Ruthenium-Catalyzed Annulation of N -Cbz Hydrazones via C-H/N-N Bond Activation for the Rapid Synthesis of Isoquinolines

Article abstract of DOI:10.1055/s-0037-1611795

In this work, N -Cbz hydrazone has been employed as a rarely explored directing group for the synthesis of isoquinolines by annulation with internal alkynes via C-H/N-N activation using Ru catalyst. Additive as well as external oxidant-free rapid protocol

Full text of DOI:10.1055/s-0037-1611795

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–I
special topic
A
en
D. S. Deshmukh, B. M. Bhanage
Special Topic
Synthesis
Ruthenium-Catalyzed Annulation of N-Cbz Hydrazones via
C–H/N–N Bond Activation for the Rapid Synthesis of Isoquinolines
Dewal S. Deshmukh
Bhalchandra M. Bhanage*
Department of Chemistry, Institute of Chemical Technology,
N. Parekh Marg, Matunga, Mumbai 400 019, India
bm.bhanage@gmail.com
bm.bhanage@ictmumbai.edu.in
Published as part of the Special Topic Ruthenium in Organic
Synthesis
Received: 26.02.2019
Accepted: 19.03.2019
Published online: 10.04.2019
DOI: 10.1055/s-0037-1611795; Art ID: ss-2019-c0127-st
oxidant too.4 Further, this strategy has additional advantag-
es like enhanced reactivity as well as selectivity with im-
proved yields and the simultaneous breaking of the direct-
ing group.
Abstract In this work, N-Cbz hydrazone has been employed as a rarely
explored directing group for the synthesis of isoquinolines by annula-
tion with internal alkynes via C–H/N–N activation using Ru catalyst. Ad-
ditive as well as external oxidant-free rapid protocol has been estab-
lished for the synthesis of isoquinolines using microwave strategy. Use
of non-volatile and biodegradable PEG as a green solvent with lower
catalyst loading makes the proposed protocol environmentally benign.
Further, higher functional group tolerance and wide substrate scope
has been observed under the stated methodology with higher yields.
On the other hand, most of the previous reports for C–H/
N–N activation use volatile organic solvents, convicted for
serious ecological hazards. Thus, in order to reduce the eco-
logical pressures by conventional organic solvents, replac-
ing it with polyethylene glycols (PEGs) is one of the best
solutions.5 Owing to the properties like negligible vapor
pressure, inexpensiveness, thermal stability, degradable, re-
usable, relatively inexpensive, and less harmful, PEGs serve
as an appropriate media for safe and ecologically gentle
chemical conversions. Taking into consideration the impor-
tance of PEG as a solvent, our research group has communi-
cated some scientific reports.6
The beginning of twenty-first century has witnessed a
revolutionary advancement in the area of microwave-as-
sisted organic synthesis.7 Due to the capability of expedi-
tious heating and thermal quenching, the methodology has
several advantages of improvement into rates, efficiency,
and yields of chemical transformations. Uniform and selec-
tive heating throughout the material with minimal heat
loss, low operating cost, and minimal side reactions makes
it a promising and environmentally benign technique.
Moreover, many novel organic transformations could be
achieved using microwave strategy, which could not suc-
ceed by conventional heating.
Key words C–H/N–N activation, ruthenium, microwave-assisted, iso-
quinolines, annulation, hydrazones
Currently, the strategy of transition-metal-catalyzed di-
rect C–H activation has become a powerful technique for
chemical transformations in the area of synthetic method-
ology.1 Because of step and atom efficiency, nobility and in-
fluence on ecology, it represents a potent approach above
conventional methods of organic synthesis, opening new
opportunities in retrosynthetic directions. In the past de-
cade, among transition metals, ruthenium has been
emerged as a capable and cost-effective catalyst for the
chemical transformations using C–H bond functionaliza-
tion approach.2
Directing groups, by acting as Lewis base to co-ordinate
the transition metals, play vital role in selective C–H bond
activation.3 Considering the reaction pathway, in order to
recycle metal catalysts in its active form, equivalent or ex-
cessive quantity of external oxidants are often required.
These external oxidants are responsible for generation of
equivalent amount of waste, causing environmental nui-
sance. Thus, in order to avoid the use of external oxidants,
researchers have pioneered a concept called redox-neutral
strategy, in which directing group itself acts as an internal
Isoquinolines have emerged as an important class of
heterocyclic scaffolds that is present in various natural as
well as pharmaceutical products with broad range of bio-
logical activities8 (Figure 1). Moreover, isoquinoline moi-
eties are employed for the development of ligands, photo-
sensitizers, alkaloids, OLEDs, and inhibitors.9 For instance,
tetrahydropalmatine, sanguinarine, and papaverine are the
naturally occurring alkaloids containing isoquinoline scaf-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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D. S. Deshmukh, B. M. Bhanage
Special Topic
Synthesis
O
O
O
O
O
N
N
N
O
O
O
O
O
O
O
Sanguinarine
Papaverine
Tetrahydropalmitine
Alkaloids
O
N
N
N
OH
OH
Cl
Ir
N
3
Ligand for asymmetric catalysis
Photosensitizer
OLED-Material
Figure 1 Examples of isoquinoline moieties with pharmaceutical and other importance
folds, which are widely used as analgesic, antibacterial, and
vasodilator, respectively.10
very short time without use of any additives and external
oxidants.
Due to the prosperity of isoquinoline moieties, chemists
have developed progressively effective approaches toward
their synthesis. In this regard, many researchers reported
synthesis of isoquinolines using multistep approaches.11
However, these are suffered with lacunas such as lesser
yields, poor regioselectivity, and lengthier reaction times.
Overcoming these issues, later, annulation reactions with
alkynes by C–H functionalization using different directing
groups and catalysts provided an efficient alternate route
for their synthesis. Transition metals like Rh12 and Co13 as-
sisted with various directing groups are very well known
for the synthesis of isoquinolines by these kinds of transfor-
mations, while Ru is rarely utilized for the isoquinoline syn-
thesis by C–H activation reactions.14 Likewise, N-Cbz hydra-
zone is rarely examined as a directing group for C–H/N–N
activation reactions. On the other hand, almost all previous
approaches for the synthesis of isoquinolines are reported
in volatile organic solvents using conventional heating
method for longer reaction time involving use of additives
and oxidants, having its own disadvantages. However, re-
cently, the Bolm and Huang research groups reported addi-
tive-free C–H functionalization reactions using Ru(II) cata-
lysts.15
We initiated our studies by investigating the annulation
reactions of acetophenone N-Cbz hydrazone with diphenyl-
acetylene in the presence of [Ru(p-cymene)Cl2]2 and AgSbF6
in PEG-400 at 100 °C for 10 minutes as model reaction.
Monitoring the reaction at different temperatures, we
found that there was no satisfactory yield at 100 °C (Table 1,
entry 1). While, increasing the temperature to 110 °C, iso-
quinoline 3aa was produced in 87% yield (entry 2). Only a
slight improvement in the product yield was observed on
further increase in temperature (entry 3). Next, screening
the reaction at different periods of time, increase in the re-
action time from 10 minutes to 12 minutes did not induce
Previous reports:
R1
R1
R2
R3
X
N
M
N
Ar
Ar
R3
H
R2
X = OH, OR, NH2, NR2
Use of additives and oxidants
Lenghthier reaction time
Considering all these facts, there continues to be the
need to develop a protocol for the synthesis of isoquinolines
which is rapid and free from additives as well as external
oxidants using non-volatile greener solvent. In this per-
spective, continuing our endeavors to develop N-hetero-
cycles,14b,16 herein, we disclose the ruthenium-catalyzed
microwave-assisted synthesis of isoquinolines by C–H/N–N
activation using rarely explored acetophenone N-Cbz hy-
drazone as a directing group in PEG-400 as a green solvent
(Scheme 1). Furthermore, the proposed strategy works in
This work:
R1
R1
H
R2
NHCbz
N
Ru
N
Ar
Ar
R3
R3
R2
Microwave-assisted rapid synthesis
Rarely explored directing group
No external oxidant
PEG as a biodegradable green solvent
Wide substrate scope
Easy work up process
No additives
Easily prepared substrates
Scheme 1 Transition-metal-catalyzed synthesis of isoquinolines
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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D. S. Deshmukh, B. M. Bhanage
Special Topic
Synthesis
Table 1 Optimization of the Reaction Conditionsa
PEG-400 proved to be a compatible solvent for the stated
methodology. The reaction was also attempted without mi-
crowave irradiation (conventional oil-bath heating) under
standard condition, however, only 34% product yield was
obtained (entry 13).
Having established optimization conditions, the scope
of the annulation reaction of substituted acetophenone N-
Cbz hydrazones 1a–q with diphenylacetylenes 2a–d was
explored as shown in Table 2. The annulation proceeded
smoothly for a wide range of substrates in good to excellent
yields. Acetophenone N-Cbz hydrazone without any substi-
tution led to the formation of desired isoquinoline product
3aa in an isolated yield of 87% (Table 2, entry 1). N-Cbz Hy-
drazones with electron-donating groups (i.e., methyl and
methoxy) at para-position led to a considerable increase in
yields of products 3ba and 3ca to 90% and 92% yield, respec-
tively (entries 2 and 3).
Notably, the presence of electron-withdrawing groups
(e.g., bromo, chloro, fluoro, and nitro) at para-position of
hydrazones provided the corresponding products 3da, 3ea,
3fa, and 3ga in 82%, 84%, 79% and 80% yield, respectively
(Table 2, entries 4–7). Next, the reactions of meta-substitut-
ed acetophenone N-Cbz hydrazones were investigated. It
was noted that hydrazones containing Me, Cl, and NO2 at
meta-position preferentially annulated with alkynes at the
less hindered position to form the corresponding products
3ha, 3ja, and 3ka particularly in 85%, 78% and 74% yield, re-
spectively, while N-Cbz hydrazone with OMe at the meta-
position generated two regioselective products 3ia and 3ia′
in 48% and 34% yield, respectively (entries 8–11). Further-
more, the disubstituted acetophenone N-Cbz hydrazone,
gave the respective product 3la with exclusive regioselec-
tivity in 82% isolated yield (entry 12). In the next set of ex-
periments, N-Cbz hydrazones derived from various ketones
such as propiophenone, cyclopropyl phenyl ketone, and
benzophenone were explored as substrates, which led to
the formation of corresponding isoquinoline products 3ma,
3na, and 3oa, respectively in very good yields (entries 13–
15). Fused N-Cbz hydrazone derived from 1-acetylnaphtha-
lene could also be converted into the desired product 3pa in
81% yield (entry 16). In addition, N-Cbz hydrazone of het-
erocyclic ketone also could be smoothly converted into the
corresponding product 3qa in 79% yield (entry 17).
Ph
[Ru(p-cymene)Cl2]2
NHCbz
additive
N
N
solvent
Ph
temp (°C), time (min)
Ph
Ph
1a
2a
3aa
Entry Additive
Solvent
Temp (°C) Time (min) Yield (%)b
1
2
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
AgSbF6
–
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-400
PEG-200
PEG-600
100
110
120
110
110
110
110
110
110
110
110
10
10
10
12
8
62
87
90
88
76
78
86
55
87
58
71
28
34
3
4
5
6c
10
10
10
10
10
10
10
10
7d
8e
9d
10d
11d
12d
13d,f
–
–
–
ethylene glycol 110
PEG-400 110
–
a Reaction conditions: N-Cbz hydrazone 1a (0.5 mmol), diphenylacetylene
(2a; 0.6 mmol), [Ru(p-cymene)Cl2]2 (5 mol%), additive (10 mol%), solvent
(2 mL).
b GC yield.
c [Ru(p-cymene)Cl2]2 used: 7.5 mol%.
d [Ru(p-cymene)Cl2]2 used: 2.5 mol%.
e [Ru(p-cymene)Cl2]2 used: 1.5 mol%.
f Under standard conditions without microwave irradiation (conventional
oil-bath heating).
any noteworthy progress in the product yield (entry 4), al-
though a consequent decrease in time to 8 minutes reduced
the product yield to 76% (entry 5).
In addition, organized optimization with respect to cat-
alyst loading, within the 1.5–7.5 mol% range (Table 1, en-
tries 6–8), allowed the identification of its optimal quantity
(2.5 mol%), which leads to the higher yield and the product
was obtained in 86% yield. Considering the environmental
threats by the use of antimonate salt, we checked the ne-
cessity of AgSbF6 as an additive for the proposed transfor-
mation. Pleasantly, the reaction worked also in the absence
of silver salt with the same efficiency (entry 9). The catalyt-
ic reaction was also tested with various solvents such as
ethylene glycol and with some biodegradable solvents like
PEG-200, PEG-400, and PEG-600. PEG-200 and PEG-600
gave product in 58% and 71% yield, respectively (entries 10
and 11). While in the presence of ethylene glycol, the unsat-
isfactory product yield 28% was obtained (entry 12). Finally,
Further, the scope of the symmetrical and unsymmetri-
cal substituted internal alkynes for the stated methodology
was investigated. Hex-3-yne, 1-phenylbut-1-yne, and 1-
phenylprop-1-yne reacted hassle-free with acetophenone
N-Cbz hydrazone to generate corresponding products 3ab,
3ac, and 3ad in 76%, 82% and 80% yield, respectively (Table
2, entries 18–20).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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D. S. Deshmukh, B. M. Bhanage
Special Topic
Synthesis
Table 2 Ruthenium-Catalyzed Annulation of N-Cbz Hydrazones with Alkynesa
R2
R2
R3
[Ru(p-cymene)Cl2]2
NHCbz
N
(2.5 mol%)
R1
N
+
R1
PEG-400
R4
110 °C, 10 min
R4
2
R3
1
3
Entry
1
1
2
Product 3
Yield (%)b
N
NHCbz
N
Ph
2a
Ph
87
90
92
82
84
79
80
85
Ph
Ph
1a
1b
3aa
3ba
N
NHCbz
N
2
3
4
5
6
7
8
2a
2a
2a
2a
2a
2a
2a
Ph
Ph
NHCbz
N
N
O
Ph
O
1c
Ph
3ca
NHCbz
NHCbz
NHCbz
NHCbz
N
N
Br
Ph
Br
1d
Ph
3da
N
N
Cl
Ph
Cl
1e
Ph
3ea
N
N
F
Ph
F
1f
Ph
3fa
N
N
O2N
Ph
O2N
Ph
N
1g
3ga
NHCbz
N
Ph
Ph
1h
3ha
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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D. S. Deshmukh, B. M. Bhanage
Special Topic
Synthesis
Table 2 (continued)
Entry
1
2
Product 3
Yield (%)b
O
N
48
34
Ph
Ph
Ph
O
NHCbz
3ia
N
9
2a
1i
N
O
Ph
3ia′
Cl
N
Cl
NHCbz
N
10
11
12
2a
78
74
82
Ph
Ph
1j
3ja
O2N
N
O2N
NHCbz
N
2a
Ph
Ph
1k
3ka
NHCbz
N
N
2a
Cl
Ph
Cl
1l
Ph
3la
Et
Et
N
NHCbz
N
13
2a
89
Ph
Ph
1m
3ma
N
NHCbz
14
15
16
2a
2a
2a
88
93
81
N
Ph
Ph
Ph
1n
1o
3na
3oa
Ph
N
NHCbz
N
Ph
Ph
N
NHCbz
N
Ph
Ph
1p
3pa
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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D. S. Deshmukh, B. M. Bhanage
Special Topic
Synthesis
Table 2 (continued)
Entry
1
2
Product 3
Yield (%)b
S
N
NHCbz
S
N
17
2a
79
Ph
1q
Ph
3qa
N
Et
Et
18
19
20
1a
1a
1a
76
82
80
2b
Et
Et
3ab
3ac
3ad
N
Et
2c
Ph
Ph
Et
N
Ph
2d
Ph
a Reaction conditions: ketazine 1 (0.5 mmol), alkyne 2 (0.6 mmol), [Ru(p-cymene)Cl2]2 (2.5 mol%), PEG-400 (2 mL), 110 °C (microwave heating), 10 min.
b Isolated yield.
In conclusion, we have developed a microwave-assisted
rapid protocol for the synthesis of isoquinolines by annula-
tion reaction with internal alkynes via C–H/N–N activation.
N-Cbz Hydrazones were employed as directing group for re-
dox-neutral Ru-catalyzed transformation. Additionally, the
stated methodology works efficiently in the absence of any
additives as well as external oxidants. This protocol is appli-
cable to a wide range of N-Cbz hydrazones possessing elec-
tron-donating and electron-withdrawing groups as well as
internal alkynes for the synthesis of isoquinolines, produc-
ing corresponding products in good to excellent yields. Use
of non-volatile and biodegradable solvent is the additional
advantage of the present system.
shifts were reported in parts per million () relative to TMS as an in-
ternal standard. Coupling constant (J) values were reported in hertz
(Hz). Standard abbreviations were used for describing the splitting
patterns of proton in 1H NMR spectroscopic analysis. The products
were confirmed by GCMS, 1H, and 13C NMR spectroscopy analysis.
Ruthenium-Catalyzed Isoquinoline Synthesis; 1-Methyl-3,4-di-
phenylisoquinoline (3aa);13d Typical Procedure
A microwave vessel was charged with N-Cbz hydrazone 1a (134 mg,
0.5 mmol), diphenylacetylene (2a; 107 mg, 0.6 mmol), [Ru(p-cy-
mene)Cl2]2 (8 mg, 2.5 mol%), and PEG-400 (2 mL). The closed reaction
vessel was irradiated at 110 °C using microwave irradiation of 50 W
power for 10 min. At the end of the reaction, the reaction mixture was
cooled, and diluted with Et2O. The upper layer of Et2O containing the
product mixture was separated, the solvent evaporated, and the resi-
due was purified through a silica gel column using PE and EtOAc as
eluents to give pure 3aa; yield: 134 mg (87%); pale yellow solid; mp
154–156 °C.
All chemicals and solvents were purchased with high purities and
used without further purification. PEGs were dried prior to use by the
literature methods. Microwave-assisted annulation reactions were
carried out in ‘Discover’ (CEMSP 1245) CEM Corporation USA) micro-
wave reactor. The progress of the reaction was monitored by GC with
a flame ionization detector (FID) using a capillary column (30 m ×
0.25 mm × 0.25 m) and TLC (using silica gel 60 F-254 plates). The
products were visualized with a 254 nm UV lamp. GC-MS [Rtx-17, 30
1H NMR (400 MHz, CDCl3):  = 8.21–8.19 (m, 1 H), 7.65 (d, J = 3.1 Hz, 1
H), 7.60–7.57 (m, 2 H), 7.37–7.32 (m, 5 H), 7.24–7.17 (m, 5 H), 3.08 (s,
3 H).
13C NMR (101 MHz, CDCl3):  = 157.70, 149.29, 140.80, 137.49,
136.02, 131.37, 130.25, 129.97, 129.24, 128.17, 127.58, 127.03,
126.94, 126.54, 126.23, 126.13, 125.52, 22.62.
GCMS (EI 70 eV): m/z = 295 (M+), 294, 278, 253, 145.
6-Methoxy-1-methyl-3,4-diphenylisoquinoline (3ca)13d
Yield: 150 mg (92%); pale yellow solid; mp 179–181 °C.
m × 25 mm ID, film thickness (df = 0.25 m) (column flow 2 mL min–1
,
80 to 240 °C at 10 °C min–1 rise] was used for the mass analysis of the
products. Products were purified by column chromatography on 100–
200 mesh silica gel. The 1H NMR spectra were recorded on an Agilent
Technologies 400 MHz spectrometer using TMS as an internal stan-
dard. The 13C NMR spectra were recorded on 100 MHz and chemical
1H NMR (400 MHz, CDCl3):  = 8.10 (d, J = 9.1 Hz, 1 H), 7.35–7.29 (m, 5
H), 7.24–7.14 (m, 6 H), 6.91 (d, J = 2.2 Hz, 1 H), 3.71 (s, 3 H), 3.02 (s, 3
H).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–I

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D. S. Deshmukh, B. M. Bhanage
Special Topic
Synthesis
13C NMR (101 MHz, CDCl3):  = 160.61, 156.95, 149.97, 140.97,
138.10, 137.78, 131.25, 130.20, 128.63, 128.24, 127.53, 127.46,
127.08, 126.88, 121.84, 118.71, 104.50, 55.18, 22.51.
GCMS (EI 70 eV): m/z = 325 (M+), 324, 281, 154, 146.
6-Bromo-1-methyl-3,4-diphenylisoquinoline (3da)13d
Yield: 153 mg (82%); slightly yellow solid; mp 192–194 °C.
1H NMR (400 MHz, CDCl3):  = 8.04 (d, J = 8.8 Hz, 1 H), 7.80 (d, J = 1.8
Hz, 1 H), 7.66–7.64 (m, 1 H), 7.34 (m, 5 H), 7.24–7.17 (m, 5 H), 3.04 (s,
3 H).
13C NMR (101 MHz, CDCl3):  = 157.76, 150.53, 140.50, 137.40,
136.77, 131.26, 130.18, 130.03, 128.41, 128.33, 128.30,
127.63,127.45, 127.29, 127.19, 125.10, 124.57, 22.61.
1H NMR (400 MHz, CDCl3):  = 8.90 (d, J = 8.3 Hz, 1 H), 7.91 (d, J = 7.4
Hz, 1 H), 7.79–7.71 (m, 2 H), 7.65 (t, J = 7.1 Hz, 1 H), 7.55 (d, J = 9.1 Hz,
1 H), 7.42 (d, J = 5.9 Hz, 2 H), 7.35 (d, J = 6.5 Hz, 3 H), 7.25–7.19 (m, 5
H), 3.44 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 155.39, 150.80, 140.43, 137.95,
137.27, 132.96, 131.64, 131.22, 130.21, 129.73, 128.74, 128.26,
127.64, 127.58, 127.27, 127.19, 126.88, 126.64, 124.19, 123.95, 30.43.
GCMS (EI 70 eV): m/z = 345 (M+), 344, 343, 342, 307, 265, 154, 146.
7-Methyl-4,5-diphenylthieno[2,3-c]pyridine (3qa)13d
Yield: 113 mg (79%); white solid; mp 145–147 °C.
1H NMR (400 MHz, CDCl3):  = 7.61 (d, J = 5.4 Hz, 1 H), 7.35–7.29 (m, 5
H), 7.24–7.18 (m, 6 H), 2.91 (s, 3 H).
GCMS (EI 70 eV): m/z = 375 (M+, 2%), 373 (M+), 374, 372, 293, 292,
252, 147, 139, 125.
1,7-Dimethyl-3,4-diphenylisoquinoline (3ha)13d
13C NMR (101 MHz, CDCl3):  = 151.33, 150.78, 145.76, 140.14,
138.16, 134.24, 131.08, 130.51, 130.30, 128.27, 128.23, 127.69,
127.15, 127.10, 124.25, 23.52.
GCMS (EI 70 eV): m/z = 301 (M+), 300, 258, 150, 149.
4-Ethyl-1-methyl-3-phenylisoquinoline (3ac)13d
Yield: 101 mg (82%); white solid; mp 121–123 °C.
Yield: 131 mg (85%); slightly yellow solid; 131–133 °C.
1H NMR (400 MHz, CDCl3):  = 7.96 (s, 1 H), 7.56 (d, J = 8.6 Hz, 1 H),
7.43–7.32 (m, 6 H), 7.24–7.17 (m, 5 H), 3.05 (s, 3 H), 2.57 (s, 3 H).
13C NMR (101 MHz, CDCl3)  = 156.98, 148.55, 140.97, 137.71, 136.40,
134.19, 132.08, 131.36, 130.25, 129.09, 128.13, 127.55, 127.03,
126.80, 126.32, 126.10, 124.49, 22.66, 21.86.
1H NMR (400 MHz, CDCl3):  = 8.17 (d, J = 8.0 Hz, 1 H), 8.07 (d, J = 8.4
Hz, 1 H), 7.73 (t, J = 7.6 Hz, 1 H), 7.59 (t, J = 7.6 Hz, 1 H), 7.51–7.37 (m,
5 H), 3.01–2.97 (m, 5 H), 1.25 (t, J = 7.4 Hz, 3 H).
GCMS (EI 70 eV): m/z = 309 (M+), 308, 293, 252, 146, 139.
7-Methoxy-1-methyl-3,4-diphenylisoquinoline (3ia)13d
Yield: 78 mg (48%); slightly yellow solid; mp 142–144 °C.
13C NMR (101 MHz, CDCl3):  = 155.82, 150.56, 141.66, 135.16,
129.89, 129.19, 128.62, 128.14, 127.41, 126.68, 126.38, 126.20,
124.13, 22.38, 21.64, 15.66.
GCMS (EI 70 eV): m/z = 247 (M+), 246, 232, 231, 230, 115.
1H NMR (400 MHz, CDCl3):  = 7.57 (d, J = 9.2 Hz, 1 H), 7.38–7.31 (m, 6
H), 7.25–7.14 (m, 6 H), 3.98 (s, 3 H), 3.04 (s, 3 H).
13C NMR (101 MHz, CDCl3):  = 157.90, 155.95, 147.46, 140.60, 137.5,
131.39, 131.31, 130.22, 129.26, 128.14, 128.01, 127.54, 127.31,
127.09, 126.77, 122.37, 103.52, 55.48, 22.68.
GCMS (EI 70 eV): m/z = 325 (M+), 324, 308, 293, 154, 146.
5-Methoxy-1-methyl-3,4-diphenylisoquinoline (3ia′)12a
Yield: 55 mg (34%); white solid; mp 145–147 °C.
Funding Information
The author D. S. D. would like to thank the University Grants Commis-
sion (UGC), New Delhi, India for providing a Senior Research Fellow-
ship under Basic Science Research (BSR) scheme [F.25-1/2014-15, F.7-
227/2009, 16th Feb 2015].
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ersityGrants
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(F.25-1/2
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o
n
(F.7-2
2
7/2
0
0
9)
1H NMR (400 MHz, CDCl3) :  = 7.79 (d, J = 8.4 Hz, 1 H), 7.52 (t, J = 7.8
Hz, 1 H), 7.23–7.21 (m, 2 H), 7.16–7.08 (m, 8 H), 6.95 (d, J = 7.7 Hz, 1
H), 3.39 (s, 3 H), 3.04 (s, 3 H).
13C NMR (101 MHz, CDCl3) :  = 157.04, 156.86, 150.91, 141.38,
141.34, 130.35, 130.21, 127.91, 127.48, 127.45, 127.26, 127.16,
126.48, 125.61, 118.04, 110.18, 55.53, 23.24.
Acknowledgment
The author D. S. D. would like to acknowledge Ph.D. research student,
Harshada Salvi and M.Sc. research project student, Neha Gangwar for
their help during the preparation of this manuscript.
GCMS (EI 70 eV): m/z = 325 (M+), 324, 281, 162, 139.
1-Cyclopropyl-3,4-diphenylisoquinoline (3na)12c
Yield: 141 mg (88%); white solid; mp 149–151 °C.
Supporting Information
Supporting information for this article is available online at
1H NMR (400 MHz, CDCl3):  = 8.50–8.48 (m, 1 H), 7.65–63 (m, 1 H),
7.59–7.56 (m, 2 H), 7.36–7.33 (m, 5 H), 7.27–7.21 (m, 2 H), 7.16 (d, J =
2.8 Hz, 3 H), 2.83–2.81 (m, 1 H), 1.40–1.25 (m, 2 H), 1.16–1.13 (m, 2
H).
https://doi.org/10.1055/s-0037-1611795.
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References
13C NMR (101 MHz, CDCl3):  = 160.55, 148.50, 141.42, 138.33,
136.21, 131.40, 130.42, 129.73, 128.30, 128.23, 127.32, 127.07,
126.87, 126.40, 126.26, 126.24, 124.90, 13.60, 9.39.
GCMS (EI 70 eV): m/z = 321 (M+), 320, 243, 152, 146.
1-Methyl-3,4-diphenylbenzo[h]isoquinoline (3pa)13d
Yield: 140 mg (81%); slightly yellow solid; mp 142–144 °C.
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