Transition Metal-Free Visible Light-Driven Photoredox Oxidative Annulation of Arylamidines

Article abstract of DOI:10.1021/acs.joc.5b02366

A fast catalytic synthesis of multisubstituted quinazolines from readily available amidines via visible light-mediated oxidative C(sp³)-C(sp²) bond formation has been established. This reaction is a metal-free oxidative coupling catalyzed by a photoredox organocatalyst. The protocol features low catalyst loading (1 mol %).

Full text of DOI:10.1021/acs.joc.5b02366

Subscriber access provided by UNIV OF NEBRASKA - LINCOLN
Note
Transition-Metal-Free Visible-Light driven
Photoredox Oxidative Annulation of Arylamidines
Zi-chao Shen, Pan Yang, and Yu Tang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.5b02366 • Publication Date (Web): 07 Dec 2015
Downloaded from http://pubs.acs.org on December 8, 2015
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
TransitionꢀMetalꢀFree VisibleꢀLight driven Photoredox
Oxidative Annulation of Arylamidines
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Ziꢀchao Shen, Pan Yang, Yu Tang.*‡
School of Pharmaceutical Science and Technology, Key Laboratory for Modern Drug Delivery &
HighꢀEfficiency, Tianjin University, Tianjin, 300072 P. R. China
‡ School of Medicine and Pharmacy, Ocean University of China, 5 Yushan Road, Qingdao, China.
Eꢀmail:yutang@tju.edu.cn
TOC Graphic
Abstract
A fast catalytic synthesis of multisubstituted quinazolines from readily available amidines, via visible
light mediated oxidative C(sp3)ꢀC(sp2) bond formation has been established. This reaction is a
metalꢀfree oxidative coupling catalyzed by a photoredox organocatalyst. The protocols feature low
catalyst loadings (1 mol %).
The development of a novel C−C bondꢀforming reaction is one of the most important topics in the
field of organic chemistry. Many organic reactions conducted in the presence of visible light have
drawn attentions of synthetic organic chemists because of their sustainability, cost efficiency, and
attractive environmental performance.1 Recent studies in photochemistry have reported the formation
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 28
1
2
3
4
5
6
7
8
9
of C−C and C–heteroatom bonds by using visibleꢀlight and either ruthenium or iridium complexes, or
organic dyes as photoredox catalysts.2 However, the high cost and potential toxicity of the ruthenium
and iridium salts as well as their limited availability in the future are disadvantages of these
metalꢀbased methods. The organic dyes, for example, commercially readily available Rose Bengal,
display similar photocatalytic activity in some reactions.3 These dye photosensitizers therefore
attracted our particular attention.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 1. Approaches To Access Quinazolines and Benzimidazoles via Oxidative sp3CꢀH/sp2CꢀH
Cyclization of Amidines
Quinazolines are classes of fused heterocycles that are of considerable interest because of the
diverse range of their biological properties,4 for example, antiꢀlung cancer,5 αꢀadrenergic blocker.6
Because of the wide demand for substituted quinazolines, many synthetic strategies have been
ACS Paragon Plus Environment

Page 3 of 28
The Journal of Organic Chemistry
1
2
3
4
5
developed. Recent methods toward quinazolines starting from a variety of substrates, such as
6
7
8
2ꢀaminobenzylamines, 2ꢀaminobenzoketones, Nꢀarylamidines were reported.7,
(Scheme 1)
8
9
Nonetheless, these methods all require the use of either strongly acidic or basic conditions, and/or the
preparation of activated intermediates. Recently, we developed a C−H oxidative functionalization and
Nꢀacyliminium cyclization for the synthesis of βꢀhaloꢀpyrrolidinones9 and pyrrolones.10 Herein we
report a method for the synthesis of quinazolines through the versatile metalꢀfree oxidative
C(sp3)ꢀC(sp2) bondꢀforming under photoredox conditions.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 1. Optimization of Reaction Conditionsa
entry
catalyst (mol %)
oxidant (eq)
solvent
base (eq)
temp. (oC)
1a
2a
3a
(%)b
(%)b
(%)b
1
2
Eosin Y ( 0.1)
Rose Bengal (0.1 )
Ir(ppy)3 (0.1 )
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
DMF
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
Cs2CO3 (1)
100
100
100
100
100
100
100
100
100
100
100
100
15
10
4
65
75
60
56
42
50
62
42
28
13
8
20
11
31
20
17
22
25
19
9
3
4
Ru(bpy)3Cl2 (0.1 )
Rhodamine B (0.1)
CdS (0.1)
20
8
5
6
17
13
9
7
Rose Bengal (0.1 )
Rose Bengal (0.1)
Rose Bengal (0.1)
Rose Bengal (0.1)
Rose Bengal (0.1)
Rose Bengal (0.1)
8
9
DCE e
64
54
50
72
10
11
12
MeCN e
THF e
17
25
4
EtOAc e
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 28
1
2
3
4
5
6
7
8
9
13
14
15
16
17
18
19
20
21c
22
23
24d
Rose Bengal (0.1 )
Rose Bengal (0.1 )
Rose Bengal (0.1 )
Rose Bengal (0.01 )
Rose Bengal (0.005 )
Rose Bengal (0.01 )
Rose Bengal (0.01 )
Rose Bengal (0.01 )
Rose Bengal (0.01 )
ꢀ
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBrCl3 (1.2)
DTBP (1.2)
ꢀ
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Cs2CO3 (1)
Cs2CO3 (1)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
K2CO3 (1.5)
ꢀ
120
80
16
25
5
70
68
90
91
85
90
12
trace
3
12
5
100
100
100
100
100
100
100
100
100
100
trace
trace
5
6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
5
4
trace
ꢀ
87
95
97
14
10
none
ꢀ
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
CBr4 (1.2)
0
53
40
93
32
Rose Bengal (0.01 )
Rose Bengal (0.01 )
48
DMSO K2CO3 (1.5)
trace
a Reaction conditions: 1a (0.2 mmol), photocatalyst (1 mol %), solvent (4 mL), using a 18 W fluorescent
b
c
lamp as the visible light source, 4 h. GC yield (based on external standard calibration curve method).
without light. d [1a] = 0.05 M. e using sealed tube.
NꢀbenzylꢀN’ꢀphenyl benzimidamide8 1a was used as substrate to build quinazoline via a visible
light photocatalysis strategy. Inspired by the common photoredox catalysts, the model reaction was
performed with Eosin Y (10 mol%) as photocatalyst,11 CBr4 as an oxidant and Cs2CO3 as the base
under irradiation from a fluorescent bulb (18 W) for 4 hours in DMSO.12 Considering that the
catalysts usually play important roles in photoredox catalysis, several typical photocatalysts such as
Rose Bengal, Ir(ppy)3, Ru(bpy)3Cl2, Rhodamine B and CdS were investigated to improve the reaction
efficiency (Table 1, entries 2−6). 75% GC yield of the corresponding 2a was achieved when Rose
Bengal as photocatalyst (Table 1, entry 2).13 While under these conditions a side reaction also leads to
a small quantity of the brominated product 3a, most of the simple photocatalysts were effective for
this transformation under this conditions, albeit with different yields. We proposed that CBr4 could be
cracked into CBr3 radical and bromide radical under the condition of visible light. The bromide radical
ACS Paragon Plus Environment

Page 5 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
could sequentially convert into the bromine for the bromination of 1a, thus generating 3a.17
Subsequently, the examination of solvents showed that the reaction in toluene, DMF, DCE, MeCN, THF,
EtOAc did not improve the yield (Table 1, entries 7−12). In comparison with Cs2CO3 as the additive,
K2CO3 led to higher yield (Table 1, entry 15).14 To improve the conversion, we changed temperature,
lower temperatures or higher temperatures resulted in lower yields, only 68% yield was generated at
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
o
80 C and 70% yield was obtained at 120 C (Table 1, entries 13−14). Subsequently, different
equivalent of photocatalyst and oxidants were evaluated. We noticed that even lowering the amount of
Rose bengal from 10 mol% to 0.5 mol% also can restrain brominated product 3a dramatically (Table 1,
entries 16−17). CBrCl3 have the same efficiency with CBr4 (Table 1, entry 18).15 Light together with
CBr4 proved essential for this transformation and almost all the starting material was recovered when
where was no light or CBr4 (Table 1, entries 19−21).16 The reaction also can be conducted without
photocatalysts or base (Table 1, entries 22−23). The product was generated in a lower yield mainly
due to the side reaction that took place in the catalytic process.
Table 2. Substrate Scope for the Photoinduced Oxidative sp3CꢀH/sp2CꢀH Cyclization of
Amidinesa,b
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 28
1
2
3
4
5
6
7
8
N
N
N
N
N
N
N
N
MeO
Me
Cl
2a 88%
2b 91%
2c 94%
2d 81%
9
OMe
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
N
N
N
N
N
N
N
N
NC
2f 83%
2g 62%
2e 48%
2h 89%
Cl
CF3
NO2
R
N
N
N
N
N
N
N
N
2l R = H trace
2m R = Me trace
2n R = C3H7 36%
2i 84%
2j 85%
2k 91%
N
N
N
N
2p 30%
2o 41%
a Reaction conditions: 1a (0.2 mmol), photocatalyst (1 mol %), solvent (4 mL), using a 18 W fluorescent lamp as the visible light
source, 4 h. b isolated yield.
Equipped with a set of optimized conditions, we explored the substrate scope of the visible light
photocatalysis reaction delivering quinazolines, as depicted in Table 2. First, we investigated the scope
of the R1 substituent. Various aromatic groups with electronꢀdonating and electronꢀwithdrawing
substituents were well tolerated, affording the corresponding quinazolines in good to excellent yields
(2a−2d). Aromatic groups with strong electronꢀwithdrawing substituents disfavored the formation of
quinazoline (2e, 48%). Meanwhile the bulky naphthyl group had little influence on the reaction (2f,
83%). Notably, 2ꢀtertbutyl substituted quinazoline was generated in a comparable yield (2g, 62%).
Next, we investigated the scope of the R2 substituent. A range of substrates bearing electronꢀdonating
ACS Paragon Plus Environment

Page 7 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
or weak electronꢀwithdrawing group substituted aromatic rings all underwent the oxidative cyclization
smoothly and gave the desired quinazoline products in excellent yields (2h−2k). However, no desired
products were obtained when the R3 was H or methyl under conditions (2l, 2m). To our delight, when
the R3 was propyl or cycloalkyl substituted groups, the corresponding products were generated in
moderate yields (2n−2p).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Table 3. Substrate Scope for the Photoinduced Oxidative sp3CꢀH/sp2CꢀH Cyclization of
Amidinesa,b
a Reaction conditions: 1a (0.2 mmol), photocatalyst (1 mol %), solvent (4 mL), using a 18 W fluorescent lamp as the visible light
source, 4 h. b isolated yield.
Then the effect of the substituent attached on the aniline ring (i.e., R3) was examined. (Table 3)
The anilines ring with electronꢀrich, bromo, chloro, or fluoro group substituents were readily
accommodated and provided the corresponding quinazolines in good to excellent yields, thus offering
the possibility of introducing further substituents by additional coupling reactions (5a−5f). When the
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 28
1
2
3
4
5
6
7
8
9
aniline ring was substituted at the meta position, there were two positions for the oxidative coupling to
occur, favoring the less sterically hindered C−H bond (5c, 86% 5:4). However, the anilines ring with
strong electronꢀwithdrawing groups at the para position led to the decrease of the yields (5g−5i).8
Notably, the bulky naphthyl substituted quinazoline was generated in a good yield (5j, 82%).
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Scheme 2. Plausible Reaction Mechanism
On the basis of the above studies and literature reports, a possible mechanism is proposed.
(Scheme 2) There is more than one reaction pathway involved.16−19 If without Rose Bengal, CBr4
could be cracked into CBr3 radical and bromide radical under the condition of visible light.20 The CBr3
radical abstracts a hydrogen atom of another molecule of benzimidamide to produce the αꢀamino
radical intermediate A, which once again enters the radical chain process with CBr4 to generate
iminium ion C. The iminium ion C underwent an intramolecular Friedel−Craft reaction to give
intermediate D. Further dehydrogenation afforded the hydroquinone E, which was finally aromatized
to give the stable product quinazoline. The difference of another pathway is that the oxidative
ACS Paragon Plus Environment

Page 9 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
quenching of the visibleꢀlightꢀexcited Rose Bengal (RB*) by benzimidamide resulted in the formation
of Rose Bengal radical anion (RB•−) and radical cation B. Upon transfer of an electron to CBr4 to form
the superoxide radical anion, Rose Bengal was regenerated and completed the photoredox cycle. On
the other hand, the radical cation B gave up a hydrogen atom, presumably to the radical anion to
afford CBr3 radical , bromide anion and radical intermediate A. There may be another pathway that
CBr3 radical abstracts a hydrogen atom from radical cation B to generate iminium ion C directly.
After following the same procedure to give the stable product quinazoline.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
In summary, we have described a direct metalꢀfree protocol for the synthesis of quinazolines
from common NꢀalkylꢀN′ꢀarylamidine under photoredox conditions. The reaction was found to
tolerate a wide range of functional groups. Our method avoids the use of potentially toxic and
expensive transitionꢀmetal catalysts while also providing improved reaction efficiency with lower
catalyst loadings.
EXPERIMENTAL SECTION
o
General Remarks. All reactions were carried out at 100 C without precaution of air and stirred
1
magnetically. H and 13C NMR spectra were recorded on 600 MHz and 400 MHz spectrometer at 25
oC. Chemical shifts values are given in parts per million and referred as the internal standard to TMS:
0.00 ppm. The peak patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; qui,
quintet; m, multiplet and dd, doublet of doublets. The coupling constants J, are reported in Hertz (Hz).
Lowꢀresolution mass spectra and highꢀresolution mass spectra were obtained using a QꢀTOF micro
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 28
1
2
3
4
5
spectrometer. Melting points were determined by
a
Laboratory Device and were
6
7
8
9
uncorrected/calibrated. Flash column chromatography was performed over silica gel 100ꢀ200 m and
the eluent was a mixture of ethyl acetate and petroleum ether. Organic solutions were concentrated by
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
rotary evaporation below 40 C in vacuum. TLC plates were visualized by exposure to ultraviolet
light.
General Experimental Procedure.
General Procedure for Synthesis of Imidamide Derivatives (Method A).21, 22
To a cold solution of 82.5 mmol of aniline in dry DCM (20 mL) was added dropwise 38.8 mmol of
acyl chloride in dry DCM 10 mL. The mixture was stirred at room temperature for 2 h. Water 15 mL
and concentrated HCl (1 mL at 37%) were added. The mixture was filtered and the solid product
washed with water to afford taget amide. The filtrate was concentrated to provide another part of
amide. Combine with these two parts used to next step directly. A solution of amide (15mmol, 1 equiv)
in thionyl chloride (90 mmol, 6 equiv) was stirred at the reflux (80 oC) for 6 h. After cooling to room
temperature, the mixture was concentrated under reduced pressure. The residue was dissolved in
toluene (15 mL x 2) and the mixture was evaporated again to generate the corresponding
imidoylchloride as a TLC pure residual oil. Amine or benzyl amine (30 mmol, 2 equiv) and Et3N (90
mmol, 3 equiv) were mixed in dry DCM (100 mL) and stirred at 0 oC for 10 min. To this mixture, was
added a solution of the aboveꢀobtained imidoyl chloride in dry DCM (50 mL). The reaction mixture
ACS Paragon Plus Environment

Page 11 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
was stirred at 0 oC for 20 min and heated at 50 °C for another 2 h. After cooling to room temperature,
the reaction mixture was extracted with ethyl acetate (100 mL x 3) and then washed with 1M HCl
(100 mL x 2). The organic layer was dried over anhydrous Na2SO4 followed by the filtration and then
condensed. The residue was purified by recrystallization to afford the corresponding product.
General Procedure for Synthesis of Imidamide Derivatives (Method B).21, 22
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To a cold solution of 82.5 mmol of amine or benzyl amine in dry DCM (20 mL) was added dropwise
38.8 mmol of acyl chloride in dry DCM 10 mL. The mixture was stirred at room temperature for 2 h.
Water 15 mL and concentrated HCl (1 mL at 37%) were added. The mixture was filtered and the solid
product washed with water to afford taget amide. The filtrate was concentrated to provide another part
of amide. Combine with these two parts used to next step directly. A solution of amide (15mmol, 1
equiv) in thionyl chloride (90 mmol, 6 equiv) was stirred at the reflux (80 oC) for 6 h. After cooling to
room temperature, the mixture was concentrated under reduced pressure. The residue was dissolved in
toluene (15 mL x 2) and the mixture was evaporated again to generate the corresponding
imidoylchloride as a TLC pure residual oil. Aniline (30 mmol, 2 equiv) and Et3N (90 mmol, 3 equiv)
o
were mixed in dry DCM (100 mL) and stirred at 0 C for 10 min. To this mixture, was added a
solution of the aboveꢀobtained imidoyl chloride in dry DCM (50 mL). The reaction mixture was
stirred at 0 oC for 20 min and heated at 50 °C for another 2 h. After cooling to room temperature, the
reaction mixture was extracted with ethyl acetate (100 mL x 3) and then washed with 1M HCl (100
mL x 2). The organic layer was dried over anhydrous Na2SO4 followed by the filtration and then
condensed. The residue was purified by recrystallization to afford the corresponding product.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 28
1
2
3
4
5
General Procedure for Synthesis of Quinazolines.
6
7
8
9
To a solution of imidamide 1 (0.2 mmol, 1 equiv) and K2CO3 (0.3 mmol, 1.5 equiv) in DMSO (4 ml)
at 100 oC was added CBr4 (0.24mmol, 1.2 equiv). The solution was stirred at this temperature for 4 h,
on the condition of visible light (18 W fluorescent lamp). After cooling to room temperature, the
reaction mixture was extracted with ethyl acetate (20 ml x 3) and then washed with brine (20 ml). The
organic layer was dried over anhydrous Na2SO4 followed by the filtration and then condensed. The
residue was purified by silica gel column chromatography to afford the corresponding product 2.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NꢀbenzylꢀN'ꢀphenylbenzimidamide (1a):8 3.2 g; white solid; yield 75 % (Method A); mp. 100ꢀ101
oC. 1H NMR (600 MHz, CDCl3) δ 7.45 (s, 2H), 7.37 (t, J = 6.7 Hz, 2H), 7.30 (t, J = 6.7 Hz, 1H), 7.24
(m, 5H), 7.07 (t, J = 6.5 Hz, 2H), 6.82 (s, 1H), 6.68 (s, 2H), 4.77 (brs, 1H), 4.70 (s, 2H). 13C NMR
(150 MHz, CDCl3) δ 157.2, 150.8, 139.0, 135.1, 129.2, 128.7, 128.6, 128.4, 128.3, 128.2, 127.5, 123.1,
121.4, 46.2. mass spectrum (ESI): m/e (% relative intensity) 287.1 (100) (M+H)+.
Nꢀbenzylꢀ4ꢀmethoxyꢀN'ꢀphenylbenzimidamide (1b):8 4.1 g; colorless oil; yield 87 % (Method A);.
1H NMR (600 MHz, DMSO) δ 7.48 (s, 1H), 7.43 (d, J = 5.9 Hz, 2H), 7.35 (t, J = 7.2 Hz, 2H), 7.24 (t,
J = 7.1 Hz, 1H), 7.18 (d, J = 6.9 Hz, 2H), 7.00 (t, J = 6.9 Hz, 2H), 6.82 (d, J = 7.9 Hz, 2H), 6.71 (d, J
= 6.5 Hz, 1H), 6.47 (d, J = 6.9 Hz, 2H), 4.58 (s, 2H), 3.71 (s, 3H). 13C NMR (151 MHz, DMSO) δ
159.4, 156.5, 151.7, 140.3, 130.2, 128.2, 128.1, 127.1, 126.9, 126.4, 122.5, 120.1, 113.3, 55.1, 44.0.
mass spectrum (ESI): m/e (% relative intensity) 312.1 (100) (M+H)+.
ACS Paragon Plus Environment

Page 13 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Nꢀbenzylꢀ4ꢀmethylꢀN'ꢀphenylbenzimidamide (1c): 3.8 g; white solid; yield 86 % (Method A); mp.
69ꢀ71 oC. 1H NMR (600 MHz, DMSO) δ 7.45 (s, 1H), 7.41 (s, 2H), 7.34 (t, J = 7.3 Hz, 2H), 7.23 (t, J
= 7.1 Hz, 1H), 7.12 (s, 2H), 7.07 (d, J = 7.5 Hz, 2H), 6.98 (t, J = 6.9 Hz, 2H), 6.68 (t, J = 6.5 Hz, 1H),
6.45 (d, J = 5.6 Hz, 2H), 4.57 (s, 2H), 2.23 (s, 3H). 13C NMR (150 MHz, DMSO) δ 156.8, 151.6,
140.3, 138.3, 132.0, 128.6, 128.5, 128.1, 127.1, 126.4, 122.6, 122.5, 120.2, 44.0, 20.8. mass spectrum
(ESI): m/e (% relative intensity) 301.1 (100) (M+H)+; HRMS (ESI): m/e calcd for C21H19N2 (MꢀH)ꢀ:
299.1528, found 299.1532.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀbenzylꢀ4ꢀchloroꢀN'ꢀphenylbenzimidamide (1d):8 4.1 g; white solid; yield 85 % (Method A); mp.
o
1
84ꢀ85 C. H NMR (400 MHz, DMSO) δ 7.59 (s, 1H), 7.43 (d, J = 6.9 Hz, 2H), 7.34 (t, J = 8.3 Hz,
4H), 7.24 (d, J = 7.5 Hz, 3H), 7.00 (t, J = 7.3 Hz, 2H), 6.71 (t, J = 7.1 Hz, 1H), 6.48 (d, J = 7.4 Hz,
2H), 4.59 (s, 2H). 13C NMR (100 MHz, DMSO) δ 156.3, 151.7, 140.5, 134.2, 134.0, 131.1, 128.8,
128.7, 128.5, 127.7, 127.0, 123.1, 121.0, 44.6. mass spectrum (ESI): m/e (% relative intensity) 321.1
(100) (M+H)+.
Nꢀbenzylꢀ4ꢀcyanoꢀN'ꢀphenylbenzimidamide (1e): 3.3 g; white solid; yield 71 % (Method A); mp.
158ꢀ162 oC. 1H NMR (600 MHz, CDCl3) δ 7.49 (s, 2H), 7.42 (s, 2H), 7.37 (s, 2H), 7.33 (d, J = 7.5 Hz,
3H), 7.07 (s, 2H), 6.84 (s, 1H), 6.61 (d, J = 4.9 Hz, 2H), 4.83 (brs, 1H), 4.68 (s, 2H). 13C NMR (150
MHz, CDCl3) δ 155.2, 149.8, 139.4, 138.4, 132.1, 129.3, 128.8, 128.6, 128.1, 127.6, 122.8, 122.0,
118.1, 113.0, 46.2. mass spectrum (ESI): m/e (% relative intensity) 312.1 (100) (M+H)+; HRMS (ESI):
m/e calcd for C21H18N3 (M+H)ꢀ: 312.1495, found 312.1504.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 28
1
2
3
4
5
6
7
8
9
NꢀbenzylꢀN'ꢀphenylꢀ1ꢀnaphthimidamide (1f):8 3.3 g; white solid; yield 65 % (Method A); mp.
88ꢀ90 oC. 1H NMR (600 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.79 – 7.67 (m, 2H), 7.42 – 7.47 (m,
4H), 7.40 – 7.26 (m, 5H), 6.89 (s, 2H), 6.67 (s, 3H), 4.83 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
156.6, 150.5, 138.9, 133.2, 130.3, 129.2, 128.7, 128.3, 128.2, 128.1, 127.4, 126.8, 126.7, 126.2, 125.6,
124.8, 122.4, 121.6, 46.1. mass spectrum (ESI): m/e (% relative intensity) 337.1 (100) (M+H)+.
NꢀbenzylꢀN'ꢀphenylpivalimidamide (1g):8 2.2 g; white solid; yield 55 % (Method A); mp. 59ꢀ60 oC.
1H NMR (600 MHz, CDCl3) δ 7.29 (t, J = 7.1 Hz, 2H), 7.24 (t, J = 6.9 Hz, 1H), 7.16 (t, J = 7.0 Hz,
4H), 6.85 (t, J = 7.1 Hz, 1H), 6.79 (d, J = 7.6 Hz, 2H), 4.59 (s, 1H), 3.98 (s, 2H), 1.25 (s, 9H). 13C
NMR (150 MHz, CDCl3) δ 160.2, 151.3, 139.3, 129.0, 128.7, 128.6, 128.4, 127.7, 127.4, 121.2, 120.7,
48.4, 38.8, 29.3. mass spectrum (ESI): m/e (% relative intensity) 267.1 (100) (M+H)+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(4ꢀmethoxybenzyl)ꢀN'ꢀphenylbenzimidamide (1h):8 3.8 g; white solid; yield 81 % (Method A);
mp. 82ꢀ84 oC. 1H NMR (600 MHz, CDCl3) δ 7.35 (s, 2H), 7.22 (m, 5H), 7.05 (s, 2H), 6.89 (d, J = 7.2
Hz, 2H), 6.80 (s, 1H), 6.67 (s, 2H), 4.70 (s, 1H), 4.61 (s, 2H), 3.79 (s, 3H). 13C NMR (150 MHz,
CDCl3) δ 159.0, 157.2, 150.9, 135.2, 131.1, 129.5, 129.2, 128.6, 128.4, 128.3, 123.1, 121.3, 114.1,
55.3, 45.7. mass spectrum (ESI): m/e (% relative intensity) 317.1 (100) (M+H)+.
Nꢀ(4ꢀchlorobenzyl)ꢀN'ꢀphenylbenzimidamide (1i): 4.0 g; white solid; yield 83 % (Method A); mp.
120ꢀ122 oC. 1H NMR (600 MHz, DMSO) δ 7.59 (s, 1H), 7.45 (s, 2H), 7.40 (d, J = 7.5 Hz, 2H), 7.31 –
7.18 (m, 5H), 6.97 (s, 2H), 6.69 (s, 1H), 6.46 (d, J = 6.6 Hz, 2H), 4.57 (s, 2H). 13C NMR (150 MHz,
DMSO) δ 156.7, 151.3, 139.3, 134.8, 130.9, 129.1, 128.8, 128.6, 128.1, 128.1, 128.0, 122.5, 120.4,
ACS Paragon Plus Environment

Page 15 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
43.4. mass spectrum (ESI): m/e (% relative intensity) 321.1 (100) (M+H)+; HRMS (ESI): m/e calcd
for C20H16ClN2 (MꢀH)ꢀ: 319.0997, found 319.0998.
7
8
9
N'ꢀphenylꢀNꢀ(4ꢀ(trifluoromethyl)benzyl)benzimidamide (1j): 4.2 g; white solid; yield 80 %
(Method A); mp. 140ꢀ141 oC. 1H NMR (600 MHz, CDCl3) δ 7.62 (s, 2H), 7.56 (s, 2H), 7.24 (m, 5H),
7.06 (s, 2H), 6.82 (s, 1H), 6.65 (s, 2H), 4.89 (s, 1H), 4.76 (s, 2H). 13C NMR (150 MHz, CDCl3) δ
156.9, 150.4, 143.3, 134.8, 129.7, 129.4, 128.5, 128.4, 128.1, 125.6, 125.6, 125.1, 123.3, 122.9, 121.6,
45.3. mass spectrum (ESI): m/e (% relative intensity) 355.1 (100) (M+H)+; HRMS (ESI): m/e calcd
for C21H16F3N2 (MꢀH)ꢀ: 353.1260, found 353.1274.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Nꢀ(3ꢀnitrobenzyl)ꢀN'ꢀphenylbenzimidamide (1k): 3.2 g; white solid; yield 65 % (Method A); mp.
222ꢀ225 oC. 1H NMR (400 MHz, DMSO) δ 8.53 (s, 1H), 8.23 (d, J = 7.8 Hz, 1H), 8.14 (s, 1H), 7.75 (t,
J = 7.9 Hz, 1H), 7.60 (s, 1H), 7.53 (d, J = 6.4 Hz, 3H), 7.43 (t, J = 7.2 Hz, 2H), 7.24 (t, J = 7.3 Hz,
2H), 7.20 – 7.14 (m, 1H), 7.09 (d, J = 7.5 Hz, 2H), 5.31 (s, 2H). 13C NMR (100 MHz, DMSO) δ 163.1,
148.3, 138.3, 137.2, 135.5, 132.8, 130.6, 130.2, 129.3, 129.1, 128.9, 127.3, 126.5, 123.7, 123.3, 46.6.
mass spectrum (ESI): m/e (% relative intensity) 332.1 (100) (M+H)+; HRMS (ESI): m/e calcd for
C20H16N3O2 (MꢀH)ꢀ: 330.1237, found 330.1259.
NꢀmethylꢀN'ꢀphenylbenzimidamide (1l):7b 1.7 g; white solid; yield 53 % (Method A); mp. 132ꢀ133
oC. 1H NMR (600 MHz, CDCl3) δ 7.20 (m, 5H), 7.04 (s, 2H), 6.79 (s, 1H), 6.64 (s, 2H), 4.63 (brs, 1H),
3.05 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 158.3, 151.0, 135.3, 129.1, 128.6, 128.3, 128.2, 123.2,
121.2, 28.9. mass spectrum (ESI): m/e (% relative intensity) 211.0 (100) (M+H)+.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 28
1
2
3
4
5
6
7
8
9
o
NꢀethylꢀN'ꢀphenylbenzimidamide (1m): 1.8 g; white solid; yield 55 % (Method A); mp. 71ꢀ72 C.
1H NMR (600 MHz, CDCl3) δ 7.21 (m, 5H), 7.04 (s, 2H), 6.79 (s, 1H), 6.63 (d, J = 4.8 Hz, 2H), 4.49
(brs, 1H), 3.53 (s, 2H), 1.29 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 157.5, 151.1, 135.5, 129.0, 128.5,
128.3, 128.2, 123.1, 121.2, 36.6, 14.6. mass spectrum (ESI): m/e (% relative intensity) 225.1 (100)
(M+H)+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NꢀbutylꢀN'ꢀphenylbenzimidamide (1n):24 2.5 g; white solid; yield 65 % (Method A); mp. 100ꢀ101
oC. 1H NMR (600 MHz, DMSO) δ 7.24 (d, J = 6.4 Hz, 3H), 7.16 (s, 2H), 6.96 (t, J = 6.7 Hz, 3H), 6.67
(t, J = 6.6 Hz, 1H), 6.46 (d, J = 4.4 Hz, 2H), 3.33 (s, 2H), 1.59 (s, 2H), 1.39 (d, J = 6.7 Hz, 2H), 0.93 (t,
J = 6.9 Hz, 3H). 13C NMR (150 MHz, DMSO) δ 157.0, 151.7, 135.2, 128.6, 128.1, 127.9, 122.7,
122.6, 120.0, 40.7, 30.6, 19.9, 13.9. mass spectrum (ESI): m/e (% relative intensity) 253.1 (100)
(M+H)+.
Nꢀ(cyclopropylmethyl)ꢀN'ꢀphenylbenzimidamide (1o):8 2.4 g; white solid; yield 63 % (Method A);
mp. 90ꢀ91 oC. 1H NMR (400 MHz, DMSO) δ 7.25 (d, J = 4.4 Hz, 3H), 7.18 (s, 2H), 7.05 (s, 1H), 6.97
(s, 2H), 6.68 (d, J = 4.4 Hz, 1H), 6.46 (d, J = 3.6 Hz, 2H) , 3.22 (s, 2H), 1.16 (s, 1H), 0.45 (d, J = 4.8
Hz, 2H), 0.2529 (s, 2H). 13C NMR (150 MHz, DMSO) δ 157.0, 151.7, 135.1, 128.7, 128.1, 127.9,
123.6, 122.6, 120.1, 45.3, 10.5, 3.3. mass spectrum (ESI): m/e (% relative intensity) 251.1 (100)
(M+H)+.
Nꢀ(cyclohexylmethyl)ꢀN'ꢀphenylbenzimidamide (1p): 3.1 g; white solid; yield 71 % (Method A);
o
1
mp. 94ꢀ95 C. H NMR (600 MHz, DMSO) δ 7.24 (s, 2H), 7.16 (s, 2H), 6.96 (s, 3H), 6.66 (s, 1H),
6.44 (s, 2H), 3.35 (s, 1H), 3.19 (s, 2H), 1.81 (s, 2H), 1.70 (s, 3H), 1.64 (s, 1H), 1.20 (d, J = 10.7 Hz,
ACS Paragon Plus Environment

Page 17 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
3H), 0.98 (s, 2H). 13C NMR (150 MHz, DMSO) δ 157.1, 151.8, 135.3, 128.7, 128.6, 128.1, 127.8,
122.6, 119.9, 47.2, 36.8, 30.8, 26.2, 25.6. mass spectrum (ESI): m/e (% relative intensity) 293.2 (100)
(M+H)+; HRMS (ESI): m/e calcd for C20H23N2 (MꢀH)ꢀ: 291.1856, found 291.1867.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NꢀbenzylꢀN'ꢀpꢀtolylbenzimidamide (4a):8 3.6 g; white solid; yield 80 % (Method B); mp. 126ꢀ127
oC. 1H NMR (600 MHz, DMSO) δ 7.46 (brs, 1H), 7.42 (s, 2H), 7.34 (t, J = 7.1 Hz, 2H), 7.27 (s, 3H),
7.25 – 7.17 (m, 3H), 6.77 (d, J = 6.7 Hz, 2H), 6.34 (d, J = 6.4 Hz, 2H), 4.57 (s, 2H), 2.10 (s, 3H). 13
C
NMR (150 MHz, DMSO) δ 156.8, 148.7, 140.3, 135.1, 128.7, 128.7, 128.6, 128.1, 128.0, 127.1, 126.4,
122.4, 122.4, 43.9, 20.2. mass spectrum (ESI): m/e (% relative intensity) 301.1 (100) (M+H)+.
NꢀbenzylꢀN'ꢀ(4ꢀmethoxyphenyl)benzimidamide (4b):8 4.2 g; white solid; yield 88 % (Method B);
o
mp. 115ꢀ117 C. 1H NMR (600 MHz, DMSO) δ 7.42 (m, 3H), 7.34 (t, J = 7.0 Hz, 2H), 7.27 (s, 3H),
7.23 (d, J = 13.4 Hz, 3H), 6.56 (d, J = 7.5 Hz, 2H), 6.37 (d, J = 6.7 Hz, 2H), 4.58 (s, 2H), 3.58 (s, 3H).
13C NMR (150 MHz, DMSO) δ 156.9, 153.3, 144.5, 140.3, 135.2, 128.6, 128.1, 128.0, 127.2, 126.4,
123.2 (d, J = 8.3 Hz), 113.51, 113.46, 54.9 (d, J = 7.1 Hz), 43.9. mass spectrum (ESI): m/e (% relative
intensity) 317.1 (100) (M+H)+.
NꢀbenzylꢀN'ꢀmꢀtolylbenzimidamide (4c):8 3.2 g; white solid; yield 72 % (Method B); mp. 106ꢀ107
1
oC. H NMR (600 MHz, DMSO) δ 7.54 (brs, 1H), 7.41 (s, 2H), 7.34 (t, J = 7.2 Hz, 2H), 7.31 – 7.18
(m, 6H), 6.83 (s, 1H), 6.51 (d, J = 5.1 Hz, 1H), 6.36 (d, J = 14.6 Hz, 1H), 6.21 (s, 1H), 4.58 (s, 2H),
2.08 (s, 3H). 13C NMR (150 MHz, DMSO) δ 156.7, 151.1, 148.5, 140.2, 137.1, 134.9, 128.8, 128.6,
128.1, 127.9, 127.1, 126.4, 123.3, 121.2, 119.6, 44.0, 21.0. mass spectrum (ESI): m/e (% relative
intensity) 301.1 (100) (M+H)+.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 28
1
2
3
4
5
NꢀbenzylꢀN'ꢀ(4ꢀchlorophenyl)benzimidamide (4d):8 4.0 g; white solid; yield 83 % (Method B); mp.
6
7
o
101ꢀ102 C. 1H NMR (600 MHz, CDCl3) δ 7.43 (s, 2H), 7.37 (t, J = 6.7 Hz, 2H), 7.30 (t, J = 7.1 Hz,
8
9
2H), 7.27 – 7.18 (m, 4H), 7.01 (d, J = 7.1 Hz, 2H), 6.59 (d, J = 5.6 Hz, 2H), 4.83 (brs, 1H), 4.68 (s,
2H); 13C NMR (150 MHz, CDCl3) δ 157.6, 149.5, 138.7, 134.7, 129.4, 129.1, 128.9, 128.7, 128.5,
128.4, 128.1, 127.5, 127.0, 126.4, 124.3, 46.2. mass spectrum (ESI): m/e (% relative intensity) 321.1
(100) (M+H)+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
NꢀbenzylꢀN'ꢀ(4ꢀbromophenyl)benzimidamide (3a):8 4.1 g; white solid; yield 75 % (Method B); mp.
105ꢀ106 oC. 1H NMR (600 MHz, CDCl3) δ 7.42 (s, 2H), 7.37 (t, J = 6.4 Hz, 2H), 7.33 – 7.28 (m, 2H),
7.25 (s, 2H), 7.22 (s, 2H), 7.15 (d, J = 6.6 Hz, 2H), 6.54 (s, 2H), 4.83 (brs, 1H), 4.68 (s, 2H). 13C
NMR (150 MHz, CDCl3) δ 157.5, 150.0, 138.7, 134.6, 132.1, 131.3, 129.5, 128.7, 128.5, 128.1, 127.5,
124.8, 114.1, 46.1. mass spectrum (ESI): m/e (% relative intensity) 365.1 (100) (M+H)+.
NꢀbenzylꢀN'ꢀ(4ꢀfluorophenyl)benzimidamide (4f):8 3.2 g; white solid; yield 70 % (Method B); mp.
108ꢀ109 oC. 1H NMR (600 MHz, CDCl3) δ 7.43 (s, 2H), 7.37 (t, J = 6.7 Hz, 2H), 7.32 – 7.22(m, 6H),
6.75 (t, J = 7.7 Hz, 2H), 6.59 (s, 2H), 4.78 (brs, 1H), 4.68 (s, 2H). 13C NMR (150 MHz, CDCl3) δ
159.1, 157.6, 146.9, 138.8, 134.9, 129.3, 128.7, 128.5, 128.4, 128.1, 127.5, 124.0, 123.9, 115.0, 114.9,
46.1. mass spectrum (ESI): m/e (% relative intensity) 305.1 (100) (M+H)+.
NꢀbenzylꢀN'ꢀ(4ꢀ(trifluoromethyl)phenyl)benzimidamide (4g):8 3.8 g; white solid; yield 71 %
(Method B); mp. 88ꢀ89 oC. 1H NMR (600 MHz, DMSO) δ 7.92 (s, 1H), 7.43 (s, 2H), 7.38 – 7.34 (m,
2H), 7.32 (m, 5H), 7.27 (s, 3H), 6.62 (s, 2H), 4.61 (s, 2H). 13C NMR (150 MHz, DMSO) δ 157.8,
ACS Paragon Plus Environment

Page 19 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
155.3, 139.8, 134.1, 129.3, 128.7, 128.2, 127.2, 126.5, 125.7, 125.3, 124.0, 122.9, 120.5 (d, J = 32.6
Hz), 44.2. mass spectrum (ESI): m/e (% relative intensity) 355.1 (100) (M+H)+.
8
9
NꢀbenzylꢀN'ꢀ(4ꢀcyanophenyl)benzimidamide (4h): 2.8 g; white solid; yield 61 % (Method B); mp.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
117ꢀ119 C. 1H NMR (600 MHz, DMSO) δ 8.05 (s, 1H), 7.41 (t, J = 8.1 Hz, 4H), 7.34 (dt, J = 19.6,
7.2 Hz, 5H), 7.25 (d, J = 6.6 Hz, 3H), 6.57 (d, J = 8.3 Hz, 2H), 4.60 (d, J = 5.4 Hz, 2H). 13C NMR
(150 MHz, DMSO) δ 158.0, 156.4, 139.6, 133.9, 132.5 (d, J = 4.3 Hz), 129.5, 128.7, 128.2 (d, J = 4.4
Hz), 127.2, 126.6, 123.5, 123.4, 119.7, 101.7, 44.2. mass spectrum (ESI): m/e (% relative intensity)
312.1 (100) (M+H)+; HRMS (ESI): m/e calcd for C21H16N3 (MꢀH)ꢀ: 310.1339, found 310.1337.
NꢀbenzylꢀN'ꢀ(4ꢀnitrophenyl)benzimidamide hydrochloride (4i): 3.5 g; yellow solid; yield 71 %
(Method B); mp. 194ꢀ195 oC. 1H NMR (600 MHz, DMSO) δ 12.75 (brs, 1H), 11.06 (brs, 1H), 8.10 (d,
J = 6.9 Hz, 2H), 7.59 (s, 3H), 7.53 (s, 2H), 7.50 – 7.40 (m, 4H), 7.37 (s, 1H), 7.27 (s, 2H), 5.09 (s, 2H).
13C NMR (150 MHz, DMSO) δ 162.4, 144.6, 135.4, 132.7, 130.0, 128.9, 128.6, 128.2, 127.9, 125.8,
124.7, 124.3, 119.9, 47.6. mass spectrum (ESI): m/e (% relative intensity) 332.1 (100) (M+H)+;
HRMS (ESI): m/e calcd for C20H16N3O2 (MꢀH)ꢀ: 330.1237, found 330.1234.
NꢀbenzylꢀN'ꢀ(naphthalenꢀ1ꢀyl)benzimidamide (4j): 3.2 g; white solid; yield 63 % (Method B); mp.
101ꢀ102 oC. 1H NMR (600 MHz, CDCl3) δ 8.19 (s, 1H), 7.75 (s, 1H), 7.51 (s, 2H), 7.43 (s, 4H), 7.33
(s, 2H), 7.22 – 7.01 (m, 6H), 6.39 (s, 1H), 5.00 (s, 1H), 4.85 (s, 2H). 13C NMR (150 MHz, CDCl3) δ
157.0, 147.4, 139.1, 134.2, 129.3, 128.8, 128.0, 127.9, 127.7, 127.4, 125.9, 125.7, 124.9, 124.3, 121.4,
117.0, 46.2. mass spectrum (ESI): m/e (% relative intensity) 337.1 (100) (M+H)+; HRMS (ESI): m/e
calcd for C24H19N2 (MꢀH)ꢀ: 335.1543, found 335.1536.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 28
1
2
3
4
5
6
7
8
9
o
1
2,4ꢀdiphenylquinazoline (2a):7d 49.6 mg; white solid; yield 88 %; mp. 112ꢀ113 C. H NMR (600
MHz, CDCl3) δ 8.70 (d, J = 7.1 Hz, 2H), 8.19 (d, J = 6.8 Hz, 1H), 8.14 (d, J = 8.2 Hz, 1H), 7.90 (s,
3H), 7.60 (s, 3H), 7.54 (dt, J = 19.1, 9.7 Hz, 4H). 13C NMR (150 MHz, CDCl3) δ 168.5, 160.2, 151.8,
138.0, 137.6, 133.7, 130.6, 130.2, 130.0, 128.7, 128.6, 127.1, 127.1, 121.7. mass spectrum (ESI): m/e (%
relative intensity) 283.1 (100) (M+H)+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀ(4ꢀmethoxyphenyl)ꢀ4ꢀphenylquinazoline (2b):7d 56.8 mg; white solid; yield 91 %; mp. 162ꢀ163 oC.
1H NMR (600 MHz, CDCl3) δ 8.65 (d, J = 8.3 Hz, 2H), 8.09 (dd, J = 15.9, 8.3 Hz, 2H), 7.91 – 7.81
(m, 3H), 7.57 (s, 3H), 7.48 (t, J = 7.2 Hz, 1H), 7.03 (d, J = 8.3 Hz, 2H), 3.88 (s, 3H). 13C NMR (150
MHz, CDCl3) δ 168.2, 161.7, 160.0, 152.0, 137.7, 133.5, 130.8, 130.3, 130.1, 129.8, 128.9, 128.5,
126.9, 126.5, 121.3, 113.8, 55.4. mass spectrum (ESI): m/e (% relative intensity) 313.1 (100) (M+H)+.
4ꢀphenylꢀ2ꢀ(pꢀtolyl)quinazoline (2c):7d 55.6 mg; white solid; yield 94 %; mp. 160ꢀ161 C. H NMR
(600 MHz, CDCl3) δ 8.59 (d, J = 7.7 Hz, 2H), 8.15 (d, J = 8.3 Hz, 1H), 8.11 (d, J = 8.3 Hz, 1H), 7.88
(t, J = 7.6 Hz, 3H), 7.59 (s, 3H), 7.53 (t, J = 7.5 Hz, 1H), 7.33 (d, J = 7.7 Hz, 2H), 2.44 (s, 3H). 13C
NMR (150 MHz, CDCl3) δ 168.3, 160.3, 151.9, 140.8, 137.7, 135.4, 133.5, 130.2, 129.9, 129.3, 129.0,
128.6, 128.5, 127.0, 126.8, 121.6, 21.6. mass spectrum (ESI): m/e (% relative intensity) 297.1.1 (100)
(M+H)+.
o
1
2ꢀ(4ꢀchlorophenyl)ꢀ4ꢀphenylquinazoline (2d):7d 51.2 mg; white solid; yield 81 %; mp. 179ꢀ181 C.
o
1H NMR (600 MHz, CDCl3) δ 8.66 (d, J = 8.0 Hz, 2H), 8.18 (d, J = 7.7 Hz, 1H), 8.14 (d, J = 8.2 Hz,
1H), 7.88 – 7.92 (m, 3H), 7.61 (s, 3H), 7.58 (t, J = 7.5 Hz, 1H), 7.50 (d, J = 8.0 Hz, 2H). 13C NMR
ACS Paragon Plus Environment

Page 21 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(150 MHz, CDCl3) δ 168.5, 159.2, 151.8, 137.5, 136.8, 136.6, 133.8, 130.2, 130.1, 129.0, 128.7, 128.6,
127.3, 127.1, 121.7. mass spectrum (ESI): m/e (% relative intensity) 317.1 (100) (M+H)+.
4ꢀ(4ꢀphenylquinazolinꢀ2ꢀyl)benzonitrile (2e): 29.5 mg; white solid; yield 48 %; mp. 198ꢀ200 oC. 1H
NMR (600 MHz, CDCl3) δ 8.84 (d, J = 7.2 Hz, 2H), 8.23 (d, J = 7.0 Hz, 1H), 8.18 (d, J = 8.1 Hz, 1H),
7.96 (s, 1H), 7.89 (s, 2H), 7.82 (d, J = 7.0 Hz, 2H), 7.63 (s, 4H). 13C NMR (150 MHz, CDCl3) δ 168.8,
158.2, 151.7, 142.2, 137.2, 134.1, 132.4, 130.3, 130.2, 129.3, 129.2, 128.7, 128.0, 127.2, 122.0, 119.0,
113.7. mass spectrum (ESI): m/e (% relative intensity) 308.1 (100) (M+H)+; HRMS (ESI): m/e calcd
for C21H12N3 (MꢀH)ꢀ: 306.1037, found 306.1055.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
2ꢀ(naphthalenꢀ1ꢀyl)ꢀ4ꢀphenylquinazoline (2f):7d 55.1 mg; white solid; yield 83 %; colorless oil. H
NMR (600 MHz, CDCl3) δ 8.77 (d, J = 8.3 Hz, 1H), 8.25 (t, J = 6.8 Hz, 2H), 8.21 (d, J = 8.3 Hz, 1H),
8.02 – 7.91 (m, 3H), 7.90 (d, J = 5.7 Hz, 2H), 7.67 – 7.48 (m, 7H). 13C NMR (150 MHz, CDCl3) δ
168.6, 162.8, 151.6, 137.4, 136.5, 134.2, 133.9, 131.4, 130.4, 130.2, 130.1, 129.8, 129.1, 128.7, 128.5,
127.6, 127.1, 126.8, 126.1, 125.9, 125.4, 121.3. mass spectrum (ESI): m/e (% relative intensity) 333.1
(100) (M+H)+.
2ꢀtertꢀbutylꢀ4ꢀphenylquinazoline (2g):8 48.9 mg; white solid; yield 62 %; mp. 115ꢀ117 oC. 1H NMR
(600 MHz, CDCl3) δ 8.09 (d, J = 8.1 Hz, 2H), 7.83 (t, J = 9.9 Hz, 3H), 7.56 (s, 3H), 7.51 (t, J = 7.5 Hz,
1H), 1.55 (s, 9H). 13C NMR (150 MHz, CDCl3) δ 172.8, 167.5, 151.3, 137.9, 133.0, 130.3, 129.7,
128.8, 128.5, 126.7, 126.6, 120.9, 39.7, 29.7. mass spectrum (ESI): m/e (% relative intensity) 363.1
(100) (M+H)+.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 22 of 28
1
2
3
4
5
6
7
8
9
4ꢀ(4ꢀmethoxyphenyl)ꢀ2ꢀphenylquinazoline (2h):7d 55.5 mg; white solid; yield 89 %; mp. 115ꢀ116 oC.
1H NMR (600 MHz, CDCl3) δ 8.69 (d, J = 7.1 Hz, 2H), 8.16 (t, J = 6.8 Hz, 2H), 7.94 – 7.82 (m, 3H),
7.51 (dd, J = 14.1, 7.0 Hz, 4H), 7.11 (d, J = 8.0 Hz, 2H), 3.92 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
167.8, 161.3, 160.1, 151.9, 138.2, 133.5, 131.9, 130.5, 130.1, 129.0, 128.7, 128.6, 127.1, 126.9, 121.6,
114.1, 55.5. mass spectrum (ESI): m/e (% relative intensity) 313.1 (100) (M+H)+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
4ꢀ(4ꢀchlorophenyl)ꢀ2ꢀphenylquinazoline (2i):7d 53.1 mg; white solid; yield 84 %; mp. 142ꢀ143 C.
1H NMR (600 MHz, CDCl3) δ 8.67 (d, J = 6.9 Hz, 2H), 8.16 (d, J = 8.3 Hz, 1H), 8.07 (d, J = 8.3 Hz,
1H), 7.89 (t, J = 7.4 Hz, 1H), 7.84 (d, J = 8.0 Hz, 2H), 7.58 (d, J = 8.2 Hz, 2H), 7.56 – 7.48 (m, 4H).
13C NMR (150 MHz, CDCl3) δ 167.1, 160.2, 152.0, 138.0, 136.3, 136.1, 133.8, 131.6, 130.7, 129.3,
128.9, 128.7, 128.6, 127.3, 126.6, 121.5. mass spectrum (ESI): m/e (% relative intensity) 317.1 (100)
(M+H)+.
2ꢀphenylꢀ4ꢀ(4ꢀ(trifluoromethyl)phenyl)quinazoline (2j): 59.5 mg; white solid; yield 85 %; mp.
114ꢀ115 oC. 1H NMR (600 MHz, CDCl3) δ 8.67 (d, J = 6.6 Hz, 2H), 8.17 (d, J = 8.4 Hz, 1H), 8.02 (d,
J = 8.3 Hz, 1H), 7.98 (d, J = 7.6 Hz, 2H), 7.90 (t, J = 7.6 Hz, 1H), 7.86 (d, J = 7.7 Hz, 2H), 7.58 –
7.47 (m, 4H). 13C NMR (150 MHz, CDCl3) δ 166.9, 160.2, 152.0, 141.1, 137.8, 133.9, 131.8 (d, J =
32.5 Hz), 130.8, 130.5, 129.3, 128.6 (d, J = 4.5 Hz), 127.4, 126.4, 125.5 (d, J = 4.5 Hz), 121.4. mass
spectrum (ESI): m/e (% relative intensity) 351.1 (100) (M+H)+; HRMS (ESI): m/e calcd for
C21H12F3N2 (MꢀH)ꢀ: 349.0947, found 349.0936.
4ꢀ(3ꢀnitrophenyl)ꢀ2ꢀphenylquinazoline (2k):7c 59.5 mg; white solid; yield 91 %; mp. 180ꢀ182 oC. 1H
NMR (600 MHz, CDCl3) δ 8.77 (s, 1H), 8.68 (d, J = 6.9 Hz, 2H), 8.46 (d, J = 7.8 Hz, 1H), 8.26 – 8.15
ACS Paragon Plus Environment

Page 23 of 28
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
(m, 2H), 8.03 (d, J = 8.3 Hz, 1H), 7.95 (t, J = 7.5 Hz, 1H), 7.80 (t, J = 7.8 Hz, 1H), 7.61 (t, J = 7.5 Hz,
1H), 7.54 (d, J = 7.4 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 165.7, 160.3, 152.1, 148.4, 139.3, 137.6,
136.1, 134.2, 130.9, 129.8, 129.5, 128.7, 128.7, 127.8, 125.9, 125.1, 124.7, 121.2. mass spectrum
(ESI): m/e (% relative intensity) 328.1 (100) (M+H)+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2ꢀphenylꢀ4ꢀpropylquinazoline (2n):7d 17.9 mg; white solid; yield 36 %; mp. 60ꢀ62 oC. 1H NMR (600
MHz, CDCl3) δ 8.64 (d, J = 7.2 Hz, 2H), 8.11 (dd, J = 15.8, 8.2 Hz, 2H), 7.85 (t, J = 7.3 Hz, 1H), 7.54
(ddd, J = 22.3, 14.9, 6.9 Hz, 4H), 3.32 (t, J = 7.4 Hz, 2H), 2.03 (dd, J = 14.5, 7.2 Hz, 2H), 1.12 (t, J =
7.1 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 170.4, 159.0, 149.5, 137.3, 132.4, 129.4, 128.3, 127.6,
127.5, 125.7, 123.6, 121.6, 35.5, 20.9, 13.3. mass spectrum (ESI): m/e (% relative intensity) 249.1
(100) (M+H)+.
4ꢀcyclopropylꢀ2ꢀphenylquinazoline (2o):23 20.1 mg; white solid; yield 41 %; mp. 75ꢀ77 oC. 1H NMR
(600 MHz, CDCl3) δ 8.61 (d, J = 7.3 Hz, 2H), 8.32 (d, J = 8.3 Hz, 1H), 8.15 (s, 1H), 7.87 (t, J = 7.6
Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.57 – 7.45 (m, 3H), 2.89 – 2.78 (m, 1H), 1.57 (s, 2H), 1.29 (d, J =
4.8 Hz, 2H). mass spectrum (ESI): m/e (% relative intensity) 247.1 (100) (M+H)+.
4ꢀcyclohexylꢀ2ꢀphenylquinazoline (2p):7d 17.3 mg; white solid; yield 30 %; mp. 94ꢀ95 oC. 1H NMR
(600 MHz, CDCl3) δ 8.68 (d, J = 7.3 Hz, 2H), 8.16 (d, J = 8.2 Hz, 1H), 8.12 (d, J = 7.7 Hz, 1H), 7.84
(t, J = 7.4 Hz, 1H), 7.57 (t, J = 7.6 Hz, 1H), 7.55 – 7.47 (m, 3H), 3.58 (t, J = 11.1 Hz, 1H), 2.07 – 1.91
(m, 6H), 1.85 (d, J = 12.2 Hz, 1H), 1.62 – 1.51 (m, 2H), 1.48 – 1.38 (m, 1H). 13C NMR (150 MHz,
CDCl3) δ 175.0, 159.9, 150.7, 138.4, 133.2, 130.4, 129.4, 128.6, 128.5, 126.6, 124.1, 121.7, 41.5, 32.1,
26.5, 26.1. mass spectrum (ESI): m/e (% relative intensity) 289.2 (100) (M+H)+.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 24 of 28
1
2
3
4
5
6
7
8
9
o
1
6ꢀmethylꢀ2,4ꢀdiphenylquinazoline (5a):8 54.5 mg; white solid; yield 92 %; mp. 167ꢀ170 C. H
NMR (600 MHz, CDCl3) δ 8.67 (d, J = 7.5 Hz, 2H), 8.05 (d, J = 8.5 Hz, 1H), 7.87 (d, J = 8.0 Hz, 3H),
7.70 (d, J = 8.5 Hz, 1H), 7.59 (d, J = 5.5 Hz, 3H), 7.55 – 7.44 (m, 3H), 2.49 (s, 3H). 13C NMR (150
MHz, CDCl3) δ 167.5, 159.5, 150.4, 138.2, 137.8, 137.2, 135.8, 130.3, 130.1, 129.8, 128.8, 128.5,
125.6, 121.6, 21.9. mass spectrum (ESI): m/e (% relative intensity) 297.1 (100) (M+H)+.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
o
1
6ꢀmethoxyꢀ2,4ꢀdiphenylquinazoline (5b):8 59.9 mg; white solid; yield 96 %; mp. 142ꢀ144 C. H
NMR (600 MHz, CDCl3) δ 8.65 (d, J = 7.3 Hz, 2H), 8.08 (d, J = 9.0 Hz, 1H), 7.90 (d, J = 6.7 Hz, 2H),
7.60 (d, J = 7.1 Hz, 3H), 7.58 – 7.43 (m, 4H), 7.39 (s, 1H), 3.85 (s, 3H). 13C NMR (150 MHz, CDCl3)
δ 166.6, 158.6, 158.1, 148.1, 138.3, 138.0, 130.6, 130.2, 129.9, 129.8, 128.7, 128.5, 128.3, 126.3,
122.5, 104.3, 55.7. mass spectrum (ESI): m/e (% relative intensity) 313.1 (100) (M+H)+.
o
1
7ꢀmethylꢀ2,4ꢀdiphenylquinazoline (5c):8 50.9 mg; white solid; yield 86 % ; mp. 135ꢀ140 C. H
NMR (600 MHz, CDCl3) δ 8.68 (d, J = 7.5 Hz, 2H), 7.99 (d, J = 8.5 Hz, 1H), 7.87 (d, J = 6.5 Hz, 2H),
7.50 (q, J = 8.6, 7.1 Hz, 8H), 2.58 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 167.8, 160.3, 153.1, 152.2,
144.6, 138.3, 137.8, 137.8, 136.2, 133.2, 130.5, 130.23, 130.19, 129.9, 129.3, 129.1, 129.0, 128.7,
128.5, 128.3, 128.0, 127.5, 126.7, 119.9, 23.9, 22.2. mass spectrum (ESI): m/e (% relative intensity)
297.1 (100) (M+H)+.
6ꢀchloroꢀ2,4ꢀdiphenylquinazoline (5d):8 55.0 mg; white solid; yield 87 %; mp. 194ꢀ195 oC. 1H NMR
(600 MHz, CDCl3) δ 8.68 (d, J = 6.6 Hz, 2H), 8.11 (d, J = 13.6 Hz, 2H), 7.87 (d, J = 3.4 Hz, 2H), 7.82
(d, J = 8.7 Hz, 1H), 7.62 (s, 3H), 7.53 (d, J = 6.9 Hz, 3H). 13C NMR (150 MHz, CDCl3) δ 167.6, 160.4,
ACS Paragon Plus Environment

Page 25 of 28
The Journal of Organic Chemistry
1
2
3
4
5
150.4, 137.6, 137.0, 134.6, 132.6, 130.81, 130.79, 130.3, 130.1, 128.8, 128.7, 128.6, 125.8, 122.2.
6
7
mass spectrum (ESI): m/e (% relative intensity) 317.1 (100) (M+H)+.
8
9
6ꢀbromoꢀ2,4ꢀdiphenylquinazoline (5e):8 62.6 mg; white solid; yield 87 %; mp. 203ꢀ205 C. H
NMR (600 MHz, CDCl3) δ 8.67 (d, J = 7.0 Hz, 2H), 8.26 (s, 1H), 8.03 (d, J = 9.0 Hz, 1H)), 7.94 (d, J
= 8.4 Hz, 1H)), 7.86 (d, J = 3.6 Hz, 2H), 7.62 (s, 3H), 7.52 (d, J = 6.5 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ 167.5, 160.5, 150.7, 137.1， 137.8, 137.1, 131.0, 130.9, 130.3, 130.1, 129.1, 128.8, 128.7,
128.6, 122.7, 120.7. mass spectrum (ESI): m/e (% relative intensity) 361.1 (100) (M+H)+.
6ꢀfluoroꢀ2,4ꢀdiphenylquinazoline (5f):8 54.0 mg; white solid; yield 90 %; mp. 173ꢀ174 oC. 1H NMR
(600 MHz, CDCl3) δ 8.67 (d, J = 7.2 Hz, 2H), 8.20 – 8.12 (m, 1H), 7.87 (d, J = 3.3 Hz, 2H), 7.74 (d, J
= 8.9 Hz, 1H), 7.65 (t, J = 8.4 Hz, 1H), 7.60 (s, 3H), 7.51 (t, J = 8.3 Hz, 3H). 13C NMR (150 MHz,
CDCl3) δ 167.8 (d, J = 5.5 Hz), 161.2, 159.9 (d, J = 2.5 Hz), 159.5, 149.1, 137.8, 137.2, 131.8 (d, J =
8.6 Hz), 130.6, 130.2, 129.9, 128.7, 128.6 (d, J = 5.8 Hz), 124.0, 123.8, 122.1 (d, J = 9.0 Hz), 110.5,
110.3. mass spectrum (ESI): m/e (% relative intensity) 301.1 (100) (M+H)+.
o
1
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
2,4ꢀdiphenylꢀ6ꢀ(trifluoromethyl)quinazoline (5g):8 44.8 mg; white solid; yield 64 %; mp. 145ꢀ147
oC. 1H NMR (600 MHz, CDCl3) δ 8.72 (d, J = 3.1 Hz, 2H), 8.43 (s, 1H), 8.27 (d, J = 8.8 Hz, 1H), 8.05
(d, J = 8.3 Hz, 1H), 7.89 (s, 2H), 7.65 (s, 3H), 7.54 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 169.4,
161.9, 153.2, 137.4, 136.8, 131.7, 131.3, 131.0, 130.6, 130.5, 130.2, 129.3 (d, J = 2.9 Hz), 129.0,
128.9, 128.7, 125.1 (d, J = 4.4 Hz), 124.6, 122.8, 120.7. mass spectrum (ESI): m/e (% relative
intensity) 351.1 (100) (M+H)+.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 26 of 28
1
2
3
4
5
6
7
8
9
2,4ꢀdiphenylquinazolineꢀ6ꢀcarbonitrile (5h): 26.8 mg; white solid; yield 44 %; mp. 224ꢀ225 C. 1H
NMR (600 MHz, CDCl3) δ 8.74 (s, 2H), 8.52 (s, 1H), 8.29 (d, J = 6.2 Hz, 1H), 8.03 (d, J = 5.0 Hz,
1H), 7.88 (d, J = 3.9 Hz, 2H), 7.67 (s, 3H), 7.57 (s, 3H). 13C NMR (150 MHz, CDCl3) δ 169.1, 162.4,
153.2, 137.1, 136.4, 134.1, 133.7, 131.6, 130.9, 130.8, 130.2, 129.2, 129.0, 128.8, 121.2, 118.3, 110.4.
mass spectrum (ESI): m/e (% relative intensity) 330.1 (100) (M+Na)+; HRMS (ESI): m/e calcd for
C21H12N3 (MꢀH)ꢀ: 306.1037, found 306.1046.
o
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
6ꢀnitroꢀ2,4ꢀdiphenylquinazoline (5i): 7d 24.2 mg; white solid; yield 37 %; mp. 245ꢀ247 oC. 1H NMR
(600 MHz, CDCl3) δ 9.07 (s, 1H), 8.75 (d, J = 4.5 Hz, 2H), 8.66 (d, J = 9.0 Hz, 1H), 8.31 (d, J = 9.1
Hz, 1H), 7.94 – 7.89 (m, 2H), 7.68 (d, J = 5.0 Hz, 3H), 7.57 (s, 3H). 13C NMR (150 MHz, CDCl3) δ
170.6, 162.8, 154.3, 145.5, 137.0, 136.4, 131.8, 131.1, 130.9, 130.3, 129.3, 129.1, 128.8, 127.1, 124.3,
120.5. mass spectrum (ESI): m/e (% relative intensity) 328.1 (100) (M+H)+.
2,4ꢀdiphenylbenzo[h]quinazoline (5j):7d 54.4 mg; white solid; yield 82 %; mp. 152ꢀ153 oC. 1H NMR
(600 MHz, CDCl3) δ 9.53 (d, J = 7.1 Hz, 1H), 8.84 (d, J = 7.6 Hz, 2H), 7.95 (d, J = 9.0 Hz, 1H), 7.91
(d, J = 6.6 Hz, 3H), 7.81 – 7.79 (m, 2H), 7.76 (d, J = 9.1 Hz, 1H), 7.52 – 7.61 (m, 6H). 13C NMR (150
MHz, CDCl3) δ 166.7, 160.1, 151.9, 138.4, 138.0, 135.1, 130.7, 130.5, 130.3, 130.1, 129.7, 128.7,
128.5, 127.8, 127.8, 127.3, 125.3, 122.8, 119.2. mass spectrum (ESI): m/e (% relative intensity) 333.1
(100) (M+H)+.
Acknowledgment : YT thanks National Natural Science Foundation of China (21172169) and the
National Basic Research Project (2014CB932201) for financial support.
ACS Paragon Plus Environment

Page 27 of 28
The Journal of Organic Chemistry
1
2
3
4
5
Supporting Information: Available Supporting Information. NMR spectra of compounds.
6
7
This material is available free of charge via internet at http://pubs.acs.org.
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
References
1
Review on photochemistry: (a) Roth, H. D. Angew. Chem. Int. Ed. Engl. 1989, 28, 1193.; (b)
Yoon, T. P.; Ischay, M. A.; Du, J.; Nat. Chem. 2010, 2, 527.; (c) Albini, A.; Fagnoni, M. Green
Chem. 2004, 6, 1.
2
Selected recent reviews on visibleꢀlight photoredox catalysis: (a) Prier, C. K.; Rankic, D. A.;
MacMillan, D. W. C. Chem. Rev. 2013, 113, 5322; (b) Schultz, D. M.; Yoon, T. P. Science. 2014,
343, 1239176; (c) Narayanam, J. M. R.; Stephenson, C. R. J. Chem. Soc. Rev. 2011, 40, 102.; (d)
Shi, L.; Xia, W. J. Chem. Soc. Rev. 2012, 41, 7687.; (e) Xi, Y. M.; Yi, H.; Lei, A.W. Org.
Biomol. Chem. 2013, 11, 2387.
3
(a) Pan, Y. H.; Wang, S.; Kee, C. W.; Dubuisson, E.; Yang, Y. Y.; Loh, K. P.; Tan, C. H. Green
Chem. 2011, 13, 3341. (b) Zhong, J. J.; Meng, Q. Y.; Liu, B.; Li, X. B.; Gao, X. W.; Lei, T.; Wu,
C. J.; Li, Z. J.; Tung, C. H.; Wu, L. Z. Org. Lett. 2014, 16, 1988. (c) Rueping, M.; Vila, C.;
Bootwicha, T. ACS Catal. 2013, 3, 1676. (d) Meng, Q. Y.; Zhong, J. J.; Liu, Q.; Gao, X. W.;
Zhang, H. H.; Lei, T.; Li, Z. J.; Feng, K.; Chen, B.; Tung, C. H.; Wu, L. Z. J. Am. Chem. Soc.
2013, 135, 19052. (e) Hari, D. P.; König, B. Org. Lett. 2011, 13, 3852.
4
Biological activities of quinazolines, see: (a) Foster, B. A.; Coffrey, H. A.; Morin, M. J.;
Rastinejad, F. Science. 1999, 286, 2507. (b) Michael, J. P. Nat. Prod. Rep. 2008, 25, 166. (c)
Lüth, A.; Löwe, W. Eur. J. Med. Chem. 2008, 43, 1478. (d) Doyle, L. A.; Ross, D. D. Oncogene.
2003, 22, 7340.
5
6
7
Gundla, R.; Kazemi, R.; Sanam, R.; Muttineni, R.; Sarma, J. A. R. P.; Dayam, R.; Neamati, N. J.
Med. Chem. 2008, 51, 3367.
Mendes da Silva, J. F.; Walters, M.; AlꢀDamluji, S.; Ganellin, C. R. Bioorg. Med. Chem. 2008,
16, 7254.
For the synthesis of quinazolines, see: (a) Wang, C.; Li, S. F.; Liu, H. X.; Jiang, Y. Y.; Fu, H. J.
Org. Chem. 2010, 75, 7936. (b) Han, B.; Yang, X. L.; Wang, C.; Bai, Y. W.; Pan, T. C.; Chen, X.;
Yu. W.; J. Org. Chem. 2012, 77, 1136. (c) Zhang, W.; Guo, F.; Wang, F.; Zhao, N.; Liu, L.; Li, J.;
Wang, Z. H. Org. Biomol. Chem. 2014, 12, 5752. (d) Zhao, D.; Shen, Q.; Li, J. X. Adv. Synth.
Catal. 2015, 357, 339.
8
Lin, J. P.; Zhang, F. H.; Long, Y. Q. Org. Lett. 2014, 16, 2822.
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 28 of 28
1
2
3
4
9
Tang, Y.; Han, R. R.; Lv, M. C.; Chen,Y.; Yang, P. Tetrahedron. 2015, 71, 4334.
5
6
7
8
10 Liu, L.W.; Wang, Z. Z.; Zhang, H. H.; Wang, W. S.; Zhang, J. Z.; Tang, Y. Chem. Commun.
2015, 51, 9531.
9
11 (a) Neumann, M.; Füldner, S.; König, B.; Zeitler K. Angew. Chem. Int. Ed. 2011, 50, 951. (b)
Nicewicz, D. A.; Nguyen, T. M. ACS Catal. 2014, 4, 355.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
12 Majek, M.; Wangelin, A. J. von. Chem. Commun. 2013, 49, 5507.
13 Konieczynska, M. D.; Dai, C. H.; Stephenson, C. R. J. Org. Biomol. Chem. 2012, 10, 4509.
14 Singh, A.; Arora, A.; Weaver, J. D. Org. Lett. 2013, 15, 5390.
15 Bergonzini, G.; Schindler, C. S.; Wallentin, C. J.; Jacobsen, E. N.; Stephenson, C. R. J. Chem.
Sci. 2014, 5, 112.
16 Kee, C. W.; Chan, K. M.; Wong, M. W.; Tan, C.H. Asian J. Org. Chem. 2014, 3, 536
17 Zhao, Y. T.; Li, Z.; Yang, C.; Lin, R.; Xia, W. J. Beilstein J. Org. Chem. 2014, 10, 622.
18 Hu, J.; Wang, J.; Nguyen, T. H.; Zheng, N. Beilstein J. Org. Chem. 2013, 9,1977.
19 Li, X.; Gu, X. Y.; Li, Y. J.; Li, P. X.; ACS Catal. 2014, 4, 1897
20 Franz, J. F.; Kraus, W. B.; Zeitler, K. Chem. Commun. 2015, 51, 8280.
21 Bihan, G. L.; Rondu, F.; PeléꢀTounian, A.; Wang, X.; Lidy, S.; Touboul, E.; Lamouri, A.;
Dive, G.; Huet, J.; Pfeiffer, B.; Renard, P.; GuardiolaꢀLemaître, B.; Manéchez, D.; Pénicaud,
L.; Ktorza, A.; Godfroid, J. J. J. Med. Chem. 1999, 42, 9.
22 Sadig, J. E. R.; Foster, R.; Wakenhut, F.; Willis, M. C. J. Org. Chem. 2012, 77, 9473.
23 Yan, Y. Z.; Wang, Z. Y. Chem. Commun. 2011, 47, 9513.
24 Katritzky, A. R.; Cai, C. M.; Singh, S. K. J. Org. Chem. 2006, 71, 3375.
ACS Paragon Plus Environment