Indium(III) triflate-catalyzed reactions of AZA-michael adducts of chalcones with aromatic amines: Retro-michael addition versus quinoline formation

Article abstract of DOI:10.1021/acs.joc.7b03151

The indium(III) triflate-catalyzed reaction of aza-Michael adducts of chalcones with aromatic amines has been investigated. The Michael adducts derived from substituted anilines and chalcones underwent retro-Michael addition to give the original starting materials, whereas the adducts derived from 1-naphthylamines and chalcones afforded quinolines. A six-membered cyclic transition state has been proposed to explain the retro-Michael addition, while a Povarov mechanism has been put forward to explain the quinoline formation.

Full text of DOI:10.1021/acs.joc.7b03151

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Note
Indium(III) Triflate-Catalyzed Reactions of Aza-Michael Adducts of Chalcones
with Aromatic Amines: Retro-Michael Addition versus Quinoline Formation
Thangavel Selvi, and Sivan Velmathi
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 02 Mar 2018
Downloaded from http://pubs.acs.org on March 2, 2018
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Indium(III) Triflate-Catalyzed Reactions of Aza-Michael
Adducts of Chalcones with Aromatic Amines: Retro-Michael
Addition versus Quinoline Formation
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Thangavel Selvi and Sivan Velmathi*
Department of Chemistry, National Institute of Technology,
Tiruchirappalli-620 015, Tamil Nadu, India
*velmathis@nitt.edu
Tel.: +91-431-2503640 & Fax: +91-431-2500133
Abstract:
Ar3
In(OTf)3
(10 mol%)
In(OTf)3
(10 mol%)
H
N
Ar3
Ar2
Ar3
Ar1
Ar1NH2
+
Ar1
CH2Cl2, rt
CH2Cl2, rt
N
Ar2
Ar2
O
O
When Ar1 = substituted phenyl
When Ar1 = 1-naphthyl
The indium(III) triflate-catalyzed reaction of aza-Michael adducts of chalcones with
aromatic amines has been investigated. The Michael adducts derived from substituted anilines
and chalcones underwent retro-Michael addition to give the original starting materials, whereas
the adducts derived from 1-naphthylamines and chalcones afforded quinolines. A six-membered
cyclic transition state has been proposed to explain the retro-Michael addition, while a Povarov
mechanism has been put forward to explain the quinoline formation.
The quinoline structural motif is ubiquitous among bioactive natural products1 and
pharmaceutically important compounds including drugs.2 This fact has triggered the
development of several new methods for the synthesis of quinolines,3 in addition to traditional
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methods.4 Traditionally, quinolines were synthesized by reacting (1) aromatic amines with ,-
unsaturated carbonyl compounds (the Skraup-Doebner-Miller synthesis5), 1,3-diketones (the
Combes synthesis6) or -ketoesters (the Conrad-Limpach synthesis7), (2) imines derived from
aromatic amines and aldehydes with alkenes or alkynes (the Povarov reaction8) or (3) o-
aminobenzaldehydes with carbonyl compounds (the Friedlander synthesis9). Among them, the
Skraup-Doebner-Miller synthesis has attracted a great deal of attention owing to its simple, yet
complex mechanism.10
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The scope of the Skraup and Doebner-Miller synthesis is somewhat limited with respect
to the ,-unsaturated carbonyl compound used in the reaction.5 Apart from ,-unsaturated
aldehydes and methyl ketones, no other ,-unsaturated carbonyl compounds (such as
chalcones) could be employed in the synthesis and this surprising fact stimulated us to
investigate the reason behind it. As the direct quinoline synthesis from aromatic amines and
chalcones at the best stops at the aza-Michael adduct stage, we prepared the aza-Michael adducts
independently11 and subjected them to further cyclization. We found that the Michael adducts
derived from substituted anilines and chalcones underwent retro-Michael addition to give the
original starting materials, whereas the adducts derived from 1-naphthylamine and chalcones
afforded the expected quinoline derivatives in good yields. Further study gave new insights on
the mechanism of the transformations and herein the results are presented.
The formation of quinoline from aza-Michael adducts of aromatic amines with chalcones
is likely to take place via SEAr cyclization followed by dehydration and aromatization.5 As
Lewis acids are capable of promoting such dehydrative cyclizations, we selected the aza-Michael
adduct 1a as a model substrate and treated with various Lewis/Bronsted acids [10 mol% of
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In(OTf)3, Cu(OTf)2, Sc(OTf)3, Yb(OTf)3, Bi(OTf)3, Zn(OTf)2, InCl3, ZnCl2, AlCl3, FeCl3,
BF3OEt2 or TfOH] under different reaction conditions (CH2Cl2, 1,2-dichloroethane, THF, EtOH
at rt or under reflux) in order to identify optimal catalyst and reaction conditions for the
transformation (Scheme 1). Unfortunately, none of the Lewis/Bronsted acids is capable of
promoting the desired transformation of 1a into quinoline 4a. Instead, 1a underwent retro-
Michael addition to yield aniline (2a) and chalcone 3a with most of the Lewis acids (1a was
recovered with FeCl3, BF3OEt2 and TfOH). The best result for retro-Michael addition was
obtained when the reaction was carried out with In(OTf)3 in CH2Cl2 at rt for 2 h (the yield of
isolated chalcone was 95%). It is interesting to note that the retro-Michael addition is essentially
dehydroamination which is usually promoted by bases12 and in the present case, it is catalyzed by
a Lewis acid.
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Ph
In(OTf)3
(10 mol%)
PhNH2 2a
H
N
Ph
+
Ph
CH2Cl2
rt, 2 h
Ph
Ph
Ph
O
N
Ph
4a
1a
O
Not formed
3a, 95%
Scheme 1. Retro-Michael addition of 1a.
The retro-Michael addition was not specific to adduct 1a alone. Similar Michael adducts
1b-q derived from substituted anilines and chalcones also underwent retro-Michael addition with
In(OTf)3 to give the respective parent compounds 2 and 3 (Table 1). Obviously, the presence of
electron donating, electron withdrawing and halogen substituents on the phenyl rings of the
adducts 1b-p (entries 1-16) or the placement of a naphthyl ring as Ar2 as in 1q did not have any
influence on the reaction outcome (entry 17).
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Table 1. The scope of retro-Michael addition for various aza-Michael adducts
5
6
7
8
9
In(OTf)3
H
(10 mol%)
Ar2
Ar3
N
Ar3
Ar1NH2
+
Ar1
CH2Cl2
rt, 2-4 h
Ar2
O
O
2
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3
1
Entry Ar1, Ar2, Ar3
Time (h) Yield of 3 (%)a,b
1
2
Ph, Ph, Ph (1a)
4-MeC6H4, Ph, Ph (1b)
2
3
4
2
2.5
3
4
2
2
2
2.5
2
3
3
3
3a, 95
3a, 82
3a, 86
3a, 92
3a, 89
3b, 81
3c, 89
3d, 87
3e, 90
3e, 89
3e, 87
3e, 91
3f, 79
3g, 87
3h, 87
3i, 88
3j, 83
3
4
4-MeOC6H4, Ph, Ph (1c)
4-ClC6H4, Ph, Ph(1d)
5
6
4-O2NC6H4, Ph, Ph (1e)
Ph, 4-MeC6H4, Ph (1f)
7
8
Ph, 4-MeOC6H4, Ph (1g)
Ph, 4-BrC6H4, Ph (1h)
9
Ph, 4-ClC6H4, Ph (1i)
10
11
12
13
14
15
16
17
4-MeC6H4, 4-ClC6H4, Ph (1j)
4-MeOC6H4, 4-ClC6H4, Ph (1k)
4-ClC6H4, 4-ClC6H4, Ph(1l)
Ph, 4-(O2N)C6H4, Ph (1m)
Ph, 3,4-(MeO)2C6H3, Ph (1n)
Ph, 2,4-Cl2C6H3, Ph (1o)
Ph, 4-ClC6H4, 4-O2NC6H4 (1p)
Ph, 1-naphthyl, Ph (1q)
4
4
aIsolated yield; bThe yield of anilines 2 could not be calculated reliably
as we used silica gel for column chromatography.
In contrast to the above findings, the Michael adducts 5a-h derived from 1-
naphthylamines and chalcones afforded benzo-fused quinolines 6a-h under similar reaction
conditions (Table 2). The reaction tolerated the presence of different substituents on the chalcone
phenyl rings and also the replacement of a phenyl ring by a naphthyl ring in the chalcone unit
(entries 1-8).
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Table 2. Synthesis of benzo-fused quinolines from Michael adducts derived from 1-
naphthylamine and chalcones
7
8
9
Ar2
R
Ar1
O
In(OTf)3
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R
(10 mol%)
N
Ar2
N
Ar1
H
CH2Cl2
rt, 0.5-1 h
5
6
Entry Ar1, Ar2, R
Time (min) Yield of 6 (%)a
1
2
3
4
5
6
7
8
Ph, Ph, H (5a)
30
30
30
15
60
30
60
60
6a, 90
6b, 89
6c, 87
6d, 92
6e, 90
6f, 92
6g, 88
6h, 84
4-MeC6H4, Ph, H (5b)
4-MeOC6H4, Ph, H (5c)
4-ClC6H4, Ph, H (5d)
2,4-(MeO)2C6H3, Ph, H (5e)
4-ClC6H4, 4-O2NC6H4, H (5f)
1-Naphthyl, Ph, H (5g)
Ph, Ph, Br (5h)
aIsolated yield
Denmark and Venkatraman have reported that the aza-Michael adduct formed in the
Skraup-Doebner-Miller synthesis undergoes fragmentation to give an imine before undergoing
further changes. We conducted few control experiments in order to include or exclude the
involvement of imine intermediates in our transformations (Scheme 2). Accordingly, we
prepared imines 7 and 8 independently and reacted with acetophenone under similar reactions
conditions. The reaction between 7 and acetophenone gave aniline and chalcone 3a through the
Aza-Michael adduct 1a. On the other hand, the reaction between 8 and acetophenone gave
quinoline 6a readily.
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O
5
Ph
6
7
8
9
In(OTf)3
(10 mol%)
Ph
Ph
N
Ph
+
PhNH2
Ph
CH2Cl2
rt, 0.5 h
quant.
O
3a
2a
7
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O
Ph
Ph
N
In(OTf)3
(10 mol%)
N
Ph
Ph
CH2Cl2
rt, 0.5 h
quant.
8
6a
Scheme 2. Control experiments
Based on the above observations, we envisage that the aza-Michael adduct 1a probably
undergoes retro-Michael addition without the formation of the imine intermediate 7 (even if the
imine intermediate 7 is formed, it goes back to the aza-Michael adduct 1a immediately). We
propose a six-membered cyclic transition state13 A for the retro-Michael addition step as shown
in Scheme 3. In contrast, the aza-Michael adduct 5a undergoes fragmentation to give imine 8 and
acetophenone and the subsequent Povarov [4+2] cycloaddition between 8 and enol form of
acetophenone via transition state C leads to 6a after dehydration and aromatization. It may be
noted that the transition state C is energetically more favorable than a similar (unlikely)
transition state B that could be written for imine 7 and acetophenone enol due to partial bond
fixation in the naphthyl ring.14
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O
In(OTf)3
Ph
H
N
N
Ph

Ph
+
Ph
Ph
Ph
O
7
1a
In(OTf)3
Ph
(TfO)3In
HO
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OTf
In
TfO
TfO
O
Ph
B
N
Ph
NH
Ph
In(OTf)3
Ph
Unfavorable TS
OTf
In
Ph
Ph
Ph
N
Ph
+
Ph
OTf
H
PhNH2
H
OTf
O
O
2a
3a
A
Ph
O
In(OTf)3
N
Ph
Ph
N
Ph
H
O
+
5a
8
Ph
(TfO)3In
HO
HO Ph
6a
C
H2O
H2
N
Ph
In(OTf)3
Favorable TS
N
Ph
Scheme 3. Mechanisms for the retro-Michael addition and quinoline formation
In summary, the aza-Michael adducts derived from chalcones and aromatic amines
show distinct reactivity patterns depending on the nature of the aromatic amines employed. The
Michael adducts derived from substituted anilines and chalcones preferentially undergo retro-
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Michael addition via six-membered cyclic transition state rather than Povarov reaction. On the
other hand, the adducts derived from 1-naphthylamines and chalcones prefer Povarov pathway
owing to partial bond fixation in the naphthyl ring to afford quinolines.
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EXPERIMENTAL SECTION
General remarks: Melting points were determined by the open capillary tube method and are
1
uncorrected. The H and 13C NMR spectra were recorded on a Bruker 500 MHz NMR
spectrometer. High resolution mass spectra were recorded on Exactive Plus EMR Orbitrap mass
spectrometer. Low resolution mass spectra was recorded on Thermo Fisher Q-trap mass
spectrometer. Elemental analyses was performed on a CHN analyzer. Thin layer chromatography
(TLC) was performed on pre-coated alumina sheets and detected under UV light. Silica gel (100-
200 mesh) was used for column chromatography.
General procedure for the retro-Michael addition/synthesis of quinolines 6: To a solution of
aza-Michal adduct (1.0 mmol) in dichloromethane (5 mL) was added indium(III) triflate (56 mg,
0.1 mmol) and stirred at room temperature. After the reaction was complete, the reaction mixture
was mixed with water and the organic layer was separated. The layer was washed with water and
dried (anhydrous Na2SO4), and the solvent was removed under reduced pressure. The crude
product was purified by column chromatography using hexane-ethylacetate (95:5) as the eluent
to afford chalcones 3 (and also anilines 2) or quinolines 6.
(E)-1,3-Diphenylprop-2-en-1-one (3a): White solid; M.p.: 55-57 C (lit.15 56-57 C); Yield:
198 mg, 95% (Table 1, entry 1); 170 mg, 82% (Table 1, entry 2); 179 mg, 86% (Table 1, entry
1
3); 191 mg, 92%, (Table 1, entry 4); 185 mg, 89%, (Table 1, entry 5); H NMR (500 MHz,
CDCl3):  7.41-7.40 (m, 3H), 7.52-7.48 (m, 2H), 7.59-7.55 (m, 2H), 7.65-7.63 (m, 2H), 7.81 (d,
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J = 15.5 Hz, 1H), 8.02 (d, J = 7.5 Hz, 2 H) ppm; 13C NMR (125 MHz, CDCl3):  122.1, 128.49,
5
6
128.54, 128.7, 129.0, 130.6, 132.8, 134.9, 138.2, 144.9, 190.6 ppm.
7
8
9
(E)-1-Phenyl-3-p-tolylprop-2-en-1-one (3b)15: Yellow solid; M.p.: 94-96 C; Yield: 180 mg,
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1
81%; H NMR (500 MHz, CDCl3):  2.40 (s, 3H), 7.23 (d, J = 7.5 Hz, 2H), 7.60-7.48 (m, 6H),
13
7.80 (d, J = 16.0 Hz, 1H), 8.02 (d, J = 7.5 Hz, 2H) ppm; C NMR (125 MHz, CDCl3):  21.6,
121.1, 128.50, 128.51, 128.6, 129.7, 132.2, 132.7, 138.4, 141.1, 145.0, 190.7 ppm.
(E)-3-(4-Methoxyphenyl)-1-phenylprop-2-en-1-one (3c): Yellow solid; M.p.: 118-120 C
(lit.15,16 73-75 C); Yield: 212 mg, 89%; H NMR (500 MHz, CDCl3):  3.85 (s, 3H), 6.93 (d, J ꞊
1
8.5 Hz, 2H), 7.41 (d, J ꞊ 15.5 Hz, 1H), 7.51-7.48 (m, 3H), 7.61-7.55 (m, 2H), 7.79 (d, J = 15.5
13
Hz, 1H), 8.01 (d, J = 7.5 Hz, 2H) ppm; C NMR (125 MHz, CDCl3):  55.4, 114.5, 119.8,
127.6, 128.4, 128.6, 130.3, 132.6, 138.5, 144.7, 161.7, 190.6 ppm.
(E)-3-(4-Bromophenyl)-1-phenylprop-2-en-1-one (3d)16: Yellow powder; M.p.: 117-119 C;
Yield: 249 mg, 87%; 1H NMR (500 MHz, CDCl3):  7.49-7.42 (m, 4H), 7.64 (d, J = 8.0 Hz, 4H),
7.81 (d, J = 15.5 Hz, 1H), 7.89 (d, J = 8.5 Hz, 2H) ppm; 13C NMR (125 MHz, CDCl3):  121.5,
127.9, 128.5, 129.0, 130.0, 130.8, 132.0, 134.7, 137.0, 145.4, 189.4 ppm.
(E)-3-(4-Chlorophenyl)-1-phenylprop-2-en-1-one (3e)16: Pale yellow solid; M.p.: 113-115 C
(lit.16 111-113 C); Yield: 218 mg, 90% (Table 1, entry 9); 215 mg, 89% (Table 1, entry 10);
1
210 mg, 87% (Table 1, entry 11); 220 mg, 91%, (Table 1, entry 12); H NMR (500 MHz,
CDCl3): δ 7.38 (d, J ꞊ 8.5 Hz, 2H), 7.51-7.48 (m, 3H), 7.60-7.55 (m, 3H), 7.75 (d, J ꞊ 16.0 Hz,
13
1H), 8.01 (d, J ꞊ 7.5 Hz, 2H) ppm; C NMR (125 MHz, CDCl3): δ 122.5, 128.5, 128.7, 129.3,
129.6, 133.0, 133.4, 136.4, 138.1, 143.3, 190.2 ppm.
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(E)-3-(4-Nitrophenyl)-1-phenylprop-2-en-1-one (3f)16: Yellow solid; M.p.: 164-166 C; Yield:
200 mg, 79%; 1H NMR (500 MHz, CDCl3):  7.66-7.46 (m, 6H), 7.84 (d, J = 16.0 Hz, 1H), 8.14
(d, J = 8.0 Hz, 2H), 8.35 (d, J = 8.0 Hz, 2H) ppm; 13C NMR (125 MHz, CDCl3):  121.3, 123.9,
128.7, 129.1, 129.4, 131.3, 134.3, 143.1, 146.8, 150.1, 189.0 ppm.
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(E)-3-(3,4-Dimethoxyphenyl)-1-phenylprop-2-en-1-one (3g)16,17: Yellow solid; M.p.: 88-90
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C; Yield: 233 mg, 87%; H NMR (500 MHz, CDCl3):  3.92 (s, 3H), 3.95 (s, 3H), 6.90 d, J =
8.0 Hz, 1H), 7.16 (s, 1H), 7.23 (d, J = 9.5 Hz, 1H), 7.39 (d, J = 15.5 Hz, 1H), 7.50 (t, J = 7.5 Hz,
2H), 7.57 (t, J = 7.5 Hz, 1H), 7.76 (d, J = 15.5 Hz, 1H), 8.01 (d, J = 7.5 Hz, 2H) ppm; 13C NMR
(125 MHz, CDCl3):  55.99, 56.01, 110.2, 111.2, 120.1, 123.2, 127.9, 128.4, 128.6, 132.6, 138.5,
145.0, 149.3, 151.5, 190.6 ppm.
(E)-3-(2,4-Dichlorophenyl)-1-phenylprop-2-en-1-one (3h)18: Yellow solid; M.p.: 78-80 C;
Yield: 240 mg, 87%; 1H NMR (500 MHz, CDCl3): δ 7.28 (d, J = 5.5 Hz, 1H), 7.59-7.45 (m, 5H),
7.67 (d, J = 7.0 Hz, 1H), 8.00 (d, J = 6.5 Hz, 2H), 8.09 (d, J = 15.5 Hz, 1H) ppm; 13C NMR (125
MHz, CDCl3): δ 125.0, 127.6, 128.5, 128.6, 128.7, 130.1, 131.9, 133.1, 136.1, 136.5, 137.8,
139.3, 190.0 ppm.
(E)-3-(4-Chlorophenyl)-1-(4-nitrophenyl)prop-2-en-1-one (3i)19: Light yellow solid;
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M.p.:150-152 C; Yield: 252 mg, 88%; H NMR (500 MHz, CDCl3):  7.47-7.41 (m, 3H), 7.59
(d, J = 8.0 Hz, 2H), 7.79 (d, J = 16.0 Hz, 1H), 8.14 (d, J = 8.5 Hz, 2H), 8.35 (d, J = 8.5 Hz, 2H)
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ppm; C NMR (125 MHz, CDCl3):  121.7, 123.9, 129.4, 129.5, 129.8, 132.8, 137.2, 142.8,
145.3, 150.2, 188.7 ppm.
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(E)-3-(Naphthalen-4-yl)-1-phenylprop-2-en-1-one (3j)16: Yellow solid; M.p.: 61-63 C; Yield:
214 mg, 83%; 1H NMR (500 MHz, CDCl3):  7.65-7.51 (m, 7H), 7.94-7.89 (m, 3H), 8.08 (d, J =
13
8.0 Hz, 2H), 8.26 (d, J = 8.0 Hz, 1H), 8.67 (d, J = 15.5 Hz, 1H) ppm; C NMR (125 MHz,
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CDCl3):  123.5, 124.8, 125.1, 125.5, 126.3, 127.0, 128.6, 128.7, 128.8, 130.8, 131.8, 132.4,
132.9, 133.8, 138.2, 141.8, 190.4 ppm.
2,4-Diphenylbenzo[h]quinoline (6a): White solid; M.p.: 163-165 C; (lit.20 163-165 C);Yield:
298 mg, 90%; 1H NMR (500 MHz, CDCl3):  7.60-7.47 (m, 8H), 7.81-7.70 (m, 4H), 7.90 (d, J =
8.0 Hz, 1H), 7.97 (s, 1H), 8.38 (d, J = 7.5 Hz, 2H), 9.58 (d, J = 8.5 Hz, 1H) ppm; 13C NMR (125
MHz, CDCl3):  119.5, 122.9, 123.4, 125.2, 126.9, 127.3, 127.5, 127.6, 128.25, 128.31, 128.6,
128.8, 129.3, 129.7, 132.0, 133.6, 138.9, 139.7, 146.8, 149.1, 154.9 ppm.; HRMS (ESI-ion trap)
m/z: [M + H]+ Calcd for C25H18N 332.1434; found: 332.1434.
4-Phenyl-2-p-tolylbenzo[h]quinoline (6b): White semisolid; M.p.: 70-72 C; Yield: 307 mg,
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89%; H NMR (500 MHz, CDCl3):  2.50 (s, 3H), 7.36 (d, J = 8.0 Hz, 2H), 7.58-7.52 (m, 5H),
7.79-7.69 (m, 4H), 7.89 (d, J = 7.5 Hz, 1H), 7.93 (s, 1H), 8.28 (d, J = 8.0 Hz, 2H), 9.58 (d, J =
8.5 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3):  21.4, 119.3, 123.0, 123.2, 125.2, 126.8, 127.1,
127.4, 127.6, 128.2, 128.3, 128.6, 129.6, 129.7, 132.1, 133.6, 137.0, 138.9, 139.3, 146.7, 149.0,
154.9 ppm.; HRMS (ESI-ion trap) m/z: [M + H]+ Calcd for C26H20N 346.1590; found: 346.1590.
2-(4-Methoxyphenyl)-4-phenylbenzo[h]quinoline (6c): Yellow solid; M.p.: 167-169 C; Yield:
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314 mg, 87%; H NMR (500 MHz, CDCl3):  3.87 (s, 3H), 7.05 (d, J = 8.5 Hz, 2H), 7.55-7.49
(m, 5H), 7.76-7.66 (m, 4H), 7.86 (d, J = 11.5 Hz, 2H), 8.32 (d, J = 8.5 Hz, 2H), 9.55 (d, J = 8.0
Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3):  55.4, 114.2, 118.9, 122.95, 122.97, 125.2, 126.8,
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126.9, 127.6, 128.2, 128.3, 128.6, 128.8, 129.7, 132.0, 132.4, 133.7, 139.0, 146.7, 149.0, 154.9,
160.8 ppm.; HRMS (ESI-ion trap) m/z: [M + H]+ Calcd for C26H20NO 362.1539; found:
362.1539.
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2-(4-Chlorophenyl)-4-phenylbenzo[h]quinoline (6d): White crystalline solid; M.p.: 173-175
C; Yield: 336 mg, 92%; 1H NMR (500 MHz, CDCl3):  7.58-7.52 (m, 7H), 7.80-7.71 (m, 4H),
7.90 (d, J = 9.5 Hz, 2H), 8.32 (d, J = 8.5 Hz, 2H), 9.55 (d, J = 8.5 Hz, 1H) ppm; 13C NMR (125
MHz, CDCl3):  119.1, 122.9, 123.5, 125.1, 127.0, 127.6, 127.7, 128.38, 128.41, 128.65, 128.71,
129.0, 129.7, 131.9, 133.7, 135.4, 138.2, 138.7, 146.8, 149.3, 153.6 ppm.; HRMS (ESI-ion trap)
m/z: [M + H]+ Calcd for C25H17ClN 366.1044; found: 366.1044.
2-(3,4-Dimethoxyphenyl)-4-phenylbenzo[h]quinoline (6e): Semi solid; Yield: 352 mg, 90%;
1H NMR (500 MHz, CDCl3):  3.96 (s, 3H), 3.98 (s, 3H), 6.96 (d, J = 8.0 Hz, 1H), 7.03 (d, J =
8.0 Hz, 1H), 7.47-7.42 (m, 2H), 7.75-7.67 (m, 2H), 7.82-7.79 (m, 3H), 7.91-7.89 (m, 2H), 8.04
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(s, 1H), 8.09 (d, J = 8.5 Hz, 1H), 8.30 (d, J = 9.0 Hz, 1H), 9.48 (d, J = 8.0 Hz, 1H) ppm; C
NMR (125 MHz, CDCl3):  56.0, 56.2, 109.0, 110.4, 110.5, 111.1, 119.6, 120.0, 121.3, 123.9,
125.0, 126.7, 126.8, 126.9, 127.7, 127.9, 129.3, 132.1, 132.9, 133.6, 144.5, 145.9, 149.7, 150.3,
154.6 ppm.; HRMS (ESI-ion trap) m/z: [M + H]+ Calcd for C27H22NO2 392.1645; found:
392.1646.
2-(4-Chlorophenyl)-4-(4-nitrophenyl)benzo[h]quinoline (6f): Semi solid; Yield: 377 mg,
92%; 1H NMR (500 MHz, CDCl3):  7.59-7.52 (m, 4H), 7.83-7.74 (m, 4H), 7.93 (d, J = 8.0 Hz,
1H), 7.97 (s, 1H), 8.41 (d, J = 8.0 Hz, 2H), 8.54 (d, J = 8.5 Hz, 2H), 9.53 (d, J = 8.0 Hz, 1H)
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ppm; C NMR (125 MHz, CDCl3):  119.5, 122.3, 123.9, 124.1, 125.1, 127.5, 127.9, 128.2,
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128.77, 128.83, 129.0, 130.9, 131.8, 133.7, 134.9, 136.7, 145.4, 147.1, 148.4, 152.2 ppm.;
HRMS (ESI-ion trap) m/z: [M + H]+ Calcd for C25H1635ClN2O2 411.0895; found: 411.0896.
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2-(Naphthalen-1-yl)-4-phenylbenzo[h]quinoline (6g): Colourless liquid; Yield: 335 mg, 88%;
1H NMR (500 MHz, CDCl3):  7.65-7.52 (m, 7H), 7.77-7.71 (m, 3H), 7.89-7.80 (m, 4H), 8.05-
7.95 (m, 2H), 8.50 (d, J = 7.5 Hz, 1H), 8.71 (d, J = 8.0 Hz, 1H), 9.64 (d, J = 8.5 Hz, 1H) ppm;
13C NMR (125 MHz, CDCl3):  110.8, 122.4, 122.9, 124.0, 125.0, 125.4, 125.9, 126.2, 126.46,
126.52, 126.6, 127.1, 127.6, 127.9, 128.3, 128.6, 128.7, 129.0, 129.2, 129.8, 130.7, 131.3, 131.9,
134.1, 137.8, 147.6, 157.3 ppm.; HRMS (ESI-ion trap) m/z: [M + H]+ Calcd for C29H20N
382.1590; found: 382.1593.
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6-Bromo-2,4-diphenylbenzo[h]quinoline (6h): Yellow semisolid; Yield: 344 mg, 84%; H
NMR (500 MHz, CDCl3):  7.47 (d, J = 6.5 Hz, 2H), 7.52 (d, J = 9.0 Hz, 1H), 7.71-7.62 (m,
4H), 7.79-7.76 (m, 1H), 7.91-7.84 (m, 5H), 8.34 (d, J = 8.0 Hz, 1H), 8.71 (d, J = 8.0 Hz, 1H),
9.64 (d, J = 8.5 Hz, 1H) ppm; 13C NMR (125 MHz, CDCl3):  122.6, 123.8, 124.0, 125.5, 125.7,
127.3, 127.5, 127.6, 127.8, 128.0, 128.5, 128.7, 128.9, 129.5, 130.5, 133.0, 133.6, 135.9, 144.7,
145.1, 145.8 ppm. MS (ESI-ion trap) m/z: [M + Na]+ Calcd for C25H1881BrNaN 434.04; found:
434.17: C 73.18, H 3.93, N 3.41; found: C 73.30, H 4.05, N 3.53.
ACKNOWLEDGMENTS
T.S. thanks Science and Engineering Research Board (SERB), India for a National Post-Doctoral
Fellowship (Project No.: PDF/2015/000012/CS). The authors thank the Director, National
Institute of Technology Tiruchirappalli for providing infrastructure and instrumentation facilities.
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Supporting Information.
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1H and C NMR spectra of products. This material is available free of charge via the Internet at
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http://pubs.acs.org.
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