6
Tetrahedron
ACCEPTED MANUSCRIPT
compound corresponded well to that previously published.28
4-Nitrophthalonitrile (2.0 g, 11.5 mmol) and 2-
Yield: 71%, colorless liquid; δH (CDCl3, 500 MHz) 7.38–7.23 (m,
3H, ArH), 7.27–7.14 (m, 2H, ArH), 2.95 (t, J = 7.4 Hz, 2H,
SCH2), 1.66 (p, J = 7.5 Hz, 2H, CH2), 1.48 (sex, J = 7.5 Hz, 2H,
CH2), 0.95 (t, J = 7.4 Hz, 3H, CH3); δC (CDCl3, 126 MHz) 137.0,
129.4, 129.0, 128.8, 128.7, 125.6, 33.2, 31.2, 21.9, 13.6.
methylpropane-2-thiol (1.9 g, 20.7 mmol) were dissolved in
anhydrous DMF (35 mL) under an argon atmosphere. The
mixture was stirred and sonicated for 10 min at rt, and K2CO3
(4.3 g, 31 mmol) was added in several small portions. The
reaction mixture was then stirred at 45 °C for 24 h under an
argon atmosphere. The reaction mixture was poured onto ice, and
the resulting precipitate was filtered and washed with a mixture
of methanol and water (1:1). The solid was then recrystallized
from methanol/water. The data obtained in the analysis of the
compound corresponded well to that previously published.31
Yield: 2.15 g (86%); white-greenish solid; m.p. 63-67 °C; δH
(CDCl3, 500 MHz) 7.91 (d, J = 1.7 Hz, 1H, H-3), 7.85 (dd, J =
8.1, 1.7 Hz, 1H, H-5), 7.75 (dd, J = 8.1, 0.5 Hz, 1H, H-6), 1.37
(s, 9H, tBu); δC (CDCl3, 126 MHz) 141.9, 140.2, 140.0, 133.1,
116.0, 115.1, 114.9, 114.8, 48.5, 31.0.
4.5. Pent-3-ylphenylsulfide (3)
Compound 3 was prepared according to above mentioned
general procedure. The data obtained in the analysis of the
compound corresponded well to that previously published.29
Yield: 63%, colorless liquid; δH (CDCl3, 500 MHz) 7.48–7.39 (m,
2H, ArH), 7.32–7.26 (m, 2H, ArH), 7.24–7.19 (m, 1H, ArH),
3.01 (p, J = 6.5 Hz, 1H, CH), 1.71–1.53 (m, 4H, CH2), 1.03 (t, J
= 7.4 Hz, 6H, CH3); δC (CDCl3, 126 MHz) 135.9, 131.7, 128.7,
126.4, 52.2, 26.7, 11.2.
4.12. 2-tert-butylsulfanylpyrazine (11)
4.6. Neopentylphenylsulfide (4)
Sodium hydride (60% suspension in mineral oil, 1.01 g, 25.3
mmol) was dissolved in anhydrous THF (40 mL) under an argon
atmosphere, and 2-methylpropane-2-thiol (2.83 mL, 2.26 g, 25
mmol) was added. 2-Chlorpyrazine (2.31 g, 20 mmol) was
dissolved in anhydrous THF (5 mL) and added dropwise into the
reaction. The mixture was refluxed for 4.5 h, diluted with water
(20 mL) and extracted twice with ethylacetate (50 mL). The
combined organic phases were washed with brine (20 mL), dried
with Na2SO4, filtered and evaporated. The crude product was
purified by column chromatography on silica with
hexane:ethylacetate (9:1) as the mobile phase. Yield: 2.4 g
(71%); colorless oil; νmax (ATR) 3065, 2963, 2921, 1505, 1453,
1378, 1363, 1280 cm-1; δH (CDCl3, 500 MHz) 8.46 (d, J = 1.6 Hz,
1H, H-3), 8.40 (dd, J = 2.6, 1.6 Hz, 1H, H-5), 8.24 (d, J = 2.6 Hz,
1H, H-6), 1.51 (s, 9H, tBu); δC (CDCl3, 126 MHz) 156.8, 146.7,
143.7, 140.4, 48.3, 30.7; HRMS (ESI): MH+, found 169.0798.
C8H12N2S + H+ requires 169.0794.
Compound 4 was prepared according to above mentioned
general procedure. The data obtained in the analysis of the
compound corresponded well to that previously published.30
Yield: 87%, colorless liquid; δH (CDCl3, 500 MHz) 7.40–7.34 (m,
2H, ArH), 7.32–7.21 (m, 2H, ArH), 7.20–7.11 (m, 1H, ArH),
2.92 (s, 2H), 1.07 (s, 9H); δC (CDCl3, 126 MHz) 138.4, 129.4,
129.0, 128.8, 128.7, 125.4, 48.6, 32.44, 29.02.
4.7. Tert-butyl(4-methoxyphenyl)sulfide (6)
Compound 6 was prepared according to above mentioned
general procedure. The data obtained in the analysis of the
compound corresponded well to that previously published.26
Yield: 95%, colorless liquid; δH (CDCl3, 500 MHz) 7.45 (d, J =
8.8 Hz, 2H, ArH), 6.87 (d, J = 8.8 Hz, 1H, ArH), 3.82 (s, 3H,
OCH3), 1.27 (s, 9H, tBu); δC (CDCl3, 126 MHz) 160.2, 138.9,
123.6, 114.0, 55.3, 45.5, 30.8.
4.8. Tert-butyl(4-methylphenyl)sulfide (7)
4.13. 5-(tert-butylsulfanyl)pyrazine-2,3-dicarbonitrile (12)
Compound 7 was prepared according to above mentioned
general procedure. The data obtained in the analysis of the
compound corresponded well to that previously published.26
Yield: 98%, colorless liquid; δH (CDCl3, 500 MHz) 7.46–7.40 (m,
2H, ArH), 7.18–7.12 (m, 2H, ArH), 2.37 (s, 3H, CH3), 1.29 (s,
9H, tBu); δC (CDCl3, 126 MHz) 138.7, 137.4, 129.2, 129.1, 45.5,
30.9, 21.2.
2-Methylpropane-2-thiol (0.86 g, 1.05 mL, 9.6 mmol) was
added to a 1 M aq. NaOH solution (10 mL, 10 mmol) and stirred
at rt for 15 min. Subsequently, a solution of 5-chloropyrazine-
2,3-dicarbonitrile32 (1.28 g, 7.8 mmol) in THF (10 mL) was
added, and the reaction was stirred at rt for 1.5 h. Then, water (30
mL) was added, and the product was extracted with ethylacetate
(3 × 50 mL). The combined organic phases were dried (Na2SO4),
filtered and purified by column chromatography on silica with
hexane:ethylacetate (8:1) as the mobile phase to produce a
slightly brown solid. Yield: 1.1 g (64%); slightly brown solid;
m.p. 65.6-66.6 °C; δH (CDCl3, 500 MHz) 8.50 (s, 1H, ArH), 1.66
(s, 9H, tBu); δC (CDCl3, 126 MHz) 164.8, 146.9, 132.2, 126.9,
113.4, 113.0, 51.6, 29.6; νmax (ATR) 2972 (CH), 2240 (CN),
1539, 1490, 1473, 1419, 1366, 132, 1232 cm-1; [Found: C, 54.97;
H, 4.52; N, 25.59. C10H10N4S requires: C, 55.03; H, 4.62; N,
25.67%].
4.9. Tert-butylnapht-2-ylsulfide (8)
Compound 8 was prepared according to above mentioned
general procedure. The data obtained in the analysis of the
compound corresponded well to that previously published.26
Yield: 68%, white solid; δH (CDCl3, 500 MHz) 8.09 (t, J = 1.2
Hz, 1H), 7.87 (dt, J = 9.6, 3.8 Hz, 2H), 7.81 (d, J = 8.4 Hz, 1H),
7.62 (dd, J = 8.4, 1.7 Hz, 1H), 7.57–7.48 (m, 2H), 1.36 (s, 9H,
tBu); δC (CDCl3, 126 MHz) 137.0, 134.3, 133.4, 133.0, 130.2,
127.9, 127.7, 127.6, 126.6, 126.2, 46.3, 31.0.
4.14. 1-Methyl-3-(tert-butylsulfanyl)pyrazinium iodide
4.10. Tert-butyl(4-trifluoromethylphenyl)sulfide (9)
Compound 11 (212 mg, 1.26 mmol) was dissolved in DMF (2
mL), and MeI (785 ꢀL, 1.79 g, 12.6 mmol) was added. The
reaction was heated at 80 °C for 2 h. Water (5 mL) was added,
and the mixture was washed with diethyl ether (3 × 20 mL). The
water phase was collected and evaporated to dryness. The brown-
red oil that remained after evaporation turned into a dark yellow
solid after the addition of diethyl ether. The solid was collected
and crystallized from methanol/diethyl ether. The dark yellow
crystals were collected and washed slightly with acetone. Yield:
300 mg (77%); dark yellow solid. Yield: 300 mg (77%); dark
Compound 9 was prepared according to above mentioned
general procedure. The data obtained in the analysis of the
compound corresponded well to that previously published.26
Yield: 88%, colorless liquid; δH (CDCl3, 500 MHz) 7.69–7.63 (m,
2H, ArH), 7.62–7.56 (m, 2H, ArH), 1.32 (s, 9H, tBu); δC (CDCl3,
126 MHz) 137.6, 137.3, 130.6 (q, J = 32.6 Hz), 125.2 (q, J = 3.8
Hz), 124.0 (q, J = 272.0 Hz), 46.7, 31.0.
4.11. 4-(tert-butylsulfanyl)phthalonitrile (10)