Paper
RSC Advances
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ꢁ1
8
1
(
3%). H NMR (400 MHz, acetone-d
6
) d 7.06 (s, 1H, 2H), 6.98 (s, (2C), 120.1, 107.3, 103.4, 64.1, 63.3, 15.1. FT IR (ZnSe, cm ):
H, 6H 6-(2,5-dimethoxyphenyl)), 6.94 (d, J ¼ 8.9 Hz, 1H, 3H 6- 2350, 1610, 1503, 1360, 1261, 1147, 1037, 803, 632. HRMS (TOF-
+
2,5-dimethoxyphenyl)), 6.85 (d, J ¼ 8.9 Hz, 1H, 4H 6-(2,5- ES): calculated for C H BrN O (M + H) 331.0441, found
1
6
16
2
dimethoxyphenyl)), 6.74 (s, 1H, 4H), 5.70 (s, 1H, 6H), 3.79 (s, 3H, 331.0445.
1
3
OMe), 3.74 (s, 3H, OMe). C NMR (101 MHz, acetone-d
6
)
d 150.4, 150.2, 144.5, 137.4, 131.3, 120.6, 112.5, 112.3, 103.6,
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Preparation of (5-bromo-3,4-pyrimidin-4-yl)-benzenes (general
procedure)
6
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2.8, 56.2, 56.1. FT IR (ZnSe, cm ): 2350, 1695, 1532, 1253,
2 2
125, 1033, 763. HRMS (TOF-ES): calculated for C12 14BrN O
H
+
(M + H) 297.0233, found 297.0233.
Method C. A 10 mL round bottomed ask equipped with
2
-(5-Bromo-3,4-dihydropyrimidin-4-yl)-4-uorophenol (15i). magnetic stirring bar was charged with DMSO (5 mL), potas-
ꢀ
Light-yellow solid, mp 173–175 C. Yield 203 mg (0.75 mmol, sium hydroxyde (112 mg, 2.00 mmol), and the corresponding (5-
5%). H NMR (400 MHz, acetone-d ) d 7.20 (s, 1H, 2H 2-pyr), bromo-3,4-dihydropyrimidine-4-yl)benzene (1.00 mmol). The
1
7
7
3
6
ꢀ
.04 (dd, J ¼ 9.3, 3.0 Hz, 1H, 5H), 6.94–6.76 (m, 3H, 6H 2-pyr, mixture was stirred for 4 h at 60 C, then poured into cold water
1
3
H, 6H), 5.71 (s, 1H, 4H 2-pyr). C NMR (101 MHz, acetone-d
6
)
(10 mL). Formed precipitate is collected, washed on a lter with
d 157.4 (d, J ¼ 234.5 Hz), 151.9, 145.1, 131.7 (d), 131.2, 117.7 (d), small portions of water and dried on air. Thus obtained crude
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15.8 (d), 115.2 (d), 99.4, 57.3. FT IR (ZnSe, cm ): 3287, 2400, material was puried by column chromatography eluting with
1
635, 1576, 1447, 1356, 1254, 1179, 1024, 731. HRMS (TOF-ES): a mixture of petroleum ether and ethyl acetate (1 : 1).
+
calculated for C H BrFN O (M + H) 270.9877, found 270.9879.
Method D. 10 mL round bottomed ask equipped with
1
0
9
2
5
-Bromo-6-(4-bromo-2-methoxyphenyl)-1,6-dihydropyrimidine magnetic stirring bar was charged with water (5 mL), potassium
ꢀ
(
(
8
2
(
15j). Colorless crystalline solid, mp 69–72 C, Yield 248 mg ferricyanide (658 mg, 2.00 mmol), and potassium hydroxyde
0.72 mmol, 72%). H NMR (400 MHz, acetone-d
1
6
) 7.48 (d, J ¼ (224 mg, 4.00 mmol). (5-Bromo-3,4-dihydropyrimidine-4-yl)
.6 Hz, 1H, 4H), 7.16–7.11 (m, 2H, 2H 4-pyr, 6H), 7.03 (dd, J ¼ 8.6, benzene (1.00 mmol) was added to the formed solution, and
.6 Hz, 1H, 3H), 6.74 (s, 1H 6H 2-pyr), 5.74 (s, 1H, 4H 2-pyr), 3.83 the mixture was stirred at room temperature for 2 h. Aqueous
13
s, 3H, –OMe). C NMR (101 MHz, acetone) d 160.7, 144.1, 135.4, work up, isolation and purication of the product was per-
1
31.8 (2C), 123.4, 118.3, 115.4, 101.3, 61.8, 56.0. FT IR formed in the same way as described for Method C.
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(ZnSe, cm ): 2820, 1589, 1485, 1225, 1029, 852. HRMS (TOF-ES):
4-(5-Bromopyrimidin-4-yl)phenol (20a). Colorless solid, mp
+
ꢀ
calculated for C H Br N O (M + H) 344.9233, found 344.9231. 120–121 C. Rf 0.20 (EtOAc/hexanes, 1 : 1). Yield 44 mg
1
1
11
2 2
5
-Bromo-6-(naphthalene-1-yl)-1,6-dihydropyrimidine and 5- (0.18 mmol, 18% via Method C); 138 mg (0.55 mmol, 55% via
1
bromo-6-(naphthalene-2-yl)-1,6-dihydropyrimidine (15k). Pale- Method D). H NMR (400 MHz, DMSO-d ) d 10.09 (s, 1H, –OH),
6
ꢀ
yellow solid, mp 110–115 C. Yield 237 mg (0.83 mmol, 83%). 9.13 (s, 1H, 2H 4-pyr), 9.02 (s, 1H, 6H 4-pyr), 7.73 (d, J ¼ 8.6 Hz,
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H NMR (400 MHz, DMSO-d
6
) d 8.37 (d, J ¼ 7.9 Hz, 1H), 8.02– 2H, 3,5H), 6.90 (d, J ¼ 8.7 Hz, 2H, 2,6H). C NMR (101 MHz,
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1
.76 (m, 4H), 7.54 (d, J ¼ 7.5 Hz, 5.5H), 7.18 (s, 0.5H), 7.06 (s, DMSO-d
6
) d 162.9, 160.1, 159.6, 156.8, 131.2 (2C), 127.1, 118.1,
115.0 (2C). FT IR (ZnSe, cm ): 2923, 1701, 1558, 1436, 1390,
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H), 6.83 (s, 1H), 6.71 (s, 0.5H), 6.07 (s, 1H), 5.41 (s, 0.5H).
C
NMR (101 MHz, DMSO-d ) d 144.5, 143.9, 141.5, 138.7, 134.1, 1150, 1028, 822. HRMS (TOF-ES): calculated for C H BrN O (M
6
10
8
2
+
1
(
6
33.2, 133.1, 131.1, 129.0, 128.9, 128.6, 128.4, 128.0, 126.8, 126.7 + H) 250.9815, found 250.9816.
2C), 126.6, 126.3, 126.2 (2C), 126.1, 126.0, 124.4, 101.5, 99.7,
2.6, 59.6, 40.6. FT IR (ZnSe, cm ): 1631, 1510, 1352, 1257, solid, mp 99–101 C. Rf 0.26 (EtOAc/hexanes, 1 : 1). Yield 73 mg
28
5-Bromo-4-(4-methoxyphenyl)pyrimidine (20b). Colorless
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ꢀ
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010, 771, 646. HRMS (TOF-ES): calculated for C14
H12BrN
2
(M + (0.28 mmol, 28% via Method C); 169 mg (0.64 mmol, 64% via
+
1
H) 287.0178, found 287.0181.
Method D). H NMR (400 MHz, CDCl ) d 9.11 (s, 1H, 2H), 8.87 (s,
3
6
-(5-Bromo-3,4-dihydropyrimidin-4-yl)naphthalen-2-ol (15l). 1H, 6H), 7.87 (d, J ¼ 8.8 Hz, 2H, 2,6H 4-(4-methoxyphenyl)), 7.01
ꢀ
Pale-yellow solid, mp 150–152 C. Yield 237 mg (0.78 mmol, (d, J ¼ 8.8 Hz, 2H, 3,5H 4-(4-methoxyphenyl)), 3.88 (s, 3H, OMe).
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13
7
4
8
6
8%). H NMR (400 MHz, DMSO-d ) d 7.77 (d, J ¼ 8.7 Hz, 1H,
3
C NMR (101 MHz, CDCl ) d 163.7, 161.5, 160.3, 156.9, 131.3
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H), 7.70 (d, J ¼ 8.5 Hz, 1H,8H), 7.64 (s, 1H, 5H), 7.41 (d, J ¼ (2C), 129.1, 118.8, 113.8 (2C), 55.6. FT IR (ZnSe, cm ): 2955,
.5 Hz, 1H, 7H), 7.18–7.05 (m, 3H, 1H, 3H, 2H 6-pyr), 6.68 (s, 1H, 2325, 1895, 1726, 1607, 1554, 1431, 1259, 1154, 1023, 825, 776.
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3
+
H 6-pyr), 5.31 (s, 1H, 4H 6-pyr). C NMR (101 MHz, acetone-d
6
)
11 10 2
HRMS (TOF-ES): calculated for C H BrN O (M + H) 264.9971,
d 156.5, 144.7, 139.1, 135.7, 131.3, 130.5, 128.9, 127.6, 126.8 found 264.9974
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1
(
1
2C), 119.5, 109.7, 103,4, 63.4. FT IR (ZnSe, cm ): 3150, 2354,
4-(5-Bromopyrimidin-4-yl)-2-methylphenol (20c). Colorless
ꢀ
610, 1350, 1247, 1150, 1010, 854, 673. HRMS (TOF-ES): calcu- solid, mp 160–165 C. Rf 0.22 (EtOAc/hexanes, 1 : 1). Yield
+
lated for C14
H12BrN
2
O (M + H) 303.0128, found 303.0124.
-Bromo-6-(6-ethoxynaphthalen-2-yl)-1,6-dihydropyrimidine
15m). Light-grey solid, mp 123–125 C. Yield 303 mg 4-pyr), 8.92 (s, 1H, 6H 4-pyr), 8.88 (s, 1H, –OH), 7.70 (s, 1H, 5H),
46 mg (0.18 mmol, 18% via Method C); 155 mg (0.59 mmol, 59%
1
5
via Method D). H NMR (400 MHz, acetone-d ) d 9.07 (s, 1H, 2H
6
ꢀ
(
(
9
7
1
1
1
0.914 mmol, 91%). H NMR (400 MHz, acetone-d ) d 7.82 (d, J ¼ 7.65 (d, J ¼ 8.3 Hz, 1H, 3H), 6.96 (d, J ¼ 8.3 Hz, 1H, 2H), 2.28 (s,
6
1
3
.4 Hz, 2H, 4H, 8H), 7.76 (s, 1H, 5H), 7.56 (d, J ¼ 9.4 Hz, 1H, 7H), 3H, –Me). C NMR (101 MHz, acetone-d ) d 164.3, 160.9, 158.4,
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.29 (s, 2H, 1H, 2H 6-pyr), 7.16 (d, J ¼ 8.9 Hz, 1H, 3H), 6.73 (s, 157.6, 133.2, 129.6, 128.9, 119.1, 115.0, 16.2. FT IR (ZnSe, cm ):
H, 4H 6-pyr), 5.46 (s, 1H, 6H 6-pyr), 4.17 (q, J ¼ 7.0 Hz, 2H, –Et), 3049, 2358, 2217, 1565, 1485, 1401, 1279, 1116, 917, 788. HRMS
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3
+
.43 (t, J ¼ 7.0 Hz, 3H, –Et). C NMR (101 MHz, acetone-d
6
)
2
(TOF-ES): calculated for C11H10BrN O (M + H) 264.9971, found
d 158.9, 144.9, 139.4, 135.5, 130.6, 130.4, 129.4, 128.2, 126.9 264.9968.
This journal is © The Royal Society of Chemistry 2020
RSC Adv., 2020, 10, 10315–10321 | 10319