J. S. Dickschat, H. Reichenbach, I. Wagner-Döbler, S. Schulz
FULL PAPER
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(29), 139 (3), 119 (14), 108 (3), 91 (77), 77 (5), 65 (41), 51 (6), 43 0.24. GC: I = 1326. H NMR (400 MHz, CDCl3, TMS): δ = 1.34
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(100).
(d, JH,H = 7.0 Hz, 6 H, 2×CH3), 1.60 (s, JC,H = 127.0 Hz, 6 H,
3
2×CH3), 3.13 (sept, JH,H = 6.9 Hz, 1 H, CH), 4.21 (br. s, 1 H,
Preparation of 2,5-Dialkylpyrazines: According to the method of
Zbiral and Stroh,[19] a solution of PPh3 (1 equiv.) in dry benzene
(1 molL–1) was added to a solution of the α-azido ketone (1 equiv.)
in dry benzene (1 molL–1). In the case of asymmetrically substi-
tuted 2,5-dialkylpyrazines two different α-azido ketones (each
0.5 equiv.) were used. The reaction mixture was stirred at room
temperature for 24 h and then concentrated. The residue was puri-
fied by column chromatography on silica gel with pentane/diethyl
ether (2:1) to obtain the 2,5-dialkylpyrazines as pale-yellow liquids.
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OH), 8.38 (d, JH,H = 1.4, JC,H = 180.1 Hz, 1 H, CH), 8.69 (d,
1
5JH,H = 1.4, JC,H = 181.2 Hz, 1 H, CH) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 22.1 (2×CH3), 30.3 (2×CH3), 33.6
(CH), 71.3 (C), 140.1 (CH), 140.3 (CH), 158.5 (C), 160.2 (C) ppm.
EI-MS (70 eV): m/z (%) = 180 (7) [M+], 165 (100), 147 (20), 132
(8), 122 (19), 107 (26), 94 (13), 80 (10), 67 (9), 59 (20), 52 (19), 43
(47). C10H16N2O (180.25): calcd. C 66.63, H 8.95, N 15.54; found
C 66.49, H 8.80, N 15.27.
Preparation of 2-(1-Methylethenyl)-5-(1-methylethyl)pyrazine (7): A
solution of 58 (110 mg, 0.61 mmol) in acetic acid (0.8 mL) and
conc. H2SO4 (0.2 mL) was heated to 70 °C for 2 h (Scheme 5). The
reaction mixture was made alkaline with 2 NaOH and extracted
with diethyl ether (3×10 mL). The combined extracts were dried
(MgSO4) and concentrated. The crude product was purified by col-
umn chromatography on silica gel with pentane/diethyl ether (1:1)
to yield 7 (77 mg, 0.48 mmol, 78%) as a colourless liquid. TLC
(pentane/diethyl ether, 1:1): Rf = 0.79. GC: I = 1272. 1H NMR
2,5-Bis(1-methylethyl)pyrazine (6): This compound was prepared
from 34a (Scheme 4). Yield: 40% (660 mg, 4.02 mmol). TLC (pen-
tane/diethyl ether, 2:1): Rf = 0.57. GC: I = 1198. 1H NMR
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(400 MHz, CDCl3, TMS): δ = 1.33 (d, JH,H = 6.9, JC,H
=
126.7 Hz, 12 H, 4×CH3), 3.08 (sept, 3JH,H = 6.9 Hz, 2 H, 2×CH),
8.39 (s, 1JC,H = 178.5, 3JC,H = 9.2 Hz, 2 H, 2×CH) ppm. 13C NMR
(100 MHz, CDCl3, TMS): δ = 22.2 (4×CH3), 33.5 (2×CH), 141.8
(2×CH), 159.3 (2×C) ppm. EI-MS (70 eV): m/z (%) = 164 (25)
[M+], 149 (100), 136 (43), 121 (19), 107 (5), 94 (4), 80 (4), 67 (7),
53 (11), 41 (13).
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(400 MHz, CDCl3, TMS): δ = 1.33 (d, JH,H = 6.9 Hz, 6 H,
4
2×CH3), 2.22 (d, JH,H = 0.8 Hz, 3 H, CH3), 5.34–5.36 (m, 1 H,
Preparation of 2-(1-Bromo-1-methylethyl)-5-(1-methylethyl)pyrazine
2
CH2), 5.88 (d, JH,H = 0.6 Hz, 1 H, CH2), 8.42 (s, 1 H, CH), 8.69
(57):
A solution of 6 (450 mg, 2.74 mmol), AIBN (45 mg,
(s, 1 H, CH) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 19.7
(CH3), 21.8 (2×CH3), 33.3 (CH), 116.0 (CH2), 140.0 (CH), 140.5
(C), 141.2 (CH), 150.6 (C), 159.9 (C) ppm. EI-MS (70 eV): m/z (%)
= 162 (38) [M+], 147 (100), 134 (49), 119 (6), 106 (4), 92 (6), 80 (5),
65 (24), 52 (19), 39 (46). C10H16N2O (180.25): calcd. C 66.63, H
8.95, N 15.54; found C 66.49, H 8.80, N 15.27.
0.27 mmol) and NBS (400 mg, 2.2 mmol) in dry CCl4 (20 mL) was
heated under reflux for 4 h (Scheme 5). The precipitated suc-
cinimide was removed by filtration and the filtrate was concen-
trated. The residue was purified by column chromatography on sil-
ica gel with pentane/diethyl ether (10:1) to yield 57 (280 mg,
1.15 mmol, 42%), 2,5-bis(1-bromo-1-methylethyl)pyrazine (80 mg,
0.25 mmol, 9%) and recovered starting material (180 mg,
1.09 mmol, 40%).
Preparation of 2,5-Dimethyl-3-(methylsulfanyl)pyrazine (67): Cau-
tion! NaSMe forms highly malodorous MeSH in contact with moist-
ure. Therefore, the reaction should be carried out in a well-venti-
lated hood. A stainless-steel autoclave was charged with 69 (1.00 g,
7.04 mmol), NaSMe (986 mg, 14.1 mmol) and dry dimethoxy-
ethane (20 mL, Scheme 6). The reaction mixture was stirred at
150 °C for 12 h and then quenched by the addition of water
(100 mL). The aqueous layer was extracted with diethyl ether
(3×100 mL). The combined extracts were dried (MgSO4) and con-
centrated under reduced pressure. The residue was purified by col-
umn chromatography on silica gel with pentane/diethyl ether (5:1)
to give 67 (1.04 g, 6.75 mmol, 96%) as a pale-yellow liquid. TLC
(pentane/diethyl ether, 5:1): Rf = 0.36. GC: I = 1260. 1H NMR
(400 MHz, CDCl3, TMS): δ = 2.45 (s, 1JC,H = 127.8 Hz, 3 H, CH3),
2-(1-Bromo-1-methylethyl)-5-(1-methylethyl)pyrazine (57): TLC
(pentane/diethyl ether, 10:1): Rf = 0.29. GC: I = 1459. 1H NMR
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(400 MHz, CDCl3, TMS): δ = 1.34 (d, JH,H = 6.9, JC,H
=
1
126.9 Hz, 6 H, 2×CH3), 2.23 (s, JC,H = 129.6 Hz, 6 H, 2×CH3),
3.13 (sept, JH,H = 6.9, JC,H = 128.2 Hz, 1 H, CH), 8.42 (d, JH,H
3
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5
1
5
= 1.3, JC,H = 181.6 Hz, 1 H, CH), 8.87 (d, JH,H = 1.3 Hz, 1 H,
CH) ppm. 13C NMR (100 MHz, CDCl3, TMS): δ = 22.1 (2×CH3),
33.6 (2×CH3), 33.7 (CH), 61.4 (C), 141.0 (CH), 141.1 (CH), 156.4
(C), 160.7 (C) ppm. EI-MS (70 eV): m/z (%) = 163 (100) [M+ – Br],
148 (26), 133 (9), 120 (4), 107 (4), 92 (4), 80 (5), 65 (11), 52 (14),
39 (30). C10H14BrN2 (243.14): calcd. C 49.40, H 6.22, N 11.52;
found C 49.54, H 6.04, N 11.60.
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2.46 (s, JC,H = 127.5 Hz, 3 H, CH3), 2.55 (s, JC,H = 141.6 Hz, 3
2,5-Bis(1-bromo-1-methylethyl)pyrazine: TLC (pentane/diethyl
ether, 10:1): Rf = 0.41. GC: I = 1718. 1H NMR (400 MHz, CDCl3,
H, CH3), 7.95 (s, JC,H = 180.4 Hz, 1 H, CH) ppm. 13C NMR
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(100 MHz, CDCl3, TMS): δ = 12.4 (CH3), 20.8 (CH3), 20.9 (CH3),
137.1 (CH), 147.8 (C), 150.0 (C), 154.4 (C) ppm. EI-MS (70 eV):
m/z (%) = 154 (100) [M+], 139 (26), 121 (83), 107 (24), 98 (15), 80
(21), 71 (14), 52 (12), 39 (36).
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TMS): δ = 2.24 (s, JC,H = 129.8 Hz, 12 H, 4×CH3), 8.90 (s, JC,H
= 183.5, JC,H = 9.0 Hz, 2 H, 2×CH) ppm. 13C NMR (100 MHz,
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CDCl3, TMS): δ = 33.5 (4×CH3), 60.8 (2×C), 140.4 (2×CH),
157.5 (2×C) ppm. EI-MS (70 eV): m/z (%) = 241 (35) [M+ – Br],
241 (40), 161 (100), 147 (30), 133 (10), 119 (10), 106 (6), 92 (8), 80
(10), 65 (26), 51 (25), 39 (61). C10H14Br2N2 (322.04): calcd. C 37.30,
H 4.38, N 8.70; found C 37.22, H 4.43, N 8.32.
Supporting Information Available: The structures of all pyrazines
already identified in a previous study (Figure S1),[10] complete re-
sults of the headspace analysis of Chondromyces crocatus (Table
S1), and physical and spectroscopic data for all synthesised com-
pounds that are not given here.
Preparation of 2-(1-Hydroxy-1-methylethyl)-5-(1-methylethyl)pyra-
zine (58): A solution of 57 (254 mg, 1.05 mmol) in acetone (1 mL)
was added to a suspension of freshly prepared AgOH (0.26 g,
2.1 mmol) in water (20 mL, Scheme 5). The reaction mixture was
stirred at 30 °C for 4 h. The aqueous layer was extracted with di-
ethyl ether (3×50 mL). The combined organic layers were dried
with MgSO4 and concentrated. Purification by column chromatog-
raphy with pentane/diethyl ether (1:1) gave 58 (110 mg, 0.61 mmol,
58%) as a colourless liquid. TLC (pentane/diethyl ether, 1:1): Rf =
Acknowledgments
J. S. D. thanks the Fond der Chemischen Industrie and the BMBF
for a stipend. Financial support by the DFG is gratefully acknowl-
edged.
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 4141–4153