Rh(III)-Catalyzed One-Pot Synthesis of Benzimidazoquinazolines via C-H Amidation-Cyclization of N-LG-2-phenylbenzoimidazoles

Article abstract of DOI:10.1021/acs.joc.8b02396

An efficient protocol to synthesize substituted benzo[4,5]imidazo[1,2-c]quinazolines starting from N-LG-2-phenylbenzoimidazole and dioxazolones catalyzed by Rh(III) or Ir(III) has been developed. Various substituted benzo[4,5]imidazo[1,2-c]quinazolines co

Full text of DOI:10.1021/acs.joc.8b02396

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Article
Rh(III)-Catalyzed One-Pot Synthesis of Benzimidazoquinazolines
via C-H Amidation-Cyclization of N-LG-2-phenylbenzoimidazoles
Linhua Xu, Tingfang Li, Lianhui Wang, and Xiuling Cui
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b02396 • Publication Date (Web): 15 Nov 2018
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Rh(III)-Catalyzed One-Pot Synthesis of Benzimidazoquinazolines via
C−H Amidation−Cyclization of N-LG-2-phenylbenzoimidazoles
8
9
Linhua Xu, Tingfang Li, Lianhui Wang, and Xiuling Cui*
Engineering Research Center of Molecular Medicine, Ministry of Education, Key Laboratory of Fujian
Molecular Medicine, Key Laboratory of Xiamen Marine and Gene Drugs, School of Biomedical
Sciences, Huaqiao University, Xiamen, 361021, P. R. China.
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O
R1
N
N
R1
O
O
N
Rh(III) or Ir(III) cat.
- CO2, - LG
+
N
LG
N
R2
N
R2
99%
R1 = Me, OMe, F, Cl, Br, I, CN, CF3, isobutyl, etc
R2 = aryl, alkyl, benzyl, etc
up to
yield
LG = leaving group (Ts, Boc)
ABSTRACT:
An
efficient
protocol
to
synthesize
substituted
benzo[4,5]imidazo[1,2-c]quinazolines starting from N-LG-2-phenylbenzoimidazole and
dioxazolones catalyzed by Rh(III) or Ir(III) has been developed. Various substituted
benzo[4,5]imidazo[1,2-c]quinazolines could be easily provided in up to 99% yield. Large range of
the substrates and functional groups are compatible for this transformation. This method features
low catalyst loading, acids free and low solvent consumed.
INTRODUCTION
Benzimidazoquinazoline is an important structural moiety and wide applications in biological and
medicinal studies since many molecules containing this framework exhibit a wide range of
therapeutic activities, such as anticancer,1 antiviral,2 antimicrobial,3 anti-inflammatory,4 and
anticonvulsants.5 Therefore, tremendous efforts have been devoted to build such a skeleton.
Conventionally,
2-(2-aminophenyl)benzoimidazoles
and
their
precursors,
2-(2-nitrophenyl)benzoimidazoles, are used as the starting materials to synthesize the
benzimidazoquinazolines.6
of
Copper-catalyzed
coupling/condensation
2-(2-bromophenyl)-1H-benzo[d]imidazole with phenylethylamine or its derivatives provides an
alternative pathway reported by Fu, Zhang and other groups (path A, Scheme 1).7 However, these
synthetic methodologies suffer from some limitations, such as functionalized starting materials, 6-7
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narrow scope of substrates, low tolerance of functional groups, and requirement of external base
or acid,10e which greatly impedes discovery of more potent biologically active molecules. Thus,
development of a straightforward and systematical process to access benzimidazoquinazolines
remains high challenge.
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Over the past decade, transition-metal-catalyzed direct amination/amidation of C−H bonds using
amines, amides, imidoiodinanes, chloroamines, organic azides, hydroxylamines,
1,4,2-dioxazol-5-ones, anthranils, N-fluorobenzenesulfonimide (NFSI), amidobenziodoxolones,
isocyanates and nitrosoarenes as nitrogen sources have been established as straightforward and
step economic processes in the construction of various C−N bonds.8 In particular,
1,4,2-dioxazol-5-one as a nitrene-transfer reagent is especially prominent with high reactivity,
compatibility, and versatility. In 2015, Chang and other groups independently reported Rh(III),
Ir(III) or Co(III)-catalyzed amidation of aryl and alkyl C−H bonds under the mild reaction
conditions.9 In these studies, only simple amidation was realized. Meanwhile, most of the
directing groups were not easily removed or modified. The shortcomings can be attenuated if the
chelating groups can be converted into the desired functional groups in the final products.
Following this strategy, construction of azacycles using 1,4,2-dioxazol-5-one as the nitrogen
source has received attention.10 In 2017, our group has developed an efficient synthetic route to
access
substituted
N-Ts-2-phenylbenzimidazoles
via
Cp*Ir(III)-catalyzed
C−H
activation/annulation of easily available N-phenylbenzimidamides with TsN3 (path B, Scheme
1).11 As a continuation of our interest in C−H activation/annulation reactions, we aimed to explore
the synthesis of benzimidazoquinazolines via C−H activation of 2-phenylbenzimidazoles with
1,4,2-dioxazol-5-one as an amidation reagent. The desired benzimidazoquinazoline 3aa was
isolated in only 20% yield when [Cp*RhCl2]2/AgNTf2 was used as a catalyst (path C, Scheme 1).
To our surprise, when N-Ts-2-phenylbenzimidazole was used as the substrate in the same catalytic
system, the target product was isolated in 99% (path D, Scheme 1). Herein we report a
convenient,
efficient,
and
via
straightforward
approach
C−H
to
synthesize
substituted
of
benzimidazoquinazolines
Cp*Rh(III)-catalyzed
activation/annulation
N-Ts-2-phenylbenzimidazoles with 1,4,2-dioxazol-5-ones.
RESULTS AND DISCUSSION
Scheme 1. Synthesis of Benzimidazoquinazolines
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N
H2N
R
N
N
(A)
Cu
+
N
H
N
base
7
X
8
9
X= Br, I
R = H, NH, COOH
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[Cp*IrCl2]2 (4 mol %)
AgNTf2 (16 mol %)
N
H
N
TsN3
+
Phenylacetic acid (1 equiv)
DCE(2 mL), 80 oC, 12 h
N
(B)
NH
N
Ts
This work:
N
O
O
[Cp*RhCl2]2 (2.5 mol %)
AgNTf2 (10 mol %)
O
N
+
(C)
(D)
N
N
H
N
Ph
R
20%
O
O
N
N
O
[Cp*RhCl2]2 (2.5 mol %)
AgNTf2 (10 mol %)
+
N
N
N
Ph
N
Ts
R
up to 99%
This study commenced with the reaction of 2-phenyl-1-tosyl-1H-benzo[d]imidazole 1a with
3-phenyl-1,4,2-dioxazol-5-one 2a catalyzed by [Cp*RhCl2]2 (Table 1). The desired product,
6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline 3aa was obtained in 81% yield (entry 1).
[Cp*IrCl2]2 showed similar catalytic activity as [Cp*RhCl2]2 (entry 5). Control experiments
revealed that both [Cp*RhCl2]2 and a silver salt were necessary (entries 2-4). Both of
[Ru(p-cymene)Cl2]2 and [Cp*Co(CO)I2] lowered the coupling efficiency (entries 6−7). Double
amount of DCE (2 mL) as solvent resulted in a lower yield of 59% (entry 8), which encouraged us
to decrease the amount of solvent. Product 3aa was isolated in 95% yield when the amount of
DCE was decreased to 0.5 mL (entry 9). Among various silver salts tested, AgNTf2 gave the best
yield (entries 9-13). Subsequently, screening solvents revealed that DCE was optimal (entries
14-17). In comparison, lowering the reaction temperature or the reaction time resulted in slightly
lower yields (entry 10 vs entries 18-19). Decreasing the catalyst loading to 2 mol % also slightly
reduced the reaction efficiency (entry 20). Finally, the optimized reaction conditions were
identified as follows: [Cp*RhCl2]2 (2.5 mol %), AgNTf2 (10 mol %) in DCE (0.5 mL) at 120 °C
for 13 h in sealed tube under air.
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Table 1. Optimization of the Reaction Conditionsa-e
5
6
7
8
N
N
O
O
O
N
N
catalyst, salt
solvent, T, t
N
+
9
N
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Ts
1a
2a
3aa
Entry Catalyst
Salt
Solvent
Yield(%)b
1
[Cp*RhCl2]2
AgSbF6
DCE (1 mL)
DCE (1 mL)
DCE (1 mL)
DCE (1 mL)
DCE (1 mL)
DCE (1 mL)
DCE (1 mL)
DCE (2 mL)
DCE (0.5 mL)
DCE (0.5 mL)
DCE (0.5 mL)
DCE (0.5 mL)
DCE (0.5 mL)
Toluene (0.5 mL)
81
0
2
-
-
3
-
AgSbF6
-
0
4
[Cp*RhCl2]2
[Cp*IrCl2]2
0
5
AgSbF6
72
15
trace
59
95
99
0
6
[Ru(p-cymene)Cl2]2 AgSbF6
7
[Cp*Co(CO)I2]
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
AgSbF6
AgSbF6
AgSbF6
AgNTf2
AgBF4
8
9
10
11
12
13
14
AgOAc
NaOAc
AgNTf2
62
0
0
15
16
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
AgNTf2
AgNTf2
AgNTf2
MeOH (0.5 mL)
33
74
0
1,4-Dioxane (0.5 mL)
DMSO (0.5 mL)
17
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
AgNTf2
AgNTf2
AgNTf2
DCE (0.5 mL)
DCE (0.5 mL)
DCE (0.5 mL)
83
85
95
18c
19d
20e
aReaction conditions: 1a (0.2 mmol), 2a (1.5 equiv), catalyst (2.5 mol %), salt (10
mol %), solvent, 120 °C, 13 h in sealed tube under air. bIsolated yields. cT = 100 °C.
dt = 10 h. e[Cp*RhCl2]2 (2 mol %), AgNTf2 (8 mol %).
With the optimized conditions established, the scope of 2-phenyl-1-tosyl-1H-benzo[d]imidazoles
was then examined by employing 2a as the coupling partner (Scheme 2). To our delight, various
2-phenyl-1-tosyl-1H-benzo[d]imidazoles reacted smoothly to furnish the corresponding
benzimidazoquinazolines in good to excellent yields. The alteration of methyl group location from
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para- and meta- to the ortho-position results in an analogous reactivity (3ba, 3ea, 3ha), which
suggested that the steric effect of 2-benzene ring had no significant influence on the reactivity.
2-(2-Bromophenyl)-1-tosyl-1H-benzo[d]imidazole (1d) was suitable and gave the target product
3da in 99% yield. Br could survive in the final product, which provides further chance to build
complicated molecules through coupling reactions. N-Boc-2-phenylbenzoimidazole also worked
well and afforded the corresponding product 3aa in 94% yield. The meta-substituted
2-phenyl-1-tosyl-1H-benzo[d]imidazoles (1e, 1f, 1g) displayed exclusive regiospecificity for C−H
coupling at the less hindered site, highlighting the more pronounced steric effect. Substrates
bearing electronically diverse para-substituents on the phenyl ring, including alkyl (1h, 1k),
halogen (1i, 1j), methoxyl (1l), trifluoromethyl (1m) and cyano (1n) groups, could provide the
targeted products in good yields, thus offering plentiful opportunities for further synthetic
elaboration.
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Scheme 2. Scope of 2-Phenyl-1-tosyl-1H-benzo[d]imidazolesa-d
N
R
O
O
[Cp*RhCl2]2 (2.5 mol %)
AgNTf2 (10 mol %)
N
O
N
N
R
N
N
+
DCE, 120 oC, 13 h
Ts
3aa-na
1a-n
2a
R
c
d
3aa
R = H,
, 99%( 94%, 97%)
N
N
3ba
R = Me,
, 93%
R
N
N
3ca
R = F,
, 64%
N
3ea
R = Me,
, 97%
3da
R = Br,
, 99%
3fa
R = F,
, 71%
N
3ga
R = Br,
, 99%
3ha
R = Me,
, 81%
3ia
, 73%
N
N
R = Cl,
R = I,
R
3ja
, 72%
3ka
R = isobutyl,
R = OMe,
, 83%
N
3la
, 86%
, 81%
, 74%
3ma
R = CF3,
R = CN,
3na
aReaction conditions: 1a-n (0.2 mmol), 2a (1.5 equiv), [Cp*RhCl2]2 (2.5 mol %),
AgNTf2 (10 mol %), DCE (0.5 mL), 120 °C, 13 h in sealed tube under air. bIsolated yields.
c
d
Exchange of Ts with Boc. 1a (1 mmol), 2a (1.5 equiv), [Cp*RhCl2]2 (2.5 mol %),
AgNTf2 (10 mol %), DCE (2.5 mL), 120 °C, 13 h in sealed tube under air.
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Next, we investigated the scope of dioxazolones using 1a as the reaction partner under the
optimized conditions (Scheme 3). It was found that a broad range of functional groups on phenyl
ring of the 3-phenyl-1,4,2-dioxazol-5-one could be tolerated. The phenyl ring with an o-methyl
group (3ab) exhibited dramatic decreased reactivity, presumably due to steric hindrance. Aromatic
ring substituted with halogens worked well, providing the desired products in moderate to
excellent yields (3ac, 3ad, 3af, 3ah, 3ai). Furthermore, aryl-substituted dioxazolones bearing both
electron-donating and electron-withdrawing groups are all viable in this system (3aj, 3ak). In
addition, 3-alkyl and 3-benzyl dioxazolones exhibited good reactivity (3am, 3an).
3-(Naphthalen-2-yl)-1,4,2-dioxazol-5-one was compatible under the standard reaction conditions,
although only 28% yield was obtained (3al). No target product was obtained when
3-(naphthalen-1-yl)-1,4,2-dioxazol-5-one was applied.
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Scheme 3. Scope of Dioxazolonesa,b
[Cp*RhCl2]2 (2.5 mol %)
AgNTf2 (10 mol %)
DCE, 120 oC, 13 h
5
6
7
8
N
N
O
O
N
N
O
+
N
N
R
R
Ts
9
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3aa-an
2a-n
1a
N
N
N
'
'
3ab
R = Me,
, 11%
3ae
R = Me,
, 87%
N
'
'
3ac
R = F,
, 86%
3af,
R = Br,
83%
N
N
'
3ad
R = Cl,
, 99%
R'
R'
N
N
N
N
'
3ag
R = Me,
, 99%
'
3ah
R = F,
, 98%
N
'
N
3ai
R = Br,
, 56%
'
3aj
R = OMe,
, 58%
, 75%
'
3ak
R = CF3,
R'
3al
, 28%
N
N
N
N
N
N
3an
, 87%
3am
, 56%
aReaction conditions: 1a (0.2 mmol), 2a-n (1.5 equiv), [Cp*RhCl2]2 (2.5 mol %), AgNTf2
(10 mol %), DCE (0.5 mL), 120 °C, 13 h in sealed tube under air. bIsolated yields.
To investigate the catalytic mechanism of this cyclization process, several experiments
were performed. When 2-phenyl-1-tosyl-1H-indole was treated with 2a under the standard
conditions, no product was detected, suggesting that imine played as the directing group
rather than the quaternary amine (Scheme 4a). No reaction was detected in the absence of
2a (Scheme 4b), suggesting that N-Ts bond cleavage was not the first-step in this C-H
activation process. When 2-phenyl-1H-benzo[d]imidazole was used as starting material
instead of 1a and 1 equiv TsOH as additives, 49% of product was attained as well as 51%
recovery of starting material (Scheme 4c). The result indicated that N-Ts played an
important role to improve the efficiency of the transformation.
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Scheme 4. Mechanistic Studies
5
O
6
7
8
O
O
standard conditions
(a)
N.R.
N
+
N
9
Ts
2a
standard conditions
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N
N
N
N
+
(b)
(c)
N
H
N
Ts
Ts
0%
+
99%
1a
O
N
N
O
O
N
N
standard conditions
TsOH 1equiv
N
N
H
+
N
N
H
2a
51%
49%
On the basis of these observations and literature reports,10,12 a plausible reaction mechanism is
proposed as in Scheme 5. Firstly, an active catalyst [Cp*Rh(NTf2)2] was generated through anion
exchange. Cyclometalation of 1a generated an iridacyclic intermediate A’. Coordination of the
dioxazolone 2a to intermediate B’ with further intramolecular migratory insertion gave an iridium
species C’ with release of CO2. The complex C’ may undergo protonation to regenerate the active
[Cp*Rh(NTf2)2] for a next catalytic cycle and give the intermediate D’ simultaneously, which
underwent cyclization to afford the benzimidazoquinazoline 3aa.
Scheme 5. A Plausible Mechanism
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[Cp*RhCl2]
[Cp*RhCl2]2
2AgNTf2
Ts
N
2AgCl
N
N
HN
R
[Cp*Rh(NTf2)2]
N
O
D'
Ts
1a
9
-
HNTf2
10
11
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N
N
TsOH
HNTf2
N
Ts
N
3aa
Ts
N
N
Rh
Cp*
L
N
N
R
Rh
Cp*
O
L
A'
C'
O
O
O
N
R
CO2
Ts
N
2a
N
Rh
Cp*
R
N
O
O
B'
O
CONCLUSION
In summary, we have developed a synthetic route to access benzimidazoquinazolines via Rh(III)
catalyzed C−H activation/annulation of readily available 2-phenyl-1-LG-1H-benzo[d]imidazoles
in the coupling with dioxazolones. Good functional group tolerance, high atom economy and
efficiency make this protocol useful in preparing various substituted benzimidazoquinazolines.
Further mechanistic studies and other transformations of benzoimidazoles are underway in our
laboratory.
EXPERIMENTAL SECTION
General information. Unless otherwise stated, all commercial materials and solvents were used
directly without further purification. Melting points were determined in open glass capillaries and
were uncorrected. H NMR spectra were recorded on 400 MHz spectrometers, and 13C NMR
1
spectra were recorded on a 100 MHz spectrometer. Chemical shifts (δ in ppm) were referenced to
tetramethylsilane (δ = 0 ppm) in CDCl3 as an internal standard at room temperature. 13C NMR
spectra were obtained by using the same NMR spectrometer and were calibrated with CDCl3 (δ =
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77.00 ppm). High-resolution mass spectra (HRMS) were equipped with an ESI source and a TOF
detector. Column chromatography was performed on silica gel (70-230 mesh ASTM) using the
reported eluents. Thin-layer chromatography (TLC) was carried out on 4×15 cm plates with a
layer thickness of 0.2 mm (silica gel 60 F254). Starting materials 111,13 and 29 were prepared
according to the literatures.
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Representative procedure for the preparation of compounds 3. Under air atmosphere, a tube
was charged with a magnetic stirrer bar, 2-phenyl-1-LG(leaving group)-1H-benzo[d]imidazole 1
(0.2 mmol), 1,4,2-dioxazol-5-one 2 (0.3 mmol), [Cp*RhCl2]2 (2.5 mol %), AgNTf2 (10 mol %),
and 1,2-dichloroethane (0.5 mL). The reaction mixture was stirred at 120 °C for 13 h in sealed
tube. After cooled to room temperature, the resulting mixture was diluted by moderate ethyl
acetate, extracted with saturated NaHCO3. The organic phases were removed under reduced
pressure, and the residue was purified by chromatography on silica gel (eluent: petroleum
ether/ethyl acetate =10:1 to 5:1 to 3:1) to give the desired product 3.
Procedure for the synthesis of product 3aa at a 1 mmol scale. A reaction tube equipped with a
magnetic stirrer bar was charged with 2-phenyl-1-tosyl-1H-benzo[d]imidazole 1a (1 mmol, 0.3541
g), 3-phenyl-1,4,2-dioxazol-5-one 2a (1.5 equiv, 0.2405 g), [Cp*RhCl2]2 (2.5 mol %, 15.3 mg),
AgNTf2 (10 mol %, 37.8 mg), and 1,2-dichloroethane (2.5 mL). The reaction mixture was stirred
at 120 °C for 13 h in sealed tube. After cooled to room temperature, the resulting mixture was
diluted by moderate ethyl acetate, extracted with saturated NaHCO3. The organic phases were
removed under reduced pressure, and the residue was purified by chromatography on silica gel
(eluent: petroleum ether/ethyl acetate = 10:1 to 5:1) to give the desired product 3aa (0.2915 g,
97%).
6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3aa)6a: White solid, 58.4 mg, 99% yield, mp:
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244-245 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400 MHz,
CDCl3) δ 8.75 (dd, J = 7.9, 1.2 Hz, 1H), 7.99 (t, J = 8.2 Hz, 2H), 7.82 – 7.63 (m, 7H), 7.49 – 7.42
(m, 1H), 7.14 – 7.07 (m, 1H), 6.61 (d, J = 8.4 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3) δ 148.5,
148.0, 144.3, 142.4, 134.3, 131.8, 130.9, 129.3, 129.1, 128.33, 128.26, 128.2, 125.6, 124.2, 122.5,
119.9, 118.4, 114.3. HRMS: [M + H]+ calculated for C20H14N3: 296.1182, found 296.1183.
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1-methyl-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3ba): Light yellow solid, 57.5 mg, 93%
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yield, mp: 234-235 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR
(400 MHz, CDCl3) δ 7.99 (d, J = 8.1 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H), 7.74 – 7.60 (m, 6H), 7.50
– 7.40 (m, 2H), 7.08 (t, J = 7.4 Hz, 1H), 6.54 (d, J = 8.4 Hz, 1H), 3.27 (s, 3H). 13C{H} NMR (100
MHz, CDCl3) δ 148.4, 148.2, 144.5, 143.4, 138.2, 134.5, 130.8, 130.7, 130.3, 129.2, 128.3, 126.0,
125.1, 122.4, 120.2, 117.4, 114.1, 23.6. HRMS: [M + H]+ calculated for C21H16N3: 310.1339,
found 310.1339.
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1-fluoro-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3ca): White solid, 40.1 mg, 64% yield,
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mp: 270-271 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400
MHz, CDCl3) δ 8.07 (d, J = 8.2 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.77 – 7.64 (m, 6H), 7.49 –
7.39 (m, 2H), 7.16 – 7.09 (m, 1H), 6.58 (d, J = 8.4 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3)
δ159.1 (d, JC-F = 261.8 Hz), 149.4 (d, JC-F = 0.6 Hz), 144.6 (d, JC-F = 1.8 Hz), 144.5 (d, JC-F = 7.2
Hz), 144.0 (d, JC-F = 0.9 Hz), 133.9, 131.7 (d, JC-F = 9.4 Hz), 131.1, 129.3, 128.3, 125.7, 124.0 (d,
JC-F = 4.0 Hz), 123.0, 120.7, 114.6 (d, JC-F J = 20.3 Hz,), 114.2, 108.3 (d, JC-F = 11.1 Hz). 19F
NMR (376 MHz, CDCl3) δ -109.2. HRMS: [M + H]+ calculated for C20H13FN3: 314.1088, found
314.1087.
1-bromo-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3da): White solid, 73.8 mg, 99% yield,
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mp: 256-257 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400
MHz, CDCl3) δ 8.08 (d, J = 8.2 Hz, 1H), 7.95 (d, J = 7.9 Hz, 2H), 7.75 – 7.63 (m, 5H), 7.55 (t, J =
8.0 Hz, 1H), 7.44 (t, J = 8.0 Hz, 1H), 7.10 (t, J = 7.8 Hz, 1H), 6.56 (d, J = 8.4 Hz, 1H). 13C{H}
NMR (100 MHz, CDCl3) δ 149.1, 146.2, 144.2, 144.1, 134.3, 134.0, 131.2, 131.1, 129.3, 128.5,
128.3, 127.9, 125.5, 123.2, 121.0, 119.0, 118.2, 114.1. HRMS: [M + H]+ calculated for
C20H13BrN3: 374.0287, found 374.0287.
1-phenyl-2-(m-tolyl)-1H-benzo[d]imidazole (3ea)7a: White solid, 59.9 mg, 97% yield, mp:
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252-253 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400 MHz,
CDCl3) δ 8.55 (s, 1H), 7.97 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 8.3 Hz, 1H), 7.76 – 7.72 (m, 2H), 7.70
– 7.62 (m, 3H), 7.59 (dd, J = 8.3, 1.8 Hz, 1H), 7.47 – 7.42 (m, 1H), 7.11 – 7.06 (m, 1H), 6.60 (d, J
= 8.4 Hz, 1H), 2.61 (s, 3H). 13C{H} NMR (100 MHz, CDCl3) δ 148.0, 147.6, 144.3, 140.4, 138.6,
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134.3, 133.3, 130.8, 129.3, 129.2, 128.4, 127.9, 125.5, 123.7, 122.4, 119.8, 118.0, 114.3, 21.6.
HRMS: [M + H]+ calculated for C21H16N3: 310.1339, found 310.1339.
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2-fluoro-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3fa): White solid, 44.4 mg, 71% yield,
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mp: 226-227 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400
MHz, CDCl3) δ 8.34 (dd, J = 8.5, 2.9 Hz, 1H), 8.00 – 7.93 (m, 2H), 7.69 (dddd, J = 15.9, 8.5, 3.9,
1.7 Hz, 5H), 7.46 (ddd, J = 11.1, 8.5, 1.9 Hz, 2H), 7.13 – 7.07 (m, 1H), 6.61 (d, J = 8.4 Hz, 1H).
13C{H} NMR (100 MHz, CDCl3) δ161.7 (d, JC-F = 249.8 Hz), 147.8 (d, JC-F = 2.5 Hz), 147.3 (d,
JC-F = 4.3 Hz), 144.3, 139.0, 139.0, 134.1, 131.0, 130.6 (d, JC-F = 8.9 Hz), 129.3, 128.3, 125.8,
122.9, 120.4, 120.1, 119.8 (d, JC-F = 10.2 Hz), 114.4, 109.4 (d, JC-F = 24.7 Hz). 19F NMR (376
MHz, CDCl3) δ -110.2. HRMS: [M + H]+ calculated for C20H13FN3: 314.1088 , found 314.1086.
2-bromo-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3ga): White solid, 73.8 mg, 99% yield,
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mp: 253-254 C (purified by flash chromatography using PE/EA = 10:1). H NMR (400 MHz,
CDCl3) δ 8.89 (s, 1H), 7.97 (d, J = 8.2 Hz, 1H), 7.85 (d, J = 1.1 Hz, 2H), 7.75 – 7.63 (m, 5H), 7.50
– 7.44 (m, 1H), 7.15 – 7.09 (m, 1H), 6.63 (d, J = 8.4 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3) δ
148.8, 146.7, 144.3, 141.1, 135.0, 134.0, 131.1, 129.8, 129.3, 129.2, 128.3, 126.8, 125.8, 122.9,
121.9, 120.2, 119.8, 114.4. HRMS: [M + H]+ calculated for C20H13BrN3: 374.0287 , found
374.0288.
3-methyl-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3ha): White solid, 50.1 mg, 81% yield,
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mp: 251-252 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400
MHz, CDCl3) δ 8.61 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.78 (s, 1H), 7.76 – 7.71 (m,
2H), 7.70 – 7.62 (m, 3H), 7.51 (dd, J = 8.1, 1.0 Hz, 1H), 7.46 – 7.40 (m, 1H), 7.10 – 7.03 (m, 1H),
6.58 (d, J = 8.4 Hz, 1H), 2.56 (s, 3H). 13C{H} NMR (100 MHz, CDCl3) δ 148.4, 148.2, 144.4,
142.54, 142.46, 134.4, 130.8, 129.8, 129.2, 128.3, 128.0, 125.4, 123.9, 122.2, 119.7, 115.8, 114.2,
21.9. HRMS: [M + H]+ calculated for C21H16N3: 310.1339, found 310.1339.
3-chloro-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3ia): White solid, 48.0 mg, 73% yield,
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mp: 263-264 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400
MHz, CDCl3) δ 8.65 (d, J = 8.5 Hz, 1H), 7.96 (dd, J = 10.4, 5.1 Hz, 2H), 7.72 (ddd, J = 9.8, 5.5,
1.5 Hz, 3H), 7.69 – 7.62 (m, 3H), 7.48 – 7.43 (m, 1H), 7.13 – 7.08 (m, 1H), 6.61 (d, J = 8.4 Hz,
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1H). 13C{H} NMR (100 MHz, CDCl3) δ 149.6, 147.4, 144.4, 143.2, 137.6, 133.9, 131.1, 129.3,
129.1, 128.8, 128.3, 127.8, 125.8, 125.4, 122.8, 120.0, 116.9, 114.3. HRMS: [M + H]+ calculated
for C20H13ClN3: 330.0793, found 330.0793.
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3-iodo-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3ja): Light yellow solid, 60.6 mg, 72%
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yield, mp: 253-254 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR
(400 MHz, CDCl3) δ 8.51 – 8.28 (m, 2H), 8.01 – 7.88 (m, 2H), 7.80 – 7.62 (m, 5H), 7.50 – 7.38
(m, 1H), 7.16 – 7.04 (m, 1H), 6.61 (d, J = 8.4 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3) δ 149.3,
147.4, 144.3, 143.0, 137.1, 137.0, 133.9, 131.1, 129.2, 129.1, 128.3, 125.8, 125.2, 122.8, 120.0,
117.6, 114.3, 97.6. HRMS: [M + H]+ calculated for C20H13IN3: 422.0149, found 422.0150.
3-isopropyl-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3ka): White solid, 55.9 mg, 83%
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yield, mp: 191-192 C (purified by flash chromatography using PE/EA = 10:1 - 5:1) . H NMR
(400 MHz, CDCl3) δ 8.65 (d, J = 8.2 Hz, 1H), 7.95 (d, J = 8.1 Hz, 1H), 7.88 (d, J = 1.5 Hz, 1H),
7.75 – 7.62 (m, 5H), 7.59 (dd, J = 8.3, 1.6 Hz, 1H), 7.46 – 7.39 (m, 1H), 7.06 (ddd, J = 8.3, 7.3,
1.1 Hz, 1H), 6.59 (d, J = 8.4 Hz, 1H), 3.13 (hept, J = 6.9 Hz, 1H), 1.37 (d, J = 6.9 Hz, 6H).
13C{H} NMR (100 MHz, CDCl3) δ 153.4, 148.4, 148.1, 144.4, 142.5, 134.3, 130.8, 129.2, 128.3,
127.6, 125.4, 125.2, 124.0, 122.2, 119.7, 116.1, 114.2, 34.3, 23.7. HRMS: [M + H]+ calculated for
C23H20N3: 338.1652, found 338.1651.
3-methoxy-6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline (3la):. Light yellow solid, 55.9 mg,
86% yield, mp: 208-209 oC (purified by flash chromatography using PE/EA = 5:1 – 3:1). 1H NMR
(400 MHz, CDCl3) δ 8.62 (d, J = 8.8 Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.76 – 7.63 (m, 5H), 7.45
– 7.39 (m, 2H), 7.31 – 7.26 (m, 1H), 7.09 – 7.02 (m, 1H), 6.58 (d, J = 8.4 Hz, 1H), 3.94 (s, 3H).
13C{H} NMR (100 MHz, CDCl3) δ 162.7, 149.1, 148.2, 144.6, 144.3, 134.3, 130.9, 129.2, 129.1,
128.3, 125.5, 122.0, 119.6, 118.3, 114.2, 111.8, 109.3, 55.6. HRMS: [M + H]+ calculated for
C21H16N3O: 326.1288, found 326.1289.
6-phenyl-3-(trifluoromethyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ma): White solid, 58.8 mg,
81% yield, mp: 224-226 oC (purified by flash chromatography using PE/EA = 5:1 – 3:1). 1H NMR
(400 MHz, CDCl3) δ 8.80 (d, J = 8.3 Hz, 1H), 8.26 (s, 1H), 7.96 (d, J = 8.2 Hz, 1H), 7.87 (d, J =
8.2 Hz, 1H), 7.72 (ddd, J = 22.7, 11.2, 6.8 Hz, 5H), 7.46 (t, J = 7.6 Hz, 1H), 7.13 (t, J = 7.7 Hz,
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1H), 6.65 (d, J = 8.4 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3) δ 149.7, 146.8, 144.3, 142.0,
133.8, 133.3 (d, J = 33.0 Hz), 131.3, 129.3, 129.1, 128.2, 126.0, 125.6 (q, JC-F = 4.0 Hz), 125.0,
124.2 (q, JC-F = 3.3 Hz), 123.6 (q, JC-F = 272.7 Hz), 123.2, 120.8, 120.3, 114.4. 19F NMR (376
MHz, CDCl3) δ -62.7. HRMS: [M + H]+ calculated for C21H13F3N3: 364.1056, found 364.1058.
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6-phenylbenzo[4,5]imidazo[1,2-c]quinazoline-3-carbonitrile (3na): Yellow solid, 47.3 mg, 74%
yield, mp: 272-273 oC (purified by flash chromatography using PE/EA = 5:1 – 3:1). 1H NMR (400
MHz, CDCl3) δ 8.82 (d, J = 8.2 Hz, 1H), 8.28 (d, J = 1.1 Hz, 1H), 8.01 (d, J = 8.2 Hz, 1H), 7.88
(dd, J = 8.2, 1.5 Hz, 1H), 7.79 – 7.72 (m, 3H), 7.72 – 7.67 (m, 2H), 7.55 – 7.48 (m, 1H), 7.21 –
7.15 (m, 1H), 6.68 (d, J = 8.5 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3) δ 150.2, 146.4, 144.4,
142.0, 133.6, 132.7, 131.4, 130.1, 129.4, 129.2, 128.2, 126.2, 125.3, 123.7, 121.7, 120.5, 118.0,
114.9, 114.5. HRMS: [M + H]+ calculated for C21H13N4: 321.1135, found 321.1136.
6-(o-tolyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ab): Yellow solid, 6.8 mg, 11% yield, mp:
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207-209 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400 MHz,
CDCl3) δ 8.78 (dd, J = 7.9, 1.3 Hz, 1H), 8.01 (dd, J = 16.7, 7.9 Hz, 2H), 7.85 – 7.80 (m, 1H), 7.74
(dd, J = 11.0, 4.1 Hz, 1H), 7.63 – 7.58 (m, 1H), 7.55 – 7.46 (m, 4H), 7.09 (ddd, J = 8.3, 7.3, 1.0
Hz, 1H), 6.29 (d, J = 8.4 Hz, 1H), 2.14 (s, 3H). 13C{H} NMR (100 MHz, CDCl3) δ 148.4, 147.7,
144.4, 142.4, 136.5, 134.0, 131.8, 131.0, 130.9, 129.1, 128.4, 128.32, 128.28, 127.0, 125.7, 124.2,
123.1, 119.9, 118.5, 113.3, 18.9. HRMS: [M + H]+ calculated for C21H16N3: 310.1339, found
310.1338.
6-(2-fluorophenyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ac): White solid, 53.8 mg, 86% yield,
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mp: 223-224 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400
MHz, CDCl3) δ 8.77 (dd, J = 7.9, 1.1 Hz, 1H), 8.01 (t, J = 7.4 Hz, 2H), 7.85 – 7.78 (m, 1H), 7.76
– 7.68 (m, 3H), 7.53 – 7.44 (m, 2H), 7.41 – 7.33 (m, 1H), 7.19 – 7.12 (m, 1H), 6.62 (d, J = 8.4 Hz,
1H). 13C{H} NMR (100 MHz, CDCl3) δ160.2 (d, J = 251.2 Hz), 147.6, 144.3, 143.7, 142.2, 133.0
(d, JC-F = 8.0 Hz), 131.8, 130.5 (d, JC-F = 2.3 Hz), 129.1, 128.6, 128.3, 125.7, 125.3 (d, JC-F = 3.7
Hz), 124.2, 123.0, 122.6 (d, JC-F = 16.0 Hz), 120.0, 118.6, 116.6 (d, JC-F = 20.3 Hz), 113.0. 19F
NMR (376 MHz, CDCl3) δ -113.7. HRMS: [M + H]+ calculated for C20H13FN3: 314.1088, found
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yield, mp: 250-251 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR
(400 MHz, CDCl3) δ 8.78 (dd, J = 7.9, 1.2 Hz, 1H), 8.01 (dd, J = 11.5, 8.2 Hz, 2H), 7.84 – 7.78
(m, 1H), 7.75 – 7.65 (m, 4H), 7.62 – 7.56 (m, 1H), 7.51 – 7.44 (m, 1H), 7.16 – 7.10 (m, 1H), 6.39
(d, J = 8.4 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3) δ 147.4, 145.7, 144.2, 142.1, 133.5, 133.4,
132.1, 131.8, 130.2, 128.8, 128.6, 128.3, 127.9, 125.7, 124.2, 123.1, 112.0, 118.6, 112.8. HRMS:
[M + H]+ calculated for C20H13ClN3: 330.0793, found 330.0794.
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6-(m-tolyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ae): White solid, 53.7 mg, 87% yield, mp:
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209-210 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400 MHz,
CDCl3) δ 8.75 (dd, J = 7.9, 1.3 Hz, 1H), 8.00 (dd, J = 12.8, 4.4 Hz, 2H), 7.82 – 7.75 (m, 1H), 7.73
– 7.67 (m, 1H), 7.57 – 7.49 (m, 4H), 7.48 – 7.44 (m, 1H), 7.11 (ddd, J = 8.3, 7.3, 1.1 Hz, 1H),
6.64 (d, J = 8.4 Hz, 1H), 2.50 (s, 3H). 13C{H} NMR (100 MHz, CDCl3) δ 148.7, 148.0, 144.3,
142.4, 139.3, 134.1, 131.8, 131.6, 129.3, 129.1, 128.8, 128.2, 128.2, 125.5, 125.3, 124.1, 122.5,
119.9, 118.4, 114.4, 21.5. HRMS: [M + H]+ calculated for C21H16N3: 310.1339, found 310.1339.
6-(3-bromophenyl)benzo[4,5]imidazo[1,2-c]quinazoline (3af)15: White solid, 61.9 mg, 83%
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yield, mp: 243-244 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR
(400 MHz, CDCl3) δ 8.71 (dd, J = 7.9, 1.1 Hz, 1H), 7.95 (dd, J = 7.5, 5.1 Hz, 3H), 7.83 (ddd, J =
8.1, 1.9, 1.0 Hz, 1H), 7.79 – 7.74 (m, 1H), 7.71 – 7.64 (m, 2H), 7.52 (t, J = 7.9 Hz, 1H), 7.47 –
7.42 (m, 1H), 7.13 (ddd, J = 8.3, 7.3, 1.0 Hz, 1H), 6.68 (d, J = 8.4 Hz, 1H). 13C{H} NMR (100
MHz, CDCl3) δ 147.8, 146.7, 144.2, 142.1, 135.9, 134.0, 131.9, 131.5, 130.7, 128.9, 128.5, 128.1,
127.0, 125.7, 124.2, 123.2, 122.7, 120.0, 118.3, 114.0. HRMS: [M + H]+ calculated for
C20H13BrN3: 374.0287, found 374.0289.
6-(p-tolyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ag): White solid, 61.1 mg, 99% yield, mp:
o
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217-219 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400 MHz,
CDCl3) δ 8.74 (dd, J = 7.9, 1.1 Hz, 1H), 7.98 (dd, J = 7.9, 4.9 Hz, 2H), 7.80 – 7.75 (m, 1H), 7.71 –
7.61 (m, 3H), 7.49 – 7.42 (m, 3H), 7.15 – 7.09 (m, 1H), 6.71 (d, J = 8.4 Hz, 1H), 2.55 (s, 3H).
13C{H} NMR (100 MHz, CDCl3) δ 148.7, 148.1, 144.3, 142.4, 141.2, 131.8, 131.4, 129.8, 129.3,
128.2, 128.1, 128.1, 125.5, 124.1, 122.4, 119.9, 118.3, 114.5, 21.6. HRMS: [M + H]+ calculated
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for C21H16N3: 310.1339, found 310.1339.
6-(4-fluorophenyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ah)6e: White solid, 61.3 mg, 98%
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yield, mp: 227-228 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR
(400 MHz, CDCl3) δ 8.73 (dd, J = 7.9, 1.2 Hz, 1H), 8.01 – 7.95 (m, 2H), 7.82 – 7.74 (m, 3H), 7.73
– 7.67 (m, 1H), 7.51 – 7.44 (m, 1H), 7.40 – 7.32 (m, 2H), 7.18 – 7.10 (m, 1H), 6.68 (d, J = 8.4 Hz,
1H). 13C {H}NMR (100 MHz, CDCl3) δ164.2 (d, JC-F = 251.9 Hz), 148.0, 147.5, 144.4, 142.2,
131.9, 130.7 (d, JC-F = 8.6 Hz), 130.4 (d, JC-F = 3.5 Hz), 129.1, 128.3 (d, JC-F = 24.0 Hz), 125.7,
124.2, 122.6, 120.1, 118.4, 116.5 (d, JC-F = 22.0 Hz), 114.1. 19F NMR (376 MHz, CDCl3) δ
-108.1. HRMS: [M + H]+ calculated for C20H13FN3: 314.1088, found 314.1089.
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6-(4-bromophenyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ai): White solid, 41.7 mg, 56% yield,
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mp: 247-249 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR (400
MHz, CDCl3) δ 8.74 (dd, J = 7.9, 0.9 Hz, 1H), 8.02 – 7.96 (m, 2H), 7.83 – 7.77 (m, 3H), 7.73 –
7.63 (m, 3H), 7.49 (dd, J = 11.4, 3.9 Hz, 1H), 7.17 (t, J = 7.8 Hz, 1H), 6.75 (d, J = 8.4 Hz, 1H).
13C{H} NMR (100 MHz, CDCl3) δ 148.0, 147.4, 144.4, 142.2, 133.1, 132.5, 131.9, 130.1 129.0,
128.5, 128.2, 125.8, 125.5, 124.2, 122.7, 120.2, 118.4, 114.1. HRMS: [M + H]+ calculated for
C20H13BrN3: 374.0287, found 374.0287.
6-(4-methoxyphenyl)benzo[4,5]imidazo[1,2-c]quinazoline (3aj)6e: Yellow solid, 37.7 mg, 58%
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yield, mp: 253-254 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR
(400 MHz, CDCl3) δ 8.73 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 8.1 Hz, 2H), 7.79 – 7.74 (m, 1H), 7.72
– 7.64 (m, 3H), 7.48 – 7.43 (m, 1H), 7.17 – 7.11 (m, 3H), 6.80 (d, J = 8.4 Hz, 1H), 3.96 (s, 3H).
13C{H} NMR (100 MHz, CDCl3) δ 161.6, 148.4, 148.2, 144.4, 142.5, 131.7, 130.0, 129.4, 128.1,
128.0, 126.6, 125.5, 124.1, 122.4, 119.9, 118.3, 114.5, 114.5, 55.5. HRMS: [M + H]+ calculated
for C21H16N3O: 326.1288, found 326.1288.
6-(4-(trifluoromethyl)phenyl)benzo[4,5]imidazo[1,2-c]quinazoline (3ak): White solid, 54.4 mg,
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75% yield, mp: 256-257 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H
NMR (400 MHz, CDCl3) δ 8.75 (dd, J = 7.9, 1.0 Hz, 1H), 8.02 – 7.90 (m, 6H), 7.84 – 7.77 (m,
1H), 7.76 – 7.69 (m, 1H), 7.52 – 7.45 (m, 1H), 7.19 – 7.12 (m, 1H), 6.65 (d, J = 8.4 Hz, 1H).
13C{H} NMR (100 MHz, CDCl3) δ 147.9, 146.9, 144.4, 142.1, 137.7 (d, JC-F = 1.1 Hz), 133.0 (q,
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JC-F = 32.9 Hz), 131.9, 129.1, 128.9, 128.7, 128.2, 126.3 (q, JC-F = 3.7 Hz), 125.8, 124.2, 123.7 (q,
JC-F = 272.7 Hz), 122.8, 120.2, 118.4, 113.8. 19F NMR (376 MHz, CDCl3) δ -62.8. HRMS: [M +
H]+ calculated for C21H13F3N3: 364.1056, found 364.1058.
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6-(naphthalen-2-yl)benzo[4,5]imidazo[1,2-c]quinazoline (3al): Light yellow solid, 19.3 mg, 28%
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yield, mp: 229-230 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). H NMR
(400 MHz, CDCl3) δ 8.77 (dd, J = 7.9, 1.2 Hz, 1H), 8.31 (s, 1H), 8.10 (d, J = 8.5 Hz, 1H), 7.99
(dt, J = 16.5, 7.9 Hz, 4H), 7.84 – 7.74 (m, 2H), 7.73 – 7.59 (m, 3H), 7.48 – 7.40 (m, 1H), 7.01
(ddd, J = 8.4, 7.3, 1.1 Hz, 1H), 6.65 (d, J = 8.4 Hz, 1H). 13C{H} NMR (100 MHz, CDCl3) δ 148.5,
148.1, 144.4, 142.4, 134.2, 133.0, 131.8, 131.5, 129.2, 129.1, 128.8, 128.6, 128.3, 128.2, 128.0,
127.8, 127.1, 125.6, 125.0, 124.2, 122.5, 119.9, 118.4, 114.5. HRMS: [M + H]+ calculated for
C24H16N3: 346.1339, found 346.1338.
6-benzylbenzo[4,5]imidazo[1,2-c]quinazoline (3am): Light yellow solid, 34.6 mg, 56% yield, mp:
o
200-202 C (purified by flash chromatography using PE/EA = 10:1 - 5:1). 1H NMR (400 MHz,
CDCl3) δ 8.73 (dd, J = 7.9, 1.2 Hz, 1H), 8.00 (d, J = 8.1 Hz, 1H), 7.94 (d, J = 7.9 Hz, 1H), 7.87 (d,
J = 8.4 Hz, 1H), 7.81 – 7.75 (m, 1H), 7.71 – 7.65 (m, 1H), 7.53 – 7.48 (m, 1H), 7.35 – 7.25 (m,
6H), 4.88 (s, 2H). 13C{H} NMR (100 MHz, CDCl3) δ 148.5, 148.1, 144.4, 142.1, 134.3, 131.7,
129.1, 128.7, 128.3, 128.0, 127.8, 127.2, 125.5, 124.2, 123.1, 120.1, 118.3, 114.4, 42.0. HRMS:
[M + H]+ calculated for C21H16N3: 310.1339, found 310.1339.
6-methylbenzo[4,5]imidazo[1,2-c]quinazoline (3an)7a: White solid, 40.5 mg, 87% yield, mp:
181-182 oC (purified by flash chromatography using PE/EA = 5:1). 1H NMR (400 MHz, CDCl3) δ
8.69 (dd, J = 7.9, 1.0 Hz, 1H), 8.05 (t, J = 8.8 Hz, 2H), 7.89 (d, J = 8.1 Hz, 1H), 7.80 – 7.74 (m,
1H), 7.68 – 7.62 (m, 1H), 7.61 – 7.55 (m, 1H), 7.50 – 7.43 (m, 1H), 3.22 (s, 3H). 13C{H} NMR
(100 MHz, CDCl3) δ 147.8, 147.7, 144.4, 142.3, 131.7, 129.5, 127.7, 127.4, 125.6, 124.1, 123.1,
120.3, 118.1, 114.0, 24.1. HRMS: [M + H]+ calculated for C15H12N3: 234.1026, found 234.1026.
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website. General
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procedures, relevant NMR spectra, HRMS and catalytic experiments.
AUTHOR INFORMATION
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Corresponding Author
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* E-mail: cuixl@hqu.edu.cn
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This research was supported by NSF of China (Nos. 21572072 and 21602064), Xiamen Southern
Oceanographic Center (15PYY052SF01), Science and Technology Bureau of Xiamen City
(3502Z20150054). We thank Xiuping Zhu and Rongyi Zhang for the help with the cover art.
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