In situ air oxidation and photophysical studies of isoquinoline-fused N-heteroacenes

Article abstract of DOI:10.1039/d0ob00375a

An efficient, metal free and environment friendly synthesis of isoquinoline-fused benzimidazole has been developed via in situ air oxidation. Also, syntheses of isoquinoline-fused quinazolinone heteroacenes were successfully achieved. The synthesized isoquinoline-fused benzimidazole and isoquinoline-fused quinazolinone derivatives showed λ_max, F_max and Φ_f values in the ranges 356-394 nm, 403-444 nm and 0.063-0.471, respectively, in CHCl₃,.

Full text of DOI:10.1039/d0ob00375a

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DOI: 10.1039/D0OB00375A
Organic and Biomolecular Chemistry
ARTICLE
The In-Situ Air Oxidation and Photophysical Studies of Isoquinoline-
fused N-Heteroacenes
Received 00th January 20xx,
Accepted 00th January 20xx
a
a
a
a
Amol D. Sonawane, Rohini A. Sonawane, Khin Myat Noe Win, Masayuki Ninomiya,
and Mamoru Koketsu*,a
DOI: 10.1039/x0xx00000x
An efficient, metal free and environment friendly synthesis of isoquinoline-fused
benzimidazole has been developed via in-situ air oxidation. Also, syntheses of isoquinoline-
fused quinazolinone heteroacenes were successfully achieved. The synthesized isoquinoline-
fused benzimidazole and isoquinoline-fused quinazolinone derivatives showed λmax, Fmax and
www.rsc.org/
Φ
f
3
values in the range from 356-394 nm, 403-444 nm and 0.063-0.471, respectively in CHCl .
Open Flask
Isoqui
O
R2
noline
X
noline
H
R1
NH2
NH2
Ar
Isoqui
Ar
R1
Air Oxidation
Ar
NH2
N
O
N
NH2
o
DMSO, 120 C
R1
N
o
N
DMSO, 120 C
R1
O
Metal Free
. E+ = Fe(III)/
(R X)
2
Benzimidazole
4 Examples
C-Se/C-N bond formation
In-situ Oxidation
Good functional group tolerance
Fluorescence properties
Quinazolinone
X = S, Se
2
2
1
13 Examples
In the literature survey, reports are available towards the
construction of isoquinoline-fused benzimidazole
Introduction
heteroacenes in the presence of various expensive Lewis
acidic catalysts such as silver, gold, copper, magnesium and
Among the N-heterocycles, isoquinoline-fused benzimidazole
and isoquinoline-fused quinazolinone have attracted
considerable attention due to their immense and
outstanding biological properties . It is also known that many
synthetic methods have been developed and documented
for their analogs due to their intrinsic anticancer, anti-HIV-1,
5
rhodium-catalyst . The cascade cyclizations of alkynes via
diorganyl diselenides are gaining considerable attentions due
1
6
to novel seleno-heterocycles and further applications in the
preparation of physical materials that shows potentially
7
useful optical and fluorescent properties . The interesting
2
antiviral, antimicrobial, and antifungal properties .
biological and optical properties of isoquinoline and
selenophene-heterocycles encouraged synthetic chemists to
develop novel synthetic strategies to access structurally
Therefore, molecules containing this motif have attracted
considerable attention in medicinal chemistry and much
effort has been focused on the synthetic methods of
isoquinoline-fused benzimidazole ring system. The
commonly used synthetic routes involve cascade cyclization
8
different motifs . Recently, we have successfully synthesized
the novel cascade cyclizations resulted into various seleno-
9
fused heteroacenes . Herein, we have successfully
strategies
with
2-ethynylbenzaldehydes
and
attempted the two core heterosystems, isoquinoline-fused
benzimidazole and isoquinoline-fused quinazolinone in the
open flask. Isoquinoline-fused benzimidazoles were achieved
by metal free catalyst. The reaction was found to occur in
three major steps involving first imine formations, further
benzenediamines or 2-amino benzamide as substrates to
give isoquinoline-fused benzimidazole and isoquinoline-
fused quinazolinone polycyclic skeletons (Fig. 1)
3
, 4
.
aDepartment of Chemistry and Biomolecular Science, Faculty of
Engineering, Gifu University, Gifu 501-1193, Japan. Email:
koketsu@gifu-u.ac.jp
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Journal Name
cyclization, and finally air oxidation. Meanwhile, the Scheme 1. Synthesis of isoquinoline-fused benzimidazole 4
View Article Online
DOI: 10.1039/D0OB00375A
isoquinoline-fused quinazolinone heteroacenes were and isoquinoline-based quinazolinone 5 heteroacenes
successfully achieved by intramolecular cascade cyclization Table 1 shows the variety of substrate scopes for
by Fe(III) catalyst which resulted into various substituted isoquinoline-fused benzimidazole derivatives. The reactions
sulfur and selenium-heteroacenes.
are facile for electron-donating as well as electron
withdrawing substituents, on the controversy reaction did
not proceeded for the substituted TMS-alkyne which did not
resulted into the product 4o and 4p respectively. All the
reactions were carried out in open flask at 120 C in DMSO
solvent, the yield of reaction drastically decreased under the
nitrogen atmosphere.
Previous work
H
R
R
H2N
R
EtOH
N
(1)
+
R
O
H2N
N
o
R = H
H
Ar
Ar
H2N
H2N
AgNO3
+
N
(2)
(3)
R
o
H2O, 80 C
O
2
h
N
Table 1. Substrate scopes for Isoquinoline-fused
benzimidazole derivatives 4.
H
O
Ar
Ar
H2N
Cat. Au (I)
N
+
R
H
Ar
Cat. Chiral HA
Ar
O
H2N
HN
o
H2N
H2N
R1
R2
o
DCE, 0 C
DMSO, 120 C
N
O
O
Open Flask
R1
N
This Work
Ar
X
N
2
1
. 2-Amino-
benzamide
4
R2
H
Ar
Ar
Ar
Benzene
o
1
,2-diamine
DMSO, 120 C
N
N
N
R
Ph
Ph
2. E+ = Fe (III)
(R'X)2
o
O
DMSO, 120 C
Metal free
N
N
Open Flask
X = S, Se
O
16 Examples
N
N
1
3 Examples
N
N
N
c, 74%
N
Fig. 1
4a, 75%
4b, 73%
4
4
d, 68%
O
Result and Discussion
O
F
F
Our investigations were started with the easily available
starting materials amines and 2-bromobenzaldehydes 1
which were readily converted to aryl alkynes 2 under
Sonogashira coupling conditions, the compounds 1 were
alkylated with various aromatic alkynes to afford the
corresponding substituted aryl alkynes 2 in 60-70% yields.
Further, compounds 2 were successfully converted to
intermediate 3 by reacting with substituted 2-amino
N
N
N
N
N
N
N
N
4
e, 80%
4g, 78%
4
f, 78%
4
h, 79%
F
F
F
F
N
N
N
N
N
N
N
N
4
i, 72%
4
j, 70%
4k, 80%
4l, 84%
Ph
o
benzamides in DMSO solvent at 120 C in open atmosphere.
Ph
Si
Si
N
At the same time, if compounds 2 were treated with
substituted 1,2-diamine benzenes which resulted into the
cyclized products 4 with good yields under the same reaction
conditions. Further, compound 3 in hand was successfully
N
N
N
N
N
N
N
4
m, 78%
4
n, 82%
4o, n.r.
4p, n.r.
With the standard compound 3a in hand, we have
transformed to the substituted sulfur and selenium- optimized the synthesis of isoquinoline-based quinazolinone
heterocycles 5 in the presence of disulfide and diselenide derivative 5a. We first examined the selenocyclization
respectively via Fe(III) catalyst (Scheme 1). The structures of reaction of aryl alkyne 3a with 1.5 equiv. of FeCl ·6H O and
3
2
1
0
1
13
2
3, 4 and 5 were confirmed by the IR, H-NMR, C-NMR (PhSe)2 (1.5 equiv.) in CHCl3 at room temperature, the
and HRMS spectral analysis.
reaction did not proceeded and the starting 3a was isolated
by column chromatography. Further, the reaction was
carried out with 1.0 equiv. of FeCl ·6H O and (PhSe) (0.5
3 2 2
R2
R3
R2
Br
(i)
R1
R1
(iii)
H
N
equiv.) in DCM under reflux conditions. Interestingly, the
reaction resulted in the formation of 12-phenyl-13-
(phenylselanyl)-6H-isoquinolino[2,1-a]quinazolin-6-one
derivative 5a in 56% yield. To improve the yield of cyclization
product, different reaction conditions were screened (Table
2, entries 1-12). The best result was obtained, when the
selenocyclization reaction was carried out using 1.5 equiv. of
R1
O
O
N
1
3
2
O
(iv)
(ii)
R2
R'
X
R2
R1
R1
N
N
R3
N
R4
N
3 2 2
FeCl ·6H O and (PhSe) (1.0 equiv.) in DCM under reflux
4
R3
O
X = S, Se
conditions to afford desired 12-phenyl-13-(phenylselanyl)-
6H-isoquinolino[2,1-a] quinazolin-6-one derivative 5a in 65%
yield (Table 2, entry 4). With the standard conditions in
hands, we have successfully synthesized various substituted
Reagents: (i) Aryl alkynes (1.1 equiv.), Pd(PPh3)2Cl2(5 Mol%), CuI (6 Mol%), NEt3, THF, rt, 12 h
5
o
(
(
(
ii) 1,2-diaminobenzene (1.2 equiv.), DMSO, 120 C (Oil Bath), 12 h
o
iii) 2-aminobenzamide (1.2 equiv.), DMSO, 120 C (Oil Bath), 12 h
iv) FeCl3·6H2O (2.0 equiv.), Diorganyl diselenides (1.0) / disulfides (1.5 equiv.)
DCM, reflux (Oil Bath), 5-6 h
2
| J. Name., 2012, 00, 1-3
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Journal Name
ARTICLE
sulfur and selenium heteroacenes (Table 3). Additionally, it Table 3. Substrate scopes for synthesis of isoquinoline-fused
View Article Online
DOI: 10.1039/D0OB00375A
was found that the reaction with dibenzyl disulfide (PhCH
and dibutyl selenide (Bu) Se did not proceed toward the
expected products (5n and 5o).
2 2
S)
quinazolinone derivatives 5.
2
Ar
R'
X
N
R1
Ar
H
N
(R'X)2 (1.0 equiv.)
R1
R2
N
Table 2. Optimization table for synthesis of 12-phenyl-13-
R2
FeCl3·6H2O (1.5 equiv.)
N
(phenylselanyl)-6H-isoquinolino[2,1-a]quinazolin-6-one (5a)
DCM, reflux
O
O
S
5
X = S, Se
3
Ph
SeBu
Ph
S
Ph
O
Se
N
Se
N
O
Ph
Ph
Ph
Ph
N
N
N
N
N
O
N
O
(PhSe)2
N
O
N
O
N
N
N
N
Fe (III)
H
5a
5b, 54%
O
5d, 63%
,
65%
5c, 59%
5e, 70%
Ph
F
Se
S
Ph
Ph
F
Ph
F
F
Ph
S
Se
N
S
S
3
a
5a
N
O
N
N
N
O
N
N
N
N
N
Entry Solvent
No.
E+
(Eq.)
(PhSe)
2
Time Temp.
5a
Yield
%)
n.r.
5f, 69%
5g, 66%
5h, 67%
O
O
5i, 71%
5j, 64%
O
S
ο
a
(Eq.)
0.5
0.5
2.0
1.0
2.0
1.5
3.0
1.0
1.0
1.0
1.0
1.0
(h)
12
12
12
8
( C)
Ph
Se
Ph
S
S
BuSe
Ph
(
Ph
Ph
Ph
Ph
Ph
1
2
3
4
5
6
7
CHCl
3
FeCl
1.0)
FeCl ·6H
1.0)
FeCl ·6H
1.5)
FeCl ·6H
1.5)
FeCl ·6H
2.5)
3
·6H
2
2
2
2
2
O
O
O
O
O
rt
N
Cl
N
Cl
N
O
Cl
N
O
N
O
(
N
N
N
N
N
5
k, 58%
O
5o, n.r.
DCM
DCM
DCM
DCM
reflux
reflux
reflux
reflux
65
56
5l, 55%
5
m, 63%
O
5n
, n.r.
3
(
Route B shows the formation of isoquinoline-fused
3
61
quinazolinone derivatives 5. The reaction 2-aminobenzamide
with 2-alkynyl benzamide 2 does not resulted into the
cyclized product C, instead we isolated the intermediate 3.
Further, the intermediate 3 was cyclized via novel cascade
cyclization pathway. In the first step, iron salt reacts with
dibutyl diselenide promoting the cleavage of Se-Se bond to
give an organoselenyl cation and an organoselenyl anion .
The Fe(III) coordinates with one selenium atom from dibutyl
diselenide, which results in the intermediate I’, further the
nucleophilic anti-attack on activated seleniranium ion I’ takes
place by internal amine as nucleophile results into the
intermediate cyclized product II’. Finally, the cascade cyclized
product 5 was successfully achieved in good yields.
(
3
65
(
3
8
62
(
CHCl
DCM
DMF
DMSO
DCM
DCM
DCM
3
FeCl
3
(2.0)
12
8
42
1
1
FeCl
3.5)
FeCl ·6H
1.5)
FeCl ·6H
1.5)
CuI (0.1)/I
3
·6H
2
2
2
O
reflux
80
59
(
8
.
.
3
O
O
8
n.r.
n.r.
n.r.
n.r.
n.r.
(
9
3
8
80
(
1
1
1
0.
1.
2.
2
12
12
12
reflux
reflux
reflux
(
1.0)
CuCl
2
(0.1)
FeCl3·6H2O
O
Ph
BuHSe
Ph
Ph
H2N
H2N
R2
R1
R1
H
N
BuSe+
H
N
H
N
O
[O]
CuI(0.1)/NIS
1.0)
R1
R2 FeCl3·6H2O+ BuSe-
R2
SeBu
FeCl3·6H2
DMSO, 120oC
N
N
HN
-
2
Ph
Route B
(
O
(BuSe)2
I'
O
O
O
Isolated intermediate
aThe reaction was performed by addition of diphenyl diselenide (1.0
equiv.) to a solution of FeCl ·6H O (1.5 equiv.) in DCM (4 mL), under
an air atmosphere, at room temperature. After 15 min at this
temperature, alkyne 3a (1.0 equiv.) was added. The resulting mixture
was refluxed for 8 h. n.r.: No reaction.
3
FeCl3·6H2O
FeCl3·6H2
O
DMSO
20oC
H2N
H2N
BuSe
N
1
R2
H
N
6-endo-dig
Ph
3
2
Ph
R1
Route A
R2
H
N
SeBu
R2
N
R1
O
II'
Ph
O
C
-SeBuH
R1
N
R2
H
SeBu
H
H2N
6-endo-dig
Ph
Ph
Ph
R1
[O]
R1
R1
I
N
N
N
N
In this study, we have hypothesized the plausible reaction
mechanism for the synthesis of isoquinoline-fused
benzimidazole 4 as well as the novel cascade cyclization for
the synthesis of isoquinoline-fused quinazolinone 5 in Scheme
H
R2
R2
HN
N
R2
4
O
II
5
Scheme 3. Plausible mechanism
The UV-vis absorption spectra of 4a, 4e, 4i, 4k, 5a, 5c, 5h
3
. Route A shows the formation of isoquinoline-fused
benzimidazole 4. The reaction 1,2-benezediammine and 2- and 5k in DCM are shown in Fig. 2. In the isoquinoline-fused
alkynylbenzaldehyde 2 gives rise to imine which results into benzimidazole derivatives 4a, 4e, 4i and 4k, the absorption
the formation of intermediate I. The intermediate I on 6- maximum (λmax) and molar extinction coefficient () values of
endo-dig cyclization delivers intermediate II. Finally, the isoquinoline-based benzimidazole (4a: λmax = 360 nm,  =
intermediate II on in-situ oxidation delivers the desire 4,972), (4e: λmax = 360 nm,  = 5,942), (4i: λmax = 356 nm,  =
isoquinoline-fused benzimidazole derivatives 4.
6,897) and (4k: λmax = 359 nm,  = 4,935) derivatives were
almost the same (Fig. 2a, Table 4). While, In the case of
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isoquinoline-fused quinazolinone derivatives 5a, 5c, 5h and
k, the absorption maximum (λmax) and molar extinction
coefficient () values of isoquinoline-fused quinazolinone (5a:
Fmax / nm
V w Article Online
Si et okes shift / nm
f
DOI: 10.1039/D0OB00375A
b
Compound
max () / nm
5
4a
286 (56,187), 329 (9,629), 344 (7,396), 360 (4,972)
403
406
434
412
43
46
78
53
0.370
0.427
0.327
0.471
4e
287 (64,085), 342 (9,458), 360 (5,942)
λ
λ
max = 394 nm,  = 9,262), (5c: λmax = 393 nm,  = 11,688), (5h:
max = 394 nm,  = 11,549) and (5k: λmax = 393 nm,  = 11,845)
4i
4k
5a
286 (53,804), 327 (10,279), 341 (8,847), 356 (6,897)
286 (56,023), 328 (9,093), 343 (7,251), 359 (4,935)
derivatives were almost the same (Fig. 2b, Table 4). The
isoquinoline-fused benzimidazole derivatives 4a, 4e, 4i and
289 (33,068), 356 (13,856), 375 (13,987), 394 (9,262)
440
46
0.135
5c
289 (36,841), 357 (16,264), 374 (17,138), 393 (11,688)
289 (39,269), 355 (16,742), 374 (17,882), 394 (11,549)
291 (37,042), 357 (14,838), 374 (16,352), 393 (11,845)
437
439
444
44
45
51
0.123
0.074
0.063
4
k have higher absorbance maxima (λmax = 393-394 nm) than
5h
the isoquinoline-fused quinazolinone derivatives 5a, 5c, 5h
and 5k (λmax = 356-360 nm).
5k
aMeasured at a concentration of 1.0 x 10-5 mol dm-3. bMeasured using an integrating sphere method.
Conclusion:
In conclusion, we have successfully developed an
efficient, metal free and environment friendly pathway for
the synthesis of isoquinoline-fused benzimidazole and also
successfully achieved the isoquinoline-fused quinazolinone
heteroacenes via Fe(III) catalyst. The synthesized
isoquinoline-fused benzimidazole and isoquinoline-fused
quinazolinone derivatives showed λmax, Fmax and Φ
the range from 356-394 nm, 403-444 nm and 0.063-0.471,
respectively in CHCl . We believed that this methodology
provides a novel pathway for the synthesis of isoquinoline-
f
values in
Fig. 2. UV-vis absorption spectra of isoquinoline-fused
benzimidazole (a) and isoquinoline-fused quinazolinone (b)
derivatives in CHCl .
3
3
The fluorescence spectra of 4a, 4e, 4i, 4k 5a, 5c, 5h and fused benzimidazole and isoquinoline-fused quinazolinone
k in DCM are shown in Fig. 3. The fluorescence maximum heteroacenes. Also, the DFT mechanistic studies and
Fmax) and Stokes shift values were in the range of 403 to 444 biological evaluation for such novel heterocycles are in
5
(
nm and 43 to 78 nm, respectively (Table 4). The fluorescence progress.
quantum yield ( ) values obtained for isoquinoline-based
f
benzimidazole were (
f
:
0.370-0.471), while the Experimental: General
fluorescence quantum yield ( ) values obtained for
isoquinoline-based quinazolinone derivatives (5) were
f
All solvents and reagents were purchased from the suppliers
and used without further purification. IR spectra were
recorded on a JASCO FT/IR-460 Plus spectrophotometer.
Reactions were monitored by TLC on silica plates using UV-
light chamber for visualization. Evaporation and
condensation were carried out in vacuo. NMR spectra were
recorded with JEOL JNM-ECS 400 spectrometers with
tetramethylsilane as an internal standard. Chemical shifts δ
and coupling constants J are given in ppm (parts per million)
and Hz (hertz) respectively. The following abbreviations were
used as follows: s: singlet, d: doublet, t: triplet, m: multiplet.
All known compounds data are in consistent with the given
literature reports. Melting points were measured by a
Yanaco micromelting point apparatus. The HRMS were
recorded with the Acquity XEVO QTof MS analyzer. UV-vis
spectra were taken on a Hitachi U4100 spectrophotometer.
f
relatively low ( : 0.063-0.135) probably because of heavy
1
2
atom effect . Interestingly, the fluorescence spectra of
isoquinoline-fused benzimidazole 4a, 4e, 4i and 4k (Fig. 3a)
showed the higher fluorescence than the isoquinoline-fused
quinazolinone derivatives 5a, 5c, 5h and 5k (Fig. 3b) because
of the heavy atom effect.
Fluorescence spectra were measured on
a FP-8600
spectrofluorometer. Fluorescence quantum yields were
recorded on a Quantaurus-QY.
General procedure and spectral data for the synthesized
compounds 2a-2g.
To a solution of 2-bromobenzaldehyde 1a (350 mg, 2.43
Fig. 3. Fluorescence spectra of isoquinoline-fused
benzimidazole (a) and isoquinoline-fused quinazolinone (b)
derivatives in CHCl
3
.
mmol, 1.0 equiv.) in dry THF (10 mL) was added Pd(PPh
3 2 2
) Cl
Table 4. Optical properties in DCM
(62 mg, 6 mol%), triethylamine (574 mg, 7.29 mmol, 3.0
equiv.), phenyl acetylene (372.50 mg, 3.65 mmol, 1.2 equiv.),
and copper(I) iodide (18 mg, 5 mol%) under nitrogen. The
4
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mixture was stirred at room temperature for 15 h. After 130.2, 129.0, 127.7, 127.7, 127.5, 126.3, 124.3, 124.2, 118.6,
View Article Online
DOI: 10.1039/D0OB00375A
completion of reaction; the solvent was evaporated under 118.4, 116.6, 116.4, 94.9, 94.9, 85.9; HRMS (ESI-TOF) m/z:
+
19
reduced pressure. The residue was extracted with ethyl [M+H] Calcd. for C15
acetate and the organic phase was washed successively with 2-((4-Fluoro-3-methylphenyl)ethynyl)benzaldehyde (2f)
water and brine. The organic layer was dried over Na SO Yield: 70%; Sticky; IR (KBr): 3036, 1851, 1774, 1693, 1588,
The resulting crude product was purified by column 1497, 1448, 1291, 1262, 1230, 1114, 1086, 886, 830, 635,
H10O F 225.0716; Found 225.0688.
2
4
.
-1 1
chromatography using n-hexane: ethyl acetate (92:8) as the 532 cm ; H-NMR (400 MHz, CDCl
eluent to afford 2a as brown liquid. = 8.0 Hz, 1H), 7.56-7.62 (m, 2H), 7.35-7.46 (m, 3H), 7.01 (t, J =
-(phenylethynyl)benzaldehyde (2a)
Yield: 74%; brown liquid; IR (KBr): 3062, 2216, 1787, 1698, 162.7, 160.8, 135.9, 135.0, 135.0, 133.9, 133.2, 131.1, 131.0,
3
) δ 10.62 (s, 1H), 7.94 (d, J
1
3
2
3
8.9 Hz, 1H), 2.28 (s, 3H); C-NMR (100 MHz, CDCl ) δ 191.8,
-1
1
1
592, 1443, 1266, 1070, 817, 756, 689, 517 cm ; H-NMR 128.7, 127.4, 126.9, 125.7, 125.6, 118.2, 115.7, 115.5, 95.7,
+
(
400 MHz, CDCl
3
) δ 10.65 (d, J = 0.9 Hz, 1H), 7.94-7.96 (m, 84.4, 14.5; HRMS (ESI-TOF) m/z: [M+H] Calcd for C16
H12OF
1
7
H), 7.64 (dd, J = 7.8, 0.9 Hz, 1H), 7.55-7.59 (m, 3H), 7.43- 239.0872; Found 239.0867.
1
3
.47 (m, 1H), 7.38 (dt, J = 7.3, 2.9 Hz, 3H); C-NMR (100 2-(4-Phenylbut-1-yn-1-yl)benzaldehyde (2g)
) δ 191.8, 136.0, 133.9, 133.3, 131.8, 129.2, 128.7, Yield: 75%; Sticky; IR (neat): 3029, 2228, 1852, 1788, 1775,
28.6, 127.4, 125.0, 122.4, 96.4, 85.0; HRMS (ESI-TOF) m/z: 1697, 1595, 1497, 1477, 1244, 1193, 1030, 823, 761, 699,
MHz, CDCl
3
1
+
-1 1
[
M+H] Calcd for C15
-(p-Tolylethynyl)benzaldehyde (2b)
Yield: 76%; Melting point: 34-35°C; IR (neat): 3026, 2214, Hz, 3H), 7.26 (t, J = 6.9 Hz, 3H), 2.95 (t, J = 7.4 Hz, 2H), 2.79 (t,
H11O 207.0810; Found 207.0782.
637, 507 cm ; H-NMR (400 MHz, CDCl
3
) δ 10.35 (s, 1H), 7.86
2
(d, J = 8.0 Hz, 1H), 7.45-7.51 (m, 2H), 7.35 (dt, J = 19.9, 7.4
1
3
1
6
3
774, 1693, 1591, 1509, 1388, 1262, 1191, 1018, 816, 758, J = 7.4 Hz, 2H); C-NMR (100 MHz, CDCl ) δ 192.2, 140.3,
-1 1
33, 519 cm ; H-NMR (400 MHz, CDCl
) δ 10.63 (d, J = 0.9 136.1, 133.8, 133.4, 128.6, 128.6, 128.1, 127.7, 127.0, 126.7,
3
+
Hz, 1H), 7.92 (d, J = 7.8 Hz, 1H), 7.59-7.61 (m, 1H), 7.54 (td, J 97.1, 34.9, 21.9; HRMS (ESI-TOF) m/z: [M+H] Calcd for
=
2
1
8
7.6, 1.4 Hz, 1H), 7.38-7.45 (m, 3H), 7.16 (d, J = 8.2 Hz, 2H),
.36 (s, 3H); C-NMR (100 MHz, CDCl
C
17
H
15O 235.1123; Found 235.1105.
) δ 191.9, 139.5, 135.9, General procedure and spectral data for the synthesized
3
1
3
33.9, 133.2, 131.8, 129.4, 128.5, 127.3, 127.3, 119.4, 96.8, compounds 3a-3e.
+
4.5, 77.5, 77.20, 76.9, 21.7; HRMS (ESI-TOF) m/z: [M+H] To a solution of 2-(phenylethynyl)benzaldehyde 2a (0.100 g,
Calcd for C16
2
H13O 221.0966; Found 221.0938.
5.91 mmol, 1.0 equiv.) in DMSO solvent (4 mL) was added 2-
aminobenzamide (0.105 g, 1.3 equiv.), the resulting reaction
-((4-Methoxyphenyl)ethynyl)benzaldehyde (2c)
Yield: 69%; Melting point: 38-39°C; IR (neat): 2837, 2210, mixture was heated at 120°C in open flast. After completion
1
5
687, 1592, 1505, 1457, 1288, 1248, 1157, 1025, 812, 670, of reaction; the reaction mixture was extracted with ethyl
-1 1
37, 521 cm ; H-NMR (400 MHz, CDCl
3
) δ 10.65 (d, J = 1.1 acetate and the organic phase was washed successively with
SO
.58 (m, 1H), 7.50 (dd, J = 6.9, 1.8 Hz, 2H), 7.43 (d, J = 7.8 Hz, The resulting crude product was purified by column
H), 6.90 (dd, J = 6.6, 2.1 Hz, 2H), 3.84 (s, 3H); 13C-NMR (100 chromatography using n-hexane: acetone (90:10) as the
) δ 192.0, 160.3, 135.8, 133.9, 133.3, 133.1, 128.3, eluent to afford 3a as white solid.
27.4, 127.3, 114.5, 114.3, 96.7, 83.9, 77.4, 77.1, 76.8, 55.4; 2-(2-(Phenylethynyl)phenyl)quinazolin-4(1H)-one (3a)
Hz, 1H), 7.93 (d, J = 8.2 Hz, 1H), 7.61 (d, J = 7.8 Hz, 1H), 7.54- water and brine. The organic layer was dried over Na
7
1
2
4
.
MHz, CDCl
3
1
+
HRMS (ESI-TOF) m/z: [M+Na] Calcd for C16
H O Na Yield: 69%; Melting point: 156-158°C; IR (neat): 3180, 1673,
12 2
2
2
59.0735; Found 259.0714.
-((2-Fluorophenyl)ethynyl)benzaldehyde (2d)
1598, 1557, 1466, 1303, 1219, 1149, 948, 813, 756, 692, 615,
518 cm ; H-NMR (400 MHz, CDCl ) δ 10.94 (s, 1H), 8.32-8.34
3
-1 1
Yield: 75%; Melting point: 37-38°C; IR (neat): 3055, 2357, (m, 1H), 8.25-8.27 (m, 1H), 7.76-7.84 (m, 2H), 7.66-7.69 (m,
1
6
1
1
7
1
1
1
682, 1592, 1471, 1450, 1262, 1222, 1192, 1099, 823, 796, 1H), 7.60 (td, J = 3.8, 2.0 Hz, 2H), 7.48-7.52 (m, 3H), 7.34-7.36
3 3
92 cm ; H-NMR (400 MHz, CDCl ) δ 10.64 (d, J = 0.9 Hz, (m, 3H); C-NMR (100 MHz, CDCl ) δ 161.9, 151.4, 149.4,
H), 7.93 (dd, J = 7.8, 0.9 Hz, 1H), 7.63 (dd, J = 7.8, 0.9 Hz, 134.8, 133.9, 133.5, 131.8, 131.0, 130.3, 129.3, 129.2, 128.7,
-1
1
13
H), 7.50-7.58 (m, 2H), 7.42-7.46 (m, 1H), 7.31-7.37 (m, 1H), 128.2, 127.1, 126.6, 121.8, 121.3, 120.6, 97.0, 86.8; HRMS
1
3
+
.08-7.16 (m, 2H); C-NMR (100 MHz, CDCl
64.1, 161.6, 136.0, 133.8, 133.4, 133.4, 133.3, 131.0, 131.0, Found 345.0977.
3
) δ 191.7, 191.6, (ESI-TOF) m/z: [M+Na] Calcd for C22H N ONa 345.1004;
1
4
2
29.1, 127.3, 126.4, 124.3, 124.2, 115.9, 115.8, 115.7, 115.6, 2-(2-(p-Tolylethynyl)phenyl)quinazolin-4(1H)-one (3b)
11.2, 111.1, 90.1, 90.0, 89.7; HRMS (ESI-TOF) m/z: [M+H]+ Yield: 66%; Melting point: 162-164°C; IR (neat): 3130, 1673,
Calcd for C15
-((3-Fluorophenyl)ethynyl)benzaldehyde (2e)
Yield: 79%; Sticky; IR (KBr): 3072, 2212, 1776, 1698, 1608, 11.05 (s, 1H), 8.33 (d, J = 7.8 Hz, 1H), 8.24-8.27 (m, 1H), 7.75-
H10OF 225.0716; Found 225.0693.
1593, 1557, 1466, 1448, 1302, 1148, 1110, 949, 879, 819,
743, 729, 701, 615, 510 cm ; H-NMR (400 MHz, CDCl ) δ
3
-1
1
2
-1
1
1
593, 1580, 1193, 1122, 943, 872, 786, 761cm ; H-NMR 7.83 (m, 2H), 7.63-7.66 (m, 1H), 7.46-7.51 (m, 5H), 7.13 (d, J
1
3
(400 MHz, CDCl
3
) δ 10.60 (s, 1H), 7.93-7.95 (m, 1H), 7.56-7.64 = 8.2 Hz, 2H), 2.33 (s, 3H); C-NMR (100 MHz, CDCl ) δ 162.0,
3
(
7
m, 2H), 7.46 (t, J = 7.6 Hz, 1H), 7.34 (dq, J = 4.9, 1.5 Hz, 2H), 151.5, 149.4, 139.6, 134.7, 133.8, 133.4, 131.7, 131.0, 130.2,
1
3
.25 (dd, J = 9.4, 2.5 Hz, 1H), 7.06-7.11 (m, 1H); C-NMR (100 129.4, 129.0, 128.1, 127.0, 126.6, 121.4, 120.9, 118.8, 97.3,
) δ 191.4, 163.7, 161.3, 136.0, 133.9, 133.4, 130.3,
MHz, CDCl
3
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J. Name., 2013, 00, 1-3 | 5
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 6 of 11
ARTICLE
Journal Name
+
8
3
2
6.3, 21.7; HRMS (ESI-TOF) m/z: [M+H] Calcd for C23
37.1341; Found 337.1317.
-(2-((3-Fluorophenyl)ethynyl)phenyl)quinazolin-4(1H)-one
H
17
N
2
O
(d, J = 8.2 Hz, 1H), 7.57-7.68 (m, 8H), 7.37 (t, J = 7.1 Hz, 1H),
View Article Online
DOI: 10.1039/D0OB00375A
6.99 (t, J = 7.8 Hz, 1H), 6.87 (s, 1H), 6.48 (d, J = 8.7 Hz, 1H);
1
3
3
C-NMR (100 MHz, CDCl ) δ 148.4, 144.3, 137.6, 134.7,
(
3c)
131.7, 130.8, 130.2, 130.0, 129.5, 129.1, 128.0, 126.7, 125.2,
Yield: 41%; Melting point: 150-151°C; IR (neat): 3067, 1661, 124.3, 123.01, 121.3, 119.8, 114.2, 112.7; HRMS (ESI-TOF)
1
5
+
605, 1578, 1438, 1202, 1148, 944, 866, 846, 760, 748, 695, m/z: [M+H] Calcd for C21
31 cm ; H-NMR (400 MHz, CDCl ) δ 10.92 (s, 1H), 8.32-8.34 9,10-Dimethyl-6-phenylbenzo[4,5]imidazo[2,1-
H N
15 2
295.1235; Found 295.1218.
-1 1
3
(
m, 1H), 8.22 (q, J = 3.1 Hz, 1H), 7.77-7.84 (m, 2H), 7.67-7.69 a]isoquinoline (4b)
(m, 1H), 7.49-7.54 (m, 3H), 7.36 (dd, J = 6.4, 1.4 Hz, 1H), 7.30 Yield: 73%; Melting point: 225-227°C; IR (neat): 1637, 1527,
(
td, J = 7.9, 5.6 Hz, 1H), 7.23-7.26 (m, 1H), 7.04 (td, J = 8.1, 1494, 1453, 1397, 1299, 998, 962, 847, 836, 762, 748, 654,
3 3
.1 Hz, 1H); C-NMR (100 MHz, CDCl ) δ 163.7, 162.0, 161.2, 640, 538 cm ; H-NMR (400 MHz, CDCl ) δ 8.84 (d, J = 9.6 Hz,
51.3, 149.3, 134.9, 134.0, 131.0, 130.4, 130.3, 130.2, 129.5, 1H), 7.73 (s, 1H), 7.67-7.69 (m, 1H), 7.61-7.65 (m, 3H), 7.58
1
3
-1 1
2
1
1
1
28.1, 127.8, 127.7, 127.2, 126.6, 123.8, 123.7, 121.3, 120.3, (d, J = 4.6 Hz, 4H), 6.85 (s, 1H), 6.19 (s, 1H), 2.37 (s, 3H), 2.12
1
3
3
18.6, 118.4, 116.8, 116.5, 95.2, 87.6; HRMS (ESI-TOF) m/z: (s, 3H); C-NMR (100 MHz, CDCl ) δ 147.78, 143.0, 137.6,
+
19
[
M+H] Calcd for C22
H
14
N
2
O F 341.1090; Found 341.1081.
134.9, 133.4, 131.5, 130.4, 129.8, 129.8, 129.5, 129.2, 128.9,
2
4
-(2-((4-Fluoro-3-methylphenyl)ethynyl)phenyl)quinazolin-
(1H)-one (3d)
127.8, 126.7, 125.0, 123.1, 119.6, 114.3, 112.1, 20.8, 20.5;
+
HRMS (ESI-TOF) m/z: [M+H] Calcd for C23
H N
19 2
323.1548;
Yield: 57%; Melting point: 136-137°C; IR (neat): 3069, 1661, Found 323.1541.
1
8
606, 1578, 1588, 1438, 1426, 1202, 1148, 1107, 944, 866, 6-(p-Tolyl)benzo[4,5]imidazo[2,1-a]isoquinoline (4c)
-1 1
46, 780, 765, 748, 674, 531 cm ; H-NMR (400 MHz, CDCl
3
)
Yield: 74%; Melting point: 148-150°C; IR (neat): 1639, 1529,
δ 10.87 (s, 1H), 8.34 (d, J = 8.0 Hz, 1H), 8.29-8.30 (m, 1H), 1508, 1447, 1329, 1310, 1112, 1014, 844, 823, 752, 662, 609,
-
1 1
7
7
.78-7.85 (m, 2H), 7.66-7.67 (m, 1H), 7.52 (t, J = 4.6 Hz, 3H), 494 cm ; H-NMR (400 MHz, CDCl
3
) δ 8.88-8.90 (m, 1H), 7.99
.40-7.44 (m, 2H), 6.98 (t, J = 8.9 Hz, 1H), 2.26 (s, 3H); C- (d, J = 8.2 Hz, 1H), 7.65-7.70 (m, 3H), 7.47 (d, J = 8.2 Hz, 2H),
) δ 161.9, 151.4, 149.4, 135.1, 135.1, 7.39 (dd, J = 7.3, 5.0 Hz, 3H), 7.02 (t, J = 7.8 Hz, 1H), 6.87 (s,
1
3
NMR (100 MHz, CDCl
3
1
3
1
1
9
C
7
34.8, 133.8, 133.45, 131.3, 131.2, 131.1, 130.3, 129.2, 1H), 6.56 (d, J = 8.2 Hz, 1H), 2.53 (s, 3H); C-NMR (100 MHz,
) δ 148.4, 144.19, 140.1, 137.7, 131.8, 131.8, 130.8,
6.3, 86.2, 14.5; HRMS (ESI-TOF) m/z: [M+H] Calcd for 130.2, 129.7, 129.3, 127.9, 126.7, 125.2, 124.3, 122.9, 121.3,
28.2, 127.1, 126.6, 125.6, 121.4, 120.6, 117.5, 115.8, 115.6, CDCl
3
+
+
23
H
16
N
2
OF 355.1247; Found 355.1241.
119.7, 114.3, 112.7, 21.7; HRMS (ESI-TOF) m/z: [M+H] Calcd
-Chloro-2-(2-(phenylethynyl)phenyl)quinazolin-4(1H)-one
for C22
H
17
N
2
309.1392; Found 309.1363.
9,10-Dimethyl-6-(p-tolyl)benzo[4,5]imidazo[2,1-
Yield: 43%; Melting point: 152-154°C; IR (neat): 3323, 1700, a]isoquinoline (4d)
(
3e)
1
7
1
598, 1556, 1491, 1431, 1420, 1219, 1139, 1099, 1072, 910, Yield: 68%; Melting point: 170-172°C; IR (neat): 1636, 1531,
-1 1
46, 682, 691, 639 cm ; H-NMR (400 MHz, CDCl
H), 8.22-8.26 (m, 2H), 7.79 (d, J = 2.3 Hz, 1H), 7.66 (q, J = 3.1 840, 812, 749, 664, 539 cm ; H-NMR (400 MHz, CDCl
3
) δ 11.10 (s, 1510, 1463, 1454, 1372, 1300, 1219, 1022, 999, 866, 847,
-1
1
3
) δ
Hz, 1H), 7.58 (q, J = 3.2 Hz, 2H), 7.48-7.52 (m, 2H), 7.43 (dd, J 8.84 (t, J = 4.6 Hz, 1H), 7.73 (s, 1H), 7.62-7.70 (m, 3H), 7.47
=
CDCl
1
3
8.5, 2.1 Hz, 1H), 7.34 (t, J = 3.4 Hz, 3H); C-NMR (100 MHz, (d, J = 7.8 Hz, 2H), 7.39 (d, J = 7.8 Hz, 2H), 6.84 (s, 1H), 6.30
1
3
) δ 161.3, 152.5, 150.3, 141.0, 134.0, 133.0, 131.8, (s, 1H), 2.54 (s, 3H), 2.38 (s, 3H), 2.15 (s, 3H); C-NMR (100
) δ 147.8, 143.0, 139.9, 137.7, 133.4, 132.0, 131.6,
19.8, 97.2, 86.7; HRMS (ESI-TOF) m/z: [M+H] Calcd for 130.3, 129.8, 129.5, 129.4, 129.3, 127.7, 126.6, 125.0, 123.1,
3
1
1
C
31.3, 130.3, 129.4, 129.2, 128.7, 128.0, 127.6, 121.7, 120.7, MHz, CDCl
3
+
22 14 2
H N OCl 357.0795; Found 357.0794.
119.6, 114.4, 112.1, 21.6, 20.9, 20.5; HRMS (ESI-TOF) m/z:
+
General procedure and spectral data for the synthesized [M+H] Calcd for C24
H N
21 2
337.1705; Found 337.1679.
compounds 4a-4n.
6-(4-Methoxyphenyl)benzo[4,5]imidazo[2,1-a]isoquinoline
To a solution of 2-(phenylethynyl)benzaldehyde 2a (0.100 g, (4e)
5
1
.91 mmol, 1.0 equiv.) in DMSO solvent (4 mL) was added Yield: 80%; Melting point: 184-186°C; IR (neat): 1643, 1607,
,2-diaminebenzene (0.083 g, 7.69 mmol, 1.3 equiv.), the 1527, 1507, 1448, 1328, 1312, 1246, 1178, 1122, 1109, 1017,
-1
1
3
resulting reaction mixture was heated at 120°C in open flast. 831, 813, 740, 610, 482 cm ; H-NMR (400 MHz, CDCl ) δ
After completion of reaction; the reaction mixture was 8.87 (t, J = 4.6 Hz, 1H), 7.98 (d, J = 8.2 Hz, 1H), 7.64-7.69 (m,
extracted with ethyl acetate and the organic phase was 3H), 7.49 (dd, J = 6.6, 2.1 Hz, 2H), 7.39 (t, J = 7.1 Hz, 1H), 7.09
washed successively with water and brine. The organic layer (dd, J = 6.6, 2.1 Hz, 2H), 7.00-7.04 (m, 1H), 6.86 (s, 1H), 6.59
1
3
was dried over Na
2
SO . The resulting crude product was (d, J = 8.2 Hz, 1H), 3.94 (s, 3H); C-NMR (100 MHz, CDCl ) δ
4
3
purified by column chromatography using n-hexane: acetone 160.8, 148.4, 144.3, 137.5, 131.8, 130.9, 130.8, 130.2, 127.8,
(
90:10) as the eluent to afford 3a as white solid.
-Phenylbenzo[4,5]imidazo[2,1-a]isoquinoline (4a)
127.1, 126.7, 125.2, 124.2, 122.9, 121.3, 119.7, 114.39,
6
114.3, 112.7, 77.5, 77.2, 76.8, 55.6; HRMS (ESI-TOF) m/z:
+
Yield: 75%; Melting point: 163-165°C; IR (neat): 1640, 1525, [M+H] Calcd for C22
17 2
H N O 325.1341; Found 325.1329.
1
4
494, 1448, 1330, 1310, 1219, 1118, 833, 737, 699, 650, 547, 6-(4-Methoxyphenyl)-9,10-dimethylbenzo[4,5]imidazo[2,1-
-1 1
86 cm ; H-NMR (400 MHz, CDCl
) δ 8.87-8.89 (m, 1H), 7.98 a]isoquinoline (4f)
3
6
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 7 of 11
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
ARTICLE
Yield: 78%; Melting point: 216-217°C; IR (neat): 1634, 1574, 147.7, 143.0, 136.8, 136.7, 136.0, 133.6, 131.2, 130.7, 130.7,
View Article Online
DOI: 10.1039/D0OB00375A
1
8
8
=
1
531, 1509, 1452, 1395, 1290, 1251, 1178, 1024, 999, 844, 130.6, 129.9, 129.0, 128.1, 126.8, 125.4, 125.4, 125.0, 123.2,
-1
1
35, 813, 762, 624, 543 cm ; H-NMR (400 MHz, CDCl ) δ 119.8, 117.0, 116.9, 116.8, 116.7, 114.0, 112.5, 20.9, 20.5;
3
+
19
.82-8.84 (m, 1H), 7.73 (s, 1H), 7.60-7.67 (m, 3H), 7.49 (dd, J HRMS (ESI-TOF) m/z: [M+H] Calcd for C23
18 2
H N F 341.1454;
6.6, 2.1 Hz, 2H), 7.08 (d, J = 9.2 Hz, 2H), 6.81 (s, 1H), 6.34 (s, Found 341.1438.
1
3
H), 3.94 (s, 3H), 2.37 (s, 3H), 2.16 (s, 3H); C-NMR (100 6-(4-Fluoro-3-methylphenyl)benzo[4,5]imidazo[2,1-
) δ 160.8, 147.8, 143.0, 137.4, 133.4, 131.6, 130.8, a]isoquinoline (4k)
30.3, 129.7, 129.3, 127.6, 127.3, 126.6, 125.0, 123.0, 119.6, Yield: 80%; Melting point: 160-162°C; IR (neat): 1637, 1527,
14.4, 114.2, 112.3, 55.6, 20.9, 20.5; HRMS (ESI-TOF) m/z: 1503, 1447, 1333, 1318, 1247, 1232, 1127, 825, 758, 735,
MHz, CDCl
3
1
1
+
-1 1
[
M+H] Calcd for C24
-(2-Fluorophenyl)benzo[4,5]imidazo[2,1-a]isoquinoline
4g)
21 2
H N O 353.1654; Found 353.1646.
3
728, 548, 528, 480 cm ; H-NMR (500 MHz, CDCl ) δ 8.88 (t, J
6
(
= 4.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.66-7.71 (m, 3H), 7.38-
7.44 (m, 3H), 7.22 (t, J = 8.6 Hz, 1H), 7.04 (t, J = 7.7 Hz, 1H),
1
3
Yield: 78%; Melting point: 144-146°C; IR (neat): 1605, 1581, 6.86 (s, 1H), 6.54 (d, J = 8.0 Hz, 1H), 2.39 (s, 3H); C-NMR
1
7
8
7
528, 1487, 1453, 1298, 1210, 1165, 1002, 879, 831, 767, (125 MHz, CDCl
74, 710, 698, 520, 482 cm ; H-NMR (400 MHz, CDCl
.90 (dd, J = 7.6, 1.6 Hz, 1H), 8.00 (d, J = 8.2 Hz, 1H), 7.55- 126.1, 126.0, 125.2, 124.3, 123.0, 121.4, 119.9, 115.9, 115.7,
.73 (m, 5H), 7.36-7.42 (m, 2H), 7.31 (t, J = 8.7 Hz, 1H), 7.05 114.1, 112.8, 14.8; HRMS (ESI-TOF) m/z: [M+H] Calcd for
3
) δ 163.2, 161.2, 148.4, 144.3, 136.8, 132.7,
) δ 132.7, 131.6, 130.7, 130.5, 130.3, 128.7, 128.7, 128.0, 126.7,
3
-1
1
+
(
td, J = 7.9, 1.2 Hz, 1H), 6.97 (s, 1H), 6.55 (d, J = 8.7 Hz, 1H);
C
22
H
16
N
2
F 327.1298; Found 327.1279.
) δ 162.0, 159.5, 148.2, 144.2, 6-(4-Fluoro-3-methylphenyl)-9,10-
3
1
3
C-NMR (100 MHz, CDCl
1
1
1
32.3, 131.8, 131.5, 131.3, 130.9, 130.2, 128.3, 126.9, 125.2, dimethylbenzo[4,5]imidazo[2,1-a]isoquinoline (4l)
25.0, 124.5, 124.6, 123.3, 122.8, 122.6, 121.9, 119.9, 116.6, Yield: 84%; Melting point: 212-214°C; IR (neat): 1635, 1592,
16.4, 116.3, 116.2, 113.9, 113.8, 112.9; HRMS (ESI-TOF) 1499, 1450, 1380, 1229, 1203, 1166, 1124, 1023, 995, 856,
+
-1 1
m/z: [M+H] Calcd for C21
-(2-Fluorophenyl)-9,10-dimethylbenzo[4,5]imidazo[2,1-
a]isoquinoline (4h)
14 2
H N F 313.1141; Found 313.1129.
3
833, 825, 746, 698, 654, 481 cm ; H-NMR (400 MHz, CDCl )
δ 8.83 (dd, J = 5.7, 3.4 Hz, 1H), 7.74 (s, 1H), 7.62-7.69 (m, 3H),
7.43 (d, J = 7.3 Hz, 1H), 7.39 (dd, J = 8.2, 5.0 Hz, 1H), 7.20-
6
Yield: 79%; Melting point: 170-172°C; IR (neat): 1643, 1530, 7.25 (m, 1H), 6.82 (s, 1H), 6.30 (s, 1H), 2.40 (d, J = 1.8 Hz, 3H),
1
3
1
6
7
7
1
1
1
1
1
492, 1452, 1398, 1311, 1237, 1103, 995, 866, 799, 841, 749, 2.38 (s, 3H), 2.18 (s, 3H); C-NMR (100 MHz, CDCl
54, 482 cm ; H-NMR (400 MHz, CDCl
3
) δ 163.4,
) δ 8.85-8.87 (m, 1H), 161.0, 147.8, 143.0, 136.7, 133.5, 132.7, 132.7, 131.4, 130.6,
3
-1 1
.74 (s, 1H), 7.61-7.70 (m, 4H), 7.56 (td, J = 7.4, 1.5 Hz, 1H), 130.5, 129.8, 129.2, 128.8, 128.7, 127.9, 126.6, 125.9, 125.7,
.36-7.40 (m, 1H), 7.30 (t, J = 8.7 Hz, 1H), 6.92 (s, 1H), 6.25 (s, 125.0, 123.1, 119.8, 119.7, 115.7, 114.3, 114.1, 112.4, 112.3,
1
3
H), 2.37 (s, 3H), 2.14 (s, 3H); C-NMR (100 MHz, CDCl
3
) δ 20.9, 20.6, 20.5, 14.7, 14.7, 14.7; HRMS (ESI-TOF) m/z:
+
62.0, 159.5, 147.6, 142.9, 133.5, 132.1, 131.9, 131.4, 131.1, [M+H] Calcd for C24
H N
20 2
F 355.1611; Found 355.1592.
30.86, 129.8, 129.3, 128.1, 126.8, 125.0, 125.0, 123.4, 6-Phenethylbenzo[4,5]imidazo[2,1-a]isoquinoline (4m)
23.0, 122.8, 119.8, 119.8, 116.4, 116.3, 116.2, 116.1, 113.3, Yield: 78%; Melting point: 164-166°C; IR (neat): 1644, 1610,
13.2, 113.0, 112.9, 21.0, 20.6, 20.5; HRMS (ESI-TOF) m/z: 1600, 1559, 1526, 1450, 1427, 1350, 1018, 834, 774, 752,
+
-1
1
[
6
M+H] Calcd for C23
-(3-Fluorophenyl)benzo[4,5]imidazo[2,1-a]isoquinoline (4i) 8.82 (t, J = 4.3 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.98 (d, J = 8.0
Yield: 72%; Melting point: 162-163°C; IR (neat): 1614, 1581, Hz, 1H), 7.58-7.61 (m, 3H), 7.49 (t, J = 7.7 Hz, 1H), 7.24-7.37
18 2
H N F 341.1454; Found 341.1440.
3
744, 728, 699, 591, 505 cm ; H-NMR (500 MHz, CDCl ) δ
1
8
526, 1484, 1449, 1319, 1332, 1146, 1123, 1014, 908, 884, (m, 6H), 6.71 (s, 1H), 3.57 (t, J = 8.0 Hz, 2H), 3.19 (t, J = 8.0
-1
1
13
35, 792, 730, 648, 520, 479 cm ; H-NMR (400 MHz, CDCl
3
)
3
Hz, 2H); C-NMR (125 MHz, CDCl ) δ 148.6, 144.4, 140.1,
δ 8.87-8.90 (m, 1H), 7.99 (d, J = 7.8 Hz, 1H), 7.67-7.73 (m, 138.1, 131.6, 130.7, 130.1, 128.9, 128.5, 127.4, 126.7, 126.1,
3
H), 7.55-7.60 (m, 1H), 7.41 (td, J = 7.7, 1.1 Hz, 2H), 7.32-7.36 125.1, 124.3, 122.5, 122.0, 120.2, 114.3, 110.0, 35.0, 33.7;
+
(m, 2H), 7.03-7.07 (m, 1H), 6.91 (s, 1H), 6.55 (d, J = 8.2 Hz, HRMS (ESI-TOF) m/z: [M+H] Calcd for C23
H N
19 2
323.1548;
1
3
1
1
1
1
H); C-NMR (100 MHz, CDCl ) δ 164.1, 161.7, 148.3, 144.3, Found 323.1532.
3
36.6, 136.6, 136.1, 131.4, 130.9, 130.8, 130.5, 130.3, 128.3, 9,10-Dimethyl-6-phenethylbenzo[4,5]imidazo[2,1-
26.9, 125.4, 125.4, 125.2, 124.4, 123.1, 121.6, 120.0, 117.2, a]isoquinoline (4n)
17.0, 116.9, 116.7, 113.9, 113.0; HRMS (ESI-TOF) m/z: Yield: 82%; Melting point: 148-150°C; IR (neat): 1645, 1530,
+
19
[
M+H] Calcd for C21
H
14
N
2
F 313.1141; Found 313.1111.
-(3-Fluorophenyl)-9,10-dimethylbenzo[4,5]imidazo[2,1-
1455, 1437, 1334, 1265, 1197, 906, 858, 825, 773, 745, 697,
-1 1
6
585, 506, 461 cm ; H-NMR (500 MHz, CDCl
1H), 7.77 (s, 1H), 7.70 (s, 1H), 7.55-7.58 (m, 3H), 7.36 (t, J =
Yield: 70%; Melting point: 261-262°C; IR (neat): 1643, 1605, 7.7 Hz, 2H), 7.28 (q, J = 6.7 Hz, 3H), 6.65 (s, 1H), 3.51 (t, J =
3
) δ 8.77-8.78 (m,
a]isoquinoline (4j)
1
7
581, 1528, 1486, 1452, 1431, 1314, 1210, 1002, 879, 831, 8.3 Hz, 2H), 3.15 (t, J = 8.0 Hz, 2H), 2.43 (s, 3H), 2.40 (s, 3H);
-1
1
13
97, 745, 710, 618, 520, 482 cm ; H-NMR (400 MHz, CDCl
3
)
3
C-NMR (125 MHz, CDCl ) δ 148.0, 143.1, 140.2, 138.0,
δ 8.83-8.85 (m, 1H), 7.74 (s, 1H), 7.64-7.71 (m, 3H), 7.54-7.58 133.4, 131.4, 131.1, 129.6, 129.1, 128.9, 128.5, 127.2, 126.7,
(
3
m, 1H), 7.32-7.40 (m, 3H), 6.86 (s, 1H), 6.27 (s, 1H), 2.38 (s, 126.0, 124.9, 122.6, 120.0, 114.3, 109.7, 34.9, 33.9, 21.0,
1
3
H), 2.16 (s, 3H); C-NMR (100 MHz, CDCl
3
) δ 164.1, 161.6,
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 7
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O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Page 8 of 11
ARTICLE
Journal Name
2
3
0.5; HRMS (ESI-TOF) m/z: [M+H]+ Calcd for C25
51.1861; Found 351.1852.
H
23
N
2
13-(Methylthio)-12-phenyl-6H-isoquinolino[2,1-View Article Online
a]quinazolin-6-one (5d)
DOI: 10.1039/D0OB00375A
General procedure and spectral data for the synthesized Yield: 63%; Melting point: 180-181°C; IR (neat): 1702, 1604,
compounds 5a-5m. 1588, 1557, 1538, 1465, 1443, 1321, 1288, 1135, 1007, 759,
To a solution of 2-(2-(phenylethynyl)phenyl)quinazolin-4(1H)- 717, 696, 680, 653, 598, 576, 538 cm ; H-NMR (400 MHz,
one 3a (0.100 g, 5.91 mmol, 1.0 equiv.) in DCM solvent (4 CDCl ) δ 9.03 (d, J = 7.3 Hz, 1H), 8.40 (d, J = 8.7 Hz, 1H), 8.10
mL) was added (n-BuSe) (0.083 g, 7.69 mmol, 1.0 equiv.) (d, J = 8.2 Hz, 1H), 7.78-7.83 (m, 3H), 7.66 (t, J = 7.1 Hz, 1H),
and FeCl ·6H O (1.5 equiv.), the resulting reaction mixture 7.43 (t, J = 3.2 Hz, 3H), 7.35-7.40 (m, 3H), 1.98 (s, 3H); C-
was refluxed for 8 h. After completion of reaction; the NMR (100 MHz, CDCl ) δ 160.9, 147.2, 146.8, 141.9, 137.7,
-1 1
3
2
1
3
3
2
3
reaction mixture was extracted with DCM, the organic phase 134.7, 132.9, 132.6, 128.8, 128.75, 128.2, 128.0, 127.6,
was washed successively with water and brine. The organic 127.4, 127.3, 126.9, 126.5, 125.9, 122.6, 120.4, 19.0; HRMS
+
layer was dried over Na
2
SO
4
. The resulting crude product was (ESI-TOF) m/z: [M+H] Calcd for C23
17 2
H N OS 369.1062; Found
purified by column chromatography using n-hexane: ethyl 369.1041.
acetate (95:05) as the eluent to afford 5a as white solid.
2-Phenyl-13-(phenylselanyl)-6H-isoquinolino[2,1-
a]quinazolin-6-one (5a)
13-(Phenylselanyl)-12-(p-tolyl)-6H-isoquinolino[2,1-
a]quinazolin-6-one (5e)
Yield: 70%; Melting point: 130-132°C; IR (neat): 1688, 1609,
1
Yield: 65%; Melting point: 204-205°C; IR (neat): 1700, 1602, 1589, 1542, 1507, 1463, 1304, 1219, 1136, 1185, 955, 811,
-
1
1
1
7
8
7
589, 1557, 1540, 1480, 1463, 1336, 1257, 1134, 1003, 761, 733, 673, 668, 642, 537 cm ; H-NMR (400 MHz, CDCl
38, 693, 676, 573, 535 cm ; H-NMR (400 MHz, CDCl
3
) δ
) δ 8.97-9.00 (m, 1H), 8.17-8.20 (m, 1H), 8.13 (d, J = 7.8 Hz, 1H),
3
-1 1
.99-9.01 (m, 1H), 8.20-8.22 (m, 1H), 8.12 (d, J = 7.3 Hz, 1H), 7.78-7.85 (m, 2H), 7.56-7.58 (m, 2H), 7.39 (td, J = 7.4, 1.5 Hz,
.79-7.85 (m, 2H), 7.58-7.60 (m, 2H), 7.34-7.41 (m, 4H), 7.29 1H), 7.18 (dd, J = 13.1, 8.5 Hz, 4H), 7.07-7.10 (m, 5H), 2.40 (s,
1
3
13
(
dd, J = 8.0, 1.6 Hz, 2H), 7.09 (s, 5H); C-NMR (100 MHz, 3H); C-NMR (100 MHz, CDCl
CDCl ) δ 161.0, 147.5, 146.8, 142.9, 139.0, 134.8, 133.7, 137.9, 136.1, 134.7, 133.7, 132.7, 132.5, 129.6, 129.3, 128.8,
32.6, 132.6, 129.7, 129.3, 128.9, 128.6, 128.2, 128.1, 127.4, 128.5, 128.3, 128.0, 127.4, 127.2, 126.9, 126.4, 126.0, 120.5,
3
) δ 161.1, 147.6, 146.77, 143.0,
3
1
1
7
7
+
27.4, 127.3, 127.0, 126.4, 126.0, 120.5, 118.7; Se-NMR (75 118.7, 77.5, 21.7; HRMS (ESI-TOF) m/z: [M+H] Calcd for
+
MHz, CDCl
3
) δ 193.97; HRMS (ESI-TOF) m/z: [M+H] Calcd for
29 21 2
C H N OSe 493.0819; Found 493.0796.
C
28
H
19
N
2
OSe 479.0663; Found 479.0639.
13-(Methylthio)-12-(p-tolyl)-6H-isoquinolino[2,1-
a]quinazolin-6-one (5f)
1
3-(Butylselanyl)-12-phenyl-6H-isoquinolino[2,1-
a]quinazolin-6-one (5b)
Yield: 69%; Melting point: 152-154°C; IR (neat): 1699, 1608,
Yield: 54%; Melting point: 128-130°C; IR (neat): 1700, 1650, 1589, 1556, 1508, 1464, 1289, 1262, 1137, 974, 869, 817,
-
1
1
1
1
608, 1591, 1156, 1509, 1439, 1324, 1291, 1159, 1141, 1076, 758, 697, 681, 650, 458 cm ; H-NMR (400 MHz, CDCl
3
) δ
023, 816, 755, 740, 715, 683, 590, 535, 491 cm ; H-NMR 9.02 (d, J = 8.2 Hz, 1H), 8.39 (d, J = 8.2 Hz, 1H), 8.12 (d, J = 8.2
) δ 9.03 (dd, J = 8.2, 0.9 Hz, 1H), 8.43 (d, J = Hz, 1H), 7.76-7.83 (m, 3H), 7.63-7.67 (m, 1H), 7.38 (td, J =
.3 Hz, 1H), 8.10-8.12 (m, 1H), 7.75-7.85 (m, 3H), 7.64-7.68 7.3, 1.4 Hz, 1H), 7.22-7.27 (m, 4H), 2.44 (s, 3H), 1.99 (s, 3H);
-1 1
(400 MHz, CDCl
3
7
1
3
(m, 1H), 7.37-7.41 (m, 4H), 7.32 (q, J = 3.2 Hz, 2H), 2.46 (t, J =
C-NMR (100 MHz, CDCl
3
) δ 161.0, 147.3, 146.8, 142.0,
7
.3 Hz, 2H), 1.19-1.27 (m, 2H), 1.06 (q, J = 7.3 Hz, 2H), 0.68 (t, 137.7, 134.7, 134.6, 133.0, 132.5, 128.7, 128.6, 128.2, 127.6,
1
3
J = 7.3 Hz, 3H); C-NMR (100 MHz, CDCl
3
) δ 160.9, 147.5, 127.3, 126.9, 126.5, 125.9, 122.5, 120.5, 21.7, 19.0; HRMS
+
1
1
1
3
4
1
19 2
46.8, 141.4, 139.2, 134.6, 133.7, 132.5, 129.21, 129.2, (ESI-TOF) m/z: [M+H] Calcd for C24H N OS 383.1218; Found
28.7, 127.9, 127.9, 127.4, 127.3, 127.2, 126.9, 125.9, 120.5, 383.1191.
7
7
18.8, 31.8, 28.9, 22.6, 13.4; Se-NMR (75 MHz, CDCl
3
) δ 12-(3-Fluorophenyl)-13-(methylthio)-6H-isoquinolino[2,1-
+
19.75; HRMS (ESI-TOF) m/z: [M+H] Calcd for C26
H N OSe a]quinazolin-6-one (5g)
23 2
59.0976; Found 459.0952.
2-Phenyl-13-(phenylthio)-6H-isoquinolino[2,1-
918, 799, 782, 694, 681, 674, 537 cm ; H-NMR (400 MHz,
) δ 9.04 (d, J = 7.8 Hz, 1H), 8.40 (d, J = 8.7 Hz, 1H), 8.10-
592, 1545, 1467, 1340, 1291, 1272, 1146, 1136, 1067, 763, 8.12 (m, 1H), 7.78-7.84 (m, 3H), 7.66-7.70 (m, 1H), 7.35-7.42
Yield: 66%; Melting point: 184-185°C; IR (neat): 1704, 1607,
1591, 1557, 1540, 1467, 1339, 1292, 1272, 1187, 1127, 949,
-1 1
a]quinazolin-6-one (5c)
Yield: 59%; Melting point: 207-208°C; IR (neat): 1690, 1604, CDCl
3
1
7
-1
1
13
43, 727, 705, 690, 681, 598, 543, 492 cm ; H-NMR (400 (m, 2H), 7.11 (ddd, J = 17.1, 7.7, 1.9 Hz, 3H), 2.01 (s, 3H); C-
) δ 9.01-9.03 (m, 1H), 8.11-8.15 (m, 2H), 7.78-7.85 NMR (100 MHz, CDCl ) δ 160.8, 160.7, 147.0, 146.7, 140.4,
m, 2H), 7.58-7.63 (m, 2H), 7.30-7.41 (m, 6H), 7.13 (dd, J = 139.7, 139.7, 134.8, 132.7, 132.6, 129.1, 128.8, 128.7, 128.3,
MHz, CDCl
(
3
3
1
3
8
.2, 6.9 Hz, 2H), 6.99-7.07 (m, 3H); C-NMR (100 MHz, CDCl
3
)
127.6, 127.3, 127.0, 126.6, 126.1, 124.6, 124.6, 123.0, 120.2,
+
δ 161.0, 147.3, 146.7, 143.8, 137.4, 137.3, 134.9, 133.2, 116.2, 115.9, 115.0, 114.8, 19.0; HRMS (ESI-TOF) m/z: [M+H]
1
1
7
4
16 2
32.6, 129.1, 129.0, 128.3, 128.2, 128.2, 127.5, 127.4, 127.3, Calcd for C23H N OFS 387.0967; Found 387.0946.
27.0, 126.9, 126.8, 126.1, 125.6, 120.5, 118.9, 77.5, 77.3, 12-(4-Fluoro-3-methylphenyl)-13-(phenylselanyl)-6H-
+
7.1, 76.8; HRMS (ESI-TOF) m/z: [M+H] Calcd for C28
H N OS isoquinolino[2,1-a]quinazolin-6-one (5h)
19 2
31.1218; Found 431.1197.
Yield: 67%; Melting point: 184-186°C; IR (neat): 1688, 1610,
1
591, 1557, 1544, 1467, 1346, 1272, 1124, 831, 761, 740,
8
| J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 20xx
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Page 9 of 11
O rP gl ea na si ce &d Bo i on mo to al e dc juu l sa tr mC ha er mg i ins ts ry
Journal Name
ARTICLE
-
1
1
7
9
7
30, 691, 677, 541, 473 cm ; H-NMR (400 MHz, CDCl
3
) δ 8.99-9.01 (m, 1H), 8.15-8.17 (m, 1H), 8.04 (d, J = 8.7 Hz, 1H),
View Article Online
DOI: 10.1039/D0OB00375A
.00-9.02 (m, 1H), 8.23-8.25 (m, 1H), 8.12-8.15 (m, 1H), 7.80- 7.84 (d, J = 2.3 Hz, 1H), 7.61-7.66 (m, 2H), 7.29-7.39 (m, 6H),
.86 (m, 2H), 7.59-7.64 (m, 2H), 7.40-7.44 (m, 1H), 7.04-7.12 7.12-7.16 (m, 2H), 7.04-7.08 (m, 1H), 6.99-7.01 (m, 2H); C-
m, 7H), 6.98 (t, J = 8.7 Hz, 1H), 2.23 (d, J = 1.8 Hz, 3H); C- NMR (100 MHz, CDCl
NMR (100 MHz, CDCl ) δ 162.2, 161.1, 159.7, 147.4, 146.7, 137.2, 137.1, 133.4, 133.0, 129.1, 128.9, 128.3, 127.9, 127.5,
42.1, 134.9, 134.7, 133.7, 132.7, 132.6, 131.8, 131.7, 129.8, 127.5, 127.0, 126.8, 126.7, 126.4, 125.7, 119.4, 118.7; HRMS
1
3
1
3
(
3
) δ 160.4, 148.3, 147.6, 143.6, 141.1,
3
1
1
1
+
17 2
29.6, 129.4, 129.3, 129.0, 128.0, 127.6, 127.4, 127.3, 127.0, (ESI-TOF) m/z: [M+Na] Calcd for C28H N ONaSCl 487.0648;
26.4, 126.2, 126.0, 124.1, 123.9, 120.4, 119.2, 14.8; 77Se- Found 487.0651.
+
NMR (75 MHz, CDCl
Calcd for C29 OFSe 511.0725; Found 511.0711.
2-(4-Fluoro-3-methylphenyl)-13-(phenylthio)-6H-
isoquinolino[2,1-a]quinazolin-6-one (5i)
3
) δ 320.52; HRMS (ESI-TOF) m/z: [M+H] 9-Chloro-13-(methylthio)-12-phenyl-6H-isoquinolino[2,1-
H N
20 2
a]quinazolin-6-one (5m)
1
Yield: 63%; Melting point: 262-264°C; IR (neat): 1646,
1614, 1598, 1586, 1501, 1430, 1314, 1289, 1134, 1099, 867,
-1 1
3
Yield: 71%; Melting point: 160-162°C; IR (neat): 1686, 1610, 836, 733, 694, 666, 582, 459 cm ; H-NMR (400 MHz, CDCl )
1
8
590, 1557, 1542, 1476, 1466, 1277, 1221, 1220, 1094, 832, δ 8.99 (d, J = 8.2 Hz, 1H), 8.43 (d, J = 7.8 Hz, 1H), 8.19 (d, J =
-1
1
07, 771, 753, 760, 734, 695, 684, 541, 484 cm ; H-NMR 8.2 Hz, 1H), 7.88-7.92 (m, 1H), 7.70 (t, J = 7.1 Hz, 1H), 7.39-
) δ 9.01-9.04 (m, 1H), 8.13-8.18 (m, 2H), 7.47 (m, 5H), 7.29 (dd, J = 8.7, 1.8 Hz, 1H), 7.00 (d, J = 2.0 Hz,
(400 MHz, CDCl
3
1
3
7
3
.81-7.87 (m, 2H), 7.61-7.66 (m, 2H), 7.41-7.45 (m, 1H), 7.15 1H), 1.94 (s, 3H); C-NMR (100 MHz, CDCl ) δ 167.3, 154.0,
(
t, J = 7.3 Hz, 2H), 7.07 (t, J = 7.3 Hz, 3H), 6.95-7.00 (m, 3H), 141.3, 139.9, 137.3, 135.4, 134.1, 134.0, 131.2, 129.8, 129.3,
1
3
2
1
1
1
.22 (d, J = 1.8 Hz, 3H); C-NMR (100 MHz, CDCl
61.01, 147.2, 146.7, 143.0, 137.3, 134.9, 133.2, 133.0, HRMS (ESI-TOF) m/z: [M+H] Calcd for C23
3
) δ 162.2, 128.9, 128.5, 127.3, 126.9, 126.6, 122.6, 122.1, 121.0, 18.7;
+
16 2
H N OSCl
32.6, 131.5, 129.2, 129.1, 128.2, 127.3, 127.0, 126.9, 126.8, 403.0672; Found 403.0669.
26.7, 126.1, 125.7, 124.1, 124.0, 120.4, 119.3, 14.8; HRMS
+
(
ESI-TOF) m/z: [M+H] Calcd for C29
H N
OFS 463.1280; Conflicts of interest
20 2
“
There are no conflicts to declare”.
Acknowledgements
This study was supported by JSPS KAKENHI Grant Number
17550099 (to MK). Author ADS and KMNW are thankful to
MEXT: Monbukagakusho for scholarship and also thankful to
Daiki Kaneko for help in elemental analysis characterization.
1
7
639, 1589, 1554, 1541, 1481, 1337, 1285, 1272, 1135, 925,
62, 689, 678, 642, 647, 474 cm ; H-NMR (400 MHz, CDCl )
3
-1 1
δ 9.04 (d, J = 8.2 Hz, 1H), 8.40 (d, J = 8.2 Hz, 1H), 8.13 (d, J =
8
7
.2 Hz, 1H), 7.79-7.85 (m, 3H), 7.68 (t, J = 8.2 Hz, 1H), 7.39-
.43 (m, 1H), 7.13-7.18 (m, 2H), 7.05 (t, J = 8.7 Hz, 1H), 2.32
Supporting Information:
1
3
(d, J = 1.8 Hz, 3H), 2.00 (s, 3H); C-NMR (100 MHz, CDCl
3
) δ
Experimental procedures, characterization data for the new
1
1
1
62.1, 161.0, 159.6, 147.16, 146.8, 141.1, 134.8, 133.2,
32.8, 132.6, 131.9, 131.8, 128.9, 128.2, 127.8, 127.6, 127.3,
1
13
compounds, and copies of H and C-NMR spectra. This
material is available free of charge via the Internet at http://
27.0, 126.6, 126.0, 124.0, 123.9, 122.9, 120.4, 18.9, 14.9;
+
HRMS (ESI-TOF) m/z: [M+H] Calcd for
24 18 2
C H N OFS
References
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9
01.1124; Found 401.1124.
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3
37, 687, 673, 575, 462 cm ; H-NMR (400 MHz, CDCl ) δ
This journal is © The Royal Society of Chemistry 20xx
J. Name., 2013, 00, 1-3 | 9
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0 | J. Name., 2012, 00, 1-3
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Page 11 of 11
Organic & Biomolecular Chemistry
View Article Online
DOI: 10.1039/D0OB00375A
Open Flask
Isoqui
O
R2
noline
X
noline
H
R1
NH2
NH2
Ar
Isoqui
Ar
R1
Air Oxidation
Ar
NH2
N
N
NH2
o
DMSO, 120 C
R1
N
O
o
N
DMSO, 120 C
R1
O
Metal Free
+
2
. E = Fe(III)/
Benzimidazole
4 Examples
C-Se/C-N bond formation
In-situ Oxidation
Good functional group tolerance
Fluorescence properties
(
R X)
Quinazolinone
X = S, Se
2
2
1
13 Examples