An efficient synthesis of 5,6-dihydrobenzo[h]quinazoline derivatives under solvent-free conditions

Article abstract of DOI:10.1002/jhet.318

(Chemical Equation Presented) An efficient and convenient method for the preparation of 5,6-dihydrobenzo[h]quinazoline derivatives by the multicomponent reactions of aromatic aldehydes, 3,4-dihydronaphthalen-1(2H)-one and urea or acetamidine hydrochloride

Full text of DOI:10.1002/jhet.318

358
An Efficient Synthesis of 5,6-Dihydrobenzo[h]quinazoline
Derivatives under Solvent-Free Conditions
Vol 47
Lijiu Gao, Honglou Ji, Liangce Rong,* Hongxia Han, Yanhui Shi, and
Shujiang Tu
College of Chemistry and Chemical Engineering, Xuzhou Normal University, Key Laboratory of
Biotechnology for Medicinal Plant, Xuzhou 221116, Jiangsu, People’s Republic of China
*E-mail: lcrong2005@yahoo.com
Received July 27, 2009
DOI 10.1002/jhet.318
Published online 2 March 2010 in Wiley InterScience (www.interscience.wiley.com).
An efficient and convenient method for the preparation of 5,6-dihydrobenzo[h]quinazoline derivatives
by the multicomponent reactions of aromatic aldehydes, 3,4-dihydronaphthalen-1(2H)-one and urea or
acetamidine hydrochloride, in the presence of sodium hydroxide under solvent-free conditions was
reported. This method has the advantages of excellent yields, mild reaction conditions, easy work-up,
and environmentally friendly procedure.
J. Heterocyclic Chem., 47, 358 (2010).
INTRODUCTION
dihydrobenzo[h]quinazoline derivatives under solvent-
free conditions.
The quinazoline skeleton is a very important and use-
ful scaffold in medicinal chemistry: it can be found as a
pharmacophore in a wide variety of biologically active
compounds, such as antitumors [1], antimicrobials [2],
antivirals [3,4]. Benzoquinazoline, the important con-
taining quinazoline skeleton system derivatives, is often
found in different natural alkaloids, and these com-
pounds also display specific biological activities, and
often used as asdiuretic, anticancer, anticonvulsant, and
antihypertensive agents [5–8].
RESULTS AND DISCUSSION
The synthesis process could be depicted as follows: at
first, we try to prepare 4-aryl-5,6-dihydrobenzo[h]quina-
zolin-2(1H)-one derivatives under solvent-free condi-
tions (Scheme 1). The aromatic aldehydes 1 (1 mmol),
3,4-dihydronaphthalen-1(2H)-one 2 (1 mmol) and urea 3
(1.5 mmol) were chosen as starting materials, and the
reactants were blent enough in a mortar in presence of
NaOH (0.1 g) as catalyst, then the mixture was intro-
duced into a round flask and reacted under 70ꢀC. To our
delight, the reaction could be finished about 30 min and
Recently, there was an increasing emphasis on devel-
oping new environmentally safer chemical transforma-
tions by lessening/removing the toxic waste, where by-
products from the chemical processes were avoided or
minimized making them ecologically more acceptable.
It is highly desirable to develop eco-friendly methods
for producing organic fine chemicals. One of the major
problems encountered in various chemical processes is
the use of organic solvents. Hence, the organic transfor-
mations under solvent-free conditions are attracting
increasing attentions [9–11]. Herein, we would like to
report an efficient and facile method to synthesize 5,6-
the
4-aryl-5,6-dihydrobenzo[h]quinazolin-2(1H)-one
Scheme 1
C
V
2010 HeteroCorporation

March 2010
An Efficient Synthesis of 5,6-Dihydrobenzo[h]quinazoline Derivatives under
Solvent-Free Conditions
359
Table 1
Table 2
The results of synthesis of 4-aryl-5,6-dihydrobenzo[h]quinazolin-
2(1H)-one.
The results of synthesis of 4-aryl-5,6-dihydro-2-methylbenzo[h]
quinazoline.
Entry
Ar
Product
Yields (%)
Entry
Ar1
Product
Yields (%)
1
2
3
C6H5
4-CH3C6H4
3,4-(CH3)2C6H3
3,4-(CH3O)2C6H3
4-FC6H4
4a
4b
4c
4d
4e
4f
4g
4h
4i
80
85
83
87
90
88
80
91
82
80
1
2
3
4
5
6
7
4-CH3C6H4
4-CH3OC6H4
3,4-(CH3O)2C6H3
4-FC6H4
3-ClC6H4
4-ClC6H4
3,4-Cl2C6H3
6a
6b
6c
6d
6e
6f
78
80
76
85
79
89
88
4
5
6
7
4-BrC6H4
2-ClC6H4
6g
8
4-ClC6H4
2,4-Cl2C6H3
3,4-Cl2C6H3
9
10
4j
dronaphthalen-1(2H)-one, and urea or acetamidine
hydrochloride under solvent-free conditions. The mild
reaction conditions, short reaction times, good to high
yields, low cost, easy preparation, easy handling, and
reusability of catalyst are the advantages of this method.
derivatives could be gained with excellent yields. The
result of reaction is shown in Table 1. From Table 1 we
could see the reaction was carried out smoothly and a
series of 4-aryl-5,6-dihydrobenzo[h]quinazolin-2(1H)-
one derivatives were obtained ignoring the properties of
substitute groups on the aromatic aldehydes. So, we
could say that substitute groups on the aromatic alde-
hydes do not affect this reaction. In addition, in this
reaction the catalyst NaOH was necessary.
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. X-ray
diffractions were recorded on a Siemens P4 or Simart-1000
diffractometer. HRMS spectra were obtained with a Bruker
micrOTOF-Q 134 instrument.
General procedure for the synthesis of 5,6-dihydroben-
zo[h]quinazoline derivatives. The mixture of aromatic alde-
hydes 1 (1 mmol), 3,4-dihydronaphthalen-1(2H)-one 2 (1
mmol), urea 3 (1.5 mmol) or acetamidine hydrochloride 5 (1.5
mmol), and NaOH (0.1 g) was put in a reaction flask, and the
reagents were reacted at 70ꢀC about 30 min. When the reac-
tions were completed, the reaction mixture was poured into
water (0.5% HCl), and then washed with water thoroughly.
The product was filtered, dried, and recrystallized from 95%
ethanol.
To extend this reaction to prepare more benzo[h]qui-
nazoline derivatives, we replaced urea by acetamidine
hydrochloride to react with aromatic aldehydes 1 and
3,4-dihydronaphthalen-1(2H)-one 2 under similar condi-
tion (Scheme 2), and we found that other benzo[h]quina-
zoline derivatives, 4-aryl-5,6-dihydro-2-methylbenzo[h]-
quinazoline could be gained with good yields. The result
of reaction was listed in Table 2. In this reaction, we
thought that two functions were played by NaOH, one it
was used as catalyst to promote the reaction, and the
another it reacted with acetamidine hydrochloride to
release acetamidine.
1
The structures of 4 and 6 were characterized by H
NMR, IR, and HRMS spectra, and the structures of 6d
[12] was additionally confirmed by X-ray diffraction
analysis. The crystal structure of is shown in Figure 1.
In conclusion, we have developed an efficient and
facile process to synthesize a variety of 4-aryl-5,6-dihy-
drobenzo[h]quinazolin-2(1H)-one and 4-aryl-5,6-dihy-
dro-2-methylbenzo[h] quinazoline derivatives via one-
pot reaction of different aromatic aldehydes, 3,4-dihy-
5,6-Dihydro-4-phenylbenzo[h]quinazolin-2(1H)-one (4a). m.p.
251–253ꢀC; IR (KBr, n, cmꢁ1): 3327, 3232, 3089, 3019, 2943,
2890, 2830, 1689, 1550, 1488, 1454, 1431, 1366, 1342, 1319,
1298, 1279, 1262, 1228, 1191, 1180, 1162, 1122, 1072, 1046,
1026, 981, 943, 895, 826, 770, 723, 700, 656, 638, 608, 595
1
cmꢁ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 2.59 (2H, t,
J ¼ 7.6 Hz, J ¼ 7.6 Hz, CH2), 2.69 (2H, t, J ¼ 7.2 Hz, J ¼
7.2 Hz, CH2), 7.15 (1H, d, J ¼ 6.4 Hz, ArH), 7.20 (2H, t, J ¼
5.2 Hz, J ¼ 5.4 Hz, ArH), 7.32–7.38 (4H, m, ArH), 7.58 (1H,
d, J ¼ 6.8 Hz, ArH), 8.57 (1H, br, ArH), 11.95 (1H, s, NH);
HRMS m/z calculated for C18H14N2O [MþH]: 275.1184,
found: 275.1185.
Scheme 2
5,6-Dihydro-4-p-tolylbenzo[h]quinazolin-2(1H)-one (4b). m.p.
243–244ꢀC; IR (KBr, n, cmꢁ1): 3462, 3275, 3062, 3000, 2909,
2859, 1667, 1595, 1509, 1465, 1427, 1375, 1323, 1231, 1150,
1
1091, 1064, 824, 759, 733 cmꢁ1; H NMR (400 MHz, DMSO-
d6) (d, ppm): 2.39 (3H, s, CH3), 2.67 (2H, t, J ¼ 6.0 Hz, J ¼
7.6 Hz, CH2), 2.80 (2H, t, J ¼ 6.4 Hz, J ¼ 7.2 Hz, CH2), 7.37
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

360
L. Gao, H. Ji, L. Rong, H. Han, Y. Shi, and S. Tu
Vol 47
Figure 1. Structure of compound 6d.
(3H, t, J ¼ 6.8 Hz, J ¼ 7.6 Hz, ArH), 7.41 (1H, t, J ¼ 7.2
Hz, J ¼ 7.2 Hz, ArH), 7.49 (3H, t, J ¼ 5.6 Hz, J ¼ 7.6 Hz,
ArH), 8.18 (1H, J ¼ 7.6 Hz, ArH), 11.84 (1H, s, NH); HRMS
m/z calculated for C19H16N2O [MþH]: 289.1341, found:
289.1342.
s, NH); HRMS m/z calculated for C18H13FN2O [MþH]:
293.1090, found: 293.1089.
4-(4-Bromophenyl)-5,6-dihydrobenzo[h]quinazolin-2(1H)-one
(4f). m.p. 252–256ꢀC; IR (KBr, m, cmꢁ1): 3305, 3087, 2936,
2819, 1643, 1465, 1429, 1372, 1182, 1010,836,738 cmꢁ1; 2.68
(2H, t, J ¼ 6.4 Hz, J ¼ 6.4 Hz, CH2), 2.81 (2H, t, J ¼ 6.4
Hz, J ¼ 6.4 Hz, CH2), 7.34 (1H, d, J ¼ 7.8 Hz, ArH), 7.41
(1H, t, J ¼ 7.2 Hz, J ¼ 7.2 Hz, ArH), 7.49 (1H, t, J ¼ 7.2
Hz, J ¼ 7.2 Hz, ArH), 7.55 (2H, d, J ¼ 7.8 Hz, ArH), 7.74
(2H, d, J ¼ 8.0 Hz, ArH), 8.18 (1H, d, J ¼ 7.2 Hz, ArH),
1.91 (1H, s, NH); HRMS m/z calculated for C18H13BrN2O
[MþH]: 353.0290, found: 353.0278.
5,6-Dihydro-4-(3,4-dimethylphenyl)benzo[h]quinazolin-2(1H)-
one (4c). m.p. 277–279ꢀC; IR (KBr, m, cmꢁ1): 3330, 3229,
3090, 3001, 2931, 2886, 2831, 1687, 1488, 1454, 1384, 1362,
1314, 1297, 1278, 1261, 1230, 1204, 1178, 1158, 1124, 1090,
1
1047, 1026, 998, 942, 891, 773, 735, 725, 639, 608 cmꢁ1; H
NMR (400 MHz, DMSO-d6) (d, ppm): 2.19 (3H, s, CH3), 2.20
(3H, s, CH3), 2.58 (2H, t, J ¼ 7.2 Hz, J ¼ 8.0 Hz, CH2), 2.68
(2H, t, J ¼ 7.2 Hz, J ¼ 8.0 Hz, CH2), 7.03 (1H, d, J ¼ 7.6
Hz, ArH), 7.09 (1H, d, J ¼ 8.6 Hz, ArH), 7.16–7.21 (3H, m,
ArH), 7.57 (1H, d, J ¼ 6.8 Hz, ArH), 8.50 (1H, s, ArH), 11.82
(1H, s, NH); HRMS m/z calculated for C20H18N2O [MþH]:
303.1497, found: 303.1496.
4-(2-Chlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2(1H)-one
(4g). m.p. > 290ꢀC; IR (KBr, m, cmꢁ1): 3322, 3238, 3103,
2945, 2893, 2833, 1683, 1596, 1483, 1328, 1276, 1162, 1046,
;
822, 756 cmꢁ1 1H NMR (400 MHz, DMSO-d6) (d, ppm):
2.57 (2H, t, J ¼ 6.4 Hz, J ¼ 6.4 Hz, CH2), 2.69 (2H, t, J ¼
6.4 Hz, J ¼ 6.4 Hz, CH2), 7.15 (1H, s, ArH), 7.27 (2H, s,
ArH), 7.36 (2H, d, J ¼ 3.2 Hz, ArH), 7.42 (1H, s, ArH), 7.99
(2H, d, J ¼ 6.4 Hz, ArH), 11.89 (1H, s, NH); HRMS m/z cal-
culated for C18H13ClN2O [MþH]: 309.0795, found: 309.0778.
4-(4-Chlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2(1H)-one
(4h). m.p. 287–289ꢀC; IR (KBr, m, cmꢁ1): 3312, 3071, 3021,
2967, 2848, 1638, 1464, 1403, 1372, 1231, 1146, 1089, 1059,
5,6-Dihydro-4-(3,4-dimethoxyphenyl)benzo[h]quinazolin-2(1H)-
one (4d). m.p. 240–241ꢀC; IR (KBr, m, cmꢁ1): 3465, 3213,
2938, 2836, 1634, 1538, 1510, 1424, 1372, 1261, 1143, 1024,
1
853, 780, 765, 613 cmꢁ1; H NMR (400 MHz, DMSO-d6) (d,
ppm): 2.75 (2H, t, J ¼ 2.8 Hz, J ¼ 4.0 Hz, CH2), 2.80 (2H, t,
J ¼ 2.8 Hz, J ¼ 4.0 Hz, CH2), 3.82 (3H, s, OCH3), 3.83 (3H,
s, OCH3), 7.09 (1H, d, J ¼ 8.4 Hz, ArH), 7.14 (1H, d, J ¼ 8.4
Hz, ArH), 7.19 (1H, d, J ¼ 1.6 Hz, ArH), 7.33 (1H, d, J ¼
7.2 Hz, ArH), 7.40 (1H, t, J ¼ 7.2 Hz, J ¼ 7.2 Hz, ArH), 7.47
(1H, t, J ¼ 7.2 Hz, J ¼ 7.2 Hz, ArH), 8.17 (1H, d, J ¼ 7.6
Hz, ArH), 11.81 (1H, s, NH); HRMS m/z calculated for
C20H18N2O3 [MþH]: 335.1396, found: 335.1393.
888, 737 cmꢁ1 1H NMR (400 MHz, DMSO-d6) (d, ppm):
;
2.70 (2H, t, J ¼ 6.0 Hz, J ¼ 6.4 Hz, CH2), 2.82 (2H, t, J ¼
6.4 Hz, J ¼ 7.6 Hz, CH2), 7.34 (1H, d, J ¼ 7.2 Hz, ArH),
7.41 (1H, t, J ¼ 7.2 Hz, J ¼ 7.6 Hz, ArH), 7.49 (1H, t, J ¼
7.2 Hz, J ¼ 7.2 Hz, ArH), 7.62 (4H, dd, J ¼ 8.8 Hz, J ¼ 8.8
Hz, ArH), 8.18 (1H, d, J ¼ 7.6 Hz, ArH), 11.90 (1H, s, NH);
HRMS m/z calculated for C18H13ClN2O [MþH]: 309.0795,
found: 309.0791.
4-(2,4-Dichlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2(1H)-
one (4i). m.p. 286–288ꢀC; IR (KBr, m, cmꢁ1): 3411, 3043, 2935,
2836, 1635, 1466, 1429, 1376, 1316, 1150, 1100, 1046, 847, 762
cmꢁ1; 1H NMR (400 MHz, DMSO-d6) (d, ppm): 2.40 (2H, t, J ¼
6.8 Hz, J ¼ 6.8 Hz, CH2), 2.83 (2H, t, J ¼ 6.8 Hz, J ¼ 6.8 Hz,
5,6-Dihydro-4-(4-fluorophenyl)benzo[h]quinazolin-2(1H)-one
(4e). m.p. 270–273ꢀC; IR (KBr, m, cmꢁ1): 3334, 3068, 3009,
2944, 2901, 2835, 1628, 1587, 1506, 1467, 1426, 1376, 1228,
1146, 1062, 844, 762 cmꢁ1
;
1H NMR (400 MHz, DMSO-d6)
(d, ppm): 2.69 (2H, t, J ¼ 6.4 Hz, J ¼ 6.4 Hz, CH2), 2.80
(2H, t, J ¼ 6.4 Hz, J ¼ 6.4 Hz, CH2), 7.33–7.43 (4H, m,
ArH), 7.48 (1H, d, J ¼ 7.2 Hz, ArH), 7.66 (2H, t, J ¼ 5.6 Hz,
J ¼ 7.2 Hz, ArH), 8.18 (1H, d, J ¼ 7.2 Hz, ArH), 11.89 (1H,
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An Efficient Synthesis of 5,6-Dihydrobenzo[h]quinazoline Derivatives under
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361
CH2), 7.34 (1H, d, J ¼ 7.2 Hz, ArH), 7.42 (1H, t, J ¼ 7.2 Hz, J
¼ 7.6 Hz, ArH), 7.50 (1H, t, J ¼ 6.4 Hz, J ¼ 7.6 Hz, ArH),
7.58–7.64 (2H, m, ArH), 7.80 (1H, br, ArH), 8.20 (1H, d, J ¼ 7.6
Hz, ArH), 12.02 (1H, s, NH); HRMS m/z calculated for
C18H12Cl2N2O [MþH]: 343.0405, found: 343.0413.
2839, 1604, 1585, 1572, 1478, 1441, 1369, 1321, 1228, 1184,
1079, 930, 892, 786, 762, 738, 722, 697, 657, 626 cmꢁ1 1H
;
NMR (400 MHz, DMSO-d6) (d, ppm): 2.69 (3H, s, CH3), 2.84
(2H, t, J ¼ 6.4 Hz, J ¼ 7.2 Hz, CH2), 2.94 (2H, t, J ¼ 8.0
Hz, J ¼ 6.4 Hz, CH2), 7.33 (1H, d, J ¼ 7.2 Hz, ArH), 7.40–
7.48 (2H, m, ArH), 7.53–7.61 (3H, m, ArH), 7.69 (1H, s,
ArH), 8.28 (1H, d, J ¼ 7.2 Hz, ArH); HRMS m/z calculated
for C19H15ClN2 [MþH]: 307.1002, found: 307.1000.
4-(3,4-Dichlorophenyl)-5,6-dihydrobenzo[h]quinazolin-2(1H)-
one (4j). m.p. > 290ꢀC; IR (KBr, m, cmꢁ1): 3378, 3069, 2894,
2843, 2737, 1743, 1600, 1469, 1393, 1199, 1065, 873, 738
1
cmꢁ1; H NMR (400 MHz, DMSO-d6) (d, ppm): 2.72 (2H, t,
4-(4-Chlorophenyl)-5,6-dihydro-2-methylbenzo[h]quinazoline
(6f). m.p.120–121ꢀC; IR (KBr, m, cmꢁ1): 3044, 2940, 2901,
2837, 1595, 1587, 1574, 1541, 1490, 1431, 1413, 1373, 1317,
1275, 1225, 1183, 1157, 1110, 1091, 1036, 1012, 956, 919,
J ¼ 7.6 Hz, J ¼ 8.8 Hz, CH2), 2.82 (2H, t, J ¼ 7.6 Hz, J ¼
5.6 Hz, CH2), 7.35 (1H, d, J ¼ 7.6 Hz, ArH), 7.42 (1H, t, J ¼
7.2 Hz, J ¼ 7.6 Hz, ArH), 7.50 (1H, t, J ¼ 6.8 Hz, J ¼ 7.2
Hz, ArH), 7.61 (1H, d, J ¼ 7.2 Hz, ArH), 7.81 (1H, t, J ¼ 4.0
Hz, J ¼ 4.0 Hz, ArH), 7.79 (1H, s, ArH), 8.18 (1H, d, J ¼ 7.6
Hz, ArH), 11.93 (1H, s, NH); HRMS m/z calculated for
C18H12Cl2N2O [MþH]: 343.0405, found: 343.0406.
893, 874, 849, 830, 761, 732, 710, 647 cmꢁ1 1H NMR (400
;
Hz, DMSO-d6), (d, ppm): 2.51 (3H, s, CH3), 2.84 ( 2H, t, J ¼
6.4 Hz, J ¼ 7.2 Hz, CH2), 2.99 (2H, t, J ¼ 6.4 Hz, J ¼ 7.2
Hz, CH2), 7.34 ( 1H, d, J ¼ 7.2 Hz, ArH), 7.40–7.45 (2H, m,
ArH), 7.60 (2H, d, J ¼ 8.4 Hz, ArH), 7.68 (2H, d, J ¼ 8.4
Hz, ArH), 8.28 (1H, d, J ¼ 7.6 Hz, ArH); HRMS m/z calcu-
lated for C19H15ClN2 [MþH]: 307.1002, found: 307.1001.
4-(3,4-Dichlorophenyl)-5,6-dihydro-2-methylbenzo[h]quina-
zoline (6g). m.p. 98–101ꢀC; IR (KBr, m, cmꢁ1): 3084, 2939,
2899, 2836, 1603, 1586, 1540, 1470, 1431, 1411, 1363, 1315,
1222, 1183, 1133, 1021, 933, 905, 839, 763, 742, 728, 677,
5,6-Dihydro-2-methyl-4-p-tolylbenzo[h]quinazoline (6a). m.p.
104–105ꢀC; IR (KBr, m, cmꢁ1): 3029, 2941, 2896, 2834, 1605,
1585, 1539, 1429, 1410, 1376, 1318, 1227, 1185, 1157, 1115,
1
1017, 894, 837, 805, 756, 725, 651, 571 cmꢁ1; H NMR (400
MHz, DMSO-d6) (d, ppm): 2.39 (3H, s, CH3), 2.67(3H, s,
CH3), 2.81 (2H, t, J ¼ 6.4 Hz, J ¼ 7.6 Hz, CH2), 2.94 (2H, t,
J ¼ 8.0 Hz, J ¼ 6.4 Hz, CH2), 7.32 (3H, d, J ¼ 8 Hz, ArH),
7.38–7.46 (2H, m, ArH), 7.52–7.54 (2H, d, J ¼ 8.0 Hz, ArH),
8.27 (1H, d, J ¼ 6.8 Hz, ArH); HRMS m/z calculated for
C20H18N2 [MþH]: 287.1548, found: 287.1549.
641 cmꢁ1 1H NMR (400 MHz, DMSO-d6) (d, ppm): 2.69
;
(3H, s, CH3), 2.84 (2H, t, J ¼ 6.4 Hz, J ¼ 7.8 Hz, CH2), 2.95
(2H, t, J ¼ 7.6 Hz, J ¼ 6.0 Hz, CH2), 7.33 (1H, d, J ¼ 7.2
Hz, ArH), 7.39 ~ 7.48 (2H, m, ArH), 7.63 (1H, dd, J ¼ 2.0
Hz, J ¼ 1.6 Hz, ArH), 7.79 (1H, d, J ¼ 8.4 Hz, ArH), 7.89
(1H, d, J ¼ 2.0 Hz, ArH), 8.27 (1H, d, J ¼ 7.2 Hz, ArH);
HRMS m/z calculated for C19H14N2Cl2 [MþH]: 341.0612,
found: 341.0613.
5,6-Dihydro-4-(4-methoxyphenyl)-2-methylbenzo[h]quinazoline
(6b). m.p. 98–99ꢀC; IR (KBr, m, cmꢁ1): 3040, 2980, 2934,
2843, 1606, 1579, 1540, 1508, 1441, 1419, 1375, 1302, 1248,
1174, 1112, 1027, 847, 772, 759, 750, 729, 587 cmꢁ1 1H
;
NMR (400 MHz, DMSO-d6) (d, ppm): 2.67 (3H, s, CH3), 2.82
(2H, t, J ¼ 6.4 Hz, J ¼ 8.0 Hz, CH2), 2.98 (2H, t, J ¼ 7.6
Hz, J ¼6.4 Hz, CH2), 3.83 (3H, s, OCH3), 7.07 (2H, d, J ¼
8.8 Hz, ArH), 7.33 (1H, d, J ¼ 7.2 Hz, ArH), 7.38–7.47 (2H,
m, ArH), 7.62 (2H, d, J ¼ 8.4 Hz, ArH), 8.26 (1H, d, J ¼ 7.2
Hz, ArH); HRMS m/z calculated for C20H18N3O [MþH]:
303.1497, found: 303.1494.
Acknowledgments. This work was supported by the Natural
Science Foundation of Jiangsu Education Department (No.
08KJB150017), PeiYu Foundation of Xuzhou Normal University
(07PYL06), and the Qing Lan Project (No. 08QLT001).
5,6-Dihydro-4-(3,4-dimethoxyphenyl)-2-methylbenzo[h]quina-
zoline (6c). m.p. 161–163ꢀC; IR (KBr, m, cmꢁ1): 3074, 2959,
2936, 2837, 1603, 1541, 1513, 1464, 1442, 1407, 1386, 1318,
REFERENCES
1257, 1173, 1138, 1102, 877, 806, 762, 729, 680, 609 cmꢁ1
;
[1] (a) Klutchko, S. R.; Zhou, H.; Winters, R. T.; Tran, T. P.;
Bridges, A. J.; Althaus, I. W.; Amato, D. M.; Elliott, W. L.; Ellis, P.
A.; Meade, M. A.; Roberts, B. J.; Fry, D. W.; Gonzales, A. J.; Harvey,
P. J.; Nelson, J. M.; Sherwood, V.; Han, H.-K.; Pace, G.; Smaill, J. B.;
Denny, W. A.; Showalter, H. D. H. J Med Chem 2006, 49, 1475; (b)
Mazitschek, R.; Giannis, A. Curr Opin Chem Biol 2004, 8, 432.
[2] (a) Ellsworth, E. L.; Tran, T. P.; Showalter, H. D.; Sanchez,
J. P.; Watson, B. M.; Stier, M. A.; Domagala, J. M.; Gracheck, S. J.;
Joannides, E. T.; Shapiro, M. A.; Dunham, S. A.; Hanna, D. L.;
Huband, M. D.; Gage, J. W.; Bronstein, J. C.; Liu, J. Y.; Nguyen, D.
Q.; Singh, R. J Med Chem 2006, 49, 6435; (b) Kunes, J.; Bazant, J.;
Pour, M.; Waisser, K.; Slosarek, M.; Janota, J. Farmaco 2000, 55, 725.
[3] (a) Herget, T.; Freitag, M.; Morbitzer, M.; Kupfer, R.;
Stamminger, T.; Marschall, M. Antimicrob Agents Chemother 2004,
48, 4154; (b) Yang, H.; Kim, S.; Kim, M.; Reche, P. A.; Morehead, T.
J.; Damon, I. K.; Welsh, R.-M.; Reinherz, E. L. J Clin Invest 2005,
115, 379.
1H NMR (400 MHz, DMSO-d6) (d, ppm): 2.68 (3H, s, CH3),
2.83 (2H, t, J ¼ 6.4 Hz, J ¼ 7.6 Hz, CH2), 2.99 (2H, t, J ¼
7.6 Hz, J ¼ 6.4 Hz, CH2), 3.81 (3H, s, OCH3), 3.84 (3H, s,
OCH3), 7.08 (1H, d, J ¼ 8.0 Hz, ArH), 7.20 (1H, d, J ¼ 8.4
Hz, ArH), 7.24 (1H, s, ArH), 7.33 (1H, d, J ¼ 6.8 Hz, ArH),
7.39–7.47 (2H, m, ArH), 8.26 (1H, d, J ¼ 7.6 Hz, ArH);
HRMS m/z calculated for C21H20N2O2 [MþH]: 333.1603,
found: 333.1602.
4-(4-Fluorophenyl)-5,6-dihydro-2-methylbenzo[h]quinazoline
(6d). m.p. 127–128ꢀC; IR (KBr, m, cmꢁ1): 3058, 2962, 2935,
2840, 1604, 1542, 1413, 1377, 1322, 1295, 1179, 1222, 1156,
1
1099, 1012, 895, 847, 812, 759, 749, 728, 665, 576 cmꢁ1; H
NMR (400 MHz, DMSO-d6) (d, ppm): 2.68 (3H, s, CH3), 2.84
(2H, t, J ¼ 6.4 Hz, J ¼7.6 Hz, CH2), 2.95 (2H, t, J ¼ 6.4 Hz,
J ¼7.6 Hz, CH2), 7.32–7.38 (3H, m, ArH), 7.39–7.46 (2H, m,
ArH), 7.69–7.73 (2H, dd, J ¼ 5.6 Hz, J ¼ 5.6 Hz, ArH), 8.28
(1H, d, J ¼ 7.2 Hz, ArH); HRMS m/z calculated for
C19H15FN2 [MþH]: 291.1298, found: 291.1296.
[4] Vogtle, M. M.; Marzinzik, A. L. QSAR Comb Sci 2004,
23, 440.
[5] Chan, J. H.; Hong, J. S.; Kuyper, L. F.; Jones, M. L.; Bac-
canari, D. P.; Tansik, R. L.; Boytos, C. M.; Rudolph, S. K.; Brown, A.
D. J Heterocycl Chem 1997, 34, 145.
4-(3-Chlorophenyl)-5,6-dihydro-2-methylbenzo[h]quinazoline
(6e). m.p. 97–98ꢀC; IR (KBr, m, cmꢁ1): 3020, 2939, 2898,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

362
L. Gao, H. Ji, L. Rong, H. Han, Y. Shi, and S. Tu
Vol 47
[6] Connolly, D. J.; Cusack, D.; O’Sullivan, T. P.; Guiry, P. J.
[11] Liang, B.; Wang, X. T. Wang, J. X.; Du, Z. Y. Tetrahedron,
2007, 63, 1981.
Tetrahedron 2005, 61, 10153.
[7] Dempcy, R. O.; Skibo, E. B. Biochemistry 1991, 30, 8480.
[8] Connolly, D. J.; Cusack, D.; O’Sullivan, T. P.; Guiry, P. J.
Tetrahedron 2005, 61, 10153.
[12] X-ray crystallography for 5: Empirical formula C19H15FN2,
Fw ¼ 290.33, T ¼ 298(2) K, monoclinic, space group p 2(1)/c, a
ꢀ
˚
˚
˚
¼12.6454 (13) A, b ¼ 15.214 (2) A, c ¼ 7.7432 (10) A, a ¼ 90 , b ¼
ꢀ
ꢀꢀ
3
90.952(2) , c ¼ 90 , V ¼ 1489.5 (3) A , Z ¼ 4, Dc ¼ 1.295 Mg/m3,
˚
[9] (a) Tanaka,T.; Toda, F. Chem Rev 2000, 100, 1025; (b)
Cave, G. W. V.; Raston, C. L. Chem Commun 2000, 22, 2199.
[10] Babak Kaboudin, B.; Karimi, M. Bioorg Med Chem Lett
2006, 16, 5324.
ꢀ
k (MoKa) ¼ 0.71073 A, l ¼ 0.086 mmꢁ1, F(000) ¼ 608. 1.61 < y
˚
< 25.00ꢀ, R ¼ 0.0536 Rw ¼ 0.1424. S ¼ 1.118, largest diff. peak and
ꢁ3
˚
hole: 0.141 and -0.146 e. A
.
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet