Visible light-induced N-methyl activation of unsymmetric tertiary amines

Article abstract of DOI:10.1016/j.tet.2020.131891

In the presence of methylene group, selective N-methyl activation of tertiary amines has been accomplished with the aid of visible light using organic photocatalyst under air. This protocol explores numerous aliphatic and aromatic substituted tetra-hydroquinoline analogues from various tertiary amines and maleimides. Furthermore, this approach was applied to activate the methyl group of N-methyl carbazole to generate the biologically active molecule.

Full text of DOI:10.1016/j.tet.2020.131891

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Visible Light-Induced N-methyl Activation of Unsymmetric Tertiary Amines
Gopi Perumal, Mohanraj Kandasamy, Balaji Ganesan, Karthick Govindan, Harsha
Sathya, Min-Yuan Hung, Gopal Chandru Senadi, Ya-Ching Wu, Wei-Yu Lin
PII:
S0040-4020(20)31155-8
https://doi.org/10.1016/j.tet.2020.131891
TET 131891
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 28 August 2020
Revised Date: 9 December 2020
Accepted Date: 16 December 2020
Please cite this article as: Perumal G, Kandasamy M, Ganesan B, Govindan K, Sathya H, Hung M-Y,
Chandru Senadi G, Wu Y-C, Lin W-Y, Visible Light-Induced N-methyl Activation of Unsymmetric Tertiary
Amines, Tetrahedron, https://doi.org/10.1016/j.tet.2020.131891.
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FULL PAPER
Visible Light-Induced N-methyl Activation of Unsymmetric
Tertiary Amines
Gopi Perumal, [a] Mohanraj Kandasamy, [a] Balaji Ganesan, [a] Karthick Govindan, [a] Harsha Sathya, [a]
Min-Yuan Hung, [b] Gopal Chandru Senadi, [c] Ya-Ching Wu [d] and Wei-Yu Lin* [a],[d],[e],[f]
[a]
Gopi Perumal, Mohanraj Kandasamy, Balaji Ganesan, Karthick Govindan, Harsha Sathya, Prof. Wei-Yu-Lin
Department of Medicinal and Applied Chemistry
Kaohsiung Medical University
Kaohsiung 80708, Taiwan, ROC. Tel: 886-7-312-1101 ext 2807 Fax: 886-7-312-5339, Email: wylin@kmu.edu.tw
[b]
Min-Yuan Hung,
Centre for Research Resources and Development
Kaohsiung Medical University
Kaohsiung 80708, Taiwan, ROC
[c]
Gopal Chandru Senadi
Department of Chemistry
Faculty of Engineering and Technology
SRM Institute of Science and Technology
Kattankulathur, Chennai -603203, India
[d]
[e]
[f]
Ya-Ching Wu, Prof. Wei-Yu-Lin
Division of Safety and Health, Office of Safety, Health and Environment
Kaohsiung Medical University
Kaohsiung 80708, Taiwan, ROC
Prof. Wei-Yu-Lin
Department of Medical Research
Kaohsiung Medical University Hospital
Kaohsiung 80708, Taiwan, ROC
Prof. Wei-Yu-Lin
Drug Development and Value Creation Research Centre
Kaohsiung Medical University
Kaohsiung 80708, Taiwan, ROC
Supporting information for this article is given via a link at the end of the document. ((Please delete this text if not appropriate))
Dedicated to Professor Tien-Yau Luh on the Occasion of His 75th Birthday
Abstract: In the presence of methylene group, selective N-methyl
activation of tertiary amines has been accomplished with the aid of
visible light using organic photocatalyst under air. This protocol
explores numerous aliphatic and aromatic substituted tetra-
hydroquinoline analogues from various tertiary amines and
maleimides. Furthermore, this approach was applied to activate the
methyl group of N-methyl carbazole to generate the biologically
active molecule.
Introduction
To develop a new synthetic methodology with good selectivity
and high efficiency in a sustainable route for the small molecules
and natural products, is always strengthening the organic
synthetic utility.1,2 The metal-free chemical transformations
under thermal conditions contributed many achievements in
developing sustainable synthetic route with a mild reaction
condition. Of late, visible-light-induced photochemical reactions
are becoming modish with atom economy, high selectivity and
efficiency.3,4 Along the line, metal-free organic photocatalyst
mediated visible-light-induced chemical transformations are
Scheme 1: Previous reports on the synthesis of tetrahydroquinoline
5
prominent with environmentally benign methodology.
example, Eosin Y,6,7 Rose Bengal,8 salicylaldehyde, 9 9-
For
fluorenone10 are in the rely on to enhance the sustainability of
the visible light-mediated photochemical reactions and are
promising photocatalysts in the near future.
1

FULL PAPER
Organic photocatalysts are in high demand for organic
transformations. Representatively, Eosin Y is a well-known
organic photocatalyst and economical alternative for transition
metal catalyst in visible-light-driven organic reactions. Broadly,
Eosin Y had been used in photocatalytic organic transformations
due to its, easy access, typically inexpensive and productive
photocatalytic performance.11 It is noteworthy that a variety of
All the reactions were performed under 10 W blue LEDs irradiation at room
temperature for 24 h, Isolated yields are given, a under O2, b under air, c 5.0
12,13,
Entry
1a:2a
Solvent
Additive
Product
reactive radical intermediates including α-aminoalkyl,
arene,14 azole,15 perfluoroaryl16 can be generated using the
triplet excited Eosin Y17,18. These reactive intermediates are
used in various visible light-mediated photocatalysis in particular
oxidative cyclization,19,20C-H activation,21,22hydrogen atom
transfer reactions,6 dehydrogenative coupling.23,24
(equiv.)
(10 mol%)
1a
2b
3
5:1
5:1
5:1
1,4-dioxane
1,4-dioxane
1,4-dioxane
-
-
22 %
20 %
85 %
Eosin Y
4
5
6
5:1
5:1
5:1
1,4-dioxane
Rose Bengal
Eosin Y
78 %
N.R.
N.R.
-
The amino radical cation is an interesting intermediate
generated by single-electron oxidation of amines and this sole
intermediate can produce lots of α-substituted amines.12
Oxidative cyclization of the α-aminoalkyl radical with maleimide
under visible light has been studied extensively in recent
years.19,25,26 Such extended literature, either dimethyl20 or diethyl
aniline was employed for the oxidative cyclization with
maleimide to produce tetrahydroquinoline analogues. 27-31 Only
few reports were contributed to N-methyl activation or
unsymmetrical tertiary amine 26 in the propinquity of methylene
group using metal photocatalyst Ru(bpy)3Cl2,26 CuCl2,32 surface
Toluene
Eosin Y
7
8
5:1
5:1
5:1
4:1
3:1
2:1
4:1
4:1
DCM
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Y
Eosin Yc
Eosin Yd
N.R.
10 %
43 %
85 %
58 %
30 %
85 %
79 %
DMF
9
THF
10
11
12
13
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
14
mol%, d 4.0 mol%.
modified TiO2 with NiO33, relay catalyst Ru(bpy)3
-
The equivalent of 1a was lowered from 5.0 to 4.0 the yield
was improved (entry 10), but it was dropped to 58% and 30%
with 3.0 equiv. and 2.0 equiv. of 1a, respectively. (entry 11 and
12). On altering the mol% of Eosin Y, there was no yield
difference up to 5.0 mol% then it was reduced to 79% with 4.0
mol% of catalyst (entry 13 and 14). Finally, the standard reaction
condition (Table 1, entry 13) was optimized in terms of 1a (4.0
equiv.), 2a (1.0 equiv.) and Eosin Y (5.0 mol%) in 1,4-dioxane
under blue LEDs light for 24 h at room temperature.
Co(dmgH)2pyCl34 and Eosin Y 20 but dispirit with very limited
examples, inadequate yield, selectivity and restrained with
symmetric tertiary amines. In this account, we aspired to
introduce a methylene group in unsymmetrical tertiary amines
instead of a methyl in dimethylaniline to investigate the reaction
conditions and mechanisms under photochemical pathway using
organic photocatalyst. (Scheme 1).
Having successfully optimized reaction condition, we have
focused on the scope of derivatives generality with electron
donating, electron-withdrawing, alkyl and aryl groups. First and
foremost, various methylene groups were introduced in aniline to
get the variety of unsymmetric tertiary amines. Gratifyingly, the
unsymmetric tertiary amines were synthesized from N-methyl
aniline reacting with alkyl halide in the presence of K2CO3 at
50˚C (See Supporting Information ). The alkyl (benzyl,
cyclohexyl, ethyl, n-butyl, dodecyl, phenethyl, isobutyl,) and
alkenyl (allyl, 2-methyl allyl, 1-pentene) tertiary amines have
been cyclized with (N)-phenyl maleimide (2a) and afford
corresponding tetrahydroquinolines 3aa-3ka in good yields 71%
- 85% (Scheme 2). Among all alkyl tertiary amines, the benzyl
substitution brought the highest yield 85%. All alkene substrates
were well tolerated in standard reaction conditions and never
observed the decomposition.
Results and Discussion
We began our investigation with cyclization of 1a (5.0
equiv.), 2a (1.0 equiv.) using O2, and air as an oxidant in 1,4-
dioxane (Table 1). Fortunately, selective product 3aa was
obtained uniquely 22% and 20% yield under 10 W blue LEDs
irradiation at room temperature for 24 h. (entry 1 and 2). 3aa’s
structure was further confirmed by the X-ray crystallography
(CCDC: 2002654). With this propitious result, various organic
photocatalysts such as Eosin Y, Rose Bengal in air were
examined, surprisingly the yield was increased to 85% and 78%
individually (entry 3 and 4). Unfortunately, there was no product
formation without solvent (entry 5). The effect of solvent was
also
investigated
with
toluene,
dichloromethane,
dimethylformamide and tetrahydrofuran, however the major yield
was obtained only in 1,4-dioxane (entry 6-9).
Table 1: Optimization conditions for the cyclization of 1a with 2a
O
N
Eosin Y (5 mol%)
N
2
+
N
O
1,4 - Dioxane
Blue LED, Air
O
N
O
1a
2a
3aa

FULL PAPER
Scheme 2: Scope of alkyl substitution in unsymmetric tertiary amine
Further, the scope of the derivatives were explored by
various N-phenyl maleimide (2b-i) analogues35 (Scheme 3). The
reaction of tertiary amine 1a with numerous distinctive N-phenyl
(4-bromo, 4-methoxy, 4-fluoro, 2-cyano, 4-chloro, 4-ethyl ester,)
and N-benzyl maleimide proceeded smoothly to produce their
respective tetrahydroquinoline 3ab-3ah in good yield 61% - 81%.
All electron-withdrawing substituents of maleimide afforded good
yield except the 2-cyano (3ae) in 61% yield. The N-benzyl
maleimide provided the highest yield of 81% (3ag) across this
scope of derivatives and electron donating substituent methoxy
phenyl maleimide gave 73% of yield (3ac). Hence, decisively the
electron donating substituents at maleimide part favors the
cyclization than electron-withdrawing substituent. To pursue the
functional group tolerance, 4-phenyl ethyl ester and 4-phenyl
hydroxy maleimide were used. Ethyl ester substituent afforded
the desired product (3ah, 69%) whereas the hydroxyphenyl
maleimide could not be produced desired product (3ai). 3af’s
structure was further confirmed by the X-ray crystallography
(CCDC: 2002653).
Scheme 4: Scope of phenyl and benzyl substitution of unsymmetric tertiary
amine
Reaction condition: All the reactions were performed with 1.2 mmol of 1a-k,
0.3 mmol of 2, Eosin Y (0.015 mmol), and 1.5 mL of 1,4-dioxane. The
reactions were under 10 W blue LEDs irradiation at room temperature for 24 h.
Isolated yields are given.
Scheme 3: Scope of N-substituted maleimide
Reaction condition: All the reactions were performed with 1.2 mmol of 1(l-q),
0.3 mmol of 2(a-j), Eosin Y (0.015 mmol) and 1.5 mL of 1,4-dioxane. The
reactions were under 10 W blue LEDs irradiation at room temperature for 24 h.
Isolated yields are given. a Reaction for 48 h.
Furthermore, the scope of phenyl- and benzyl- ring of
tertiary amines were scrutinized as presented in Scheme 4.
Introducing an electron-withdrawing (chloro-, fluoro-), electron-
donating (methoxy-) functionalities in the phenyl ring and
substitution of the m-, p- nitro group in benzyl ring of tertiary
amines were reacted with various maleimides. The desired
tetrahydroquinoline analogues 3ma, 3nf, 3ng, 3nc, 3nh, 3ne
(CCDC: 2002655) and 3qa were obtained in moderate to good
yield except 3nj (46%) which depends on the substituent at
phenyl part of maleimide. Perhaps, the m-nitrobenzyl group
Reaction condition: All the reactions were performed with 1.2 mmol of 1a, 0.3
mmol of 2(b-i), Eosin Y (0.015 mmol) and 1.5 mL of 1,4-dioxane. The
reactions were under 10 W blue LEDs irradiation at room temperature for 24 h.
Isolated yields are given.
3

FULL PAPER
influenced the stability of tertiary amine radical; as
a
quenching with oxygen molecule present in the air and forms
superoxide (IV). The superoxide associates with the proton
which releases from (II) and produces peroxide radical (V). The
methylene radical (II) reacts with maleimide and produces the
radical intermediate (III). Then the radical intermediate (III) is
cyclized to give the desired product 3 by hydrogen atom transfer
of peroxide radical (V) to hydrogen peroxide (VI). On the other
hand, the radical cation (I) may form benzyl radical (VII). The
benzyl radical may either decompose to imine radical (VIII) or a
mixture of tolyl or N-methyl aniline radical. Imine radical (VIII)
may also decompose into phenyl or phenylmethanimine radical.
(See Supporting Information Scheme S4). Hence, the reactive
species of methyl radical (II) can only produce
tertrahydroquinoline 3. Thus, the protocol exists as regiospecific
and benzyl activated product was not obtained in this process.
Since benzyl radical tends to form imine, it is one of the causes
consequence, the rate of reaction was slower (48 h) than the p-
nitrobenzyl substitution in the amine. The chloro- and fluoro-
substituted phenyl tertiary amines afforded the desired product
3la, 3lc, 3lg, 3pa and 3pg in good yield 68%-78%. Although the
methoxy substituted phenyl tertiary amine gave corresponding
tetrahydroquinoline (3oa) in lowered yield 49% but we did not
observe the regioisomer.
Scheme 5: Control experiments
Generally, the benzyl radical is more stable than
methylene radical nonetheless, surprisingly in all the situations
we uniquely obtained methyl activated product. Hence, we keen
to investigate mechanistic insight into the reaction. Furthermore,
few control experiments were carried out to ensure the
specificity and pathway of the reaction (Scheme 5). A set of
experiments in dark (a) and in the presence of nitrogen (b)
evidenced that the necessity of light and oxygen. Reaction with
radical scavenger (c) TEMPO (2.0 equiv.) did not provide the
desired product, perhaps the reaction undergoes in radical
that the reaction requires 4.0 equiv. of the tertiary amine.
Scheme 6: Plausible mechanism
pathway.
Dual methylene group substituted unsymmetric
Albeit tetrahydroquinoline core structure itself has several
medicinal values viz antitumour36 (Segolines
A
and B)
tertiary amines, N-benzyl N-ethyl aniline 4 and N, N-dibenzyl
aniline 5 were reacted with (2a) in standard reaction condition
but both the reactions (d, e) were not proceeded to yield
respective tetrahydroquinoline. Excluding the methylene group,
methine group substituted tertiary amine (1h) also utilized.
Nevertheless, gratefully activated methyl group rather than the
methine, merely yielded 3ha in 74% yield (f). It indicates that the
process specific for N-methyl activation. Then we analyzed the
decomposition of tertiary amine 1a in the reaction condition and
found that the mass of imine (See Supporting Information
Scheme S4).
37
38
antipsychotic,
and serotinin agonists,
furthermore we wish
to illustrate the synthetic utility of the process excluding
unsymmetric tertiary amine. Hence, in addition, the methyl group
of N-methyl carbazole (10) has been activated and obtained
biologically39 significant carbazole-based compound 11 with
O
O
Standard Condition
+
N
N
N
N
O
2a
O
10
11 45%
45% yield (Scheme 7).
Scheme 7: Synthetic application
Conclusion
19,33,26,34
Based on these findings and previous results,
a
plausible mechanism for the cyclization is outline in Scheme 6.
Upon irradiation of blue LEDs, tertiary amine 1 is oxidized by
triplet excited state of Eosin Y through single electron transfer
(SET). The radical cation (I) deprotonates and forms methylene
radical (II). The reduced form of Eosin Y (ES·) oxidatively
In summary, we have effectively developed an adaptable
methodology for selective activation of methyl group over the
methylene group to synthesis tetrahydroquinoline from
4

FULL PAPER
unsymmetric tertiary amine and maleimide in a mild reaction
condition under visible light using organic photocatalyst. The
scope of derivatives proved by synthesizing variety of
tetrahydroquinoline analogues and selectivity of the method has
been demonstrated through various control experiments. The
functional group tolerance of the process also investigated with
various alkene, ester and hydroxy functionalized substrates. The
imine formation has been identified during the reaction greatly
supports to elucidate the mechanistic pathway and selectivity of
the reaction.
Title compound was synthesized according to the general
procedure and obtain as yellow oil ( 85% ) ;1H-NMR (400 MHz,
CDCl3) δ 7.53 (d, J = 7.6 Hz, 1H), 7.44 (td, J = 7.6, 1.8 Hz, 2H),
7.36 (t, J = 6.80 Hz, 1H), 7.29-7.21 (m, 8H), 7.13 (t, J = 7.8 Hz,
1H), 6.88 (t, J = 7.6 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 4.47 (d, J
= 15.6 Hz, 1H), 4.28-4.17 (m, 2H), 3.68 (dt, J = 11.7, 2.3 Hz, 1H),
3.57-3.53 (m, 1H), 3.27 (dq, J = 11.7, 2.1 Hz, 1H); 13C-NMR
(100 MHz, CDCl3) δ 177.6, 175.9, 147.6, 137.8, 132.1, 130.6,
129.1, 128..6, 127.5, 127.4, 126.4, 119.8, 118.9, 113.5, 55.4,
49.1, 44.2, 42.5; HRMS (ESI) calcd. for C24H20N2O2Na [M+Na]+:
391.1417, found for 391.1413.
Experimental Section
5-cyclohexyl-2-pheny-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-
c]quinolone-1,3(2H)-dione (3ba)
All chemicals were purchased from commercial vendors
(Sigma Aldrich, Alfa Aesar, TCI, and matrix scientific) and used
directly without further purification, unless otherwise noted. A
well cleaned and oven dried glassware were used for the
experiments. The reaction was monitored by Thin Layer
Chromatography (TLC), purchased as pre-coated with silica gel
60 F254 from Merck. Column chromatography was carried out
using the silica gel 60-120 mesh (purchased from Merck) with
mixture of ethyl acetate/hexane or hexane as the eluent. 1H
NMR spectra were recorded on 400 MHz, JEOL NMR
spectrometer using CDCl3 or DMSO-d6 as solvent. 13C-NMR
spectra were recorded on 100 MHz, JEOL NMR spectrometer
using CDCl3 or DMSO-d6 as solvent. The spectra were recorded
and presented in chemical shifts (ppm) with tetramethylsilane
(TMS) used as internal standard. Multiplicities were provided in s
(singlet), d (doublet), dd (doublet of the doublets), t (triplet), q
(quartet) and m (multiplet), coupling constants (J) were reported
in Hz. All the HRMS (either ESI or EI mode) were recorded on
JMS-700 spectrometer. Melting points (MP-2D) was determined
from Fargo instruments.
Title compound was synthesized according to the general
procedure and obtain as white solid ( 71% ) m.p. 186 ℃ -
188 ℃; H-NMR (400 MHz, CDCl3): δ 7.47-7.39 (m, 3H), 7.35-
1
7.31 (m, 1H), 7.25-7.18 (m, 3H), 6.83 (t, J = 12.00 Hz, 1H), 6.76
(d, J = 8.00 Hz, 1H), 4.10 (d, J = 12.00 Hz, 1H), 3.76 (dd, J =
4.00, 12.00 Hz, 1H), 3.55-3.51 (m, 1H), 3.46-3.43 (m, 1H), 2.93
(dd, J = 4.00, 12.00 Hz, 1H), 1.83-1.93 (m, 3H), 1.69 (d, J =
16.00 Hz, 1H), 1.57 (s, 3H), 1.12-1.37 (m, 4H).13C-NMR (100
MHz, CDCl3): δ 178.0, 175.9, 148.2, 132.1, 131.0, 129.1, 128.6,
128.5, 126.4, 119.7, 118.9, 112.8, 55.4, 45.0, 42.8, 42.2, 31.3,
27.4, 26.3, 26.0, 25.8; HRMS (ESI) calcd. for C23H24N2O2Na
[M+Na]+: 383.1730, found for 383.1730.
5-ethyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]
quinolone-1,3(2H)-dione (3ca)
Title compound was synthesized according to the general
procedure and obtain as white solid ( 81% ) m.p. 214℃ -
216 ℃;1H-NMR (400 MHz, CDCl3): δ 7.50 (d, J = 6.0 Hz, 1H),
7.43-7.39 (m, 2H), 7.35-7.32 (m, 1H), 7.25-7.16 (m, 3H), 6.86-
6.82 (m, 1H), 6.76-6.74 (m, 1H), 4.12 (dd, J = 9.0, 2.2 Hz, 1H),
3.66-3.61 (m, 1H), 3.54-3.51 (m, 1H), 3.32-3.24 (m, 2H), 3.16-
3.13 (m, 1H), 1.18-1.14 (m, 3H); 13C-NMR (100 MHz, CDCl3): δ
177.8, 175.9, 147.3, 132.0, 130.7, 129.1, 128.6, 128.5, 126.4,
119.0, 118.6, 112.6, 47.2, 44.7, 44.0, 42.4, 10.9; HRMS (ESI)
calcd. for C19H19N2O2 [M+H] +: 307.1441, found for 307.1434.
General procedure for preparation of unsymmetric tertiary
amines and its characterization data (1a-k): 40
In a 100 mL round bottom flask, N-methyl aniline (10.0
mmol), dimethyl formamide (15 mL), potassium carbonate (25.0
mmol) and alkyl halide (15.0 mmol) were added and stirred at
60˚ C for four hours. The reaction mixture was quenched with ice
water and extracted with ethyl acetate. Solvent was removed
under reduced pressure. The crude product was purified by
column chromatography (Eluent: Hexane).
5-butyl-2-phenyl)-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-
c]quinolone-1,3(2H)-dione (3da)
Title compound was synthesized according to the general
procedure and obtain as brown oil (78% ) ; 1H-NMR (400 MHz,
CDCl3): δ 7.53-7.49 (m, 1H), 7.46-7.32 (m, 3H), 7.28-7.17 (m,
3H), 6.89-6.82 (m, 1H), 6.75 (t, J = 10.0, Hz, 1H), 4.12 (t, J =
10.0 Hz, 1H), 3.65 (td, J = 11.8, 2.5 Hz, 1H), 3.54-3.50 (m, 1H),
3.32-3.04 (m, 3H), 1.62-1.52 (m, 2H), 1.40-1.25 (m, 2H), 0.97-
0.82 (m, 3H); 13C-NMR (100 MHz, CDCl3): δ 177.8, 175.9, 147.6,
132.1, 130.7, 129.1, 128.6, 126.4, 119.0, 118.6, 112.6, 50.6,
48.3, 44.1, 42.4, 28.2, 20.4, 13.9; HRMS (m/z, ESI) calcd
[C21H23N2O2]+ [M+H]+ 335.1754, observed 335.1749.
General procedure for preparation of tetrahydroquinoline
In an 8.0 mL glass vial quipped with stir bar was added
unsymmetric tertiary amine (1.2 mmol), dioxane (1.5 mL),
maleimide (0.3 mmol), Eosin Y (0.015 mmol) and the solution
was irradiated under four 10 W blue LEDs for 24h in ambient
temperature. The reaction was stopped and solvent was
removed under vacuum. The residue was dissolved in ethyl
acetate and washed with water. Again, solvent was removed
under vacuum. The crude product was purified by column
chromatography using 60-200 silica gel (Eluent; Ethyl
acetate:Hexane = 15:85).
5-dodecyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-
c]quinoline-1,3(2H)-dione (3ea)
Title compound was synthesized according to the general
procedure and obtain as brown oil ( 73% ) ; 1H-NMR (400 MHz,
CDCl3): δ 7.50 (d, J = 6.8 Hz, 1H), 7.41 (t, J = 7.6 Hz, 2H), 7.34
(t, J = 7.4 Hz, 1H), 7.25-7.23 (m, 2H), 7.21-7.16 (m, 1H), 6.84 (t,
J = 7.4 Hz, 1H), 6.73 (d, J = 8.0 Hz, 1H), 4.12 (d, J = 9.6 Hz, 1H),
3.64 (dd, J = 11.4, 2.6 Hz, 1H), 3.52 (dt, J = 9.5, 3.5 Hz, 1H),
5-benzyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-
c]quinolone-1,3(2H)-dione (3aa)
5

FULL PAPER
3.28-3.21 (m, 1H), 3.17 (dd, J = 11.8, 4.2 Hz, 1H), 3.11-3.04 (m,
1H), 1.35-1.23 (20H), 0.87 (t, J = 6.6 Hz, 3H); 13C-NMR (100
MHz, CDCl3): δ 177.7, 175.8, 147.5, 131.9, 130.6, 128.9, 128.5,
128.4, 126.3, 118.9, 118.5, 112.5, 50.8, 48.2, 44.0, 42.3, 31.8,
30.9, 29.5, 29.4, 29.3, 27.2, 26.0, 22.6, 14.1, 0.9; HRMS (m/z,
ESI) calcd [C29H39N2O2]+ [M+H]+ 447.3006, observed 447.3014.
5-(pent-4-en-1-yl)-2-phenyl)-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c]quinolone-1,3(2H)-dione (3ja)
Title compound was synthesized according to the general
1
procedure and obtain as yellow liquid (76% ) ; H-NMR (400
MHz, CDCl3): δ 7.51-7.49 (m, 1H), 7.44-7.39 (m, 2H), 7.36-7.32
(m, 1H), 7.25-7.17 (m, 3H), 6.85 (dd, J = 10.4, 4.0, 3.2 Hz, 1H),
6.74 (dd, J = 8.4, 3.2 Hz, 1H), 5.84-5.75 (m, 1H), 5.05-4.97 (m,
2H), 4.12 (q, J = 4.9 Hz, 1H), 3.65 (dq, J = 11.6, 2.6 Hz, 1H),
3.54-3.50 (m, 1H), 3.31-3.25 (1H), 3.19-3.05 (2H), 2.09 (m, 2H),
1.72-1.63 (m, 2H). 13C-NMR (100 MHz, CDCl3): δ 177.6, 175.7,
147.3, 137.7, 131.9, 130.6, 128.9, 128.5, 128.4, 126.2, 119.0,
118.5, 115.2, 112.4, 50.0, 48.2, 43.9, 42.2, 31.0, 25.1; HRMS
(m/z, EI) calcd [C22H22N2O2] + [M]+ 346.1681, observed 346.1682.
5-phenethyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-
c]quinolone-1,3(2H)-dione (3fa)
Title compound was synthesized according to the general
procedure and obtain as white solid (80%) m.p. 207 ℃ - 209 ℃;
1H-NMR (400 MHz, CDCl3): δ 7.54 (t, J = 8.00 Hz, 1H), 7.43-
7.38 (m, 1H), 7.36-7.19 (m, 10H), 6.89-6.81 (m, 2H), 4.10-4.15
(m, 1H), 3.71-3.66 (m, 1H), 3.56-3.41 (m, 3H), 3.27-3.22 (m, 1H),
2.94-2.86 (m, 2H). 13C-NMR (100 MHz, CDCl3): δ 177.4, 175.7,
146.7, 139.2, 131.9, 130.7, 128.9, 128.5, 128.4, 126.2, 119.1,
118.2, 112.4, 52.5,48.0, 43.7, 42.1, 32.2; HRMS (m/z, ESI) calcd
[C25H22N2O2Na] + [M+Na] + 405.1573, observed 405.1566.
5-isobutyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-
c]quinoline-1,3(2H)-dione (3ka)
Title compound was synthesized according to the general
procedure and obtain as brown oil (77%); 1H-NMR (400 MHz,
CDCl3): δ 7.50 (d, J = 7.2 Hz, 1H), 7.43-7.32 (m, 3H), 7.25-7.17
(m, 3H), 6.85 (t, J = 7.6 Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 4.13 (d,
J = 9.6 Hz, 1H), 3.65 (dt, J = 11.6, 2.2 Hz, 1H), 3.52-3.49 (m,
1H), 3.22-3.10 (m, 2H), 2.69-2.63 (m, 1H), 1.97 (p, J = 6.4 Hz,
1H), 0.92-0.88 (m, 6H). 13C-NMR (100 MHz, CDCl3): δ 177.7,
175.8, 147.9, 131.9, 130.6, 129.0, 128.4, 126.2, 119.0, 118.6,
112.5, 59.2, 49.8, 44.1, 42.2, 26.7, 20.5, 20.3. HRMS (EI) calcd.
5-allyl-2-pheny-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]
quinoline-1,3(2H)-dione (3ga)
Title compound was synthesized according to the general
procedure and obtain as white solid (83%) m.p. 205 ℃ - 207 ℃;
1H-NMR (400 MHz, CDCl3): δ 7.52-7.47 (m, 1H), 7.44-7.29 (m,
3H), 7.25-7.12 (m, 3H), 6.89-6.71 (m, 2H), 5.90-5.78 (1H), 5.27-
5.18 (m, 2H), 4.15-4.09 (m, 1H), 3.89-3.74 (m, 1H), 3.70-3.61 (m, for C21H22N2O4 [M]+: 334.1681, found for 334.1673.
1H), 3.55-3.49 (m, 1H), 3.34-3.28 (m, 1H), 3.15-3.08 (m, 1H).
13C-NMR (100 MHz, CDCl3): δ 177.6, 175.7, 147.3, 133.1, 130.5, 5-benzyl-2-(4-bromophenyl)-3a,4,5,9b-tetrahydro-1H-
129.5, 128.9, 128.4, 126.2, 122.3, 119.4, 118.6, 118.0, 113.0,
53.4, 47.6, 43.9, 42.3; HRMS (m/z, ESI) calcd [C20H18N2O2Na]+
[M+Na]+ 341.1260, observed 341.1257.
pyrrolo[3,4-c]quinolone-1,3(2H)-dione (3ab)
Title compound was synthesized according to the general
procedure and obtain as brown oil ( 71% ); 1H-NMR (400 MHz,
CDCl3): δ 7.57-7.50 (m, 3H), 7.26-7.11 (m, 8H), 6.89 (d, J = 7.6
Hz, 1H), 6.73 (d, J = 8.4 Hz, 1H), 4.46 (d, J = 15.2 Hz, 1H), 4.26-
4.16 (m, 2H), 3.73-3.64 (m, 1H), 3.54-3.52 (m, 1H), 3.26-3.23 (m,
1H); 13C-NMR (100 MHz, CDCl3): δ 177.1, 175.4, 137.6, 132.2,
130.9, 130.5, 128.7, 128.6, 127.8, 127.4, 119.8, 118.7, 113.5,
55.3, 48.9, 44.2, 42.4; HRMS (m/z, EI) calcd [C24H19BrN2O2]+
[M]+ 446.0630, observed 446.0636.
5-isopropyl-2-phenyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]
quinoline-1,3(2H)-dione (3ha)
Title compound was synthesized according to the general
procedure and obtain as white solid ( 74% ) m.p. 200 ℃ -
1
202 ℃; H-NMR (400 MHz, CDCl3): δ 7.39 (d, J = 7.6 Hz, 1H),
7.32 (td, J = 6.6, 1.7 Hz, 2H), 7.26-7.22 (m, 1H), 7.17-7.09 (m,
3H), 6.77-6.70 (m, 2H), 4.01 (d, J = 9.6 Hz, 1H), 3.84 (q, J = 6.6
Hz, 1H), 3.62 (dd, J = 12.0, 2.4 Hz, 1H), 3.46-3.42 (m, 1H), 2.78
(dd, J = 11.8, 4.2 Hz, 1H), 1.13 (d, J = 6.8 Hz, 3H), 1.04 (d, J =
6.4 Hz, 3H). 13C-NMR (100 MHz, CDCl3): δ 177.8, 175.8, 148.0,
132.0, 130.8, 128.9, 128.5, 128.4, 126.2, 119.5, 118.8, 112.6,
46.2, 44.5, 42.6, 40.6, 20.8, 16.2; HRMS (m/z, ESI) calcd
[C20H20N2O2Na]+ [M+Na]+ 343.1417, observed 343.1420.
5-benzyl-2-(4-methoxyphenyl)-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c]quinolone-1,3(2H)-dione (3ac)
Title compound was synthesized according to the general
procedure and obtain as white solid (73%) m.p. 231 ℃ - 233 ℃;
1H-NMR (400 MHz, CDCl3): δ 7.53 (t, J = 7.0 Hz, 1H), 7.29-7.10
(m, 10H), 6.98-6.93 (m, 1H), 6.89-6.85 (m, 1H), 6.73 (t, J = 7.4
Hz, 1H), 4.47 (dd, J = 15.0, 7.4 Hz, 1H), 4.27 (q, J = 7.7 Hz, 1H),
4.17 (t, J = 8.6 Hz 1H), 3.80 (s, 3H), 3.69-3.65 (m, 1H), 3.54-
3.50 (m, 1H), 3.29-3.23 (m, 1H). 13C-NMR (100 MHz, CDCl3): δ
177.8, 176.1, 159.5, 147.6, 137.8, 130.6, 128.6, 127.6, 127.5,
127.4, 124.7, 119.8, 119.0, 114.4, 113.5, 55.5, 55.4, 49.1, 44.1,
5-(2-methylally-2-phenyl-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3ia)
Title compound was synthesized according to the general
1
procedure and obtain as brown oil( 79% ); H-NMR (400 MHz,
+
+
CDCl3): δ 7.51 (d, J = 7.6 Hz, 1H), 7.44-7.39 (m, 2H), 7.36-7.32
(m, 1H), 7.25-7.20 (m, 2H), 7.17 (d, J = 8.4 Hz, 1H), 6.88 (td, J =
7.6, 1.8 Hz, 1H), 6.73 (d, J = 8.2 Hz, 1H), 4.91 (d, J = 16.4 Hz,
2H), 4.16-4.10 (m, 1H), 3.82 (d, J = 15.6 Hz, 1H), 3.67 (dt, J =
11.8, 2.8 Hz, 1H), 3.55-3.50 (m, 2H), 3.15 (td, J = 7.9, 4.2 Hz,
1H), 1.70 (s, 3H). 13C-NMR (100 MHz, CDCl3): δ 177.8, 175.9,
147.7, 141.1, 134.2, 132.1, 130.5, 129.1, 128.6, 126.4, 126.1,
122.4, 119.6, 118.6, 113.2, 113.0, 57.7, 48.4, 44.0, 42.4, 20.2.;
HRMS (m/z, ESI) calcd [C16H14NO]+ [M+H]+ 333.1525, observed
333.1025
42.4; HRMS (m/z, ESI) calcd [C25H22N2O3Na]
421.1522, observed 421.1525.
[M+Na]
5-benzyl-2-(4-fluorophenyl)-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c]quinolone-1,3(2H)-dione (3ad)
Title compound was synthesized according to the general
procedure and obtain as yellow liquid (64% ); H-NMR (400
MHz, CDCl3): δ 7.45 (t, J = 6.2 Hz, 1H), 7.21-7.14 (m, 7H), 7.08-
7.03 (m, 3H), 6.80 (t, J = 7.4 Hz, 1H), 6.66 (t, J = 7.0 Hz, 1H),
4.40 (dd, J = 15.2, 5.6 Hz, 1H), 4.18 (dd, J = 15.2, 5.2 Hz, 1H),
4.13-4.09 (m, 1H), 3.59 (dd, J = 12.0, 2.8 Hz, 1H), 3.48-3.44 (m,
1
6

FULL PAPER
1H), 3.21-3.15 (m, 1H). 13C-NMR (100 MHz, CDCl3): δ 177.4,
175.7, 147.5, 137.6, 130.5, 128.69, 128.62, 128.2, 128.1, 127.9,
127.4, 127.3, 119.8, 118.7, 116.2, 116.0, 113.5, 55.3, 49.0, 44.1,
5-benzyl-8-fluoro-2-phenyl-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c] quinolone-1,3(2H)-dione (3la)
Title compound was synthesized according to the general
+
+
1
42.4; HRMS (m/z, ESI) calcd [C24H19FN2O2Na]
409.1322, observed 409.1317.
[M+Na]
procedure and obtain as yellow liquid (74% ); H-NMR (400
MHz, CDCl3): δ 7.49-7.44 (m, 2H), 7.41-7.36 (m, 1H), 7.33-7.23
(m, 8H), 6.83 (td, J = 8.5, 2.9 Hz, 1H), 6.67-6.62 (m, 1H), 4.42
(dd, J = 15.2, 5.6 Hz, 1H), 4.23 (dd, J = 15.2, 5.6 Hz, 1H), 4.17-
4.11 (m, 1H), 3.68-3.64 (m, 1H), 3.54-3.50 (m, 1H), 3.24-3.19 (m,
1H); 13C-NMR (100 MHz, CDCl3): δ 177.3, 175.3, 144.0, 137.5,
132.0, 129.2, 128.7, 127.5, 127.4, 126.4, 120.6, 117.3, 117.1,
115.2, 115.0, 114.57, 114.50, 55.8, 49.6, 44.1, 42.6; HRMS (m/z,
ESI) calcd [C24H19N2O2FNa]+ [M+Na]+ 409.1322, observed
(5-benzyl-1,3-dioxo-1,3,3a,4,5,9b-hexahydro-2H-pyrrolo[3,4-
c]quinolin-2-yl)benzonitrile (3ae)
Title compound was synthesized according to the general
procedure and obtain as brown solid (61% ) m.p. 172 ℃ -
174 ℃; 1H-NMR (400 MHz, CDCl3): δ 7.69 (t, J = 52.00 Hz, 1H),
7.52-7.49 (m, 2H), 7.25-7.07 (m, 8H), 6.88-6.75 (m, 2H), 4.49-
4.40 (m, 1H), 4.28 (s, 2H), 3.66-3.28 (m, 3H).13C-NMR (100 MHz, 409.1332.
CDCl3): δ 176.4, 174.9, 147.6, 137.7, 133.8, 130.6, 129.6, 129.1,
128.8, 128.6, 127.6, 127.4, 119.9, 113.5, 112.2, 55.4, 48.9, 44.4,
5-benzyl-8-fluoro-2-(4-methoxyphenyl)-3a,4,5,9b-tetrahydro-
42.7; HRMS (m/z, ESI) calcd [C25H19N3O2Na]+ [M+Na]+ 416.1369, 1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3lc)
observed 416.1360.
Title compound was synthesized according to the general
procedure and obtain as white solid ( 76% ) m.p. 224 ℃ -
1
226 ℃; H-NMR (400 MHz, CDCl3): δ 7.29-7.14 (m, 8H), 6.95
5-benzyl-2-(4-chlorophenyl)-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c]quinolone-1,3(2H)-dione (3af)
(dd, J = 9.2, 2.4 Hz, 2H), 6.82 (td, J = 8.4, 3.1 Hz, 1H), 6.63 (q, J
= 4.5 Hz, 1H), 4.39 (t, J = 14.2 Hz, 1H), 4.20 (t, J = 14.2 Hz, 1H),
4.12-4.06 (m, 1H), 3.81 (s, 3H), 3.63 (t, J = 11.4 Hz, 1H), 3.52-
3.49 (m, 1H), 3.22-3.16 (m, 1H). 13C-NMR (100 MHz, CDCl3): δ
177.4, 175.4, 159.5,143.9, 137.4, 128.6, 127.5, 127.3, 124.5,
120.6, 120.5, 117.2, 116.9, 115.1, 114.8, 114.4, 55.7, 55.4, 49.5,
43.9, 42.4; HRMS (m/z, ESI) calcd [C25H21N2O3FNa]+ [M+Na]+
439.1428, observed 439.1425.
Title compound was synthesized according to the general
procedure and obtain as white solid (66%) m.p. 217 ℃ - 219 ℃;
1H-NMR (400 MHz, CDCl3): δ 7.51 (t, J = 5.6 Hz, 1H), 7.42-7.39
(m, 2H), 7.27-7.21 (m, 7H), 7.15-7.10 (m, 1H), 6.88 (t, J = 6.2 Hz,
1H), 6.74-6.71 (m, 1H), 4.45 (dd, J = 15.0, 4.6 Hz, 1H), 4.26-
4.15 (m, 2H), 3.69-3.64 (m, 1H), 3.54-3.52 (m, 1H), 3.24 (dt, J =
8.2, 3.5 Hz, 1H). 13C-NMR (100 MHz, CDCl3): δ 177.2, 175.5,
147.5, 137.5, 134.2, 130.4,129.2, 128.6, 128.5, 127.5, 127.4,
119.8, 118.7, 111.4, 55.2, 48.9, 44.1, 42.3; HRMS (m/z, EI)
calcd [C24H19N2O2Cl] + [M]+ 402.1135, observed 402.1136.
8-chloro-5-(3-nitrobenzyl)-2-phenyl-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3ma)
Title compound was synthesized according to the general
1
procedure and obtain as brown oil (70% ); H-NMR (400 MHz,
2,5-dibenzyl-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]
quinoline-1,3(2H)-dione (3ag)
CDCl3): δ 8.07 (d, J = 7.2 Hz, 2H), 7.50-7.02(m, 9H), 6.48 (d, J =
8.0 Hz, 1H), 4.48 (d, J = 15.6 Hz, 1H), 4.27 (d, J = 15.2 Hz, 1H),
4.13 (d, J = 9.2 Hz, 1H), 3.67 (d, J = 12.0 Hz, 1H), 3.55 (s, 1H),
3.25 (d, J = 11.6 Hz, 1H). 13C-NMR (100 MHz, CDCl3): δ 176.9,
174.8, 148.5, 147.4, 145.3, 139.6, 135.0, 133.2, 131.6, 130.4,
0130.2, 129.7, 129.2, 129.0, 128.8, 128.5, 128.3, 126.2, 125.4,
122.7, 122.1, 120.7, 114.5, 55.0, 49.2, 43.6, 42.0.; HRMS (m/z,
ESI) calcd [C24H18N3O4ClNa]+ [M+Na]+ 470.0878, observed
470.0882.
Title compound was synthesized according to the general
1
procedure and obtain as brown oil (81% ); H-NMR (400 MHz,
CDCl3): δ 7.48 (d, J = 7.6 Hz, 1H), 7.31-7.21 (m, 8H), 7.12-7.07
(m, 3H), 6.86 (t, J = 7.6 Hz, 1H), 6.67 (d, J = 8.0 Hz, 1H), 4.66
(dd, J = 31.6, 14.4 Hz, 2H), 4.37 (d, J = 15.0 Hz, 1H), 4.18 (d, J
= 15.0 Hz, 1H), 4.02 (d, J = 8.8 Hz, 1H), 3.55-3.51 (m, 1H), 3.36-
3.33 (m, 1H), 3.13 (ddd, J = 11.6, 4.4, 1.6 Hz, 1H). 13C-NMR
(100 MHz, CDCl3): δ 177.9, 176.4, 147.4, 137.4, 135.5, 130.3,
128.59, 128.56, 128.53, 128.4, 127.8, 127.3, 127.1, 119.6, 118.8,
113.4, 55.4, 48.5, 43.8, 42.7, 42.2; HRMS (m/z, EI) calcd
[C25H22N2O2] + [M]+ 382.1681, observed 382.1689.
2-(5-(4-nitrobenzyl)-1,3-dioxo-1,3,3a,4,5,9b-hexahydro-2H-
pyrrolo[3,4-c] quinolin-2-yl) benzonitrile (3nf)
Title compound was synthesized according to the general
1
procedure and obtain as brown liquid ( 60% ); H-NMR (400
ethyl
4-(5-benzyl-1,3-dioxo-1,3,3a,4,5,9b-hexahydro-2H-
MHz, CDCl3): δ 8.07-8.04 (m, 2H), 8.15 (d, J = 8.00 Hz, 1H),
7.81-7.71 (m, 2H), 7.58-7.43 (m, 4H), 7.17-7.12 (m, 2H), 6.63
(dd, J = 8.00, 16.00 Hz, 1H), 4.59 (d, J = 16.00 Hz, 1H), 4.46-
4.27 (m, 1H), 3.73 (d, J = 12.00 Hz, 2H), 3.37 (d, J = 8.00 Hz,
1H).13C-NMR (100 MHz, CDCl3): δ 176.2,174.6, 147.2, 146.5,
145.4, 133.7, 133.6, 130.6, 130.4, 129.7, 129.4, 128.87, 128.81,
128.5, 128.0, 123.8, 113.4, 112.1, 55.1, 44.1, 42.5, 41.7.; HRMS
(m/z, ESI) calcd [C25H18N4O4Na]+ [M+Na]+ 461.1220, observed
461.1217
pyrrolo[3,4-c]quinolin-2-yl) benzoate (3ah)
Title compound was synthesized according to the general
1
procedure and obtain as brown oil (69%); H-NMR (400 MHz,
DMSO-d6): δ 7.51-7.49 (m, 1H), 7.44-7.32 (m, 3H), 7.35-7.17 (m,
3H), 6.85 (ddd, J = 10.4, 4.0, 3.2 Hz, 1H), 6.74 (dd, J = 8.4, 3.2
Hz, 1H), 5.83-5.76 (m, 1H), 5.05-4.97 (m, 2H), 4.12 (q, J = 4.8
Hz 1H), 3.65 (dq, J = 11.6, 2.8 Hz, 1H), 3.53-3.50 (m, 1H), 3.31-
3.25 (m, 1H), 3.19-3.05 (m, 2H), 2.13-2.04 (m, 2H), 1.72-1.63 (m,
3H). 13C-NMR (100 MHz, DMSO-d6): δ 178.2, 176.4, 165.6,
148.1, 138.9, 136.9, 130.9, 130.4, 130.1, 128.9, 128.5, 127.7,
127.5, 127.4, 120.3, 119.4, 113.6, 61.5, 54.9, 49.9, 44.5, 42.7,
14.6; HRMS (m/z, EI) calcd [C27H24N2O4]+ [M]+ 440.1736,
observed 440.1742.
2-benzyl-5-(4-nitrobenzyl)-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c] quinoline-1,3(2H)-dione (3ng)
Title compound was synthesized according to the general
procedure and obtain as brown oil ( 69% ); 1H-NMR (400 MHz,
CDCl3): δ 8.00 (dt, J = 6.5, 2.1 Hz, 2H), 7.50 (d, J = 7.6 Hz, 1H),
7

FULL PAPER
7.30-7.24 (m, 5H), 7.15-7.06 (m, 3H), 6.91-6.88 (m, 1H), 6.47 (d,
J = 8.4 Hz, 1H), 4.74 (dd, J = 14.0, 2.4 Hz, 1H), 4.62 (dd, J =
14.0, 2.4 Hz, 1H), 4.44 (d, J = 16.0 Hz, 1H), 4.21 (d, J = 16.0 Hz,
1H), 4.07 (d, J = 9.2 Hz, 1H), 3.56 (d, J = 11.6 Hz, 1H), 3.41-
3.38 (m, 1H), 3.22-3.14 (m, 1H). 13C-NMR (100 MHz, CDCl3): δ
178.0, 176.3, 147.1, 146.7, 145.3, 135.5, 130.6, 128.6, 128.5,
128.0, 127.8, 123.8, 120.4, 119.2, 113.2, 55.1, 49.3, 43.8, 42.9,
42.2.; HRMS (m/z, EI) calcd [C25H21N3O4]+ [M]+ 427.1532,
observed 427.1534.
129.0, 128.9, 128.7, 128.6, 128.5, 127.5, 127.4, 127.3, 126.3,
111.1, 106.7, 104.4, 103.6, 100.3, 55.5, 55.1, 48.8, 43.8, 41.7.;
HRMS (m/z, ESI) calcd [C25H22N2O3]+ [M+H]+ 398.1630,
observed 398.1640
2,5-dibenzyl-8-fluoro-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]
quinoline-1,3(2H)-dione (3lg)
Title compound was synthesized according to the general
procedure and obtain as yellow liquid (78%); 1H-NMR (400 MHz,
CDCl3): δ 7.33 (dd, J = 4.00, 8.00 Hz, 1H), 7.29-7.21 (m, 8H),
7.06-7.04 (m, 2H), 4.75-4.62 (m, 2H), 4.33 (dd, J = 8.00, 14.00
Hz, 1H), 4.14 (dd, J = 8.00, 16.00 Hz, 1H), 3.96 (d, J = 8.00 Hz,
1H), 3.51 (dd, J = 4.00, 10.00 Hz, 1H), 3.28-3.35 (m, 1H), 3.06-
3.12 (m, 1H).). 13C-NMR (100 MHz, CDCl3): δ 177.7, 175.8,
157.7, 155.3, 143.9, 137.2, 135.4, 128.6, 128.5, 127.9, 127.3,
2-(4-methoxyphenyl)-5-(4-nitrobenzyl)-3a,4,5,9b-tetrahydro-
1H-pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3nc)
Title compound was synthesized according to the general
procedure and obtain as brown oil ( 75% ); 1H-NMR (400 MHz,
CDCl3): δ 8.14 (d, J = 8.00 Hz, 2H), 7.56 (d, J = 8.00 Hz, 1H),
7.41 (d, J = 8.00 Hz, 2H), 7.10-7.19 (m, 4H), 6.98 (d, J = 8.00 Hz, 127.2, 120.58, 120.51, 117.0, 116.8, 114.9, 114.7, 114.4, 114.3,
1H), 6.94-6.87 (m, 1H), 6.57 (d, J = 8.00 Hz, 1H), 4.56 (d, J =
16.00 Hz, 1H), 4.34 (d, J = 16.00 Hz, 1H), 4.21 (d, J = 8.00 Hz,
1H), 3.83 (s, 3H), 3.70-3.72 (m, 1H), 3.57-3.59 (m, 1H), 3.32 (dd,
J = 4.00, 12.00 Hz, 1H). 13C-NMR (100 MHz, CDCl3): δ 177.6,
175.7, 159.5, 147.2, 146.6, 145.6, 130.7, 129.1, 128.6,127.8,
127.3, 124.4, 123.9, 120.4, 119.1, 114.4, 114.3,113.2, 55.4, 55.1,
49.5, 43.9, 42.2. HRMS (EI) calcd. for C25H21N3O5 [M]+:
443.1481, found for 443.1473.
55.8, 49.0, 43.6, 42.9, 42.2.
HRMS (m/z, ESI) calcd
[C25H21FN2O2] + [M+Na] + 423.1479, observed 423.1487
2-(4-chlorophenyl)-5-(4-nitrobenzyl)-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c]quinoline-1,3(2H)-dione (3ne)
Title compound was synthesized according to the general
procedure and obtain as yellow oil ( 65% ); 1H-NMR (400 MHz,
CDCl3): δ 8.13 (d, J = 8.00 Hz, 2H), 7.55 (d, J = 8.00 Hz, 1H),
7.39 (d, J = 12.00 Hz, 2H), 7.28-7.24 (m, 2H), 7.15-7.10 (m, 3H),
6.92 (t, J = 8.00 Hz, 1H), 6.57 (d, J = 8.00 Hz, 1H), 4.56 (d, J =
16.00 Hz, 1H), 4.35 (d, J = 16.00 Hz, 1H), 4.23 (d, J = 12.00 Hz,
1H), 3.70 (dd, J = 0.00, 10.00 Hz, 1H), 3.60-3.58 (m, 1H), 3.29
(dd, J = -52.00, 40.00 Hz, 1H). 177.3, 175.5, 147.4, 146.6, 145.5,
130.8, 128.8, 128.1, 128.0, 127.8, 124.0, 120.6, 118.9, 116.4,
116.2, 113.4, 55.2, 49.4, 44.0, 42.3. HRMS (EI) calcd. for
C24H18N3O4Cl [M]+: 447.0986, found for 447.0994.
ethyl-4-(5-(4-nitrobenzyl)-1,3-dioxo-1,3,3a,4,5,9b-hexahydro-
2H-pyrrolo[3,4-c]quinolin-2-yl)benzoate (3nh)
Title compound was synthesized according to the general
1
procedure and obtain brown oil ( 67% ) ; H-NMR (400 MHz,
CDCl3): δ 8.16-8.08 (m, 4H), 7.56 (t, J = 6.6 Hz, 1H), 7.42-7.35
(m, 4H), 7.15-7.08 (m, 1H), 6.95-6.89 (m, 1H), 6.58 (t, J = 7.4 Hz,
1H), 4.56 (dd, J = 16.4, 6.6 Hz, 1H), 4.40-4.31 (m, 4H), 4.26-
4.22 (m, 1H), 3.72-3.58 (m, 1H), 3.33-3.29 (m, 1H), 1.39 (t, J =
7.2 Hz, 3H). 13C-NMR (100 MHz, CDCl3): δ 176.9, 175.1, 147.2,
146.6, 145.4, 135.6, 130.7, 130.3, 129.1, 128.7, 127.8, 125.8,
123.9, 120.5, 118.7, 113.3, 61.2, 555.0, 49.2, 44.0, 42.2, 14.2.
HRMS (m/z, ESI) calcd [C27H23N3O6Na]+ [M+Na]+ 508.1479,
observed 508.1475.
5-benzyl-8-chloro-2-phenyl-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c] quinoline-1,3(2H)-dione (3pa)
Title compound was synthesized according to the general
procedure and obtain as brown liquid (68% ); 1H-NMR (400 MHz,
CDCl3): δ 7.51-7.35 (m, 5H), 7.29-7.19 (m, 6H), 7.07-7.03 (m,
1H), 6.66-6.59 (m, 1H), 4.41 (dd, J = 8.00, 16.00 Hz, 1H), 4.27
(dd, J = 12.00, 16.00 Hz, 1H), 4.15-4.06 (m, 1H), 3.70-3.53 (m,
2H), 3.29-3.23 (m, 1H). 13C-NMR (100 MHz, CDCl3): δ 177.0,
175.1, 146.0, 137.1, 130.0, 129.9, 129.1, 129.0, 128.6, 128.4,
127.4, 127.2, 126.2, 124.5, 120.2, 114.6, 55.5, 48.9, 43.8, 42.1.
HRMS (EI) calcd. for C24H19N2O2Cl [M]+: 402.1135, found for
402.1136.
2-(2,4-dichlorophenyl)-5-(4-nitrobenzyl)-3a,4,5,9b-
tetrahydro-1H-pyrrolo[3,4-c] quinoline-1,3(2H)-dione (3nj)
Title compound was synthesized according to the general
procedure and obtain as brown oil ( 46% ); 1H-NMR (400 MHz,
CDCl3): δ 8.14 (td, J = 6.2, 2.1 Hz, 2H), 7.56-7.30 (m, 6H), 7.21-
7.08 (m, 1H), 6.94-6.87 (m, 1H), 6.57 (dd, J = 28.6, 8.6 Hz, 1H),
4.55 (dd, J = 16.4, 8.8 Hz, 1H), 4.40-4.25 (m, 2H), 3.75-3.60 (m,
2H), 3.38-3.31 (1H). 13C-NMR (100 MHz, CDCl3): δ 176.5, 174.7,
147.3, 146.6, 146.4, 145.6, 136.4, 130.8, 130.6, 130.5, 128.9,
128.3, 128.0, 124.0, 120.6, 120.2, 117.8, 113.4, 55.6, 49.2, 44.0,
42.6HRMS. HRMS (m/z, EI) calcd [C24H17N3O4Cl2]+ [M]+
481.0596, observed 481.0604.
2,5-dibenzyl-8-choro-3a,4,5,9b-tetrahydro-1H-pyrrolo[3,4-c]
quinoline-1,3(2H)-dione (3pg)
Title compound was synthesized according to the general
procedure and obtain as yellow brown oil (76%); H-NMR (400
MHz, CDCl3): δ 7.41-7.18 (m, 11H), 7.00 (s, 1H), 6.65-6.51 (m,
1H), 4.67-4.54 (m, 4H), 4.21 (dd, J = 16.00, 60.00 Hz, 1H), 3.92-
3.68 (m, 1H), 3.45 (dd, J = 12.00, 24.00 Hz, 1H), 3.03 (dd, J =
12.00, 44.00 Hz, 1H). 13C-NMR (100 MHz, CDCl3): δ 177.6,
175.8, 146.0, 135.4, 130.0, 129.8, 128.6, 128.3, 127.9, 127.8,
127.4, 127.2, 124.4, 114.7, 55.5, 48.5, 43.5, 42.9, 41.9. HRMS
(EI) calcd. for C25H21N2O2Cl [M]+; 416.1292, found for 416.1300.
1
5-benzyl-7-methoxy-2-phenyl-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c] quinoline-1,3(2H)-dione (3oa)
Title compound was synthesized according to the general
1
procedure and obtain as brown oil (49%); H-NMR (400 MHz,
CDCl3): δ 7.46-7.35 (m, 3H), 7.31-7.17 (m, 8H), 6.55-6.40 (m,
1H), 6.36-6.21 (m, 1H), 4.50-4.33 (m, 1H), 4.28-4.20 (m, 1H),
3.69 (s, 3H), 3.53-3.46 (m, 1H), 4.00-3.90 (m, 1H), 3.26 (dd, J =
4.00, 12.00 Hz, 1H), 3.07 (dd, J = 4.00, 12.00 Hz, 1H). 13C-NMR
(100 MHz, CDCl3): δ 177., 176.1, 137.7, 137.6, 132.0, 131.2,
5-(3-nitrobenzyl-2-phenyl)-3a,4,5,9b-tetrahydro-1H-
pyrrolo[3,4-c] quinoline-1,3(2H)-dione (3qa)
8

FULL PAPER
Title compound was synthesized according to the general
procedure and obtain as brown oil (61%); H-NMR (400 MHz,
1H-NMR (400 MHz, CDCl3): δ 7.27-7.21 (m, 2H), 6.68 (t, J
= 8.8 Hz, 3H), 3.14-3.09 (2H), 2.99-2.93 (m, 3H), 2.12-2.03 (m,
1H), 0.94 (td, J = 12.3, 6.6 Hz, 6H). 13C-NMR (100 MHz, CDCl3):
δ 149.5, 129.0, 115.5, 11.7, 60.8, 39.3, 27.3, 20.4.
1
CDCl3): δ 8.05-8.01 (m, 2H), 7.51-7.49 (m, 2H), 7.40-7.27 (m,
6H), 7.07-7.03 (m, 1H), 6.86-6.82 (m, 1H), 6.61-6.52 (m, 1H),
4.48 (d, J = 16.00 Hz, 1H), 4.25-4.14 (m, 2H), 3.64 (d, J = 12.00
Hz, 1H), 3.52-3.43 (m, 1H), 3.24-3.20 (m, 1H). 13C-NMR (100
MHz, CDCl3): δ 177.3, 175.5, 146.7, 140.1, 133.3, 130.7, 129.8,
129.6, 129.1, 128.6, 126.2, 122.5, 122.3, 122.2, 120.5, 119.3,
119.2, 113.2, 112.3, 55.0, 49.3, 43.9, 42.2. HRMS (ESI) calcd.
for C24H19N3O4Na [M+Na]+; 436.1267, found for 436.1277.
N-benzyl-N-ethylaniline (4)
1H-NMR (400 MHz, CDCl3): δ 7.33-7.16 (m, 8H), 6.71 (m,
3H), 4.53 (s, 2H), 3.48 (q, J = 7.0 Hz, 2H), 1.21 (td, J = 7.1, 1.8
Hz, 3H). 13C-NMR (100 MHz, CDCl3): δ 148.4, 139.2, 129.1,
12.5, 126.7, 126.5, 115.9, 112.0, 53.8, 45.0, 12.0. HRMS (m/z,
ESI) calcd [C23H16N2O2] + [M+H] + 352.1212, observed 352.1011
5-phenyl-6a,7-dihydropyrrolo[3’,4’:4,5]pyrido[3,2,1-
jk]carbazole-4,6(3bH,5H)-dione (11) Title compound was
synthesized according to the general procedure and obtain as
white solid (45 %). H-NMR (400 MHz, CDCl3): δ 8.08-8.06 (m,
2H), 7.61-7.60 (m, 1H), 7.41-7.39 (m, 4H), 7.20-7.14 (m, 4H),
4.80 (d, J = 5.6 Hz, 2H), 4.57 (s, 1H). 13C-NMR (100 MHz,
CDCl3): δ 176.6, 174.6, 140.7, 132.6, 129.4, 128.9, 127.4, 126.3,
122.8, 120.8, 119.6, 109.9, 71.3, 49.2.
ACKNOWLEDGMENT
1
The authors gratefully acknowledge funding and support
from the Ministry of Science and Technology (Taiwan) (MOST
109-2113-M-037-013-);
Kaohsiung
Medical
University;
Kaohsiung Medical University Research Foundation (KMU-
M109004) and the Center for Research Resources and
Development of Kaohsiung Medical University for Mass and 400
MHz NMR analyses. G. Perumal, and H. Sathya special thanks
TEEP@AsiaPlus from the Ministry of Education (Taiwan) for
their support.
N-cyclohexyl-N-methylaniline (1b)
1H-NMR (400 MHz, CDCl3): δ 7.26-7.21 (m, 2H), 6.79 (d, J
= 8.0 Hz, 2H), 6.71-6.67 (m, 1H), 3.58 (tt, J = 11.4, 3.4 Hz, 1H),
2.79 (s, 3H), 1.87-1.67 (m, 5H), 1.51-1.31 (m, 4H), 1.15 (qt, J =
12.7, 3.5 Hz, 1H). 13C-NMR (100 MHz, CDCl3): δ 150.1, 129.0,
116.1, 113.1, 58.0, 31.1, 30.0, 26.1, 25.9.
Keywords: Visible light • photocatalyst • tetrahydroquinoline • N-
methyl carbazole
N-Methyl-N-undecylaniline (1e)
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Table of Contents
A metal free regioselective methodology has been developed for the synthesizing of various tetrahydroquinoline through
photocatalytic pathway in presence of visible light and air. The regioselectivity of the method was evidenced with diverse control
experiments.
11

Declaration of interests
☒ The authors declare that they have no known competing financial interests or personal relationships
that could have appeared to influence the work reported in this paper.
☐The authors declare the following financial interests/personal relationships which may be considered
as potential competing interests: