Fused azolium salts XVIII [1]. Synthesis and reactivity of a novel fused heteroaromatic system : [1,2,3]triazolo[1,5-b]isoquinolinium salts

Article abstract of DOI:10.1007/PL00013497

Oxidative cyclization of 3-isoquinolyl ketone hydrazones afforded the novel tricyclic heteroaromatic [1,2,3]triazolo[1,5-b]isoquinolinium salts. The reactivity of the ring system towards nucleophiles proved to be regioselective. Secondary amines induced r

Full text of DOI:10.1007/PL00013497

Monatshefte fuÈr Chemie 129, 897±908 (1998)
Fused Azolium Salts XVIII [1]. Synthesis and
Reactivity of a Novel Fused Heteroaromatic
System: [1,2,3]Triazolo[1,5-b]isoquinolinium
Salts
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Mariann Beres, Gyorgy Hajos , Zsuzsanna Riedl, Geza Timari,
and Andras Messmer
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Chemical Center, Institute of Chemistry, Hungarian Academy of Science, Budapest, Hungary
Summary. Oxidative cyclization of 3-isoquinolyl ketone hydrazones afforded the novel tricyclic
heteroaromatic [1,2,3]triazolo[1,5-b]isoquinolinium salts. The reactivity of the ring system towards
nucleophiles proved to be regioselective. Secondary amines induced ring opening of the pyridine
moiety, forming a triazolyl substituted benzaldehyde derivative; sodium borohydride afforded
partially reduced derivatives of the parent compound.
Keywords. Triazolium salt; Ring closure; Regiospeci®city, Ring opening; Indole synthesis.
È
Kondensierte Azoliumsalze, 18. Mitt. [1]. Synthese und Reaktivitat eines neuen kondensierten
heteroaromatischen Systems: [1,2,3]Triazolo[1,5-b]isochinoliniumsalze
Zusammenfassung. Die oxidierende Cyclisierung von 3-Isochinolylketonhydrazonen ergab die
È
neuen tricyclischen [1,2,3]Triazolo[1,5-b]isochinoliniumsalze. Die Reaktivitat des Ringsystems
È
gegenuÈber Nukleophilen erwies sich regioselektiv. Bei Reaktion mit sekundaren Aminen trat
È
Offnung des Pyridinringes ein; die Reaktion mit Natriumborhydrid fuÈhrte zu partiell reduzierten
Derivaten der Ausgangsverbindung.
Introduction
In continuation of our studies on fused azolium salts [1], the synthesis and the
investigation of the reactivity of the hitherto unknown linearly fused heteroaro-
matic system of [1,2,3]triazolo[1,5-b]isoquinolinium salts attracted our interest. In
this paper we report their synthesis and discuss some reactions of these new
compounds.
Results and Discussion
Commercially available 3-cyanoisoquinoline (1) was transformed to various
ketones (3) with Grignard reagents (2). The ketones in turn reacted with p-
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Corresponding author

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M. Beres et al.
898
Fig. 1. Comparison of the UV spectra (acetonitrile, 25ꢀC) of hydrazone 4a and triazolium salt 5a
bromophenylhydrazine to give the corresponding hydrazones 4. Inspection of the
1H NMR spectra of 4 revealed that the majority of these compounds were obtained
as pure geometric isomers and proved to be E isomers; only in some cases (e.g. 4d,
f, and i) the Z isomer was formed. In this respect, the NH shift seemed to be of
diagnostic importance: in the Z isomers (i.e. those containing the NH group in a
chelate form), the ꢀ value of this proton is larger than 12 ppm, whereas that of the E
derivatives amounts to less than 8 ppm.
In order to achieve the desired ring closure of the appropriate isoquinolyl
ketone arylhydrazones (4), a well established synthetic path (oxidative cyclization)
was applied [1]. Treatment of compounds 4 with N-bromosuccinimide (NBS) or
2,4,4,6-tetrabromo-cyclohexa-2,5-dien-1-one (TBB) afforded the novel linearly
fused heteroaromatic [1,2,3]triazolo[1,5-b]isoquinolinium salts 5. The spectro-
scopic characteristics of 5 support the formation of the extended heteroaromatic
system: the blue shift of the ®rst maximum and the disappearance of the
absorbance at 260 nm in the UV (Fig. 1) indicate the change of the chromophore,
whereas the appearance of two down®eld shifted singlets of H-4 and H-9 in the
1H NMR spectrum of the product reveals the formation of the positively charged
heteroaromatic cation.
Two unexpected problems arose in the course of this preparative route:
(1) The synthesis of the hydrazones 4 can be carried out both in a neutral organic
solvent and in acetic acid. Although traces of acetic acid could never be
removed entirely from the product obtained by the acidic method, we routinely
applied this method because the yield was higher and the impurity did not
affect the subsequent ring closure reaction. However, in the case of the reaction
of 3d, e, f with 4-bromophenylhydrazine we found that isoquinolylindoles 7±9
were formed instead of the expected hydrazones 4. These compounds are
obviously products of a Fischer type indole synthesis derived from the
primarily formed hydrazones 4 d, e, f. They can exist in the hydro form (7 and
9) or in the heteroaromatic from (8), depending on whether C-3 of the indole
moiety bears a hydrogen available for the tautomerism.
(2) Unlike our earlier observations with the analogous triazolopyridazinium and
tetrazoloisoquinolinium ring systems [2, 3] we experienced that, in some cases,

[1,2,3]Triazolo[1,5-b]isoquinolinium Salts
899
Scheme 1
Scheme 2
an excessive bromination at C-4 takes place during the ring closure (presence
of 6 as an impurity was detected in the NMR spectrum of the crude product),
which apparently is due to the high reactivity of this position towards electro-
philes. In order to avoid this undesired side reaction, in some cases (e.g. for
R ˆ CH3 and C4H9) ring closure had to be carried out at low temperatures
using exactly three molar equivalents of the reagent. This is the minimal
amount of the reagent needed because the primarily formed ring closed
bromide salt rapidly takes up one molecule of bromine to form the perbromide
salt.
Investigation of the reactivity of the linearly fused tricyclic salts 5 revealed that
± according to our expectations ± this ring system reacts with nucleophiles

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M. Beres et al.
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Ar ˆ 4-BrC6H4; R : ꢁa† CH3 ꢁc† 4-ClC6H4 ꢁg† ꢁCH3†3C
Scheme 3
selectively at position 9. Thus, when a solution of 5a, 5c, or 5g (A ˆ BF4) in
acetonitrile was treated with morpholine at room temperature, the colour of the
reaction mixture turned deep yellow or red, and work-up of the mixture by addition
of water afforded the aldehydes 11. The course of the reaction leading to these
compounds can be rationalized by the formation of the intermediate 10 which ®rst
undergoes cycloreversion; a subsequent hydrolytic step removes the morpholino
group to yield the ®nal product 11.
A different behaviour was observed when the triazolium salts 5a, 5c, and 5g
(A ˆ BF4) reacted with sodium borohydride. Although the nucleophilic attack of
the hydride anion is expected to afford the same type of intermediate as above (12),
a rapid subsequent reduction took place at C-3a±C-4, preventing the cycloreversion
reaction observed with 10 and affording the tricyclic compound 13.
The high regioselectivity of the new linearly fused tricyclic triazolium salts 5
(A ˆ BF4) towards nucleophiles seems to be in good accordance with our earlier
®ndings with related heteroaromatic salts [3, 4, 5]. Further study of the reactivity of
this ring system is in progress.
Experimental
Melting points were determined with a BuÈchi apparatus; NMR spectra were recorded on Varian
VXR-200 and Varian Unity Inova 400 spectrometers; mass spectra were measured on an MS-902
spectrometer (EI technique, resolution: 10000).
General procedure for the synthesis of 3a±h
To a stirred solution of 15.4 g (0.1 mol) 3-cyanoisoquinoline (1; Sigma-Aldrich) in 350 ml dry ether,
a solution of the appropriate Grignard reagent (0.12 mol) in 150 ml of dry ether was added dropwise
at 0ꢀC. Stirring was continued at 0ꢀC for 2 h, and the reaction mixture was kept at 5ꢀC for 12 h. After
pouring on ice containing 10 g ammonium chloride, the mixture was acidi®ed with 20% sulfuric acid
(pH ˆ 1), thoroughly shaken, and neutralized with 20% sodium hydroxide solution. The aqueous
layer was separated and extracted with dichloromethane. The combined organic extracts were dried
over Na2SO4, and the solvent was evaporated under reduced pressure. The crude product was
dissolved in dichloromethane, ®ltered through alumina, and evaporated to dryness. 3f and 3g were
puri®ed by vacuum distillation.

[1,2,3]Triazolo[1,5-b]isoquinolinium Salts
Methyl 3-isoquinolyl ketone (3a; C11H9NO)
901
The Grignard reagent was prepared from methyl iodide; yield: 8.5 g (50%); m.p.: 84±86ꢀC; the
1
crude product (Ref. [6]: m.p.: 92±92.8ꢀC) proved to be suitable for further conversions; H NMR
(200 MHz, CDCl3): ꢀ ˆ 9.28 (s, 1H, H-1), 8.47 (s, 1H, H-4), 8.07±7.96 (m, 2H, H-5, 8), 7.81±7.69
(m, 2H, H-6, 7), 2.83 (s, 3H, H-Me) ppm.
n-Butyl 3-isoquinolyl ketone (3b; C14H15NO)
The Grignard reagent was prepared from n-butyl bromide; yield: 14.5 g (40.0%); m.p.: 58±59ꢀC;
1H NMR (200 MHz, CDCl3); ꢀ ˆ 9.27 (s, 1H, H-1), 8.46 (s, 1H, H-4), 8.05±7.96 (m, 2H, H-5, 6),
7.79±7.66 (m, 2H, H-6, 7), 3.31 (t, J ˆ 7.4 Hz, 2H, CH2), 1.76 (m, 2H, CH2), 1.44 (m, 2H, CH2), 0.96
(t, J ˆ 7.3 Hz, 3H, CH3) ppm; C14H15NO (213.28); calcd.: C 78.84, H 7.09, N 6.57; found: C 78.93,
H 6.98, N 6.76.
4-p-Chlorophenyl 3-isoquinolyl ketone (3c; C16H10ClNO)
The Grignard reagent was prepared from 4-bromochlorobenzene; m.p.: 127±128ꢀC (Ref. [7]: m.p.:
1
125±127ꢀC); H NMR (200 MHz, CDCl3): ꢀ ˆ 9.32 (s, 1H, H-1), 8.49 (s, 1H, H-4), 8.10±7.98 (m,
2H, H-5, 8), 8.09±7.45 (AA0BB0, 4H, H-aryl), 7.83±7.91 (m, 2H, H-6, 7) ppm.
Cyclohexyl 3-isoquinolyl ketone (3d; C16H17NO)
The Grignard reagent was prepared from cyclohexyl chloride; the crude product (m.p.: 81±82ꢀC,
Ref. [8]: m.p.: 85±87ꢀC, yield: 12.6 g (52.6%)) proved to be suitable for further conversions;
1H NMR (200 MHz, CDCl3): ꢀ ˆ 9.28 (s, 1H, H-1), 8.46 (s, 1H, H-4), 8.07±7.96 (m, 2H, H-5, 8),
7.80±7.67 (m, 2H, H-6, 7), 3.97 (m, 1H, H-10), 2.00±1.25 (m, 10H, H-cyclohexyl) ppm.
Benzyl 3-isoquinolyl ketone (3e; C17H13NO)
The Grignard reagent was prepared from benzyl bromide; this compound has been reported earlier
without complete analytical characterization [9]; yield: 12.6 g (51.1%); m.p.: 77ꢀC; 1H NMR
(200 MHz, CDCl3): ꢀ ˆ 9.31 (s, 1H, H-1), 8.49 (s, 1H, H-4), 8.08±7.93 (m, 2H, H-5, 8), 7.79±7.19
(m, 2H, H-6, 7), 7.42±7.23 (m, 5H, H-phenyl), 4.66 (s, 2H, H-CH2) ppm; C17H13NO (247.30);
calcd.: C 82.57, H 5.30, N 5.66; found: C 82.41, H 5.07, N 5.46.
Isopropyl 3-isoquinolyl ketone (3f; C13H11NO)
The Grignard reagent was prepared from isopropyl bromide; yield: 12.3 g (61.9%); colourless oil;
1H NMR (400 MHz, CDCl3): ꢀ ˆ 9.28 (s, 1H, H-1), 8.49 (s, 1H, H-4), 8.04 (dd, J ˆ 7 Hz, 1.5 Hz, 1H,
H-8), 7.98 (dd, J ˆ 7 Hz, 1.5 Hz, 1H, H-5) 7.76 (ddd, J ˆ 7 Hz, 7 Hz, 1.5 Hz, 1H, H-7), 7.72 (ddd,
J ˆ 7 Hz, 7 Hz, 1.5 Hz, 1H, H-6), 4.22 (qq, J ˆ 7 Hz, 1H, CH); 1.27 (d, J ˆ 7 Hz, 6H, CH3) ppm;
C13H11NO (197.24); calcd.: C 79.17, H 5.62, N 7.10; found: C 79.16, H 5.87, N 7.01.
t-Butyl 3-isoquinolyl ketone (3g; C14H13NO)
The Grignard reagent was prepared from t-butyl chloride; yield: 11.5 g (52.5%); colourless oil;
1H NMR (400 MHz, CDCl3): ꢀ ˆ 9.23 (s, 1H, H-1), 8.36 (s, 1H, H-4), 8.02 (dd, J ˆ 7 Hz, 1.5 Hz, 1H,
H-8), 7.96 (dd, J ˆ 7 Hz, 1.5 Hz, 1H, H-5), 7.75 (ddd, J ˆ 7 Hz, 7 Hz, 1.5 Hz, 1H, H-7), 7.70 (ddd,
J ˆ 7 Hz, 7 Hz, 1.5 Hz, 1H, H-6), 1.53 (s, 9H, CH3) ppm; C14H13NO (211.27); calcd.: C 79.59, H
6.20, N 6.63; found: C 79.34, H 6.37, N 6.66.

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M. Beres et al.
902
2-Thienyl 3-isoquinolyl ketone (3h; C14H9NOS)
The Grignard reagent was prepared from 2-bromothiophene; yield: 19.6 g (81.9%); m.p.: 120±
122ꢀC (Refs. [10, 11]: m.p.: 124ꢀC); the crude product proved to be suitable for further conversions.
3-Thienyl 3-isoquinolyl ketone (3i; C14H9NOS)
To a stirred solution of 7.9 g (0.03 mol) 3-bromothiophene in 20 ml dry ether, to a solution of n-
butyllithium in hexane (16.5 ml, 2 M, 0.033 mol) was added dropwise under argon at ꢂ70ꢀC. After
stirring for 15 min, 3-cyanoisoquinoline (1, 4.6 g, 0.03 mol) in 40 ml ether was added. The stirred
reaction mixture was allowed to warm up to room temperature and was kept at 5ꢀC for 12 h. Water
(20 ml) was added under ice-cooling, and the mixture was acidi®ed with 10% hydrochloric acid
( pH ˆ 1). After stirring for 1 h, the mixture was neutralized with solid sodium hydrogencarbonate.
The layers were separated, and the aqueous phase was extracted with ether. The combined organic
extracts were dried over Na2SO4, and the solvent was evaporated under reduced pressure. The crude
product was recrystallized from isopropyl alcohol.
Yield: 12.7 g (53%); m.p.: 86±87ꢀC. (Refs. [10, 11]: m.p.: 89±90ꢀC); C14N9NOS (239.30);
calcd.: C 70.27, H 3.79, N 5.85; found: C 70.16, H 3.87, N 6.06.
General procedure for the synthesis of 3-isoquinolyl ketone arylhydrazones 4a±i
To a solution of 3-isoquinolyl ketones 4a±i (0.04 mol) in 70 ml chloroform, a solution of 4-
bromophenylhydrazine hydrochloride (8.9 g, 0.044 mol) and sodium acetate (3.6 g, 0.044 mol) in
ethanol (70 ml) was added at room temperature. After stirring for 12 h, H2O was added, and the
mixture was extracted with chloroform. The organic layer was evaporated, the residue was triturated
with hot methanol, and the precipitate was ®ltered off and recrystallized from ethanol.
(E)-Methyl 3-isoquinolyl ketone 4-bromophenylhydrazone (4a; C17H14BrN3)
Yield: 8.1 g (59.6%); m.p.: 183±187ꢀC; 1H NMR (200 MHz, CDCl3): ꢀ ˆ 9.20 (s, 1H, H-1), 8.41 (s,
1H, H-4), 7.91 (dd, J ˆ 8.5 Hz, 8.5 Hz, 2H, H-5, 8), 7.67 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7),
7.54 (s, N-H), 7.54 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.42±7.12 (AA0BB0, 4H, H-aryl), 2.47
(s, 3H, CH3) ppm; C17H14BrN3 (340.22); calcd.: C 60.02, H 4.15, N 12.35; found: C 59.87, H 4.01,
N 12.17.
(E)-n-Butyl 3-isoquinolyl ketone 4-bromophenylhydrazone (4b; C20H18BrN3)
Yield: 10.7 g (70.0%); m.p.: 185±187ꢀC; 1H NMR (200 MHz, CDCl3): ꢀ ˆ 9.21 (s, 1H, H-1), 8.40 (s,
1H, H-4), 7.91 (dd, J ˆ 8.5 Hz, 8.5 Hz, 2H, H-5, 8), 7.67 (s, N-H), 7.66 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-7), 7.55 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.42±7.10 (AA0BB0, 4H, H-aryl),
3.02 (m, 2H, CH2), 1.64±1.42 (m, 4H, CH2), 0.96 (m, 3H, CH3) ppm; C20H20BrN3 (382.30); calcd.:
C 62.83, H 5.27, N 10.99; found: C 62.56, H 5.28, N 10.87.
4-p-Chlorophenyl 3-isoquinolyl ketone 4-bromophenyl hydrazone (4c; C22H15ClBrN3)
Yield: 10.0 g (85.8%); m.p.: 138±141ꢀC (mixture of E and Z isomers); 1H NMR (400 MHz, CDCl3,
(E)-4c): ꢀ ˆ 9.17 (s, 1H, H-1), 8.20 (s, 1H, H-4), 7.94 (d, J ˆ 8.5 Hz, 1H, H-8), 7.88 (d, J ˆ 8.5 Hz,
1H, H-5), 7.77 (s, N-H), 7.68 (dd, J ˆ 8.5 Hz, 8.5 Hz, 1H, H-7), 7.58 (dd, J ˆ 8.5 hz, 8.5 Hz, 1H,
H-6), 7.59±7.36 (AA0BB0, 4H, H-chlorophenyl), 7.36±7.06 (AA0BB0, 4H, H-bromophenyl) ppm;
C22H15BrClN3 (436.74); calcd.: C 60.50, H 3.46, N 9.62; found: C 60.61, H 3.51, N 9.52.

[1,2,3]Triazolo[1,5-b]isoquinolinium Salts
903
(Z)-Cyclohexyl 3-isoquinolyl ketone 4-bromophenyl hydrazone (4d; C22H22BrN3)
1
Yield: 12.7 g (78.1%); m.p.: 176±178ꢀC; H NMR (400 MHz, CDCl3); ꢀ ˆ 13.05 (s, N-H), 9.28 (s,
1H, H-1), 8.00 (d, J ˆ 8.15 Hz, 1H, H-8), 7.90 (d, J ˆ 8.15 Hz, 1H, H-5), 7.84 (s, 1H, H-4), 7.73 (dd,
J ˆ 8.5 Hz, 8.5 Hz, 1H, H-7), 7.63 (dd, J ˆ 8.5 Hz, 8.5 Hz, 1H, H-6), 7.34±7.07 (AA0BB0, 4H, H-
aryl), 2.93 (m, 1H, H-10), 2.04±1.30 (m, 10H, H-cyclohexyl) ppm; C22H22BrN3 (408.34); calcd.: C
64.71, H 5.43, N 10.29; found: C 64.48, H 5.35, N 10.07.
(E)-Benzyl 3-isoquinolyl ketone 4-bromophenyl hydrazone (4e; C23H18BrN3)
Yield: 11.5 g (68.3%); m.p.: 188±189ꢀC; 1H NMR (400 MHz, CDCl3): ꢀ ˆ 9.22 (s, 1H, H-1), 8.52 (s,
1H, H-4), 7.94 (dd, J ˆ 8.5 Hz, 8.5 Hz, 2H, H-5, 6), 7.74 (s, N-H), 7.68 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-7), 7.56 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.35±6.97 (AA0BB0, 4H, H-
bromophenyl), 7.33±7.19 (m, 5H, H-phenyl), 4.54 (s, 2H, CH2) ppm; C23H18BrN3 (416.32); calcd.:
C 66.36, H 4.36, N 10.09; found: C 66.14, H 4.22, N 9.86.
(Z)-Isopropyl 3-isoquinolyl ketone 4-bromophenyl hydrazone (4f; C19H16BrN3)
1
Yield: 12.2 g (82.5%); m.p.: 155±157ꢀC; H NMR (400 MHz, CDCl3); ꢀ ˆ 13.12 (s, N-H), 9.00 (s,
1H, H-1), 8.00 (d, J ˆ 8.5 Hz, 1H, H-8), 7.89 (d, J ˆ 8.5 Hz, 1H, H-5), 7.89 (s, 1H, H-4), 7.73 (ddd,
J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.64 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.37±7.09
(AA0BB0, 4H, H-aryl), 3.34 (m, 1H, CH), 1.35 (d, J ˆ 6.7 Hz, 6H, CH3) ppm; C19H18BrN3 (368.28);
calcd.: C 61.97, H 4.93, N 11.41; found: C 61.86, H 4.95, N 11.32.
(E)-t-Butyl 3-isoquinolyl ketone 4-bromophenyl hydrazone (4g; C20H18BrN3)
Yield: 12.3 (80.3%); m.p.: 140±144ꢀC; 1H NMR (400 MHz, CDCl3): ꢀ ˆ 9.40 (s, 1H, H-1), 8.06 (dd,
J ˆ 8.5 Hz, 1.5 Hz, 1H, H-8), 7.88 (dd, J ˆ 8.5 Hz, 1.5 Hz, 1H, H-5), 7.78 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-7), 7.70 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.64 (s, N-H), 7.30 (s, 1H, H-4),
7.26±6.82 (AA0BB0, 4H, H-aryl), 1.31 (s, 9H, CH3) ppm; C20H20BrN3 (382.30); calcd.: C 62.83, H
5.27, N 10.99; found: C 62.70, H 5.17, N 10.74.
2-Thienyl 3-isoquinolyl ketone 4-bromophenyl hydrazone (4h, C20H14BrN3)
Yield: 9.2 (55.9%); m.p.: 117±121ꢀC (mixture of E and Z isomers); 1H NMR (400 MHz, CDCl3, (Z)-
4h): ꢀ ˆ 12.15 (s, N-H), 9.38 (s, 1H, H-1), 8.08 (s, 1H, H-4), 8.06 (d, J ˆ 8.5 Hz, 1H, H-8), 7.86 (d,
J ˆ 8.5 Hz, 1H, H-5), 7.75 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.69 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-6), 7.36±7.09 (AA0BB0, 4H, H-bromophenyl), 7.32 (dd, J ˆ 5 Hz, 1 Hz, 1H, H-50), 7.14
(dd, J ˆ 3.8 Hz, 1 Hz, 1H, H-30), 7.04 (dd, J ˆ 5 Hz, 3.8 Hz, 1H, H-40) ppm; C20H14BrN3S1 (408.32);
calcd.: C 58.83, H 3.46, N 10.29; found: C 59.17, H 3.49, N 11.33.
(Z)-3-Thienyl 3-isoquinolyl ketone 4-bromophenyl hydrazone (4i; C20H14BrN3)
Yield: 14 g (81.7%); m.p.: 125±126ꢀC; 1H NMR (400 MHz, CDCl3): ꢀ ˆ 12.47 (s, N-H), 9.40 (s, 1H,
H-1), 8.06 (d, J ˆ 8.5 Hz, 1H, H-8), 7.92 (s, 1H, H-4), 7.83 (d, J ˆ 8.5 Hz, 1H, H-5), 7.74 (ddd,
J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.69 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.51 (dd,
J ˆ 5 Hz, 1 Hz, 1H, H-40), 7.42 (dd, J ˆ 2.9 Hz, 1 Hz, 1H, H-20), 7.39 (dd, J ˆ 5 Hz, 2.9 Hz, 1H, H-50),
7.36±7.11 (AA0BB0, 4H, H-bromophenyl) ppm; C20H14BrN3S (408.32); calcd.: C 58.83, H 3.46, N
10.29; found: C 59.81, H 3.52, N 10.22.

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904
Table 1. Experimental conditions for the ring closure reactions affording 5; NBS: N-bromosuccini-
mide, TBB: 2,4,4,6-tetrabromo-cyclohexa-2,5-diene-1-one
R
Reagent
Solvent
T (ꢀC)
t (h)
5a
5b
5c
5f
CH3
NBS
NBS
TBB
TBB
TBB
NBS
NBS
ethyl acetate
ethyl acetate
CH2Cl2
ꢂ17
0
3
n-C4H9
2
4-Cl-C6H4
CH(CH3)2
tert.-C4H9
2-thienyl
3-thienyl
r.t.
0
0.5
1.5
1
CH2Cl2
5g
5h
5i
CH2Cl2
0
ethyl acetate
ethyl acetate
ꢂ20
ꢂ17
1.5
1
General procedure for the ring closure of 4 to [1,2,3]triazolo[1,5-b]isoquinolinium
salts 5a±c, f±i
To a stirred solution of hydrazone 4 in the appropriate solvent, the ring closure reagent (3
equivalents) was added in portions at the temperature given in Table 1. Stirring was continued; after
the reaction time given in Table 1, ether was added, and the precipitate formed was ®ltered off. The
yellow crystals were suspended in nitromethane, cyclohexene was added at room temperature
(except 5a which was treated at 0ꢀC), and the mixture was stirred for 30 min. Ether was added again,
and the resultant precipitate was ®ltered off to yield crude bromide salts (5, A ˆ Br). Conversion into
the tera¯uoroborate salts 5 (A ˆ BF4) was carried out by addition of an aqueous solution of NH4BF4
to the hot solution of the bromide salt in aqueous ethanol. The precipitate was ®ltered off and
recrystallized from acetonitrile/ether.
1-(4-Bromophenyl)-3-methyl[1,2,3]triazolo[1,5-b]isoquinolinium tetra¯uoroborate
(5a; A ˆ BF4; C17H13BBrF4N3)
1
Starting from 4a (3.4 g, 10 mmol), 1.7 g (41%) of 5a were obtained. M.p.: 204±205ꢀC; H NMR
(400 MHz, CD3CN‡TFA): ꢀ ˆ 9.87 (s, 1H, H-9), 9.13 (s, 1H, H-4), 8.39 (dd, J ˆ 8.5 Hz, 1.5 Hz, 1H,
H-8), 8.31 (dd, J ˆ 8.5 Hz, 1,5 Hz, 1H, H-5), 8.06 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 8.00
(ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.98±7.71 (AA0BB0, 4H, H-aryl), 2.91 (s, 3H, CH3) ppm;
C17H13BBrF4N3 (426.02); calcd.: C 47.93, H 3.08, N 9.86; found: C 46.34, H 2.97, N 9.62.
1-(4-Bromophenyl)-3-n-butyl[1,2,3]triazolo[1,5-b]isoquinolinium tetra¯uoroborate
(5b; A ˆ BF4; C20H19BBrF4N3)
1
Starting from 4b (3.8 g, 10 mmol), 2.5 g (53%) of 5b were obtained. M.p.: 143±146ꢀC; H NMR
(400 MHz, CD3CN): ꢀ ˆ 10.00 (s, 1H, H-9), 9.13 (s, 1H, H-4), 8.38 (d, J ˆ 8.5 Hz, 1H, H-8), 8.28 (d,
J ˆ 8.5 Hz, 1H, H-5), 8.04 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.99 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-6), 7.98±7.69 (AA0BB0, 4H, H-aryl), 3.30 (m, 2H, CH2), 1.98 (m, 2H, CH2), 1.57 (m,
2H, CH2), 1.02 (m, 3H, CH3) ppm; C20H19BBrF4N3 (468.10); calcd.: C 51.32, H 4.09, N 9.98;
found: C 51.12, H 4.07, N 9.76.
1-(4-Bromophenyl)-3-(4-chlorophenyl)[1,2,3]triazolo[1,5-b]isoquinolinium tetra¯uoroborate
(5c; A ˆ BF4; C22H14BBrClF4N3)
1
Starting from 4c (4.3 g, 10 mmol), 3.7 g (70%) of 5c were obtained. M.p.: 206±208ꢀC; H NMR
(400 MHz, CD3CN‡TFA): ꢀ ˆ 9.91 (s, 1H, H-9), 9.39 (s, 1H, H-4), 8.45 (d, J ˆ 8.5 Hz, 1H, H-8),

[1,2,3]Triazolo[1,5-b]isoquinolinium Salts
905
8.34 (d, J ˆ 8.5 Hz, 1H, H-5), 8.21±7.74 (AA0BB0, 4H, H-chlorophenyl), 8.09 (ddd, J ˆ 8.5 Hz,
8.5 Hz, 1.5 Hz, 1H, H-7), 8.03 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 8.02±7.81 (AA0BB0, 4H, H-
bromophenyl) ppm; C22H14BBrClF4N3 (522.53); calcd.: C 50.57, H 2.70, N 8.04; found: C 50.76,
H 2.71, N 7.93.
1-(4-Bromophenyl)-3-isopropyl[1,2,3]triazolo[1,5-b]isoquinolinium tetra¯uoroborate
(5f; A ˆ BF4; C19H17BBrF4N3)
1
Starting from 4f (3.7 g, 10 mmol), 2.5 g (55%) of 5f were obtained. M.p.: 164±167ꢀC; H NMR
(400 MHz, CD3CN‡TFA): ꢀ ˆ 9.87 (s, 1H, H-9), 9.19 (s, 1H, H-4), 8.40 (d, J ˆ 8.5 Hz, 1H, H-8),
8.30 (d, J ˆ 8.5 Hz, 1H, H-5), 8.06 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.99 (ddd, J ˆ 8.5 Hz,
8.5 Hz, 1.5 Hz, 1H, H-6), 7.99±7.71 (AA0BB0, 4H, H-aryl), 3.78 (m, 1H, CH), 1.60 (d, J ˆ 7 Hz, 6H,
CH3) ppm; C19H17BBrF4N3 (454.07); calcd.: C 50.26, H 3.77, N 9.25; found: C 50.03, H 3.49,
N 9.12.
1-(4-Bromophenyl)-3-tert.±butyl[1,2,3]triazolo[1,5-b]isoquinolinium tetra¯uoroborate
(5g; A ˆ BF4; C20H19BBrF4N3)
1
Starting from 4g (3.8 g, 10 mmol), 2.8 g (60%) of 5g were obtained. M.p.: 221±223ꢀC; H NMR
(400 MHz, CD3CN‡TFA): ꢀ ˆ 9.84 (s, 1H, H-9), 9.31 (s, 1H, H-4), 8.44 (d, J ˆ 8.5 Hz, 1H, H-8),
8.28 (d, J ˆ 8.5 Hz, 1H, H-5, H-5), 8.06 (dd, J ˆ 8.5 Hz, 8.5 Hz, 1H, H-7), 7.98 (dd, J ˆ 8.5 Hz,
8.5 Hz, 1H, H-6), 8.00±7.73 (AA0BB0, 4H, H-aryl), 1.70 (s, 9H, CH3) ppm; C20H19BBrF4N3
(468.10); calcd.: C 51.32, H 4.09, N 9.98; found: C 51.26, H 4.15, N 9.13.
1-(4-Bromophenyl)-3(2-thienyl)[1,2,3]triazolo[1,5-b]isoquinolinium tetra¯uoroborate
(5h; A ˆ BF4; C20H13BBrF4N3S)
1
Starting from 4h (0.82 g, 2 mmol), 0.23 g (23%) of 5h were obtained M.p.: 205±206ꢀC; H NMR
(400 MHz, CD3CN‡TFA): ꢀ ˆ 9.91 (s, 1H, H-9), 9.45 (s, 1H, H-4), 8.49 (dd, J ˆ 8.5 Hz, 1.5 Hz, 1H,
H-8), 8.33 (dd, J ˆ 8.5 Hz, 1.5 Hz, 1H, H-5), 8.11 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 8.04
(ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 8.03±7.79 (AA0BB0, 4H, H-aryl), 8.20 (dd, J ˆ 5 Hz, 1 Hz,
1H, H-50), 7.85 (dd, J ˆ 4 Hz, 1 Hz, 1H, H-30), 7.44 (dd, J ˆ 5 Hz, 4 Hz, 1H, H-40) ppm;
C20H13BBrF4N3S; calcd.: C 48.62, H 2.65, N 8.50; found: C 48.89, H 2.67, N 8.68.
1-(4-Bromophenyl)-3(3-thienyl)[1,2,3]triazolo[1,5-b]isoquinolinium tetra¯uoroborate
(5i; A ˆ BF4; C20H13BBrF4N3S)
1
Starting from 4i (0.41 g, 1 mmol), 0.2 g (40%) of 5i were obtained. M.p.: 188±189ꢀC; H NMR
(400 MHz, CD3CN‡TFA): ꢀ ˆ 9.84 (s, 1H, H-9), 9.40 (s, 1H, H-4), 8.44 (dd, J ˆ 2.9 Hz, 1.2 Hz, 1H,
H-20), 8.42 (d, J ˆ 8.5 Hz, 1H, H-8), 8.28 (d, J ˆ 8.5 Hz, 1H, H-5), 8.06 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-7), 7.99 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-6), 7.98±7.75 (AA0BB0,4H, H-aryl),
7.87 (dd, J ˆ 5 Hz, 1.2 Hz, 1H, H-40), 7.76 (dd, J ˆ 5 Hz, 2.9 Hz, 1H, H-50) ppm; C20H13BBrF4N3S
(494.11); calcd.: C 48.62, H 2.65, N 8.50; found: C 48.78, H 2.67, N 8.66.
General procedure for the synthesis of indoles 7±9
A solution of 3-isoquinolyl ketone 3d±f (12.5 mmol), 4-bromophenylhydrazine hydrochloride (2.8 g,
15 mmol), and sodium acetate (0.54 g, 15 mmol) in 40 ml acetic acid was re¯uxed for 3 h. After
cooling, the pale yellow precipitate was ®ltered off and recrystallized from acetonitrile.

Â
M. Beres et al.
906
3-(50-Bromo-30H-spiro[cyclohexan-1,30-indol]-20-yl)isoquinoline (7; C22H19BrN2)
Yield: 3.4 g (69.3%); m.p.: 185±187ꢀC; 1H NMR (400 MHz, CDCl3): ꢀ ˆ 9.32 (s, 1H, H-1), 8.84 (s,
1H, H-4), 8.02 (dd, J ˆ 8.5 Hz, 1.5 Hz, 1H, H-8), 8.01 (d, J ˆ 2 Hz, 1H, H-40), 7.96 (dd, J ˆ 8.5 Hz,
1.5 Hz, 1H, H-5), 7.72 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.66 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-6), 7.63 (d, J ˆ 8 Hz, 1H, H-70), 7.54 (dd, J ˆ 8 Hz, 2 Hz, 1H, H-60), 3.18 (m, 2H,
CH2), 2.05±1.67 (m, 6H, CH2), 1.36 (d, 2H, CH2) ppm; 13C NMR (400 MHz, CDCl3): ꢀ ˆ 183.18
(C-20), 152.80, 151.11, 149.12, 146.83 (C-3,4a,70a), 135.88, 128.76, (C-8a,30a), 130.50, 128.42,
127.80, 127.77, 127.33, 122.38, 121.32 (C-4, 5, 6, 7, 8, 40, 60, 70), 118.90 (C-50), 59.66 (C-30), 30.10
(C-cyclohexyl-2,6), 24.92 (C-cyclohexyl-4), 21.94 (C-cyclohexyl-3,5) ppm; C22H19BrN2(391.31);
calcd.: C 67.53, H 4.89, N 7.16; found: C 67.68, H 4.91, N 7.17.
3-(5-Bromo-3-phenyl-1H-indol-20-yl)isoquinoline (8; C23H15BrN2)
1
Yield: 2.8 g (55.7%); m.p.: 175±178ꢀC; H NMR (400 MHz, CDCl3): ꢀ ˆ 10.46 (s, 1H, NH), 9.19
(s, 1H, H-1), 7.92 (dd, J ˆ 8.5 Hz, 1.5 Hz, 1H, H-8), 7.69 (s, 1H, H-4), 7.65 (d, J ˆ 2 Hz, 1H, H-40),
7.58 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.56±7.41 (m, 7H, H-5, 6, phenyl), 7.34 (d, J ˆ 8 Hz,
1H, H-70), 7.30 (dd, J ˆ 8 Hz, 1.5 Hz, 1H, H-60) ppm; 13C NMR (400 MHz, CDCl3): ꢀ ˆ 151.78
(C-1), 143.32, 136.01, 134.79, 134.08, 133.19, 131.28, 127.58, 115.55, 113.40 (C-3,4a,8a,20,30,30a,
50,70a,phenyl-1), 130.45, 129.02 (C-phenyl-2,3,5,6), 130.88, 127.60, 127.40, 127.33, 127.08, 125.98,
122.20, 118.47, 112.77 (C-4,5,6,7,8,40,60,70,C-phenyl-4) ppm; C23H15BrN2 (399.29); calcd.: C 69.19,
H 3.79, N 7.02; found: C 69.16, H 3.77, N 7.06.
3-(5-Bromo-3,3-dimethyl-3H-indol-20-yl)isoquinoline (9; C19H15BrN2)
Yield: 2.5 g (56.0%); m.p.: 146±149ꢀC; C19H15BrN2 (351.25); 1H NMR (400 MHz, CDCl3):
ꢀ ˆ 9.32 (s, 1H, H-1), 8.83 (s, 1H, H-4), 8.02 (dd, J ˆ 8.5 Hz, 1.5 Hz, 1H, H-8), 7.98 (dd, J ˆ 8.5 Hz,
1.5 Hz, 1H, H-5), 7.73 (ddd, J ˆ 8.5 Hz, 8.5 Hz, 1.5 Hz, 1H, H-7), 7.67 (ddd, J ˆ 8.5 Hz, 8.5 Hz,
1.5 Hz, 1H, H-6), 7.60 (d, J ˆ 8 Hz, 1H, H-70), 7.52 (d, J ˆ 2 Hz, 1H, H-40), 7.50 (dd, J ˆ 8 Hz,
2 Hz, 1H, H-60), 1.77 (s, 6H, CH3) ppm; 13C NMR (400 MHz, CDCl3): ꢀ ˆ 184.18 (C-20), 151.93
(C-1), 152.55, 150.72, 146.64 (C-3,4a,70a), 136.16, 129.25 (C-8a,30a), 130.97, 130.89, 128.82,
128.12, 127.71, 125.03, 122.55, 121.08 (C-4,5,6,7,8,40,60,70), 120.16 (C-50), 55.26 (C-30), 24.19
(C-methyl) ppm; C19H15BrN2 (351.25); calcd.: C 64.97, H 4.30, N 7.98; found: C 65.02, H 4.40,
N 8.14.
General procedure for the synthesis of the ring opened products 11a, c, g
To a stirred solution of 0.88 (5 mmol) morpholine in aqueous acetonitrile (2 ml water and 6 ml
acetonitrile), a solution of 5a, c, g (A ˆ BF4, 0.5 mmol) in acetonitrile (20 ml) was added dropwise.
After stirring for 2 h H2O was added, and the mixture was extracted with dichloromethane. The
organic layer was dried over Na2SO4, and the solvent was removed in vacuo. The crude product was
puri®ed by ¯ash chromatography (alumina; n-hexane:ethyl acetate ˆ 5:1).
2-(2-(4-Bromophenyl)-4-methyl-[1,2,3]-triazol-5-ylmethyl)benzaldehyde
(11a; C17H14BrN3O)
Yield: 72 mg (40.0%); m.p.: 90±92ꢀC; 1H NMR (200 MHz, CDCl3): ꢀ ˆ 10.30 (s, 1H, CHO), 7.86±
7.38 (m, 3H, H-4, 5, 6), 7.81±7.47 (AA0BB0, 4H, H-bromophenyl), 7.24 (d, J ˆ 8 Hz, 1H, H-3), 4.50
(s, 2H, CH2), 2.25 (s, 3H, CH3) ppm; HRMS: m/z: calcd.: 355.032, found: 355.032.

[1,2,3]Triazolo[1,5-b]isoquinolinium Salts
907
2-(2-(4-Bromophenyl)-4-(4-chlorophenyl)[1,2,3]-triazol-5-ylmethyl)benzaldehyde
(11c; C22H15BrClN3O)
Yield: 60 mg (26.6%); m.p.: 119±120ꢀC; 1H NMR (400 MHz, CDCl3): ꢀ ˆ 10.27 (s, 1H, CHO),
7.93±7.38 (AA0BB0, 4H, H-bromophenyl), 7.88 (m, 1H, H-6), 7.64±7.56 (AA0BB0, 4H, H-
chlorophenyl), 7.52±7.45 (m, 2H, H-4, 5), 7.19 (m, 1H, H-3), 4.76 (s, 2H, CH2) ppm; HRMS: m/z:
calcd.: 451.008, found: 451.010.
2-(2-(4-Bromophenyl)-4-dimethylethyl-[1,2,3]-triazol-5-yl)benzaldehyde
(11g; C20H20BrN3O)
Yield: 105 mg (53.0%); colourless oil; 1H NMR (200 MHz, CDCl3): ꢀ ˆ 10.28 (s, 1H, CHO), 7.92±
7.40 (m, 3H, H-4, 5, 6), 7.94±7.48 (AA0BB0, 4H, H-bromophenyl), 7.17 (d, J ˆ 8 Hz, 1H, H-3), 4.72
(s, 2H, CH2), 1.40 (s, 9H, CH3) ppm; HRMS: m/z: calcd.: 397.078, found: 397.077.
General procedure for the synthesis of 1,3a,4,9-tetrahydro[1,2,3]triazolo[1,5-b]isoquinolines
13a,c,g
To a stirred solution of 5a,c,g (A ˆ Br, 0.5 mmol) in 5 ml methanol, sodium borohydride (94 mg,
2.5 mmol) was added. After stirring for 2 h at room temperature, 10 ml H20 were added, and stirring
was continued for 30 min. The reaction mixture was extracted with CH2Cl2, the organic layer was
dried over Na2SO4, and the solvent was removed in vacuo. The crude product was recrystallized
from acetonitrile.
1-(4-Bromophenyl)-3-methyl-1,3a,4,9-tetrahydro[1,2,3]triazolo[1,5-b]isoquinoline
(13a; C17H16BrN3)
Yield: 140 mg (81.6%); m.p.: 137ꢀC; 1H NMR (400 MHz, CDCl3): ꢀ ˆ 7.37±7.14 (AA0BB0, 4H, H-
bromophenyl), 7.28±7.15 (m, 4H, H-5, 6, 7, 8), 4.64 (m, 1H, H-3a), 4.02 (d, J ˆ 14.5 Hz, 1H, H-9ꢁ),
3.93 (d, J ˆ 14.5 Hz, 1H, H-9ꢂ), 3.10 (dd, J ˆ 15 Hz, 6 Hz, 1H, H-4ꢁ), 2.96 (dd, J ˆ 15 Hz, 4 Hz, 1H,
H-4ꢂ), 1.87 (d, J ˆ 1.2 Hz, 3H, H-CH3) ppm; C17H16BrN3 (342.24); calcd.: C 59.66, H 4.71, N
12.28; found: C 59.91, H 4.78, N 12.38.
1-(p-Bromophenyl)-3-(4-chlorophenyl)-1,3a,4,9-tetrahydro[1,2,3]triazolo[1,5-b]isoquinoline
(13c; C22H17BrClN3)
Yield: 190 mg (85.9%); m.p.: 157±158ꢀC; 1H NMR (400 MHz, CDCl3): ꢀ ˆ 7.50±7.22 (AA0BB0, 4H,
H-bromophenyl), 7.40±7.36 (AA0BB0, 4H, H-chlorophenyl), 7.26±7.16 (m, 3H, H-5, 6, 7), 7.97 (d,
1H, H-8), 5.29 (m, 1H, H-3a), 4.10 (d, J ˆ 14.5 Hz, 1H, H-9ꢁ), 4.03 (d, J ˆ 14.5 Hz, 1H, H-9ꢂ), 3.16
(dd, J ˆ 15 Hz, 6 Hz, 1H, H-4ꢁ), 3.08 (dd, J ˆ 15 Hz, 4.5 Hz, 1H, H-4ꢂ) ppm; C22H17BrClN3
(438.75); calcd.: C 60.23, H 3.91, N 9.58; found: C 60.17, H 3.86, N 9.46.
1-(p-Bromophenyl)-3-tert.±butyl-1,3a,4,9-tetrahydro[1,2,3]triazolo[1,5-b]isoquinoline
(13g; C20H22BrN3)
1
Yield: 130 mg (67.8%); m.p.: 76±78ꢀC; H NMR (400 MHz, CDCl3): ꢀ ˆ 7.39±7.18 (AA0BB0, 4H,
H-bromophenyl), 7.26±7.15 (m, 4H, H-aryl), 4.63 (m, 1H, H-3a), 4.04 (s, 2H, H-9ꢁ, 9ꢂ) 3.22 (dd,
J ˆ 15 Hz, 7 Hz, 1H, H-4ꢁ), 3.16 (dd, J ˆ 15 Hz, 6 Hz, 1H, H-4ꢂ), 1.26 (s, 9H, CH3) ppm;
C20H22BrN3 (384.32); calcd.: C 62.51, H 5.77, N 10.93; found: C 62.59, H 5.63, N 10.87.

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M. Beres et al.: [1,2,3]Triazolo[1,5-b]isoquinolinium Salts
908
Acknowledgements
OTKA funds (T-026476) are gratefully acknowledged.
References
  Â
[1] For Part 17, see Beres M, Hajos G, Riedl Z, Timari G, Messmer A, Holly S, Schantl JG (1997)
Tetrahedron 53: 9393
Â
[2] Riedl Z, Hajos G, Messmer A, Kollenz G (1993) J Heterocycl Chem 30: 819
Â
Â
[3] Messmer A, Hajos G, Gelleri A, Radics L (1986) Tetrahedron 42: 5415
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[4] Messmer A, Hajos G, Koritsanszky T (1987) J Org Chem 52: 2015
Â
Â
[5] Kotschy A, Hajos G, Messmer A, Jones G (1995) Tetrahedron 52: 1399
[6] Crowne FR, Breckenridge JG (1954) Can J Chem 32: 641
Â
[7] Batori S, Hajos G, Sandor P, Messmer A (1989) J Org Chem 54: 3062
Â
Â
[8] Yamamoto Y, Yanagi A (1982) Chem Pharm Bull 30: 2003
[9] Schnekenburger J, Kaufmann R (1971) Arch Pharm 304: 254
[10] Aubert T, Farnier M, Hanquet B, Guilard R (1987) Synth Comm 17: 1831
[11] Aubert T, Farnier M, Guilard R (1990) Can J Chem 68: 842
Received January 14, 1998. Accepted (revised) March 10, 1998.