F
A. Seballos-Resendiz et al.
Paper
Synthesis
4-(Dimethylamino)-4-(2-methylphenyl)-2-(trichloromethyl)-1,3-
diaza-1,3-butadiene (4e)
1H NMR (300 MHz, CDCl3): δ = 7.23 (s, 4 H), 3.78–3.24 (m, 8 H), 2.37
(s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 166.60, 163.34, 140.13, 129.49, 128.32,
From 1e (380 mg, 3.5 mmol), 4e was obtained after purification by
flash column chromatography (silica gel, hexanes–EtOAc, 7:3).
127.53, 97.41, 66.74, 47.88, 45.27, 21.42.
MS: m/z (%) = 350 (22) [M+ + 4], 348 (49) [M+ + 2], 346 (43) [M+], 230
(96), 119 (43), 118 (100), 91 (46), 69 (29), 42 (22).
Yield: 460 mg (65%); white solid; crystallization (hexanes–CH2Cl2);
mp 73–75 °C (EtOAc).
1H NMR (300 MHz, CDCl3): δ = 7.31–7.19 (m, 4 H), 3.28 (s, 3 H), 2.77
(s, 3 H), 2.31 (s, 3 H).
6-Aryl-2-(trichloromethyl)pyrimidines 5; General Procedure
13C NMR (75 MHz, CDCl3): δ = 165.92, 163.80, 135.74, 132.53, 130.00,
129.41, 126.47, 126.09, 97.93, 38.29, 37.24, 19.42.
MS: m/z (%) = 308 (12) [M+ + 4], 306 (17) [M+ + 2], 304 (9) [M+], 290
(62), 188 (99), 118 (43), 91 (30), 71 (100), 65 (20), 44 (31).
DMAD (2.0 equiv) was added dropwise to a stirred solution of 1,3-di-
azabutadiene 4 in anhydrous CH2Cl2 (1mL/mmol 4) under N2 atmo-
sphere at r.t. (usually an exothermic reaction was observed) and the
reaction mixture was stirred 2–3 h. After this time, two products
were observed by TLC analysis (5 and the addition product of the cor-
responding dialkylamine to DMAD). CH2Cl2 (20 mL) was added and
the organic phase was washed with saturated NaCl solution, dried
over Na2SO4, and concentrated in vacuo. The residue was purified by
column chromatography (silica gel, hexanes–EtOAc); this gave 5.
4-(3,4-Dimethoxyphenyl)-4-(dimethylamino)-2-(trichlorometh-
yl)-1,3-diaza-1,3-butadiene (4f)
From 1f (483 mg, 2.3 mmol), 4f was obtained after purification by
flash column chromatography (silica gel, hexanes–EtOAc, 1:1).
Yield: 540 mg (66%); oil.
1H NMR (300 MHz, CDCl3): δ = 6.92–6.89 (m, 3 H), 3.90–3.85 (m, 6 H),
Dimethyl 6-Phenyl-2-(trichloromethyl)pyrimidine-4,5-dicarbox-
ylate (5a)
3.21–2.92 (m, 6 H).
From 4a (530 mg, 1.8 mmol), 5a was obtained after purification by
flash column chromatography (silica gel, hexanes–EtOAc, 9:1).
13C NMR (75 MHz, CDCl3): δ = 164.17, 153.28, 150.07, 149.12, 120.73,
110.82, 110.63, 110.17, 97.88, 56.00, 55.84, 39.69, 37.88.
Yield: 622 mg (88%); white solid; crystallization (CH2Cl2–hexanes);
mp 136–137 °C.
1H NMR (300 MHz, CDCl3): δ = 7.84–7.81 (m, 2 H), 7.57–7.52 (m, 3 H),
4.05 (s, 3 H), 3.87 (s, 3 H).
4-(4-Methoxyphenyl)-4-morpholino-2-(trichloromethyl)-1,3-di-
aza-1,3-butadiene (4g)
13C NMR (75 MHz, CDCl3): δ = 166.33, 166.30, 165.22, 163.74, 155.10,
135.48, 131.60, 128.96, 125.28, 95.68, 53.89, 53.40.
From 1g (520 mg, 2.3 mmol), 4g was obtained after purification by
flash column chromatography (silica gel, hexanes–EtOAc, 65:35).
MS: m/z (%) = 392 (5) [M+ + 4], 390 (16) [M+ + 2], 388 (17) [M+], 353
(89), 272 (47), 142 (63), 127 (70), 59 (100).
Yield: 260 mg (52%); white solid; crystallization (EtOAc); mp 93–
95 °C.
1H NMR (300 MHz, CDCl3): δ = 7.30 (d, J = 9.0 Hz, 2 H), 6.94 (d, J = 9.0
Hz, 2 H), 3.82 (m, 11 H).
13C NMR (75 MHz, CDCl3): δ = 166.69, 163.25, 160.74, 132.35, 129.23,
Dimethyl 6-(4-Fluorophenyl)-2-(trichloromethyl)pyrimidine-4,5-
dicarboxylate (5b)
123.23, 114.21, 113.53, 97.42, 66.74, 55.28, 48.12.
From 4b (320 mg, 1.0 mmol), 5b was obtained after purification by
flash column chromatography (silica gel, hexanes–EtOAc, 9:1).
MS: m/z (%) = 366 (14) [M+ + 4], 364 (33) [M+ + 2], 362 (31) [M+], 246
(76), 135 (100), 134 (89), 77 (32).
Yield: 360 mg (85%); white solid; crystallization (CH2Cl2–hexanes);
mp 124–125 °C.
1H NMR (300 MHz, CDCl3): δ = 7.88–7.83 (m, 2 H), 7.24–7.19 (m, 2 H),
4.06 (s, 3 H), 3.96 (s, 3 H).
4-(4-Chlorophenyl)-4-morpholino-2-(trichloromethyl)-1,3-diaza-
1,3-butadiene (4h)
13C NMR (75 MHz, CDCl3): δ = (CDCl3) 166.61, 166.28, 165.21, 165.08,
163.66, 155.14, 131.40, 131.28, 125.08, 116.43, 116.14, 95.58, 53.96,
53.53.
MS: m/z (%) = 410 [M+ + 4], 408 (16) [M+ + 2], 406 (16) [M+], 371 (42),
292 (50), 290 (52), 59 (100).
From 1h (520 mg, 2.3 mmol), 4h was obtained after purification by
flash column chromatography (silica gel, hexanes–EtOAc, 65:35).
Yield: 460 mg (54%); crystals; crystallization (EtOAc); mp 106–
109 °C.
1H NMR (300 MHz, CDCl3): δ = 7.42–7.30 (m, 4 H), 3.78–3.22 (m, 8 H).
13C NMR (75 MHz, CDCl3): δ = 166.03, 161.93, 136.04, 129.73, 129.16,
129.00, 96.99, 66.65, 45.65.
MS: m/z (%) = 370 (16) [M+ + 4], 368 (31) [M+ + 2], 366 (24) [M+], 252
(34), 250 (100), 140 (29), 139 (75), 138 (76), 113 (30), 111 (44), 86
(30), 75 (29), 69 (45), 44(35).
Dimethyl 6-(4-Nitrophenyl)-2-(trichloromethyl)pyrimidine-4,5-
dicarboxylate (5c)
From 4c (290 mg, 0.85 mmol), 5c was obtained after purification by
flash column chromatography (silica gel, hexanes–EtOAc, 9:1).
Yield: 350 mg (96%); white solid; crystallization (CH2Cl2–hexanes);
mp 118–119 °C.
1H NMR (300 MHz, CDCl3): δ = 8.38 (d, J = 9 Hz, 2 H), 7.98 (d, J = 9 Hz,
4-(4-Methylphenyl)-4-morpholino-2-(trichloromethyl)-1,3-diaza-
1,3-butadiene (4i)
2 H), 4.08 (s, 3 H), 3.90 (s, 3 H), 2.34 (s, 6 H).
From 1i (479 mg, 2.3 mmol), 4i was obtained after purification by
13C NMR (75 MHz, CDCl3): δ = 165.55, 164.17, 163.35, 155.68, 149.52,
flash column chromatography (silica gel, hexanes–EtOAc, 65:35).
141.10, 130.13, 125.67, 124.04, 95.26, 54.12, 53.79.
MS: m/z (%) = 437 (3) [M+ + 4], 435 (7) [M+ + 2], 433 (6) [M+], 398 (85),
Yield: 500 mg (63%); crystals; crystallization (hexanes–CH2Cl2); mp
122–125 °C.
368 (83), 317 (88), 59 (100).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2015, 47, A–H