Photocatalytic Approach for Construction of 5,6-Dihydroimidazo[2,1- A[isoquinolines and Their Luminescent Properties

Article abstract of DOI:10.1021/acs.joc.1c00590

A visible-light-driven photoredox reaction of tetrahydroisoquinoline with 2H-azirines is described. 4,7-Bis(4-methoxyphenyl)benzo[c][1,2,5]thiadiazole, a benzothiadiazole (BTD) derived fluorophore, is used as an organic photoredox catalyst, and the reacti

Full text of DOI:10.1021/acs.joc.1c00590

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Photocatalytic Approach for Construction of 5,6-
Dihydroimidazo[2,1‑a]isoquinolines and Their Luminescent
Properties
Zaibin Wang, Hanjie Li, Zhichao Wang, Muhammad Suleman, Yanguang Wang,* and Ping Lu*
Cite This: J. Org. Chem. 2021, 86, 8101−8111
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ABSTRACT: A visible-light-driven photoredox reaction of
tetrahydroisoquinoline with 2H-azirines is described. 4,7-Bis(4-
methoxyphenyl)benzo[c][1,2,5]thiadiazole, a benzothiadiazole
(BTD) derived fluorophore, is used as an organic photoredox
catalyst, and the reaction offers an efficient access to 5,6-
dihydroimidazo[2,1-a]isoquinolines with a broad range of func-
tional groups. The resulting 5,6-dihydroimidazo[2,1-a]-
isoquinolines present strong photoluminecence in solutions and
powders and could be applied in the fabrication of blue OLED
devices.
isoquinolines with high efficiency. In our case, the CN
cleavage of 2H-azirines was observed (Scheme 1C).
INTRODUCTION
■
Because of the additional double bond in 2H-azirines in
comparison with aziridines, 2H-azirines present much higher
reactivity and are valuable precursors in modern organic
synthesis.1 In general, the ring of 2H-azirines could be
isomerized and opened in two manners under heat, light, or
transition metal catalysts. One leads to the formation of vinyl
nitrenes via C−N cleavage,2 while another forms nitrile ylides
via C−C cleavage3 as illustrated in Scheme 1A. In contrast to
C−N and C−C cleavage of 2H-azirines, the CN bond
cleavage presents fewer examples. As one of the examples,
transition-metal catalyzed formal [2 + 2] cycloadditions could
selectively break the CN bond, thanks to the highly reactive
intermediate of 1-azabicyclo[2.1.0]pent-2-ene generated from
the formal [2 + 2] cycloaddition between the CN of 2H-
azirines and electron-deficient triple bond of alkynes.4 Based
on these three strategies, various heterocycles, especially five-
membered rings, have been effectively prepared. Recently,
photoinduced reactions have been widely investigated due to
being transition metal free and the environmental benign
which fit the basic requirements of green chemistry. In the
presence of a photosensitizer and UV or visible light, highly
active species, 2H-azirines radical cation A, could be generated
from 2H-azirines through single electron transfer and further
isomerized into radical cation B5 or radical cation C6
depending on the substituents on the 2H-azirine ring (Scheme
1B). In this report, we tried the visible-light-driven reaction
between tetrahydroisoquinolines and 2H-azirines using benzo-
thiadiazole derivatives as organic photocatalysts. To our
delight, the reaction furnished 5,6-dihydroimidazo[2,1-a]-
RESULTS AND DISCUSSION
■
The initial trial was carried out between 1,2,3,4-tetrahydro-
isoquinoline (1a) and 2,3-diphenyl-2H-azirine (2a) in the
presence of Ru(bpy)3Cl2·6H2O in air. After the cumene
mixture was irradiated at 450−455 nm at room temperature
for 10 h, 5,6-dihydroimidazo[2,1-a]isoquinoline 3a was
isolated in 59% yield (Table 1, entry 1). The structure of 3a
1
was determined by H NMR, 13C NMR, and HRMS and
further established by the single crystal analysis of its analogs
(3l and 3u) (CCDC 2016722, 2050830). By altering the
catalyst to other transition metal complexes, such as Ru-
(bpy)3(PF6)2, Ir(bpy)3, and Ir(ppy)2(bpy)PF6,7 3a was
afforded in similar yields (Table 1, entries 2−4). As the
transition-metal-free photocatalysts such as Eosin Y8 and
4CzIPN9 were used, 3a was isolated in lower yields of 43% and
40%, respectively (Table 1, entries 5 and 6). Benzothiadiazole
(BTD) derived fluorophores PC-110 and PC-211 (Scheme 2)
are seldom reported as photocatalysts. They present the
maximum absorption wavelengths at 440 and 405 nm with a
molar absorptivity of 2.26 × 104 and 1.21 × 104 L mol−1 cm−1,
respectively (Scheme 2, Figure S1). We then screened their
Received: March 12, 2021
Published: June 1, 2021
https://doi.org/10.1021/acs.joc.1c00590
© 2021 American Chemical Society
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Scheme 1. Representative Bond Cleavage of 2H-Azirines and This Work
catalytic efficiency for this transformation. When PC-1 was
tested, 3a was obtained in 56% yield under visible light
irradiation at 435−445 nm (Table 1, entry 7). The optimal
photocatalyst was determined to be PC-2 which provided 3a in
an improved yield (63%). Finally, the optimal wavelength
(Table 1, entries 8−12), solvent (Table 1, entries 13−17), and
reaction time (Table 1, entries 18−20) were also screened and
determined to be 450−455 nm, cumene, and 5 h, respectively.
Without the photocatalyst, 3a could be obtained but in much
lower yields either with or without the light irradiation (Table
1, entries 21 and 22). When the reaction was carried out in
oxygen or nitrogen, 3a was afforded in 13% and 45% yields,
respectively (Table 1, entries 23 and 24). When 2 equiv of
TEMPO were added into the reaction mixture under the
standard reaction conditions, only a trace amount of 3a was
detected by TLC tracking (Table 1, entry 25).
With the optimized reaction conditions (Table 1, entry 19),
various substrates were tested and the results are summarized
in Scheme 3. When the 6-position of tetrahydroisoquinoline
was occupied by an electron-donating (CH3O) and electron-
withdrawing (Cl) substituent, 3b and 3c were obtained in
lower yields (62% and 55%) in comparison to the yield of the
unsubstituted 3a. 7-Methyl tetrahydroisoquinoline afforded 3d
in 48% yield. By moving bromo from the 5-, 6-, and 7-position
to the 8-position of tetrahydroisoquinolines, 3e, 3f, 3g, and 3h
were afforded in yields of 61%, 62%, 49%, and 59%,
respectively. Aryl at the 3-position of 2H-azirine could be 4-
fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methoxy-
phenyl, 4-tert-butylphenyl, and 4-trifluoromethylphenyl. Thus,
3i−3n were obtained in yields ranging from 39% to 69%. 3o
could be prepared in 52% yield when 3-chlorophenyl was
substituted at the 3-position of 2H-azirine. Furthermore, the
aryl at the 3-position of 2H-azirine could be changed to 2-
naphthlenyl, 1-naphthlenyl, and 9-phenanthrenyl. Thus, 3p,
3q, and 3r were prepared in yields of 55%, 47%, and 57%,
respectively. The aryl at the 2-position of 2H-azirine could be
4-fluorophenyl, 4-chlorophenyl, 4-bromophenyl, 4-methyl-
phenyl and 4-trifluoromethylphenyl. In this way, 3s−3w were
obtained in yields ranging from 47% to 63%. 3x and 3y were
afforded in yields of 58% and 45% by moving chloro from the
para to meta position. 2,3-Bis(4-chlorophenyl)-2H-azirine and
2,3-bis(4-bromophenyl)-2H-azirine furnished 3z and 3A in
43% and 52% yields, respectively. 3-(4-Methoxyphenyl)-2-(4-
(trifluoromethyl)phenyl)-2H-azirine provided the desired
product 3B in 71% yield. A relatively lower yield (28%) was
observed when 3-benzyl-2-phenyl-2H-azirine was used as the
substrate. Limited to the volume of the photoirradiate reactor,
the maximum amounts of 1a and 2a in one batch were loaded
as 1 and 1.5 mmol. Based on this, 152 mg of 3a were obtained
in 47% yield.
In order to gain insights into the mechanism, we recorded
the absorptive spectra of the cumene solutions of 1a, 2a, PC-2,
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a
Table 1. Optimization of the Reaction Conditions
b
entry
PC
wavelength (nm)
solvent
time (h)
yield (%)
1
2
3
4
5
6
7
8
Ru(bpy)3Cl2·6H2O
Ru(bpy)3(PF6)2
Ir(bpy)3
Ir(ppy)2(bpy)PF6
Eosin Y
4CzIPN
PC-1
PC-2
PC-2
PC-2
PC-2
PC-2
PC-2
PC-2
PC-2
PC-2
PC-2
PC-2
PC-2
450−455
450−455
450−455
450−455
530−535
530−535
435−445
410−415
390−395
430−435
450−455
470−475
450−455
450−455
450−455
450−455
450−455
450−455
450−455
450−455
450−455
−
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
p-Cymene
toluene
MeCN
1,4-dioxane
DCE
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
Cumene
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
10
7
59
57
50
56
43
40
56
63
58
67
68
62
44
43
35
38
40
69
72
55
30
15
13
45
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
5
3
5
5
5
5
5
PC-2
−
−
PC-2
PC-2
PC-2
c
450−455
450−455
450−455
d
e
Cumene
trace
d
a
b
c
Reaction conditions: 1a (0.2 mmol), 2a (0.3 mmol), catalyst (3 mol %), solvent (2 mL). Isolated yield. Under an O2 atmosphere. Under an N2
atmosphere. 2 equiv of TEMPO was added.
e
Scheme 2. Structure of Photocatalysts PC-1 and PC-2 and Their Major Photophysical Properties
[1a + 2a] and [1a + 2a + PC-2] in a concentration in line with
standard reaction conditions, respectively (Figure 1a). Initially,
both 1a and 2a are nonabsorptive as the wavelength started
from 375 nm to a longer wavelength. By combination of the
equivalents 1a and 2a, a shift of the intense absorption band far
from the individual absorbances was apparently observed
which indicated the formation of an electron-donor−acceptor
(EDA) complex between 1a and 2a.12 Further coupled
interaction between PC-2 and the EDA complex was
evidenced by the intense and red-shifted absorption of the
mixture of PC-2 and the EDA complex. Upon addition of
TEMPO, the synthesis was effectively inhibited (Table 1, entry
25). Stern−Volmer experiments indicated that [1a + 2a] could
efficiently quench PC-2 (Figure 2, Figure S2). These results
imply that a single electron transfer may be involved during the
reaction process. When TEMP was added to the mixture [1a +
2a + PC-2], an amplified ESR signal of TEMPO was observed
by irradiation of the mixture with blue LED for 15 min (Figure
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Scheme 3. Preparation of Compounds 3a−3C
1b). This result indicated that the singlet oxygen (1O2) might
be the reactive species appearing during the process.
PC− to the ground state of PC. A subsequent hydrogen atom
transfer (HAT) from radical cation B to reduced oxygen
(O2−•) generates iminium intermediate C and HOO−.13
Intramolecular trapping of iminium with aziridine leads to
the formation of the active 1,7-diazatricycle D. Followed by
deprotonation and partial aromatization, 5,6-dihydroimidazo-
[2,1-a]isoquinoline 3a is finally produced.
During the preparation, we observed that the synthesized
2,3-diaryl-5,6-dihydroimidazo[2,1-a]isoquinolines (3a−3B)
are highly emissive in solids and the emissive color could be
tuned by the substitutents (Figure 3, Table S1, and Figure S3)
Combining the above observations, we postulated a cascade
mechanism as illustrated in Scheme 4. First, the EDA complex
between 1a and 2a is in situ generated and equilibrates with
adduct A through the nucleophilic addition of 1a to the CN
double bond of 2H-azirine 2a. Under light, the excited state of
PC abstracts an electron from adduct A via the single electron
transfer (SET) process and forms radical cation B and radical
anion PC−•. On the other hand, in the presence of light and
photocatalyst, singlet oxygen (1O2) is produced and reduces
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Figure 1. (a) Absorption spectra recorded in cumene solutions in 1 cm quartz cell. [1a] = 0.1 M, [2a] = 0.15 M. (b) Electron spin resonance
(ESR) spectra with blue LED irradiation for 15 min (sample), without blue LED irradiation (blank).
Figure 2. Stern−Volmer quenching experiment.
which indicated that these compounds might exhibit potential
application as emitters in OLED. In order to know the effect of
structure on the photophysical property, we selected five
respective compounds (3a, 3l, 3n, 3w, and 3B) and the data
are shown in Table 2. Absorption of these five compounds are
almost identical with the maximum absorption wavelength set
around 314 nm and molar absorptivity ranging from 2.04 ×
104 to 4.08 × 104. The values of Stokes shift rely on the 3-aryl
of 5,6-dihydroimidazo[2,1-a]isoquinoline. The one with an
electron-withdrawing group (3n, 4-CF3C6H4) presents a larger
Stokes shift than the one with the electron-donating group (3l,
4-CH3OC6H4), indicating a better intramolecular charge
transfer (ICT) in 3n from the imidazole ring to 4-
trifluoromethylphenyl. When 4-CF3C6H4 was substituted at
the 2-position of 5,6-dihydroimidazo[2,1-a]isoquinoline, 3w
presented a smaller Stokes shift, but the highest quantum yield
(14.1%) in CH2Cl2 solution among these five compounds.14
When both electron-withdrawing and electron-donating
groups exist on the molecule, 3B absorbs light at 316 nm
with the largest molar absorptivity. The direction of the
molecular dipole moment, from imidazole to 3-aryl, is
consistent with the solvent-dependence emissive spectra of
these five compounds (Figure S4). Moreover, the larger the
dipole moment changes are from the ground state to excited
state, the larger the solvatofluorochromic effect is.15 Among
these five compounds, the largest dipole moment change is
observed for 3n.
Three compounds (3d, 3i, and 3w) were selected to be the
emitters for fabrication of blue OLED because they provided
the good quantum yields in solids. As listed in Table S2, the
quantum yields for 3d, 3i, and 3w in solids are 61.0%, 41.4%,
and 35.0%, respectively. When the OLED devices with the
sandwich structure of ITO/PEDOT:PSS (40 nm)/compound
(65 nm)/TBPI (40 nm)/LiF (1.5 nm)/Al (100 nm) were
fabricated by respectively applying 3d, 3i, and 3w as emitters,
Devices A, B, and C were manufactured. Electrolumenicent
spectra and the current−density−voltage characteristics were
shown in Figures S5−S7, and data were summarized in Table
S3. Device 3w emitted light at 407 nm at a voltage of 8.1 V. At
a brightness of 100 cd m−2, the external quantum yield
(0.54%), the luminous efficiency (0.19 cd A−1), and the power
efficiency (0.06 lm W1−) were approached.
CONCLUSIONS
■
In conclusion, we have developed a visible-light-driven (3 + 2)
annulation of 2H-azirines with tetrahydroisoquinolines using
benzothiadiazole (BTD) derived 4,7-bis(4-methoxyphenyl)-
benzo[c][1,2,5]thiadiazole as an organic photoredox catalyst.
The reaction furnished a series of 5,6-dihydroimidazo[2,1-
a]isoquinolines through a novel and photoactive EDA
complex. This approach features a metal-free organic photo-
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Scheme 4. Proposed Reaction Mechanism
Figure 3. Photos of compounds 3a−3B under UV lamp.
redox catalyst, mild conditions, a broad substrate scope, good
functional group compatibility, and high yields. More
importantly, the synthesized 5,6-dihydroimidazo[2,1-a]-
isoquinolines products showed strong photoluminescence in
solutions and powders and could be applied as blue OLED
device emitters.
EXPERIMENTAL SECTION
■
General Information. Unless otherwise mentioned, solvents and
reagents were purchased from commercial sources and used as
received. 1H NMR spectra were obtained on a 400 MHz spectrometer
at room temperature. The chemical shifts were reported relative to
internal TMS (0 ppm) in CDCl3. The following abbreviations were
used to describe peak patterns when appropriate: s = singlet, d =
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Table 2. Photophysical Properties of Five Compounds
a
a
b
c
λmax (ε/104)
λmax
384
fwhm
Stokes
Φ (%)
λpowder
fwhm
QY (%)
CIE(x,y)powder
abs
em
em
3a
3l
313 (2.85)
314 (2.49)
312 (2.04)
315 (2.79)
316 (4.08)
51
54
71
63
71
73
104
79
90
13.7
13.8
10.5
14.1
10.9
438
372
399
387
397
72
48
50
46
61
16.4
19.1
20.2
61.0
15.4
(0.1389, 0.0939)
(0.1579, 0.0186)
(0.1598, 0.016)
(0.167, 0.0088)
(0.1532, 0.0289)
387
416
394
406
3n
3w
3B
72
a
b
Measured in CH2Cl2 solution, c = 2 × 10−5 M. Quantum yields (Φ) in CH2Cl2 solution were calculated based on Anthracene (Φ = 0.27 in
Ethanol). Powder quantum yields were obtained from an integrating sphere.
c
doublet, t = triplet, q = quartet, m = multiplet. J values were reported
in Hz. 13C NMR spectra were recorded on a 100 MHz spectrometer,
and the chemical shifts were referenced to the central line of the
triplet of CDCl3 (77.00 ppm). Infrared spectra were obtained on an
FTIR spectrometer. All high-resolution mass spectra (HRMS) data
were obtained by using EI ionization on a time-of-flight (TOF) mass
spectrometer or ESI ionization on an LCMS-IT-TOF mass
spectrometer. Melting points were measured with a micro melting
point apparatus. Flash column chromatography was performed
employing 300−400 mesh silica gel. Thin layer chromatography
(TLC) was performed on silica gel HSGF254. FL spectra were
recorded on a fluorospectro photometer with a xenon lamp excitation
MHz, CDCl3) δ 162.7, 141.0, 135.8, 132.3, 130.6, 130.4, 130.1, 129.6,
129.3, 128.3, 128.1, 127.8, 127.3, 127.0, 126.2, 125.9, 123.0, 122.9,
118.6, 31.5; HRMS (ESI) m/z: [M + H]+ calcd for C22H16N
294.1277; found 294.1278; IR: 3028, 1732, 1603, 1527, 1495, 1452,
1264, 1181, 1143, 1076, 905, 765, 725 cm−1.
General Procedure for the Synthesis of Products 3. To a 20
mL reaction tube equipped with a magnetic stir bar were added 1 (0.2
mmol), 2 (0.3 mmol, 1.5 equiv), photocatalyst (3 mol %), and
cumene (2 mL). The solution was stirred irradiated with blue LEDs
(450−455 nm) at room temperature for 5 h under air. Upon
completion of the reaction monitored by TLC, the crude product was
purified by flash chromatography on silica gel to provide pure product
3.
Preparation of 3a in 1 mmol Scale. To a 20 mL reaction tube
equipped with a magnetic stir bar were added 1a (1 mmol, 133.1 mg),
2a (1.5 mmol, 289.7 mg), PC (3 mol %, 10.4 mg), and cumene (5
mL). The solution was stirred irradiated with 10 W blue LED light
(450−455 nm) at room temperature for 5 h under air. Upon
completion of the reaction monitored by TLC, the crude product was
purified by flash chromatography on silica gel to provide product 3a
(152 mg, 47%).
Device Fabrication. Before device fabrication, the ITO glass
substrates were precleaned carefully. Then hole transporting material
PEDOT:PSS was made with 4000 r/s for 45 s and annealing for 25
min at 150 °C. The emission layer was prepared by spin coating the
chlorobenzene solution of compounds. Then it was made with 3000
r/s for 45 s and annealing for 25 min at 50 °C. After the organic film
deposition, 40 nm of TPBi, 1.5 nm of LiF, and 100 nm of aluminum
were thermally evaporated onto the organic surface.
2,3-Diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline (3a). Beige
solid; column chromatography (PE/EtOAc = 15:1); yield: 46 mg,
72%; mp 163.1−163.7 °C. 1H NMR (400 MHz, CDCl3) δ 8.21 (d, J
= 7.2 Hz, 1H), 7.57 (d, J = 8.4 Hz, 2H), 7.35−7.47 (m, 6H), 7.22−
7.31 (m, 4H), 7.15−7.19 (m, 1H), 3.98 (t, J = 6.8 Hz, 2H), 3.10 (t, J
= 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.6, 138.7,
134.7, 132.7, 130.5, 130.5, 128.9, 128.4, 128.4, 128.1, 127.6, 127.6,
127.2, 126.4, 124.0, 41.5, 28.6; HRMS (EI) m/z: [M]+ calcd for
C23H18N2 322.1470; found 322.1469; IR: 3058, 2925, 1602, 1580,
1533, 1503, 1475, 1457, 1444, 1347, 1121, 1029, 962, 774, 700 cm−1.
8-Methoxy-2,3-diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline
(3b). Light yellow solid; column chromatography (PE/EtOAc = 9:1);
yield: 43 mg, 62%; mp 168.2−168.9 °C. 1H NMR (400 MHz,
CDCl3) δ 8.15 (d, J = 8.0 Hz, 1H), 7.56 (d, J = 8 Hz, 2H), 7.35−7.45
(m, 5H), 7.15−7.26 (m, 3H), 6.90−6.93 (dd, J1 = 2.4 Hz, J2 = 8.4 Hz,
1H), 6.78 (s, 1H), 3.97 (t, J = 6.8 Hz, 2H), 3.85 (s, 3H), 3.08 (t, J =
6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 159.9, 143.9,
138.2, 134.6, 130.5, 128.9, 128.3, 128.1, 127.8, 127.2, 126.4, 125.7,
120.2, 113.3, 112.8, 55.3, 41.4, 28.9; HRMS (EI) m/z: [M]+ calcd for
C24H20N2O 352.1576; found 352.1577; IR: 2999, 2946, 1612, 1546,
1480, 1464, 1348, 1242, 1174, 1030, 838, 778 cm−1.
source. Cyclic voltammetry measurements were performed on an
electrochemical analyzer in solution at room temperature. EPR
spectra were recorded at room temperature on a Bruker BioSpin
GmbH spectrometer operating at 9.852 GHz with the cavity equipped
with a Bruker Aquax liquid sample cell. Typical spectrometer
parameters were as follows: scan range, 120 G; field set, 3455.6 G;
time constant, 81.92 ms; scan time, 40 s; modulation amplitude 1 G;
modulation frequency 100 kHz; receiver gain 3.17; microwave power,
20.46 mW. 2,2,6,6-Tetramethylpiperidine (TEMP) was used to
1
capture O2, by mixing PC (3 mol %), 1a (0.2 mmol), and 1b (0.3
mmol) in cumene under blue LED irradiation (λ = 450−455 nm) for
15 min (sample), without blue LED irradiation (blank).
The starting materials of 1 were supplied by commercial vendors
without further purification. 2H-Azirines 2 were known compounds
except for 3-(phenanthren-9-yl)-2-phenyl-2H-azirine (2k) and pre-
pared according to the published methods.5a,16 The ketones were
supplied by commercial vendors without further purification or
prepared according to the published methods.17 PC-1 and PC-2 were
prepared according to the published methods.10,11
Typical Procedure for the Synthesis of 3-(Phenanthren-9-
yl)-2-phenyl-2H-azirine (2k)..5a,16 The mixture of 1-(phenanthren-
9-yl)-2-phenylethan-1-one (894 mg, 3.02 mmol), NH2OH·HCl (315
mg, 4.53 mmol, 1.5 equiv), and sodium acetate was dissolved in
MeOH/H2O (20:1, v/v, 105 mL) at room temperature and
monitored by TLC. After the reaction completed, the mixture was
concentrated under vacuum to remove most of the solvent. The
solution was sequentially washed with saturated NaHCO3 and brine.
The aqueous layer was extracted with DCM, and the organic layer was
dried over Na2SO4. Removal of the solvent gave 1-(phenanthren-9-
yl)-2-phenylethan-1-one oxime. The crude product was directly used
for the next step without purification.
Triethylamine (455 mg, 4.5 mmol, 1.5 equiv) and methanesulfonyl
chloride (516 mg, 4.5 mmol, 1.5 equiv) were added sequentially to a
solution of 1-(phenanthren-9-yl)-2-phenylethan-1-one oxime (933
mg, 3.0 mmol) in dry THF (30 mL) at 0 °C. The solution became
cloudy after the addition of methanesulfonyl chloride. Then, the
resulting mixture was stirred for 30 min, and DBU (685 mg, 4.5
mmol, 1.5 equiv) was added slowly. After stirring for additional 30
min, the reaction mixture was passed through a pad of silica gel and
washed with petroleum ether (PE). The mixture was concentrated in
vacuo, and the resulting residue was purified by column
chromatography on silica gel (PE/EtOAc = 15:1, v/v) to give pure
2k as a white solid; yield: 299 mg, 34%; 1H NMR (400 MHz, CDCl3)
δ 9.19−9.21 (m, 1H), 8.75−8.78 (m, 1H), 8.71 (d, J = 8.4 Hz, 1H),
8.17 (s, 1H), 7.91 (d, J = 8.0 Hz, 1H), 7.78−7.83 (m, 3H), 7.63 (t, J =
7.6 Hz, 1H), 7.25−7.32 (m, 5H), 3.38 (s, 1H); 13C{1H} NMR (100
8-Chloro-2,3-diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline
(3c). Beige solid; column chromatography (PE/EtOAc = 15:1); yield:
1
39 mg, 55%; mp 217.2−218.1 °C. H NMR (400 MHz, CDCl3) δ
8.14 (d, J = 8.4 Hz, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.41−7.48 (m,
3H), 7.34−7.37 (m, 3H), 7.16−7.26 (m, 4H), 3.99 (t, J = 6.8 Hz,
2H), 3.09 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
142.8, 138.8, 134.4, 134.3, 133.9, 130.5, 130.2, 129.0, 128.6, 128.2,
127.9, 127.8, 127.2, 126.7, 126.6, 125.8, 125.4, 41.3, 28.4; HRMS
8107
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J. Org. Chem. 2021, 86, 8101−8111

The Journal of Organic Chemistry
pubs.acs.org/joc
Article
(ESI) m/z: [M + H]+ calcd for C23H18ClN2 357.1153; found
357.1153; IR: 3062, 2951, 1637, 1599, 1501, 1487, 1428, 1346, 1111,
1085, 962, 828, 779 cm−1.
3-(4-Chlorophenyl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3j). White solid; column chromatography (PE/EtOAc
1
= 15:1); yield: 35 mg, 50%; mp 175.0−175.8 °C. H NMR (400
MHz, CDCl3) δ 8.21 (d, J = 7.6 Hz, 1H), 7.55 (d, J = 7.2 Hz, 2H),
7.36−7.44 (m, 3H), 7.18−7.32 (m, 7H), 3.98 (t, J = 6.8 Hz, 2H),
3.12 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.9,
139.0, 134.5, 134.2, 132.6, 131.8, 129.3, 128.8, 128.6, 128.3, 127.7,
127.6, 127.3, 127.0, 126.9, 126.7, 124.2, 41.6, 28.6; HRMS (ESI) m/z:
[M + H]+ calcd for C23H18ClN2 357.1153; found 357.1154; IR: 3058,
2955, 2925, 1734, 1601, 1500, 1474, 1445, 1348, 1122, 1091, 1015,
962, 838, 753, 715 cm−1.
9-Methyl-2,3-diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline
(3d). Beige solid; column chromatography (PE/EtOAc = 15:1); yield:
1
32 mg, 48%; mp 187.7−188.2 °C. H NMR (400 MHz, CDCl3) δ
8.04 (s, 1H), 7.57 (d, J = 7.6 Hz, 2H), 7.42−7.48 (m, 3H), 7.36−7.38
(m, 2H), 7.09−7.26 (m, 5H), 3.97 (t, J = 6.8 Hz, 2H), 3.06 (t, J = 6.8
Hz, 2H), 2.41 (s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.8,
137.3, 134.6, 130.5, 130.5, 129.7, 129.2, 129.0, 128.9, 128.4, 128.3,
128.1, 127.5, 127.3, 126.9, 126.4, 124.5, 41.7, 28.2, 21.1; HRMS (ESI)
m/z: [M + H]+ calcd for C24H21N2 337.1699; found 337.1699; IR:
2955, 2924, 2854, 1602, 1496, 1453, 1378, 1339, 1158, 1107, 965,
775, 699 cm−1.
3-(4-Bromophenyl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3k). White solid; column chromatography (PE/EtOAc
1
= 15:1); yield: 55 mg, 69%; mp 168.7−169.6 °C. H NMR (400
MHz, CDCl3) δ 8.20 (d, J = 7.6 Hz, 1H), 7.54−7.59 (m, 4H), 7.37 (t,
J = 7.6 Hz, 1H), 7.18−7.32 (m, 7H), 3.98 (t, J = 6.8 Hz, 2H), 3.12 (t,
J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.0, 139.1,
134.3, 132.6, 132.2, 132.1, 129.3, 128.6, 128.3, 127.6, 127.3, 127.0,
127.0, 126.7, 124.1, 122.7, 41.6, 28.6; HRMS (ESI) m/z: [M + H]+
calcd for C23H18BrN2 401.0648; found 401.0651; IR: 3060, 2955,
2925, 1601, 1497, 1340, 1299, 1122, 1071, 1011, 962, 835, 774, 697
cm−1.
7-Bromo-2,3-diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline
(3e). Beige solid; column chromatography (PE/EtOAc = 15:1); yield:
1
49 mg, 61%; mp 194.7−195.3 °C. H NMR (400 MHz, CDCl3) δ
8.19 (d, J = 7.2 Hz, 1H), 7.52−7.57 (m, 3H), 7.44−7.49 (m, 3H),
7.36−7.38 (m, 2H), 7.16−7.26 (m, 4H), 4.00 (t, J = 6.8 Hz, 2H),
3.25 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.7,
139.2, 134.4, 132.3, 132.1, 130.4, 130.1, 129.1, 129.0, 128.8, 128.6,
128.2, 127.2, 126.6, 123.5, 123.2, 41.0, 28.4; HRMS (EI) m/z: [M]+
calcd for C23H17N2Br 400.0575; found 400.0573; IR: 3060, 2956,
2925, 2834, 1601, 1474, 1457, 1378, 1346, 1129, 964, 913, 776, 697
cm−1.
3-(4-Methoxyphenyl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3l). Beige solid; column chromatography (PE/EtOAc =
15:1); yield: 43 mg, 61%; mp 185.1−185.7 °C. 1H NMR (400 MHz,
CDCl3) δ 8.19 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 7.2 Hz, 2H), 7.37 (t, J
= 7.6 Hz, 1H), 7.23−7.30 (m, 6H), 7.15−7.18 (m, 1H), 6.98 (d, J =
8.8 Hz, 2H), 3.96 (t, J = 6.8 Hz, 2H), 3.87 (s, 3H), 3.10 (t, J = 6.8 Hz,
2H); 13C{1H} NMR (100 MHz, CDCl3) δ 159.7, 143.4, 138.4, 134.8,
132.6, 131.8, 128.3, 128.2, 128.1, 127.6, 127.5, 127.3, 127.1, 126.3,
124.0, 122.6, 114.4, 55.3, 41.3, 28.6; HRMS (EI) m/z: [M]+ calcd for
C24H20N2O 352.1576; found 352.1576; IR: 2956, 2925, 2853, 1610,
1558, 1510, 1481, 1378, 1287, 1249, 1178, 1031, 963, 838, 774 cm−1.
3-(4-(Tert-butyl)phenyl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3m). White solid; column chromatography (PE/EtOAc
8-Bromo-2,3-diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline
(3f). Beige solid; column chromatography (PE/EtOAc = 15:1); yield:
1
50 mg, 62%; mp 229.8−230.4 °C. H NMR (400 MHz, CDCl3) δ
8.07 (d, J = 8.0 Hz, 1H), 7.55 (d, J = 7.2 Hz, 2H), 7.49−7.52 (dd, J1 =
2.0 Hz, J2 = 8.4 Hz, 1H), 7.41−7.46 (m, 4H), 7.35−7.37 (m, 2H),
7.16−7.24 (m, 3H), 3.98 (t, J = 6.8 Hz, 2H), 3.09 (t, J = 6.8 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 142.8, 138.9, 134.5, 134.3,
130.8, 130.6, 130.5, 130.2, 129.0, 128.6, 128.6, 128.2, 127.2, 126.6,
126.1, 125.6, 122.1, 41.3, 28.4; HRMS (EI) m/z: [M]+ calcd for
C23H17N2Br 400.0575; found 400.0574; IR: 3050, 2958, 1654, 1599,
1500, 1478, 1442, 1427, 1343, 1075, 962, 826, 779 cm−1.
1
= 15:1); yield: 52 mg, 68%; mp 153.5−154.6 °C. H NMR (400
MHz, CDCl3) δ 8.21 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 7.2 Hz, 2H),
7.45 (d, J = 8.0 Hz, 2H), 7.36 (t, J = 7.2 Hz, 1H), 7.21−7.29 (m, 6H),
7.15−7.18 (m, 1H), 3.97 (t, J = 6.8 Hz, 2H), 3.08 (t, J = 6.8 Hz, 2H),
1.37 (s, 9H); 13C{1H} NMR (100 MHz, CDCl3) δ 151.4, 143.4,
138.4, 134.7, 132.7, 130.1, 128.4, 128.4, 128.1, 127.6, 127.5, 127.2,
127.2, 126.4, 125.8, 124.0, 41.5, 34.7, 31.3, 28.6; HRMS (EI) m/z:
[M]+ calcd for C27H26N2 378.2096; found 378.2095; IR: 3049, 2960,
2895, 1600, 1508, 1481, 1458, 1348, 1267, 1116, 1028, 962, 853, 774
cm−1.
9-Bromo-2,3-diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline
(3g). White solid; column chromatography (PE/EtOAc = 15:1);
yield: 39 mg, 49%; mp 219.6−220.4 °C. 1H NMR (400 MHz,
CDCl3) δ 8.36 (s, 1H), 7.55 (d, J = 7.2 Hz, 1H), 7.35−7.48 (m, 6H),
7.17−7.26 (m, 4H), 7.11(d, J = 8.4 Hz, 1H), 3.98 (t, J = 6.8 Hz, 2H),
3.06 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 142.3,
139.0, 134.3, 131.3, 131.1, 130.5, 130.1, 129.2, 129.0, 128.8, 128.6,
128.2, 127.2, 126.7, 126.6, 121.5, 41.4, 28.1; HRMS (EI) m/z: [M]+
calcd for C23H17N2Br 400.0575; found 400.0575; IR: 3049, 2951,
1654, 1599, 1501, 1481, 1452, 1342, 1248, 1070, 961, 776, 699 cm−1.
10-Bromo-2,3-diphenyl-5,6-dihydroimidazo[2,1-a]isoquinoline
(3h). Beige solid; column chromatography (PE/EtOAc = 15:1); yield:
2-Phenyl-3-(4-(trifluoromethyl)phenyl)-5,6-dihydroimidazo[2,1-
a]isoquinoline (3n). White solid; column chromatography (PE/
1
EtOAc = 15:1); yield: 30 mg, 39%; mp 166.2−167−3 °C. H NMR
1
(400 MHz, CDCl3) δ 8.21 (d, J = 7.6 Hz, 1H), 7.70 (d, J = 8.4 Hz,
2H), 7.47−7.54 (m, 4H), 7.38 (t, J = 7.6 Hz, 1H), 7.19−7.33 (m,
5H), 4.01 (t, J = 6.8 Hz, 2H), 3.13 (t, J = 6.8 Hz, 2H); 13C{1H} NMR
(100 MHz, CDCl3) δ 144.3, 139.7, 134.2, 134.1, 132.6, 130.8, 130.2
(q, J = 32.7 Hz), 128.8, 128.3, 127.7 (q, J = 4.0 Hz), 127.5, 126.9,
126.8, 126.7, 125.9 (q, J = 3.7 Hz), 124.2, 124.0 (q, J = 270.6 Hz),
41.7, 28.6; 19F NMR (CDCl3, 376 MHz) δ − 62.60; HRMS (EI) m/
z: [M]+ calcd for C24H17N2F3 390.1344; found 390.1346; IR: 3047,
2920, 1620, 1595, 1481, 1325, 1169, 1123, 1067, 962, 852, 777, 698
cm−1.
47 mg, 59%; mp 178.1−178.6 °C. H NMR (400 MHz, CDCl3) δ
7.63−7.67 (m, 3H), 7.45−7.51 (m, 3H), 7.37−7.40 (m, 2H), 7.14−
7.24 (m, 4H), 7.08 (t, J = 7.6 Hz, 1H), 3.91 (t, J = 6.8 Hz, 2H), 3.08
(t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 141.2,
138.0, 136.3, 134.6, 134.2, 130.6, 130.5, 129.0, 128.7, 128.5, 128.2,
128.1, 126.9, 126.7, 126.4, 124.3, 119.5, 40.9, 30.1; HRMS (EI) m/z:
[M]+ calcd for C23H17N2Br 400.0575; found 400.0573. IR: 3059,
2955, 2925, 2853, 1602, 1559, 1473, 1456, 1343, 1189, 1027, 966,
774, 696 cm−1.
3-(4-Fluorophenyl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3i). Beige solid; column chromatography (PE/EtOAc =
15:1); yield: 44 mg, 64%; mp 193.8−194.6 °C. 1H NMR (400 MHz,
CDCl3) δ 8.21 (d, J = 7.6 Hz, 1H), 7.54−7.56 (m, 2H), 7.24−7.40
(m, 7H), 7.13−7.21 (m, 3H); 3.96 (t, J = 6.8 Hz, 2H), 3.12 (t, J = 6.8
Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 162.8 (d, J = 247.2
Hz), 143.7, 138.8, 134.4, 132.6, 132.4(d, J = 8.1 Hz), 128.5, 128.2,
127.6, 127.2, 127.2, 127.0, 126.6, 126.4 (d, J = 3.0 Hz), 124.1, 116.1
(d, J = 21.5 Hz), 41.5, 28.6; 19F NMR (CDCl3, 376 MHz) δ −
112.58; HRMS (EI) m/z: [M]+ calcd for C23H17N2F 340.1376; found
340.1377; IR: 3062, 2956, 2925, 1600, 1558, 1509, 1480, 1378, 1225,
1157, 963, 843, 774,718 cm−1.
3-(3-Chlorophenyl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3o). White solid; column chromatography (PE/EtOAc
1
= 15:1); yield: 37 mg, 52%; mp 125.6−126.4 °C. H NMR (400
MHz, CDCl3) δ 8.20 (d, J = 7.6 Hz, 1H), 7.55 (d, J = 7.2 Hz, 2H),
7.36−7.41 (m, 4H), 7.20−7.33 (m, 6H), 3.99 (t, J = 6.8 Hz, 2H),
3.13 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.0,
139.2, 134.7, 134.2, 132.6, 132.3, 130.3, 130.2, 129.0, 128.9, 128.8,
128.6, 128.6, 128.3, 127.6, 127.3, 127.0, 126.8, 124.2, 41.6, 28.6;
HRMS (ESI) m/z: [M + H]+ calcd for C23H18ClN2 357.1153; found
357.1157; IR: 3058, 2955, 2925, 1599, 1566, 1485, 1465, 1341, 1078,
1029, 970, 771, 737, 697 cm−1.
8108
https://doi.org/10.1021/acs.joc.1c00590
J. Org. Chem. 2021, 86, 8101−8111

The Journal of Organic Chemistry
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Article
3-(Naphthalen-2-yl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
1592, 1498, 1474, 1351, 1339, 1122, 1298, 1010, 963, 841, 766, 742
cm−1.
isoquinoline (3p). Beige solid; column chromatography (PE/EtOAc
1
= 15:1); yield: 41 mg, 55%; mp 190.2−190.8 °C. H NMR (400
3-Phenyl-2-(p-tolyl)-5,6-dihydroimidazo[2,1-a]isoquinoline (3v).
Beige solid; column chromatography (PE/EtOAc = 15:1); yield: 35
MHz, CDCl3) δ 8.25 (d, J = 6.0 Hz, 1H), 7.84−7.92 (m, 4H), 7.53−
7.61 (m, 4H), 7.43−7.45 (dd, J1 = 0.6 Hz, J2 = 6.8 Hz, 1H), 7.39 (t, J
= 6.0 Hz, 1H), 7.31 (t, J = 6.0 Hz, 1H), 7.20−7.25 (m, 3H), 7.15−
7.18 (m, 1H), 4.04 (t, J = 5.6 Hz, 2H), 3.13 (t, J = 5.6 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 143.77, 138.9, 134.4, 134.4,
1
mg, 52%; mp 189.6−190.2 °C. H NMR (400 MHz, CDCl3) δ 8.20
(d, J = 7.6 Hz, 1H), 7.35−7.47 (m, 8H), 7.22−7.30 (m, 2H), 7.05 (d,
J = 8 Hz, 2H), 3.98 (t, J = 6.8 Hz, 2H), 3.10 (t, J = 6.8 Hz, 2H), 2.30
(s, 3H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.5, 138.7, 136.1,
132.7, 131.7, 130.5, 128.9, 128.3, 128.3, 128.0, 127.6, 127.5, 127.2,
127.1, 124.0, 41.5, 28.6, 21.2; HRMS (EI) m/z: [M]+ calcd for
C24H20N2 336.1626; found 336.1627; IR: 2955, 2924, 2854, 1606,
1511, 1487, 1457, 1378, 1341, 1182, 1120,963, 824, 772 cm−1.
3-Phenyl-2-(4-(trifluoromethyl)phenyl)-5,6-dihydroimidazo[2,1-
a]isoquinoline (3w). White solid; column chromatography (PE/
133.4, 132.9, 132.7, 129.6, 128.6, 128.7, 128.5, 128.3, 128.2, 128.1,
128.1, 127.8, 127.6, 127.3, 127.1, 126.7, 126.6, 41.6, 28.6; HRMS
(ESI) m/z: [M + H]+ calcd for C27H21N2 373.1699; found 373.1701;
IR: 3054, 2956, 2925, 1602, 1486, 1463, 1349, 1269, 1157, 1029, 974,
824, 775, 739 cm−1.
3-(Naphthalen-1-yl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
1
isoquinoline (3q). White solid; column chromatography (PE/EtOAc
EtOAc = 15:1); yield: 37 mg, 47%; mp 190−1−191.0 °C. H NMR
1
= 15:1); yield: 35 mg, 47%; mp 223.4−224.3 °C. H NMR (400
(400 MHz, CDCl3) δ 8.18 (d, J = 7.6 Hz, 1H), 8.67 (d, J = 8 Hz, 2H),
7.46−7.49 (m, 5H), 7.31−7.38 (m, 4H), 7.24−7.25 (m, 1H), 3.98 (t,
J = 6.8 Hz, 2H), 3.11 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3): δ (ppm) 144.0, 138.2, 137.2, 132.7, 130.4, 130.0, 129.5,
129.2, 128.9, 128.7, 128.1 (q, J = 32.1 Hz), 127.7 (q, J = 3.4 Hz),
127.0, 126.9, 125.1 (q, J = 3.8 Hz), 124.1, 124.4 (q, J = 270.0 Hz),
41.5, 28.5; 19F NMR (CDCl3, 376 MHz) δ −62.32; HRMS (EI) m/z:
[M]+ calcd for C24H17N2F3 390.1344; found 390.1345; IR: 3053,
2924, 1617, 1486, 1458, 1417, 1324, 1164, 1120, 1066, 963, 849, 771,
718 cm−1.
MHz, CDCl3) δ 8.29 (d, J = 7.6 Hz, 1H), 7.95−8.01 (m, 2H), 7.65
(d, J = 8.4 Hz, 1H), 7.50−7.57 (m, 5H), 7.39−7.45 (m, 2H), 7.28−
7.32 (m, 1H), 7.22 (d, J = 7.6 Hz, 1H), 7.06−7.15 (m, 3H), 3.70 (t, J
= 6.8 Hz, 2H), 3.04 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 143.9, 139.4, 134.4, 133.8, 132.9, 132.7, 129.7, 129.6, 128.6,
128.5, 128.1, 127.7, 127.6, 127.1, 127.1, 126.4, 126.4, 126.3, 126.3,
125.7, 125.3, 124.0, 41.4, 28.5; HRMS (ESI) m/z: [M + H]+ calcd for
C27H21N2 373.1699; found 373.1701; IR: 3055, 2923, 2856, 1603,
1507, 1485, 1459, 1324, 1120, 944, 809, 775, 738 cm−1.
3-(Phenanthren-9-yl)-2-phenyl-5,6-dihydroimidazo[2,1-a]-
2-(3-Chlorophenyl)-3-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3r). White solid; column chromatography (PE/EtOAc
isoquinoline (3x). Beige solid; column chromatography (PE/EtOAc
1
= 15:1); yield: 48 mg, 57%; mp 238.5−239.4 °C. H NMR (400
1
= 15:1); yield: 41 mg, 58%; mp 161.0−161.7 °C. H NMR (400
MHz, CDCl3) δ 8.77−8.82 (q, J1 = 8.4 Hz, J2 = 3.6 Hz, 2H), 8.29 (d,
J = 7.6 Hz, 1H), 7.88 (d, J = 8.0 Hz, 1H), 7.85 (s, 1H), 7.60−7.77 (m,
6H), 7.52 (t, J = 7.6 Hz, 1H), 7.41 (t, J = 7.6 Hz, 1H), 7.30 (t, J = 7.6
Hz, 1H), 7.21 (t, J = 7.2 Hz, 1H), 7.04−7.13 (m, 3H), 3.66−3.78 (m,
2H), 3.02 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
144.0, 139.6, 134.4, 132.6, 131.4, 131.3, 130.9, 130.8, 130.7, 129.1,
128.5, 128.2, 127.7, 127.6, 127.4, 127.2, 127.0, 126.3, 126.1, 126.1,
124.0, 123.2, 122.7, 41.3, 28.5; HRMS (ESI) m/z: [M + H]+ calcd for
C31H23N2 423.1856; found 423.1857; IR: 3057, 2929, 1602, 1533,
1483, 1449, 1416, 1349, 1299, 1081, 903, 774, 744, 696 cm−1.
2-(4-Fluorophenyl)-3-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3s). Beige solid; column chromatography (PE/EtOAc =
15:1); yield: 43 mg, 63%; mp 173.1−173.9 °C. 1H NMR (400 MHz,
CDCl3) δ 8.19 (d, J = 7.6 Hz, 1H), 7.51−7.54 (m, 2H), 7.43−7.49
(m, 3H), 7.23−7.40(m, 5H), 6.93 (t, J = 8.8 Hz, 2H), 3.99 (t, J = 6.8
Hz, 2H), 3.11 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)
δ 161.7 (d, J = 243.7 Hz), 143.6, 137.8, 132.7, 130.7, 130.7, 130.5,
130.2, 129.0, 128.8 (d, J = 7.9 Hz), 128.5, 128.1, 127.6 (d, J = 2.7
Hz), 127.0, 124.0, 115.0 (d, J = 21.2 Hz), 41.5, 28.6; 19F NMR
(CDCl3, 376 MHz) δ − 116.21; HRMS (ESI) m/z: [M + H]+ calcd
for C23H18FN2 341.1449; found 341.1448; IR: 2956, 2925, 2853,
1603, 1539, 1509, 1476, 1378, 1345, 1221, 1156, 963, 840, 793 cm−1.
2-(4-Chlorophenyl)-3-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3t). Beige solid; column chromatography (PE/EtOAc =
15:1); yield: 40 mg, 56%; mp 167.6−168.7 °C. 1H NMR (400 MHz,
CDCl3) δ 8.20 (d, J = 7.6 Hz, 1H), 7.66 (s, 1H), 7.45−7.50 (m, 3H),
7.24−7.41 (m, 6H), 7.10−7.14 (m, 2H), 3.99 (t, J = 6.4 Hz, 2H),
3.12 (t, J = 6.4 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.7,
137.0, 136.2, 134.1, 132.7, 130.4, 129.8, 129.3, 129.1, 129.0, 128.8,
128.8, 127.7, 127.1, 126.8, 126.5, 125.1, 124.2, 41.5, 28.5; HRMS
(ESI) m/z: [M + H]+ calcd for C23H18ClN2 357.1153; found
357.1152; IR: 3057, 2954, 2925, 1597, 1568, 1496, 1465, 1341, 1299,
1128, 1075, 970, 816, 771 cm−1.
MHz, CDCl3) δ 8.18 (d, J = 7.6 Hz, 1H), 7.66 (s, 1H), 7.44−7.48 (m,
3H), 7.22−7.39 (m, 6H), 7.09−7.13 (m, 2H), 3.97 (t, J = 6.8 Hz,
2H), 3.10 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ
143.77, 137.21, 136.52, 134.08, 133.35, 132.67, 130.41, 129.94,
129.28, 129.04, 128.95, 128.72, 128.58, 127.65, 127.61, 126.98,
126.37, 125.05, 123.99, 41.49, 28.53; HRMS (ESI) m/z: [M + H]+
calcd for C23H18ClN2 357.1153; found 357.1154; IR: 3059, 2955,
2925, 1597, 1568, 1496, 1465, 1341, 1128, 1075, 970, 816, 771, 701
cm−1.
2-(2-Chlorophenyl)-3-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3y). Beige solid; column chromatography (PE/EtOAc
1
= 15:1); yield: 32 mg, 45%; mp 164.8−165.3 °C. H NMR (400
MHz, CDCl3) δ 8.17(d, J = 6.0 Hz, 1H), 7.48−7.50(m, 1H), 7.30−
7.37(m, 6H), 7.20−7.28(m, 5H), 4.18(t, J = 5.6 Hz, 2H), 3.17(t, J =
5.6 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 143.6, 137.2,
134.0, 133.9, 132.7, 132.7, 130.0, 129.9, 129.7, 129.4, 128.9, 128.8,
128.6, 128.5, 127.8, 127.6, 127.1, 126.6, 124.2, 41.9, 28.7; HRMS
(ESI) m/z: [M + H]+ calcd for C23H18ClN2 357.1153; found
357.1156; IR: 3056, 2955, 2925, 1598, 1497, 1469, 1341, 1265, 1125,
1055, 965, 814, 772, 741 cm−1.
2,3-Bis(4-chlorophenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline
(3z). White solid; column chromatography (PE/EtOAc = 15:1);
yield: 34 mg, 43%; mp 202.1−202.8 °C. 1H NMR (400 MHz,
CDCl3) δ 8.16 (d, J = 7.6 Hz, 1H), 7.43−7.49 (m, 4H), 7.35−7.39
(m, 1H), 7.21−7.33 (m, 6H), 3.96 (t, J = 6.8 Hz, 2H), 3.12 (t, J = 6.8
Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3) δ 144.1, 138.0, 134.7,
132.9, 132.6, 132.4, 131.7, 129.4, 128.7, 128.6, 128.4, 128.4, 127.7,
127.2, 126.9, 124.0, 41.5, 28.5; HRMS (ESI) m/z: [M + H]+ calcd for
C23H17Cl2N2 391.0763; found 391.0763; IR: 2938, 1638, 1618, 1497,
1473, 1384, 1341, 1120, 1091, 1015, 962, 839, 769 cm−1.
2,3-Bis(4-bromophenyl)-5,6-dihydroimidazo[2,1-a]isoquinoline
(3A). White solid; column chromatography (PE/EtOAc = 15:1);
yield: 50 mg, 52%; mp 220.5−221.0 °C. 1H NMR (400 MHz,
CDCl3) δ 8.18 (d, J = 7.2 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.36−
7.43 (m, 5H), 7.29−7.33 (m, 1H), 7.21−7.26 (m, 3H), 3.96 (t, J =
6.8 Hz, 2H), 3.12 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz,
CDCl3) δ 144.1, 137.8, 133.1, 132.6, 132.4, 132.0, 131.4, 128.9, 128.8,
128.8, 127.7, 127.7, 127.3, 126.7, 124.2, 123.0, 120.7, 41.6, 28.5;
HRMS (EI) m/z: [M]+ calcd for C23H16N2Br2 477.9680; found
477.9681; IR: 3049, 2942, 1654, 11495, 1468, 1415, 1344, 1119,
1071, 1012, 961, 836, 770 cm−1.
2-(4-Bromophenyl)-3-phenyl-5,6-dihydroimidazo[2,1-a]-
isoquinoline (3u). White solid; column chromatography (PE/EtOAc
1
= 15:1); yield: 46 mg, 58%; mp 231.2−231.9 °C. H NMR (400
MHz, CDCl3) δ 8.18 (d, J = 7.6 Hz, 1H), 7.43−7.47 (m, 5H), 7.23−
7.39 (m, 7H), 3.97 (t, J = 6.8 Hz, 2H), 3.11 (t, J = 6.8 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3) δ 143.8, 137.5, 133.6, 132.7,
131.2, 130.4, 130.1, 129.1, 128.7, 128.6, 128.6, 127.7, 127.6, 127.0,
124.0, 120.3, 41.5, 28.6; HRMS (ESI) m/z: [M + H]+ calcd for
C23H18BrN2 401.0648; found 401.0648; IR: 3030, 2956, 2922, 1608,
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3-(4-Methoxyphenyl)-2-(4-(trifluoromethyl)phenyl)-5,6-dihydro-
imidazo[2,1-a]isoquinoline (3B). Beige solid; column chromatog-
raphy (PE/EtOAc = 15:1); yield: 60 mg, 71%; mp 196.5−197.3 °C.
1H NMR (400 MHz, CDCl3) δ 8.19 (d, J = 7.6 Hz, 1H), 7.70 (d, J =
ACKNOWLEDGMENTS
■
This work was financially supported by the National Natural
Science Foundation of China (Nos. 21871229 and 21632003).
8.0 Hz, 2H), 7.48 (d, J = 8.4 Hz, 2H), 7.39 (t, J = 6.8 Hz, 1H), 7.24−
7.33 (m, 4H), 7.02(d, J = 8.4 Hz, 2H), 3.96 (t, J = 6.8 Hz, 2H), 3.89
(s, 3H), 3.12 (t, J = 6.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3)
δ 160.0, 143.7, 138.3, 136.9, 132.7, 131.7, 129.4, 128.7, 127.9 (q, J =
31.8 Hz), 127.7 (q, J = 3.4 Hz), 126.9, 126.8, 125.0 (q, J = 3.8 Hz),
124.0, 121.9, 124.4 (q, J = 270.0 Hz), 114.6, 55.3, 41.4, 28.5; 19F
NMR (CDCl3, 376 MHz) δ − 62.29; HRMS (EI) m/z: [M]+ calcd
for C25H19N2OF3 420.1449; found 420.1448; IR: 2956, 2924, 1616,
1521, 1492, 1460, 1324, 1251, 1163, 1121, 1066, 839, 771,717 cm−1.
3-Benzyl-2-phenyl-5,6-dihydroimidazo[2,1-a]isoquinoline (3C).
Yellow oil; column chromatography (PE/EtOAc = 15:1); yield: 19
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ASSOCIATED CONTENT
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sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.joc.1c00590.
Experimental procedures and spectral for all new
compounds (1H NMR, 13C NMR, 19F NMR, and
HRMS) (PDF)
Accession Codes
CCDC 2016722 and 2050830 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
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Corresponding Authors
Ping Lu − Department of Chemistry, Zhejiang University,
Hangzhou, P. R. China; orcid.org/0000-0002-3221-
3647; Email: pinglu@zju.edu.cn
Yanguang Wang − Department of Chemistry, Zhejiang
University, Hangzhou, P. R. China; orcid.org/0000-
0002-5096-7450; Email: orgwyg@zju.edu.cn
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fluorescent chemosensor and a white OLED component. J. Mater.
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Authors
Zaibin Wang − Department of Chemistry, Zhejiang University,
Hangzhou, P. R. China
Hanjie Li − Department of Chemistry, Zhejiang University,
Hangzhou, P. R. China
Zhichao Wang − Department of Chemistry, Zhejiang
University, Hangzhou, P. R. China
Muhammad Suleman − Department of Chemistry, Zhejiang
University, Hangzhou, P. R. China
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