November 2009
Novel Synthetic Route for 5-Substituted 6-Arylmethylluracils from
2,4,6-Trichloropyrimidines
1299
Cl2F2N3, Mþþ4). Anal. Calcd. for C12H5Cl2F2N3 (300.09): C,
48.03; H, 1.68; N, 14.00. Found: C, 48.15; H, 1.58; N, 13.93.
2-(2,6-Dichloropyrimidin-4-yl)-2-(3,5-dimethylphenyl)aceto-
troleum ether:ether (1:1, v/v) as eluent to afford compounds
4a,b.
2-(2,6-Dichloropyrimidin-4-yl)-2-phenylpropanenitrile (4a). This
compound was obtained as colorless prisms; 1H nmr (CDCl3,
400 MHz): d 2.18 (s, 3H, CH3), 7.36–7.45 (m, 3H, Harom),
7.47 (s, 1H, H5), 7.49–7.51 ppm (m, 2H, Harom); 13C nmr
(CDCl3, 100 MHz): d 25.80 (CH3), 48.30 (CACN), 117.63
(CN), 120.61 (C5), 126.19, 129.01, 129.41, 137.11 (Carom),
160.93 (C4), 163.68 (C2), 171.49 ppm (C6); ms: (70 eV, elec-
tron impact) m/z 77 (100%), 277 (52%, C13H935Cl2N3, Mþ),
279 (30%, C13H935Cl37ClN3, Mþþ2), 281 (6%, C13H937Cl2N3,
Mþþ4). Anal. Calcd. for C13H9Cl2N3 ( 278.14): C, 56.14; H,
3.26; N, 15.11. Found: C, 56.70; H, 3.22; N, 15.11.
1
nitrile (3c). This compound was obtained as white crystals; H
nmr (CDCl3, 400 MHz) d: 2.33 (s, 6H, (CH3)2N), 5.12 (s, 1H,
CHACN), 7.03 (s, 3H, Harom), 7.39 ppm (s, 1H, H5); 13C nmr
(CDCl3, 100 MHz) d: 21.21 [(CH3)2N], 44.31 (CHACN),
116.87 (C5), 117.87 (CN), 125.46, 131.10, 131.41, 139.64
(Carom), 161.02 (C4), 163.78 (C2), 167.91 (C4) ppm; ms: (70
eV, electron impact) m/z 144 (100%), 291 (86%,
C14H1135Cl2N3, Mþ), 293 (51%, C14H1135Cl37ClN3, Mþþ2),
295 (6%, C14H1137Cl2N3, Mþþ4). Anal. Calcd. for
C14H11Cl2N3 (292.16): C, 57.55; H, 3.79; N, 14.38. Found: C,
58.11; H, 3.85; N, 14.14.
2-(2,6-Dichloropyrimidin-4-yl)-2-(3,5-dimethylphenyl)propa-
nenitrile (4b). This compound was obtained as colorless
(2,6-Dichloropyrimidin-4-yl)(mesityl)acetonitrile
(3d). This
compound was obtained as yellow crystals 1H nmr (CDCl3,
300 MHz): d 2.30 (s, 6H, 3CH3), 5.62 (CHACN), 6.95 (s, 2H,
Harom), 7.14 ppm (s, 1H, H5); 13C nmr (CDCl3, 75 MHz): d
20.67 [(CH3)2Ar], 20.90 (CH3Ar), 38.52 (CHACN), 115.96
(CN), 117.20 (C5), 125.74, 130.57, 136.92, 139.53 (Carom),
161.19 (C4), 163.60 (C2), 167.86 ppm (C6); ms: (70 eV, elec-
tron impact) m/z 32 (100%), 305 (78%, C15H1335Cl2N3, Mþ),
prisms; H nmr (CDCl3, 400 MHz): d 2.14 (s, 3H, CH3), 2.33
1
[s, 6H, (CH3)2Ar], 6.99 (s, 1H, Harom), 7.06 (s, 2H, Harom),
7.43 ppm (s, 1H, H5); 13C nmr (CDCl3, 100 MHz): d 21.36
[(CH3)2Ar], 25.65 (CH3), 48.16 (CACN), 117.77 (CN), 120.85
(C5), 123.87, 130.64, 136.99, 139.21 (Carom), 160.85 (C4),
163.53 (C2), 171.80 ppm (C6); ms: (70 eV, electron impact)
m/z 158 (100%), 305 (47%, C15H1335Cl2N3, Mþ), 307 (47%,
C15H1335Cl37ClN3, Mþþ2), 309 (9%, C15H1337Cl2N3, Mþþ4).
Anal. Calcd. for C15H13Cl2N3 (306.19): C, 58.84; H, 4.28; N,
13.72. Found: C, 58.71; H, 4.23; N, 13.57.
General procedure for synthesis of 6-arylalkylpyrimi-
dine-2,4(1H,3H)-dione derivatives 5a–h. Each compound of
3a–f and 4a,b (5 mmol) was refluxed in a mixture of concen-
trated hydrochloric acid (30 mL) and acetic acid (5 mL) for 50
h. The reaction mixture was cooled to room temperature and
the solid product formed was filtered off, washed with water,
and dried to furnish compounds 5a–h.
307 (55%, C15H1335Cl37ClN3, Mþþ2), 309 (9%, C15H13
37
Cl2N3, Mþþ4). Anal. Calcd. for C15H13Cl2N3 (306.19): C,
58.84; H, 4.28; N, 13.72. Found: C, 58.96; H, 4.05; N, 13.75.
2-(2,6-Dichloro-5-ethylpyrimidin-4-yl)-2-(2,6-difluorophenyl)
acetonitrile (3e). This compound was obtained as yellow crys-
tals; 1H nmr (CDCl3, 300 MHz): d 1.09 (t, 3H, J ¼ 7.2 Hz,
CH3CH2), 2.81 (q, 2H, J ¼ 7.2 Hz, CH3CH2), 5.72 (s, 1H,
CHACN), 7.03 (t, 2H, J ¼ 8.4 Hz, Harom), 7.26–7.44 ppm (m,
1H, Harom); 13C nmr (CDCl3, 75 MHz): d 11.76 (CH3CH2),
21.54 (CH3CH2), 31.66 (t, J ¼ 2.6 Hz, CHACN), 105.87 (C5),
108.81 (t, J ¼ 16.9 Hz, Carom), 112.27 (dd, J ¼ 3.2, 22.3 Hz,
Carom), 114.69 (CN), 131.96 (t, J ¼ 10.4 Hz, Carom), 157.54
(C2), 158.84 (d, J ¼ 6.1 Hz, Carom), 161.95 (C4), 162.19 (d, J
¼ 6.2 Hz, Carom), 163.72 ppm (C6); ms: (70 eV, electron
impact) m/z 308 (100%), 327 (69%, C14H935Cl2F2N3, Mþ),
6-(2,6-Difluorobenzyl)pyrimidine-2,4(1H,3H)-dione (5b). This
compound was obtained as a white solid; H nmr (DMSO-d6,
1
400 MHz): d 3.75 (s, 2H, CH2), 4.78 (s, 1H, H5), 7.18 (t, J ¼
8.0 Hz, 2H, Harom), 7.44–7.51 (m, 1H, Harom), 11.09 ppm (bs,
2H, 2NH) ; 13C nmr (DMSO-d6, 100 MHz): d 24.42 (CH2),
97.41 (C5), 110.80 (t, J ¼ 20.2 Hz, Carom), 111.69 (dd, J ¼
18.7, 6.2 Hz, Carom), 130.21 (t, J ¼ 10.3Hz, Carom), 151.31
(C6), 153.54 (C2), 160.76 (dd, J ¼ 246.8, 7.7 Hz, Carom),
163.79 ppm (C4); ms: (70 eV, electron impact) m/z
68 (100%), 238 (79%, Mþ). Anal. Calcd. for C11H8F2N2
O2.0.4H2O (245): C, 53.93; H, 3.46; N, 11.43. Found: C,
53.82; H, 3.15; N, 11.33.
329 (36%, C14H935Cl37ClF2N3, Mþþ2), 331 (7%, C14H9
37
Cl2F2N3, Mþþ4). Anal. Calcd. for C14H9Cl2F2N3 (328.14): C,
51.24; H, 2.76; N, 12.81. Found: C, 51.31; H, 2.26; N, 12.71.
2-(2,6-Dichloro-5-ethylpyrimidin-4-yl)-2-(3,5-dimethylphenyl)
acetonitrile (3f). This compound was obtained as white crys-
tals; 1H nmr (CDCl3, 300 MHz): d 1.01 (t, 3H, J ¼ 7.6 Hz,
CH3CH2), 2.31 [s, 6H, (CH3)2Ar], 2.75 (q, 2H, J ¼ 7.6 Hz,
CH3CH2), 5.35 (s, 1H, CHACN), 6.98 ppm (s, 3H, Harom);
6-(3,5-Dimethylbenzyl)pyrimidine-2,4(1H,3H)-dione (5c). This
1
13C nmr (CDCl3, 75 MHz):
d 11.91 (CH3CH2), 21.21
compound was obtained as a white solid; H nmr (DMSO-d6,
400 MHz): d 2.25 (s, 6H, (CH3)2Ar)), 3.54 (s, 2H, CH2), 5.23
(s, 1H, H5), 6.90 (s, 1H, Harom), 6.93 (s, 2H, Harom), 10.93
ppm (s, 2H, 2NH); 13C nmr (DMSO-d6, 100 MHz): d 20.75
[(CH3)2Ar], 37.30 (CH2), 98.70 (C5), 126.65, 128.29, 135.82,
137.44 (Carom), 151.53 (C6), 155.61 (C2), 164.02 ppm (C4);
ms: (70 eV, electron impact) m/z 187 (100%), 230 (49%, Mþ).
Anal. Calcd. for C13H14N2O2ꢂ0.25 H2O (232.07): C, 67.28; H,
6.17; N, 12.07. Found: C, 67.15; H, 6.13; N, 12.08
(CH3CH2), 21.67 [(CH3)2Ar], 116.94 (CN), 125.43, 130.87,
131.67, 139.45 (Carom), 132.04 (C5), 157.57 (C2), 163.98
(C4), 164.58 ppm (C6); hrms: (maldi) m/z calcd. for
C16H16Cl2N3 (MHþ) 320.0716, found 320.0719.
Synthesis of 2-aryl-2-(2,6-dichloropyrimidin-4-yl)propa-
nenitriles (4a,b). To a solution of 3a,b (2 mmol) in dry dime-
thylformamide (10 mL) sodium hydride (131 mg, 3 mmol,
55% suspension in paraffin oil) was added portionwise at 0ꢀC.
The mixture was stirred for 1 h and then methyl iodide (0.19
mL, 3 mmol) was added at 0ꢀC. The reaction mixture was
stirred for 6 h at room temperature then poured on ice-cold
water (100 mL). The mixture was extracted with ether (2 ꢁ
20 mL) and the combined ether phases were dried (MgSO4)
and evaporated under reduced pressure. The residual material
was purified by a silica gel column chromatography using pe-
6-(Mesitylmethyl)pyrimidine-2,4(1H,3H)-dione (5d). This
compound was obtained as a white solid; H nmr (DMSO-d6,
1
300 MHz): d 2.15 (s, 6H, 2CH3), 2.23 (s, 3H, CH3), 3.62 (s,
2H, CH2), 4.40 (s, 1H, H5), 6.89 (s, 2H, Harom), 10.98 ppm
(bs, 2H, 2NH); 13C nmr (DMSO-d6, 75 MHz): d 19.32
(2CH3), 20.47 (CH3), 30.94 (CH2), 96.55 (C5), 128.68, 128.76,
136.00, 136.61 (Carom), 151.47 (C4), 155.18 (C2), 163.97 ppm
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet