E. Lewandowska, D. C. Chatfield
FULL PAPER
7.1 Hz, 2 H), 7.01 (d, J = 16.2 Hz, 1 H), 7.24–7.29 (m, 2 H, col-
lapsed with solvent), 7.54–7.57 (m, 1 H), 8.01 (d, J = 16.2 Hz, 1
H), 8.27–8.29 (m, 1 H) ppm. 13C NMR: δ = 14.6, 61.4, 125.3, 125.4,
125.8, 126.1, 126.2, 134.3, 140.9, 145.7, 166.7 ppm. MS (EI): m/z
= 193 (10) [M+], 148 (20) [M+ – 45] 120 (80) [M+ – 73], 92 (100)
was detected by TLC (CHCl3/MeOH, 9:1; Rf = 0.75). To this solu-
tion, still kept at –70 °C, (ethoxycarbonylmethylene)triphenylphos-
phorane (0.27 g, 0.79 mmol) was added and the mixture was al-
lowed to warm to room temp. over 1 h. The reaction was quenched
with satd. aq. NH4Cl (6 mL) and the organic phase was washed
[M+ – 101]. C10H11NO3 (193.20): calcd. C 62.17, H 5.74, N 7.25; (brine), dried (MgSO4) and the solvents were evaporated. Column
found C 62.57, H 5.37, N 7.62.
chromatography (EtOAc/hexane, 20 Ǟ 50%) gave 9 (58 mg, 48%)
1
as an oil. IR (CHCl ): ν = 1716, 1648w cm–1. H NMR: δ = 1.34
˜
3
Ethyl 3-Propylthio-3-(pyridin-3-yl)propenoate (4). Procedure B: Pro-
panethiol (0.13 mL, 112 mg, 1.47 mmol) was added to a stirred
solution of EtONa in EtOH [prepared from Na (30 mg, 1.30 mmol)
and EtOH (2 mL)] at ambient temperature. After 15 min, a solu-
tion of 2 (65 mg, 0.37 mmol) in EtOH (4 mL) was added, and the
mixture was allowed to stand for 24 h. The resulting mixture was
concentrated to dryness under vacuum and the residue was parti-
tioned CHCl3/H2O. The organic layer was washed with H2O
(5 mL), dried (MgSO4), concentrated and column-chromato-
(t, J = 7.1 Hz, 3 H), 4.28 (q, J = 7.1 Hz, 2 H), 7.20 (d, J = 15.8 Hz,
1 H), 7.23 (t, J = 4.9 Hz, 1 H), 7.70 (d, J = 15.8 Hz, 1 H), 8.78 (d,
J = 4.7 Hz, 2 H). 13C NMR: δ = 14.6, 61.3, 120.6, 127.9, 143.1,
157.6, 163.4, 166.6 ppm. MS (EI): m/z = 178 (20) [M+], 133 (100)
[M+ – 45]. C9H10N2O2 (178.19): calcd. C 60.66, H 5.66, N 15.72;
found C 60.37, H 5.57, N 15.65.
Ethyl (E)-3-(1-Oxidopyrimidin-2-yl)propenoate (10): Treatment of 9
(85 mg, 0.48 mmol) with mCPBA (70%; 0.13 g, 0.53 mmol) accord-
graphed (CHCl3 Ǟ 1% MeOH) to give 4 (68 mg, 73%) as a yellow ing to procedure A [column chromatography (CHCl3 Ǟ 5%
1
oil. IR (CHCl ): ν = 1725 cm–1. H NMR: δ = 0.90 (t, J = 7.3 Hz,
MeOH/CHCl3)] gave 10 (52 mg, 56%) and starting material 9
˜
3
3 H), 1.17 (t, J = 7.1 Hz, 3 H), 1.50 (sept, J = 7.3 Hz, 2 H), 2.40
(t, J = 7.3 Hz, 3 H), 2.92 (dd, J = 16.2, 6.7 Hz, 1 H), 3.20 (dd, J
= 16.2, 8.6 Hz, 1 H), 4.08 (dq, J = 11.5, 7.2 Hz, 2 H), 4.36 (dd, J
= 8.5, 6.7 Hz, 1 H), 7.14 (ddd, J = 5.8, 4.9, 1.1 Hz, 1 H), 7.35 (d,
J = 7.8 Hz, 1 H), 7.64 (td, J = 7.7, 1.8 Hz, 1 H), 8.53 (dd, J = 4.8,
0.8 Hz, 1 H) ppm. 13C NMR: δ = 13.8, 14.5, 23.1, 33.2, 39.8, 46.5,
61.0, 122.5, 123.1, 136.9, 149.6, 161.1, 171.6 ppm. HRMS (EI):
m/z = 253.1142 (10) [M+]; calcd. for C13H19NO2S 253.1136.
(15 mg). IR (CHCl ): ν = 1717 cm–1. 1H NMR: δ = 1.34 (t, J =
˜
3
7.1 Hz, 3 H), 4.30 (q, J = 7.1 Hz, 2 H), 7.24 (t, J = 4.5 Hz, 1 H),
7.30 (d, J = 15.8 Hz, 1 H), 8.26 (d, J = 15.8 Hz, 1 H), 8.28 (dd, J
= 1.4, 4.1 Hz, 1 H), 8.42 (dd, J = 1.5, 6.6 Hz, 1 H) ppm. 13C NMR:
δ = 14.6, 61.5, 121.2, 130.1, 132.1, 144.0, 146.1, 155.6, 166.2 ppm.
MS (EI): m/z = 194 (8) [M+], 149 (20) [M+ – 45] 121 (100) [M+
–
73]. C9H10N2O3 (194.19): calcd. C 55.67, H 5.19, N 14.43; found
C 55.37, H 5.37, N 14.65.
Ethyl 3-Propylthio-3-(1-oxidopyridin-3-yl)propenoate (5) and Ethyl Ethyl 3-Propylthio-3-(pyrimidin-2-yl)propenoate (11): Treatment of
2-propylthio-3-(1-oxidopyridin-3-yl)propenoate (6): Treatment of 3
(40 mg, 0.21 mmol) with propanethiol (0.07 mL, 64 mg,
9
(44 mg, 0.25 mmol) with propanethiol (0.09 mL, 76 mg,
1.0 mmol) according to procedure B [column chromatography
(CHCl )] gave 11 (42 mg, 67%) as an oil. IR (CHCl ): ν =
0.84 mmol) by procedure B [column chromatography (CHCl3
Ǟ
˜
3
3
2% MeOH/CHCl3)] gave 5 and 6 [38 mg, 68%; as an inseparable 1729 cm–1. 1H NMR: δ = 0.91 (t, J = 7.3 Hz, 3 H), 1.15(t, J =
mixture of β (5) and α (6) adduct in a 1:2 ratio as estimated on the
7.16 Hz, 3 H), 1.54 (sept, J = 7.3 Hz, 2 H), 2.53 (m, J = 7.3 Hz, 2
H), 2.96 (dd, J = 16.5, 6.0 Hz, 1 H), 3.20 (dd, J = 16.5, 9.6 Hz, 1
basis of the 1H NMR spectrum] as an oil. IR (CHCl ): ν =
˜
3
1723 cm–1. 1H NMR: δ = 0.92 (t, J = 7.3 Hz, 3 H from β, and 3 H H), 4.08 (qt, J = 7.14, 3.6 Hz 2 H), 4.45 (dd, J = 9.6, 6.0 Hz, 1 H),
from α), 1.21 (t, J = 7.1 Hz, 3 H from β), 1.24 (t, J = 7.1 Hz, 3 H
from α), 1.59 (sept, J = 7.3 Hz, 2 H from α), 1.62 (sept, J = 7.3 Hz,
2 H from β), 2.49–2.56 (m, 2 H, SCH2 from β), 2.58–2.71 (m, 2 H,
7.15 (t, J = 4.9 Hz, 1 H), 8.67 (d, J = 4.9 Hz, 1 H) ppm. 13C NMR:
δ = 13.8, 14.5, 23.2, 33.4, 38.7, 46.9, 61.0, 119.5, 157.6, 170.7, 171.5
ppm. HRMS (EI): m/z
=
254.1103 (10) [M+]; calcd. for
SCH2 from α), 2.96 (dd, J = 16.2, 7.6 Hz, 1 H from β), 3.12 (dd, J C12H18N2O2S 254.1089.
= 16.2, 6.7 Hz, 1 H from β), 3.26 (dd, J = 13.7, 7.3 Hz, 1 H from
Ethyl 2-Propylthio-3-(1-oxidopyrimidin-2-yl)propenoate (12): Treat-
ment of 4 (26 mg, 0.134 mmol) with propanethiol (0.05 mL, 41 mg,
0.54 mmol) according to procedure B [column chromatography
α), 3.42 (dd, J = 13.7, 7.9 Hz, 1 H from α), 4.09–4.19 (m, 2 H from
α, 2 H from β and 1 H from α), 4.99 (t, J = 7.15 Hz, 1 H from β),
7.15–7.22 (m, 2 HAr from α, and 2 HAr from β), 7.31–7.35 (m, 1
HAr from α), 7.64 (dd, J = 2.8, 7.9 Hz, 1 HAr from β), 8.17–8.24
(m, 1 HAr from α, and 1 HAr from β) ppm. 13C NMR: δ = 13.7
(CH3 α),13.8 (CH3 β), 14.5, 23.0 (CH2 α), 23.1 (CH2 β), 30.1, 34.4,
35.2 38.5, 40.1, 42.3, 61.2, 61.7, 124.5, 124.9, 125.7, 125.9, 126.0,
128.4, 140.0, 140.1, 148.7, 152.2 170.8, 172.7 ppm. HRMS (EI):
m/z = 269.1092 (25) [M+]; calcd. for C13H19NO3S 269.1086.
(CHCl3 Ǟ 2% MeOH/CHCl3)] gave 12 (24 mg, 67%) as an oil. IR
1
(CHCl ): ν = 1730 cm–1. H NMR: δ = 0.98 (t, J = 7.3 Hz, 3 H),
˜
3
1.26 (t, J = 7.2 Hz, 3 H), 1.64 (sept, J = 7.3 Hz, 2 H), 2.71 (m, J
= 7.3 Hz, 2 H), 3.51 (dd, J = 17.8, 5.7 Hz, 1 H), 3.70 (dd, J = 17.8,
9.7 Hz, 1 H), 4.02 (dd, J = 9.7, 5.7 Hz, 1 H), 4.42 (q, J = 7.2 Hz,
2 H) 7.23 (dd, J = 6.3, 4.9 Hz, 1 H), 8.18 (dd, J = 4.7, 1.2 Hz, 1
H), 8.40 (dd, J = 6.5, 1.3 Hz, 1 H) ppm. 13C NMR: δ = 13.8, 14.6,
22.9, 33.7, 34.5, 42.0, 61.6, 119.9, 143.1, 144.8, 160.1, 172.2 ppm.
HRMS (EI): m/z = 270.1030 (27) [M]+; calcd. for C12H18N2O3S
270.1038.
Methyl Pyrimidine-2-carboxylate (7): 2-Cyanopyrimidine[20]
(420 mg, 4.0 mmol) was dissolved in methanol (20 mL), saturated
with HCl, and the resulting mixture was heated to reflux for 2 h.
The volatiles were evaporated to dryness under vacuum and the
residue was partitioned with CHCl3/H2O. The organic layer was
washed (NaHCO3, H2O, brine), dried (MgSO4) and the solvents
were evaporated. Column chromatography (CHCl3 Ǟ 4% MeOH/
CHCl3) gave (350 mg, 80%) of the desired compound:[21] 1H NMR:
δ = 4.11 (s, 3 H), 7.53 (t, J = 4.9 Hz, 1 H), 8.98 (d, J = 4.9 Hz, 2
H) ppm. 13C NMR: δ = 54.1, 123.6, 156.8, 158.4, 164.1 ppm.
Computational Methods: Fully optimized reactants and transition
states were computed in the gas phase for each model compound
at the B3LYP/6-31+G(d)[22–25] level using the software packages
Gaussian98 and Gaussian03.[26] The level of theory was chosen on
the basis of previous work in which the α- and β-addition of cya-
nide anion to a set of 22 α,β-unsaturated carbonyl compounds
yielded average differences of 2 kcal/mol between HF/6-31+G(d)
and B3LYP/6-31+G(d) energies for reactants and transition
states.[12] Energy differences at these levels of theory also compared
Ethyl (E)-3-(Pyrimidin-2-yl)propenoate (9): DIBAL/hexane (0.1 m;
0.13 mL, 0.73 mmol) was added over 20 min to a stirred solution of
methyl pyrimidine-2-carboxylate (7, 0.10 g, 0.73 mmol) in CH2Cl2 well to previously published MP2 values. Frequency calculations
(10 mL) at –70 °C (dry ice/acetone). After 1 h, no starting material were performed to verify the nature of all stationary points, transi-
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 3297–3303