E
M. Vidal et al.
Paper
Synthesis
13C NMR (101 MHz, CDCl3): δ = 177.2, 166.3, 163.2, 136.8, 132.0,
131.1, 129.3, 109.2, 17.2, 9.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C13H13N2O: 213.1023; found:
213.1028.
6-Isopropyl-2-phenyl-4-pyrimidyl Tosylate (5e)
Yellow oil; yield: 256 mg (65%); Rf = 0.88 (hexane/EtOAc, 1:1).
IR (ATR): 2925, 2860, 2790, 1625, 1550, 1460, 1095, 765 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.24 (d, J = 6.6 Hz, 2 H, PhC2-H, C6-H),
8.02 (2 d, J = 7.6 Hz, 2 H, TsC2-H, C6-H), 7.64–7.29 (m, 5 H, Ph, Ts),
6.80 (s, 1 H, C5-H), 3.19–2.88 (m, 1 H, i-PrC-H), 2.46 (s, 3 H, TsCH3),
1.34, 1.33 (2 s, 3 H each, i-PrCH3).
Ultrasound-Promoted Synthesis of 4-Pyrimidyl Tosylates 5; Gen-
eral Procedure 2
The corresponding 4-pyrimidinol (1.07 mmol) and DMAP (1.61
mmol) were dissolved in CH2Cl2 (5.0 mL) in a 20-mL vessel, then TsCl
(1.07 mmol) was added and the resulting mixture was irradiated for 5
min. The mixture was then diluted with sat. aq NaHCO3 (5.0 mL) and
extracted with CH2Cl2 (3 × 15 mL). The combined organic phases were
dried (anhyd Na2SO4) and filtered. The filtrate was rotary evaporated
and the crude product was purified by column chromatography (sili-
ca gel, hexane/EtOAc mixtures).
13C NMR (101 MHz, CDCl3): δ = 178.0, 164.9, 164.4, 145.7, 136.7,
134.2, 131.2, 129.8, 128.9, 128.6, 128.4, 105.6, 36.3, 21.8, 21.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C20H21N2O3S: 369.1268;
found: 369.1271.
6-Ethyl-2-phenyl-4-pyrimidyl Tosylate (5f)
Yellow oil; yield: 265 mg (70%); Rf = 0.80 (hexane/EtOAc, 1:1).
IR (ATR): 3025, 2925, 2790, 1630, 1545, 1375, 1190, 765 cm–1
.
6-Methyl-2-phenyl-4-pyrimidyl Tosylate (5a)
1H NMR (400 MHz, CDCl3): δ = 8.29–8.15 (m, 2 H, PhC2-H, C6-H), 8.00
(d, J = 8.3 Hz, 2 H, TsC2-H, C6-H), 7.51–7.34 (m, 5 H, Ph, Ts), 6.81 (s, 1
H, C5-H), 2.85 (q, J = 7.6 Hz, 2 H, CH2), 2.47 (s, 3 H, TsCH3), 1.35 (t, J =
7.6 Hz, 3 H, CH3).
Colorless solid; yield: 274 mg (75%); mp 132–133 °C; Rf = 0.87 (hex-
ane/EtOAc, 1:1).
IR (ATR): 2925, 2850, 2765, 1680, 1610, 1410, 1185, 770 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 8.19 (d, J = 7.8 Hz, 2 H, PhC2-H, C6-H),
7.99 (d, J = 8.1 Hz, 2 H, TsC2-H, C6-H), 7.51–7.33 (m, 5 H, Ph, Ts), 6.82
(s, 1 H, C5-H), 2.58, 2.46 (2 s, 3 H each, CH3).
13C NMR (101 MHz, CDCl3): δ = 176.2, 164.8, 164.6, 145.7, 136.7,
134.2, 131.3, 129.8, 129.1, 128.8, 128.5, 106.8, 31.6, 21.9, 12.7.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H19N2O3S: 355.1111;
found: 355.1116.
13C NMR (101 MHz, CDCl3): δ = 171.3, 164.69, 164.64, 145.7, 136.5,
134.1, 131.3, 129.9, 128.9, 128.6, 128.5, 108.1, 24.6, 21.9.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C18H17N2O3S: 341.0955;
5,6-Dimethyl-2-phenyl-4-pyrimidyl Tosylate (5g)
found: 341.0958.
Yellow oil; yield: 235 mg (62%); Rf = 0.71 (hexane/EtOAc, 1:1).
IR (ATR): 3080, 3025, 2785, 1630, 1540, 1405, 1180, 760 cm–1
.
2,6-Dimethyl-4-pyrimidyl Tosylate (5b)11
Colorless solid; yield: 381 mg (85%); mp 96–98 °C (Lit.11 97–98 °C);
Rf = 0.37 (hexane/EtOAc, 1:1).
1H NMR (400 MHz, CDCl3): δ = 7.96, 7.36 (2 d, J = 7.9 Hz, 2 H each, Ts),
1H NMR (400 MHz, CDCl3): δ = 8.11–8.06 (m, 2 H, PhC2-H, C6-H), 8.01
(d, J = 8.3 Hz, 2 H, TsC2-H, C6-H), 7.46–7.34 (m, 5 H, Ph, Ts), 2.57 (s, 3
H, C6-CH3), 2.49 (s, 3 H, C5-CH3), 2.30 (s, 3 H, TsCH3).
13C NMR (101 MHz, CDCl3): δ = 169.8, 162.8, 161.2, 145.5, 136.7,
130.8, 129.8, 129.0, 128.5, 128.2, 117.2, 22.8, 21.9, 11.4.
6.77 (s, 1 H, C5-H), 2.57, 2.49, 2.46 (3 s, 3 H each, CH3).
HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H19N2O3S: 355.1111;
found: 355.1119.
2-Ethyl-6-methyl-4-pyrimidyl Tosylate (5c)
Yellow oil; yield: 225 mg (72%); Rf = 0.77 (hexane/EtOAc, 1:1).
IR (ATR): 2980, 2930, 2795, 1630, 1550, 1440, 1190, 755 cm–1
.
2-Cyclopropyl-6-(trifluoromethyl)-4-pyrimidyl Tosylate (5h)
1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 7.7 Hz, 2 H, TsC2-H, C6-H),
7.34 (d, J = 7.7 Hz, 2 H, TsC3-H, C5-H), 6.76 (s, 1 H, C5-H), 2.81 (q, J =
7.2 Hz, 2 H, CH2), 2.49 (s, 3 H, C6-CH3), 2.44 (s, 3 H, TsCH3), 1.19 (t, J =
7.2 Hz, 3 H, CH2CH3).
13C NMR (101 MHz, CDCl3): δ = 172.5, 170.6, 164.4, 145.8, 133.7,
129.7, 129.1, 107.3, 32.2, 24.2, 21.8, 12.3.
Colorless solid; yield: 311 mg (81%); mp 103–105 °C; Rf = 0.36 (hex-
ane/EtOAc, 1:1).
IR (ATR): 3095, 2955, 2790, 1630, 1580, 1430, 1151, 750 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.95, 7.40 (2 d, J = 8.2 Hz, 2 H each, Ts),
7.04 (s, 1 H, C5-H), 2.48 (s, 3 H, CH3), 2.27–2.18, 1.15–1.09, 1.05–0.98
(3 m, 1 H, 2 H, 2 H, cPr).
13C NMR (101 MHz, CDCl3): δ = 172.1, 162.8, 161.4, 138.2, 133.8,
129.9, 129.1, 126.1, 108.3, 24.5, 13.6, 9.2.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C14H17N2O3S: 293.0955;
found: 293.0961.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H14F3N2O3S: 359.0672;
found: 359.0675.
2-Cyclopropyl-6-methyl-4-pyrimidyl Tosylate (5d)
Yellow oil; yield: 261 mg (80%); Rf = 0.76 (hexane/EtOAc, 1:1).
IR (ATR): 3015, 2965, 2780, 1630, 1580, 1435, 1190, 755 cm–1
.
2-Ethyl-5,6-dimethyl-4-pyrimidyl Tosylate (5i)
1H NMR (400 MHz, CDCl3): δ = 7.88, 7.33 (2 d, J = 8.1 Hz, 2 H each),
6.61 (s, 1 H), 2.43, 2.41 (2 s, 3 H each), 2.11–1.96 (m, 1 H), 0.98–0.89,
0.88–0.80 (2 m, 2 H each).
13C NMR (101 MHz, CDCl3): δ = 172.6, 170.3, 164.4, 145.6, 134.0,
129.7, 128.7, 106.5, 24.2, 21.8, 18.1, 11.1.
Yellow oil; yield: 239 mg (73%); Rf = 0.71 (hexane/EtOAc, 1:1).
IR (ATR): 2970, 2850, 2795, 1630, 1545, 1415, 1175, 760 cm–1
.
1H NMR (400 MHz, CDCl3): δ = 7.99, 7.35 (2 d, J = 7.8 Hz, 2 H each, Ts),
2.74 (q, J = 7.4 Hz, 2 H, CH2), 2.45 (s, 6 H, C5-CH3, C6-CH3), 2.19 (s, 3 H,
Ts-CH3), 1.16 (t, J = 7.4 Hz, 3 H, CH3).
13C NMR (101 MHz, CDCl3): δ = 169.4, 169.0, 162.9, 145.8, 134.7,
129.9, 129.5, 116.1, 32.1, 22.7, 22.1, 12.7, 11.4.
HRMS (ESI-TOF): m/z [M + H]+ calcd for C15H17N2O3S: 305.0955;
found: 305.0958.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2016, 48, A–G