A Green synthesis of pyrrolo[1,2-a]quinazolin-5(1H)-one derivatives in ionic liquids catalyzed by iodine

Article abstract of DOI:10.1002/jhet.1768

A series of 2,3,3a,4-tetrahydro-3a-methylpyrrolo[1,2-a]quinazolin-5(1H)-one derivatives were synthesized by a reaction of 2-aminobenzamide and 5-chloropentan-2-one at 80 °C catalyzed by iodine in ionic liquid of [BMIm]Br. Compared with the other methods, this novel method has the advantages of milder reaction conditions, high yields, environmental benignity, and metal-free catalyst. A series of 2,3,3a,4-tetrahydro-3a-methylpyrrolo[1,2-a]quinazolin-5(1H)-one derivatives were synthesized by a reaction of 2-aminobenzamide and 5-chloropentan-2-one at 80 °C catalyzed by iodine in ionic liquid of [BMIm]Br.

Full text of DOI:10.1002/jhet.1768

1472
A Green Synthesis of Pyrrolo[1,2-a]quinazolin-5(1H)-one Derivatives in
Vol 51
Ionic Liquids Catalyzed by Iodine
Jie-Xing Zhou, Lian Lu, Tuan-Jie Li, Chang-Sheng Yao, and Xiang-Shan Wang
a
b
b
b
b
*
aDepartment of Chemical Engineering, Huaihai Institute of Technology, Lianyungang, 222005, People’s Republic China
bSchool of Chemistry and Chemical Engineering, Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional
Materials, Jiangsu Normal University, Xuzhou Jiangsu, 221116, People’s Republic China
*
E-mail: xswang1974@yahoo.com
Received February 12, 2012
DOI 10.1002/jhet.1768
Published online 3 February 2014 in Wiley Online Library (wileyonlinelibrary.com).
O
O
R
O
NHR
N
I2
+
Cl
[BMIm]Br
NH2
N
A series of 2,3,3a,4-tetrahydro-3a-methylpyrrolo[1,2-a]quinazolin-5(1H)-one derivatives were synthesized
by a reaction of 2-aminobenzamide and 5-chloropentan-2-one at 80 ꢀC catalyzed by iodine in ionic liquid
of [BMIm]Br. Compared with the other methods, this novel method has the advantages of milder reaction
conditions, high yields, environmental benignity, and metal-free catalyst.
J. Heterocyclic Chem., 51, 1472 (2014).
INTRODUCTION
As a continuation of our research devoted to the
development of new methods for the preparation of
heterocycles in ionic liquid and with iodine-catalyzed
reaction [11], we would like to report the synthesis of
2,3,3a,4-tetrahydro-3a-methylpyrrolo [1,2-a]quinazolin-5
(1H)-one derivatives in ionic liquids. This method involves
the reaction of 2-aminobenzamides with 5-chloropentan-2-
one catalyzed by iodine.
Pyrroloquinazoline and its derivatives are important
heterocycles found in a variety of biologically molecules
with a wide range of biological activities that confer
applications as antitumor [1], modulators of chemokine
[2], and anti-inflammatory activity [3]. In addition, some
of them are used as thrombin receptor antagonists [4].
Therefore, much attention has been submitted to the synthe-
sis of these interesting heterocyclic compounds both in
organic synthetic and pharmaceutical chemistry. It was
reported that they could be achieved by the reaction of
isatoic anhydride, amine and 2-formylbenzoic acid [5],
reduction of 2-nitrobenzamide with g-ketonic acid or
halogenated ketone in the presence of SnCl2 [6], coupling
cyclization of 2-aminobenzamide with 3-butynoic acid
catalyzed by Platinum salt [7], or condensation cyclization
of 2-aminobenzamide with g-ketone acid ester [8].
Although a number of useful synthetic procedures to
prepare these compounds have been developed [5–8], still
several limitations remain, as well. For example, most of
the procedures involve several steps, low yields, metal
catalysts or in organic solvents. Thus, simple, efficient, and
green method to synthesize pyrroloquinazoline would
be attractive.
RESULTS AND DISCUSSION
Treatment of 2-aminobenzamides 1a-l and 5-chloropentan-
2-one 2 in ionic liquid of [BMIm]Br in the presence of 5 mol
% iodine at 80 ꢀC resulted in the corresponding 2,3,3a,
4-tetrahydro-3a-methylpyrrolo[1,2-a]quinazolin-5(1H)-one
derivatives 3a–l in high yields (Scheme 1).
Using the conversion of 2-aminobenzamide 1a and 5-
chloropentan-2-one 2 as a model, several parameters,
such as Lewis acids, catalyst amount, reaction temperature
and solvents, were explored as shown in Table 1. 3a was
obtained successfully in the presence of various quantities
of the catalyst, reaching a maximum of 90% yield using
5 mol% iodine as a catalyst (Table 1, entry 4). Different
imidazolium ionic liquids and Lewis acids were also tested,
and iodine-[BMIm]Br system appeared to be the best
medium for this transformation (entry 4 vs 8–16).
After reaction completion as monitored by TLC,
products were isolated by simple filtration after the
addition of a small amount of water to the cooled reaction
mixture. Water in the filtrate was removed by distillation
under reduced pressure, and the [BMIm]Br in the residue
could be reused after being evaporated at 80 ꢀC for 4 h in
vacuum. Successive reuse of the recycled ionic liquid in
Ionic liquids have attracted increasing interest in the
context of green chemistry in the past few years. They were
initially introduced as alternative green reaction media
because of their unique chemical and physical properties
of non-volatility, non-flammability, thermal stability, and
controlled miscibility [9]. The possibility of recycling them
and the low vapor frame also ensure their utility in environ-
mentally friendly technologies for a large number of
organic transformations [10].
© 2014 HeteroCorporation

September 2014
A Green Synthesis of Pyrrolo[1,2-a]quinazolin-5(1H)-one Derivatives in Ionic
1473
Liquids Catalyzed by Iodine
Table 2
Scheme 1. The reaction of 2-aminobenzamide and 5-chloropentan-2-one.
The reaction time and yields of the products 3aÀl.
O
O
R
O
NHR
Entry
R
Time/h
Product
Yields /%
N
I2
+
Cl
[BMIm]Br
NH2
1
2
3
4
5
6
7
8
H
6
8
8
8
7
7
6
6
8
8
6
6
3a
3b
3c
3d
3e
3f
3g
3h
3i
90
92
89
86
92
90
86
86
90
86
90
88
N
4-MeC6H4
4-MeOC6H4
4-FC6H4
Piperonylethyl
C6H5
C6H5CH2
4-MeOC6H4CH2
4-i-PrC6H4
3-Cl-4-FC6H3
Furan-2-ylmethyl
C6H5CH2CH2
1a-l
2
3a-l
Table 1
Synthetic results of 3a under different reaction conditionsa.
9
10
11
12
3j
3k
3l
Cat.
(mol %)
Yield
Entry
Temp/ꢀC
Ionic liquidb
(%)c
aReaction condition: 2-aminobenzamides (2.0 mmol), 2 (0.240 g,
1
2
3
4
5
6
7
8
9
10
80
RT.
50
80
100
80
80
80
80
80
[BMIm]Br
[BMIm]Br
[BMIm]Br
[BMIm]Br
[BMIm]Br
[BMIm]Br
[BMIm]Br
[EMIm]Br
[PMIm]Br
[EMIm]
I2(0)
0
Trace
72
90
90
86
87
85
86
2.0 mmol), iodine (0.025 g, 0.1 mmol), [BMIm]Br 2.0 mL, 80 ꢀC.
I2(5)
I2(5)
I2(5)
I2(5)
I2(10)
I2(20)
I2(5)
I2(5)
I2(5)
using a Bruker-micro-TOF-Q-MS analyzer (Bruker Corporation:
Karlsruhe, DE). The 2-aminobenzamides were prepared from isa-
toic anhydride and amines according to reference [12].
General procedure for the synthesis of pyrrolo[1,2-a]
quinazolin-5(1H)-one derivatives 3.
A dry 50 mL flask
was charged with 2-aminobenzamides
1
(2.0 mmol), 5-
88
chloropentan-2-one 2 (0.240 g, 2.0 mmol), iodine (0.025 g,
0.1 mmol), and ionic liquid of [BMIm]Br (2mL). The reaction
mixture was stirred at 80ꢀC for 6–8 h, and then a small amount of
water (5mL) was added to the mixture, and the generated yellow
solid was filtered off. The water in the filtrate was removed by
distillation under reduced pressure, and the ionic liquid in the
residue could be reusable by being evaporated at 80ꢀC for 4 h at
vacuum. The crude yellow products were washed with water and
purified by recrystallization from 95% EtOH, then dried at 80ꢀC
[BF4]
[PMIm]
[BF4]
[BMIm]
11
12
80
80
I2(5)
I2(5)
87
89
[BF4]
13
14
15
80
80
80
[BMIm]Br
[BMIm]Br
[BMIm]Br
CuI(5)
ZnCl2(5)
Yb(OTf)3
(5)
Sc(OTf)3
(5)
Trace
Trace
78
16
80
[BMIm]Br
82
for 2 h under vacuum to give 3.
3a-Methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazolin-5(1H)-
one 3a: mp 167–168 ꢀC (Lit. [6] 166–167 ꢀC); 1H NMR
(CDCl3, 400 MHz): dH 1.40 (s, 3H, CH3), 2.02–2.19
(m, 4H, 2CH2), 3.43–3.57 (m, 2H, CH2), 6.47 (s, 1H, NH),
6.58 (d, J = 8.0 Hz, 1H, ArH), 6.77–6.81 (m, 1H, ArH), 7.35–
7.39 (m, 1H, ArH), 7.92 (d, J = 8.0 Hz, 1H, ArH). IR (KBr):
3166, 3040, 2971, 2877, 1658, 1606, 1504, 1488, 1476, 1455,
1436, 1389, 1365, 1341, 1313, 1210, 1189, 1164, 1146, 1123,
1035, 1007, 801, 757 cm–1. HRMS (ESI, m/z): calcd for
C12H14N2NaO [M + Na]+ 225.1004, found 225.1004.
aReaction condition: 2 mL solvent, 2-aminobenzamide (0.272 g, 2 mmol),
and 2 (0.240 g, 2.0 mmol).
bBMIm = 1-butyl-3-methylimidazolium; EMIm = 1-ethyl-3-methylimidazolium;
PMIm = 1-propyl-3-methylimidazolium.
cIsolated yields.
the model reaction gave high yields of 3a (88%) even after
the fourth cycle.
First of all, these optimized conditions were applied for
the conversion of various kinds of 2-aminobenzamides
1a-l into the corresponding pyrrolo[1,2-a]quinazolin-5
(1H)-one analogs (Table 2, entries 1–12). All the structures
of the products were characterized by H NMR, IR, and
HRMS, their data were in good agreement to the
corresponding structures.
3a-Methyl-4-(p-tolyl)-2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazolin-
1
5(1H)-one 3b: mp 177–178 ꢀC (Lit. [6] 172–174 ꢀC); H NMR
(CDCl3, 400 MHz): dH 1.55 (s, 3H, CH3), 1.63–1.68
(m, 1H, CH), 1.96–2.01 (m, 1H, CH), 2.09–2.26 (m, 2H, CH2),
2.38 (s, 3H, CH3), 3.47–3.59 (m, 2H, CH2), 6.58 (d, J = 8.0Hz,
1H, ArH), 6.79–6.83 (m, 1H, ArH), 7.15 (d, J = 7.6 Hz, 2H, ArH),
7.22 (d, J = 8.4 Hz, 2H, ArH), 7.37–7.41 (m, 1H, ArH),
7.97 ~ 7.98 (m, 1H, ArH). IR (KBr): 3083, 2931, 1655, 1602,
1508, 1484, 1468, 1456, 1386, 1346, 1326, 1290, 1264, 1235,
1221, 1211, 1194, 1154, 1140, 1093, 1078, 1035, 1015, 831, 808,
1
EXPERIMENTAL
761, 724, 715, 700 cmÀ1
. HRMS (ESI, m/z): calcd for
C19H20N2NaO [M + Na]+ 315.1473. Found 315.1488.
Melting points were determined in open capillaries and
are uncorrected. IR spectra were recorded on a Tensor 27 spectrom-
eter (Bruker Corporation: Karlsruhe, DE) in KBr pellet. 1H NMR
spectra was obtained from a solution in DMSO-d6 or CDCl3 with
Me4Si as internal standard using a Bruker-400 spectrometer (Bruker
Corporation: Karlsruhe, DE). HRMS analyses were carried out
4-(4-Methoxyphenyl)-3a-methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]
1
quinazolin-5(1H)-one 3c: mp 171–172 ꢀC (Lit. [6] 164–166 ꢀC); H
NMR (CDCl3, 400 MHz): dH 1.53 (s, 3H, CH3), 1.64–1.68
(m, 1H, CH), 1.94 ~ 1.99 (m, 1H, CH), 2.08–2.27 (m, 2H, CH2),
3.47–3.59 (m, 2H, CH2), 3.83 (s, 3H, CH3O), 6.58 (d, J=8.0Hz, 1H,
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

1474
J.-X. Zhou, L. Lu, T.-J. Li C.-S. Yao, and X.-S. Wang
Vol 51
ArH), 6.79–6.83 (m, 1H, ArH), 6.94 (d, J= 8.8 Hz, 2H, ArH), 7.19 (d,
J= 7.6 Hz, 2H, ArH), 7.37–7.41 (m, 1H, ArH), 7.96–7.98 (m, 1H,
ArH). IR (KBr): 3075, 3043, 2955, 2934, 2909, 2859, 2837, 1645,
1604, 1511, 1499, 1486, 1470, 1443, 1389, 1355, 1337, 1310, 1297,
1246, 1228, 1195, 1182, 1173, 1149, 1135, 1120, 1106, 1034, 999,
910, 849, 810, 755, 697 cmÀ1. HRMS (ESI, m/z): calcd for
C19H20N2NaO2 [M + Na]+ 331.1422, found 331.1431.
4-(4-Fluorophenyl)-3a-methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]
quinazolin-5(1H)-one 3d: mp 151–153 ꢀC (Lit. [6] 152–154 ꢀC); 1H
NMR (CDCl3, 400 MHz): dH 1.54 (s, 3H, CH3), 1.64–1.68 (m, 1H,
CH), 1.96–2.03 (m, 1H, CH), 2.11–2.24 (m, 2H, CH2), 3.48–3.60
(m, 2H, CH2), 6.59 (d, J= 8.4 Hz, 1H, ArH), 6.81–6.84 (m, 1H,
ArH), 7.09–7.13 (m, 2H, ArH), 7.23–7.25 (m, 2H, ArH), 7.38–7.42
(m, 1H, ArH), 7.97 (d, J= 7.6 Hz, 1H, ArH). IR (KBr): 3063, 3047,
2976, 2933, 2870, 1649, 1603, 1508, 1495, 1471, 1386, 1357,
1335, 1310, 1212, 1194, 1180, 1156, 1132, 1116, 1094, 1045,
1016, 995, 940, 875, 851, 825, 752, 697 cm-1. HRMS (ESI, m/z):
calcd for C18H18N2OF [M + H]+ 297.1403, found 297.1413.
4-(2-Piperonylethyl)-3a-methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]
quinazolin-5(1H)-one 3e: mp 115–116 ꢀC; 1H NMR
(CDCl3, 400MHz): dH 1.27 (s, 3H, CH3), 2.02–2.23
(m, 4H, 2CH2), 2.76–2.80 (m, 1H, CH), 3.02–3.11 (m, 2H, CH2),
3.44–3.49 (m, 2H, CH2), 3.93–3.98 (m, 1H, CH), 5.93 (s, 2H, CH2),
6.50 (d, J= 8.4 Hz, 1H, ArH), 6.70–6.74 (m, 2H, ArH), 6.76–6.81
(m, 2H, ArH), 7.33–7.37 (m, 1H, ArH), 7.94 (d, J= 8.0 Hz, 1H,
ArH). 13C NMR (CDCl3, 100MHz): dC 15.5, 15.8, 30.5, 32.5, 39.9,
41.4, 74.4, 95.6, 103.0, 104.1, 107.0, 110.1, 112.0, 116.5, 123.5,
128.1, 128.4, 138.9, 140.8, 142.4, 158.9. IR (KBr): 2963, 2940,
2923, 2902, 2847, 1635, 1607, 1499, 1480, 1446, 1402, 1382, 1356,
1328, 1313, 1255, 1185, 1167, 1143, 1117, 1101, 1044, 1005, 944,
925, 853, 819, 753, 702cmÀ1. HRMS (ESI, m/z): calcd for
C21H23N2O3 [M + H]+ 351.1709, found 351.1729.
3.77 (s, 3H, CH3O), 4.23 (d, J= 15.2 Hz, 1H, CH), 5.10 (d,
J= 15.2 Hz, 1H, CH), 6.51 (d, J= 8.0 Hz, 1H, ArH), 6.78–6.84 (m,
3H, ArH), 7.25–7.27 (m, 2H, ArH), 7.34–7.38 (m, 1H, ArH), 7.98
(d, J= 7.6 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): dC 20.7,
20.8, 37.5, 44.9, 45.9, 55.3, 79.8, 112.2, 113.8, 115.3, 117.2, 128.7,
129.2, 131.3, 133.7, 144.4, 158.6, 164.3. IR (KBr): 2974, 2929,
2909, 2850, 1635, 1606, 1585, 1511, 1484, 1472, 1431, 1395,
1372, 1353, 1321, 1309, 1288, 1248, 1185, 1166, 1144, 1122,
1109, 1029, 1004, 980, 843, 833, 819, 758 cm-1. HRMS (ESI, m/z):
calcd for C20H22N2NaO2 [M + Na]+ 345.1618, found 345.1618.
4-(4-Isopropylphenyl)-3a-methyl-2,3,3a,4-tetrahydropyrrolo
[1,2-a]quinazolin-5(1H)-one 3i: mp 146–148 ꢀC; 1H NMR
(CDCl3, 400 MHz): dH 1.26 (d, J= 6.8 Hz, 6H, 2CH3), 1.55 (s, 3H,
CH3), 1.64–1.69 (m, 1H, CH), 1.96–2.03 (m, 1H, CH), 2.09–2.13
(m, 1H, CH), 2.18–2.26 (m, 1H, CH), 2.89–2.96 (m, 1H, CH),
3.46–3.59 (m, 2H, CH2), 6.58 (d, J= 8.0 Hz, 1H, ArH), 6.79–6.83
(m, 1H, ArH), 7.18 (d, J= 7.6 Hz, 2H, ArH), 7.25–7.27 (m, 2H,
ArH), 7.37–7.41 (m, 1H, ArH), 7.80 (d, J= 8.0 Hz, 1H, ArH). 13C
NMR (CDCl3, 100 MHz): dC 21.1, 22.2, 23.9, 33.8, 38.6, 45.8,
80.2, 112.7, 116.0, 117.5, 127.2, 129.2, 129.5, 133.8, 136.5, 144.6,
148.3, 163.9. IR (KBr): 3056, 3030, 2959, 2924, 2867, 1648, 1605,
1498, 1471, 1390, 1363, 1344, 1311, 1252, 1227, 1212, 1196,
1178, 1148, 1130, 1116, 1102, 1069, 1055, 1042, 1026, 993, 944,
868, 820, 751, 699 cmÀ1. HRMS (ESI, m/z): calcd for C21H25N2O
[M + H]+ 321.1967, found 321.1981.
4-(3-Chloro-4-fluorophenyl)-3a-methyl-2,3,3a,4-tetrahydro-
pyrrolo[1,2-a]quinazolin-5(1H)-one 3j: mp 144–146 ꢀC; 1H
NMR (CDCl3, 400 MHz): dH 1.54 (s, 3H, CH3), 1.68–1.73
(m, 1H, CH), 1.95–2.07 (m, 1H, CH), 2.14–2.23 (m, 2H, CH2),
3.49–3.59 (m, 2H, CH2), 6.59 (d, J = 8.0 Hz, 1H, ArH),
6.81–6.85 (m, 1H, ArH), 7.18–7.22 (m, 2H, ArH), 7.35–7.43
(m, 2H, ArH), 7.96 (d, J = 7.6 Hz, 1H, ArH). 13C NMR
(CDCl3, 100 MHz): dC 21.1, 22.1, 38.6, 45.7, 80.2, 112.9,
115.3, 117.0, 121.3, 121.5, 129.5, 131.9, 134.3, 135.6, 144.6,
156.3, 158.7, 164.0. IR (KBr): 3061, 2971, 2869, 1649, 1608,
1500, 1471, 1397, 1377, 1359, 1311, 1287, 1259, 1213, 1183,
1149, 1137, 1126, 1060, 1029, 954, 919, 822, 751, 709,
3a-Methyl-4-phenyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]quinazo-
1
lin-5(1H)-one 3f: mp 122–124 ꢀC; H NMR (CDCl3, 400MHz):
dH 1.57 (s, 3H, CH3), 1.64–1.69 (m, 1H, CH), 1.95–2.02 (m, 1H,
CH), 2.10–2.25 (m, 2H, CH2), 3.47–3.59 (m, 2H, CH2), 6.59
(d, J = 8.0 Hz, 1H, ArH), 6.81–6.84 (m, 1H, ArH), 7.28
(d, J = 7.6 Hz, 2H, ArH), 7.35–7.44 (m, 4H, ArH), 7.98
(d, J = 7.6 Hz, 1H, ArH). 13C NMR (CDCl3, 100 MHz): dC
21.1, 22.3, 38.6, 45.7, 80.2, 112.8, 115.9, 117.6, 127.8, 128.6,
129.2, 129.5, 133.9, 139.1, 144.7, 164.0. IR (KBr): 3061,
3039, 2989, 2969, 2907, 2833, 1649, 1607, 1494, 1480, 1469,
1385, 1353, 1336, 1311, 1225, 1196, 1180, 1160, 1148, 1120,
1074, 1047, 1030, 998, 946, 849, 751, 699 cmÀ1. HRMS (ESI,
m/z): calcd for C18H19N2O [M + H]+ 279.1497, found 279.1515.
4-Benzyl-3a-methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]quina-
zolin-5(1H)-one 3g: mp 145–146 ꢀC (Lit. [6] 140–142 ꢀC); 1H
NMR (CDCl3, 400 MHz): dH 1.29 (s, 3H, CH3), 1.94–1.99
(m, 1H, CH), 2.02–2.10 (m, 2H, CH2), 2.17–2.85 (m, 1H, CH),
3.38–3.49 (m, 2H, CH2), 4.23 (d, J = 15.6 Hz, 1H, CH), 5.23
(d, J = 15.6 Hz, 1H, CH), 6.52 (d, J = 8.0 Hz, 1H, ArH), 6.79–
6.82 (m, 1H, ArH), 7.20–7.23 (m, 1H, ArH), 7.27–7.35 (m, 4H,
ArH), 7.37–7.39 (m, 1H, ArH), 7.99 (d, J = 7.6 Hz, 1H, ArH). IR
(KBr): 3069, 2969, 2924, 2852, 1634, 1606, 1499, 1483, 1470,
1454, 1432, 1396, 1372, 1352, 1321, 1310, 1292, 1274, 1187,
1165, 1155, 1142, 1121, 1076, 1064, 1038, 1028, 1005, 974,
950, 786, 755, 710, 769, 630 cmÀ1. HRMS (ESI, m/z): calcd for
C19H20N2NaO [M + Na]+ 315.1473, found 315.1500.
695 cmÀ1
. HRMS (ESI, m/z): calcd for C18H17ClFN2O
[M + H]+ 331.1013, found 331.1026.
4-(Furan-2-ylmethyl)-3a-methyl-2,3,3a,4-tetrahydropyrrolo
[1,2-a]quinazolin-5(1H)-one 3k: mp 130–131 ꢀC; 1H NMR
(CDCl3, 400 MHz): dH 1.19 (s, 3H, CH3), 2.03–2.11 (m, 1H, CH),
2.17–2.21 (m, 2H, CH2), 2.46–2.54 (m, 1H, CH), 3.40–3.51 (m,
2H, CH2), 4.54 (d, J= 15.6 Hz, 1H, CH), 4.80 (d, J= 15.6 Hz, 1H,
CH), 6.31–6.33 (m, 2H, ArH), 6.49 (d, J= 8.4 Hz, 1H, ArH), 6.75–
6.79 (m, 1H, ArH), 7.33–7.36 (m, 2H, ArH), 7.95 (d, J=7.6Hz,
1H, ArH). 13C NMR (CDCl3, 100 MHz): dC 20.6, 20.8, 37.6, 39.4,
45.0, 79.4, 108.5, 110.6, 112.3, 115.2, 117.2, 129.2, 133.7, 141.5,
144.3, 151.8, 163.9. IR (KBr): 3103, 3070, 2963, 2888, 2856,
1644, 1608, 1497, 1482, 1457, 1420, 1396, 1350, 1321, 1299,
1249, 1232, 1186, 1160, 1142, 1121, 1075, 1063, 1041, 1020,
1005, 964, 938, 877, 818, 809, 786, 773, 747, 695 cmÀ1
.
HRMS (ESI, m/z): calcd for C17H18N2NaO2 [M + Na]+
305.1266, found 305.1267.
3a-Methyl-4-phenethyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]
quinazolin-5(1H)-one 3l: mp 91–93 ꢀC; 1H NMR
(CDCl3, 400 MHz): dH 1.27 (s, 3H, CH3), 1.98–2.21 (m, 4H,
2CH2), 2.85–2.91 (m, 1H, CH), 3.07–3.13 (m, 2H, CH2), 3.41–
3.49 (m, 2H, CH2), 3.98 ~ 4.04 (m, 1H, CH), 6.50 (d, J = 8.4Hz,
1H, ArH), 6.77–6.81 (m, 1H, ArH), 7.20–7.26 (m, 1H, ArH),
7.27–7.37 (m, 5H, ArH), 7.95 (d, J = 8.0 Hz, 1H, ArH). 13C NMR
(CDCl3, 100MHz): dC 20.8, 21.2, 36.0, 37.7, 45.2, 46.5, 79.7,
4-(4-Methoxybenzyl)-3a-methyl-2,3,3a,4-tetrahydropyrrolo[1,2-a]
quinazolin-5(1 H)-one 3h: mp 155–156 ꢀC; 1H NMR (CDCl3,
400 MHz): dH 1.26 (s, 3H, CH3), 1.94–2.02 (m, 1H, CH), 2.04–2.11
(m, 2H, CH2), 2.23–2.31 (m, 1H, CH), 3.38–3.48 (m, 2H, CH2),
Journal of Heterocyclic Chemistry
DOI 10.1002/jhet

September 2014
A Green Synthesis of Pyrrolo[1,2-a]quinazolin-5(1H)-one Derivatives in Ionic
1475
Liquids Catalyzed by Iodine
112.2, 115.4, 117.2, 126.4, 128.5, 128.8, 129.0, 133.6, 139.6,
144.2, 164.2. IR (KBr): 3060, 3025, 2971, 2943, 2865, 1638,
1606, 1497, 1486, 1472, 1433, 1398, 1374, 1356, 1319, 1308,
1295, 1247, 1205, 1182, 1164, 1140, 1040, 1030, 1004, 954, 944,
848, 744, 698cmÀ1. HRMS (ESI, m/z): calcd for C20H23N2O
[M + H]+ 307.1810, found 307.1812.
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CONCLUSION
In conclusion, we found a mild and green method for
the synthesis of 2,3,3a,4-tetrahydro-3a-methylpyrrolo
[1,2-a]quinazolin-5(1H)-one derivatives via a reaction of
2-aminobenzamide and 5-chloropentan-2-one catalyzed
by iodine in ionic liquid. The features of this procedure
are mild reaction conditions, high yields, operational
simplicity and metal-free catalyst.
Acknowledgments. We are grateful to the National Natural
Science foundation of China (20802061), the Priority Academic
Program Development of Jiangsu Higher Education Institutions,
Qing Lan Project (10QLD008) of Jiangsu Education Committee
and College Industrialization Project (JHB2012-31) of Jiangsu
Province for financial support.
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Journal of Heterocyclic Chemistry
DOI 10.1002/jhet