Novel methods for the synthesis of 4-arylisoquinolinium perchlorates and 4-arylisoquinolin-1-ones

Article abstract of DOI:10.1080/00397910500189841

2-Benzylamino-1-phenyl-ethanones 1 were converted to the corresponding isoquinolinium perchlorates 2 in high yields using 70% HClO₄- FeCl₃ mixture as a cyclization and oxidation reagent. A mild and high yielding method for the oxidat

Full text of DOI:10.1080/00397910500189841

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Novel Methods for
the Synthesis of
4‐Arylisoquinolinium
Perchlorates and
4‐Arylisoquinolin‐1‐ones
Necdet Coşkun a & Yunus Tolga Kızılkuşak a
a Uludağ University, Department of Chemistry,
Görükle Bursa, Turkey
Version of record first published: 18 Aug 2006.
To cite this article: Necdet Coşkun & Yunus Tolga Kızılkuşak (2005): Novel Methods
for the Synthesis of 4‐Arylisoquinolinium Perchlorates and 4‐Arylisoquinolin‐1‐ones,
Synthetic Communications: An International Journal for Rapid Communication of
Synthetic Organic Chemistry, 35:18, 2435-2443
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Synthetic Communicationsw, 35: 2435–2443, 2005
Copyright # Taylor & Francis, Inc.
ISSN 0039-7911 print/1532-2432 online
DOI: 10.1080/00397910500189841
Novel Methods for the Synthesis of
4-Arylisoquinolinium Perchlorates and
4-Arylisoquinolin-1-ones
Necdet Cos¸kun and Yunus Tolga Kızılkus¸ak
˘
¨ ¨
Uludag University, Department of Chemistry, Gorukle Bursa, Turkey
Abstract: 2-Benzylamino-1-phenyl-ethanones 1 were converted to the corresponding
isoquinolinium perchlorates 2 in high yields using 70% HClO4-FeCl3 mixture as a
cyclization and oxidation reagent. A mild and high yielding method for the
oxidation of perchlorates 2 to isoquinolin-1-ones 3 involving the treatment of 2 with
KOH and K3[Fe(CN)6] in THF-H2O two-phase system at room temperature was
developed. Compounds 2a–g were shown to be disproportionate to 3 and the corres-
ponding 1,2-dihydroisoquinoline 4 in the presence of base, which in turn is oxidized
by K3[Fe(CN)6] to 2.
Keywords: 4-Aryldihydroisoquinolines, 4-arylisoquinolin-1-ones, 4-arylisoquino-
lines, disproportionation, isoquinolines, isoquinolinium perchlorates, isoquinolinones,
oxidation with Fe(III), oxidative cyclization
INTRODUCTION
Isoquinolines have been extensively studied because of their interesting
pharmacological properties. In particular, 4-aryltetrahydroisoquinolines are
of considerable interest because compounds possessing this unit display
biological activities of medicinal interest.[1a–e] Nomifensine[1f] and dichlofen-
sine[1g] exhibit central nervous activity and inhibit serotonin- and dopamine-
uptake mechanisms. The 4-aryltetrahydroisoquinoline unit also represents the
basic skeleton of the naturally occurring alkaloids latifine and cherylline,
which have been isolated from Amaryllidaceae plants.[2]
Received in the U.K. January 16, 2005
Address correspondence to Necdet Cos¸kun, Uludag University, Department of
¨ ¨
Chemistry, 16059 Gorukle Bursa, Turkey. E-mail: coskun@uludag.edu.tr
˘
2435

2436
N. Cos¸kun and Y. T. Kızılkus¸ak
The 4-aryl-1(2H)-isoquinolone skeleton has previously been constructed
starting from 3-aryl phtalides[3a] or trimethoxy-o-aroyldiphenylphosphoryl-
methylbenzamide, which can be cyclized by treatment with KHMDS at
2788C.[3b,c] The appropriate 4-aryl-1(2H)-isoquinolones were converted to
cherylline methyl ether.[3] The 1(2H)-isoquinolone skeleton constitutes the
framework of plant alkaloids.[4] Doryanine was prepared in poor yield by
subjecting the water-soluble 6,7-methylenedioxyisoquinoline methiodide to
alkaline ferricyanide oxidation under reflux conditions.[5] Some 4-aryl-1-
isoquinolinone derivatives have been reported to be potent and selective
phosphodiesterase-5 inhibitors.[6]
RESULTS AND DISCUSSION
Previously we have reported the oxidative cyclization of N-benzyl-N-alkylar-
ylacetamides with lead tetracetate in acetic acid/trifluoroacetic acid to give
4-aryl-1,4-dihydro-3(2H)-isoquinolinones.[7a,b] We have also reported high-
yielding methods for the synthesis of 4-aryl-tetrahydroisoquinolines based
on the cyclization of N-substituted benzylaminoacetophenones in the
presence of different acids.[8a–c] N,N-Dibenzylphenacylamines were
prepared in high yields by a one-pot cyclization procedure at room tempera-
ture to give 7,12-dihydro-l2-phenyl-5H-6,12-methanodibenz[c,f]azocines
(95% H2SO4 or 70% HClO4) in high yields.[9]
We herein report the first use of HClO4-FeCl3 system as a cyclization
catalyst and oxidation reagent in the conversion of aminoketones 1 to
4-arylisoquinolinium perchlorates 2. Compounds 2 were shown to dispropor-
tionate to 4-arylisoquinolin-1-ones 3 and dihydroisoquinolines 4 in the
presence of KOH in THF-H2O. The addition of K3[Fe(CN)]6 to the mixture
led to the formation of only 3 at room temperature for a short time in
excellent yields.
The aromatic aldehydes were treated with the corresponding alkyl or
benzylamines in the presence of NaBH4 to give the corresponding amino-
ketones 1 in high yields.[7,8] Compounds 1 were converted to their maleates
.
and were treated for 16 h with two equivalents of FeCl3 6H2O dissolved in
70% perchloric acid to give the corresponding isoquinolinium perchlorates,
which were easily isolated by pouring the mixture into ice water where the
compounds precipitated.[9] In the case of 1g where an electron-donating
group is present, the cyclization required a longer time (50 h), as expected.
1
The compounds have characteristic singlets around 9.60 in the H NMR
spectra taken in CDCl3, which was assigned to the C-1 hydrogen. The
singlet corresponding to C-3 hydrogen is at approximately 8 ppm. The 13C
NMR spectra are consistent with the proposed structure. Isoquinolinium
perchlorates 2 were treated with two equiv K3[Fe(CN)6] in THF-H2O
(2 : 1 mL) at room temperature for a short time in the presence of KOH
(31 equiv) to give in high yields the corresponding isoquinoline-1-ones 3

4-Arylisoquinolinium Perchlorates and 4-Arylisoquinolin-1-ones
2437
Scheme 1.
(see Scheme 1 and Table 1). The elemental analysis, 1H, 13C NMR, and mass
spectral data confirm the proposed structure. The compounds have character-
istic peaks at 1648 cm21 corresponding to the carbonyl group. The singlet in
1
the H NMR spectra of the compounds, corresponding to C-3 hydrogen,
appears approximately at 7.85 ppm. The signal in the 13C NMR spectra of
compounds 3, corresponding to C-1, appears at 161 ppm. All compounds
have molecular ion peak in their mass spectra.
The treatment of compounds 2 with KOH in the THF/water (2 : 1 mL),
two-phase system at room temperature led to the formation of a mixture of
3 and the corresponding 1,2-dihydroisoquinoline 4 (see Scheme 2). The
latter was identical in its TLC with the 1,2-dihydroisoquinoline obtained
from the treatment of corresponding 1 in methylene chloride for a short
time with conc. H2SO4.[7] Compounds 4 were also identical with the
product obtained by the reduction of 2 with NaBH4 in MeOH at room temp-
erature. The IR spectrum of the mixture obtained from the disproportionation
of 2e showed a second peak at 1650 cm21 in addition to the peak for the
Table 1. Synthesis of compounds 2 and 3
Yields
2
Mp
2
Yields Mp (8C)
Entry
R
R1
R2
R3
3
3
a
b
c
d
e
f
Me
Et
H
MeO
MeO
MeO
MeO
MeO
H
H
82(22)a 257–259.5
98
97
93
94
98
94
99
24
180–181
174–176
128–130
104–107
142–143
165–166
177–178c
146
H
H
H
H
H
H
83(12)
73(28)
84(32)
62(17)
80(27)
212–214
214–216
198–199
179–180b
169–170
226–227
180–182
n-Pr
n-Bu
Bn
H
H
H
Me
Me
Me
H
g
h
H
MeO
MeO MeO 85
85(20)
H
H
aThe yields in brackets are from the treatment of the aminoketones with HClO4
without FeCl3.
bLit.[9] mp 180.28C.
cLit.[3b] mp 178–1798C.

2438
N. Cos¸kun and Y. T. Kızılkus¸ak
Scheme 2.
carbonyl of 3e. The OH-stretching region of the spectrum did not contain any
peaks. Conversely, the treatment of this mixture with conc. H2SO4 led to the
formation of a mixture, the main components of which were the corresponding
1,2,3,4-tetrahydroisoquinoline and isoquinolin-1-one. Traces of the corre-
sponding 7,12-dihydro-l2-phenyl-5H-6,12-methanodibenz[c,f]azocine were
detected by means of TLC. This undoubtedly proves the second disproportio-
nation product to be the corresponding 1,2-dihydroisoquinoline. The addition
of two equiv of K3[Fe(CN)6] to the THF-H2O-KOH solution of the dispropor-
tionation products gave again compound 3. It is clear that at basic conditions
the pseudobase alkoxide, formed from the nucleophilic addition of the
hydroxide ion to C-1 and loss of hydrogen, transfers a hydride to the isoqui-
nolinium ion, which is in equilibrium with the pseudobase. Thus, formed
1,2-dihydroisoquinoline is oxidized by K3[Fe(CN)6] to the corresponding iso-
quinolinium cation. (The kinetics of the oxidation of isoquinolinium cations
by ferricyanide ion in the range pH 11–14 in 20% CH3CN–80% H2O is
discussed.[10] Although in this work a mechanism involving the formation
of pseudobase and its oxidation with the ferricyanide ion is discussed, we
have treated 2f at pH 14 in 20% CH3CN–80% H2O mixture and found that
the disproportionation process also occurs at these conditions.) However,
compound 2h does not undergo disproportionation, probably because of the
steric hindrance of the methoxy group at position 8 when treated with
KOH. To recover the unreacted isoquinolinium, the organic layer was
separated, the solvent evaporated, and the residue treated with 70% HClO4
and then poured onto ice water to give the starting 2h. However, the
treatment of starting material 2h with 2 equiv of K3[Fe(CN)6] according to
the developed method produced 3h and 6-benzoyl-2,3-dimethoxy-N-methyl-
benzamide both in 24% yields.
The mechanism for the oxidation of 2h probably involves the pseudobase
formation and its conversion to alkoxide A (see Scheme 3). The transfer of two

4-Arylisoquinolinium Perchlorates and 4-Arylisoquinolin-1-ones
2439
Scheme 3.
electrons from moiety A to 2 equiv of Fe(III) gives compound 3h. The
oxidation of in situ formed 1,2-dihydroisoquinolines to the corresponding 3
(Scheme 1) with FeCl3 in acidic medium and with K3[Fe(CN)6] in basic
conditions requires 2 equiv of the oxidant (Attempts to perform the reaction
with less than 2 equiv led to less satisfactory yields.)
The oxidation of compounds 4 at the mentioned conditions probably is
also a two-electron transfer process similar to those in Scheme 3.
EXPERIMENTAL
Melting points were taken on an Electrothermal Digital melting-point
apparatus. Infrared spectra were recorded on a Mattson 1000 FTIR. Proton
and 13C magnetic-resonance spectra were recorded on a Bruker Dpx
400-MHz spectrometer. Except 2a, which is taken in DMSO-d6, all spectra
were taken in deuteriochloroform. The mass spectra were recorded on a
Fisons VG Platform II instrument. Elemental analyses were performed on
a EuroEA 3000 CHNS analyser.
4-Arylisoquinolinium Perchlorates, General Procedure
Compound 1 maleate (2 mmol) was dissolved in a mixture of HClO4 (70%,
.
5 mL) and FeCl3 6H2O (4 mmol), and the mixture was stirred at room temp-
erature for 16 h. The mixture was slowly poured into ice water (20 mL) with
stirring. The amorphous solid formed was filtered and washed with water
(2 ꢀ 5 mL) and dried under vacuum. The compound was recrystallized
from ethanol. The crystals were collected by filtration and dried in air.
1
6,7-Dimethoxy-2-methyl-4-phenylisoquinolinium perchlorate 2a. H NMR
(400 MHz, DMSO-d6) d ppm 3.40 (3H, s), 4.03 (3H, s), 4.50 (3H, s), 7.65 (5H,
s), 7.70–8.13 (2H, m), 8.74 (1H, s), 10.02 (1H, s). Anal. calcd. for
C18H18ClNO6: C, 56.92; H, 4.78; N, 3.69. Found: C, 56.43; H, 4.74; N, 3.38.
2-Ethyl-6,7-dimethoxy-4-phenylisoquinolinium perchlorate 2b. 1H NMR
(400 MHz, CDCl3) d ppm 1.67 (3H, t, J ¼ 7.0), 3.87 (3H, s), 4.01 (3H, s),

2440
N. Cos¸kun and Y. T. Kızılkus¸ak
4.69 (2H, q, J ¼ 7.0), 7.17 (1H, s), 7.39–7.51 (5H, m), 7.88 (1H, s), 7.98 (1H,
s), 9.61 (1H, s). 13C NMR (100 MHz, CDCl3) d ppm 17.06; 57.09; 57.14;
57.46; 103.73; 109.09; 125.78; 129.87; 129.94; 130.27; 131.48; 133.74;
134.50; 137.80; 144.58; 153.58; 158.91. Anal. calcd. for C19H20ClNO6: C,
57.95; H, 5.12; N, 3.56. Found: C, 57.75; H, 5.24; N, 3.42.
1
6,7-Dimethoxy-4-phenyl-2-propylisoquinolinium perchlorate 2c. H NMR
(400 MHz, CDCl3) d ppm 0.95 (3H, t, J ¼ 7.3), 2.05 (2H, m, J ¼ 7.30), 3.87
(3H, s), 4.02 (3H, s), 4.59 (2H, t, J ¼ 7.3), 7.18 (1H, s), 7.44–7.55 (5H, m),
7.90 (1H, s), 7.97 (1H, s), 9.61 (1H, s). 13C NMR (100 MHz, CDCl3) d ppm
11.00; 25.21; 57.08; 57.45; 63.18; 103.70; 109.11; 125.64; 129.87; 129.92;
130.27; 131.72; 133.68; 134.44; 137.61; 144.89; 153.58; 158.93. Anal.
calcd. for C20H22ClNO6: C, 58.90; H, 5.44; N, 3.43. Found: C, 58.72; H,
5.50; N, 3.32.
2-Butyl-6,7-dimethoxy-4-phenylisoquinolinium perchlorate 2d. 1H NMR
(400 MHz, CDCl3) d ppm 0.89 (3H, t, J ¼ 7.3), 1.36 (2H, m, J ¼ 7.3), 1.99
(2H, m, J ¼ 7.3), 3.87 (3H, s), 4.02 (3H, s), 4.62 (2H, t, J ¼ 7.30), 7.17
(1H, s), 7.48–7.55 (5H, m), 7.90 (1H, s), 7.95 (1H, s), 9.63 (1H, s). 13C
NMR (100 MHz, CDCl3) d ppm 13.82; 19.87; 33.79; 57.08; 57.47; 61.69;
103.68; 109.15; 125.67; 129.88; 129.92; 130.28; 131.63; 133.70; 134.40;
137.61; 144.97; 153.58; 158.92. Anal. calcd. for C21H24ClNO6: C, 59.79;
H, 5.73; N, 3.32. Found: C, 59.66; H, 5.72; N, 3.12.
2-Benzyl-6,7-dimethoxy-4-phenylisoquinolinium perchlorate 2e. The
compound was identical with those reported previously.[9] Anal. calcd. for
C24H22ClNO6: C, 63.23; H, 4.86; N, 3.07. Found: C, 63.47; H, 4.86; N, 3.00.
7-Methoxy-2-methyl-4-phenylisoquinolinium perchlorate 2f. 1H NMR
(400 MHz, CDCl3) d ppm 4.00 (3H, s), 4.56 (3H, s), 6.71–8.00 (8H, m),
8.06 (1H, s), 9.67 (1H, s). Anal. calcd. for C17H16ClNO5: C, 58.38; H, 4.61;
N, 4.00. Found: C, 58.08; H, 4.54; N, 3.89.
6,7-Dimethoxy-4-(4-methoxy-phenyl)-2-methylisoquinolinium perchlorate
2g. 1H NMR (400 MHz, CDCl3) d ppm 3.85 (3H, s), 3.89 (3H, s), 4.03 (3H, s),
4.45 (3H, s), 7.05 (2H, d, J ¼ 8.6), 7.40 (2H, d, J ¼ 8.6), 7.8 (1H, s), 7.85 (1H,
s), 9.58 (1H, s). 13C NMR (100 MHz, CDCl3) d ppm 48.25; 55.89; 57.07;
57.47; 103.83; 105.61; 111.95; 115.35; 125.64; 131.17; 132.30; 134.53;
137.54; 145.43; 153.65; 158.91; 161.25. Anal. calcd. for C19H20ClNO7: C,
55.68; H, 4.92; N, 3.42. Found: C, 55.50; H, 4.71; N, 3.10.
1
7,8-Dimethoxy-2-methyl-4-phenylisoquinolinium perchlorate 2h. H NMR
(400 MHz, CDCl3) d ppm 4.05 (3H, s), 4.23 (3H, s), 4.61 (3H, s), 7.54 (5H, s),
7.74–7.86 (2H, m), 8.05 (1H, s), 9.67 (1H, s). 13C NMR (100 MHz, CDCl3) d

4-Arylisoquinolinium Perchlorates and 4-Arylisoquinolin-1-ones
2441
ppm 51.05; 59.02; 64.56; 123.44; 126.41; 127.77; 131.19; 131.84; 132.59;
133.72; 134.85; 141.57; 146.60; 147.72; 153.14. Anal. calcd. for
C18H18ClNO6: C, 56.92; H, 4.78; N, 3.69. Found: C, 56.43; H, 4.74; N, 3.38.
4-Aryl-2H-isoquinolin-1-ones 4, General Procedure
Compound 2 (0.2 mmol) was suspended in a mixture of THF/H2O (6 : 3 mL),
and KOH (6.2 mmol) was added to the mixture. K3[Fe(CN)6] (0.4 mmol) was
added and the mixture stirred at room temperature for 1 h. The organic phase
was separated and the solvent evaporated. The residue was extracted with
chloroform (2 ꢀ 10 mL) and the solvent evaporated. The residue was recrys-
tallized from MeOH.
6,7-Dimethoxy-2-methyl-4-phenyl-2H-isoquinolin-1-one 3a. FTIR (KBr)
1
nC55O 1648 cm21; H NMR (400 MHz, CDCl3) d ppm 3.66 (3H, s), 3.82
(3H, s), 4.04 (3H, s), 6.93 (1H, s), 6.98 (1H, s), 7.41–7.51 (5H, m), 7.93
(1H, s). MS m/z 295 (Mþ). Anal. calcd. for C18H17NO3 (295.34): C, 73.20;
H, 5.80; N, 4.74. Found: C, 73.28; H, 5.64; N, 4.49.
2-Ethyl-6,7-dimethoxy-4-phenyl-2H-isoquinolin-1-one 3b. FTIR (KBr)
1
nC55O 1648 cm21; H NMR (400 MHz, CDCl3) d ppm 1.34 (3H, t, J ¼ 7.2),
3.74 (3H, s), 3.95 (3H, s), 4.03 (2H, q, J ¼ 7.2), 6.85 (1H, s), 6.90 (1H, s),
7.32–7.45 (5H, m), 7.85 (1H, s). 13C NMR (100 MHz, CDCl3) d ppm
15.10; 44.81; 56.28; 56.55; 105.32; 108.49; 119.72; 120.58; 128.01; 129.10;
129.41; 130.13; 131.96; 137.24; 149.54; 153.46; 161.15. MS m/z 309 (Mþ).
Anal. calcd. for C19H19NO3 (309.37): C, 73.77; H, 6.19; N, 4.53. Found: C,
73.72; H, 6.40; N, 4.51.
6,7-Dimethoxy-4-phenyl-2-propyl-2H-isoquinolin-1-one 3c. FTIR (KBr)
1
nC55O 1648 cm21; H NMR (400 MHz, CDCl3) d ppm 0.93 (3H, t, J ¼ 7.3),
1.77 (2H, m, J ¼ 7.3), 3.73 (3H, s), 3.92 (2H, t, J ¼ 7.3), 3.95 (3H, s), 6.85
(1H, s), 6.88 (1H, s), 7.32-7.45 (5H, m), 7.85 (1H, s). 13C NMR (100 MHz,
CDCl3) d ppm 11.67; 23.08; 51.41; 56.29; 56.56; 105.34; 108.60; 119.36;
120.60; 128.01; 129.12; 130.03; 130.16; 131.95; 137.27; 149.55; 153.50;
161.40. MS m/z 323 (Mþ). Anal. calcd. for C20H21NO3 (323.40): C, 74.28;
H, 6.55; N, 4.33. Found: C, 74.33; H, 6.69; N, 4.43.
2-Butyl-6,7-dimethoxy-4-phenyl-2H-isoquinolin-1-one 3d. FTIR (KBr)
1
nC55O 1648 cm21; H NMR (400 MHz, CDCl3) d ppm 0.89 (3H, t, J ¼ 7.3),
1.34 (2H, m, J ¼ 7.4), 1.73 (2H, m, J ¼ 7.4), 3.73 (3H, s), 3.95 (3H, s),
3.98 (2H, t, J ¼ 7.4), 6.86 (1H, s), 6.88 (1H, s), 7.32–7.45 (5H, m), 7.85
(1H, s). 13C NMR (100 MHz, CDCl3) d ppm 14.17; 20.45; 31.94; 49.65;
56.30; 56.55; 105.34; 108.60; 119.43; 120.60; 128.02; 129.12; 130.00;
130.16; 131.94; 137.26; 149.55; 153.50; 161.40. MS m/z 337 (Mþ). Anal.

2442
N. Cos¸kun and Y. T. Kızılkus¸ak
calcd. for C21H23NO3 (337.42): C, 74.75; H, 6.87; N, 4.15. Found: C, 74.62;
H, 6.96; N, 4.01.
2-Benzyl-6,7-dimethoxy-4-phenyl-2H-isoquinolin-1-one 3e. FTIR (KBr)
nC55O 1648 cm21 c1H NMR (400 MHz, CDCl3) d ppm 3.73 (3H, s), 3.95
;
(3H, s), 5.19 (2H, s), 6.84 (1H, s), 6.92 (1H, s), 7.18–7.39 (5H, m), 7.88
(1H, s). 13C NMR (100 MHz, CDCl3) d ppm 52.38; 56.33; 56.60; 105.52;
108.85; 119.94; 120.56; 128.08; 128.20; 128.42; 129.11; 129.20; 129.55;
130.17; 132.05; 137.07; 137.44; 149.68; 153.66; 161.55. MS m/z 371 (Mþ).
Anal. calcd. for C24H21NO3 (371.44): C, 77.61; H, 5.70; N, 3.77. Found: C,
77.65; H, 5.79; N, 3.82.
7-Methoxy-2-methyl-4-phenyl-2H-isoquinolin-1-one 3f. FTIR (KBr) nC55O
1648 cm21; 1H NMR (400 MHz, CDCl3) d ppm 3.58 (3H, s), 3.86 (3H, s), 6.86
(1H, s), 7.12 (1H, dd, J ¼ 8.98, 2.8), 7.31–7.41 (6H, m), 7.86 (1H, d, J ¼ 2.8).
13C NMR (100 MHz, CDCl3) d ppm 37.48; 56.07; 108.49; 120.00; 122.78;
126.77; 127.59; 128.02; 129.02; 129.60; 130.28; 130.84; 136.91; 159.18.;
162.20. MS m/z 265 (Mþ). Anal. calcd. for C17H15NO2 (265.31): C, 76.96;
H, 5.70; N, 5.28. Found: 76.66; H, 5.93; N, 5.07.
6,7-Dimethoxy-4-(4-methoxy-phenyl)-2-methyl-2H-isoquinolin-1-one 3g.
1
FTIR (KBr) nC55O 1648 cm21; H NMR (400 MHz, CDCl3) d ppm 3.57 (3H,
s), 3.74 (3H, s), 3.80 (3H, s), 3.94 (3H, s), 6.82 (1H, s), 6.86 (1H, s), 6.93
(2H, d, J ¼ 8.57), 7.26 (2H, d, J ¼ 8.57), 7.85 (1H, s). 13C NMR
(100 MHz, CDCl3) d ppm 37.39; 55.72; 56.28; 56.58; 105.45; 108.37;
114.52; 119.14; 120.35; 129.31; 130.43; 131.23; 132.48; 149.54; 153.46;
159.56;161.79. MS m/z 325 (Mþ). Anal. calcd. for C19H19NO4 (325.37):
C, 70.14; H, 5.89; N, 4.31. Found: C, 70.19; H, 6.07; N, 4.24.
7,8-Dimethoxy-2-methyl-4-phenyl-2H-isoquinolin-1-one 3h. FTIR (KBr)
1
nC55O 1653 cm21; MS m/z 295 (Mþ). H NMR (400 MHz, CDCl3) d ppm
3.60 (3H, s), 3.95 (3H, s), 4.04 (3H, s), 6.91(1H, s), 7.25 (2H, m), 7.38–
7.49 (5H, m). Anal. calcd. for C19H19NO4 (295.34): C, 70.14; H, 5.89; N,
4.31. Found: C, 70.15; H, 6.00; N, 4.28.
6-Benzoyl-2,3-dimethoxy-N-methyl-benzamide. Colorless oil; FTIR (KBr)
C55O 1680 cm21; MS m/z 299 (Mþ). 1H NMR (400 MHz, CDCl3) d ppm 2.93
n
(3H, s), 3.88 (3H, s), 4.18 (3H, s), 5.24 (1H, s), 6.81 (1H, d, J ¼ 8.2), 7.00 (1H,
d, J ¼ 8.2), 7.16 (2H, d, J ¼ 6.7), 7.38 (3H, m). Anal. calcd. for C17H17NO4
(299.32): C, 68.21; H, 5.72; N, 4.68. Found: C, 68.28; H, 5.70; N, 4.70.
ACKNOWLEDGMENT
˘
Uludag University Research Fund is gratefully acknowledged for its financial
support (Project No 2001-2).

4-Arylisoquinolinium Perchlorates and 4-Arylisoquinolin-1-ones
REFERENCES
2443
1. (a) Dandridge, P. A.; Kaiser, C.; Brenner, M.; Gaitanopoulos, D.; Davis, L. D.;
Webb, R. L.; Foley, J. J.; Sarau, H. M. J. Med. Chem. 1984, 27, 28–35;
(b) Toome, V.; Blount, J. F.; Grethe, G.; Uskokovic, M. Tetrahedron Lett. 1970,
11, 49–52; (c) Kihara, M.; Ikeuchi, M.; Adachi, S.; Nagao, Y.; Moritoki, H.;
Yamaguchi, M.; Taira, Z. Chem. Pharm. Bull. 1995, 43, 1543–1546;
(d) Couture, A.; Deniau, E.; Grandclaudon, P.; Lebrun, S. Tetrahedron:
Asymmetry 2003, 14, 1309–1316; (e) Honda, T.; Namiki, H.; Satoh, F. Org.
Lett. 2001, 3, 631–633; (f) Ulin, J.; Gee, A. D.; Malmborg, P.; Tedroff, J.;
Laangstroem, B. Appl. Radiat. Isot. 1989, 40, 171–176; (g) Omer, L. M. Int.
J. Clin. Pharmacol. Ther. Toxicol. 1982, 20, 320–326.
2. Wildman, W. C. The Alkaloids; Manske, R. H. F., Ed.; Academic Press: New York,
1968; Vol. XI, Chapter 10.
3. (a) Narasimhan, N. S.; Patil, P. A. J. Chem. Soc. Chem. Comm. 1987, 3, 191–192;
(b) Couture, A.; Deniau, E.; Woisel, P.; Grandclaudon, P.; Carpentier, J. F.
Tetrahedron Lett. 1996, 37, 3697–3700; (c) Couture, A.; Deniau, E.;
Grandclaudon, P.; Woisel, P. Tetrahedron 1996, 52, 4433–4448.
4. Pelletier, S. W. Chemistry of the Alkaloids; Van Nostrand Reinhold Co.:
New York, 1970.
5. Cava, M. P.; Buck, K. T. Tetrahedron 1969, 23, 2795–2805.
6. (a) Ukita, T.; Nakamura, Y.; Kubo, A.; Yamamoto, Y.; Moritani, Y.; Saruta, K.;
Higashijima, T.; Kotera, J.; Takagi, M.; Kikkawa, K.; Omori, K. J. Med. Chem.
2001, 44, 2204–2218; (b) Ukita, T.; Nakamura, Y.; Kubo, A.; Yamamoto, Y.;
Moritani, Y.; Saruta, K.; Higashijima, T.; Kotera, J.; Fujishige, K.; Takagi, M.;
Kikkawa, K.; Omori, K. Bioorg. Med. Chem. Lett. 2003, 13, 2341–2345.
7. (a) Venkov, A. P.; Vodenicharov, D. M. (now N. Cos¸kun); Ivanov, I. I. Synthesis
1991, 476–478; (b) Cos¸kun, N.; Su¨mengen, D. Synth. Commun. 1993, 23,
1393–1402.
8. (a) Venkov, A. P.; Vodenicharov, D. M. (now N. Cos¸kun), Synthesis 1990,
253–255; (b) Cos¸kun, N.; Su¨mengen, D. Chim. Acta Turc. 1996, 24, 151;
(c) Cos¸kun, N.; Tirli, F. Synth. Commun. 1997, 27, 1–9.
9. Cos¸kun, N.; Bu¨yu¨kuysal, L. Heterocycles 1998, 48, 53–59.
10. Bunting, J. W.; Stefanidis, D. J. Org. Chem. 1986, 51, 2060–2067.