Preparation of (benzo)isoquinolines using in situ generated aryne intermediates

Full text of DOI:10.1007/s10593-013-1222-4

Chemistry of Heterocyclic Compounds, Vol. 48, No. 12, March, 2013 (Russian Original Vol. 48, No. 12, December, 2012)
PREPARATION OF (BENZO)ISOQUINOLINES USING
in situ GENERATED ARYNE INTERMEDIATES
D. S. Kopchuk1,2, G. V. Zyryanov1,2,*, I. S. Kovalev1, I. N. Egorov1,
V. L. Rusinov1,2, and O. N. Chupakhin1,2
Keywords: aryne intermediates, (benzo)isoquinoline, 1,2,4-triazine, cycloaddition, Diels–Alder reaction.
(Benzo)isoquinoline derivatives are of significant interest in different areas of basic and applied organic
chemistry. Of special promise are their biological [1-3], photophysical, and coordination [4-8] properties. Their
use as chiral catalysts [9, 10] is also of interest.
The most frequently used methods for preparing (benzo)isoquinoline systems are cross-coupling
reactions [11, 12], which demand the use of special catalysts. We propose a method for preparing
(benzo)isoquinoline derivatives based on an aza Diels–Alder reaction with 1,2,4-triazines as dienes and the
aryne intermediates acting as dienophiles.
The methodology for preparing diverse pyridine derivatives via reaction of the corresponding 1,2,4-triazines
has long been known [13-15]. However, there are only a few examples of using aryne intermediates in similar
reactions. The range of dienophiles in these cases is limited to certain dehydrobenzene derivatives, the
generation of which used poorly available anthranilic acids [16, 17] despite the marked growth in the chemistry
of arynes in recent years [18, 19].
In our work, we propose a highly efficient method for the preparation of (het)aryl-substituted
isoquinoline 1a and benzo[h]isoquinoline 1b, which involves the reaction of arynes 2a,b with the substituted
1,2,4-triazines 3a,b in anhydrous toluene for 24-36 h at 140°C under an argon atmosphere. The target
compounds 1a,b were obtained in 76% and 80% yield, respectively. The corresponding arynes were generated
in situ by the action of potassium tert-butoxide on the chloro- and bromo-substituted arenes 4a,b.
The structure of the obtained compounds 1a,b was confirmed from the 1H and 13C NMR spectroscopy, mass
spectrometry, and by elemental analysis data. The mass spectra of compounds 1a,b showed the presence of a
molecular ion peak.
The compounds obtained are 2,2'-bipyridine type ligands with an extended conjugated system, and are
of interest from the viewpoint of complex formation and as luminescent materials.
_______
*To whom correspondence should be addressed, e-mail: gvzyryanov@gmail.com.
1Ural Federal University named after the First President of Russia B. N. Yeltsin, 19 Mira St., Yekaterinburg
620002, Russia.
2I. Ya. Postovskii Institute of Organic Synthesis, Ural Branch, Russian Academy of Sciences, 22
Akademicheskaya St./20 S. Kovalevskoi St., Yekaterinburg 620219, Russia; e-mail: chupakhin@ios.uran.ru.
_________________________________________________________________________________________
Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1994-1997, December, 2012.
Original article submitted February 15, 2012.
0009-3122/13/4812-1871©2013 Springer Science+Business Media New York
1871

N
N
Cl
N
N
3a
t-BuOK
Toluene
140°С
N
2a
4a
N
1a
N
N
Br
N
N
t-BuOK
3b
Toluene
140°С
N
4b
N
2b
1b
1H and 13C NMR spectra were recorded on a Bruker DRX-400 spectrometer (400 and 100 MHz,
respectively) using CDCl3 with TMS as internal standard. ESI mass spectra were recorded on a Bruker
Daltonics micrOTOF-Q II mass spectrometer. Elemental analysis was conducted on a Perkin-Elmer PE 2400
series II CHN-analyzer. Melting points were determined on a Boetius hot stage apparatus. TLC analysis was
performed on Merck 60 F254 silica gel and visualized in UV light. All of the synthetic procedures were carried
out under an argon atmosphere.
The 5-phenyl-3-(2-pyridyl)-1,2,4-triazine (3a) [20] and 6-phenyl-3-(2-pyridyl)-1,2,4-triazine (3b) [15]
were synthesized by the reported methods.
Preparation of the Aryne Cycloaddition Products (General Method). A suspension of the triazine 3a,b
(0.50 mmol), the haloarene 4a,b (0.50 mmol), and t-BuOK (85 mg, 0.75 mmol) in absolute toluene (50 ml) was
stirred in an autoclave at 140°C for 24 h. After cooling to room temperature, the reaction mixture was washed with
water (250 ml), and the organic fraction was dried over anhydrous Na2SO4. Toluene was evaporated under reduced
pressure, and the residue was purified by column chromatography using CH2Cl2 as eluent.
3-Phenyl-1-(2-pyridyl)isoquinoline (1a). Yield 110 mg (80%). Colorless crystals. Mp 107-109°C.
1H NMR spectrum, , ppm (J, Hz): 7.41-7.45 (3Н, m, Н Ph); 7.51-7.53 (2Н, m, H isoquinoline); 7.57-7.59 (1Н,
m, H isoquinoline); 7.68-7.70 (1Н, m, H isoquinoline); 7.93-7.95 (2Н, m, H Ph); 8.15 (1Н, s, H-4); 8.21-8.23
3
4
3
4
(2H, m, H Py); 8.75 (1Н, dd, J = 8.4, J = 1.8, H-3 Py); 8.81 (1Н, dd, J = 4.8, J = 1.8, H-6 Py). 13C NMR
spectrum, , ppm: 117.0; 123.2; 125.6; 127.0; 127.4; 127.5; 128.0; 128.5; 128.6; 128.8; 130.1; 137.0; 138.2;
139.5; 148.3; 149.8; 157.0; 158.8. Mass spectrum, m/z (Irel, %): 283.12 [M+Н]+ (100). Found, %: С 84.81;
Н 4.80; N 9.61. C20H14N2. Calculated, %: C 85.08; H 5.00; N 9.92.
4-phenyl-1-(2-pyridyl)benzo[h]isoquinoline (1b). Yield 130 mg (76%). Colorless crystals. Mp
1
202-204°C. H NMR spectrum, , ppm (J, Hz): 7.29-7.33 (2Н, m, H-5 Py, H Ar); 7.49-7.64 (6Н, m, H Ph,
H Ar); 7.45-7.86 (6Н, m, H Ph, H Ar); 8.22-8.24 (2Н, m, H-3,6 Py). 13C NMR spectrum, , ppm: 120.4; 122.9;
124.5; 126.9; 128.1; 128.4; 128.9; 129.6; 130.1; 131.2; 131.7; 133.2; 133.9; 136.8; 137.7; 142.9; 144.2; 149.2;
149.9; 151.6; 153.7; 160.7. Mass spectrum, m/z (Irel, %): 333.15 [M+Н]+ (100). Found, %: С 86.55; Н 4.76;
N 8.21. C24H16N2. Calculated, %: C 86.72; H 4.85; N 8.43.
This work was carried out with the support of the Ministry of Education and Science of the Russian
Federation (state contract Nos. 14.740.11.1020 and 14.A18.21.0817).
1872

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