Synthesis of original thiazoloindolo[3,2-c]quinoline and novel 8-N-substituted-11H-indolo[3,2-c]quinoline derivatives from benzotriazoles. Part I

Article abstract of DOI:10.1016/j.tet.2005.09.153

Synthesis of novel thiazoloindolo[3,2-c]quinoline and 8-substituted-11H- indolo[3,2-c]quinolines was performed via Graebe-Ullmann thermal cyclization from appropriated N-arylated benzotriazoles. 7H-4,7-Diaza-benzo[de]anthracene, a by-product reaction stru

Full text of DOI:10.1016/j.tet.2005.09.153

Tetrahedron 62 (2006) 1895–1903
Synthesis of original thiazoloindolo[3,2-c]quinoline and novel
8-N-substituted-11H-indolo[3,2-c]quinoline derivatives from
benzotriazoles. Part I
Anne Beauchard,a Hadjila Chabane,a Sourisak Sinbandhit,b Pierre Guenot,b
a,
Valerie Thiery and Thierry Besson
a
*
´
´
a
´
Laboratoire de Biotechnologies et Chimie Bio-organique, FRE CNRS 2766, Universite de La Rochelle,
´
Avenue Michel Crepeau, 17042 La Rochelle, France
b
´
´
Centre Regional de Mesures Physiques de l’Ouest, Universite de Rennes 1, 35042 Rennes, France
Received 22 July 2005; revised 23 September 2005; accepted 29 September 2005
Available online 9 January 2006
Abstract—Synthesis of novel thiazoloindolo[3,2-c]quinoline and 8-substituted-11H-indolo[3,2-c]quinolines was performed via Graebe–
Ullmann thermal cyclization from appropriated N-arylated benzotriazoles. 7H-4,7-Diaza-benzo[de]anthracene, a by-product reaction
structurally closed to pyridoacridine skeleton was also identified.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
R
N
S
O
N
S
N
The thiazole ring in various natural and synthetic products
has generated interest of many groups on account of its
useful biological properties.1 Thus, in our laboratory we
launched a research program dealing with the preparation
and pharmacological evaluation of some original thiazolo
derivatives.2 We recently reported the regiocontrolled
synthesis of substituted thiazoloheterocycles (I and II)
mainly related to marine or terrestrial alkaloids (e.g.,
dercitine, kuanoniamine and ellipticine), which exhibit
interesting antitumor activity (Fig. 1).3 Numerous indolo-
quinoline alkaloids have been identified from extracts of
West African plant Cryptolepis sanguinolenta. Isocrypto-
lepine III (also referred to as cryptosanguinolentine) with a
indolo[3,2-c]quinoline (or a benzo-g-carboline) structure is
very rare in nature (Fig. 1).4 Owing to their growing use in
compounds of therapeutic importance (antibacterial, anti-
plasmodial, anticancer drugs),5 the synthesis of indoloqui-
noline derivatives has been actively pursued in the past
decade.
N
N
N
N
H
Isocryptolepine
I
II
III
RNH
R
N
S
N
RNH
NH
N
N
N
H
N
H
IV
V
VI
Figure 1. Structures of various potential biological heterocycles and
expected skeletons studied in this paper.
onto indolo[3,2-c]quinoline skeleton. Synthetic strategies
have been developed for benzo-g-carboline based on
palladium-catalyzed reactions (Heck, Buchwald/Hartwig),6
Fischer indole cyclization7 and thermal ring transformation8
(Graebe–Ullmann). For the synthesis of thiazoloindolo-
quinoline IV, we firstly turned our attention to the Graebe–
Ullmann reaction from 4-quinolinylthiazolobenzotriazole
VII as outlined in Scheme 1. To the best of our knowledge,
the chemical behaviour of 4-quinolinyl-functionalized
benzotriazole has been rarely reported; a literature survey
revealed cyclization of nude benzotriazole or 5,6-dimethyl-
benzotriazole coupled with quinoline.5b
We focussed our studies on the synthesis of biologically
active compounds in which the thiazole ring might be fused
Keywords: Indoloquinoline; Benzotriazoles; Fused ring systems; Graebe–
Ullmann; Microwaves.
Corresponding author. Tel.: C33 5 46 45 82 76; fax: C33 5 46 45 82 47;
e-mail: vthiery@univ-lr.fr
*
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.153

1896
A. Beauchard et al. / Tetrahedron 62 (2006) 1895–1903
R
S
N
R
Cl
N
R
S
S
N
N
N
N
N
+
N
N
N
N
N
H
N
H
IV
VII
Scheme 1. Retrosynthetic pathway thiazoloindoloquinoline IV.
RNH
Cl
N
N
RNH
N
RNH
+
N
N
N
N
N
N
H
H
V
VIII
N
Scheme 2. Retrosynthetic pathway to 8-functionalized indolo[3,2-c]quinoline V.
After several attempts to obtain 8-functionalized indolo[3,2-
c]quinoline V, we decided to study the thermal cyclization
of (4-quinolinyl)-5-N-substituted-benzotriazole VIII pre-
cursor (Scheme 2). The thermal cyclization of this latest
provided original 8-N-substituted-indolo[3,2-c]quinoline
together with unexpected 10-N-substituted-7H-4,7-diaza-
benzo[de]anthracene skeleton VI (Fig. 1).
of pyridine, to give the desired imino-1,2,3-dithiazolo-
benzotriazole 3 in moderate yield with cyanothioformamide
4 compound as major product. At low temperature
(K20 8C), the reaction mainly yielded the attempted
imine 3 (75%) (Scheme 3).
The thermolysis of the benzotriazole derivative 3 in a
refluxed mixture of toluene and N-methylpyrrolidinone
under microwave irradiation, gave the angular compound 5
in reasonable yield (68%) beside trace of decyanated
counterpart 6. No trace of linear isomer was detected. A
mild procedure, which consists to heat an ortho bromoimine
7 in the presence of cuprous iodide in pyridine at reflux, was
applied and afforded regioselectively this angular isomer 5
in good yield (73%) (Scheme 4).2c
In this paper, we describe the chemical transformation of
substituted benzotriazolylquinoline upon thermal cycli-
zation and the synthesis of novel substituted polyheterocyclic
compounds, which have never been described until now.
Reactions were performed under microwave irradiation.9
2. Results and discussion
2.2. Synthesis of quinolin-4-yl-1H-thiazolo[40,50:304]-
benzo[1,2-d][1,2,3]triazole-7-carbonitrile
2.1. Synthesis of 3H-thiazolo[50,40:3,4]benzo[1,2-d][1,2,3]-
triazole-7-carbonitrile precursor
The preparation of quinolinylbenzotriazole by condensation
of 4-chloroquinoline 8 and the corresponding benzotriazole
5 under neat conditions at high temperature led to
carbonaceous mixtures. We found that microwave
irradiation (160 8C, in sealed vial) of an equimolar mixture
of 4-chloroquinoline and thiazolobenzotriazole in solution
with a minimum of toluene afforded two condensed
compounds 9 and 10 in moderate yields (33 and 44%)
(Scheme 5).
Studying the chemistry of 4,5-dichloro-1,2,3-dithiazolium
chloride (Appel salt) and its derivatives, it was previously
shown that 5-(N-arylimino)-4-chloro-5H-1,2,3-dithiazoles,
which are stable crystalline solids, cyclized by vigorous
heating to give sulphur, hydrogen chloride and 2-cyano-
benzothiazoles.10 Synthesis of rare thiazolobenzotriazole
ring was then performed in two steps from the starting
commercially available 5-aminobenzotriazole. Using a
standard method applied to the preparation of N-aryl-
imino-1,2,3-dithiazoles,2,3 the starting amine was con-
densed with 4,5-dichloro-1,2,3-dithiazolium chloride in
dichloromethane at room temperature, followed by addition
The presence of regioisomers is due to the tautomeric nature
of the triazole function.11 In literature, the alkylation of
different 1,2,3-triazoles did not allow for any selective
H
N
H2N
Cl
+
Cl
S
N
N
NC
N
pyridine, –20˚C
2 h
N
S
N
N
+
+
N
N
S
N
H
N
H
N
S
Cl
-
N
H
S
Cl
1
2
3
4
Scheme 3. Synthesis of (1H-benzotriazol-5-yl)-(4-chloro-[1,2,3]dithiazol-5-yliden)amine 3.

A. Beauchard et al. / Tetrahedron 62 (2006) 1895–1903
1897
NC
S
S
N
S
toluene, NMP
N
N
N
N
N
S
S
N
N
+
N
N
N
µW, 30 min
N
H
Cl
N
H
N
H
3
3
5
7
6
NC
N
Br
S
CuI, pyridine
N
N
S
Br2, AcOH
12 h, rt
S
N
N
N
S
N
N
µW, 10 min
N
N
N
H
N
H
Cl
N
H
Cl
5
Scheme 4. Cyclization of (1H-benzotriazol-5-yl)-(4-chloro-[1,2,3]dithiazol-5-yliden)amine 3.
NC
7
S
8
N
NC
N1
N
N
6
NC
N
Cl
N
S
S
N
2
+
N
+
toluene, 160 ˚C
µW, 60 min
N
5
N
N
N
3
4
N
N
H
4'
N1'
5
8
9
10
Scheme 5. Condensation of thiazolobenzotriazole with 4-chloroquinoline.
anticipation of N-alkylation of the thiazolo condensed-
1,2,3-triazole. In order to establish unambiguously the
structure of the different regioisomers, we envisaged an
X-ray diffraction study. Unfortunately, all attempts to obtain
suitable crystals failed. Because of the steric hindrance, we
assumed that the isomer 9 generated arylation in position 3
of the thiazolobenzotriazole ring was the major compound.
N-arylated benzotriazole 9 in a quartz glassware with
pyrophosphoric acid and toluene at 250 8C for 5 min
afforded a complex mixture from which thiazolo-
indolo[3,2-c]quinoline 11 and decyanated N-arylbenzo-
triazole 12 were isolated in, respectively, 17 and 23%
yields (Scheme 6). A long exposition at high temperature
was unfruitful and led to the degradation of the material and
a longer reaction time at a lowest temperature (180 8C)
yielded mainly to compound 12. After several attempts with
various acids, the reaction was carried out in DMF at reflux.
The reaction afforded 75% of carboxamide 13. Exposing the
same benzotriazole 9 to microwave irradiation, neat in glass
vial with a screw cap lid, or with few drops of acid or polar
solvent (DMF, NMP, etc.) were also unsuccessful.
1
It must be noted that 2D H–13C correlation experiments
and 1H NMR NOESY experiments on the derivative 9 were
also non-conclusive.
2.3. Thermolysis of quinolin-4-yl-1H-thiazolo[40,50:304]-
benzo[1,2-d][1,2,3]triazole-7-carbonitrile
Classic Graebe–Ullmann conditions for the elimination of
nitrogen from 1-aryl-1H-benzo-1,2,3-triazoles involve heat-
ing the triazole derivative beyond its melting point. Inspired
by Alvarez-Builla’s procedure, we firstly used pyropho-
sphoric acid as solvent.5b,8d Microwave irradiation of the
To the best of our knowledge, the synthesis of indolo-
[3,2-c]quinoline fused onto 7,8-thiazole (or 8H-1-thia-
3,6,11-triaza-cyclopenta[d]-benzo[a]fluorene) has never
been reported until now.
O
H2N
S
H4P2O7,
NC
N
S
N
N
+
DMF, 160 ˚C
µW, 35 min
250 ˚C
N
N
S
N
S
N
N
µW, 5 min
N
N
N
N
N
H
N
N
N
N
13
9
11
12
N
Scheme 6. Thermal cyclization of 3-N-aryl-thiazolobenzotriazole.

1898
A. Beauchard et al. / Tetrahedron 62 (2006) 1895–1903
2.4. Synthesis of N-(quinolin-4-yl-1H-benzotriazol-5-yl)-
acetamide
AcHN
AcHN
N
N
6
6
N
The following part of our study was focused on the synthesis
of original N-8-substituted-indolo[3,2-c]quinoline. Accord-
ing to the results obtained above, we decided to study the
chemical transformation of N-(quinolin-4-yl-1H-benzo-
triazol-5-yl)-acetamide (Scheme 2).
N
7
7
N
N
H
H
H
5'
H
H
3'
6'
15
N
N
2'
Strong NOE contributions
Weak NOE contributions
n-Acetylation of 5-aminobenzotriazole 1 was performed
with 1 equiv of acetic anhydride in pyridine at low
temperature (K10 8C) to overcome additional acetylation
on triazole nitrogen and yielded 75% of acetamide 14
(Scheme 7).12
Figure 2. NOE contributions.
2.5. Thermolysis of N-1-quinolin-4-yl-benzotriazole 15
Expecting a similar chemical behaviour to that observed for
benzotriazole 9, the cyclization of N-protected benzotria-
zole 15 was also studied under microwave irradiation.
Various attempts under neat conditions or in boiling neutral
media (toluene or triglyme) afforded small amounts of 8-N-
acetamidoindolo[3,2-c]quinoline 18 (6%) from complicated
mixture. Thermolysis (in boiling pyrophosphoric acid at
250 8C) led to the complete degradation of the reactant
within less than 5 min. Performed at 200 8C during 3 min,
the same reaction in boiling acid appeared more efficient
and yielded, respectively, 27% of deprotected 8-amino-
11H-indolo[3,2-c]quinoline 19, 8% of N-acetamidotetra-
cycle 18 besides traces of non-cyclized amines 21 and 22.
Most unexpected was the isolation of a different fused ring
system 20 in moderate yield 35% (Scheme 9).5e,8f
H
Ac2O, pyridine
H2N
H3C
N
N
N
–10 ˚C
N
N
O
N
H
N
H
4 h
14
1
Scheme 7. Protection of 5-aminobenzotriazole 1.
Using the same procedure described in Section 2.2, the
acetamide14was subjectedtotheactionof4-chloroquinoline
8 under microwave irradiation. Whatever the solvent used
(toluene, DMF or NMP), reaction yielded mixtures of
three monoalkylated derivatives (15: 43%, 16: 30% and 17:
10%) (Scheme 8). The structures of compounds 15–17 were
confirmed by their analytical and spectroscopic data. The
isomer 17 obtained in 10% yield, was easily identified on
the basis of mass spectral evidence. In agreement with the
known behaviour of 2-substituted 1,2,3-triazoles to electron
impact, its mass spectrum did not exhibit peaks issued from
molecular ions through the initial extrusion N2.
Furthermore, the 1H NMR spectrum was different from the
normal indolo[3,2-c]quinoline pattern showing a H-C6
characteristic singulet. The theoretical signal of the quino-
line H-2 (dZ8.53 ppm, d, JZ5.2 Hz) and its coupling with
the H-3 (dZ6.83 ppm, d, JZ5.2 Hz) still appeared. All the
spectroscopic data fitted well for a fused quinolinoquinoline
structure.
To unambiguously identify the regioisomers formed by
1
The N-(7H-4,7-diaza-benzo[de]anthracen-10-yl)-acetamide
20, which is structurally closed to pyrodoacridine skeleton
present in marine alkaloid can be considered as an
interesting intermediate for the preparation of novel
rings.1d,e,13
arylation in position 1 and 3 on the triazole, 2D H–13C
NMR (HMBC and HMQC) correlation experiments were
performed on compounds 15 and 16, but the detected
1H–13C correlations were not helpful for a structural
determination. Unequivocal differenciation of substitution
of quinoline at position N-1 or N-3 was determined by
performing by 1H NMR COSY, NOESY experiments on the
derivative 15, the NOE experiments showing strong effect
between 7-H of triazole and 30-H of quinoline and weaker
effects between 7-H of triazole and 50-H of quinoline
(Fig. 2).
3. Conclusion
In conclusion, we showed that 4-(substituted-benzotriazo-
lyl)quinoline might be a convenient precursor for
the synthesis of the original fused ring like
AcNH
AcHN
4
5
N 3
N
6
AcHN
Cl
N
N
N
N
N
N
AcHN
N
N
2
N
7
N
N
DMF, 160 ˚C
1
+
+
N
+
N
µW, 60 min
N
H
14
8
15
16
17
Scheme 8. Condensation of acetamidobenzotriazole 14 with 4-chloroquinoline.

A. Beauchard et al. / Tetrahedron 62 (2006) 1895–1903
1899
NH2
NH2
+
NHAc
N
AcHN
N
N
RNH
HN
N
HN
N
N
N
+
µW
+
N
N
N
N
H
N
R = Ac, 18
R = H, 19
15
20
21
22
Scheme 9. Thermal cyclization of N-1-aryl-acetamidobenzotriazole.
thiazoloindolo[3,2-c]quinoline and quinolinoquinoline
rings system, following a microwave-assisted Graebe–
Ullmann cyclization.
of a vessel is monitored using a calibrated infrared sensor
mounted under the vessel.14 All the experiments were
performed using stirring option whereby the contents of a
vessel are stirred by means of a rotating plate located below
the floor of the microwave cavity and a Teflon-coated
magnetic stir bar in the vessel. In all experiments a target
temperature was selected together with a power. The target
temperature was reached with a ramp of 2 min and the
chosen microwave power stayed constant to hold the
mixture at this temperature. The reaction time does not
include the ramp period.
The chemical and biological interest of thiazoloindolo[3,2-
c]quinoline 11, 8-amino-11H-indolo[3,2-c]quinoline
derivatives 18, 19 and quinolinoquinoline 20 mainly
obtained in these experiments are under investigation.
This latest new ring system was identified as a suitable
starting precursor for conversion to dercitin analogs.13
4.2. Synthesis of iminodithiazoles
4. Experimental
Under an inert atmosphere of argon, 4,5-dichloro-1,2,3-
dithiazolium chloride 2 (1.71 g, 74.5 mmol) was added to a
stirred solution of commercially available 5-aminobenzo-
triazole 1 (1.00 g, 74.5 mmol) in dichloromethane (30 mL)
at K20 8C. After 45 min, pyridine (1.32 mL, 163.9 mmol)
was added and the mixture stirred for 2 h. The obtained
precipitate was filtered and purified by chromatography on
silica gel with dichloromethane–methanol (99/1) as eluent
to give the expected iminodithiazole 3 with cyanothiofor-
mamide 4.
4.1. General remarks
All solvents and reagents were reagent grade and were used
without purification. Melting points were determined using
¨
a Kofler melting point apparatus and are not corrected. IR
spectra were recorded on a Perkin-Elmer Paragon 1000PC
1
instrument. H and 13C NMR were recorded on a JEOL
JNM LA400 (400 MHz) spectrometer (Centre Commun
´
d’Analyses, Universite de la Rochelle) and on a Brucker
Avance 500 and 300 MHz (HMBC, HMQC and NOE
´
experiments) in the Centre Regional de Mesures Physiques
4.2.1. (1H-Benzotriazol-5-yl)-(4-chloro-[1,2,3]dithiazol-
5-yliden)amine 3. Yield: 75%. MpZ195–197 8C (ethanol).
1H NMR (DMSO-d6, 400 MHz) dZ15.70 (br s, 1H, NH),
8.04 (d, JZ8.8 Hz, 1H, 7-H), 7.65 (s, 1H, 4-H), 7.26 (dd,
JZ8.8, 2.2 Hz, 1H, 6-H). 13C NMR (DMSO-d6, 100 MHz)
dZ159.91, 148.90, 146.44, 138.32, 137.92, 119.39, 117.10,
de l’Ouest (CRMPO); chemical shifts (d) are reported in
part per million (ppm) downfield from tetramethylsilane
(TMS), which was used as internal standard. Coupling
constants J are given in Hz. The mass spectra (HRMS) were
recorded on a Varian MAT 311 spectrometer in the
´
CRMPO, Universite de Rennes. Column chromatography
102.19. IRZ3099, 2768, 1694, 1574, 1200, 1199, 861 cmK1
.
was performed by using Merck silica gel (70–230 mesh) at
medium pressure. Light petroleum ether refers to the
fraction boiling point 40–60 8C. Analytical thin-layer
chromatography (TLC) was performed on Merck Kieselgel
60 F254 aluminium backed plates.
HRMS (EI) [M]C% (C8H4N5Cl2): calcd 268.9597; found
268.9599.
4.2.2. N-(1H-Benzotriazol-5-yl)-2-nitrilo-thioacetamide
4. Yield: 5%. MpZ130–132 8C (ethanol). 1H NMR
(DMSO-d6CD2O, 400 MHz) dZ8.79 (s, 1H, ArH), 8.02
(d, JZ8.4 Hz, 1H, ArH), 7.67 (d, JZ8.4 Hz, 1H, ArH).
After purification by chromatography on silica gel,
compounds 3, 4, 5, 7, 9, 10, 12, 15, 16, 17 were
recrystallized in ethanol and compound 13 in DMF.
IRZ3254, 2224, 1701, 1609, 1409, 1203, 995, 620 cmK1
.
HRMS (EI) [MKHCN]C (C7H3N4S): calcd 176.0156;
found 176.0152.
Microwave experiments were carried out at atmospheric
pressure using a focused microwave reactor (CEM
Discovere or Synthewavew402 Prolabo). The instrument
consists of a continuous focused microwave power output
from 0–300 W. Reactions were performed in a glass vessel
(CEM) and in quartz reactor vessel (Prolabo) prolonged by a
condenser; it is also possible to work under dry atmosphere,
in vacuo, or under pressure (0–20 bar, tubes of 10 mL,
sealed with a septum) if necessary. The temperature content
4.3. Bromination
Under an inert atmosphere of argon, to a solution of imine 3
(0.36 g, 13.35 mmol) in dichloromethane (5 mL) was added
dropwise bromine (0.08 mL, 14.68 mmol) in solution
in acetic acid (3 mL). After 12 h under stirring at room
temperature, the residue was treated with a saturated

1900
A. Beauchard et al. / Tetrahedron 62 (2006) 1895–1903
solution of sodium thiosulfate Na2SO3 (15 mL) and
extracted with ethyl acetate. The organic layer was dried
(MgSO4) and the filtrate was concentrated under reduced
pressure. The crude residue was purified by chromatography
on silica gel, with dichloromethane–ethyl acetate (95/5) as
eluent to give the bromo derivative 7.
4.5. Synthesis of quinolinylbenzotriazoles
Under an inert atmosphere of argon, a solution of an
equimolar mixture of commercial 4-chloroquinoline
(0.12 g, 0.73 mmol) and thiazolobenzotriazole 5 (0.14 g,
0.73 mmol) in toluene (2 mL) was heated at 160 8C in a
sealed tube for 1 h. After cooling, the toluene was removed
in vacuo. The mixture was diluted with dichloromethane
(10 mL) and washed with water (10 mL). The organic layer
was dried (MgSO4) and concentrated under reduced
pressure. The crude residue was purified by column
chromatography on silica gel, with light petroleum ether–
ethyl acetate (80/20) as eluent to provide 2 regioisomers 9
and 10 in, respectively, 44 and 33% yield.
4.3.1. 4-Bromo-5-(4-chloro-5H-1,2,3-dithiazol-5-ylidena-
mino)benzotriazole 7. Yield: 87%. MpZ200–202 8C
1
(ethanol). H NMR (DMSO-d6CD2O, 400 MHz) dZ7.99
(d, JZ8.8 Hz, 1H, 7-H), 7.26 (d, JZ8.8 Hz, 1H, 6-H). 13C
NMR (DMSO-d6, 100 MHz) dZ163.55, 148.11, 146.06,
140.12, 137.07, 126.67, 118.51, 116.64. IRZ3238, 2792,
1596, 1201, 1147, 857 cmK1. HRMS (EI) [M]C% (C8H3-
N355Cl79BrS2): calcd 346.8702; found 346.8703.
4.5.1. 3-Quinolin-4-yl-1H-thiazolo[40,50:30,4]benzo[1,2-d]-
[1,2,3]triazole-7-carbonitrile 9. Yield: 44%. MpZ238–
4.4. Cyclization
1
240 8C (ethanol). H NMR (CDCl3, 400 MHz) dZ9.23 (d,
JZ4.4 Hz, 1H, 20-Hquinolin.), 8.38 (d, JZ9.2 Hz, 1H, ArH),
8.33 (d, JZ9.2 Hz, 1H, 5-H or 4-H), 7.92 (ddd, JZ2.0,
6.8, 9.2 Hz, 1H, ArH), 7.69 (d, JZ4.4 Hz, 1H, 30-Hquinolin.),
7.68 (ddd, JZ2.0, 6.8, 9.2 Hz, 1H, ArH), 7.66 (d, JZ
9.2 Hz, 1H, ArH), 7.62 (d, JZ9.2 Hz, 1H, 4-H or 5-H).
13C NMR (CDCl3, 100 MHz) dZ151.00, 150.42 (20-C),
150.12, 139.75, 136.24, 135.79, 133.81, 131.12 (70-C),
130.45, 128.77, 126.71, 125.69, 122.91, 122.55, 117.72
(30-C), 112.63, 111.09. IRZ2921, 2339, 1435, 1260, 805,
760 cmK1. HRMS (EI) [M]C% (C17H8N6S): calcd 328.0531;
found 328.0530.
Method A. Under an inert atmosphere of argon, a solution of
iminodithiazole 3 (1.0 g, 3.72 mmol) in N-methylpyrro-
lidin-2-one/toluene (5 mL, v/v) was irradiated during
30 min. The irradiation in CEM oven was programmed to
maintain a constant temperature (180 8C) with a maximal
power output of 150 W. After cooling, the toluene was
removed under reduced pressure. The mixture was diluted
with ethyl acetate (20 mL) and washed with water (3!
15 mL). The organic layer was dried (MgSO4) and the
filtrate was concentrated under reduced pressure. The crude
residue was purified by chromatography on silica gel, with
dichloromethane–ethyl acetate (90/10) as eluent to give the
thiazolo derivative 5 (68%).
4.5.2. 1-Quinolin-4-yl-1H-thiazolo[40,50:304]benzo[1,2-d]-
[1,2,3]triazole-7-carbonitrile 10. Yield: 33%. MpZ252–
1
Method B. Under an inert atmosphere of argon, a suspension
of bromo imine 7 (0.3 g, 8.6 mmol), copper iodide (0.17 g,
8.6 mmol) in pyridine (5 mL) was irradiated during 10 min.
The irradiation was programmed to obtain a constant
temperature (110 8C) with a maximal power output of
80 W. After cooling, the mixture was treated with a
saturated solution of Na2SO3 (20 mL) and extracted with
ethyl acetate. The organic layer was dried (MgSO4) and
concentrated under reduced pressure. The crude residue was
purified by chromatography on silica gel, with dichloro-
methane–ethyl acetate (90/10) as eluent to give the thiazolo
derivative 5 (85%).
254 8C (ethanol). H NMR (CDCl3, 400 MHz) dZ9.16 (d,
JZ4.9 Hz, 1H, 20-Hquinolin.), 8.84 (d, JZ8.0 Hz, 1H, 4-H or
5-H), 8.31 (d, JZ8.0 Hz, 1H, 5-H or 4-H), 8.26 (d, JZ
9.3 Hz, 1H, ArH), 8.20 (d, JZ9.3 Hz, 1H, ArH), 8.12 (d,
JZ4.9 Hz, 1H, 30-Hquinolin.), 7.91 (t, JZ7.2 Hz, 1H, ArH),
7.77 (t, JZ7.2 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz)
dZ153.09, 150.24, 150.16, 144.73, 143.09, 139.61, 139.65,
130.55, 130.24, 128.69, 125.12, 124.54, 124.03, 120.72,
119.03, 116.17, 112.70. IRZ3069, 2919, 2230, 1715, 1562,
1501, 1432, 1395, 995, 831, 774 cmK1. HRMS (EI) [M]C%
(C17H8N6S): calcd 328.0531; found 328.0530.
4.6. Cyclization of quinolinylbenzotriazole
4.4.1. 3H-Thiazolo[50,40:3,4]benzo[1,2-d][1,2,3]triazole-
7-carbonitrile 5. Yield: 85% (obtained from method A).
MpZ228–230 8C (ethanol). 1H NMR (DMSO-d6,
400 MHz) dZ16.50 (br s, 1H, NH), 8.26 (d, JZ8.8 Hz,
1H, 4-H), 8.15 (d, 1H, JZ8.8 Hz, 5-H). 13C NMR (DMSO-
d6, 100 MHz) dZ170.31, 152.2, 150.20, 135.09, 124.1,
122.79, 114.65, 113.25. IRZ3111, 2830, 2239, 1712, 1694,
1407, 1197, 804 cmK1. HRMS (EI) [M]C% (C8H3N5S):
calcd 201.0109; found 201.0108.
In a quartz reactor, a solution of the corresponding
benzotriazolylquinoline 9 (0.08 g, 0.26 mmol) and H4P2O7
(1 mL) in toluene (1 mL) placed was heated at 250 8C until
the evolution of nitrogen ceased after 5 min. The reaction
mixture was then triturated with water and basified with a
saturated solution of NaHCO3 (8 mL). The resulting
precipitate was diluted with ethyl acetate (15 mL) and
extracted. The organic layer was dried (MgSO4) and
concentrated under reduced pressure. The crude residue
was purified by chromatography on silica gel, with
dichloromethane as eluent, to give the thiazoloindolo-
[3,2-c]quinoline 11 and the compound 12.
4.4.2. 3H-Thiazolo[50,40:3,4]benzo[1,2-d][1,2,3]triazole 6.
Yield: trace (method A). MpZO260 8C. 1H NMR (DMSO-
d6, 400 MHz) dZ16.23 (br s, 1H, NH), 9.47 (s, 1H, 7-H),
8.14 (d, JZ8.8 Hz, 1H, 4-H or 5-H), 7.98 (d, 1H, JZ8.8 Hz,
5-H or 4-H). 13C NMR (DMSO-d6, 100 MHz) dZ155.21,
155.12, 152.17, 136.50, 122.37, 120.77, 113.08. IRZ3436,
3073, 2925, 1412, 1315, 1189, 876 cmK1. HRMS (EI) [M]C%
(C7H4N4S): calcd 176.0156; found 176.0152.
4.6.1. 8H-1-Thia-3,10,12-triaza-benzo[a]cyclopenta[d]-
fluorene 11. Yield: 17%. MpZO260 8C. 1H NMR
(CD3ODCD2O, 400 MHz) dZ9.47 (s, 1H, 11-Hquinolin.),
9.30 (s, 1H, 2-Hthiazol.), 8.50 (dd, JZ6.8, 1.2 Hz, 1H, ArH),

A. Beauchard et al. / Tetrahedron 62 (2006) 1895–1903
1901
8.24–8.18 (m, 2H, ArH), 7.92 (d, JZ8.8 Hz, 1H, 4-H or
5-H), 7.82 (t, JZ7.2 Hz, 1H, ArH), 7.75 (t, JZ7.2 Hz, 1H,
ArH). IRZ2920, 1787, 1713, 1288, 611 cmK1. HRMS (EI)
[M]C% (C16H9N3S): calcd 275.0517; found 275.0513.
4.8.1. N-(1-Quinolin-4-yl-1H-benzotriazol-5-yl)-aceta-
mide 15. Yield: 43% (0.72 g). MpZO260 8C (ethanol).
1H NMR (DMSO-d6, 400 MHz) dZ10.37 (s, 1H, NH), 9.21
(d, JZ4.5 Hz, 1H, 20-Hquinolin.), 8.65 (d, JZ0.9 Hz, 1H, 4-
H), 8.27 (d, 1H, JZ8.4 Hz, 80-H), 7.95 0(d, JZ4.5 Hz, 1H,
30-Hquinolin.), 7.94 (td, JZ1.5, 6.7 Hz, 7 -H), 7.79 (dd, JZ
1.0, 8.7 Hz, 1H, 50-H), 7.72 (td, JZ1.0, 6.7 Hz, 60-H
partially mixed with 6-H), 7.70 (d, 1H, 6-H), 7.63 (d, JZ
8.9 Hz, 1H, 7-H), 2.14 (s, 3H, COCH3). 13C NMR (CD3OD,
100 MHz) dZ168.68, 151.04, 149.19, 145.61, 139.46,
136.64, 130.68, 129.91, 129.51, 128.29, 123.00, 122.60,
122.33, 117.53, 110.91, 107.32, 23.96. IRZ3487, 1666,
1378, 1305, 1041, 809, 757 cmK1. MS (m/z) 303, 275
(MC%KN2). HRMS (EI) [M]C% (C17H13N5O): calcd
303.1120; found 303.1120.
4.6.2. N-(3-Quinolin-4-yl)-1H-thiazolo[50,40:3,4]benzo-
[1,2-d][1,2,3]triazole 12. Yield: 23%. MpZ228–230 8C
1
(ethanol). H NMR (CDCl3, 400 MHz) dZ9.17 (s, 1H, 7-
H), 9.14 (d, JZ4.4 Hz, 1H, 20-Hquinolin.), 8.91 (d, JZ8.8 Hz,
1H, ArH), 8.29 (d, JZ8.8 Hz, 1H, A0rH), 8.14 (d, JZ9.2 Hz,
1H, ArH), 8.12 (d, JZ4.4 Hz, 1H, 3 -Hquinolin.), 8.08 (d, JZ
9.2 Hz, 1H, ArH), 7.87 (t, JZ7.2 Hz, 1H, ArH), 7.75 (t, JZ
7.2 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz) dZ154.40,
154.25, 148.20, 144.54, 141.09, 131.56, 129.23, 128.19,
125.80, 125.10, 121.36, 120.88, 116.87, 115.62. IRZ3487,
1920, 1727, 1631, 1305, 1230, 991, 829, 760 cmK1. HRMS
(EI) [M]C% (C16H9N5S): calcd 303.0568; found 303.0566.
4.8.2. N-(3-Quinolin-4-yl-3H-benzotriazol-5-yl)-aceta-
mide 16. Yield: 30% (0.49 g). MpZO260 8C (ethanol).
1H NMR (CDCl3, 400 MHz) dZ9.15 (d, JZ4.4 Hz, 1H, 20-
Hquinolin.), 8.30 (d, 1H, JZ8.8 Hz, ArH), 8.20 (s, 1H, ArH),
8.13 (d, 1H, JZ8.8 Hz, ArH), 7.89–7.81 (m, 2H, ArH),
7.64–7.60 (m, 2H, JZ4.4 Hz, 30-Hquinolin., ArH), 7.51 (br s,
1H, NH), 7.21 (dd, 1H, JZ2.0, 8.8 Hz, ArH), 2.20 (s, 3H).
13C NMR (CDCl3, 100 MHz) dZ168.54, 150.42, 150.05,
142.71, 140.44, 138.51, 134.76, 130.73, 130.09, 128.18,
123.31, 123.09, 120.86, 118.19, 117.06, 99.94, 24.80. IRZ
3243, 3069, 1696, 1555, 1496, 1261, 813 cmK1. MS (m/z)
303, 275 (MC%KN2). HRMS (EI) [M]C% (C17H13N5O):
calcd 303.1120; found 303.1112.
4.6.3. N-(3-Quinolin-4-yl)-1H-thiazolo[50,40:3,4]benzo-
[1,2-d][1,2,3]triazole-7-carboxamide 13. Yield: 75%
1
(from DMF). MpZO260 8C. H NMR (CD3ODCD2O,
400 MHz) dZ9.15 (d, JZ4.4 Hz, 1H, 20-Hquinolin.), 8.89
(dd, JZ8.8, 0.8 Hz, 1H, ArH), 8.29 (t, JZ8.4 Hz, 1H,
ArH), 8.19 (t, JZ8.4 Hz, 1H, ArH), 8.14 (s, 1H, ArH), 7.88
(dd, JZ8.4, 0.8 Hz, 1H, ArH), 7.71 (d, JZ8.4 Hz, 1H,
ArH), 7.53 (d, JZ8.4 Hz, 1H, ArH). IRZ3313, 2904,
1712, 1663, 1505, 1400, 1118, 805, 758 cmK1. HRMS (EI)
[M]C% (C17H10N6OS): calcd 346.0636; found 346.0639.
4.8.3. N-(2-Quinolin-4-yl-3H-benzotriazol-5-yl)-aceta-
mide 17. Yield: 10% (0.17 g). MpZ226–228 8C (ethanol).
1H NMR (CDCl3, 400 MHz) dZ9.11 (d, JZ4.8 Hz, 1H, 20-
Hquinolin.), 8.88 (d, 1H, JZ8.4 Hz, ArH), 8.48 (s, 1H, ArH),
8.26 (d, 1H, JZ8.8 Hz, ArH), 8.07 (d, 1H, JZ4.8 Hz, 30-
Hquinolin.), 7.97 (d, 1H, JZ8.8 Hz, ArH), 7.85 (t, 1H, JZ
7.8 Hz, ArH), 7.72 (t, 1H, JZ7.8 Hz, ArH), 7.39 (dd, 1H,
JZ2.0, 8.8 Hz, ArH), 7.37 (s, 1H, NH), 2.29 (s, 3H). IRZ
3423, 2953, 1693, 1498, 1261, 668, 612 cmK1. MS (m/z)
303. HRMS (EI) [M]C% (C17H13N5O): calcd 303.1120;
found 303.1122.
4.7. Acetylation
Under an inert atmosphere of argon, acetic anhydride
(1.06 mL, 11.82 mmol) was added to a solution of
5-aminobenzotriazole 1 (1.50 g, 11.82 mmol) in pyridine
(7 mL) at K10 8C. After 4 h, the resulting precipitate was
filtered and purified by chromatography on silica gel with
dichloromethane as eluent, to give acetamide 14.
4.7.1. N-(1H-Benzotriazol-5-yl)-acetamide 14. Yield:
75%. MpZO260 8C. H NMR (DMSO-d6, 400 MHz) dZ
1
15.39 (s, 1H, NH), 10.14 (s, 1H, NH), 8.23 (s, 1H, 4-H), 7.83
(d, JZ8.8 Hz, 1H, 6-H or 7-H), 7.34 (d, JZ8.8 Hz, 1H, 7-H
or 6-H), 2.55 (s, 3H, CH3). 13C NMR (DMSO-d6, 100 MHz)
dZ169.54, 149.40, 137.12, 123.98, 118.73, 109.93, 30.52,
23.69. IRZ3087, 1738, 1682, 1568, 1413, 1257, 1204,
1007, 810 cmK1. HRMS (EI) [M]C% (C8H8N4O): calcd
176.0698; found 176.0694.
4.9. Cyclization of acetamidoquinolinylbenzotriazole
Method A. In a sealed vial, a solution of the corresponding
benzotriazolylquinoline 15 (0.10 g, 0.33 mmol) in DMF
(2 mL) was heated at 250 8C during 60 min. The reaction
mixture was then triturated with water (8 mL). The
precipitate formed was diluted with ethyl acetate (15 mL)
and extracted. The organic layer was dried (MgSO4) and
concentrated under reduced pressure. The crude residue was
purified by recrystallization to afford the expected acet-
amido indolo[3,2-c]quinoline 18.
4.8. Synthesis of acetamidoquinolinylbenzotriazoles
Under an inert atmosphere of argon, a solution of
4-chloroquinoline 8 (0.93 g, 5.6 mmol) and acetamidoben-
zotriazole 14 (1.0 g, 5.6 mmol) in DMF (2 mL) was heated
at 160 8C for 1 h. After cooling, the DMF was removed
under reduced pressure. The mixture was diluted with ethyl
acetate (15 mL) and washed with water (2!15 mL). The
organic layer was dried (MgSO4) and concentrated under
reduced pressure. The crude residue was purified by
chromatography on silica gel, with dichloromethane–ethyl
acetate (30/70) as eluent to provide the regioisomers 15, 16,
17 in 43, 30 and 10% yields, respectively.
4.9.1. N-(11H-Indolo[3,2-c]quinolin-8-yl)-acetamide 18.
Yield: 6% (0.007 g). MpZO260 8C. 1H NMR (DMSO-d6,
400 MHz) dZ12.71 (s, 1H, NH), 10.04 (s, 1H, NH), 9.52
(s, 1H, 6-H), 8.57 (d, JZ1.0 Hz, 1H, 7-H), 8.49 (d, 1H, JZ
8.0 Hz, 1-H), 8.11 (d, 1H, JZ8.0 Hz, 4-H), 7.74 (t, 1H, JZ
6.8 Hz, 3-H), 7.68 (t, 1H, JZ6.8 Hz, 2-H), 7.64 (d, 1H,
JZ8.8 Hz, 10-H), 7.56 (dd, 1H, JZ2.0, 8.8 Hz, 9-H), 2.11
(s, 3H, CH3). 13C NMR (DMSO-d6, 100 MHz) dZ24.39,
110.89 (7-C), 112.30 (10-C), 114.74, 115.18, 119.26 (9-C),

1902
A. Beauchard et al. / Tetrahedron 62 (2006) 1895–1903
122.51 (1-C), 123.48, 126.12 (2-C), 128.46 (3-C), 129.98
(4-C), 133.48, 135.63, 138.90, 140.66, 145.05 (6-C),
Acknowledgements
168.47. IRZ3485, 1669, 1128, 1016, 754, 514 cmK1
.
`
We thank the Ministere de la Recherche et de
l’Enseignement Superieur for PhD grant (A.B.) and the
HRMS (EI) [MCH]C% (C17H14N3O): calcd 276.1137;
found 276.1136.
´
´
‘Comite de Charente-Maritime de la Ligue Nationale
Contre le Cancer’ for financial support.
Method B. In a quartz reactor, a solution of the
corresponding benzotriazolylquinoline 15 (0.18 g,
0.54 mmol) and H4P2O7 (1 mL) in toluene (1 mL) placed
was heated at 200 8C until the evolution of nitrogen ceased
after 3 min. The reaction mixture was then triturated with
water and basified with a saturated solution of NaHCO3
(8 mL). The resulting precipitate was diluted with ethyl
acetate (15 mL) and extracted. The organic layer was dried
(MgSO4) and concentrated under reduced pressure. The
crude residue was purified by chromatography on silica gel,
with dichloromethane–methanol (90/10) as eluent to
provide 8-amino-11H-indolo[3,2-c]quinoline 19, quinoli-
noquinoline 20 and amino by-products 21.
References and notes
1. (a) Wells, G.; Bradshaw, T. D.; Diana, P.; Seaton, A.;
Shi, D.-F.; Westwell, A. D.; Stevens, M. F. G. Bioorg.
Med. Chem. Lett. 2000, 10, 513–515. (b) Bradshaw, T. D.;
Wrigley, S.; Shi, D.-F.; Schultz, R. J.; Paull, K. D.;
Stevens, M. F. G. Br. J. Cancer 1998, 77, 745–752.
(c) Molinski, T. F. Chem. Rev. 1993, 93, 1825–1838.
(d) Gunawardana, G. P.; Kohmoto, S.; Gunasekara, S. P.;
McConnel, O. J.; Koehn, F. E. J. Am. Chem. Soc. 1988,
110, 4856–4858. (e) Gunawardana, G. P.; Kohmoto, S.;
Burres, N. S. Tetrahedron Lett. 1989, 30, 4359–4362.
4.9.2. 11H-Indolo[3,2-c]quinolin-8-ylamine 19. Yield:
27% (0.06 g). MpZ180–182 8C. 1H NMR (DMSO-d6,
400 MHz) dZ12.28 (s, 1H, NH), 9.38 (s, 1H, 6-H), 8.44
(dd, JZ1.2, 8.0 Hz, 1H, 4-H or 1-H), 8.07 (d, JZ8.0 Hz,
1H, 1-H or 4-H), 7.68 (td, JZ1.2, 8.0 Hz, 1H, 2-H or 3-H),
7.63 (td, JZ1.2, 8.0 Hz, 1H, 3-H or 2-H), 7.41 (d, JZ
8.5 Hz, 1H, 10-H), 7.38 (d, JZ2.1 Hz, 1H, 7-H), 6.86 (dd,
JZ2.1, 8.5 Hz, 1H, 9-H), 5.06 (br s, 2H, NH2). 13C NMR
(DMSO-d6, 100 MHz) dZ103.40 (7-C), 112.53 (10-C),
114.45, 115.61 (9-C), 117.75, 122.40 (4-C), 123.23, 125.82
(2-C), 128.01 (3-C), 129.77 (1-C), 132.13, 140.00, 143.67,
144.98 (6-C), 145.47. IRZ3341, 1632, 1566, 1509, 1341,
1240, 1176, 755 cmK1. HRMS (EI) [M]C% (C15H11N3):
calcd 233.0953; found 233.0952.
´
2. (a) Lamazzi, C.; Chabane, H.; Thiery, V.; Pierre, A.;
´
Leonce, S.; Pfeiffer, B.; Renard, P.; Guillaumet, G.;
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` ´
Frere, S.; Thiery, V.; Bailly, C.; Besson, T. Tetrahedron 2003,
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59, 773–779. (c) Chabane, H.; Pierre, A.; Leonce, S.; Pfeiffer,
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B.; Renard, P.; Thiery, V.; Guillaumet, G.; Besson, T. J. Enz.
Inhib. Med. Chem. 2004, 19, 567–575.
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3. (a) Chabane, H.; Lamazzi, C.; Thiery, V.; Guillaumet, G.;
Besson, T. Tetrahedron Lett. 2002, 43, 2483–2486. (b)
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Chabane, H.; Lamazzi, C.; Thiery, V.; Pierre, A.;
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Leonce, S.; Pfeiffer, B.; Renard, P.; Guillaumet, G.;
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735–736. (b) Sharaf, M.; Schiff, P.; Tackie, A.; Phoebe, C.;
Martin, G. J. Heterocycl. Chem. 1996, 33, 239–243.
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Pharm. Bull. 1989, 37, 675–689. (b) Molina, A.;
Vaquero, J.-J.; Garcia-Navio, J.; Alvarez-Builla, J.;
de Pasqual-Teresa, B.; Gago, F.; Rodrigo, M.; Ballesteros,
M. J. Org. Chem. 1996, 61, 5587–5599. (c) Schmitt, P.;
Nguyen, C. H.; Sun, J. S.; Grierson, D.; Bisagni, E.;
4.9.3. N-(7H-4,7-Diaza-benzo[de]anthracen-10-yl)-aceta-
mide 20. Yield: 35% (0.054 g). MpZO260 8C. H NMR
1
(CDCl3, 400 MHz) dZ8.53 (d, JZ5.2 Hz, 1H, 5-Hquinolin.),
8.07 (d, JZ8.8 Hz, 1H, 3-H or 1-H), 7.96 (d, JZ8.8 Hz, 1H,
1-H or 3-H), 7.71 (t, JZ7.6 Hz, 1H, 2-H), 7.61 (d, JZ
2.0 Hz, 1H, 11-H), 7.56–7.50 (m, 2H, 9-H, 8-H), 6.83 (d,
1H, JZ5.2 Hz, 6-Hquinolin.), 2.60 (s, 3H, CH3). 13C NMR
(CDCl3, 100 MHz) dZ171.24, 165.30, 150.85, 148.63,
148.25, 142.72, 135.96, 130.07, 128.48, 125.40, 121.12,
119.41, 119.21, 114.92, 111.03, 101.51, 29.70. IRZ3341,
1632, 1566, 1509, 1341, 1240, 1176, 755 cmK1. HRMS (EI)
[M]C% (C17H13N3O): calcd 275.1059; found 275.1062.
´ `
Garestier, T.; Helene, C. Chem. Commun. 2000, 763–764.
´
(d) Lamazzi, C.; Leonce, S.; Pfeiffer, B.; Renard, P.;
Guillaumet, G.; Rees, C. W.; Besson, T. Bioorg. Med. Chem.
Lett. 2000, 10, 2183–2185. (e) He, L.; Chang, H.-X.; Chou,
T.-C.; Savaraj, N.; Cheng, C. C. Eur. J. Med. Chem. 2003, 38,
101–107. (f) Onyeibor, O.; Croft, S. L.; Dodson, H.;
Feiz-Haddad, M.; Kendrick, H.; Millington, N.; Paparini, S.;
Philipps, R.; Seville, S.; Shnyder, S.; Taramelli, D.; Wright, C.
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4.9.4. N-Quinolin-4-yl-benzene-1,4-diamine 21. Yield:
5% (0.006 g). MpZ152–154 8C. 1H NMR (DMSO-d6,
400 MHz) dZ8.48 (d, JZ5.5 Hz, 1H, 2-Hquinolin.), 8.06
(d, JZ8.4 Hz, 1H, ArH), 7.90 (d, JZ8.4 Hz, 1H, ArH), 7.69
(td, JZ1.2, 6.4 Hz, 1H, ArH), 7.50 (td, JZ1.2, 6.4 Hz, 1H,
ArH), 7.12 (dd, JZ2.4, 6.4 Hz, 2H, ArH), 6.76 (dd, JZ2.4,
6.4 Hz, 2H, ArH), 6.65 (d, JZ5.2 Hz, 1H, 3-Hquinolin.), 3.49
(s, 2H, NH2). 13C NMR (DMSO-d6, 100 MHz) dZ150.62,
149.40, 148.48, 144.62, 129.97, 129.74, 129.35, 126.50,
125.04, 119.39, 118.88, 116.05, 100.93. IRZ3421, 2314,
1709, 1260, 1124 cmK1. HRMS (EI) [M]C% (C15H13N3):
calcd 235.1109; found 235.1094.
6. (a) Timari, G.; Sooos, T.; Hajos, G. Synlett 1997, 1067–1068.
´ ´
(b) Godard, A.; Marsais, F.; Ple, N.; Trecourt, F.; Turck, A.;
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Queguiner, G. Heterocycles 1995, 40, 1055–1091. (c)
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Lemiere, G. Molecules 2003, 8, 480–487. (d) Mouaddib, A.;
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Joseph, B.; Hasnaoui, A.; Merour, J. Y. Synthesis 2000,
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Synthesis 1999, 326–329. (c) Graebe, C.; Ullmann, F.
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