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24
General Procedure
for the Preparation of 1,4-Dihydro-pyrimidines 2a-e
To
a stirred mixture of 1a (1 g, 3.62 mmol)
and a catalytic amount of vanadium sulfate (0.0072 g, 10 mol%)
in EtOH (2.5 mL) and H2O (2.5 mL) was added dropwise
30% H2O2 (1.52 g, 13.38 mmol) over
1 h maintaining the reaction temperature at about 50 ˚C.
After 8-12 h, the mixture was cooled and volatiles were
evaporated under vacuum. The mixture was diluted with CH2Cl2 (10
mL) and washed with H2O (30 mL). The separated organic
layer was dried with MgSO4, filtered, and concentrated
to afford crude 2a. Column chromatography
with EtOAc-n-hexane gave 2a as a white solid (397 mg, 48%).
Spectroscopic Data
Compound 2a: ¹H NMR (400 MHz,
DMSO-d
6
): δ = 9.30
(s, 1 H), 7.30-7.16 (m, 5 H), 5.40 (s, 1 H), 3.97 (q, J = 4.0 Hz, 2
H), 2.22 (s, 3 H), 1.12 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 167.4,
145.6, 143.3, 128.9, 127.7, 127.6, 100.7, 60.2, 58.0, 19.3, 14.6.
ESI-MS: m/z = 245.3 [M + 1].
Compound 2b: ¹H NMR (400 MHz,
CDCl3): δ = 8.27
(br s, 1 H), 7.26-6.92 (m, 4 H), 5.48 (s, 1 H), 4.08 (q, J = 4.0 Hz, 2
H), 2.62 (q, J = 4.0
Hz, 2 H), 2.22 (s, 3 H), 1.26-1.15 (m, 6 H). ¹³C
NMR (100 MHz, CDCl3): δ = 167.3,
145.6, 144.4, 143.9, 142.8, 128.4, 127.5, 101.0, 60.2, 57.2, 28.9,
18.8, 15.8, 14.6. ESI-MS: m/z = 273.4 [M + 1].
Compound 2c: ¹H NMR (400 MHz,
CDCl3): δ = 10.13
(s,
1 H), 9.91 (s, 1 H), 4.83 (t, J = 4.0
Hz, 1 H), 4.26 (m, 2 H), 2.48 (s, 3 H), 1.79-1.14 (m, 11
H), 0.87 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 164.3,
161.1, 142.7, 107.4, 61.7, 52.5, 51.7, 47.0, 36.9, 31.6, 23.3, 22.7,
17.9, 14.6, 14.3. ESI-MS: m/z = 239.3 [M + 1].
Compound 2d: ¹H NMR (400 MHz,
CDCl3): δ = 7.43
(s,
1 H), 7.28-7.14 (m, 5 H), 4.63 (t, J = 4.0 Hz,
1 H), 4.18 (m, 2 H), 2.80-2.67 (m, 2 H), 2.28 (s, 3 H),
1.91-1.82 (m, 2 H), 1.26 (t, J = 3.3
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 175.9,
165.8, 165.7, 144.5, 141.1, 128.9, 128.7, 126.5, 103.2, 103.1, 60.8,
60.4, 52.3, 38.3, 30.9, 18.6, 14.7. ESI-MS: m/z = 271.4 [M + 1].
Compound 2e: ¹H NMR (400 MHz,
CDCl3): δ = 7.34-6.99 (m,
4 H), 5.57 (s, 1 H), 5.40 (d, J = 4.0
Hz, 1 H), 4.09 (m,
2 H), 2.31 (s, 3 H), 1.20 (t, J = 2.7 Hz,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 167.1,
162.5 (d, J = 250.0
Hz), 145.1, 142.6, 141.4, 129.2 (d, J = 10.0
Hz), 115.6 (d, J = 20.0
Hz), 115.5, 101.2, 60.3, 57.4, 19.5, 14.6. ESI-MS: m/z = 263.3 [M + 1].
26
General Procedure
for the Preparation of 2-Unsubsti-tuted Pyrimidines 3a-e
To
a stirred solution of 2a (100 mg, 0.41
mmol) in acetone (2 mL) was added KMnO4 (87 mg, 0.55
mmol). After the complete consumption of 2a,
excess of KMnO4 was decomposed by the addition of 2-PrOH.
The reaction mixture was filtered through Celite and washed thoroughly with
acetone (10 mL). Removal of solvent afforded product 3a (72mg,
73%) as a white solid.
Spectroscopic
Data
Compound 3a: ¹H
NMR (400 MHz, CDCl3): δ = 9.16
(s, 1 H), 7.68-7.43 (m, 5 H), 4.24 (q, J = 4.0
Hz, 2 H), 2.57 (s, 3 H), 1.10 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 167.4,
164.7, 162.9, 157.8, 137.2, 131.8, 131.5, 129.9, 128.3, 128.0, 125.7,
61.7, 22.3, 13.4. ESI-MS: m/z = 243.4 [M + 1].
Compound 3b: ¹H NMR(400 MHz,
CDCl3): δ = 9.13
(s, 1 H), 7.60 (d, J = 4.0
Hz, 2 H), 7.37 (d, J = 4.0
Hz, 2 H), 4.26 (q, J = 4.0
Hz, 2 H), 2.73 (q, J = 4.0
Hz, 2 H), 2.62 (s, 3 H), 1.28 (t, J = 2.7
Hz, 3 H), 1.13 (t, J = 2.7
Hz, 3H). ¹³C NMR (100 MHz, CDCl3): δ = 168.3,
165.2, 163.6, 158.4, 147.2, 135.8, 128.8, 128.6, 126.2, 62.3, 29.1,
22.9, 15.8, 14.1. ESI-MS: m/z = 271.3 [M + 1].
Compound 3c: ¹H NMR (400 MHz,
CDCl3): δ = 9.01
(s, 1 H), 4.48 (q, J = 4.0
Hz, 2 H), 2.79 (t, J = 4.0
Hz, 2 H), 2.54 (s, 3 H), 1.77-1.22 (m, 9 H), 0.92 (t, J = 2.7 Hz,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 167.8,
167.7, 164.2, 158.3, 62.2, 36.1, 31.9, 28.9, 22.9, 22.7, 14.4, 14.2.
ESI-MS:
m/z = 237.3 [M + 1].
Compound 3d: ¹H NMR (400 MHz,
CDCl3): δ = 9.02
(s, 1 H), 7.40-7.00 (m, 5 H), 4.44 (q, J = 4.0
Hz, 2 H), 3.11-3.02 (m, 4 H), 2.54 (s, 3 H), 1.40 (t, J = 3.3 Hz,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 167.6,
166.8, 164.6, 158.5, 128.9, 128.8, 127.2, 126.7, 62.4, 38.2, 35.3,
23.2, 14.6. ESI-MS:
m/z = 271.4 [M + 1].
Compound 3e: ¹H NMR (400 MHz,
CDCl3): δ = 9.14
(s, 1 H), 7.70-7.65 (m, 2 H), 7.21-7.11 (m, 2
H), 4.27 (q, J = 4.0 Hz,
2 H), 2.63 (s, 3 H), 1.18 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 168.1,
164.4 (d, d, J = 230.0
Hz), 164.0, 162.4, 158.5, 134.0, 131.0 (d, J = 10.0
Hz), 126.2, 116.2 (d, J = 20.0
Hz), 62.5, 23.0, 14.1. ESI-MS: m/z = 261.3 [M + 1].
27
General Procedure
for the Preparation of 2-Hydroxy-pyrimidines 5a-e
To
a stirred solution of 4a (1.0 g, 3.84 mmol)
in acetone (20 mL) was added KMnO4 (1.52 g, 9.60 mmol).
After the complete consumption of 4a, the
excess KMnO4 was decomposed by the addition of 2-PrOH.
The reaction mixture was filtered through Celite and washed thoroughly with
acetone (30 mL). Removal of solvent afforded product 5a (670mg,
81%) as a white solid.
Spectroscopic
Data
Compound 5a: ¹H
NMR (400 MHz, CDCl3): δ = 7.61-7.41 (m,
5 H), 4.05 (q, J = 4.0
Hz, 2 H), 2.62 (s, 3 H), 0.94 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 167.4, 164.7,
162.9, 157.8, 137.2, 131.8, 131.7, 131.5, 129.9, 128.3, 128.0, 125.7,
61.7, 22.3, 13.4. ESI-MS: m/z = 259.3 [M + 1].
Compound 5b: ¹H NMR (400 MHz,
CDCl3): δ = 7.52-7.13 (m,
4 H), 4.80-4.26 (m, 2 H), 3.01 (q, J = 4.0
Hz, 2 H), 2.84 (s, 1 H), 2.69-2.45 (m, 2 H), 2.30 (s, 3
H), 1.26 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 165.8,
141.0, 140.4, 129.0, 128.8, 128.7, 126.9, 126.8, 62.2, 38.8, 31.8,
31.0, 30.7, 30.1, 25.5, 14.6. ESI-MS: m/z = 287.3 [M + 1].
Compound 5c: ¹H NMR (400 MHz,
CDCl3): δ = 4.42
(q, J = 2.0
Hz, 2 H), 2.80 (t, J = 2.0
Hz, 2 H), 2.53 (s, 3 H), 1.73-1.26 (m, 9 H), 0.90 (t, J = 2.7 Hz,
3 H). ¹³C NMR (100 MHz, CDCl3): δ = 166.0,
158.7, 111.8, 62.1, 32.0, 31.8, 31.5, 22.8, 14.6, 14.29, 14.26.
ESI-MS: m/z = 253.3 [M + 1].
Compound 5d: ¹H NMR (400 MHz,
CDCl3): δ = 7.52-7.13 (m,
5 H), 4.80-4.26 (m, 2 H), 3.01 (q, J = 4.0
Hz, 2 H), 2.84 (s, 1 H), 2.69-2.45 (m, 2 H), 2.30 (s, 3
H), 1.26 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 175.9,
165.8, 165.7, 144.5, 141.1, 128.9, 128.7, 126.5, 103.2, 103.1, 60.8,
52.3, 38.3, 30.9, 18.6, 14.7. ESI-MS: m/z = 287.3 [M + 1].
Compound 5e: ¹H NMR (400 MHz,
CDCl3): δ = 7.65-6.97 (m,
4 H), 4.11 (q, J = 4.0
Hz, 2 H), 2.62 (s, 3 H), 1.02 (t, J = 2.7
Hz, 3 H). ¹³C NMR (100 MHz, CDCl3): δ = 165.5, 162.4
(d, J = 250.0
Hz), 146.4, 139.7, 139.6, 128.4 (d, J = 10.0
Hz), 115.5 (d, J = 20.0
Hz), 101.4, 60.1, 55.0, 18.5, 14.2. ESI-MS: m/z = 277.3 [M + 1].