KF/Al2O3 promoted aza-Michael addition of 4-aryl-7,7-dimethyloctahydroquinazolinones to α, β-ethylenic compounds

Article abstract of DOI:10.3184/174751911X13129294387591

The aza-Michael addition reaction of 4-aryl-7,7-dimethyl-1,2,3,4,5,6,7,8- octahydroquinazoline-2-one/thione-5-ones to α,β-ethylenic compounds in the presence of KF/Al₂O₃ furnishes N3-substituted quinazolinone derivatives. Those groups (NO₂, MeO) with larger steric hindrance at the o-position of the phenyl ring of quinazolinone have an apparent affect on the chemical selectivity thus giving the N1-subsituted products.

Full text of DOI:10.3184/174751911X13129294387591

460 RESEARCH PAPER
AUGUST, 460–464
JOURNAL OF CHEMICAL RESEARCH 2011
KF/Al2O3 promoted aza-Michael addition of 4-aryl-7,7-dimethyloctahydro-
quinazolinones to α, β-ethylenic compounds
Xi-Cun Wanga,b*, Zhong-Jie Wanga,b, Zhang Zhanga,b and Zheng-Jun Quana,b
aKey Laboratory of Eco-Environment-Related Polymer Materials, Ministry of Education, Gansu 730070, P. R. China
bGansu Key Laboratory of Polymer Materials, College of Chemistry and Chemical Engineering, Northwest Normal University, Anning East
Road 967#, Lanzhou, Gansu 730070, P. R. China
The aza-Michael addition reaction of 4-aryl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2-one/thione-5-ones to
α,β-ethylenic compounds in the presence of KF/Al2O3 furnishes N3-substituted quinazolinone derivatives. Those
groups (NO2, MeO) with larger steric hindrance at the o-position of the phenyl ring of quinazolinone have an apparent
affect on the chemical selectivity thus giving the N1-subsituted products.
Keywords: quinazolinone derivatives, potassium fluoride, Michael addition
3,4-Dihydropyrimidinone (DHPM) was first reported 118
years ago by Biginelli.1 It has gained great therapeutic signifi-
cance as a calcium-channel modulator in the treatment of
cardiovascular diseases, such as hypertension, cardiac arryth-
mias or angina.2 In recent years, interest has been focused on
Biginelli-like reactions in which open chain β-dicarbonyl com-
pounds have been extended to cyclic β-diketones, β-ketolac-
tones, β-diamides, or cyclic β-diesters, benzocyclic ketones,
and α-keto acids under a variety of conditions, and the hetero-
cycles thus obtained exhibit a wide range of biological activi-
ties, such as antiviral, antitumour, antihypertensive, and neuro-
peptide Y(NPY) antagonism.3–7 Among the synthetic products
via Biginelli reaction, octahydroquinazolin-5-one derivatives
are interesting compounds because of their wide range of bio-
logical activities. Octahydroquinazolinones have exhibited
potent antibacterial activity8,9 and calcium antagonist activ-
ity.10–12 It has been reported that N-methyl substituted octahy-
droquinazolinones were more active derivatives than those
without a substituted group at the N-atom.13 However, few
methods are available for the preparation of the N-substituted
octahydroquinazolinones.13 To the best of our knowledge no
precedent for the Michael reaction of quinazoline-2,5-diones
for N-substituted derivatives has been reported.
Recently, we reported the Michael reaction of 3,4-dihydro-
pyrimidinones with α, β-ethylenic compounds to give the N3-
substituted DHPMs regioselectively using KF/Al2O3 or PEG-
400/K2CO3 as a mild and efficient reagent.14,15 When trying to
apply PEG-400/K2CO3 to N-quinazoline-2,5-diones (1) the
reaction failed to give the desired product and only the starting
materials were obtained. Using KF/Al2O3 as catalyst, N1 sub-
stituted products were isolated instead of the expected N3-
products when the aryl group of the quinazoline-2-one-5-ones
carried an o-substituent such as NO2, and MeO. Here, we
report the Michael reaction of quinazoline-2, 5-diones with α,
β-ethylenic compounds to give the N-substituted derivatives
using KF/Al2O3 as the catalyst (Scheme 1).
Results and discussion
Initially, octahydroquinazoline-2,5-diones were prepared
according to the corresponding literature procedures via the
Biginelli reaction between a cyclohexa-1,3-dione, benzalde-
hyde and urea.4,16 Then, we selected 4-phenyl-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione 1a and methyl
acrylate 2a as the model substrates to optimise reaction con-
ditions including catalysts, bases, solvents, and reaction tem-
peratures. The best yield of 3a (86%) was obtained by reaction
in DMF at 40 °C overnight using equivalent amounts of 1a,
methyl acrylate 2a, and 10 mmol% of KF/Al2O3. No reaction
was observed in the presence of Et3N or absence of any
catalyst (Table 2, entries 6 and 7). In general, the use of polar
solvents such as DMSO, DMF and MeCN resulted in better
results than those with less polar solvents (THF and DCM)
(Table 1).
Under the optimal conditions, a combination of 4-aryl-7,7-
dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2-one/thione-
5-ones 1 and α, β-ethylenic compounds 2 was investigated. As
shown in Table 2, a smooth reaction occurred to provide the
desired Michael additional products 3 in good to high yields
(69–92%). All products showed that the aza-Michael addition
occurred exclusively at the N3 position of 4-aryl-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-one/thione-5-ones.
The regioselectivity of the reaction is consistent with other
results of alkylation reactions.17 The single crystal X-ray crys-
tallography of product 3d also confirmed the structures of the
obtained products 3a–v (Fig. 1).
Scheme 1 Synthesis of N-substituted octahydroquinazoline-2-one/thione-5-ones 3 and 4.
*Correspondent. E-mail: Wangxicun@nwnu.edu.cn

JOURNAL OF CHEMICAL RESEARCH 2011 461
Table 1 Optimisation of Michael reaction conditions
Entry
1
2
3
4
5
6
7
8
9
10
11
12
Base
K2CO3 Na2CO3
NaOH
DMF
24
KOH KF/Al2O3
Et3N
No
KF/Al2O3 KF/Al2O3 KF/Al2O3 KF/Al2O3 K2CO3
Solvent
Time/h
Yield/%
DMF
48
DMF
48
<10
DMF
24
DMF
12
86
DMF DMF
DMSO
12
MeCN
12
53
CH2Cl2
24
32
THF
24
63
PEG-400
48
0
48
0
24
0
<10
<10
<10
78
a Reaction conditions: 1a (0.5 mmol), 2a (0.6 mmol), solvents (3 mL), catalysts (10 mmol %), at 40oC temperature for overnight.
b Isolated yields.
c No detected compound by TLC and 1H NMR.
Fig. 2 X-ray crystallography of product 4a.
Fig. 1 X-ray crystallography of product 3d.
1
However, groups with larger steric hindrance at the o-posi-
tion of the phenyl ring of compound 1 have an apparent affect
on the chemical selectivity of the products. For instance, the
NO2 and MeO group at the o-position of the phenyl ring only
gave the N1-subsituted products 4a–d (Table 2). The structure
of 4a was also confirmed by X-ray crystallography (Fig. 2).
(Crystallographic data for the structure analysis have been
deposited at the Cambridge Crystallographic Data Centre as
supplementary publications, CCDC No. 807623 for 3d and
No. 817452 for 4a. Copies of this information can be obtained,
free of charge on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK (fax: (44) 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk). With a group having a small steric
hindrance, such as Cl, no obvious effect was found and the
N3-products 3g, 3r (Table 2, entries 7 and 19) were obtained.
Thus, we postulate that the selectivity at N1 and N3 depended
on the hindrance, the position of the substituted groups on the
aryl group of the octahydroquinazoline-2-ones 1 and the dif-
ference in the electron density at the N1 and N3 positions.
Commonly, the nitrogen atom at N3 has higher electron
density than that of N1. So the Michael reaction potentially
gives the N3 substituted product. However, when a larger
steric group is substituted at the o-position of the aryl ring of
compound 1, the reaction gives the N1 products selectively.
The H NMR spectrum of product DHPMs 3a–v exhibited
a singlet around δ 5.4 as the C4–H, which confirmed the N3-
position of the acyloxymethyl group. Meanwhile, the C4–H
came as a doublet around δ 5 for compounds 4a–d. According
to a previous study, when the methyl or N-allyl groups were in
the N1 position, two cross peaks between the hydrogen atoms
of the N-methyl or NCH2 groups of the allyl groups and C-2
and -6 were observed.18
In conclusion, we have documented that N-substituted 4-
aryl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2-
one/thione-5-ones can be obtained through the aza-Michael
addition of 4-aryl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquin-
azoline-2-one/thione-5-ones to α, β-ethylenic compounds in
the presence of KF/Al2O3 as a catalyst.
Experimental
All reagents were obtained commercially and used without further
purification. Melting points were determined by an XT-4 electrother-
mal micromelting point apparatus which is uncorrected. IR spectra
were recorded using KBr pellets on Nicolet AVATAR 36 FT-IR spec-
trophotometer. NMR spectra were recorded at 400 (1H) and 100 (13C)
MHz, respectively, on a Varian Mercury plus-400 instrument using
CDCl3 or DMSO-d6 as solvent and TMS as internal standard. Mass
spectra were recorded on a ZAB-HS spectrometer. Elemental analyses

462 JOURNAL OF CHEMICAL RESEARCH 2011
Table 2 Synthesis of N-substituted 1,2,3,4,5,6,7,8-octahydroquinazoline-2-one/thione-5-one 3 and 4
Entry Compd
R
EWG
X
Yield/%
Entry
Compd.
R
EWG
X
Yield/%
1
2
3a
3b
3c
3d
3e
3f
3g
3h
3i
H
COOCH3
COOCH3
COOCH3
COOCH3
COOCH3
COOCH3
COOCH3
COOC4H9
CN
O
O
O
O
O
O
O
O
O
O
O
86
89
89
85
85
80
68
84
86
69
89
12
13
14
15
16
17
18
19
20
21
22
3l
H
COOCH3
COOCH3
COOCH3
COOCH3
COOCH3
COOCH3
COOCH3
COOC4H9
CN
S
S
S
S
S
S
S
S
S
S
S
88
92
90
88
84
84
65
76
88
74
82
4-OCH3
4-CH3
4-Cl
4-NO2
3-NO2
2-Cl
H
3m
3n
3o
3p
3q
3r
4-OCH3
4-CH3
4-Cl
4-NO2
3-NO2
2-Cl
H
3
4
5
6
7
8
3s
3t
3u
3v
9
H
H
H
H
H
H
10
11
3j
3k
CONH2
CONH2
COCH3
COCH3
12
13
4a
4b
OCH3
NO2
COOCH3
COOCH3
O
O
79
77
23
24
4c
4d
OCH3
NO2
COOCH3
COOCH3
S
S
77
72
a The reaction was conducted with 3,4-dihydropyrimidones (1 mmol), α, β-ethylenic compounds (1.2 mmol), and DMF (5 mL) in the
presence of KF/Al2O3 (10 mol%) at 40oC for overnight.
b Isolated yields.
were performed on a Carlo-Erba 1106 Elemental Analysis instru-
ment.
2.38–2.19 (m, 4H, 2CH2), 1.10 (s, 3H, CH3) , 0.94 (s, 3H, CH3). 13C
NMR (CDCl3): δ = 193.4, 171.9, 153.8, 150.2, 141.2, 137.2, 128.2,
115.1, 109.5, 59.2, 56.3, 52.1, 50.2, 47.3, 39.5, 33.0, 31.7, 29.5, 27.1.
MS (FAB): m/z =386 (M+ +H). Anal. Calcd for C20H26N2O5: C, 65.27;
H, 6.78; N, 7.25. Found: C, 65.46; H, 6.83; N, 7.31%.
Preparation of 4-aryl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazo-
line-2-one/thione-5-ones; general procedure
The reaction of benzaldehyde (10 mmol) 1 with urea/thiourea
(12 mmol) and 5,5-dimethylcyclohexane-1,3-dione (10 mmol) in the
presence of H2SO4 (10% mmol) as catalyst in ethanol (10 mL)
at 80 °C for 8 hours produced 4-aryl-7,7-dimethyl- 1,2,3,4,5,6,7,8-
octahydroquinazoline-2-one/thione-5-ones. After the reaction was
completed (monitored by TLC), pure product was obtained from the
crude product by filtration and recrystallisation to afford:
4-Phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-
dione (1a): White solid; m.p. 308–310 °C (EtOH) IR (KBr): 3321,
3260, 3098, 1709, 1670 cm−1. 1H NMR (DMSO-d6): δ = 9.46 (br, 1H,
NH), 7.76 (br, 1H, NH), 7.33–7.20 (m, 5H, C6H5), 5.14 (d, J = 2.8 Hz,
CH), 2.51–2.00 (m, 4H, 2CH2), 1.05 (s, 3H, CH3), 0.89 (s, 3H, CH3).
13C NMR (DMSO-d6): δ = 192.8, 152.4, 151.9, 144.6, 128.3, 127.1,
126.2, 107.4, 52.0, 51.9, 49.8, 32.3, 28.7, 26.8. MS (FAB): m/z = 270
(M+ +H). Anal. Calcd for C16H18N2O2: C, 71.09; H, 6.71; N, 10.36.
Found: C, 71.31; H, 6.78 N, 10.30%.
4-Phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydroquinazoline-2-
thione-5-one (1g): White solid; m.p. 302–304 °C (EtOH) IR (KBr):
3343, 3214, 3033, 1698, 1363 cm−1. 1H NMR (DMSO-d6): δ = 10.58
(br, 1H, NH), 9.68 (br, 1H, NH), 7.36–7.21 (m, 5H, C6H5), 5.18 (d,
J = 2.8 Hz, CH), 2.50–2.04 (m, 4H, 2CH2) 1.05 (s, 3H, CH3), 0.89(s,
3H, CH3). 13C NMR (DMSO-d6): δ = 193.6, 174.6, 148.7, 143.3,
128.5, 127.5, 126.4, 108.1, 52.2, 52.1, 49.8, 32.2, 28.8, 26.7. MS
(FAB): m/z = 286 (M+ +H). Anal. Calcd for C16H18N2OS: C, 67.10; H,
6.33; N, 9.78. Found: C, 67.28; H, 6.42 N, 9.76%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-methylphenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione (3c): White solid; m.p.
188–189 °C (EtOH) IR (KBr): 3306, 3050, 1735, 1681, 1639 cm−1.
1H NMR (CDCl3): δ = 9.26 (br, 1H, NH), 6.87 (d, 2H, J = 8.0 Hz,
C6H4), 6.44 (d, 2H, J = 8.0 Hz, C6H4), 5.87 (s, 1H, CH), 3.86–3.79 (m,
1H, CH2), 3.72 (s, 3H, OCH3), 3.70–3.66 (m, 1H, CH2), 2.71–2.64
(m, 1H, CH2), 2.53–2.41 (m, 1H, CH2), 2.37 (m, 3H, CH3), 2.36–2.18
(m, 4H, 2CH2), 1.11 (s, 3H, CH3) , 0.96 (s, 3H, CH3). 13C NMR
(CDCl3): δ = 195.2, 173.6, 152.9, 151.2, 141.2, 139.5, 129.4, 127.8,
110.2, 58.4, 53.5, 50.8, 48.4, 39.6, 33.7, 32.9, 28.7, 27.4, 22.0. MS
(FAB): m/z =370 (M+ +H). Anal. Calcd for C21H26N2O4: C, 68.09;
H, 7.07; N, 7.56. Found: C, 68.30; H, 7.15; N, 7.50%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-chlorophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione (3d): White solid;
m.p. 181–182 °C (EtOH) IR (KBr): 3308, 3048, 1733, 1684,
1638 cm−1. 1H NMR (CDCl3): δ = 9.30 (br, 1H, NH), 7.33 (d, 2H, J =
8.0. Hz, C6H4), 7.29 (d, 2H, J = 8.0 Hz, C6H4), 5.60 (s, 1H, CH),
3.85–3.82 (m, 1H, CH2), 3.66 (s, 3H, OCH3), 3.29–3.21 (m, 1H, CH2),
2.72–2.65 (m, 1H, CH2), 2.50–2.46 (m, 1H, CH2), 2.44–2.12 (m, 4H,
2CH2), 1.10 (s, 3H, CH3) , 0.94 (s, 3H, CH3). 13C NMR (CDCl3): δ =
194.2, 173.6, 154.8, 152.3, 140.2, 134.7, 129.6, 128.7, 109.4, 59.3,
51.7, 52.6, 44.6, 40.7, 31.5, 33.2, 29.5, 27.2. MS (FAB): m/z = 390,
392 (M+ +H). Anal. Calcd for C20H23N2ClO4: C, 61.46; H, 5.93;
N, 7.17. Found: C, 61.27; H, 5.99; N, 7.11%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-nitrophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione (3e): White solid;
m.p. 232–233 °C (EtOH) IR (KBr): 3356, 3046, 1748, 1663, 1617
Synthesis of compounds 3a–v, 4a–d; general procedure
To a suspension of quinazolinone 1 (1.0 mmol) and α, β-ethylenic
compound 2 (1.0 mmol) in DMF (5 mL), KF/Al2O3 (10 mol %,
0.16 g) was added in one portion. The mixture was stirred at 40 °C for
12 h and poured onto ice-water. The resulting product was purified by
recrystallisation from ethanol.
3-(2-Methoxycarbonyl-ethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-
octahydroquinazoline-2,5-dione (3a): White solid; m.p. 183–184 °C
(EtOH) IR (KBr): 3290, 3089, 1734, 1681, 1644 cm−1. 1H NMR
(CDCl3): δ = 9.32 (br,1H, NH), 7.40–7.24 (m, 5H, C6H5), 5.44 (s, 1H,
CH), 3.89–3.82 (m, 1H, CH2), 3.66 (s, 3H, OCH3), 3.28–3.21 (m, 1H,
CH2), 2.72–2.65 (m, 1H, CH2), 2.50–2.42 (m, 1H, CH2), 2.37–2.16
(m, 4H, 2CH2) , 1.10 (s, 3H, CH3) , 0.94 (s, 3H, CH3). 13C NMR
(CDCl3): δ = 193.6, 171.8, 153.3, 150.1, 141.4, 128.7, 128.0, 126.9,
109.4, 58.4, 51.8, 50.3, 42.2, 39.7, 32.8, 32.4, 29.2, 27.1. MS (FAB):
m/z = 356 (M+ +H). Anal. Calcd for C20H24N2O4: C, 67.40; H, 6.79;
N, 7.86. Found: C, 67.62; H, 6.73; N, 7.92%.
1
cm−1. H NMR (CDCl3): δ = 9.52 (br, 1H, NH), 8.22 (d, 2H, J = 8.0
Hz, C6H4), 7.61 (d, 2H, J = 8.0 Hz, C6H4), 5.56 (s, 1H, CH), 3.92–3.86
(m, 1H, CH2), 3.72 (s, 3H, OCH3), 3.33–3.30 (m, 1H, CH2), 2.76–2.72
(m, 1H, CH2), 2.56–2.48 (m, 1H, CH2), 2.40–2.15 (m, 4H, 2CH2) ,
1.10 (s, 3H, CH3) , 0.95 (s, 3H, CH3). 13C NMR (CDCl3): δ = 196.3,
172.9, 152.4, 148.6, 147.9, 144.3, 128.6, 127.2, 107.2, 62.4, 52.6,
51.3, 43.5, 40.9, 33.4, 32.7, 29.2, 27.4. MS (FAB): m/z =401 (M+ +H).
Anal. Calcd for C20H23N3O6: C, 59.84; H, 5.78; N, 10.47. Found:
C, 59.69; H, 5.83; N, 10.42%.
3-(2-Methoxycarbonyl-ethyl)-4-(3-nitrophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione (3f): White solid;
m.p. 214–215 °C (EtOH) IR (KBr): 3348, 3048, 1737, 1656, 1619
1
cm−1. H NMR (CDCl3): δ = 9.46 (br, 1H, NH), 8.22–8.13 (m, 2H,
C6H4), 7.79 (d, J = 3.2, Hz, 1H, C6H4), 7.18–7.14 (q, J = 16.0, 1H,
C6H4), 5.79 (s, 1H, CH), 4.54–4.49 (m, 1H, CH2), 3.70 (s, 3H, OCH3),
3.68–3.57 (m, 1H, CH2), 3.15–2.98 (m, 1H, CH2), 2.77–2.64 (m, 1H,
CH2), 2.52–2.31 (m, 4H, 2CH2) , 1.11 (s, 3H, CH3) , 0.92 (s, 3H, CH3).
13C NMR (CDCl3): δ = 193.4, 175.3, 172.0, 149.1, 147.5, 141.8, 138.2,
129.6 124.2, 122.3, 109.6, 59.0, 52.4, 51.1, 49.2, 39.7, 33.6, 32.2,
29.5, 27.4. MS (FAB): m/z =401 (M+ +H).Anal. Calcd for C20H23N3O6:
C, 59.84; H, 5.78; N, 10.47. Found: C, 59.95; H, 5.70; N, 10.53%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-methoxylphenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione (3b): White solid;
m.p. 226–227 °C (EtOH) IR (KBr): 3432, 3046, 1666, 1626, 1607
1
cm−1. H NMR (CDCl3): δ = 9.38 (br, 1H, NH), 6.96 (d, 2H, J =
8.0 Hz, C6H4), 6.53 (d, 2H, J = 8.0 Hz, C6H4), 5.93 (s, 1H, CH), 3.89–
3.82 (m, 1H, CH2), 3.75 (s, 3H, OCH3), 3.72–3.69 (m, 1H, CH2), 3.66
(s, 3H, OCH3), 2.72–2.65 (m, 1H, CH2), 2.56–2.44 (m, 1H, CH2),

JOURNAL OF CHEMICAL RESEARCH 2011 463
3-(2-Methoxycarbonyl-ethyl)-4-(2-chlorophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione (3g): White solid;
m.p. 174–175 °C (EtOH) IR (KBr): 3312, 3050, 1739, 1690, 1642
cm−1. 1H NMR (CDCl3): δ = 9.50 (br, 1H, NH), 7.38 (d, J = 8.0 Hz, 1H,
C6H4), 7.31–7.29 (m, 1H, C6H4), 7.23–7.19 (m, 2H, C6H4), 5.66 (s, 1H,
CH), 3.88 (s, 3H, OCH3),3.80–3.73 (m, 1H, CH2), 3.42–3.35 (m, 1H,
CH2), 2.68–2.61 (m, 1H, CH2), 2.44–2.40 (m, 1H, CH2), 2.36–2.10
(m, 4H, 2CH2), 1.11 (s, 3H, CH3) , 1.00 (s, 3H, CH3). 13C NMR
(CDCl3): δ = 197.2, 172.6, 152.8, 148.4, 138.6, 133.6, 129.1, 128.6,
128.3, 126.8, 106.5, 59.2, 51.6, 50.6, 42.5, 39.2, 33.1, 32.7, 29.4, 27.2.
MS (FAB): m/z =390, 392 (M+ +H). Anal. Calcd for C20H23N2ClO4:
C, 61.46; H, 5.93; N, 7.17. Found: C, 61.57; H, 5.98; N, 7.19%.
3-(2-Butyloxycarbonyl-ethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-
octahydroquinazoline-2,5-dione (3h): White solid; m.p. 175–176 °C
(EtOH) IR (KBr): 3302, 3026, 1738, 1690, 1669 cm−1. 1H NMR
(CDCl3): δ = 7.92 (br, 1H, NH), 7.33–7.26 (m, 5H, C6H5), 5.62 (s, 1H,
CH), 4.47–4.42 (m, 1H, CH2), 4.07–4.03 (m, 2H, OCH2), 3.72–3.70
(m, 1H, CH2), 2.93–2.91 (m, 1H, CH2), 2.89–2.84 (m, 1H, CH2), 2.64–
2.14 (m, 4H, 2CH2) , 1.55–1.48 (m, 2H, CH2), 1.40–1.30 (m, 2H,
CH2), 1.11 (s, 3H, CH3), 0.94 (t, J = 14.8 Hz, 3H, CH3) , 0.90 (s, 3H,
CH3). 13C NMR (CDCl3): δ = 192.6, 171.6, 153.8, 146.3, 144.1, 128.8,
128.2, 128.3, 109.8, 63.7, 59.7, 50.6, 48.9, 40.1, 32.9, 31.9, 30.4, 29.5,
27.5, 19.6, 14.9. MS (FAB): m/z =398 (M+ +H). Anal. Calcd for
C23H30N2O4: C, 69.32; H, 7.59; N, 7.03. Found: C, 69.53; H, 7.63;
N, 6.97%.
3-(2-Cyanoethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahy-
droquinazoline-2,5-dione (3i): White solid; m.p. 210–211 °C (EtOH)
IR (KBr): 3346, 3046, 2252, 1692, 1683, 1260 cm−1. 1H NMR (CDCl3):
δ = 8.55 (br, 1H, NH), 7.15–6.88 (m, 5H, C6H5), 5.53 (s, 1H, CH),
4.30–4.20 (m, 1H, CH2),3,93–3.68 (m, 1H, CH2), 3.09–2.98 (m, 1H,
CH2), 2.86–2.73 (m, 1H, CH2), 2.50–2.16 (m, 4H, 2CH2), 1.10 (s, 3H,
CH3) , 0.91 (s, 3H, CH3). 13C NMR (CDCl3): δ = 194.2, 154.8, 152.7,
145.3, 133.2, 129.4, 118.0, 115.2, 112.3, 60.9, 50.5, 48.3, 40.2, 33.1,
29.8, 26.9, 15.6. MS (FAB): m/z =323 (M+ +H). Anal. Calcd for
C19H21N3O2: C, 70.57; H, 6.55; N, 12.99. Found: C, 70.35; H, 6.51;
N, 12.92%.
159.5, 145.3, 142.6, 132.7, 128.1, 108.9, 59.5, 55.2, 53.1, 51.9, 48.6,
39.4, 32.9, 31.5, 29.3, 27.1 . MS (FAB): m/z =402 (M+ +H). Anal.
Calcd for C21H26N3O4S: C, 62.66; H, 6.51; N, 6.96, Found: C, 62.79;
H, 6.56; N, 6.90%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-methylphenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (3n): White
solid; m.p. 181–182 °C (EtOH) IR (KBr): 3387, 3030, 1685, 1645,
1235 cm−1. 1H NMR (CDCl3): δ = 8.50 (br, 1H, NH), 7.19 (d, J = 8.0,
2H, C6H4), 6.64 (d, J = 8.0, 2H, C6H4), 5.75 (s, 1H, CH), 3.76–3.67 (m,
1H, CH2), 3.73 (s, 3H, OCH3), 3.71–3.68 (m, 1H, CH2), 2.66–2.59
(m, 1H, CH2), 2.55–2.50 (m, 1H, CH2), 2.43 (m, 3H, CH3), 2.38–2.11
(m, 4H, CH2), 1.10 (s, 3H, CH3) , 0.94 (s, 3H, CH3). 13C NMR (CDCl3):
δ = 193.2, 174.8, 159.4, 152.3, 143.1, 137.6, 127.2, 117.5, 111.3, 59.4,
53.6, 51.5, 48.8, 39.4, 32.5, 31.9, 29.1, 27.4, 21,8 . MS (FAB):
m/z =386 (M+ +H). Anal. Calcd for C21H26N2O3S: C, 65.26; H, 6.78;
N, 7.25, Found: C, 65.48; H, 6.82; N, 7.31%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-Cl)-phenyl-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (3o): White
solid; m.p. 229–230 °C (EtOH) IR (KBr): 3364, 3044, 1706, 1669,
1224 cm−1. 1H NMR (CDCl3): δ = 8.57 (br, 1H, NH), 7.63 (d, J = 8.0
Hz, 2H, C6H4), 7.36 (d, J = 8.0 Hz, 2H, C6H4), 5.48 (s, 1H, CH), 3.73–
3.77 (m, 1H, CH2), 3.58 (s, 3H, OCH3), 3.25–3.18 (m, 1H, CH2),
2.66–2.63 (m, 1H, CH2), 2.44–2.41 (m, 1H, CH2), 2.39–2.10 (m, 4H,
2CH2), 1.11 (s, 3H, CH3) , 0.95 (s, 3H, CH3). 13C NMR (CDCl3): δ =
192.8, 172.3, 152.7, 151.1, 139.2, 133.6, 129.4, 128.7, 109.5, 58.8,
52.0, 51.3, 43.2, 40.2, 33.2, 32.8, 29.6, 27.4. MS (FAB): m/z = 406,
408 (M+ +H). Anal. Calcd for C20H23N2ClO3S: C, 59.03; H, 5.70; N,
6.88. Found: C, 58.87; H, 5.65; N, 6.85%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-nitrophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (3p): White
solid; m.p. 223–224 °C (EtOH) IR (KBr): 3342, 3036, 1738, 1674,
1224 cm−1. 1H NMR (CDCl3): δ = 8.83 (br, 1H, NH), 7.94 (d, J = 8.0,
2H, C6H4), 7.72 (d, J = 8.0, 2H, C6H4), 5.53 (s, 1H, CH), 3.84–3.78 (m,
1H, CH2), 3.84 (s, 3H, OCH3), 3.50–3.45 (m, 1H, CH2), 2.70–2.66
(m, 1H, CH2), 2.53–2.47 (m, 1H, CH2), 2.41–2.12 (m, 4H, 2CH2) ,
1.09 (s, 3H, CH3) , 0.96 (s, 3H, CH3). 13C NMR (CDCl3): δ = 196.8,
172.3, 154.4, 152.6, 148.2, 136.3, 128.9, 128.2, 109.6, 59.4, 52.2,
51.4, 50.8, 40.1, 32.9, 32.4, 29.7, 27.0. MS (FAB): m/z = 417 (M+ +H).
Anal. Calcd for C20H23N3O5S: C, 57.54; H, 5.55; N, 10.07. Found:
C, 57.63; H, 5.51; N, 10.14%.
3-(2-Aminocarbonyl-ethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-
octahydroquinazoline-2,5-dione (3j): White solid; m.p. 254–255 °C
(EtOH) IR (KBr): 3415, 3374, 3206, 3069, 1703, 1675, 1634 cm−1. 1H
NMR (CDCl3): δ = 10.71 (br, 1H, NH), 7.36–7.17 (m, 5H, C6H5), 7.08
(br, 1H, NH2), 6.89 (br, 1H, NH2), 5.44 (s, 1H, CH), 4.51–4.22 (m, 2H,
CH2), 3.74–3.34 (m, 2H, CH2), 2.54–1.96 (m, 4H, 2CH2) , 1.03 (s, 3H,
CH3), 0.89 (s, 3H, CH3). 13C NMR (CDCl3): δ = 196.0, 175.0, 162.9,
147.3, 144.2, 128.7, 128.0, 114.4, 108.6, 58.5, 50.0, 47.9, 39.7, 32.5
29.0 26.4, 18.6. MS (FAB): m/z =341 (M+ +H). Anal. Calcd for
C19H23N3O3: C, 66.84; H, 6.79; N, 12.31, Found: C, 66.97; H, 6.72;
N, 12.38%.
3-(2-Methoxycarbonyl-ethyl)-4-(3-nitrophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (3q): White
solid; m.p. 211–212 °C (EtOH) IR (KBr): 3326, 3015, 1736, 1674,
1
1210 cm−1. H NMR (CDCl3): δ = 8.35 (s, 1H, NH), 8.19–8.09 (m,
2H, C6H4), 7.74–7.66 (d, J = 3.2, Hz, 1H, C6H4), 7.56–7.52 (q, J =
16.0, 1H, C6H4), 5.83 (s, 1H, CH), 4.47–4.41 (m, 1H, CH2), 3.68 (s,
3H, OCH3), 3.63–3.56 (m, 1H, CH2), 3.00–2.93 (m, 1H, CH2), 2.72–
2.66 (m, 1H, CH2), 2.46–2.20 (m, 4H, 2CH2) , 1.12 (s, 3H, CH3) , 0.90
(s, 3H, CH3). 13C NMR (CDCl3): δ = 196.5, 175.6, 171.6, 148.6, 146.2,
142.6, 138.4, 129.8, 123.4, 121.8, 109.3, 59.3, 52.0, 50.1, 48.8, 39.4,
32.9, 31.5, 29.3, 27.0 . MS (FAB): m/z = 417 (M+ +H). Anal. Calcd for
C20H23N3O5S: C, 57.54; H, 5.55; N, 10.07. Found: C, 57.31; H, 5.50;
N, 10.12%.
3-(2-Methoxycarbonyl-ethyl)-4-(2-chlorophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (3r): White
solid; m.p. 169–170 °C (EtOH) IR (KBr): 3308, 3064, 1728, 1673,
1253 cm−1. 1H NMR (CDCl3): δ = 10.12 (br, 1H, NH), 7.56 (d, J = 8.0
Hz, 1H, C6H4), 7.45–7.34 (m, 1H, C6H4), 7.30–7.28 (m, 2H, C6H4),
5.30 (s, 1H, CH), 3.87–3.77 (m, 1H, CH2), 3.72 (s, 3H, OCH3), 3.53–
3.44 (m, 1H, CH2), 2.73–2.68 (m, 1H, CH2), 2.53–2.47 (m, 1H, CH2),
2.43–2.13 (m, 4H, 2CH2), 1.10 (s, 3H, CH3) , 0.95 (s, 3H, CH3). 13C
NMR (CDCl3): δ = 198.4, 178.2, 174.1, 159.8, 137.9, 133.2, 129.3,
128.9, 128.3, 126.8, 104.2, 63.7, 52.3, 51.2, 48.0, 40.1, 33.9, 33.2,
29.3, 27.1. MS (FAB): m/z = 406, 408 (M+ +H). Anal. Calcd for
C20H23N2ClO3S: C, 59.03; H, 5.70; N, 6.88. Found: C, 59.29; H, 5.75;
N, 6.85%.
3-(3-Oxobutyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydro-
quinazoline-2,5-dione (3k): White solid; m.p. 213–214 °C (EtOH) IR
1
(KBr): 3328, 3042, 1736, 1686, 1664 cm−1. H NMR (CDCl3): δ =
9.34 (br, 1H, NH), 7.42–7.24 (m, 5H, C6H5), 5.38 (s, 1H, CH), 3.48–
3.39 (m, 2H, CH2), 2.83–2.74 (m, 2H, CH2), 2.53–2.12 (m, 4H, 2CH2)
, 2.14 (s, 3H, CH3) , 1.10 (s, 3H, CH3) , 0.94 (s, 3H, CH3). 13C NMR
(CDCl3): δ = 202.8, 193.6, 153.5, 150.4, 141.3, 128.5, 127.9, 126.4,
110.1, 57.8, 50.3, 43.0, 39.8, 33.1, 32.8, 29.8, 29.0, 27.1. MS (FAB):
m/z =340 (M+ +H). Anal. Calcd for C20H24N2O3: C, 70.56; H, 7.11;
N, 8.23, Found: C, 70.38; H, 7.16; N, 8.19%.
3-(2-Methoxycarbonyl-ethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-
octahydroquinazoline-2-thione-5-one (3l): White solid; m.p. 189–
1
190 °C (EtOH) IR (KBr): 3386, 3034, 1724, 1649, 1246 cm−1. H
NMR (CDCl3): δ = 8.73 (br, 1H, NH), 7.33–7.21 (m, 5H, C6H5), 5.62
(s, 1H, CH), 3.74–3.64 (m, 2H, CH2), 3.66 (s, 3H, OCH3), 2.72–2.64
(m, 2H, CH2), 2.47–2.16 (m, 4H, 2CH2) , 1.10 (s, 3H, CH3) , 0.94 (s,
3H, CH3). 13C NMR (CDCl3): δ = 193.9, 175.3, 171.6, 145.8, 140.5,
128.9, 128.3, 126.7, 110.1, 59.9, 51.9, 50.3, 48.7, 39.2, 32.8, 31.5,
29.3, 27.0. MS(FAB):m/z=372(M+ +H).Anal. CalcdforC20H24N2O3S:
C, 64.49; H, 6.49; N, 7.52, Found: C, 64.63; H, 6.45; N, 7.57%.
3-(2-Methoxycarbonyl-ethyl)-4-(4-methoxylphenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (3m): White
solid; m.p. 156–156 °C (EtOH) IR (KBr): 3318, 3044, 1739, 1643,
1251 cm−1. 1H NMR (CDCl3): δ = 8.28 (br, 1H, NH), 7.26 (d, J = 8.0,
2H, C6H4), 6.83 (d, J = 8.0, 2H, C6H4), 5.54 (s, 1H, CH), 4.35–3.69 (m,
2H, CH2), 3.78 (s, 3H, OCH3), 3.66 (s, 3H, OCH3), 2.94–2.78 (m, 1H,
CH2), 2.67–2.55 (m, 1H, CH2), 2.40–2.14 (m, 4H, 2CH2), 1.11 (s, 3H,
CH3) , 0.91 (s, 3H, CH3). 13C NMR (CDCl3): δ = 194.2, 175.0, 171.6,
3-(2-Butyloxycarbonyl-ethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-
octahydroquinazoline-2-thione-5-dione (3s): White solid; m.p. 163–
1
164 °C (EtOH) IR (KBr): 3350, 3046, 1727, 1620, 1221 cm−1. H
NMR (CDCl3): δ = 8.15 (br, 1H, NH), 7.33–7.26 (m, 5H, C6H5), 5.63
(s, 1H, CH), 4.41–4.26(m, 1H, CH2), 3.79–3.64 (m, 1H, CH2), 4.05
(m, 2H, OCH2), 2.93–2.57 (m, 2H, CH2), 2.40–2.14 (m, 4H, 2CH2),
1.62–1.30 (m, 4H, 2CH2) , 1.10 (s, 3H, CH3) , 0.94 (t, J = 14.2 Hz, 3H,
CH3), 0.90 (s, 3H, CH3). 13C NMR (CDCl3): δ = 194.4, 175.3, 171.2,
145.5, 140.5, 128.9, 128.3, 126.8, 109.3, 64.8, 59.9, 50.3, 48.8, 39.5,

464 JOURNAL OF CHEMICAL RESEARCH 2011
32.9, 31.8, 30.5, 29.3, 27.0, 19.1, 13.7. MS (FAB): m/z = 414 (M+ +H).
Anal. Calcd for C23H30N2O3S: C, 66.64; H, 7.29; N, 6.76, Found:
C, 66.49; H, 7.33; N, 6.71%.
(m, 3H, C6H4), 5.88 (br, 1H, NH), 5.69 (d, J = 2.8 Hz,1H, CH), 4.01–
3.60 (m, 2H, CH2), 3.87 (s, 3H, OCH3), 3.65 (s, 3H, OCH3), 2.90–2.72
(m, 2H, CH2), 2.55–2.26 (m, 4H, 2CH2) , 1.10 (s, 3H, CH3) , 0.94
(s, 3H, CH3). 13C NMR (CDCl3): δ = 194.2, 171.8, 157.0, 153.7, 153.1,
129.1, 128.7, 126.0, 120.3, 110.7, 109.2, 55.3, 51.8, 49.4, 46.9, 39.9,
38.3, 33.8, 32.9, 29.1, 28.4. MS (FAB): m/z = 402 (M+ +H). Anal.
Calcd for C21H26N2O4S: C, 62.66; H, 6.51; N, 6.96. Found: C, 62.37;
H, 6.55; N, 6.91%.
3-(2-Cyanoethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahy-
droquinazoline-2-thione-5-one (3t): White solid; m.p. 208–209 °C
(EtOH) IR (KBr): 3324, 3048, 2246, 1682, 1620, 1172 cm−1. 1H NMR
(CDCl3): δ = 8.05 (br, 1H, NH), 6.85–6.42 (m, 5H, C6H5), 5.49 (s, 1H,
CH), 4.29–3.73 (m, 2H, CH2), 3.10–2.89 (m, 2H, CH2), 2.47–2.16 (m,
4H, 2CH2), 1.11 (s, 3H, CH3), 0.93 (s, 3H, CH3). 13C NMR (CDCl3):
δ = 195.3, 175.6, 159.8, 144.8, 132.2, 128.2, 117.2, 114.5, 110.5, 60.4,
55.3, 48.6, 39.5, 32.9, 29.3, 27.1, 15.3. MS (FAB): m/z =339 (M+ +H).
Anal. Calcd for C19H21N3OS: C, 67.23; H, 6.24; N, 12.38, Found:
C, 67.46; H, 6.28; N, 12.32%.
1-(2-Methoxycarbonyl-ethyl)-4-(2-nitrylphenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (4d): White
solid; m.p. 172–173 °C (EtOH) IR (KBr): 3310, 3082, 1668, 1631,
1
1358 cm−1. H NMR (CDCl3): δ = 7.97–7.94 (q, J = 12.0 Hz, 1H,
C6H4), 7.54–7.50 (m, 1H, C6H4), 7.43–7.40(m, 1H, C6H4), 7.29–7.26
(q, J = 12.0, 1H, C6H4), 6.18 (br, 1H, NH), 5.83 (d, J = 2.8 Hz,1H,
CH), 4.10–3.95 (m, 2H, CH2), 3.75–3.73 (m, 1H, CH2), 3.72 (s, 3H,
OCH3), 3.72–3.68 (m, 1H, CH2), 2.93–2.84 (m, 1H, CH2), 2.63–2.26
(m, 4H, 2CH2) , 1.10 (s, 3H, CH3) , 0.94 (s, 3H, CH3). 13C NMR
(CDCl3): δ = 198.7, 175.6, 171.4, 158.4, 148.1, 135.3, 131.6, 129.6,
128.6, 127.3, 104.2, 62.7, 52.0, 51.2, 47.8, 39.5, 33.9, 32.6, 27.5, 27.2.
MS (FAB): m/z = 417 (M+ +H). Anal. Calcd for C20H23N3O5S:
C, 57.54; H, 5.55; N, 10.07, Found: C, 57.28; H, 5.51; N, 10.03%.
3-(2-Aminocarbonyl-ethyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-
octahydroquinazoline-2-thione-5-dione (3u): White solid; m.p. 253–
254 °C (EtOH) IR (KBr): 3431, 3383, 3221, 3074, 1690, 1682, 1222
1
cm−1. H NMR (CDCl3): δ = 10.71 (br, 1H, NH), 7.36–7.17 (m, 5H,
C6H5), 7.12 (s, 1H, NH2), 6.96 (s, 1H, NH2), 5.35 (s, 1H, CH), 4.47–
4.25 (m, 2H, CH2), 3.64–3.37 (m, 2H, CH2), 2.58–2.42 (m, 2H, CH2),
2.38–1.92 (m, 2H, CH2) , 1.02 (s, 3H, CH3), 0.90 (s, 3H, CH3). 13C
NMR (CDCl3): δ = 194.4, 174.8, 164.2, 145.2, 142.4, 129.1, 127.7,
116.2, 109.2, 57.8, 51.2, 48.3, 40.6, 32.7, 28.6, 25.9, 19.2. MS (FAB):
m/z =357 (M+ +H). Anal. Calcd for C19H23N3O2S: C, 63.84; H, 6.49;
N, 11.75, Found: C, 63.65; H, 6.45; N, 11.80%.
3-(3-Oxobutyl)-4-phenyl-7,7-dimethyl-1,2,3,4,5,6,7,8-octahydro-
quinazoline-2-thione-5-one (3v): White solid; m.p. 221–222 °C
(EtOH) IR (KBr): 3340, 3046, 1712, 1620, 1247 cm−1. 1H NMR
(CDCl3): δ = 8.92 (br, 1H, NH), 7.33–7.15 (m, 5H, C6H5), 5.26 (s, 1H,
CH), 3.63–3.44 (m, 2H, CH2), 2.88–2.63 (m, 2H, CH2), 2.53–2.41 (m,
2H, CH2), 2.38–2.21 (m, 2H, CH2) 2.17 (s, 3H, CH3), 1.09 (s, 3H,
CH3), 0.95 (s, 3H, CH3). 13C NMR (CDCl3): δ = 201.4, 192.3, 163.5,
151.2, 142.4, 128.6, 127.8, 124.2, 111.6, 56.4, 46.2, 40.4, 34.3, 32.9,
30.2, 29.5, 29.1, 27.4. MS (FAB): m/z = 356 (M+ +H). Anal. Calcd for
C20H24N2O2S: C, 67.38; H, 6.79; N, 7.86, Found: C, 67.25; H, 6.83;
N, 7.80%.
We are thankful for the financial support from the National
Nature Science Foundation of China (No. 20902073 and
21062017), the Natural Science Foundation of Gansu Province
(No. 096RJZA116), and Scientific and Technological Innova-
tion Engineering program of Northwest Normal University
(nwnu-kjcxgc-03-64, nwnu-lkqn-10-15).
Received 6 June 2011; accepted 29 July 2011
Paper 1100732 doi: 10.3184/174751911X13129294387591
Published online: 29 August 2011
1-(2-Methoxycarbonyl-ethyl)-4-(2-methoxylphenyl)-7,7-dimethyl-
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4
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1
156 °C (EtOH) IR (KBr): 3310, 3046, 1732, 1685, 1639 cm−1. H
NMR (CDCl3): δ = 7.28–7.25 (m, 1H, C6H4), 6.86–6.78 (m, 3H, C6H4),
5.89 (br, 1H, NH), 5.68 (d, J = 2.8 Hz, 1H, CH), 4.00–3.90 (m, 2H,
CH2), 3.87 (s, 3H, OCH3), 3.65 (s, 3H, OCH3), 2.90–2.70 (m, 2H,
CH2), 2.55–2.26 (m, 4H, 2CH2), 1.20 (s, 3H, CH3), 1.07 (s, 3H, CH3).
13C NMR (CDCl3): δ = 193.8, 175.4, 158.2, 154.6, 152.7, 128.2, 127.1,
126.4, 121.9, 111.4, 109.7, 57.4, 55.8, 52.1, 49.6, 47.7, 40.9, 38.9,
33.0, 28.9, 27.3. MS (FAB): m/z = 386 (M+ +H). Anal. Calcd for
C21H26N2O5: C, 65.27; H, 6.78; N, 7.25, Found: C, 65.16; H, 6.82;
N, 7.29%.
5
6
7
8
9
J. L. Mokrosz, M. H. Paluchowska, E. Szneler and B. Drozdz, Arch. Chem.
(Weinheim, Germany). 1989, 322, 231.
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4559.
D. Prajapati, D. Bhuyan, M. Gohain and W. H. Hu, Mol. Divers., 2011, 15,
257.
M. Kidwai, S. Saxena, M. Khalilur Rahman Khan and S. S.Thukral, Eur. J.
Med. Chem., 2005, 40, 816.
M. Kidwai, D. Bhatnagar, R. Kumar, and P. M. Luthra., Chem. Pharm.
1-(2-Methoxycarbonyl-ethyl)-4-(2-nitrophenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2,5-dione (4b): White solid;
m.p. 177–178 °C (EtOH) IR (KBr): 3312, 3086, 1663, 1625, 1362
Bull., 2010, 58, 1320.
10 S. Sarac¸, M. Yarim, M. Ertan, F.S. Kilic and K. Erol., Pharmazie, 2001,
56, 298.
1
cm−1. H NMR (CDCl3): δ = 8.03–8.00 (q, J = 12.0 Hz, 1H, C6H4),
7.59–7.55 (m, 1H, C6H4), 7.48–7.47(m, 1H, C6H4), 7.35–7.38 (q, J =
12.0, 1H, C6H4), 6.20 (br, 1H, NH), 5.84 (d, J = 2.8 Hz, 1H, CH),
4.11–3.95 (m, 2H, CH2), 3.78–3.71 (m, 1H, CH2), 3.70 (s, 3H, OCH3),
3.69–3.62 (m, 1H, CH2), 2.66–2.14 (m, 4H, 2CH2) , 1.11 (s, 3H, CH3)
, 0.95 (s, 3H, CH3). 13C NMR (CDCl3): δ = 193.8, 171.9, 154.8, 151.7,
148.4, 136.5, 133.8, 128.9, 128.1, 125.1, 109.1, 51.9, 49.1, 47.7, 39.8,
38.5, 33.6, 32.8, 28.9, 28.5. MS (FAB): m/z =401 (M+ +H). Anal.
Calcd for C20H23N3O6: C, 59.84; H, 5.78; N, 10.47, Found: C, 59.63;
H, 5.82; N, 10.42%.
1-(2-Methoxycarbonyl-ethyl)-4-(2-methoxylphenyl)-7,7-dimethyl-
1,2,3,4,5,6,7,8-octahydroquinazoline-2-thione-5-one (4c): White
solid; m.p. 164–165 °C (EtOH) IR (KBr): 3316, 3044, 1732, 1689,
1213 cm−1. 1H NMR (CDCl3): δ = 7.23–7.20 (m, 1H, C6H4), 6.88–6.79
11 S. Sarac¸, M. Yarim, M. Ertan, S. Boydag and K. Erol, Pharmazie, 1998,
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16 K. S. Niralwad, B. B. Shingate and M.S. Shingare, Tetrahedron Lett., 2010,
51, 3616.
17 D. Dallinger, N. Y. Gorobets and C. O. Kappe, Org Lett., 2003, 5, 1205.
18 K. Singh, D. Arora, E. Poremsky and J. Lowery, Eur. J. Med. Chem., 2009,
44, 1997.