Two-step synthesis of 1,3-disubstituted 3,4-dihydro-4-thioxoquinazolin- 2(1h)-ones from 1-bromo-2-fluorobenzenes

Article abstract of DOI:10.1002/hlca.201000327

An efficient synthesis of 3-alkyl-3,4-dihydro-4-thioxobenzoquinazolin-2(1H) -ones 3 has been accomplished in two steps and in satisfactory yields from 1-bromo-2-fluorobenzenes 1. Thus, the reaction of 1-fluoro-2-lithiobenzenes, generated by the Br/Li exch

Full text of DOI:10.1002/hlca.201000327

Helvetica Chimica Acta – Vol. 94 (2011)
67
Two-Step Synthesis of 1,3-Disubstituted 3,4-Dihydro-4-thioxoquinazolin-
2(1H)-ones from 1-Bromo-2-fluorobenzenes
by Kazuhiro Kobayashi*, Toshihide Komatsu, Yuki Yokoi, and Hisatoshi Konishi
Division of Applied Chemistry, Department of Chemistry and Biotechnology, Graduate School of
Engineering, Tottori University, 4-101 Koyama-minami, Tottori 680-8552, Japan
(phone/fax: þ 81-857-315263; e-mail: kkoba@chem.tottori-u.ac.jp)
An efficient synthesis of 3-alkyl-3,4-dihydro-4-thioxobenzoquinazolin-2(1H)-ones 3 has been
accomplished in two steps and in satisfactory yields from 1-bromo-2-fluorobenzenes 1. Thus, the
reaction of 1-fluoro-2-lithiobenzenes, generated by the Br/Li exchange between 1 and BuLi, with alkyl
isothiocyanates, gives N-alkyl-2-fluorobenzothioamides 2, which, in turn, react with a series of
isocyanates in the presence of NaH to give the desired products 3.
Introduction. – Some compounds having the 3,4-dihydro-4-thioxobenzoquinazolin-
2(1H)-one skeleton have been reported to exhibit biological activities [1][2]. Perhaps
the most common approach for their synthesis [1][3] to date is that reported by Billon
et al. [1], involving a direct monothiation of the respective 1,2,3,4-tetrahydroquinazo-
line-2,4-diones with P2S5 [2b]. Development of a new and facile methodology for the
preparation of these derivatives is, therefore, of considerable interest. The results of our
investigation, which offer a two-step preparation of 1,3-disubstituted 3,4-dihydro-4-
thioxobenzoquinazolin-2(1H)-ones 3 from commercially available 1-bromo-2-fluoro-
benzenes 1, are described herein. It was predicted that Br/Li exchange between 1 and
BuLi would generate 1-fluoro-2-lithiobenzenes. Subsequent treatment with isothio-
cyanates would give secondary 2-fluorobenzothioamides 2, which, after deprotonation
of the amide NH with an appropriate base and subsequent treatment with isocyanates,
would furnish the desired compounds 3.
Results and Discussion. – 1-Bromo-2-fluorobenzene (1a) was treated with BuLi
under conditions reported previously by Gilmann and Gorsich [4] to generate 1-fluoro-
2-lithiobenzene. Treatment of this lithiated product with EtNCS and subsequent usual
aqueous workup gave the expected N-ethyl-2-fluorobenzothioamide (2a) in moderate-
to-fair yield (Scheme 1). We reasoned that introduction of an electron-withdrawing
group into the benzene nucleus would enable the stabilization of the corresponding Li
product and give the desired benzothioamides in much better yields. As expected, 1-
bromo-4-chloro-2-fluorobenzene (1b) delivered the corresponding desired products
2b – 2d in excellent yields, as indicated in Scheme 1, by treating its lithiated derivative
with EtNCS, BnNCS, and PhNCS, respectively.
With N-monosubstituted 2-fluorobenzothioamides 2 in hand, we then conducted
the reactions leading to 1,3-disubstituted 3,4-dihydro-4-thioxoquinazolin-2(1H)-ones 3.
The reaction conditions for the preparation of 3 involved adding isocyanates to a
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 94 (2011)
Scheme 1
solution of the thioamide anion at room temperature, generated by treating 2 with NaH
at 08 in DMF, as shown in Scheme 2, and the reactions were continued at the same
temperature for the times listed in the Table. Addition of the thioamide anion to the
isocyanate C-atom generates a carbamoyl amide anion intermediate, which undergoes
intramolecular substitution of the F-atom in ortho-position to provide 3. When the
addition of isocyanates was carried out at 08, the yield of the product decreased
considerably in each case; the reason for this observation is not clear. With a Cl-atom at
Scheme 2
Table. Preparation of 3,4-Dihydro-4-thioxoquinazolin-2(1H)-ones 3
Entry
2
Time
3
R1
R2
R3
Yielda) [%]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
2a
2a
2a
2b
2b
2b
2b
2b
2b
2c
2c
2c
2c
2d
2 h
2 h
3 h
1 h
1 h
3 h
overnight
30 min
20 h
1.5 h
10 min
24 h
1 d
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
H
H
H
Et
Et
Et
Et
Et
Et
Et
Et
Et
Bn
Bn
Bn
Bn
Ph
Ph
63
66
53
80
76
68
46
80
80
65
56
72
0b)
0b)
3-MeꢀC6H4
4-ClꢀC6H4
Ph
3-MeꢀC6H4
4-BrꢀC6H4
4-MeOꢀC6H4
Naphthalen-1-yl
Bu
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Ph
4-CF3ꢀC6H4
Bu
t-Bu
Ph
1 d
a) Yields of isolated products. b) The starting thioamides were recovered almost quantitatively.

Helvetica Chimica Acta – Vol. 94 (2011)
69
C(4) of the N-ethyl-2-fluorobenzothioamide, the reaction times were shorter, and, in
general, the product yields increased fairly (Entries 4, 5, and 8). The slight decrease in
the yield of product 3f by the use of 4-bromophenyl isocyanate is ascribed to a loss of
material during the purification procedure due to its lower solubility in volatile organic
solvents (Entry 6). An electron-rich isocyanate, such as 4-methoxyphenyl isocyanate,
resulted in a somewhat poor yield of the desired product 3g (Entry 7). Naphthalen-1-yl
isocyanate also reacted well to give the corresponding product 3h in good yield
(Entry 8). Although the reaction with an aliphatic isocyanate, such as BuNCO,
required a prolonged reaction time, it furnished the desired product 3i in good yield
(Entry 9). N-Benzyl-4-chloro-2-fluorobenzamide (2c) was successfully employed in the
present reaction to give the corresponding products 3j – 3l, but in somewhat lower
yields compared to those using 1b (Entries 10 and 12); an inductively electron-
withdrawing CF3 substituent had a strong effect on the reaction rate, but the yield of the
product 3k was moderate (Entry 11). However, the use of t-BuNCO did not give the
desired product 3m at all, and the starting amide 2c was recovered almost quantitatively
(Entry 13). This is ascribed to the lower reactivity of t-BuNCO due to its steric
bulkiness. The attempted preparation of 6-chloro-3,4-dihydro-1,3-diphenyl-4-thioxo-
benzoquinazolin-2(1H)-one (3n) by reacting the amide anion intermediate generated
from 4-chloro-2-fluoro-N-phenylbenzamide (2d) with PhNCO resulted in an almost
quantitative recovery of the starting 2d, even after an extended reaction time
(Entry 14).
In conclusion, we have demonstrated that the reaction of 1-fluoro-2-lithiobenzenes
with aliphatic isothiocyanates, followed by the addition – substitution reaction between
the resulting N-alkyl-2-fluorobenzothioamides and a range of isocyanates, enables the
efficient synthesis of 3-alkyl-3,4-dihydro-4-thioxoquinazolin-2(1H)-ones in two steps
in satisfactory overall yields from commercially available 1-bromo-2-fluorobenzenes.
The products of these reactions are of potential medicinal interest. The present
approach offers significant advantages over the previously described methods because
of the ready availability of the starting materials and simple operations.
Experimental Part
General. All of the org. solvents used in this study were dried on appropriate drying agents and
distilled prior to use. All chemicals used in this study were commercially available. TLC: Merck Kieselgel
60 PF254. Column chromatography (CC): Wako Gel C-200E. M.p.: Laboratory Devices MEL-TEMP II
melting apparatus; uncorrected. IR Spectra: Shimadzu FTIR-8300 spectrophotometer. 1H-NMR
Spectra: in CDCl3 with TMS as an internal reference; JEOL ECP500 FT NMR spectrometer operating
at 500 MHz, or JEOL LA400 FT NMR spectrometer operating at 400 MHz; 13C-NMR spectra: in CDCl3
with TMS as an internal reference; JEOL ECP500 FT NMR spectrometer operating at 125 MHz. Low-
resolution (LR) MS (EI, 70 eV): JEOL JMS AX505 HA spectrometer.
N-Alkyl-2-fluorobenzothioamides 2. These compounds were prepared by reacting 1-fluoro-2-
lithiobenzenes, generated from the respective 1-bromo-2-fluorobenzenes according to the procedure of
Gilmann et al. [4], with the corresponding alkyl isothiocyanates in Et2O at ꢀ788, followed by usual aq.
workup and subsequent purification by CC on silica gel.
N-Ethyl-2-fluorobenzenecarbothioamide (2a). Yellow solid. Rf (THF/hexane 1:7) 0.37. M.p. 62 – 648
1
(hexane). IR (KBr): 3235, 1221. H-NMR (500 MHz): 1.38 (t, J ¼ 7.3, 3 H); 3.86 – 3.92 (m, 2 H); 7.07
(ddd, J ¼ 9.6, 8.2, 1.4, 1 H); 7.20 (td, J ¼ 7.8, 1.4, 1 H); 7.38 – 7.42 (m, 1 H); 7.91 (br. s, 1 H); 8.15 (ddd, J ¼
8.2, 7.8, 1.4, 1 H). Anal. calc. for C9H10FNS (183.25): C 58.99, H 5.50, N 7.64; found: C 58.88, H 5.51, N 7.47.

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Helvetica Chimica Acta – Vol. 94 (2011)
4-Chloro-N-ethyl-2-fluorobenzenecarbothioamide (2b). Yellow oil. Rf (THF/hexane 1:7) 0.29. IR
(neat): 3239, 1605, 1219. 1H-NMR (500 MHz): 1.37 (t, J ¼ 7.3, 3 H); 3.84 – 3.89 (m, 2 H); 7.11 (dd, J ¼ 11.9,
1.8, 1 H); 7.19 (dd, J ¼ 8.7, 1.8, 1 H); 7.88 (br. s, 1 H); 8.12 (t, J ¼ 8.7, 1 H). Anal. calc. for C9H9ClFNS
(217.69): C 49.66, H 4.17, N 6.43; found: C 49.58, H 4.29, N 6.20.
4-Chloro-2-fluoro-N-(phenylmethyl)benzenecarbothioamide (2c). Yellow oil. Rf (THF/hexane 1:7)
0.27. IR (neat): 3231, 1605, 1217. 1H-NMR (500 MHz): 5.00 (d, J ¼ 5.0, 2 H); 7.09 (dd, J ¼ 11.5, 1.8, 1 H);
7.20 (dd, J ¼ 8.7, 1.8, 1 H); 7.34 – 7.39 (m, 5 H); 8.09 (br. s, 1 H); 8.13 (t, J ¼ 8.7, 1 H). Anal. calc. for
C14H11ClFNS (279.76): C 60.10, H 3.96, N 5.01; found: C 60.15, H 4.06, N 4.96.
4-Chloro-2-fluoro-N-phenylbenzenecarbothioamide (2d). Yellow solid. Rf (Et2O/hexane 1:2) 0.39.
M.p. 106 – 1088 (hexane/Et2O). IR (KBr): 3246, 1604, 1209. 1H-NMR (500 MHz): 7.18 (dd, J ¼ 11.4, 1.4,
1 H); 7.25 (d, J ¼ 8.7, 1 H); 7.33 (t, J ¼ 7.3, 1 H); 7.46 (dd, J ¼ 7.8, 7.3, 2 H); 7.75 (d, J ¼ 7.8, 2 H); 8.15 (t, J ¼
8.7, 1 H); 9.26 (br. s, 1 H). Anal. calc. for C13H9ClFNS (265.73): C 58.76, H 3.41, N 5.27; found: C 58.48, H
3.49, N 5.18.
3-Ethyl-3,4-dihydro-1-phenyl-4-thioxoquinazolin-2(1H)-one (3a). General Procedure. To a stirred
suspension of NaH (60% in mineral oil; 33 mg, 0.84 mmol) in DMF (3 ml) at 08 was added a soln. of 2a
(0.15 g, 0.76 mmol) in DMF (1 ml). After the evolution of H2 gas had ceased, PhNCO (91 mg,
0.79 mmol) was added, the mixture was stirred for 2 h at r.t., sat. aq. NH4Cl (10 ml) was added, and the
org. products were extracted with AcOEt three times (8 ml each). The combined extracts were washed
with brine, dried (anh. Na2SO4), and concentrated by evaporation. The residual solid was recrystallized
from hexane/CH2Cl2 to give 3a (0.14 g, 63%). Yellow solid. M.p. 200 – 2028. IR (KBr): 1684, 1248.
1H-NMR (500 MHz): 1.40 (t, J ¼ 7.3, 3 H); 4.79 (q, J ¼ 7.3, 2 H); 6.49 (d, J ¼ 7.8, 1 H); 7.21 (ddd, J ¼ 8.2,
7.3, 1.4, 1 H); 7.33 (dd, J ¼ 8.2, 1.4, 2 H); 7.42 (ddd, J ¼ 7.8, 7.3, 1.4, 1 H); 7.55 (tt, J ¼ 7.3, 1.4, 1 H); 7.61 (dd,
J ¼ 8.2, 7.3, 2 H); 8.76 (dd, J ¼ 8.2, 1.4, 1 H). 13C-NMR: 11.48; 44.25; 115.49; 121.96; 123.78; 128.77;
129.46; 130.37; 133.35; 134.33; 136.41; 138.24; 148.03; 190.96. MS: 282 (100, Mþ). Anal. calc. for
C16H14N2OS (282.36): C 68.06, H 5.00, N 9.92; found: C 67.83, H 5.24, N 9.75.
3-Ethyl-3,4-dihydro-1-(3-methylphenyl)-4-thioxoquinazolin-2(1H)-one (3b). Yellow solid. M.p.
1
120 – 1228 (hexane/CH2Cl2). IR (KBr): 1690, 1250. H-NMR (500 MHz): 1.40 (t, J ¼ 7.3, 3 H); 2.44 (s,
3 H); 4.78 (q, J ¼ 7.3, 2 H); 6.51 (d, J ¼ 8.2, 1 H); 7.12 (d, J ¼ 8.7, 1 H); 7.13 (s, 1 H); 7.20 (ddd, J ¼ 8.2, 7.3,
0.9, 1 H); 7.35 (d, J ¼ 7.8, 1 H); 7.42 (ddd, J ¼ 7.8, 7.3, 1.4, 1 H); 7.48 (dd, J ¼ 7.8, 7.3, 1 H); 8.75 (dd, J ¼ 8.2,
1.4, 1 H). 13C-NMR: 11.46; 21.34; 44.23; 115.60; 121.90; 123.70; 125.62; 129.16; 130.13; 130.25; 133.26;
134.29; 136.27; 138.28; 140.60; 148.03; 190.94. MS: 296 (100, Mþ). Anal. calc. for C17H16N2OS (296.39): C
68.89, H 5.44, N 9.45; found: C 68.70, H 5.61, N 9.20.
1-(4-Chlorophenyl)-3-ethyl-3,4-dihydro-4-thioxoquinazolin-2(1H)-one (3c). Yellow solid. M.p.
1
142 – 1458 (MeOH). IR (KBr): 1688, 1248. H-NMR (400 MHz): 1.39 (t, J ¼ 7.3, 3 H); 4.77 (q, J ¼ 7.3,
2 H); 6.50 (dd, J ¼ 8.4, 0.7, 1 H); 7.23 (ddd, J ¼ 8.4, 6.9, 1.1, 1 H); 7.29 (d, J ¼ 8.8, 2 H); 7.45 (ddd, J ¼ 8.4,
6.9, 1.4, 1 H); 7.59 (d, J ¼ 8.8, 2 H); 8.75 (dd, J ¼ 8.4, 1.4, 1 H). 13C-NMR: 11.47; 44.26; 115.21; 122.01;
123.98; 130.28; 130.66; 133.50; 134.41; 134.85; 135.54; 137.92; 147.88; 190.86. MS: 316 (100, Mþ). Anal.
calc. for C16H13ClN2OS (316.81): C 60.66, H 4.14, N 8.84; found: C 60.42, H 4.21, N 8.91.
7-Chloro-3-ethyl-3,4-dihydro-1-phenyl-4-thioxoquinazolin-2(1H)-one (3d). Yellow solid. M.p. 142 –
1
1458 (hexane/Et2O). IR (KBr): 1688, 1250. H-NMR (500 MHz): 1.39 (t, J ¼ 7.3, 3 H); 4.75 (q, J ¼ 7.3,
2 H); 6.48 (d, J ¼ 1.8, 1 H); 7.17 (dd, J ¼ 8.7, 1.8, 1 H); 7.32 (d, J ¼ 7.3, 2 H); 7.58 (t, J ¼ 7.3, 1 H); 7.63 (t, J ¼
7.3, 2 H); 8.69 (d, J ¼ 8.7, 1 H). 13C-NMR: 11.42; 44.31; 115.21; 120.47; 124.33; 128.63; 129.81; 130.60;
134.86; 135.90; 138.92; 141.10; 147.82; 189.87. MS: 316 (100, Mþ). Anal. calc. for C16H13ClN2OS (316.81):
C 60.66, H 4.14, N 8.84; found: C 60.71, H 4.19, N 8.79.
7-Chloro-3-ethyl-3,4-dihydro-1-(3-methylphenyl)-4-thioxoquinazolin-2(1H)-one (3e). Yellow solid.
M.p. 135 – 1378 (hexane/Et2O). IR (KBr): 1701, 1250. 1H-NMR (400 MHz): 1.38 (t, J ¼ 7.3, 3 H); 2.46 (s,
3 H); 4.75 (q, J ¼ 7.3, 2 H); 6.50 (d, J ¼ 2.2, 1 H); 7.10 – 7.12 (m, 2 H); 7.16 (dd, J ¼ 8.7, 2.2, 1 H); 7.37 (dd,
J ¼ 7.3, 0.7, 1 H); 7.51 (ddd, J ¼ 7.8, 7.3, 1.1, 1 H); 8.68 (d, J ¼ 8.7, 1 H). 13C-NMR: 11.40; 21.37; 44.26;
115.28; 120.40; 124.24; 125.43; 129.00; 130.32; 130.61; 134.76; 135.75; 138.95; 140.86; 141.02; 147.81;
189.83. MS: 330 (100, Mþ). Anal. calc. for C17H15ClN2OS (330.83): C 61.72, H 4.57, N 8.47; found: C 61.77,
H 4.55, N 8.53.
1-(4-Bromophenyl)-7-chloro-3-ethyl-3,4-dihydro-4-thioxoquinazolin-2(1H)-one (3f). Yellow solid.
M.p. 151 – 1548 (hexane/Et2O). IR (KBr): 1699, 1248. 1H-NMR (500 MHz): 1.37 (t, J ¼ 7.3, 3 H); 4.72 (q,

Helvetica Chimica Acta – Vol. 94 (2011)
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J ¼ 7.3, 2 H); 6.48 (d, J ¼ 1.4, 1 H); 7.17 (dd, J ¼ 9.2, 1.4, 1 H); 7.21 (d, J ¼ 7.8, 2 H); 7.76 (d, J ¼ 7.8, 2 H);
8.67 (d, J ¼ 9.2, 1 H). 13C-NMR: 11.41; 44.31; 114.90; 120.49; 123.99; 124.54; 130.43; 133.89; 134.86;
134.99; 138.50; 141.22; 147.60; 189.73. MS: 394 (100, Mþ). Anal. calc. for C16H12BrClN2OS (395.70): C
48.56, H 3.06, N 7.08; found: C 48.68, H 2.98, N 6.97.
7-Chloro-3-ethyl-3,4-dihydro-1-(4-methoxyphenyl)-4-thioxoquinazolin-2(1H)-one (3g). Yellow sol-
1
id. M.p. 153 – 1558 (hexane/CH2Cl2). IR (KBr): 1686, 1248. H-NMR (500 MHz): 1.38 (t, J ¼ 7.3, 3 H);
3.90 (s, 3 H); 4.74 (q, J ¼ 7.3, 2 H); 6.54 (d, J ¼ 1.8, 1 H); 7.10 (d, J ¼ 8.2, 2 H); 7.15 (dd, J ¼ 8.2, 1.8, 1 H);
7.22 (d, J ¼ 8.2, 2 H); 8.17 (d, J ¼ 8.2, 1 H). 13C-NMR: 11.42; 44.34; 55.61; 115.31; 115.76; 120.46; 124.23;
128.30; 129.63; 134.82; 139.29; 141.08; 148.06; 160.27; 189.88. MS: 346 (100, Mþ). Anal. calc. for
C17H15ClN2O2S (346.83): C 58.87, H 4.36, N 8.08; found: C 58.88, H 4.27, N 7.92.
7-Chloro-3-ethyl-3,4-dihydro-1-(naphthalen-1-yl)-4-thioxoquinazolin-2(1H)-one (3h). Yellow solid.
M.p. 150 – 1538 (hexane/Et2O). IR (KBr): 1688, 1233. 1H-NMR (500 MHz): 1.41 (t, J ¼ 7.3, 3 H); 4.74 –
4.84 (m, 2 H); 6.30 (d, J ¼ 1.8, 1 H); 7.16 (dd, J ¼ 9.2, 1.8, 1 H); 7.46 – 7.52 (m, 3 H); 7.58 (dd, J ¼ 7.8, 7.3,
1 H); 7.67 (dd, J ¼ 8.2, 7.3, 1 H); 8.01 (d, J ¼ 8.2, 1 H); 8.08 (d, J ¼ 8.2, 1 H); 8.73 (d, J ¼ 8.7, 1 H).
13C-NMR: 11.49; 44.30; 115.28; 120.43; 121.49; 124.51; 126.02; 127.07; 127.11; 128.05; 128.96; 129.58;
130.49; 132.22; 134.87; 134.94; 139.05; 141.33; 147.71; 189.96. MS: 366 (100, Mþ). Anal. calc. for
C20H15ClN2OS (366.86): C 65.48, H 4.12, N 7.64; found: C 65.40, H 4.16, N 7.77.
1-Butyl-7-chloro-3-ethyl-3,4-dihydro-4-thioxoquinazolin-2(1H)-one (3i). Yellow solid. M.p. 61 – 648
1
(hexane). IR (neat): 1693, 1246. H-NMR (500 MHz): 1.02 (t, J ¼ 7.3, 3 H); 1.35 (t, J ¼ 7.3, 3 H); 1.48
(sext., J ¼ 7.3, 2 H); 1.73 (quint., J ¼ 7.3, 2 H); 4.10 (t, J ¼ 7.3, 2 H); 4.73 (q, J ¼ 7.3, 2 H); 7.13 (d, J ¼ 1.8,
1 H); 7.18 (dd, J ¼ 8.7, 1.8, 1 H); 8.70 (d, J ¼ 8.7, 1 H). 13C-NMR: 11.39; 13.71; 20.03; 29.13; 44.20; 44.42;
113.59; 120.93; 122.87; 135.45; 137.33; 141.52; 147.92; 189.39. MS: 296 (100, Mþ). Anal. calc. for
C14H17ClN2OS (296.82): C 56.65, H 5.77, N 9.44; found: C 56.56, H 5.80, N 7.26.
7-Chloro-3,4-dihydro-1-phenyl-3-(phenylmethyl)-4-thioxoquinazolin-2(1H)-one (3j). Yellow solid.
M.p. 188 – 1918 (hexane/CH2Cl2). IR (KBr): 1688, 1204. 1H-NMR (500 MHz): 5.94 (s, 2 H); 6.49 (d, J ¼
1.8, 1 H); 7.16 (dd, J ¼ 8.7, 1.7, 1 H); 7.25 (t, J ¼ 7.3, 1 H); 7.27 – 7.31 (m, 4 H); 7.53 (d, J ¼ 7.8, 2 H); 7.56 (t,
J ¼ 7.3, 1 H); 7.61 (dd, J ¼ 7.8, 7.3, 2 H); 8.67 (d, J ¼ 8.7, 1 H). 13C-NMR: 51.32; 115.28; 120.47; 124.45;
127.58; 128.30; 128.63; 128.81; 129.85; 130.61; 135.27; 135.86; 135.94; 138.91; 141.27; 148.39; 190.45. MS:
378 (100, Mþ). Anal. calc. for C21H15ClN2OS (378.87): C 66.57, H 3.99, N 7.39; found: C 66.33, H 4.07, N
7.27.
7-Chloro-3,4-dihydro-3-(phenylmethyl)-4-thioxo-1-[4-(trifluoromethyl)phenyl]quinazolin-2(1H)-
1
one (3k). Yellow solid. M.p. 221 – 2238 (hexane/CH2Cl2). IR (KBr): 1703, 1126. H-NMR (500 MHz):
5.92 (s, 2 H); 6.44 (d, J ¼ 1.8, 1 H); 7.19 (dd, J ¼ 8.7, 1.8, 1 H); 7.24 – 7.31 (m, 3 H); 7.47 (d, J ¼ 8.7, 2 H);
7.52 (d, J ¼ 8.2, 2 H); 7.89 (d, J ¼ 8.7, 2 H); 8.68 (d, J ¼ 8.7, 1 H). 13C-NMR: 51.32; 114.85; 120.56; 124.84;
127.73; 127.81; 127.84; 128.36; 128.83; 129.56; 132.26; 135.54; 135.76; 138.21; 138.98; 141.50; 148.13;
190.27. MS: 446 (100, Mþ). Anal. calc. for C22H14ClF3N2OS (446.87): C 59.13, H 3.16, N 6.27; found: C
58.97, H 3.26, N 6.45.
1-Butyl-7-chloro-3,4-dihydro-3-(phenylmethyl)-4-thioxoquinazolin-2(1H)-one (3l). Yellow solid.
M.p. 112 – 1148 (hexane/CH2Cl2). IR (KBr): 1674, 1217. 1H-NMR (500 MHz): 1.00 (t, J ¼ 7.3, 3 H);
1.46 (sext., J ¼ 7.3, 2 H); 1.72 (quint., J ¼ 7.3, 2 H); 4.10 (t, J ¼ 7.3, 2 H); 5.92 (s, 2 H); 7.14 (s, 1 H); 7.18 (dd,
J ¼ 8.7, 1.4, 1 H); 7.24 (t, J ¼ 7.3, 1 H); 7.29 (dd, J ¼ 7.8, 7.3, 2 H); 7.44 (d, J ¼ 7.8, 2 H); 8.69 (d, J ¼ 8.7, 1 H).
13C-NMR: 13.70; 19.99; 29.09; 44.36; 51.52; 113.67; 120.91; 124.00; 127.46; 128.23; 128.31; 135.85; 135.97;
137.32; 141.72; 148.42; 190.03. MS: 358 (100, Mþ). Anal. calc. for C19H19ClN2OS (358.89): C 63.59, H 5.34,
N 7.81; found: C 63.81, H 5.30, N 7.69.
Mrs. Miyuki Tanmatsu of this university is acknowledged for her assistance in recording mass spectra
and performing combustion analyses.

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Received August 30, 2010