F. Ahmadi et al.
Catalysis Communications 157 (2021) 106331
Bomem FT-IR MB spectrometer. NMR spectra were recorded with 300
MHz Bruker DRX Avance spectrometers. Mass spectra were recorded
with an Agilent Technologies (HP) 5973 mass spectrometer. UV–Vis
spectra were recorded on a Shimadzu 2100 spectrometer using a 1-cm
path length cell at room temperature, and the fluorescence spectra
were recorded on a Perkin Elmer LS 45, using a 1-cm path length cell.
The X-ray diffraction measurements were made with a STOE IPDS-II
diffractometer with grafite-monochromated MoKa radiation. All chem-
icals were purchased from Merck or Aldrich and were used without
further purification. The 2-(4,5-diphenyl-1H-imidazol-2-yl)aniline 5
was synthesized according to a literature report [28].
the 1,4- dioxane is the superior solvent for the reaction, and the 3a was
obtained in 63% isolated yield (entry 5). Then, the effect of iodine in the
reaction was checked. In the absence of iodine, only a trace amount of 3a
was produced (entry 10). Next, the other amounts of catalyst was tested
in the reaction using 10, 15 and 25 mol% of catalyst (Table 1, entries
11–13). The 20 mol% of catalyst afforded the best isolated yield (entry
5). Notably, no better result was observed by removing the oxidant
(Table 1, entry 14). Subsequently, some commercially available oxi-
dants such as BPO, K2S2O8, H2O2 and Ag2CO3 were screened in the re-
action (entries 15–18). As shown, the reaction worked most efficiently in
the presence of TBHP as an oxidant (entry 5). We tested the reaction at
room temperature and 50 ◦C. It was found that the 3a was obtained in
lower yields (entries 19 and 20). Finally, the other iodine sources such as
NIS, KI, and CuI were tested in the reaction [29–31]. As shown in
Table 1, the product 3a was obtained in low yield (entries 21–23).
Therefore, the 1,4-dioxane using 20 mol% iodine in the presence of
TBHP at 100 ◦C was chosen as the optimized reaction conditions.
Then, the reaction of various benzimidazoloanilines with different
isocyanides was carried out to investigate the generality of the method
(Scheme 1). The reaction of substituted benzo[d]imidazol-2-yl) anilines
with aromatic and aliphatic isocyanides successfully afforded the 3a-l in
moderate to high isolated yields.
2.2. General procedure for the synthesis of benzoimidazoquinazoline
amines (3)
Isocyanide (0.75 mmol) was added to a stirred solution of 2-(1H-
benzo[d]imidazol-2-yl)aniline (0.5 mmol), I2 (0.1 mmol) and TBHP
(70% aqueous solution, 1 mmol) in 1,4-dioxane (1 mL). The mixture was
then kept under stirring at 100 ◦C for 12 h. After that, the concentrated
residue was purified by the column chromatography over silica gel using
n-hexane/ethyl acetate (4:1) as eluent to give the desired product 3.
To achieve more information about the reaction mechanism, a con-
trol radical trapping experiment was conducted using TEMPO as a
radical scavenger to trap possible radical intermediates. Surprisingly, no
considerable change took place, and the desired product 3a produced in
60% yields, thus indicating the no radical mechanism (Scheme 2, eq. 1).
When the reaction was carried out by the N-methyl imidazole derivative
4 or nitro-phenyl imidazole 5 under the standard reaction condition, the
TLC and 1H NMR spectra of the reaction mixture showed a combination
3. Results and discussion
Our investigation was initiated by the reaction of benzo[d]imidazol-
aniline 1a and tert-butyl isocyanide 2a using 20 mol% I2 as the catalyst
and TBHP as the oxidant in MeCN at 100 ◦C for 12 h. The
benzoimidazoquinazolin-6-amine 3a was produced in 39% yield
(Table 1, entry 1). To improve the yield, various reaction conditions
were then tested. First, the solvent screening (entries 1–9) revealed that
Table 1
Optimization of the reaction conditionsa.
Entry
Solvent
I2 (mol%)
Oxidant
Yield [%]
1
CH3CN
20
20
20
20
20
20
20
20
20
–
10
15
25
20
20
20
20
20
20
20
20
20
20
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
–
39
2
tBuOMe
43
3
DCM
35
4
PhCH3
59
5
1,4-Dioxane
H2O
63
6
trace
33
7
THF
8
DMF
19
9
DMSO
25
10
11
12
13
14
15
16
17
18
19b
20c
21d
22e
23f
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
trace
49
54
60
18
BPO
59
K2S2O8
H2O2
Ag2CO3
TBHP
TBHP
TBHP
TBHP
TBHP
54
48
60
trace
27
25
<20
28
a
2-amino-N-benzylbenzamide (0.5 mmol), t-BuNC (0.75 mmol), I2 (20 mol%), oxidant (2 eq), solvent (2.0 mL), 100 ◦C, 12 h.
b
room temperature.c 50 ◦C. dCat. = NIS. eCat. = KI. fCat. = CuI.
2