10.1002/asia.201900744
Chemistry - An Asian Journal
FULL PAPER
J = 6.0 Hz, 2H), 2.96 (s, 3H), 2.91 (s, 3H), 1.99 (bs, 1H) ppm; 13C NMR
(100 MHz, CDCl3) 172.1, 155.9, 135.6, 116.9, 72.6, 45.8, 26.9, 24.6 ppm;
HRMS (ESI) calcd for C8H13N3O2Na [M + Na] 206.0900 found 206.0895;
IR (neat) 3343, 2923, 1771, 1712, 1644, 1481 cm-1.
161 mg, 81% yield, 4 h; 1H NMR (500 MHz, CDCl3) 6.83-6.78 (m, 1H),
6.74-6.69 (m, 1H), 6.64-6.59 (m, 1H), 5.09 (s, 1H), 4.49 (bs, 1H), 3.03 (s,
3H), 2.96 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3) 170.4, 156.5 (dd, J =
241.3, 11.3 Hz), 155.6, 152.0 (dd, J = 241.3, 11.3 Hz), 128.9 (dd, J = 12.5,
3.8 Hz), 115.6 (dd, J = 8.8, 3.8 Hz), 111.4 (dd, J = 21.3, 3.8 Hz), 104.4 (dd,
J = 26.3, 23.8 Hz), 70.3, 27.2, 25.0 ppm; 19F NMR (470 MHz, CDCl3) -
120.47, -128.69 ppm; HRMS (ESI) calcd for C11H11F2N3NaO2 [M + Na]
278.0712 found 278.0713; IR (neat) 3355, 3084, 1776, 1717, 1610, 1528
cm-1.
5-((4-Methoxy-2-nitrophenyl)amino)-1,3-dimethylimidazolidine-2,4-
dione (8m). Brick red crystalline solid, 0.11 Rf in EtOAc:petroleum ether
(1:1), mp 166-168 ºC, 126 mg, 72% yield, 5 h; 1H NMR (400 MHz, CDCl3)
8.00 (d, J = 8.4 Hz, 1H), 7.65 (d, J = 3.2 Hz, 1H), 7.13 (dd, J = 9.2, 3.2
Hz, 1H), 6.83 (d, J = 9.2 Hz, 1H), 5.32 (d, J = 8.0 Hz, 1H), 3.79 (s, 3H),
3.09 (s, 3H), 2.98 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) 169.8, 155.6,
151.9, 137.2, 134.1, 126.2, 116.1, 108.6, 68.8, 56.1, 27.5, 25.3 ppm;
HRMS (ESI) calcd for C12H14N4NaO5 [M + Na] 317.0856 found 317.0859;
IR (neat) 3372, 3020, 1778, 1719, 1576, 1520 cm-1.
5-((2-Methoxy-4-nitrophenyl)amino)-1,3-dimethylimidazolidine-2,4-
dione (8n). Fluorescent yellow solid, 0.10 Rf in EtOAc:petroleum ether
(1:1), mp 196-198 ºC, 129 mg, 74% yield, 6 h; 1H NMR (400 MHz, CDCl3)
7.84 (dd, J = 8.8, 2.4 Hz, 1H), 7.67 (d, J = 2.4 Hz, 1H), 6.59 (d, J = 8.8
Hz, 1H), 5.47 (d, J = 8.8 Hz, 1H), 5.30 (d, J = 8.8 Hz, 1H), 3.95 (s, 3H),
3.09 (s, 3H), 2.97 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) 169.6, 155.5,
146.3, 140.7, 140.1, 118.9, 108.8, 105.6, 68.3, 56.3, 27.5, 25.3 ppm;
HRMS (ESI) calcd for C12H15N4O5 [M + H] 295.1037 found 295.1035; IR
(neat) 3385, 2935, 1777, 1715, 1594, 1483 cm-1.
5-((1,3-Dimethyl-2,5-dioxoimidazolidin-4-yl)amino)-2-
methylisoindoline-1,3-dione (8t). Pale green powder, 0.14 Rf in
EtOAc:petroleum ether (1:1), mp 228-230 ºC, 121 mg, 70% yield, 5 h; 1H
NMR (400 MHz, CDCl3) 7.64 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 2.4 Hz, 1H),
6.85 (dd, J = 8.0, 2.0 Hz, 1H), 5.31 (d, J = 8.8 Hz,1H), 4.98 (d, J = 8.8 Hz,
1H), 3.13 (s, 3H), 3.10 (s, 3H), 3.00 (s, 3H) ppm; 13C NMR (100 MHz,
CDCl3) 169.7, 168.4, 168.3, 155.5, 150.1, 135.2, 125.3, 123.1, 117.7,
107.9, 68.9, 27.7, 25.3, 24.1 ppm; HRMS (ESI) calcd for C14H14N4NaO4 [M
+ Na] 325.0907 found 325.0905; IR (neat) 3315, 3027, 1752, 1706, 1617,
1449 cm-1.
5-((4-(4-(((R)-1,3-Dimethyl-2,5-dioxoimidazolidin-4-
yl)amino)benzyl)phenyl)amino)-1,3-dimethylimidazolidine-2,4-dione
(8u). Pale yellow solid, 0.58 Rf in EtOAc:petroleum ether (3:2), mp 152-
154 ºC, 182 mg, 80% yield, 5 h; 1H NMR (400 MHz, CDCl3) 6.98 (d, J =
8.5 Hz, 4H), 6.58 (d, J = 8.5 Hz, 4H), 5.10 (d, J = 8.0 Hz, 2H), 4.20 (d, J =
8.0 Hz, 2H), 3.77 (s, 2H), 3.06 (s, 6H), 2.97 (s, 6H) ppm; 13C NMR (100
MHz, CDCl3) 170.8, 155.7, 142.5, 133.7, 130.1, 115.0, 70.4, 40.3, 27.3,
25.1 ppm; HRMS (ESI) calcd for C23H26N6NaO4 [M + Na] 473.1908 found
473.1902; IR (neat) 3368, 3020, 1773, 1712, 1615, 1519 cm-1.
2-(4-((1,3-dimethyl-2,5-dioxoimidazolidin-4-yl)amino)phenyl)-1H-
benzo[de]isoquinoline-1,3(2H)-dione (8v). Yellow solid, 0.30 Rf in
EtOAc:petroleum ether (4:1), mp 256-258 ºC, 111 mg, 77 % yield, 5 h; 1H
NMR (500 MHz, DMSO-d6) 8.47 (d, J = 8.0 Hz, 4H), 7.87 (t, J = 7.8 Hz,
2H), 7.10 (d, J = 8.0 Hz, 2H), 6.86 (d, J = 9.0 Hz, 1H), 6.72 (d, J = 8.5 Hz,
2H), 5.48 (d, J = 8.5 Hz, 1H), 2.95 (s, 3H), 2.84 (s, 3H) ppm; 13C NMR
(125 MHz, DMSO-d6) 170.9, 163.9, 155.4, 145.6, 134.3, 131.4, 130.7,
129.7, 127.7, 127.2, 125.9, 122.6, 113.0, 68.7, 26.8, 24.5 ppm; HRMS
(ESI) calcd for C23H18N4NaO4 [M + Na] 437.1220 found 437.1227; IR
(neat) 3349, 2934, 2361, 1723, 1718, 1707, 1452, 1235 cm-1.
1,3-Dimethyl-5-((4-nitrophenyl)amino)imidazolidine-2,4-dione
(8o).
Fluorescent yellow crystalline solid, 0.12 Rf in EtOAc:petroleum ether (1:1),
mp 190-192 ºC, 159 mg, 83% yield, 4 h; 1H NMR (400 MHz, DMSO-d6)
8.06 (d, J = 9.2, 2H), 7.82 (d, J = 8.8 Hz, 1H), 6.84 (d, J = 9.2 Hz, 2H), 5.65
(d, J = 9.2 Hz, 1H), 2.93 (s, 3H), 2.79 (s, 3H) ppm; 13C NMR (100 MHz,
DMSO-d6) 169.9, 155.4, 152.4, 138.0, 126.1, 112.2, 67.5, 27.0, 24.6
ppm; HRMS (ESI) calcd for C11H12N4NaO4 [M + Na] 287.0751 found
287.0753; IR (neat) 3369, 3023, 1732, 1712, 1599, 1481 cm-1.
5-((5-chloro-2-nitrophenyl)amino)-1,3-dimethylimidazolidine-2,4-
dione (8p). Fluorescent yellow solid, 0.45 Rf in EtOAc:petroleum ether
(3:2), mp 206-208 ºC, 138 mg, 80% yield, 5 h; 1H NMR (400 MHz, DMSO-
d6) 8.44 (d, J = 9.2 Hz, 1H), 8.12 (d, J = 9.2 Hz, 1H), 7.28 (bs, 1H), 6.90
(dd, J = 8.0, 2.0 Hz, 1H), 5.96 (d, J = 9.2 Hz, 1H), 2.89 (s, 3H), 2.81 (s, 3H)
ppm; 13C NMR (100 MHz, DMSO-d6) 169.9, 155.6, 143.7, 141.2, 132.0,
128.5, 117.5, 114.0, 67.0, 26.8, 24.6 ppm; HRMS (ESI) calcd for
C11H11ClN4NaO4 [M + Na] 321.0361 found 321.0369; IR (neat) 3311, 3105,
1783, 1730, 1609, 1565, 1490 cm-1.
4-((1,3-dimethyl-2,5-dioxoimidazolidin-4-yl)amino)benzonitrile (8q).
colourless crystalline solid, 0.28 Rf in EtOAc:petroleum ether (1:1), mp
142-144 ºC, 147 mg, 71% yield, 6 h; 1H NMR (400 MHz, CDCl3) 7.43 (d,
J = 8.8 Hz, 2H), 6.64 (d, J = 8.8 Hz, 2H), 5.23 (bs, 2H), 3.04 (s, 3H), 2.93
(s, 3H) ppm; 13C NMR (125 MHz, CDCl3) 196.7, 170.2, 155.5, 149.0,
130.9, 129.4, 113.1, 68.8, 27.4, 26.3, 25.1 ppm; HRMS (ESI) calcd for
C12H13N4O2 [M + H] 245.1033 found 245.1033; IR (neat) 3352, 2219, 1778,
1715, 1607, 1529, 1480 cm-1.
5-((4-Acetylphenyl)amino)-1,3-dimethylimidazolidine-2,4-dione (8r).
Off white crystalline solid, 0.13 Rf in EtOAc:petroleum ether (1:1), mp 134-
136 ºC, 158 mg, 82% yield, 4 h; 1H NMR (500 MHz, CDCl3) 7.79 (d, J =
8.5 Hz, 2H), 6.63 (d, J = 8.5 Hz, 2H), 5.26 (s, 1H), 3.04 (s, 3H), 2.94 (s,
3H), 2.48 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3) 169.9, 155.4, 148.4,
134.0, 119.6, 113.8, 102.1, 68.6, 27.4, 25.2 ppm; HRMS (ESI) calcd for
C13H15N3NaO3 [M + Na] 284.1009 found 284.1006; IR (neat) 3346, 3017,
1776, 1717, 1664, 1600 cm-1.
General procedure for the synthesis of 9a-o
In a typical procedure, 500 mg of a mixture of N,Nʹ-dimethylthiourea:L-(+)-
tartaric acid (70:30 by weight) was heated to 80 °C to obtain a deep
eutectic solvent. To this clear melt, 1.0 equiv. of corresponding aniline (100
mg) and 2 equiv. of ethyl glyoxalate (50% solution in toluene) were added
at 80 ºC. After completion of the reaction (TLC monitoring by mini work up),
the reaction mixture was quenched with water while it was still hot. The
reaction mixture was cooled to room temperature, extracted with EtOAc (3
× 10 mL) and dried over anhydrous Na2SO4. The crude products were
concentrated under reduced pressure and purified by silica gel column
chromatography using combination of EtOAc and petroleum ether as an
eluent to give the corresponding thiohydantoin derivatives 9a-o.
1,3-Dimethyl-5-(phenylamino)-2-thioxoimidazolidin-4-one (9a). Yellow
solid, 0.79 Rf in EtOAc:petroleum ether (3:2), mp 116-118 ºC, 152 mg, 60%
yield, 6 h; 1H NMR (500 MHz, CDCl3) 7.21 (t, J = 8.0 Hz, 2H), 6.88 (t, J
= 7.5 Hz, 1H), 6.58 (d, J = 8.0 Hz, 2H), 5.21 (s, 1H), 3.32 (s, 3H), 3.28 (s,
3H) ppm; 13C NMR (125 MHz, CDCl3) 182.5, 170.6, 143.8, 129.9, 121.0,
114.6, 71.4, 31.5, 28.5 ppm; HRMS (ESI) calcd for C11H13N3NaOS [M +
Na] 258.0672 found 258.0674; IR (neat) 3396, 2925,1759,1745, 1513,
1388 cm-1.
5-((3,4-Dimethylphenyl)amino)-1,3-dimethyl-2-thioxoimidazolidin-4-
one (9b). Yellow solid, 0.81 Rf in EtOAc:petroleum ether (3:2), mp 140-
142 ºC, 140 mg, 65% yield, 6 h; 1H NMR (400 MHz, CDCl3) 6.94 (d, J =
8.0 Hz 1H), 6.42 (d, J = 2.4 Hz, 1H), 6.32 (dd, J = 8.0, 2.4 Hz, 1H), 5.15 (s,
1H), 3.30 (s, 3H), 3.28 (s, 3H), 2.17 (s, 3H), 2.15 (s, 3H) ppm; 13C NMR
(100 MHz, CDCl3) 182.5, 170.8, 141.7, 138.2, 130.9, 129.3, 116.8, 111.9,
71.9, 31.5, 28.4, 20.2 18.9 ppm; HRMS (ESI) calcd for C13H17N3NaOS [M
+
Na] 286.0985 found 286.0983; IR (neat) 3396, 3010,1773,
5-(Allylamino)-1,3-dimethylimidazolidine-2,4-dione (8s). Off white
crystalline solid, 0.18 Rf in EtOAc:petroleum ether (1:1), mp 70-72 ºC, 219
mg, 68% yield, 6 h; 1H NMR (400 MHz, CDCl3) 5.85 (m, 1H), 5.14 (dd, J
= 17.2, 1.2 Hz, 1H), 5.06 (dd, J = 10.0, 0.8 Hz, 1H), 4.55 (s, 1H), 3.13 (d,
1745,1617,1505, 1394, 1381 cm-1.
5-((3-Bromophenyl)amino)-1,3-dimethyl-2-thioxoimidazolidin-4-one
(9c). Yellow crystalline solid, 0.48 Rf in EtOAc:petroleum ether (1:1), mp
This article is protected by copyright. All rights reserved.