An efficient and facile synthesis of pyrimidine and quinazoline derivatives via one-pot three-component reaction under solvent-free conditions

Article abstract of DOI:10.1002/jhet.43

An efficient and convenient method for the preparation of pyrimidine and quinazoline derivatives by the one-pot reaction of aromatic aldehydes, cyclic ketones and guanidine carbonate, in the presence of sodium hydroxide under solvent-free condition was re

Full text of DOI:10.1002/jhet.43

152
An Efficient and Facile Synthesis of Pyrimidine and Quinazoline
Derivatives via One-Pot Three-Component Reaction under
Solvent-Free Conditions
Vol 46
Liangce Rong,* Hongxia Han, Haiying Wang, Hong Jiang, Shuajiang Tu,
and Daqing Shi
Department of Chemistry, Xuzhou Normal University, Key Laboratory of Biotechnology for
Medicinal Plant, Xuzhou, Jiangsu, 221116, People’s Republic of China
*E-mail: lcrong2005@yahoo.com
Received September 19, 2007
DOI 10.1002/jhet.43
Published online 16 March 2009 in Wiley InterScience (www.interscience.wiley.com).
An efficient and convenient method for the preparation of pyrimidine and quinazoline derivatives by
the one-pot reaction of aromatic aldehydes, cyclic ketones and guanidine carbonate, in the presence of
sodium hydroxide under solvent-free condition was reported. This method has the advantages of excel-
lent yields, mild reaction conditions, easy work-up, and being environmentally friendly over the existing
procedures.
J. Heterocyclic Chem., 46, 152 (2009).
INTRODUCTION
ganic compounds [9], herein, we would like to report a
practical and simple method to prepare pyrimidine and
quinazoline derivatives by heating the starting materials
under dry conditions.
Pyrimidine and its derivatives, as the nitrogen-con-
taining heterocycles, are extremely important com-
pounds with high biological activities [1]. The quinazo-
line nucleus is also a very attractive and useful scaffold
in medicinal chemistry: it can be found as a pharmaco-
phore in a wide variety of biologically active com-
pounds, such as antitumorals [2], antibacterials [3], anti-
virals [4], and many other therapeutic agents [5].
RESULTS AND DISCUSSION
At first, cyclohexanone (2 mmol), aromatic aldehyde
(4 mmol), guanidine carbonate (1 mmol) and NaOH
(0.2 g) were chosen to react together under solvent-free
conditions at 70ꢀC, and the reaction proceeded smoothly
in short time (about 15 min) and the corresponding com-
pounds 4-aryl-8-arylidene)-5,6,7,8-tetrahydroquinaz-olin-
2-amine (4a–4h) could be gained with high yields
(Scheme 1). Then, the reagent of 3,4-dihydronaphthalen-
1(2H)-one (2 mmol) was chosen to replace cyclohexa-
none to react with aromatic aldehyde (2 mmol), guani-
dine carbonate (1 mmol) under the same conditions, and
the corresponding fused-ring quinazoline derivatives:
viz. 4-(4-bromophenyl)-5,6-dihydrobenzo[h]quinazolin-2-
amine (6a–6h), were obgained with excellent yields.
The results of reactions were listed in Table 1. As
shown in Table 1, all the reactions proceeded smoothly
with high yields. We also observed that electron-
In recent years, because of increasing environmental
concerns and the regulatory constraints faced in the
chemical and pharmaceutical industries, the develop-
ment of environmentally friendly organic synthesis has
become a crucial and demanding area in modern organic
chemical research [6]. In order to avoid using organic
solvents, solvent-free organic reactions [7], a ‘‘green’’
organic chemistry method, have been of great interest.
These have many advantages such as high efficiency
and selectivity, easy separation and purification, mild
reaction conditions, and reduction in waste produced.
Many organic reactions have been carried out just by
heating [8].
In continuation to our current studies on the applica-
tion of solvent-free conditions for the synthesis of or-
C
V
2009 HeteroCorporation

March 2009
An Efficient and Facile Synthesis of Pyrimidine and Quinazoline Derivatives
via One-Pot Three-Component Reaction under Solvent-Free Conditions
153
Scheme 1
Scheme 2
of cyclic ketone, aromatic aldehydes, and guanidine car-
bonate was successfully established under solvent-free
condition catalyzed by NaOH. The advantages of this
procedure are high yields, mild reaction conditions, easy
work-up, and environmentally friendly procedure.
withdrawing substituents (ACl, ABr), and electron-
donating substituents (ACH3, AOCH3) had no effect on
the reaction.
In order to apply this reaction to a library synthesis,
cyclopentanone and indan-1-one were chosen to react
with aromatic aldehyde, and guanidine carbonate under
same reaction conditions (Scheme 2). To our delight, all
reactions could be completed successfully, and (E)-7-
arylidene)-4-aryl-6,7-dihydro-5H-cyclopenta[d] pyrimi-
din-2-amine (8a–8f) and 4-aryl-5H-indeno[1,2-d]pyrimi-
din-2-amine (10a–10g) could be gained with good
yields. The reaction results are summarized in Table 2.
The structures of 4, 6, 8, and 10 were confirmed by ir,
1H NMR and elemental analysis, furthermore, the
reported products were identified by comparison of
melting point with those described in the literatures
[10].
EXPERIMENTAL
Melting points were determined on XT-5 microscopic melt-
ing-point apparatus and were uncorrected. IR spectra were
recorded on a FT Bruker Tensor 27 spectrometer. 1H NMR
spectra were obtained from solution in DMSO-d6 with Me4Si
as internal standard using a Bruker-400 spectrometer. Micro-
analyses were carried out using a Perkin-Elmer 2400 II
analyzer.
General procedure for the synthesis of pyrimidine and
quinazoline derivatives. The mixture of ketones 3 and 7, or 5
and 9 (2 mmol), aromatic aldehydes 2 (4 mmol or 2 mmol),
guanidine carbonate 3 (1 mmol) and NaOH (0.2 g) was put in
a reaction flask and heated at 70ꢀC for about 15 min. After
completing the reaction, the reaction mixture was poured into
water, and then washed with water thoroughly. The product
was filtered, dried, and recrystallized from 95% ethanol.
(E)-8-(4-Methylbenzylidene)-4-p-tolyl-5,6,7,8-tetrahydro-
quinazolin-2-amine (4a). This compound was obtained as yel-
low crystals, mp 210–212ꢀC, Lit. [10d] 210–212ꢀC; ir (KBr, m,
cmꢁ1): 3502, 3282, 3152, 2929, 1626, 1541, 1456, 1220; 1H
NMR (400 MHz, DMSO-d6) (d, ppm): 8.00 (1H, s, ArCH¼),
Although similar compounds have been reported in
the literature and the disadvantages of reported methods
were obvious, such as long reaction time, lower product
yields and harsh conditions, furthermore, the excess of
organic solvent was requisite.
In conclusion, an efficient method for the synthesis of
pyrimidine and quinazoline derivatives by condensation
Table 1
Synthesis of quinazoline derivatives under solvent-free conditions.
Table 2
Entry
Ar1
Product
Yields
Synthesis of pyrimidine derivatives under solvent-free conditions.
1
2
4-CH3C6H4
4-CH3OC6H4
3,4-(CH3)2C6H3
3,4-(CH3O)2C6H3
4-BrC6H4
4a
4b
4c
4d
4e
4f
4g
4h
6a
6b
6c
6d
6e
6f
90
95
96
94
92
97
90
95
96
97
96
96
98
97
93
95
Entry
Ar1
Product
Yields
3
4
1
4-CH3C6H4
4-CH3OC6H4
4-FC6H4
8a
8b
8c
8d
8e
8f
10a
10b
10c
10d
10e
10f
10g
93
92
90
93
90
95
93
92
93
90
93
90
95
5
6
2
3
4-ClC6H4
3-ClC6H4
7
4
4--ClC6H4
3-ClC6H4
4-BrC6H4
8
9
3,4-Cl2C6H3
4-CH3C6H4
4-CH3OC6H4
3,4-(CH3O)2C6H3
4-FC6H4
5
6
10
11
12
13
14
15
16
7
8
4-CH3C6H4
4-CH3OC6H4
3,4-(CH3O)2C6H3
4-FC6H4
9
4-BrC6H4
4-ClC6H4
10
11
12
13
4-ClC6H4
4-BrC6H4
3,4-Cl2C6H3
3,4-Cl2C6H
C6H5
6g
6h
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

154
L. Rong, H. Han, H. Wang, H. Jiang, S. Tu, and D. Shi
Vol 46
7.45 (2H, d, J ¼ 7.2 Hz, ArH), 7.36 (2H, d, J ¼ 8.0 Hz,
ArH), 7.26 (4H, t, J ¼ 8.8 Hz, ArH), 6.33 (2H, s, NH2), 2.78
(2H, t, J ¼ 5.2 Hz, CH2), 2.60 (2H, t, J ¼ 5.2 Hz, CH2), 2.37
(3H, s, CH3), 2.34 (3H, s, CH3), 1.63 (2H, t, J ¼ 5.2 Hz,
CH2). Anal. Calcd. For C23H23N3: C 80.90, H 6.79, N 12.31.
Found: C 80.72, H 6.73, N 12.25.
Hz, ArH), 6.41 (2H, s, NH2), 2.78 (2H, br, CH2), 2.60 (2H, t,
J ¼ 5.2 Hz, J ¼ 5.2 Hz, CH2), 1.63 (2H, t, J ¼ 5.2 Hz, J ¼
5.2 Hz, CH2). Anal. Calcd. For C21H17Cl2N3: C 65.98, H 4.48,
N 10.99. Found: C 65.72, H 4.55, N 10.68.
(E)-8-(3-Chlorobenzylidene)-4-(3-chlorophenyl)-5,6,7,8-te-
trahydroquinazolin-2-amine (4g). This compound was
obtained as yellow crystals, mp 237–238ꢀC; ir (KBr, m, cmꢁ1):
3484, 3285, 3157, 3078, 2932, 1624, 1592, 1543, 1461, 1436,
(E)-8-(4-Methoxybenzylidene)-4-(4-methoxyphenyl)-5,6,7,
8-tetrahydroquinazolin-2-amine (4b). This compound was
obtained as yellow crystals, mp 230–232ꢀC, Lit. [10d] 245–
247ꢀC; ir (KBr, m, cmꢁ1): 3482, 3377, 3202, 2934, 1606,
1579, 1538, 1509, 1447, 1406, 1356, 1333, 1298, 1247; 1H
NMR (400MHz, DMSO-d6) (d, ppm): 7.98 (1H, s, ArCH¼),
7.53 (2H, d, J ¼ 8.4 Hz, ArH), 7.42 (2H, d, J ¼ 8.4 Hz,
ArH), 7.01 (4H, dd, J ¼ 6.0 Hz, J ¼ 6.0 Hz, ArH), 6.28
(2H, s, NH2), 3.81 (3H, s, OCH3), 2.80 (3H, s, OCH3), 2.79
(2H, t, J ¼ 5.6 Hz, CH2), 2.64 (2H, t, J ¼ 5.6 Hz, CH2),
1
1411, 1351, 1334, 1268, 1219; H NMR (400MHz, DMSO-d6)
(d, ppm): 7.98 (1H, s, ArCH¼), 7.60 (1H, s, ArH), 7.38-7.54
(7H, m, ArH), 6.48 (2H, s, NH2), 2.78 (2H, t, J ¼ 5.2 Hz,
CH2), 2.61 (2H, t, J ¼ 6.0 Hz, CH2), 1.63 (2H, t, J ¼ 5.2 Hz,
CH2). Anal. Calcd. For C21H17Cl2N3: C 65.98, H 4.48, N
10.99. Found: C 65.80, H 4.50, N 10.95.
(E)-8-(3,4-Dichlorobenzylidene)-4-(3,4-dichlorophenyl)-5,6,
7,8-tetrahydroquinazolin-2-amine (4h). This compound was
obtained as yellow crystals, mp 200–202ꢀC; ir (KBr, m, cmꢁ1):
3479, 3296, 3184, 1625, 1541, 1472, 1415, 1389, 1351, 1331,
1215; 1H NMR (400MHz, DMSO-d6) (d, ppm): 7.95 (1H, s,
ArCH¼), 7.82 (1H, s, ArH), 7.74 (1H, J ¼ 8.4 Hz, ArH), 7.68
(2H, J ¼ 8.4 Hz, ArH), 7.57 (1H, J ¼ 8.4 Hz, ArH), 7.44 (1H,
J ¼ 8.4 Hz, ArH) 6.53 (2H, s, NH2), 2.77 (2H, t, J ¼ 5.2 Hz,
J ¼ 5.2 Hz, CH2), 2.61 (2H, t, J ¼ 6.0 Hz, J ¼ 6.0 Hz, CH2),
1.63 (2H, t, J ¼ 5.2 Hz, J ¼ 5.2 Hz, CH2). Anal. Calcd. For
C21H15Cl4N3: C 55.90, H 3.35, N 9.31. Found: C 55.78, H
3.34, N 9.34.
4-p-Tolyl-5,6-dihydrobenzo[h]quinazolin-2-amine (6a). This
compound was obtained as yellow crystals, mp 192–194ꢀC,
Lit. [10g] 193–194ꢀC; ir (KBr, m, cmꢁ1): 3472, 3394, 3296,
2940, 1613, 1586, 1545, 1445, 1373, 1322, 1210; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 8.18 (1H, dd, J ¼ 1.2 Hz, J
¼ 1.6 Hz, ArH), 7.48 (2H, d, J ¼ 8.0 Hz, ArH), 7.39 (2H, q,
J ¼ 6.8 Hz, J ¼ 7.2 Hz, ArH), 7.29 (3H, d, J ¼ 7.6 Hz, ArH),
6.48 (2H, s, NH2), 2.77 (4H, s, 2CH2), 2.38 (3H, s, CH3).
Anal. Calcd. For C19H17N3: C 79.41, H 5.96, N 14.62. Found:
C 79.60, H 5.89, N 14.70.
4-(4-Methoxyphenyl)-5,6-dihydrobenzo[h]quinazolin-2-
amine (6b). This compound was obtained as yellow crystals,
mp 186–187ꢀC, Lit. [10g] 182–183ꢀC; ir (KBr, m, cmꢁ1):
3467, 3287, 3178, 2940, 2830, 1609, 1578, 1547, 1510, 1453,
1405, 1374, 1322, 1302, 1277, 1251, 1214; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 8.18 (1H, dd, J ¼ 1.2 Hz, J ¼
1.6 Hz, ArH), 7.56 (2H, d, J ¼ 8.4 Hz, ArH), 7.39 (2H, q, J
¼ 6.0 Hz, J ¼ 7.2 Hz, ArH), 7.32 (1H, d, J ¼ 6.0 Hz, ArH),
7.04 (2H, d, J ¼ 8.4 Hz, ArH), 6.47 (2H, s, NH2), 3.82 (3H, s,
CH3O), 2.78 (4H, d, J ¼ 3.2 Hz, 2CH2). Anal. Calcd. For
C19H17N3O: C 75.23, H 5.65, N 13.85. Found: C 75.42, H
5.69, N 13.79.
1.62 (2H, t,
23H23N3O2: C 73.97, H 6.21, N 11.25. Found: C 73.78, H
6.27, N 11.31.
J
¼
5.2 Hz, CH2). Anal. Calcd. For
C
(E)-8-(3,4-Dimethylbenzylidene)-4-(3,4-dimethylphenyl)-
5,6,7,8-tetrahydroquinazolin-2-amine (4c). This compound
was obtained as yellow crystals, mp 191–193ꢀC; ir (KBr, m,
cmꢁ1): 3494, 3284, 3155, 2921, 1625, 1540, 1503, 1459, 1359,
1335, 1221; 1H NMR (400MHz, DMSO-d6) (d, ppm): 7.98
(1H, s, ArCH¼), 7.33 (1H, s, ArH), 7.25 (3H,m, ArH), 7.19
(2H, t, J ¼ 8.8 Hz, ArH), 6.30 (2H, s, NH2), 2.80 (2H, t, J ¼
5.2 Hz, CH2), 2.61 (2H, t, J ¼ 5.2 Hz, CH2), 2.28 (6H, s,
2CH3), 2.27 (3H, s, CH3), 2.25 (3H, s, CH3),1.61 (2H, t, J ¼
5.2 Hz, CH2). Anal. Calcd. For C25H27N3: C 81.26, H 7.37, N
11.37. Found: C 81.51, H 7.35, N 11.40.
(E)-8-(3,4-Dimethoxybenzylidene)-4-(3,4-dimethoxyphen-
yl)-5,6,7,8-tetrahydroquinazolin-2-amine (4d). This com-
pound was obtained as yellow crystals, mp 249–251ꢀC, Lit.
[10d] 231–233ꢀC; ir (KBr, m, cmꢁ1): 3484, 3280, 3154, 3074,
2936, 1619, 1541, 1459, 1260, 1234; 1H NMR (400MHz,
DMSO-d6) (d, ppm): 7.99 (1H, s, ArCH¼), 7.11–7.15 (2H, m,
ArH), 7.03 (4H, dd, J ¼ 8.0 Hz, J ¼ 8.0 Hz, ArH), 6.28 (2H,
s, NH2), 3.81 (3H, s, OCH3), 3.80 (3H, s, OCH3), 3.79 (3H, s,
OCH3), 3.77 (3H, s, OCH3), 2.84 (2H, t, J ¼ 5.2 Hz, CH2),
2.65 (2H, t, J ¼ 5.2 Hz, CH2), 1.63 (2H, t, J ¼ 5.2 Hz, CH2).
Anal. Calcd. For C25H27N3O4: C 69.27, H 6.28, N 9.69.
Found: C 69.08, H 6.35, N 9.61.
(E)-8-(4-Bromobenzylidene)-4-(4-bromophenyl)-5,6,7,8-
tetrahydroquinazolin-2-amine (4e). This compound was
obtained as yellow crystals, mp 211–213ꢀC; ir (KBr, m, cmꢁ1):
3488, 3287, 3157, 2934, 1625, 1591, 1540, 1486, 1456, 1332,
1231; 1H NMR (400MHz, DMSO-d6) (d, ppm): 7.98 (1H, s,
ArCH¼), 7.67 (2H, d, J ¼ 8.4 Hz, ArH), 7.62 (2H, d, J ¼ 8.4
Hz, ArH), 7.52 (2H, d, J ¼ 8.4 Hz, ArH), 7.41 (2H, d, J ¼
8.4 Hz, ArH), 6.45 (2H, s, NH2), 2.77 (2H, t, J ¼ 5.2 Hz,
CH2), 2.60 (2H, t, J ¼ 6.0 Hz, CH2), 1.63 (2H, t, J ¼ 5.2 Hz,
CH2). Anal. Calcd. For C21H17Br2N3: C 53.53, H 3.64, N
8.92. Found: C 53.33, H 3.62, N 8.96.
(E)-8-(4-Chlorobenzylidene)-4-(4-chlorophenyl)-5,6,7,8-te-
trahydroquinazolin-2-amine (4f). This compound was
obtained as yellow crystals, mp 195–197ꢀC, Lit. [10d] 224–
226ꢀC; ir (KBr, m, cmꢁ1): 3497, 3319, 3202, 2939, 1631,
1606, 1543, 1507, 1464, 1417, 1357, 1333, 1317, 1224; 1H
NMR (400MHz, DMSO-d6) (d, ppm): 8.01 (1H, s, ArCH¼),
7.61 (2H, dd, J ¼ 6.0 Hz, J ¼ 6.0 Hz, ArH), 7.51 (2H, dd, J
¼ 6.0 Hz, J ¼ 6.0 Hz, ArH), 7.28 (4H, q, J ¼ 8.8 Hz, J ¼ 6.4
4-(3,4-Dimethoxyphenyl)-5,6-dihydrobenzo[h]quinazolin-
2-amine (6c). This compound was obtained as yellow crystals,
mp 198–200ꢀC, Lit. [10c] 203–204ꢀC; ir (KBr, m, cmꢁ1):
3437, 3341, 3221, 2996, 2957, 1625, 1603, 1583, 1543, 1511,
1451, 1420, 1388, 1370, 1329, 1209; 1H NMR (400MHz,
DMSO-d6) (d, ppm): 8.17 (1H, dd, J ¼ 1.2 Hz, J ¼ 1.6 Hz,
ArH), 7.39 (2H, q, J ¼ 6.4 Hz, J ¼ 7.2 Hz, ArH), 7.29 (1H,
d, J ¼ 6.4 Hz, ArH), 7.18 (1H, s, ArH), 7.14 (1H, d, J ¼ 8.0
Hz, ArH), 7.05 (1H, d, J ¼ 8.0 Hz, ArH), 6.48 (2H, s, NH2),
3.82 (3H, s, CH3O), 3.79 (3H, s, CH3O), 2.82 (2H, t, J ¼ 1.6
Hz, J ¼ 4.0 Hz, CH2), 2.78 (2H, t, J ¼ 1.6 Hz, J ¼ 4.0 Hz,
CH2). Anal. Calcd. For C20H19N3O2: C 72.05, H 5.74, N
12.60. Found: C 72.21, H 5.69, N 12.71.
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An Efficient and Facile Synthesis of Pyrimidine and Quinazoline Derivatives
via One-Pot Three-Component Reaction under Solvent-Free Conditions
155
(2H, J ¼ 8.0 Hz, ArH), 6.51 (2H, s, NH2), 3.12 (2H, d, J ¼
7.2 Hz, CH2), 3.04 (2H, d, J ¼ 4.0 Hz, CH2), 2.37 (3H, s,
CH3), 2.33 (3H, s, CH3). Anal. Calcd. For C22H21N3: C 80.70,
H 6.46, N 12.83. Found: C 80.86, H 6.48, N 12.80.
4-(4-Fluorophenyl)-5,6-dihydrobenzo[h]quinazolin-2-amine
(6d). This compound was obtained as yellow crystals, mp
194–196ꢀC; ir (KBr, m, cmꢁ1): 3489, 3302, 3175, 2946, 1627,
1604, 1553, 1499, 1452, 1413, 1398, 1373, 1321, 1297, 1222;
1H NMR (400MHz, DMSO-d6) (d, ppm): 8.18 (1H, dd, J ¼
1.2 Hz, J ¼ 1.6 Hz, ArH), 7.64 (2H, dd, J ¼ 5.6 Hz, J ¼ 5.6
Hz, ArH), 7.40 (2H, q, J ¼ 7.2 Hz, J ¼ 8.0 Hz, ArH), 7.30
(3H, dd, J ¼ 5.6 Hz, J ¼ 8.0 Hz, ArH), 6.53 (2H, s, NH2),
2.77 (4H, s, 2CH2). Anal. Calcd. For C18H14FN3: C 74.21, H
4.84, N 14.42. Found: C 74.35, H 4.82, N 14.46.
4-(4-Bromophenyl)-5,6-dihydrobenzo[h]quinazolin-2-amine
(6e). This compound was obtained as yellow crystals, mp
228–230ꢀC; ir (KBr, m, cmꢁ1): 3385, 3319, 3216, 2942, 1634,
1589, 1569, 1541, 1487, 1450, 1413, 1390, 1371, 1322, 1211;
1H NMR (400MHz, DMSO-d6) (d, ppm): 8.18 (1H, dd, J ¼
1.2 Hz, J ¼ 1.6 Hz, ArH), 7.69 (2H, d, J ¼ 8.4 Hz, ArH),
7.55 (2H, d, J ¼ 8.4 Hz, ArH), 7.40 (2H, q, J ¼ 6.8 Hz, J ¼
8.4 Hz, ArH), 7.30 (1H, d, J ¼ 6.8 Hz, ArH), 6.56 (2H, s,
NH2), 2.77 (4H, s, 2CH2). Anal. Calcd. For C18H14BrN3: C
61.38, H 4.01, N 11.93. Found: C 61.50, H 4.03, N 11.90.
4-(4-Chlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2-amine
(6f). This compound was obtained as yellow crystals, mp 216–
218ꢀC, Lit. [10g] 222–223ꢀC; ir (KBr, m, cmꢁ1): 3391, 3327,
3221, 2942, 1638, 1597, 1586, 1572, 1543, 1492, 1458, 1412,
1394, 1372, 1323, 1212; 1H NMR (400MHz, DMSO-d6) (d,
ppm): 8.18 (1H, dd, J ¼ 1.2 Hz, J ¼ 1.6 Hz, ArH), 7.62 (2H,
d, J ¼ 8.4 Hz, ArH), 7.55 (2H, d, J ¼ 8.4 Hz, ArH), 7.40
(2H, q, J ¼ 6.0 Hz, J ¼ 8.4 Hz, ArH), 7.30 (1H, d, J ¼ 6.4
Hz, ArH), 6.56 (2H, s, NH2), 2.77 (4H, s, 2CH2). Anal. Calcd.
For C18H14ClN3: C 70.24, H 4.58, N 13.65. Found: C 70.43,
H 4.50, N 13.58.
4-(3,4-Dichlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2-
amine (6g). This compound was obtained as yellow crystals,
mp 210–212ꢀC, Lit. [10c] 221–223ꢀC; ir (KBr, m, cmꢁ1):
3485, 3297, 3183, 2934, 1622, 1564, 1544, 1492, 1470, 1450,
1410, 1386, 1365, 1350, 1317, 1298, 1247, 1212; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 8.18 (1H, d, J ¼ 7.2 Hz,
ArH), 7.84 (1H, d, J ¼ 2.0 Hz, ArH), 7.56 (1H, d, J ¼ 8.4
Hz, ArH), 7.58 (1H, dd, J ¼ 2.0 Hz, J ¼ 2.0 Hz, ArH), 7.40
(2H, q, J ¼ 7.2 Hz, J ¼ 8.0 Hz, ArH), 7.30 (1H, d, J ¼ 7.2
Hz, ArH), 6.63 (2H, s, NH2), 2.78 (4H, s, CH2). Anal. Calcd.
For C18H13Cl2N3: C 63.17, H 3.83, N 12.28. Found: C 63.40,
H 3.76, N 12.21.
4-Phenyl-5,6-dihydrobenzo[h]quinazolin-2-amine (6h). This
compound was obtained as yellow crystals, mp 164–165ꢀC,
Lit. [10h] 174–175ꢀC; ir (KBr, m, cmꢁ1): 3387, 3321, 3214,
2936, 1634, 1606, 1585, 1544, 1495, 1451, 1440, 1411, 1373,
1384, 1322, 1208; 1H NMR (400MHz, DMSO-d6) (d, ppm):
8.18 (1H, dd, J ¼ 1.2 Hz, J ¼ 1.6 Hz, ArH), 7.57 (2H, dd, J
¼ 1.6 Hz, J ¼ 2.0 Hz, ArH), 7.47-7.52 (3H, m, ArH), 7.40
(2H, q, J ¼ 5.6 Hz, J ¼ 7.6 Hz, ArH), 7.30 (1H, d, J ¼ 7.6
Hz, ArH), 6.51 (2H, s, NH2), 2.77 (4H, s, CH2). Anal. Calcd.
For C18H15N3: C 79.10, H 5.53, N 15.37. Found: C 79.33, H
5.48, N 15.25.
(E)-7-(4-Methoxybenzylidene)-4-(4-methoxyphenyl)-6,7-
dihydro-5H-cyclopenta[d]pyrimidin-2-amine (8b). This com-
pound was obtained as yellow crystals, mp 256–258ꢀC; ir
(KBr, m, cmꢁ1): 3475, 3370, 3217, 2934, 1624, 1606, 1582,
1542, 1510, 1460, 1440, 1399, 1366, 1308, 1248, 1220; 1H
NMR (400MHz, DMSO-d6) (d, ppm): 7.94 (2H, d, J ¼ 8.8
Hz, ArH), 7.53 (2H, d, J ¼ 8.8 Hz, ArH), 7.39 (1H, s,
ArCH¼), 7.07 (2H, d, J ¼ 8.8 Hz, ArH), 7.02 (2H, d, J ¼ 8.8
Hz, ArH), 6.42 (2H, s, NH2), 3.83 (3H, s, CH3O), 3.80 (3H, s,
CH3O), 3.17 (2H, t, J ¼ 6.4 Hz, CH2), 3.06 (2H, t, J ¼ 6.4
Hz, CH2). Anal. Calcd. For C22H21N3O2: C 73.52, H 5.89, N
11.69. Found: C 73.38, H 5.91, N 11.73.
(E)-7-(4-fluorobenzylidene)-4-(4-fluorophenyl)-6,7-dihy-
dro-5H-cyclopenta[d]pyrimidin-2-amine (8c). This com-
pound was obtained as yellow crystals, mp 187–189ꢀC; ir
(KBr, m, cmꢁ1): 3485, 3337, 3239, 3064, 2934, 1624, 1615,
1582, 1542, 1509, 1459, 1440, 1316, 1248, 1227; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 8.01(2H, dd, J ¼ 5.6 Hz, J ¼
5.6 Hz, ArH), 7.63 (2H, dd, J ¼ 5.6 Hz, J ¼ 5.6 Hz, ArH),
7.43 (1H, s, ArCH¼), 7.35 (2H, t, J ¼ 8.8 Hz, ArH), 7.27
(2H, t, J ¼ 8.8 Hz, ArH), 6.57 (2H, s, NH2), 3.15 (2H, d, J ¼
7.2 Hz, CH2), 3.08 (2H, t, J ¼ 4.4 Hz, J ¼ 4.4 Hz, CH2).
Anal. Calcd. For C20H15F2N3: C 71.63, H 4.51, N 12.53.
Found: C 71.47, H 4.53, N 12.48.
(E)-7-(4-Chlorobenzylidene)-4-(4-chlorophenyl)-6,7-dihy-
dro-5H-cyclopenta[d]pyrimidin-2-amine (8d). This com-
pound was obtained as yellow crystals, mp 165–167ꢀC; ir
(KBr, m, cmꢁ1): 3483, 3323, 3192, 2928, 1672, 1623, 1594,
1544, 1492, 1460, 1407, 1361, 1295, 1225; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 7.97 (2H, d, J ¼ 8.8 Hz,
ArH), 7.62 (2H, d, J ¼ 8.8 Hz, ArH), 7.58 (1H, s, ArCH¼),
7.50 (2H, d, J ¼ 8.8 Hz, ArH), 7.42 (2H, t, J ¼ 8.8 Hz, ArH),
6.63 (2H, s, NH2), 3.16 (2H, d, J ¼ 6.8 Hz, CH2), 3.09 (2H, t,
J ¼ 6.8 Hz, CH2). Anal. Calcd. For C20H15Cl2N3: C 65.23, H
4.11, N 11.41. Found: C 65.48, H 4.13, N 11.37.
(E)-7-(3-Chlorobenzylidene)-4-(3-chlorophenyl)-6,7-dihy-
dro-5H-cyclopenta[d]pyrimidin-2-amine (8e). This com-
pound was obtained as yellow crystals, mp 135–137ꢀC; ir
(KBr, m, cmꢁ1): 3469, 3298, 3174, 2913, 1689, 1621, 1590,
1561, 1541, 1476, 1459, 1421, 1351, 1279, 1250, 1228, 1205;
1H NMR (400MHz, DMSO-d6) (d, ppm): 8.01 (2H, d, J ¼ 7.6
Hz, ArH), 7.68 (2H, d, J ¼ 6.8 Hz, ArH), 7.61 (1H, s,
ArCH¼), 7.54 (2H, d, J ¼ 6.8 Hz, ArH), 7.40 (2H, d, J ¼ 7.6
Hz, ArH), 6.67 (2H, s, NH2), 3.18 (2H, t, J ¼ 5.6 Hz, CH2),
3.03 (2H, t, J ¼ 5.6 Hz, CH2). Anal. Calcd. For C20H15Cl2N3:
C 65.23, H 4.11, N 11.41. Found: C 65.48, H 4.13, N 11.37.
(E)-7-(4-Bromobenzylidene)-4-(4-bromophenyl)-6,7-dihy-
dro-5H-cyclopenta[d]pyrimidin-2-amine (8f). This compound
was obtained as yellow crystals, mp 180–182ꢀC; ir (KBr, m,
cmꢁ1): 3454, 3293, 3170, 2956, 1672, 1620, 1588, 1488, 1459,
1403, 1351, 1176; 1H NMR (400MHz, DMSO-d6) (d, ppm):
7.95 (2H, d, J ¼ 8.8 Hz, ArH), 7.70 (2H, d, J ¼ 8.8 Hz,
ArH), 7.66 (1H, s, ArCH¼), 7.59 (2H, d, J ¼ 8.8 Hz, ArH),
7.42 (2H, d, J ¼ 8.8 Hz, ArH), 6.98 (2H, s, NH2), 3.09 (2H, t,
J ¼ 5.6 Hz, CH2), 2.88 (2H, t, J ¼ 5.6 Hz, CH2). Anal. Calcd.
For C20H15Br2N3: C 52.54, H 3.31, N 9.19. Found: C 52.67, H
3.34, N 9.15.
(E)-7-(4-Methylbenzylidene)-4-p-tolyl-6,7-dihydro-5H-cyc-
lopenta[d]pyrimidin-2-amine (8a). This compound was
obtained as yellow crystals, mp 229–230ꢀC; ir (KBr, m, cmꢁ1):
3474, 3313, 3184, 2916, 1624, 1549, 1510, 1455, 1413, 1361,
1224, 1202; 1H NMR (400MHz, DMSO-d6) (d, ppm): 7.84
(2H, d, J ¼ 8.0 Hz, ArH), 7.45 (2H, d, J ¼ 8.0 Hz, ArH),
7.41 (1H, s, ArCH¼), 7.31 (2H, d, J ¼ 8.0 Hz, ArH), 7.24
Journal of Heterocyclic Chemistry
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L. Rong, H. Han, H. Wang, H. Jiang, S. Tu, and D. Shi
Vol 46
d, J ¼ 7.6 Hz, ArH), 7.76 (2H, d, J ¼ 8.4 Hz, ArH), 7.69
(1H, d, J ¼ 7.6 Hz, ArH), 7.56 (1H, t, J ¼ 7.2 Hz, J ¼ 7.2
Hz, ArH), 7.50 (1H, t, J ¼ 7.2 Hz, J ¼ 7.2 Hz, ArH), 6.73
(2H, s, NH2), 4.13 (2H, s, CH2). Anal. Calcd. For
C17H12BrN3: C 60.37, H 3.58, N 12.42. Found: C 60.49, H
3.51, N 12.33.
4-(3,4-Dichlorophenyl)-5H-indeno[1,2-d]pyrimidin-2-amine
(10g). This compound was obtained as yellow crystals, mp
232–233ꢀC; ir (KBr, m, cmꢁ1): 3481, 3316, 3185, 2903, 1646,
1613, 1592, 1558, 1487, 1469, 1408, 1375, 1361, 1286, 1260,
1245, 1203; 1H NMR (400MHz, DMSO-d6) (d, ppm): 8.33
(1H, d, J ¼ 1.6 Hz, ArH), 8.09 (1H, dd, J ¼ 1.6 Hz, J ¼ 2.0
Hz, ArH), 7.93 (1H, d, J ¼ 7.6 Hz, ArH), 7.81 (1H, d, J ¼
7.6 Hz, ArH), 7.70 (1H, d, J ¼ 7.6 Hz, ArH), 7.56 (1H, t, J ¼
7.6 Hz, ArH), 7.52 (1H, t, J ¼ 7.6 Hz, ArH), 6.80 (2H, s,
NH2), 4.16 (2H, s, CH2). Anal. Calcd. For C17H11Cl2N3: C
62.21, H 3.38, N 12.80. Found: C 62.35, H 3.36, N 12.77.
4-p-Tolyl-5H-indeno[1,2-d]pyrimidin-2-amine (10a). This
compound was obtained as yellow crystals, mp 199–200ꢀC; ir
(KBr, m, cmꢁ1): 3480, 3305, 3177, 2898, 1625, 1586, 1561,
1509, 1483, 1465, 1452, 1413, 1398, 1369, 1308, 1251; 1H
NMR (400MHz, DMSO-d6) (d, ppm): 8.02 (2H, d, J ¼ 8.0
Hz, ArH), 7.91 (1H, d, J ¼ 7.6 Hz, ArH), 7.68 (1H, d, J ¼
7.2 Hz, ArH), 7.54 (1H, t, J ¼ 7.2 Hz, ArH), 7.48 (1H, t, J ¼
7.2 Hz, ArH), 7.36 (2H, J ¼ 8.0 Hz, ArH), 6.64 (2H, s, NH2),
4.12 (2H, s, CH2), 2.40 (3H, s, CH3). Anal. Calcd. For
C18H15N3: C 79.10, H 5.53, N 15.37. Found: C 79.35, H 5.51,
N 15.31.
4-(4-Methoxyphenyl)-5H-indeno[1,2-d]pyrimidin-2-amine
(10b). This compound was obtained as yellow crystals, mp
206–208ꢀC, Lit. [10f] 240–241ꢀC; ir (KBr, m, cmꢁ1): 3312,
3178, 2887, 1643, 1608, 1591, 1567, 1533, 1510, 1481, 1466,
1438, 1422, 1395, 1370, 1301, 1255, 1209; 1H NMR
(400MHz, DMSO-d6) (d, ppm): 8.11 (2H, d, J ¼ 8.8 Hz,
ArH), 7.94 (1H, d, J ¼ 7.6 Hz, ArH), 7.68 (1H, d, J ¼ 7.2
Hz, ArH), 7.54 (1H, t, J ¼ 7.2 Hz, ArH), 7.48 (1H, t, J ¼ 7.2
Hz, ArH), 7.11 (2H, J ¼ 8.0 Hz, ArH), 6.60 (2H, s, NH2),
4.12 (2H, s, CH2), 3.85 (3H, s, CH3O). Anal. Calcd. For
C18H15N3O: C 74.72, H 5.23, N 14.52. Found: C 74.58, H
5.30, N 14.61.
Acknowledgments. This work was supported by the Natural
Science Foundation of Jiangsu Education Department (No.
08KJB150017), Natural Science Foundation (06XLA09) of Xuz-
hou Normal University and PeiYu Foundation of Xuzhou Normal
University (07PYL06).
4-(3,4-Dimethoxyphenyl)-5H-indeno[1,2-d]pyrimidin-2-amine
(10c). This compound was obtained as yellow crystals, mp
271–273ꢀC; ir (KBr, m, cmꢁ1): 3405, 3310, 3189, 2962, 2935,
1640, 1604, 1542, 1511, 1484, 1463, 1449, 1423, 1401, 1378,
1326, 1250, 1235, 1211; 1H NMR (400MHz, DMSO-d6) (d,
ppm): 7.91 (1H, d, J ¼ 7.6 Hz, ArH), 7.68–7.72 (3H, m,
ArH), 7.49–7.54 (2H, m, ArH), 7.12 (1H, d, J ¼ 8.0 Hz,
ArH), 6.60 (2H, s, NH2), 4.15 (2H, s, CH2), 3.88 (3H, s,
CH3O), 3.85 (3H, s, CH3O). Anal. Calcd. For C19H17N3O2: C
71.46, H 5.37, N 13.16. Found: C 71.70, H 5.35, N 13.22.
4-(4-Fluorophenyl)-5H-indeno[1,2-d]pyrimidin-2-amine
(10d). This compound was obtained as yellow crystals, mp
225–227ꢀC; ir (KBr, m, cmꢁ1): 3482, 3306, 3176, 2890, 1632,
1588, 1566, 1509, 1488, 1463, 1449, 1419, 1394, 1372, 1300,
1279, 1253, 1222; 1H NMR (400MHz, DMSO-d6) (d, ppm):
8.17 (2H, dd, J ¼ 5.6 Hz, J ¼ 5.6 Hz, ArH), 7.92 (1H, d, J ¼
7.2 Hz, ArH), 7.68 (1H, d, J ¼ 7.2 Hz, ArH), 7.54 (1H, t, J ¼
7.2 Hz, ArH), 7.49 (1H, t, J ¼ 7.2 Hz, ArH), 7.38 (2H, t, J ¼
8.8 Hz, ArH), 6.70 (2H, s, NH2), 4.13 (2H, s, CH2). Anal.
Calcd. For C17H12FN3: C 73.63, H 4.36, N 15.15. Found: C
73.78, H 4.34, N 15.18.
4-(4-Chlorophenyl)-5H-indeno[1,2-d]pyrimidin-2-amine
(10e). This compound was obtained as yellow crystals, mp
237–238ꢀC, Lit. [10f] 245–246ꢀC; ir (KBr, m, cmꢁ1): 3454,
3302, 3181, 1635, 1592, 1581, 1565, 1545, 1485, 1468, 1453,
1413, 1391, 1369, 1301, 1250, 1212; 1H NMR (400MHz,
DMSO-d6) (d, ppm): 8.14 (2H, d, J ¼ 8.8 Hz, ArH), 7.92 (1H,
d, J ¼ 7.2 Hz, ArH), 7.69 (1H, d, J ¼ 7.2 Hz, ArH), 7.62
(2H, d, J ¼ 8.4 Hz, ArH), 7.56 (1H, t, J ¼ 7.2 Hz, ArH), 7.49
(1H, t, J ¼ 7.2 Hz, ArH), 6.72 (2H, s, NH2), 4.13 (2H, s,
CH2). Anal. Calcd. For C17H12ClN3: C 69.51, H 4.12, N
14.30. Found: C 69.69, H 4.20, N 14.21.
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