Typical coupling using 2-chloroquinoxalines to give 2
temperature. Addition of aqueous sodium metabisulfite and
dichloromethane followed by separation, drying, and evapor-
ation of the organic phase under reduced pressure gave a
brown oil. Purification by column chromatography eluting with
petroleum ether–ethyl acetate (93:7) gave the pure dibromo-
alkene 3g (1.99 g, 79%) as a yellow solid, mp 98–102 ЊC;
1H-NMR (300 MHz, CDCl3): δ 7.50 (3H, m), 7.64 (2H, m), 7.90
(2H, m), 8.22 (2H, m), 9.02 (1H, s); 13C-NMR (300 MHz,
CDCl3): δ 113.6, 122.5, 128.4, 128.9, 129.2, 129.5, 130.6, 130.9,
139.2, 141.5, 141.6, 145.2, 152.8; MS (CI): m/z 389, 391, 393
([M ϩ H]ϩ, 6, 12, 6%), 231 (100).
6-Chloro-2-(hex-1-yn-1-yl)quinoxaline 2d. To a degassed solu-
tion of 2,6-dichloroquinoxaline (1.5 g, 7.5 mmol) and hex-1-yne
(0.57 ml, 9.75 mmol) in acetonitrile (40 ml) and triethylamine
(7.5 ml), palladium() acetate (130 mg), copper() iodide (182
mg), and triphenylphosphine (200 mg) were added under nitro-
gen. The mixture was heated at 60 ЊC for 6 h. After evaporation
of the solvent, the residue was diluted with water and extracted
with dichloromethane. The dried organic extract was evapor-
ated and the residue purified by column chromatography,
eluting with petroleum ether–diethyl ether (9:1) to give
6-chloro-2-(hex-1-yn-1-yl)quinoxaline 2d (944 mg, 54%) as a
brown solid, mp 42–43 ЊC; 1H-NMR (300 MHz, CDCl3): δ 1.02
(3H, t, J = 6.9 Hz), 1.55 (2H, m), 1.71 (2H, m), 2.58 (2H, t,
J = 7.0 Hz), 7.73 (1H, dd, J = 8.9 and 2.3 Hz), 7.90 (1H, d,
J = 8.9 Hz), 8.08 (1H, d, J = 2.3 Hz), 8.85 (1H, s); 13C-NMR
(300 MHz, CDCl3): δ 13.5, 19.2, 22.0, 30.0, 78.6, 96.9, 128.0,
130.1, 131.4, 135.7, 140.0, 140.5, 140.8, 148.1; MS (CI): m/z 247
([M ϩ H]ϩ, 37Cl, 30%), 245 ([M ϩ H]ϩ, 35Cl, 100%), 76 (100).
Typical ring closure to form thieno[2,3-b]quinoxalines 4
2-Phenylthieno[2,3-b]quinoxaline 4e. An aqueous solution
of disodium trithiocarbonate2 (33%, 3 ml) was added to a
hot solution of 2-(1,2-dibromo-2-phenylethenyl)quinoxaline 3g
(200 mg, 0.51 mmol) in methanol (8 ml) with stirring. The
resulting solution was cooled to room temperature and stirred
for a further 3 h. After evaporation of methanol, the residue
was diluted with water and extracted with dichloromethane.
The organic extract was dried and evaporated under reduced
pressure to leave a brown oil. Purification by column chromato-
graphy over silica gel eluting with petroleum ether–diethyl ether
(2:1) gave a red solid, which was further purified by treating
with charcoal in dichloromethane to give the pure thieno-
quinoxaline 4e (71 mg, 53%) as a yellow solid, mp 186–188 ЊC
(lit.8b mp 185 ЊC).
Typical couplings with 2-ethynylquinoxaline to give 2
(a) 2-(4-Iodophenylethynyl)quinoxaline 2o. To a degassed
solution of 2-ethynylquinoxaline (492 mg, 3.2 mmol) and 1,4-
diiodobenzene (5.3 g, 16 mmol) in acetonitrile (30 ml) and tri-
ethylamine (15 ml), palladium() acetate (36 mg, 0.16 mmol),
copper() iodide (61 mg, 0.32 mmol), and triphenylphosphine
(84 mg, 0.32 mmol), were added under nitrogen. The mixture
was stirred under nitrogen at room temperature for 3 h. After
evaporation, the residue was diluted with aqueous sodium
bicarbonate and extracted with dichloromethane. The dried
organic extract was evaporated and the residue purified by
column chromatography, eluting with dichloromethane to yield
2-(4-iodophenylethynyl)quinoxaline 2o (557 mg, 49%) as a
Typical desilylation
2-Ethynylquinoxaline 2g. To a suspension of 2-(trimethyl-
silylethynyl)quinoxaline 2e (3 g, 13.2 mmol) in dry methanol
(34 ml) at room temperature was added potassium carbonate
(188 mg, 1.32 mmol) under nitrogen and the mixture stirred for
1 h. The methanol was evaporated under reduced pressure and
the residue dissolved in dichloromethane, the solution washed
with water, dried, and evaporated under reduced pressure, to
give a brown solid. Purification by column chromatography
over silica gel eluting with dichloromethane gave 2-ethynyl-
quinoxaline 2g (1.8 g, 88%) as a white solid, mp 95–98 ЊC;
1H-NMR (300 MHz, CDCl3): δ 3.30 (1H, s), 7.72 (2H, m), 8.05
(2H, m), 8.82 (1H, s); 13C-NMR (300 MHz, CDCl3): δ 80.9,
81.2, 129.1, 129.2, 130.6, 130.7, 138.3, 141.2, 141.9, 147.0; MS
(CI): m/z 155 ([M ϩ H]ϩ, 100%).
1
crystalline yellow solid, mp 146–149 ЊC; H-NMR (300 MHz,
CDCl3): δ 7.31 (2H, d, J = 8.3 Hz), 7.67 (2H, d, J = 8.3 Hz), 7.72
(2H, m), 8.01 (2H, m), 8.88 (1H, s); 13C-NMR (300 MHz,
CDCl3): δ 88.1, 92.4, 96.1, 120.8, 129.1, 129.2, 130.4, 130.6,
133.5, 137.7, 139.9, 140.9, 142.1, 147.0; MS (CI): m/z 357
([M ϩ H]ϩ, 100%). Further elution with dichloromethane–ethyl
acetate (7:3) gave 1,4-bis(quinoxalin-2-ylethynyl)benzene (129
mg, 14%), mp 262–263 ЊC.
(b) 2-(5-Trifluoromethylpyridin-2-ylethynyl)quinoxaline 2p.
To a degassed solution of 2-ethynylquinoxaline 2g (500 mg,
3.24 mmol), and 2-iodo-5-trifluoromethylpyridine (1.7 g, 6.48
mmol) in acetonitrile (13 ml) and triethylamine (6.5 ml),
palladium() acetate (36 mg, 0.16 mmol), copper() iodide (62
mg, 0.32 mmol), and triphenylphosphine (85 mg, 0.32 mmol),
were added under nitrogen. The mixture was stirred under
nitrogen at room temperature for 3 h. After evaporation, the
residue was diluted with aqueous sodium bicarbonate and
extracted with dichloromethane. The dried organic extract was
evaporated and the residue purified by column chromato-
graphy, eluting with dichloromethane–ethyl acetate (95:5) to
yield 2-(5-trifluoromethylpyridin-2-ylethynyl)quinoxaline 2p
(450 mg, 30%), as a yellow solid, mp 152–154 ЊC (from
Acknowledgements
The work described in this paper was wholly funded by the
Nissan Chemical Company, Tokyo, Japan, through a contact
established and maintained by Dr Kenzi Makino of that com-
pany. We are most grateful to the Nissan Chemical Company
for financial support and for a studentship (M. A.), and to
Dr Makino for his interest in this work and for many stimu-
lating chemical discussions and suggestions throughout our
collaboration.
1
methanol); H-NMR (300 MHz, CDCl3): δ 7.75 (3H, m), 7.94
References
(1H, dd, J = 1.7 and 7.7 Hz), 8.06 (2H, m), 8.88 (1H, s), 9.01
(1H, s); 13C-NMR (300 MHz, CDCl3): δ 87.8, 90.1, 127.5,
129.3, 129.4 (2), 130.9, 131.7 (2), 133.5, 138.0, 141.3, 142.1,
145.2, 147.1 (2).
1 For reviews, see P. E. Baugh, D. Collison, C. D. Garner and
J. A. Joule, Comprehensive Biological Catalysis, 1998, Vol. III, 377;
C. D. Garner, P. Baugh, D. Collison, E. S. Davies, A. Dinsmore,
J. A. Joule, E. Pidcock and C. Wilson, Pure Appl. Chem., 1997, 69,
2205; D. Collison, C. D. Garner and J. A. Joule, Chem. Soc. Rev.,
1996, 25; for more recent work, see E. S. Davies, G. M. Aston,
R. L. Beddoes, D. Collison, A. Dinsmore, A. Docrat, J. A. Joule,
C. R. Wilson and C. D. Garner, J. Chem. Soc., Dalton Trans., 1998,
3647; A. Dinsmore, C. D. Garner and J. A. Joule, Tetrahedron, 1998,
54, 3291; A. Dinsmore, C. D. Garner and J. A. Joule, Tetrahedron,
1998, 54, 9559; B. Bradshaw, A. Dinsmore, C. D. Garner and
J. A. Joule, Chem. Commun., 1998, 417.
Typical addition of bromine to give 3
2-(1,2-Dibromo-2-phenylethenyl)quinoxaline 3g. A solution
of bromine (0.36 ml, 7.15 mmol) in dichloromethane (10 ml)
was added dropwise to a stirred solution of 2-(phenylethynyl)-
quinoxaline 2i (1.5 g, 6.5 mmol) dissolved in dichloromethane
(20 ml). The resultant mixture was stirred for 2 h at room
2 D. J. Martin and C. C. Greco, J. Org. Chem., 1968, 33, 1275.
J. Chem. Soc., Perkin Trans. 1, 2001, 154–158
157