Synthesis of quinazolines and tetrahydroquinazolines: Copper-catalyzed tandem reactions of 2-bromobenzyl bromides with aldehydes and aqueous ammonia or amines

Article abstract of DOI:10.1002/asia.201301296

An efficient synthesis of diversely substituted quinazolines and 1,2,3,4-tetrahydroquinazolines through copper-catalyzed tandem reactions of the readily available 2-bromobenzyl bromides, aldehydes, and aqueous ammonia or amines has been developed. By using ammonia and simple aliphatic amines as the nitrogen source, the present method provides a versatile and practical protocol for the synthesis of quinazolines and 1,2,3,4-tetrahydroquinazolines. Copper on the beat: An efficient, simple and economical synthesis of diversely substituted quinazolines and 1,2,3,4-tetrahydroquinazolines has been developed through copper-catalyzed tandem reactions of the readily available 2-bromobenzyl bromides, aldehydes, and aqueous ammonia or simple aliphatic amines. Copyright

Full text of DOI:10.1002/asia.201301296

Supporting Information
ꢀ
Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2014
Synthesis of Quinazolines and Tetrahydroquinazolines: Copper-Catalyzed
Tandem Reactions of 2-Bromobenzyl Bromides with Aldehydes and
Aqueous Ammonia or Amines
[
a]
Xuesen Fan,* Bin Li, Shenghai Guo, Yuanyuan Wang, and Xinying Zhang
asia_201301296_sm_miscellaneous_information.pdf

Supporting Information
Table of Contents
P2
I. General Experimental Information
P3-14
P15-34
P35-52
P53
II. Synthetic procedures and spectroscopic data
1
13
III. Copies of H and C NMR spectra of 4a-4t
1
13
IV. Copies of H and C NMR spectra of 5a-5r
1
13
V. Copies of H and C NMR spectra of 7
1
13
P54
VI. Copies of H and C NMR spectra of 8
P55
VII. References
1

I. General Experimental Information
All the commercial reagents and solvents were used without further purification. Melting points
1
13
were recorded with a micro melting point apparatus and uncorrected. H and C NMR spectra were
recorded at 400 and 100 MHz, respectively. High-resolution mass spectra (HRMS) were obtained by
using a MicrOTOF mass spectrometer. All reactions were monitored by thin-layer chromatography
(TLC) using silica gel plates (silica gel 60 F254 0.25 mm) and components were visualized by
observation under UV light (254 and 365 nm).
2

II. Synthetic procedures and spectroscopic data
General procedure for the preparation of quinazoline 4.
To a tube containing a solution of 2-bromobenzyl bromide 1 (0.5 mmol) in DMSO (2 mL) were
added aldehyde 2 (0.6 mmol), Cu(OAc)
2
(0.05 mmol), DMAP (0.15 mmol) and 26% aqueous ammonia
o
3
(1 mL). Then, the tube was sealed and the mixture was stirred at 80 C under air atmosphere for 24 h.
After being cooled to room temperature, the reaction was quenched with aqueous NH
4
Cl solution and
extracted with ethyl acetate. The combined organic layers were washed with H O and brine, and then
2
dried over anhydrous Na
2 4
SO . The solvent was evaporated under vacuum and the crude product was
purified by chromatography on silica-gel to afford quinazoline derivatives 4.
2
-Phenylquinazoline (4a): Eluent: petroleum ether-ethyl acetate (20:1);
5
8
4
4
a
a
3
6
7
N
1
1
yellow solid (71 mg, 68%), mp 101-103 °C (lit . mp 102-103 °C); H NMR
1
0
3
2
9
1
1
1
2
N
1
8
(400 MHz, CDCl
3
) δ: 7.51-7.55 (m, 3H; 11-H, 12-H and 13-H), 7.56-7.63 (m,
1
4
1
1
H; 6-H), 7.89-7.94 (m, 2H; 5-H and 7-H), 8.09 (d, J = 8.8 Hz, 1H; 8-H),
1
3
8
.61-8.64 (m, 2H; 10-H and 14-H), 9.47 (s, 1H). C NMR (100 MHz, CDCl
3
) δ: 123.6 (C-4a), 127.1
(C-5), 127.3 (C-6), 128.6 (C-10 and C-14), 128.7 (C-8, C-11 and C-13), 130.6 (C-12), 134.1 (C-7),
-1
1
38.1 (C-9), 150.8 (C-8a), 160.5 (C-4), 161.1 (C-2). IR (KBr) ν= 2921, 1601, 1532, 1396, 731 cm .
+
MS: m/z 207 (MH) .
2
-p-Tolylquinazoline (4b): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid (72 mg, 64%),
1
1
mp 106-108 °C (lit . mp 107-109 °C); H NMR (400 MHz, CDCl ) δ: 2.45 (s, 3H), 7.35 (d, J = 8.0 Hz,
3
2
H), 7.57-7.61 (m, 1H), 7.87-7.92 (m, 2H), 8.06-8.08 (m, 1H), 8.51 (d, J = 8.0 Hz, 2H), 9.45 (s, 1H).
1
3
C NMR (100 MHz, CDCl
3
) δ: 21.5, 123.5, 127.0, 127.1, 128.5, 128.6, 129.4, 134.0, 135.3, 140.9,
-1
+
1
50.8, 160.5, 161.2. IR (KBr) ν= 2920, 1588, 1551, 1379, 725 cm . MS: m/z 221 (MH) .
2
-(4-Bromophenyl)quinazoline (4c): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid
1
(
103 mg, 72%), mp 124-126 °C; H NMR (400 MHz, CDCl
3
) δ: 7.61-7.67 (m, 3H), 7.92 (t, J = 8.0 Hz,
13
2
3
H), 8.07 (d, J = 8.4 Hz, 1H), 8.50 (d, J = 8.0 Hz, 2H), 9.44 (s, 1H). C NMR (100 MHz, CDCl ) δ:
1
23.7, 125.4, 127.2, 127.5, 128.6, 130.2, 131.8, 134.3, 137.0, 150.7, 160.1, 160.6. IR (KBr) ν= 3030,
3

-
1
+
1
522, 1480, 1402, 755 cm . MS: m/z 285 (MH) . HRMS (ESI) calcd for C14
M+H], found: 285.0015.
-(4-Nitrophenyl)quinazoline (4d): Eluent: petroleum ether-ethyl acetate (10:1); yellow solid (94
2
H10BrN : 285.0027
[
2
2
1
mg, 74%), mp 217-219 °C (lit . mp 218-219 °C); H NMR (400 MHz, CDCl ) δ: 7.54 (q, J = 13.6 Hz,
3
2
H), 7.61-7.50 (m, 1H), 7.91-7.95 (m, 2H), 8.12 (d, J = 8.8 Hz, 1H), 8.62-8.64 (m, 2H), 9.49 (s, 1H).
1
3
C NMR (100 MHz, CDCl
3
) δ: 123.6, 127.2, 127.4, 128.6, 128.66, 128.69, 130.8, 134.3, 137.8, 150.7,
-1
+
1
60.5, 161.0. IR (KBr) ν= 2926, 1605, 1504, 1322, 742 cm . MS: m/z 252 (MH) .
4
-(Quinazolin-2-yl)benzonitrile (4e): Eluent: petroleum ether-ethyl acetate (10:1); yellow solid (77
1
mg, 66%), mp 193-196 °C; H NMR (400 MHz, CDCl ) δ: 7.69 (t, J = 7.6 Hz, 1H), 7.82 (d, J = 8.4 Hz,
3
1
3
2
H), 7.94-7.99 (m, 2H), 8.11 (d, J = 7.6 Hz, 1H), 8.75 (d, J = 8.4 Hz, 2H), 9.50 (s, 1H). C NMR (100
MHz, CDCl ) δ: 113.8, 118.9, 123.9, 127.2, 128.2, 128.8, 129.0, 132.4, 134.5, 142.2, 150.6, 159.1,
60.7. IR (KBr) ν= 2924, 1598, 1515, 1396, 742 cm . MS: m/z 232 (MH) . HRMS (ESI) calcd for
: 232.0874 [M+H], found: 232.0871.
3
-1
+
1
15 10 3
C H N
2
-(4-(Trifluoromethyl)phenyl)quinazoline (4f): Eluent: petroleum ether-ethyl acetate (20:1);
1
yellow solid (104 mg, 75%), mp 135-137 °C; H NMR (400 MHz, CDCl
3
) δ: 7.66 (t, J = 7.6 Hz, 1H),
7
1
1
.80 (d, J = 8.0 Hz, 2H), 7.92-7.96 (m, 2H), 8.10 (d, J = 8.4 Hz, 1H), 8.73 (d, J = 8.4 Hz, 2H), 9.48 (s,
1
3
3
H). C NMR (100 MHz, CDCl ) δ: 123.8, 125.48, 125.52, 125.56, 125.60, 127.2, 127.9, 128.8, 128.9,
-1
34.5, 141.2, 150.6, 159.6, 160.6. IR (KBr) ν= 2924, 1553, 1326, 1070, 804 cm . MS: m/z 275
+
(
MH) . HRMS (ESI) calcd for C15
H
10
F
3
N
2
: 275.0796 [M+H], found: 275.0795.
2
-m-Tolylquinazoline (4g): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid (75 mg, 67%),
1
mp 114-116°C; H NMR (400 MHz, CDCl ) δ: 2.49 (s, 3H), 7.33 (d, J = 7.2 Hz, 1H), 7.42-7.46 (m,
3
1H), 7.60 (t, J = 7.2 Hz, 1H), 7.88-7.92 (m, 2H), 8.09 (d, J = 8.0 Hz, 1H), 8.41-8.43 (m, 2H), 9.46 (d, J
1
3
=
3
1.2 Hz, 1H). C NMR (100 MHz, CDCl ) δ: 21.6, 123.6, 125.8, 127.16, 127.24, 128.6, 129.1, 131.5,
-1
1
34.1, 138.0, 138.3, 150.8, 160.5, 161.2. IR (KBr) ν= 2916, 1615, 1502, 1396, 721 cm . MS: m/z 221
+
(
MH) . HRMS (ESI) calcd for C15
H
13
N
2
: 221.1078 [M+H], found: 221.1065.
4

2
-(3-Fluorophenyl)qinazoline (4h): Eluent: petroleum ether-ethyl acetate (20:1); white solid (75
1
mg, 66%), mp 93-95 °C; H NMR (400 MHz, CDCl ) δ: 7.17-7.22 (m, 1H), 7.46-7.51 (m, 1H), 7.61 (t,
3
J = 7.2 Hz, 1H), 7.88-7.92 (m, 2H), 8.07 (d, J = 8.8 Hz, 1H), 8.32 (d, J = 8.8 Hz, 1H), 8.41 (d, J = 7.6
1
3
Hz, 1H), 9.43 (s, 1H). C NMR (100 MHz, CDCl
3
) δ: 115.3, 115.5, 117.4, 117.6, 123.7, 124.17,
1
24.21, 127.2, 127.6, 128.7, 130.0, 130.1, 134.3, 140.5, 150.6, 159.78, 159.82, 160.6, 162.1, 164.5. IR
-1
+
(
KBr) ν= 2926, 1584, 1516, 1358, 726 cm . MS: m/z 225 (MH) . HRMS (ESI) calcd for C H FN :
14 10 2
2
25.0828 [M+H], found: 225.0815.
-(3-Bromophenyl)quinazoline (4i): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid (92
2
2
1
mg, 64%), mp 153-155 °C (lit . mp 153-155 °C); H NMR (400 MHz, CDCl ) δ: 7.39 (t, J = 8.0 Hz,
3
1
8
1
H), 7.63 (t, J = 7.2 Hz, 2H), 7.91 (t, J = 7.6 Hz, 2H), 8.07 (d, J = 8.4 Hz, 1H), 8.55 (d, J = 8.0 Hz, 1H),
1
3
3
.78 (s, 1H), 9.44 (s, 1H). C NMR (100 MHz, CDCl ) δ: 123.0, 123.8, 127.1, 127.2, 127.7, 128.7,
-
1
30.2, 131.6, 133.5, 134.4, 140.1, 150.6, 159.6, 160.6. IR (KBr) ν= 3021, 1598, 1512, 1402, 761 cm .
+
MS: m/z 285 (MH) .
2
-(2-Chlorophenyl)quinazoline (4j): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid
2
1
(
3
81mg, 67%), mp 68-70 °C (lit . mp 69-70 °C); H NMR (400 MHz, CDCl ) δ: 7.51-7.56 (m, 2H), 7.62
(
t, J = 7.2 Hz, 1H), 7.90-7.95 (m, 2H), 8.10 (d, J = 8.8 Hz, 1H), 8.62 (d, J = 6.8 Hz, 2H), 9.48 (s, 1H).
1
3
3
C NMR (100 MHz, CDCl ) δ: 123.6, 127.1, 127.3, 128.6, 128.7, 128.9, 130.6, 134.1, 138.0, 150.8,
-1
+
1
60.5, 161.1. IR (KBr) ν= 2924, 1608, 1504, 12884, 745 cm . MS: m/z 241 (MH) .
2
-(2-Bromophenyl)quinazoline (4k): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid (76
1
mg, 53%), mp 72-74 °C; H NMR (400 MHz, CDCl
3
) δ: 7.51-7.56 (m, 2H), 7.59 (t, J = 7.6 Hz, 1H),
1
3
7
.89 (t, J = 8.4 Hz, 2H), 8.08 (d, J = 8.4 Hz, 1H), 8.62 (d, J = 8.4 Hz, 2H), 9.45 (s, 1H). C NMR (100
3
MHz, CDCl ) δ: 123.6, 127.2, 127.3, 128.60, 128.64, 128.7, 130.6, 134.2, 138.0, 150.8, 160.5, 161.1.
-1
+
IR (KBr) ν= 3062, 1550, 1485, 1402, 772 cm . MS: m/z 285 (MH) . HRMS (ESI) calcd for
14 2
C H10BrN
: 285.0027 [M+H], found: 285.0022.
2
-(2-Nitrophenyl)quinazoline (4l): Eluent: petroleum ether-ethyl acetate (10:1); yellow solid (91
1
mg, 72%), mp 93-95 °C; H NMR (400 MHz, CDCl
3
) δ: 7.51-7.56 (m, 2H), 7.60-7.64 (m, 1H), 7.89-
5

1
3
7
1
.94 (m, 2H), 8.10 (d, J = 8.0 Hz, 1H), 8.61-8.63 (m, 2H), 9.48 (s, 1H). C NMR (100 MHz, CDCl
3
) δ:
23.6, 127.2, 127.3, 127.9, 128.6, 128.7, 130.6, 133.17, 133.22, 134.2, 138.0, 150.8, 160.5, 161.1. IR
-1
+
(
KBr) ν= 2914, 1612, 1504, 1318, 736 cm . MS: m/z 252 (MH) . HRMS (ESI) calcd for C H N O :
14 10 3 2
2
52.0773 [M+H], found: 252.0788.
2
-(Pyridin-4-yl)quinazoline (4m): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid (38
1
mg, 37%), mp 124-126 °C; H NMR (400 MHz, CDCl
3
) δ: 7.69 (t, J = 7.6 Hz, 1H), 7.96 (t, J = 8.4 Hz,
1
3
2
H), 8.12 (d, J = 8.4 Hz, 1H), 8.46 (d, J = 6.0 Hz, 2H), 8.80 (d, J = 5.2 Hz, 2H), 9.50 (s, 1H). C NMR
100 MHz, CDCl ) δ: 122.4, 124.2, 127.2, 128.4, 128.9, 134.6, 145.4, 150.4, 150.6, 158.9, 160.8. IR
KBr) ν= 2921, 1617, 1544, 1402, 759 cm . MS: m/z 208 (MH) . HRMS (ESI) calcd for C13
08.0874 [M+H], found: 208.0879.
Quinazoline (4n): Eluent: petroleum ether-ethyl acetate (5:1); yellow syrup (17 mg, 27%); H NMR
400 MHz, CDCl ) δ: 7.61-7.65 (m, 1H), 7.87-7.91 (m, 2H), 8.02 (d, J = 8.4 Hz, 1H), 9.30 (s, 1H), 9.37
(
(
3
-1
+
10 3
H N :
2
1
(
(
3
-1 13
s, 1H). IR (KBr) ν= 3053, 1621, 1549, 1402, 756 cm . C NMR (100 MHz, CDCl ) δ: 125.1, 127.2,
3
+
1
28.0, 128.4, 134.2, 150.0, 155.2, 160.2. MS: m/z 131 (MH) .
5
-Chloro-2-phenylquinazoline (4o): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid (79
1
mg, 65%), mp 81-83 °C; H NMR (400 MHz, CDCl
3
) δ: 7.53-7.57 (m, 3H), 7.62 (d, J = 7.6 Hz, 1H),
13
7
.78-7.82 (m, 1H), 8.01 (d, J = 8.0 Hz, 1H), 8.62-8.64 (m, 2H), 9.84 (s, 1H). C NMR (100 MHz,
3
CDCl ) δ: 121.4, 127.2, 127.8, 128.7, 128.8, 131.0, 131.9, 133.9, 137.5, 151.9, 157.9, 161.7. IR (KBr)
-1
+
ν= 2924, 1566, 1548, 1380, 701 cm . MS: m/z 241 (MH) . HRMS (ESI) calcd for C14
2
H10ClN :
2
41.0532 [M+H], found: 241.0523.
Methyl 2-phenylquinazoline-6-carboxylate (4p): Eluent: petroleum ether-ethyl acetate (20:1);
1
yellow solid (91 mg, 68%), mp 179-182 °C; H NMR (400 MHz, CDCl ) δ: 4.02 (s, 3H), 7.55-7.56 (m,
3
3H), 8.14 (d, J = 8.8 Hz, 1H), 8.49 (d, J = 8.8 Hz, 1H), 8.64-8.65 (m, 2H), 8.69 (s, 1H), 9.57 (s, 1H).
1
3
C NMR (100 MHz, CDCl
3
) δ: 52.6, 122.8, 128.7, 128.8, 128.9, 130.2, 131.3, 133.7, 137.4, 152.7,
6

-1
+
1
61.7, 162.7, 165.9. IR (KBr) ν= 2948, 1719, 1627, 1439, 1254, 703 cm . MS: m/z 265 (MH) .
HRMS (ESI) calcd for C H N O : 265.0977 [M+H], found: 265.0980.
1
6
13
2
2
6
-Methoxy-2-phenylquinazoline (4q): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid
1
1
(
71 mg, 60%), mp 119-122 °C (lit . mp 120-122 °C); H NMR (400 MHz, CDCl ) δ: 3.96 (s, 3H), 7.40
3
(
d, J = 3.6 Hz, 1H), 7.48-7.56 (m, 4H), 7.99 (d, J = 8.8 Hz, 1H), 8.57 (dd, J
1
= 8.0 Hz, J
2
= 2.0 Hz, 2H),
1
3
9
1
.36 (s, 1H). C NMR (100 MHz, CDCl ) δ: 55.7, 103.9, 124.5, 127.2, 128.2, 128.6, 130.1, 130.2,
3
-1
38.2, 147.0, 158.3, 158.8, 159.4. IR (KBr) ν= 2924, 1604, 1532, 1386, 746 cm . MS: m/z 237
+
(
MH) .
2
-Phenylbenzo[h]quinazoline (4r): Eluent: petroleum ether-ethyl acetate (20:1); yellow solid (81
1
mg, 63%), mp 135-137 °C; H NMR (400 MHz, CDCl
.80-7.87 (m, 3H), 7.93-7.95 (m, 1H), 8.76-8.78 (m, 2H), 9.42 (s, 1H), 9.44-9.46 (m, 1H). C NMR
100 MHz, CDCl ) δ: 121.5, 123.0, 125.0, 127.5, 128.1, 128.56, 128.60, 128.7, 130.2, 130.3, 130.7,
3
) δ: 7.54-7.61 (m, 3H), 7.74 (d, J = 8.8 Hz, 1H),
1
3
7
(
3
-1
1
35.6, 138.2, 150.9, 158.5, 161.0. IR (KBr) ν= 2924, 1618, 1552, 1402, 739 cm . MS: m/z 257
+
(
MH) . HRMS (ESI) calcd for C18
H
13
N
2
: 257.1078 [M+H], found: 257.1069.
6
-(4-Chlorophenyl)-[1,3]dioxolo[4,5-g]quinazoline (4s): Eluent: petroleum ether-ethyl acetate
3
1
(
3
20:1); yellow solid (97 mg, 68%), mp 220-221 °C (lit . mp 224-226 °C); H NMR (400 MHz, CDCl )
δ: 6.16 (s, 2H), 7.10 (s, 1H), 7.31 (s, 1H), 7.46 (d, J = 8.0 Hz, 2H), 8.48 (d, J = 7.6 Hz, 2H), 9.13 (s,
1
3
1
1
H); C NMR (100 MHz, CDCl
3
) δ: 101.9, 102.2, 105.0, 120.8, 128.7, 129.5, 136.4, 136.7, 148.4,
-1
+
50.3, 154.3, 157.5, 159.1. IR (KBr) ν= 2914, 1478, 1224, 1038, 846, 795 cm . MS: m/z 285 (MH) .
2
-(4-Chlorophenyl)-7-fluoroquinazoline (4t): Eluent: petroleum ether-ethyl acetate (20:1); white
1
solid (87 mg, 67%), mp 139-141°C; H NMR (400 MHz, CDCl ) δ: 7.37-7.42 (m, 1H), 7.50 (d, J = 8.4
3
1
3
Hz, 2H), 7.67-7.70 (m, 1H), 7.93-7.97 (m, 1H), 8.56 (d, J = 8.0 Hz, 2H), 9.42 (s, 1H). C NMR (100
MHz, CDCl ) δ: 112.4, 112.6, 118.0, 118.3, 120.9, 128.9, 129.7, 129.8, 130.0, 136.1, 137.3, 152.3,
59.9, 160.8, 164.8, 167.4. IR (KBr) ν= 2924, 1614, 1539, 1412, 746 cm . MS: m/z 259 (MH) .
HRMS (ESI) calcd for C14 ClFN : 259.0438 [M+H], found: 259.0430.
3
-1
+
1
H
9
2
7

General procedure for the preparation of 1,2,3,4-tetrahydroquinazoline 5. To a tube containing
a solution of 2-bromobenzyl bromide 1 (0.5 mmol) in DMSO (2 mL) were added aldehyde 2 (0.6
mmol), Cu(OAc) (0.05 mmol), DMAP (0.15 mmol) and 40% aqueous methylamine or 65% aqueous
2
o
ethylamine 3 (1 mL). Then, the tube was sealed and the mixture was stirred at 80 C under air
atmosphere for 14 h. After being cooled to room temperature, the reaction was quenched with NH Cl
4
solution and extracted with ethyl acetate. The combined organic layers were washed with H
2
O and
brine, and then dried over anhydrous Na SO . The solvent was evaporated under vacuum and the crude
2
4
product was purified by chromatography on silica-gel to afford 1,2,3,4-tetrahydroquinazoline
derivatives 5.
1
,3-Dimethyl-2-phenyl-1,2,3,4-tetrahydroquinazoline
(5a):
Eluent:
5
4
3a
4
a
3
Me
1
6
7
N
petroleum ether-ethyl acetate (10:1); colorless liquid (81 mg, 67%); H
10
2
9
N
11
8
a
1
NMR (400 MHz, CDCl
J = 15.6 Hz, 1H; 4-H), 3.84 (d, J = 16.0 Hz, 1H; 4-H), 4.91 (s, 1H; 2-H),
.69-6.72 (m, 2H; 6-H and 8-H), 6.92 (d, J = 7.2 Hz, 1H; 5-H), 7.21-7.36 (m, 6H; 7-H, 10-H, 11-H, 12-
3
) δ: 2.56 (s, 3H; 3a-H), 2.98 (s, 3H; 1a-H), 3.42 (d,
8
Me
12
1
4
1a
13
6
1
3
H, 13-H, 14-H). C NMR (100 MHz, CDCl
3
) δ: 36.7 (C-3a), 42.4 (C-1a), 49.3 (C-4), 82.1 (C-2), 108.9
(
C-8), 115.9 (C-6), 117.9 (C-4a), 127.10 (C-10 and C-14), 127.13 (C-12), 127.8 (C-5), 127.9 (C-7),
-1
1
28.5 (C-11 and C-13), 140.7 (C-9), 143.6 (C-8a). IR (KBr) ν= 2937, 1610, 1504, 1284, 745 cm .
+
MS: m/z 239 (MH) . HRMS (ESI) calcd for C16
H
19
N
2
: 239.1548 [M+H], found: 239.1552.
2
-(4-Methoxyphenyl)-1,3-dimethyl-1,2,3,4-tetrahydroquinazoline (5b): Eluent: petroleum ether-
1
ethyl acetate (10:1); colorless liquid (93 mg, 69%); H NMR (400 MHz, CDCl
3
) δ: 2.52 (s, 3H), 2.96 (s,
3
6
4
H), 3.41 (d, J = 16.0 Hz, 1H), 3.79 (s, 3H), 3.83 (d, J = 15.6 Hz, 1H), 4.86 (s, 1H), 6.66-6.70 (m, 2H),
1
3
.85-6.87 (m, 2H), 6.91 (d, J = 7.6 Hz, 1H), 7.16-7.26 (m, 3H). C NMR (100 MHz, CDCl ) δ: 36.6,
3
2.2, 49.3, 55.3, 81.6, 108.9, 113.8, 115.8, 117.9, 127.1, 127.9, 128.3, 132.8, 143.7, 159.2. IR (KBr) ν
-1
+
=
21 2
2978, 1616, 1523, 1284, 742 cm . MS: m/z 269 (MH) . HRMS (ESI) calcd for C17H N O: 269.1654
[
M+H], found: 269.1650.
8

2
-(4-Bromophenyl)-1,3-dimethyl-1,2,3,4-tetrahydroquinazoline (5c): Eluent: petroleum ether-
1
ethyl acetate (10:1); colourless liquid (111 mg, 70%); H NMR (400 MHz, CDCl ) δ: 2.51 (s, 3H), 2.95
3
(
s, 3H), 3.38 (d, J = 16.4 Hz, 1H), 3.76 (d, J = 16.4 Hz, 1H), 4.83 (s, 1H), 6.66-6.69 (m, 2H), 6.89 (d, J
1
3
=
7.2 Hz, 1H), 7.12 (d, J = 8.4 Hz, 2H), 7.19-7.22 (m, 1H), 7.43 (d, J = 8.4 Hz, 2H). C NMR (100
MHz, CDCl ) δ: 36.8, 42.3, 49.2, 81.6, 109.0, 116.1, 117.8, 121.7, 127.2, 127.9, 128.9, 131.6, 139.9,
3
-1
+
1
43.3. IR (KBr) ν= 2960, 1604, 1506, 1282, 743 cm . MS: m/z 317 (MH) . HRMS (ESI) calcd for
16 2
C H18BrN
: 317.0653 [M+H], found: 317.0655.
1
,3-Dimethyl-2-(4-nitrophenyl)-1,2,3,4-tetrahydroquinazoline (5d): Eluent: petroleum ether-
1
ethyl acetate (5:1); yellow liquid (98 mg, 69%); H NMR (400 MHz, CDCl ) δ: 2.54 (s, 3H), 3.00 (s,
3
3
6
H), 3.40 (d, J = 16.0 Hz, 1H), 3.79 (d, J = 16.0 Hz, 1H), 4.94 (s, 1H), 6.68-6.73 (m, 2H), 6.89 (d, J =
1
3
.4 Hz, 1H), 7.22 (t, J = 7.2 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 8.16 (d, J = 8.4 Hz, 2H); C NMR (100
) δ: 37.0, 42.4, 49.2, 81.4, 109.3, 116.6, 117.6, 123.8, 127.3, 128.1, 134.4, 142.0, 143.0,
MHz, CDCl
48.3. IR (KBr) ν= 2939, 1610, 1500, 1315, 745 cm . MS: m/z 284 (MH) . HRMS (ESI) calcd for
: 284.1399 [M+H], found: 284.1394.
3
-1
+
1
16 18 3 2
C H N O
1
,3-Dimethyl-2-m-tolyl-1,2,3,4-tetrahydroquinazoline (5e): Eluent: petroleum ether-ethyl acetate
1
(
10:1); colorless liquid (82 mg, 65%); H NMR (400 MHz, CDCl
3
) δ: 2.35 (s, 3H), 2.54 (s, 3H), 2.97 (s,
3
6
2
1
H), 3.41 (d, J = 15.2 Hz, 1H), 3.86 (d, J = 15.6 Hz, 1H), 4.87 (s, 1H), 6.67-6.71 (m, 2H), 6.92 (d, J =
1
3
.8 Hz, 1H), 7.02 (d, J = 8.0 Hz, 1H), 7.12 (s, 2H), 7.19-7.25 (m, 2H). C NMR (100 MHz, CDCl
3
) δ:
1.6, 36.7, 42.4, 49.4, 82.2, 108.8, 115.8, 117.9, 124.0, 127.1, 127.87, 127.89, 128.3, 128.6, 138.2,
-1
+
40.8, 143.7. IR (KBr) ν= 2967, 1604, 1504, 1268, 745 cm . MS: m/z 253 (MH) . HRMS (ESI) calcd
for C H N : 253.1704 [M+H], found: 253.1708.
1
7
21
2
2
-(3-Fluorophenyl)-1,3-dimethyl-1,2,3,4-tetrahydroquinazoline (5f): Eluent: petroleum ether-
1
ethyl acetate (10:1); colorless liquid (86 mg, 67%); H NMR (400 MHz, CDCl
3
) δ: 2.51 (s, 3H), 2.97 (s,
3H), 3.39 (d, J = 16.4 Hz, 1H), 3.78 (d, J = 16.0 Hz, 1H), 4.86 (s, 1H), 6.67 (t, J = 8.0 Hz, 2H), 6.89 (d,
J = 7.2 Hz, 1H), 6.95 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 7.6 Hz, 1H), 7.18- 7.25 (m, 1H), 7.27-7.30 (m,
1
3
1
H). C NMR (100 MHz, CDCl
3
) δ: 29.7, 36.8, 42.3, 49.2, 81.6, 109.0, 113.9, 114.2, 114.6, 114.8,
9

116.1, 117.7, 122.6, 122.7, 127.1, 127.9, 129.9, 130.0, 143.2, 143.7, 164.2. IR (KBr) ν= 2960, 1598,
-1
+
1
2
501, 1273, 743 cm . MS: m/z 257 (MH) . HRMS (ESI) calcd for C16H18FN : 257.1454 [M+H],
found: 257.1459.
1
,3-Dimethyl-2-o-tolyl-1,2,3,4-tetrahydroquinazoline (5g): Eluent: petroleum ether-ethyl acetate
1
(
10:1); colorless liquid (90 mg, 71%); H NMR (400 MHz, CDCl ) δ: 2.48 (s, 3H), 2.55 (s, 3H), 2.91 (s,
3
3H), 3.36 (d, J = 16.0 Hz, 1H), 3.88 (d, J = 16.0 Hz, 1H), 4.96 (s, 1H), 6.68 (t, J = 6.8 Hz, 2H), 6.92 (d,
1
3
J = 7.2 Hz, 1H), 7.01 (d, J = 8.0 Hz, 1H), 7.06-7.10 (m, 1H), 7.20-7.26 (m, 3H). C NMR (100 MHz,
CDCl ) δ: 18.8, 36.3, 42.3, 49.1, 79.6, 108.3, 115.6, 117.6, 125.5, 126.1, 127.1, 127.6, 127.9, 131.0,
36.6, 138.6, 144.0. IR (KBr) ν= 2931, 1604, 1504, 1280, 743 cm . MS: m/z 253 (MH) . HRMS
ESI) calcd for C17 : 253.1704 [M+H], found: 253.1696.
3
-1
+
1
(
21 2
H N
1
,3-Dimethyl-2-(naphthalen-1-yl)-1,2,3,4-tetrahydroquinazoline (5h): Eluent: petroleum ether-
1
ethyl acetate (10:1); white solid (93 mg, 64%), mp 147-149 °C; H NMR (400 MHz, CDCl
3
) δ: 2.73 (s,
3
6
7
8
1
H), 3.03 (s, 3H), 3.44 (d, J = 15.6 Hz, 1H), 3.93 (d, J = 15.6 Hz, 1H), 5.59 (s, 1H), 6.74-6.81 (m, 2H),
.97 (d, J = 8.0 Hz, 1H), 7.25 (d, J = 6.8 Hz, 1H), 7.32 (t, J = 8.0 Hz, 1H), 7.38 (t, J = 8.0 Hz, 1H),
.55-7.59 (m, 1H), 7.63-7.67 (m, 1H), 7.83 (d, J = 8.0 Hz, 1H), 7.93 (d, J = 8.0 Hz, 1H), 8.32 (d, J =
1
3
.4 Hz, 1H). C NMR (100 MHz, CDCl
3
) δ: 36.6, 42.2, 49.5, 79.9, 108.4, 115.8, 117.4, 124.2, 124.3,
25.0, 125.7, 126.4, 127.4, 128.0, 128.7, 128.8, 131.2, 134.4, 135.3, 144.0. IR (KBr) ν= 2935, 2894,
-1
+
1
21 2
605, 1504, 1296, 748 cm . MS: m/z 289 (MH) . HRMS (ESI) calcd for C20H N : 289.1704 [M+H],
found: 289.1708.
1
,3-Dimethyl-2-(thiophen-2-yl)-1,2,3,4-tetrahydroquinazoline (5i): Eluent: petroleum ether- ethyl
1
acetate (10:1); colorless liquid (67 mg, 55%); H NMR (400 MHz, CDCl ) δ: 2.52 (s, 3H), 3.05 (s, 3H),
3
3
6
1
.51 (d, J = 16.4 Hz, 1H), 4.01 (d, J = 16.4 Hz, 1H), 5.13 (s, 1H), 6.68-6.72 (m, 2H), 6.83-6.84 (m, 1H),
1
3
.91-6.93 (m, 2H), 7.19-7.26 (m, 2H). C NMR (100 MHz, CDCl
3
) δ: 37.1, 41.6, 49.6, 78.5, 109.6,
16.5, 118.1, 125.4, 125.5, 126.5, 127.0, 127.8, 142.8, 144.4. IR (KBr) ν= 2937, 2877, 1605, 1504,
-1
+
1
2
283, 747 cm . MS: m/z 245 (MH) . HRMS (ESI) calcd for C14
17 2
H N S: 245.1112 [M+H], found:
45.1116.
1
0

1
,3-Dimethyl-1,2,3,4-tetrahydroquinazoline (5j): Eluent: petroleum ether-ethyl acetate (5:1);
1
colourless liquid (72 mg, 88%); H NMR (400 MHz, CDCl ) δ: 2.50 (s, 3H), 2.87 (s, 3H), 3.83 (s, 2H),
3
1
3
3
.90 (s, 2H), 6.65-6.71 (m, 2H), 6.92 (d, J = 7.6 Hz, 1H), 7.13 (t, J = 7.2 Hz, 1H). C NMR (100 MHz,
CDCl ) δ: 36.8, 41.6, 55.8, 73.0, 111.4, 117.2, 120.0, 126.9, 127.5, 145.0. IR (KBr) ν= 2926, 1663,
3
-1
+
1
606, 1504, 749 cm . MS: m/z 163 (MH) . HRMS (ESI) calcd for C10
15 2
H N : 163.1235 [M+H], found:
1
63.1236.
1
,2,3-Trimethyl-1,2,3,4-tetrahydroquinazoline (5k): Eluent: petroleum ether-ethyl acetate (5:1);
1
colourless liquid (75 mg, 85%); H NMR (400 MHz, CDCl ) δ: 1.24 (d, J = 6.4 Hz, 3H), 2.45 (s, 3H),
3
2
.88 (s, 3H), 3.55 (d, J = 16.8 Hz, 1H), 3.92-3.97 (m, 1H), 4.27 (d, J = 16.8 Hz, 1H), 6.58 (d, J = 8.0
1
3
Hz, 1H), 6.66 (t, J = 7.2 Hz, 1H), 6.94 (d, J = 7.2 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H). C NMR (100
MHz, CDCl ) δ: 16.2, 35.7, 42.2, 48.9, 74.9, 110.3, 116.1, 117.4, 127.0, 127.6, 143.0. IR (KBr) ν=
934, 1604, 1501, 1290, 746 cm . MS: m/z 177 (MH) . HRMS (ESI) calcd for C11
M+H], found: 177.1398.
3
-1
+
2
17 2
H N : 177.1391
[
2
-Benzyl-1,3-dimethyl-1,2,3,4-tetrahydroquinazoline (5l): Eluent: petroleum ether-ethyl acetate
1
(
5:1); colorless liquid (104 mg, 82%); H NMR (400 MHz, CDCl
3
) δ: 2.47 (s, 3H), 2.76 (s, 3H), 2.99 (d,
J = 6.4 Hz, 2H), 3.63 (d, J = 16.8 Hz, 1H), 4.07 (t, J = 6.4 Hz, 1H), 4.51 (d, J = 16.4 Hz, 1H), 6.62 (d, J
1
3
=
8.0 Hz, 1H), 6.78 (t, J = 7.2 Hz, 1H), 7.06 (d, J = 7.2 Hz, 1H), 7.24-7.40 (m, 6H). C NMR (100
MHz, CDCl ) δ: 37.8, 39.0, 42.7, 49.2, 81.6, 110.3, 116.1, 117.1, 126.4, 127.3, 127.8, 128.5, 129.6,
38.7, 142.8. IR (KBr) ν= 2932, 1604, 1504, 1286, 747 cm . MS: m/z 253 (MH) . HRMS (ESI) calcd
for C H N : 253.1704 [M+H], found: 253.1711.
3
-1
+
1
1
7
21
2
5
,7-Dimethyl-6-phenyl-5,6,7,8-tetrahydro-[1,3]dioxolo[4,5-g]quinazoline
(5m):
Eluent:
1
petroleum ether-ethyl acetate (10:1); colourless liquid (105 mg, 74%); H NMR (400 MHz, CDCl
3
) δ:
2
2
3
.51 (s, 3H), 2.92 (s, 3H), 3.31 (d, J = 16.4 Hz, 1H), 3.72 (d, J = 15.2 Hz, 1H), 4.81 (s, 1H), 5.85 (s,
1
3
H), 6.36 (s, 1H), 6.44 (s, 1H), 7.21-7.23 (m, 2H), 7.26-7.33 (m, 3H). C NMR (100 MHz, CDCl
3
) δ:
7.4, 42.2, 49.5, 81.9, 92.3, 100.3, 107.6, 109.6, 127.1, 127.8, 128.4, 138.0, 138.9, 140.6, 147.2. IR
1
1

-1
+
(
KBr) ν = 2928, 1504, 1235, 1039, 749 cm . MS: m/z 283 (MH) . HRMS (ESI) calcd for
C H N NaO : 305.1266 [M+Na], found: 305.1252.
1
7
18
2
2
5
-Chloro-1,3-dimethyl-2-phenyl-1,2,3,4-tetrahydroquinazoline (5n): Eluent: petroleum ether-
1
ethyl acetate (10:1); yellow syrup (104 mg, 76%); H NMR (400 MHz, CDCl ) δ: 2.56 (s, 3H), 3.01 (s,
3
3H), 3.65 (d, J = 16.4 Hz, 1H), 3.76 (d, J = 16.4 Hz, 1H), 4.93 (s, 1H), 6.62 (d, J = 7.6 Hz, 1H), 6.71-
1
3
6
.74 (m, 1H), 7.13 (t, J = 8.0 Hz, 1H), 7.22-7.26 (m, 2H), 7.30-7.36 (m, 3H). C NMR (100 MHz,
CDCl ) δ: 37.2, 42.6, 47.1, 81.7, 107.4, 115.6, 116.6, 127.0, 128.0, 128.2, 128.6, 133.2, 140.1, 145.0.
3
-1
+
IR (KBr) ν= 2935, 1593, 1487, 1284, 761 cm . MS: m/z 273 (MH) . HRMS (ESI) calcd for
16 2
C H17ClN
Na: 295.0978 [M+Na], found: 295.0983.
Methyl 1,3-dimethyl-2-phenyl-1,2,3,4-tetrahydroquinazoline-6-carboxylate (5o): Eluent:
1
petroleum ether-ethyl acetate (10:1); colorless liquid (101 mg, 68%); H NMR (400 MHz, CDCl ) δ:
3
2
.51 (s, 3H), 3.01 (s, 3H), 3.40 (d, J = 16.0 Hz, 1H), 3.78 (d, J = 16.0 Hz, 1H), 3.84 (s, 3H), 4.94 (s,
H), 6.66 (d, J = 8.4 Hz, 1H), 7.18-7.20 (m, 2H), 7.28-7.34 (m, 3H), 7.59 (s, 1H), 7.90 (dd, J = 8.4 Hz,
) δ: 36.8, 42.2, 48.6, 51.5, 82.2, 108.0, 116.8, 117.0, 126.8,
1
1
1
3
J
2
= 2.0 Hz 1H). C NMR (100 MHz, CDCl
3
-1
1
28.2, 128.6, 128.8, 130.4, 139.8, 147.3, 167.5. IR (KBr) ν= 2944, 1709, 1610, 1517, 1296, 768 cm .
+
MS: m/z 297 (MH) . HRMS (ESI) calcd for C18
H
21
N
2
O
2
: 297.1603 [M+H], found: 297.1611.
1
,3-Diethyl-2-phenyl-1,2,3,4-tetrahydroquinazoline (5p): Eluent: petroleum ether-ethyl acetate
1
(
(
10:1); colourless liquid (85 mg, 64%); H NMR (400 MHz, CDCl
m, 2H), 3.04-3.13 (m, 1H), 3.44 (d, J = 16.4 Hz, 1H), 3.56-3.65 (m, 1H), 3.77 (d, J = 16.4 Hz, 1H),
.05 (s, 1H), 6.60 (t, J = 7.2 Hz, 1H), 6.70 (d, J = 8.0 Hz, 1H), 6.87 (d, J = 6.4 Hz, 1H), 7.17 (t, J = 7.6
3
) δ: 1.17-1.26 (m, 6H), 2.58-2.71
5
1
3
Hz, 1H), 7.24-7.29 (m, 5H). C NMR (100 MHz, CDCl ) δ: 12.2, 13.4, 29.7, 42.8, 47.1, 77.6, 108.4,
3
1
7
15.1, 117.4, 127.3, 127.4, 127.6, 127.7, 128.3, 138.8, 142.6. IR (KBr) ν= 2968, 1610, 1504, 1274,
-1
+
45 cm . MS: m/z 267 (MH) . HRMS (ESI) calcd for C18
23 2
H N : 267.1861 [M+H], found: 267.1866.
2
-(3-Chlorophenyl)-1,3-diethyl-1,2,3,4-tetrahydroquinazoline (5q): Eluent: petroleum ether-ethyl
1
acetate (10:1); colourless liquid (101 mg, 70%); H NMR (400 MHz, CDCl ) δ: 1.19-1.26 (m, 6H),
3
2
.57-2.72 (m, 2H), 3.02-3.11 (m, 1H), 3.46 (d, J = 16.0 Hz, 1H), 3.61-3.70 (m, 1H), 3.76 (d, J = 16.4
1
2

Hz, 1H), 5.01 (s, 1H), 6.63 (t, J = 7.2 Hz, 1H), 6.72 (d, J = 7.6 Hz, 1H), 6.89 (d, J = 6.8 Hz, 1H), 7.17-
1
3
7
1
.26 (m, 4H), 7.33 (s, 1H). C NMR (100 MHz, CDCl ) δ: 12.1, 13.4, 42.8, 47.1, 77.3, 108.6, 115.4,
3
17.5, 125.5, 127.5, 127.6, 127.7, 127.8, 129.6, 134.3, 142.2, 144.3. IR (KBr) ν= 2968, 1604, 1503,
-1
+
1
273, 743 cm . MS: m/z 301 (MH) . HRMS (ESI) calcd for C18
2
H22ClN : 301.1471 [M+H], found:
3
01.1477.
1
,3-Diethyl-1,2,3,4-tetrahydroquinazoline (5r): Eluent: petroleum ether-ethyl acetate (5:1);
1
colorless liquid (82 mg, 86%); H NMR (400 MHz, CDCl ) δ: 1.15-1.21 (m, 6H), 2.63 (q, J = 7.2 Hz,
3
2
7
1
H), 3.32 (q, J = 7.2 Hz, 2H), 3.89 (s, 2H), 4.06 (s, 2H), 6.61-6.65 (m, 2H), 6.91 (d, J = 6.8 Hz, 1H),
1
3
.07-7.12 (m, 1H). C NMR (100 MHz, CDCl ) δ: 11.9, 13.0, 43.5, 47.0, 53.8, 68.5, 110.7, 116.3,
3
-1
+
19.5, 127.3, 127.5, 143.8. IR (KBr) ν= 2968, 1605, 1504, 1271, 745 cm . MS: m/z 191 (MH) .
18 2
HRMS (ESI) calcd for C12H N
Na: 213.1368 [M+Na], found: 213.1374.
Procedure for the preparation of 1-methyl-2-phenyl-1,2,3,4-tetrahydroquinazoline (7). To a
tube containing a solution of 2-bromobenzyl amine 6 (0.5 mmol) in DMSO (2 mL) were added
benzaldehyde 2a (0.6 mmol), Cu(OAc)
2
(0.05 mmol), DMAP (0.15 mmol) and 40% aqueous
o
methylamine 3b (1 mL). Then, the tube was sealed and the mixture was stirred at 80 C under air
atmosphere for 12 h. After being cooled to room temperature, the reaction was quenched with NH
solution and extracted with ethyl acetate. The combined organic layers were washed with H O and
brine, and then dried over anhydrous Na SO . The solvent was evaporated under vacuum and the crude
product was purified by chromatography on silica-gel to afford 7.
4
Cl
2
2
4
1
-Methyl-2-phenyl-1,2,3,4-tetrahydroquinazoline (7): Eluent: petroleum ether-ethyl acetate (5:1);
1
colorless liquid (87 mg, 78%); H NMR (400 MHz, CDCl
3
) δ: 2.86 (s, 3H), 3.75 (d, J = 16.8 Hz, 1H),
3
7
7
.86 (d, J = 16.0 Hz, 1H), 5.22 (s, 1H), 6.69 (t, J = 7.2 Hz, 1H), 6.74 (d, J = 8.4 Hz, 1H), 6.92 (d, J =
1
3
.6 Hz, 1H), 7.21 (t, J = 7.6 Hz, 1H), 7.30-7.39 (m, 5H). C NMR (100 MHz, CDCl
3
) δ: 35.9, 43.4,
5.8, 110.5, 116.0, 122.3, 125.4, 127.2, 127.9, 128.6, 141.1, 145.0. IR (KBr) ν= 2937, 1603, 1501,
-1
+
1
2
284, 743 cm . MS: m/z 225 (MH) . HRMS (ESI) calcd for C H N : 225.1391 [M+H], found:
15 17 2
25.1382.
1
3

Procedure for the preparation of N-methyl-2-((methylamino)methyl)aniline (8). To a tube
containing a solution of 2-bromobenzyl bromide 1a (0.5 mmol) in DMSO (2 mL) were added
Cu(OAc) (0.05 mmol), DMAP (0.15 mmol) and 40% aqueous methylamine 3b (1 mL). Then, the tube
2
o
was sealed and the mixture was stirred at 80 C under air for 12 h. After being cooled to room
temperature, the reaction was quenched with NH Cl solution and extracted with ethyl acetate. The
4
2 2 4
combined organic layers were washed with H O and brine, and then dried over anhydrous Na SO . The
solvent was evaporated under vacuum and the crude product was purified by chromatography on silica-
gel to afford 8.
N-Methyl-2-((methylamino)methyl)aniline (8): Eluent: petroleum ether-ethyl acetate (1:1);
1
colorless liquid (64 mg, 85%); H NMR (400 MHz, CDCl ) δ: 2.44 (s, 3H), 2.87 (s, 3H), 3.76 (s, 2H),
3
1
3
6
.67 (t, J = 8.0 Hz, 2H), 7.06 (d, J = 7.6 Hz, 1H), 7.24 (t, J = 8.0 Hz, 1H). C NMR (100 MHz, CDCl
3
)
δ: 30.2, 6.0, 55.4, 109.6, 116.0, 123.6, 128.7, 129.6, 149.4. IR (KBr) ν= 2924, 1652, 1591, 1264, 758
-1
+
9 15 2
cm . MS: m/z 151 (MH) . HRMS (ESI) calcd for C H N : 151.1235 [M+H], found: 151.1238.
1
4

1
13
III. Copies of H and C NMR spectra of 4a-4t
1
5

1
6

1
7

1
8

1
9

2
0

2
1

2
2

2
3

2
4

2
5

2
6

2
7

2
8

2
9