W. Liu, Q. Zhang, F. Gong, Z. Cao, and Y. Huo
Vol 0000
Scheme 1. Synthesis of the compounds 3a–m. [Color figure can be viewed
in the online issue, which is available at wileyonlinelibrary.com.]
7.72 (m, 1H, ArH), 7.44–7.24 (m, 2H, ArH), 7.07 (d, J = 8.3 Hz,
2H, ArH), 6.69 (d, J = 8.3 Hz, 2H, ArH), 4.55–4.44 (m, 2H, CH2),
2.83 (m, 2H, CH2). HRMS (ESI) [Found: m/z 321.0673 (M + Na)
+, calcd for C16H14N2O2S: M + Na, 321.0674].
3-(Furan-2-ylmethyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-
one (3c). This compound was obtained as pale yellow solid with
mp 218–219ꢀC; IR (KBr) m: 3247, 2956, 2891, 1655, 1532,
1
1163, 955, 759 cmÀ1. HNMR (DMSO-d6): 13.01 (s, 1H, NH),
7.96 (d, 1H, J = 7.7 Hz, ArH), 7.74 (t, 1H, J = 7.6 Hz, ArH ), 7.52
(s, 1H), 7.44–7.25 (m, 2H, ArH, furan-H), 6.34 (m, 2H, furanyl-H),
5.63 (s, 2H, CH2). HRMS (ESI) [Found: m/z281.0392 (M + Na)+,
calcd for C13H10N2O2S: M + Na, 281.0361].
to several minutes. It is noteworthy that the present reaction
was accomplished under mild conditions and the method is
operationally simple with satisfactory yields.
In summary, we report a rapid and efficient microwave-
3-(2-(1H-indol-3-yl)ethyl)-2-thioxo-2,3-dihydroquinazolin-4
(1H)-one (3d). This compound was obtained as brown solid with
mp 261–262ꢀC; IR (KBr) m: 3326, 3176, 3025, 2966, 1619,
assisted method to synthesize
a
series of novel
thioxoquinazolinones in good yields. Given the fact that
many 2-thioxo-2,3-dihydroquinazolin-4(1H)-ones exhibited
biological activity, we anticipate that these new compounds
described in the present report would be valuable in further
pharmaceutical research.
1541, 1144, 744, 692 cmÀ1 1HNMR (DMSO-d6): 12.97 (s,
.
1H, C = SNH), 10.84 (s, 1H, NH), 7.99 (d, J = 7.8 Hz,
1H, ArH), 7.81 (d, J = 7.6 Hz, 1H, ArH), 7.74 (m, 1H, ArH),
7.44–7.29 (m, 3H, ArH, indolyl-H), 7.20 (s, 1H, indolyl-H),
7.12–6.93 (m, 2H, indolyl-H), 4.70–4.58 (m, 2H, CH2), 3.12–
3.02 (m, 2H, CH2). HRMS (ESI) [Found: m/z 344.0834
(M + Na)+, calcd for C18H15N3OS: M + Na, 344.0833].
EXPERIMENTAL
3-(2-(Thiophen-2-yl)ethyl)-2-thioxo-2,3-dihydroquinazolin-4
(1H)-one (3e). This compound was obtained as white solid with
mp 234–235ꢀC; IR (KBr) mp: 3255, 2956, 2891, 1649, 1530,
Commercial solvents and reagents were used as received.
Microwave irradiation was carried out with a microwave oven
Emrys Creator from Personal Chemistry, (Biotage, Initiator
EXPEU, Frequtncy 2450MHz, Uppsala, Sweden). Melting points
are uncorrected. IR spectra were taken on an FTIR-Tensor 27 spec-
trometer in KBr pellets and reported in cmÀ1. 1HNMR spectra were
measured on a Bruker DPX 300-MHz spectrometer using TMS as
an internal standard and dimethyl sulfoxide (DMSO)-d6 as solvent.
J values are in hertz. Chemical shifts are expressed in parts per mil-
lion downfield from internal standard trimethylsilyl. HRMS (ESI)
was determined by using a Micro TOF-QII HRMS instrument
(BRUKER).
1
1149, 824, 760, 708 cmÀ1. HNMR (DMSO-d6): 12.98 (s, 1H,
NH), 7.95 (d, 1H, J = 7.9 Hz, ArH ), 7.73 (m, 1H, ArH), 7.50–
7.18 (m, 3H, ArH, thiophenyl-H), 6.95 (m, 2H, thiophenyl-H),
4.81–4.41 (t, 2H, CH2), 3.24–3.12 (t, 2H, CH2). HRMS (ESI)
[Found: m/z 311.0296 (M + Na)+, calcd for C14H12N2OS2:
M + Na, 311.0289].
3-(3-(1H-imidazol-1-yl)propyl)-2-thioxo-2,3-dihydroquinazolin-
4(1H)-one (3f). This compound was obtained as yellow solid with
mp 216–217ꢀC; IR (KBr) m: 3113, 2958, 1897, 1548, 1689, 1152,
926, 757 cmÀ1 1HNMR (DMSO-d6): 12.93 (s, 1H, NH), 7.94
.
General procedure for synthesis of 2-thioxo-2,3-
dihydroquinazolin-4(1H)-ones 3a–3mA. solution of 1 (0.2 mmol)
and different substituent amines 2 (0.24 mmol) in DMF (3 mL)
was stirred in a sealed pressure-proof pipe, and the pipe was
placed in the microwave oven. Then, the reaction mixture was
allowed to cool to room temperature, and carbon disulfide
was added to the pipe. The mixture was irradiated with power and
time as indicated in Scheme 1. To control the reaction, we carried
out the irradiation in two stages, with a cooling period between
each irradiation. After this period, the thin-layer chromatography
analysis of the mixture showed the reaction to be completed.
Rinsing of the crude product with water and vacuum filtration
gave the desired products. The yield of pure isolated product was
based on isatoic anhydride as indicated in Table 1.
(d, J = 6.8 Hz, 1H, ArH), 7.78–7.69 (m, 1H, ArH), 7.66 (s, 1H,
imidazolyl-H), 7.42–7.27 (m, 2H, ArH), 7.19 (s, 1H, imidazolyl-
H), 6.87 (s, 1H, imidazolyl-H), 4.55–4.26 (m, 2H, CH2), 4.06
(m, 2H, CH2), 2.24–1.87 (m, 2H, CH2). HRMS (ESI) [Found: m/z
287.0988 (M + H)+, calcd for C14H14N4OS: M + H, 287.0967].
3-(2-(Piperidin-1-yl)ethyl)-2-thioxo-2,3-dihydroquinazolin-
4(1H)-one (3g). Tꢀhis compound was obtained as yellow solid
with mp 210–211 C(lit. 199ꢀC) [14]; IR (KBr) m: 3248, 1648,
1
1119, 2928, 2850, 1532, 1335, 757cmÀ1. HNMR (DMSO-d6):
12.87 (s, 1H, NH), 7.94 (d, J = 7.9 Hz, 1H, ArH), 7.72 (m, 1H,
ArH), 7.33 (m, 2H, ArH), 4.66–4.29 (m, 2H, piperidinyl-H),
2.59–2.53 (m, 2H, piperidinyl-H), 2.51–2.36 (m, 4H, piperidinyl-
H), 1.45 (d, J=4.8Hz, 4H, CH2), 1.35 (d, J = 4.7 Hz, 2H, CH2).
HRMS (ESI) [Found: m/z 290.1454 (M+ H)+, calcd for
C15H19N3OS: M + H, 290.1327].
3-(4-Ethoxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-
one (3h). This compound was obtained as yellow solid with mp
296–297ꢀC(lit. 310-312ꢀC) [15]; IR (KBr) m: 3243, 2970, 1664,
1536, 1508, 1201, 1039, 760 cmÀ1. 1H NMR (DMSO-d6): 12.99
(s, 1H, NH), 7.95 (d, J = 7.6 Hz, 1H, ArH), 7.77 (m, 1H, ArH),
7.44 (d, J = 8.1 Hz, 1H, ArH), 7.34 (m, 1H, ArH), 7.19 (m, 2H,
ArH), 6.98 (d, J = 8.5 Hz, 2H, ArH), 4.07 (m, 2H, CH2), 1.36 (m,
3H, CH3). HRMS (ESI) [Found: m/z 321.0663 (M+ Na)+, calcd
for C16H14N2O2S: M + Na, 321.0674].
2-Amino-N-(2-hydroxyethyl)benzamide (3a). This compound was
obtained as pale yellow solid with mp 236–237ꢀC (lit. 238ꢀC)
[13]; IR (KBr) m: 3367, 3171, 2956, 2891, 1661, 1541, 1161,
760 cmÀ1 1H NMR (DMSO-d6): 12.91 (s, 1H, NH), 7.95 (d,
.
1H, J = 9.0 Hz, ArH), 7.73 (m, 1H, ArH), 7.45–7.22 (m, 2H,
ArH), 4.84 (s, 1H, OH), 4.50 (m, 2H, CH2), 3.65 (d, 2H,
J = 2.7 Hz, CH2 ). HRMS (ESI) [Found: m/z 245.0368
(M + Na)+, calcd for C10H10N2O2S: M + Na, 245.0361].
3-(4-Hydroxyphenethyl)-2-thioxo-2,3-dihydroquinazolin-4
(1H)-one (3b). This compound was obtained as yellow solid
with mp 264–265ꢀC; IR (KBr) m: 3420, 3251, 3036, 2961,
1651, 1533, 1146, 823, 759 cmÀ1. 1HNMR (DMSO-d6): 12.93
(s, 1H, NH), 9.20 (s, 1H, OH), 7.95 (d, J = 7.7 Hz, 1H, ArH),
3-(3-Methoxyphenyl)-2-thioxo-2,3-dihydroquinazolin-4(1H)-
one (3i). This compound was obtained as pale yellow solid with
mp 248–249ꢀC (lit. 255-256ꢀC) [16]; IR (KBr) m: 3243, 2945,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet