinoline-2-carbaldehyde (5d). This compound was
obtained according to the aforementioned general
ꢀ
À1
procedure; mp 255–257 C; IR (KBr, v, cm ): –CHO
1
1
660, –CO 1691; H NMR (CDCl ): d (ppm) 7.35 (d, 2H,
3
was attached to a water aspirator, and POCl (0.03 mol)
3
Ar–H), 7.6 (m, 3H, Ar–H), 7.81 (t, 1H, Ar–H), 8.42
d, 1H, Ar–H), 8.52 (d, 1H, Ar–H), 9.65 (s, 1H, –CHO);
ꢀ
was added dropwise to the ice-cold solution at 0 C with
(
1
3
constant stirring. The complex thus formed was further
stirred for 45 min, and 4-arylfuro[2,3-c]isoquinoline-1,5
2H,4H)-dione 3a–e (0.01 mol) was added to this. The
C NMR (CDCl ): d (ppm) 100.59, 122.43, 124.22,
3
1
1
3
27.96, 129.62, 130.27, 130.44, 130.49, 131.20, 134.42,
(
36.20, 142.72, 151.08, 161.27, 173.87; MS (APCI, m/z):
+
flask was placed in a CEM Discover Focused Microwave
58.19 [M + H] . Anal. Calcd for C H Cl NO : C, 60.36;
18
9
2
3
ꢀ
Synthesis System, exposed to MWI at 80 C (initial
H, 2.53; N, 3.91. Found: C, 60.37; H, 2.52; N, 3.92.
1-Chloro-4-(4-fluorophenyl)-5-oxo-4,5-dihydrofuro[2,3-c]
isoquinoline-2-carbaldehyde (5e). This compound was
power 150 W) for 10–15 min. After the reaction was
completed, the flask was removed from the MW cavity,
and the mixture was cooled to room temperature, poured
in an ice-water mixture (50–75 mL), and neutralized with
obtained according to the aforementioned general
ꢀ
À1
procedure; mp 260–262 C; IR (KBr, v, cm ): –CHO
1
a saturated NaHCO solution. The separated solid was
1650, –CO 1680; H NMR (CDCl
): d (ppm) 7.22 (m, 2H,
3
3
collected by filtration, washed with water, dried, and
recrystallized from appropriate solvent 5a–e.
Ar–H), 7.35 (m, 2H, Ar–H), 7.56 (t, 1H, Ar–H), 7.81 (s,
13
1H, Ar–H), 8.40 (m, 2H, Ar–H), 9.65 (s, 1H, –CHO);
C
1
-Chloro-4-(phenyl)-5-oxo-1,2,4,5-tetrahydrofuro[2,3-c]
NMR (CDCl ): d (ppm) 100.3, 116.7, 117.0, 122.0, 123.8,
3
isoquinoline-2-carbaldehyde (5a). This compound was obtained
according to the aforementioned general procedure; mp
50–252 C; IR (KBr, v, cm ): –CHO 1657, –CO 1687;
H NMR (CDCl ): d (ppm) 7.42 (d, 2H, Ar–H), 7.55–7.63
127.5, 128.2, 129.8, 129.9, 130.0, 134.0, 142.2, 150.9,
+
161.0, 161.6, 173.5; MS (APCI, m/z): 342.7 [M + H] .
ꢀ
À1
2
Anal. Calcd for C H ClFNO : C, 63.27; H, 2.65; N, 4.10.
18
9
3
1
3
Found: C, 63.28; H, 2.67; N, 4.09.
(
m, 4H, Ar–H), 7.84 (t, 1H, Ar–H), 8.47 (d, 2H, Ar–H), 9.71
13
Acknowledgments. We thank Dr Michael J. Collins for the very
helpful discussion and the CEM Corporation for providing the
Discover Microwave synthesizer.
(s, 1H, –CHO); C NMR (CDCl ): d (ppm) 100.3, 122.2,
3
1
1
24.1, 127.6, 128.0, 129.9, 130.1, 130.2, 132.6, 134, 142.4,
+
51.3, 161.4, 173.7; MS (APCI, m/z): 324.19 [M + H] .
Anal. Calcd for C H ClNO : C, 66.78; H, 3.11; N, 4.33.
Found: C, 66.79; H, 3.12; N, 4.34.
18
10
3
REFERENCES AND NOTES
1
-Chloro-4-(4-methylphenyl)-5-oxo-1,2,4,5-tetrahydrofuro[2,3-
[1] (a) Haimova, M. A.; Mollov, N. M.; Ivanova, S. C.; Dimitrova,
A. I.; Ognyanov, Tetrahedron 1977, 33, 331; (b) Cushman, M.; Gentry,
J.; Dekow, F. W. J. Org Chem 1977, 42, 1111; (c) Haimova,
M. A.; Ognyanov, V. I.; Mollov, N. M. Synthesis 1980, 845; (d) Cushman,
M.; Choong, T. C.; Valko J. T.; Koleck, M. P. J Org Chem 1980, 45, 5067;
(e) Coppola, G. M. J Heterocycl Chem 1981, 18, 767; (f) Cushman, M.;
Abbaspour, A.; Gupta, Y. P. J Am Chem Soc 1983, 105, 2873; (g) Cush-
man, M.; Mohan P. J Med Chem 1984, 27, 544.
c]isoquinoline-2-carbaldehyde (5b).
obtained according to the aforementioned general procedure;
mp 245–247 C; IR (KBr, v, cm ): –CHO 1627, –CO
657; H NMR (CDCl ): d (ppm) 2.48 (s, 3H, –CH ), 7.28
This compound was
ꢀ
À1
1
1
(
3 3
d, 2H, Ar–H), 7.39 (d, 2H, Ar–H), 7.57 (t, 1H, Ar–H), 7.82
(
t, 1H, Ar–H), 8.45 (m, 2H, Ar–H), 9.70 (s, 1H, –CHO);
[2] (a) Muller, E. Justus Liebigs Ann Chem 1931, 491, 251; (b)
Knabe, J.; Schaller, K. D. Arch Pharm (Weinheim Ger) 1967, 62, 300
13
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

June 2013
Microwave Promoted One-Pot Synthesis of Some Novel N-Aryl Isoquinoline Derivatives
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet