Three-component reaction between 5,5-diarylthiohydantoins and acetylenic esters
751
(1 H, dd, (AB)X system, JAX = 8.4, JAB = 16.5 Hz, CH),
3.37 (1 H, dd, (AB)X system, JBX = 6.3, JAB = 16.5 Hz,
CH), 4.02–4.29 (4 H, (AB)X3 system, 2 CH2O), 5.79 (1 H,
dd, JAX = 8.4, JBX = 6.3 Hz, CH), 7.25–7.58 (10 H, m,
CH), 10.41 (1 H, s, NH) ppm; 13C NMR (75 MHz, CDCl3):
d = 14.2 (Me), 14.5 (Me), 34.0 (CH2), 51.9 (CH), 61.6
(CH2O), 62.7 (CH2O), 78.8 (C), 127.5 (2 CH), 127.6 (2
CH), 128.1 (2 CH), 128.2 (2 CH), 129.4 (CH), 129.5 (CH),
140.2 (C), 140.8 (C), 161.1 (OC=O), 168.1 (OC=O), 170.3
reaction performed under neutral conditions, but the starting
materials can be mixed without any activation or modifi-
cation. The one-pot nature of the present procedure makes it
an interesting alternative to multistep approaches [10].
Experimental
Melting points were measured on an Electrothermal 9100
apparatus. Elemental analyses for C, H, and N were per-
formed using a Heraeus CHNO-Rapid analyzer. IR spectra
were measured on a Shimadzu IR-460 spectrometer. 1H and
13C NMR spectra were measured with a Bruker DRX-300
Advance instrument with CDCl3 as solvent at 300.1 and
75.1 MHz. Mass spectra were recorded on a Finnigan-Matt
8430 mass spectrometer operating at an ionization potential
of 70 eV. Isocyanides and dialkyl acetylenedicarboxylates
were obtained from Fluka and were used without further
ꢀ
(NC=O), 180.7 (C=S) ppm; IR (KBr): m = 3,426 (NH),
1,740 (C=O), 1,453 (C=C) cm-1; MS (70 eV): m/z = 441
(M?, 8), 367 (62), 267 (66), 166 (100), 77 (42), 73 (15).
Dimethyl 2-[4,4-bis(4-chlorophenyl)-5-oxo-2-
thioxoimidazolidin-1-yl]butanedioate
(4c, C21H18Cl2N2O5S)
1
White powder; yield 0.43 g (45%); m.p.: 170–172 °C; H
NMR (300 MHz, CDCl3): 3.09 (1 H, dd, (AB)X system,
JAX = 8.4, JAB = 16.8 Hz, CH), 3.30 (1 H, dd, (AB)X
system, JBX = 6.0, JAB = 16.8 Hz, CH), 3.62 (3 H, s, MeO),
3.72 (3 H, s, MeO), 5.77 (1 H, dd, JAX = 8.4, JBX = 6.0 Hz,
purification. 5,5-Diaryl-2-thioxoimidazolidin-4-ones
were prepared by known methods [11, 12].
1
CH), 7.25–7.45 (10 H, m, CH), 10.45 (1 H, s, NH) ppm; 13
C
Typical procedure for the preparation of 4a and 5a
NMR (75 MHz, CDCl3): d = 33.9 (CH2), 51.7 (MeO), 51.8
(CH), 52.8 (MeO), 78.1 (C), 129.3 (2 CH), 129.5 (2 CH),
129.8 (2 CH), 129.9 (2 CH), 131.5 (C), 131.6 (C), 138.4 (C),
138.5 (C), 161.0 (OC=O), 168.1 (OC=O), 170.2 (NC=O),
To a stirred solution of 0.537 g 1 (2 mmol) and 0.284 g 2a
(2 mmol) in 5 cm3 dichloromethane was added dropwise a
solution of 0.248 g 3a (2 mmol) in 2 cm3 CH2Cl2 at 5 °C
over 10 min. The reaction mixture was then allowed to warm
to room temperature and stand for 6 h. The solvent was
removed under reduced pressure and the residue was sepa-
rated by silica column chromatography (Merck 230-400
mesh) using n-hexane/AcOEt as eluent to afford 4a and 5a.
ꢀ
180.5 (C=S) ppm; IR (KBr): m = 3,425 (NH), 1,740 (C=O),
1450 (C=C) cm-1; MS (70 eV): m/z = 481 (M?, 20), 421
(72), 335 (75), 234 (100), 111 (28), 59 (10).
Diethyl 2-[4,4-bis(4-chlorophenyl)-5-oxo-2-
thioxoimidazolidin-1-yl]butanedioate
(4d, C23H22Cl2N2O5S)
Dimethyl 2-(5-oxo-4,4-diphenyl-2-thioxoimidazolidin-1-yl)-
butanedioate (4a, C21H20N2O5S)
1
White powder; yield 0.43 g (42%); m.p.: 165–167 °C; H
1
White powder; yield 0.39 g (47%); m.p.: 157–159 °C; H
NMR (300 MHz, CDCl3): d = 1.12 (3 H, t,
3
3JHH = 7.1 Hz, Me), 1.16 (3 H, t, JHH = 7.1 Hz, Me),
NMR (300 MHz, CDCl3): d = 3.11 (1 H, dd, (AB)X
system, JAX = 7.9, JAB = 15.9 Hz, CH), 3.31 (1 H, dd,
(AB)X system, JBX = 6.7, JAB = 15.9 Hz, CH), 3.55 (3 H,
s, MeO), 3.70 (3 H, s, MeO), 5.80 (1 H, dd, JAX = 7.9,
JBX = 6.7 Hz, CH), 7.35–7.51 (10 H, m, CH), 10.45 (1 H,
s, NH) ppm; 13C NMR (75 MHz, CDCl3): d = 33.8 (CH2),
51.7 (MeO), 52.0 (CH), 52.9 (MeO), 78.8 (C), 127.5 (2
CH), 127.8 (2 CH), 128.0 (2 CH), 128.2 (2 CH), 128.5
(CH), 128.6 (CH), 140.8 (C), 141.0 (C), 161.4 (OC=O),
3.08 (1 H, dd, (AB)X system, JAX = 8.5, JAB = 16.5 Hz,
CH), 3.30 (1 H, dd, (AB)X system, JBX = 6.0,
JAB = 16.5 Hz, CH), 4.02–4.34 (4 H, (AB)X3 system, 2
CH2O), 5.80 (1 H, dd, JAX = 8.5, JBX = 6.0 Hz, CH),
7.29–7.46 (10 H, m, CH), 10.40 (1 H, s, NH) ppm; 13C
NMR (75 MHz, CDCl3): d = 13.8 (Me), 14.4 (Me), 34.6
(CH2), 52.0 (CH), 61.6 (CH2O), 62.8 (CH2O), 77.4 (C),
129.3 (2 CH), 129.5 (2 CH), 129.8 (2 CH), 129.9 (2 CH),
131.5 (C), 131.6 (C), 138.4 (C), 138.5 (C), 161.0 (OC=O),
168.7 (OC=O), 170.2 (NC=O), 180.7 (C=S) ppm; IR
-1
ꢀ
(KBr): m = 3,425 (NH), 1,740 (C=O), 1,452 (C=C) cm
;
168.1 (OC=O), 170.2 (NC=O), 180.5 (C=S) ppm; IR
-1
MS (70 eV): m/z = 412 (M?, 18), 351 (75), 292 (78), 267
(60), 166 (100), 77 (32), 59 (12).
ꢀ
(KBr): m = 3,426 (NH), 1,740 (C=O), 1,453 (C=C) cm
;
MS (70 eV): m/z = 509 (M?, 16), 435 (78), 335 (72), 234
(100), 111 (25), 73 (22).
Diethyl 2-(5-oxo-4,4-diphenyl-2-thioxoimidazolidin-1-yl)-
butanedioate (4b, C23H24N2O5S)
Dimethyl 2-[4,5-dihydro-2-(methylthio)-5-oxo-4,4-
diphenylimidazol-1-yl]butanedioate (5a, C22H22N2O5S)
1
White powder; yield 0.40 g (45%); m.p.: 150–152 °C; H
3
1
NMR (300 MHz, CDCl3): d = 1.11 (3 H, t, JHH
7.1 Hz, Me), 10.15 (3 H, t, JHH = 7.1 Hz, Me), 3.15
=
White powder; yield 0.36 g (42%); m.p.: 97–99 °C; H
3
NMR (300 MHz, CDCl3): d = 2.73 (3 H, s, MeS), 3.09 (1
123