Electrophilic Cyclization of 2-Aminophenylprop-1-yn-3-ols into 3-Iodo-6-(aryldiazenyl)quinolines by Using a One-Pot Azo-Coupling and Iodocyclization Sequence

Article abstract of DOI:10.1002/ejoc.201800248

6-(Aryldiazenyl)-3-iodoquinolines were prepared from readily available 2-aminoaryl propargyl alcohols, aryldiazonium salts, and molecular iodine. This three-component one-pot process proceeded through sequential azo-coupling, regioselective iodocyclizatio

Full text of DOI:10.1002/ejoc.201800248

A Journal of
Accepted Article
Title: Electrophilic cyclization of 2-Aminophenylprop-1-yn-3-ols to 3-
Iodo-6-(aryldiazenyl)quinolines in a one-pot, Azo-coupling and
Iodo-cyclization sequence
Authors: SRINIVASARAO YARAGORLA and Abhishe Pareek
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10.1002/ejoc.201800248
European Journal of Organic Chemistry
Electrophilic cyclization of 2-Aminophenylprop-1-yn-3-ols to 3-
Iodo-6-(aryldiazenyl)quinolines in a one-pot, Azo-coupling and
Iodo-cyclization sequence
Srinivasarao Yaragorla* and Abhishek Pareek
Dedication ()
Abstract: The first synthesis of 3-iodo-6-(aryldiazenyl)quinolines
report the first one-pot synthesis of
3-iodo-
is described from easily available 2-aminoaryl propargyl alcohols, 6(aryldiazebyl)quinolines
aryldiazonium salts and molecular iodine (3-component reaction). alcohols.[12,15]
from
2-aminoaryl
propargyl
The reaction proceedes through
a one-pot, azo-coupling
followed by regioselective iodocyclization and aromatization
cascade to yield the quinoline derivatives. In the absence of
iodine, Ca(OTf)2 promoted the azo-coupling and azacyclization
to-furnish the substituted 6-aryldiazenyl quinolines. In addition,
2-aminoaryl propargyl alcohols alone gave the 2,4-disubstituted
quinolines with Ca(II). We also demonstrated the synthetic
transformations of these iodoquinolines in cross-coupling
reactions without disturbing the diazo functionality.
Scheme 1. Synthesis of quinoline derivatives from 1 via
electrophilic cyclization strategy
Introduction
Quinolines are ubiquitous natural alkaloids with a wide range of Results and Discussion
biological and medicinal importance,[1] showed applications in
material science,[2] and asymmetric catalysis.[3] Owing to these
As described in the Scheme 2, initially we aimed to the synthesis
outstanding topographies, synthesis of quinolines and their
derivatives become an active and challenging area of organic
synthesis. Amongst many synthetic protocols developed for the
synthesis of quinoline derivatives, electrophilic cyclization[4a-4f] is
considered to be one of the most important atom and step
economic synthesis. Most of these electrophilic cyclizations
involved the interaction of an electrophilic reagent with the
unsaturated carbon-carbon bonds, followed by subsequent
intramolecular addition of nitrogen-nucleophile (aza-cyclization)
to give the privileged- quinoline scaffolds (Scheme 1). For
example, propargyl alcohol 1 was treated with electrophilic
iodine under various conditions to get the 3-iodoquinolines.[5-8]
Stein et al. reported the synthesis of 3-organoseleno-substituted
quinolines through electrophilic cyclization of 1 with 1.5 equiv. of
of 2,3,4-triaryl quinoline (1aa1) by treating the 1-(2-
aminophenyl)-1,3-diphenylprop-2-yn-1-ol
(1a)
with
(4-
NO2)PhN2BF4 (2a) under the calcium catalysis (Scheme 2).
Presuming that the aryldiazonium salts are the synthons of
arylium cations,[13] Surprisingly, the obtained product was
confirmed as 6-aryl diazoquinoline along with a simple quinoline
(5a). That means the azo-coupling took place on the para-
position of aniline 1a,[14] then followed the aza-cyclization to
result in the formation of 4a. After a careful understanding of this
serendipitous result, we realized that there is still a scope to
install the iodide in the third position of quinoline 4a.
[9]
FeCl3, they had also described the synthesis of quinolines
bearing organo tellurium and sulfur in the 3-position. The
intramolecular azacyclization of 1 to the simple, 2,3-disubstituted
[10-11]
quinolines was reported using, FeCl3,[9] CuCl2
and PPTS.[7]
Very recently, we have reported a technically valuable method
for the one-pot scalable synthesis of 3-iodoquinolines from
readily available 2-arylamino ketones and terminal alkynes.[8]
In continuation of our research interest towards the synthesis of
quinoline derivatives and electrophilic cyclizations, herein we
Scheme 2. Initial reaction
Accordingly, we planned our experiments to optimize the
reaction conditions (Table 1). The mixture of 1a and 2a along
with 10 mol% Ca(OTf)2/Bu4NPF6 were heated directly at 100 oC
for 8 h, and we obtained the mixture of two products 4a and 5a
(entry 1, Table 1). When we repeated the same combination of
reactants and refluxed the reaction mixture in DCE the yield of
Srinivasarao Yaragorla, Abhishek Pareek
School of Chemistry, Gurbaksh Building, W-16, 17, University of
Hyderabad, P.O. Central University, Gachibowli, Hyderabad,
5000046, Telangana State, India
E-mail: Srinivas.yaragorla@uohyd.ac.in
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10.1002/ejoc.201800248
European Journal of Organic Chemistry
4a was increased from 5% to 35% (entry 2). Gratifyingly, the
reaction in DCE at rt gave the maximum yield of 4a (71%, entry
3) with 8% 5a. Encouraged by this observation, we performed
the further optimizations to incorporate the iodine in the 3-
position of quinoline 3a. So, repeated the condition 3, along with
1.5 equiv. of I2 and found the mixture of 3a/4a in 25% and 35%.
Encouraged by the incorporation of 3-iodo and 6-aryldiazo
functionalities on the quinoline moiety, we then went on hunting
for the best conditions. After systematic studies (entries 4-10,
Table 1) we found that when a mixture of 1a and 2a were stirred
at rt with 1.5 equiv. of molecular iodine in a closed vessel, the
reaction yielded the maximum yield of 3a (67%, entry 7).
Approximately 10% of simple 3-iodoquinoline being the by-
product.
Table 2. Synthesis of 3-iodo-6-diazo aryl quinolines in one-pot.
Table 1. Optimization of the reaction conditions
N2BF4
O2N
Ph
Ph
N
OH
N
conditionsa)
X
+
N
Ph
Ph
NH2
NO2
3a; (X=I)
2a
4a; (X=H)
1a
Yield b)
Entry
Reaction conditions
1
2
10 mol% Ca(OTf)2/Bu4NPF6, neat, 100 oC, 8 h
10 mol% Ca(OTf)2/Bu4NPF6, DCE, reflux, 2.5 h
5% (4a)e)
35% (4a)
3c)
10 mol% Ca(OTf)2/Bu4NPF6, 1,2-DCE, rt, 2.5 h
71% (4a)
4
10 mol% Ca(OTf)2/Bu4NPF6, I2 (1.5 equiv), DCE, 25%/35%
rt, 3 h
(3a/4a)
5
6
7d)
I2 (2 equiv.), 1,2-DCE, reflux, 3 h
I2 (2 equiv.), 1,2-DCE, rt, 3 h
I2 (1.5 equiv.), 1,2-DCE, rt, 3 h
51% (3a)
67% (3a)
67% (3a)
8
9
I2 (1 equiv.), 1,2-DCE, rt, 3 h
I2 (2 equiv.), EtOAc, rt, 3 h
I2 (2 equiv.), Toluene, rt, 3 h
60% (3a)
60% (3a)
32% (3a)
During the optimization studies, we observed that in the
presence of a Lewis acid catalyst [Ca(OTf)2], 1a and 2a reacted
to give the quinoline 4a with 6-aryldizao substitution in 71% yield
at room temperature in 2.5 h (Table 1, entry 3). A thorough
literature survey suggested us that these kinds of compounds
are not made earlier. Hence, we felt that owing to the privileged
nature of quinoline moiety and also due to the importance of
diazo coupling, these compounds would be useful in material
applications and also can fill the space of new chemical entities.
Hence we demonstrated the generality of this reaction as shown
in Table 3. Propargyl alcohol 1a reacted with almost nine
diazonium salts and furnished the respective diazo-quinolines
4a-4i in moderate to good yields. Similarly, propargyl alcohol 1b
also yielded the diazoquinolines 4j-4r. 66% of 4s was obtained
with 1e, and 77% of 4t was obtained with aliphatic propargyl
alcohols 1d (Table 3).
10
a)Mixture of 1a (1 equiv.), 2a (1.5 equiv.) were used; b)Isolated yields;
c)Optimum conditions for 6-diazoquinoline; d)optimum condition for 3-
iodo-6-diazoquinoline; e)remaining compound isolated as
diphenylquinoline; DCE: 1,2-dichloroethane; rt: room temperature
2,4-
After establishing the optimum condition for the one-pot,
azo-coupling and iodocyclization sequence for the synthesis of
3a (entry-7, Table 1), we were encouraged to check the
generality of this reaction. Propargyl alcohol 1a was treated with
a variety of aryl-diazonium salts such as 4-F, 4-Cl, 4-Br, and 2-I
under standard iodocyclization conditions and obtained the
corresponding 3-iodo-6-aryldiazo quinolines 3b-3e in moderate
to good yields. Similarly, propargyl alcohol 1b was also reacted
to yield the respective quinolines 3f-3j in good yields. After the
satisfactory results obtained with the propargyl alcohols bearing
arylalkyne moiety, we then investigated the reactivity of aliphatic
alkynes, interestingly, all of them showed similar reactivity in the
sequential azocoulping and iodocyclization reaction to furnish
the quinolines 3k-3o in good yields (Table 2).
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10.1002/ejoc.201800248
European Journal of Organic Chemistry
Table 3. Ca(II)-mediated regioselective synthesis of 6-
Table 4. Synthesis of quinolines by a Ca(II) mediated
regioselective cyclization.
(aryldiazenyl) quinolines.a)
After the discovery of a comprehensive synthetic method for the
synthesis of three types of quinolines, namely, 6-aryl diazo-3-
iodoquinolines (3), 6-(aryldiazenyl)quinolines (4) and simple
quinolines, we planned to show the synthetic transformations of
iodo-quinolines in cross-coupling reactions. Therefore iodide 3j
was treated with ethyl acrylate under Heck reaction[16] conditions
to obtain quinoline 6 in 82% yield. Sonagashira coupling[17]
between iodide 3j and phenyl acetylene furnished the quinoline
7 in 62% yield. Suzuki coupling[18] of 3j with phenyl boronic acid
yielded the quinoline 8 in 66% yield.
O2N
Ph
O
N
Heck
coupling
N
OEt
Me
N
6
,
82%, 18 h
a)a mixture of 1 (1 equiv.), 2 (1.5 equiv.) and 10 mol% of Ca(OTf)2/ Bu4NPF6
O2N
O2N
Sonagashira
coupling
Ph
N
Ph
Ph
N
I
N
were used.
N
N
N
7,
Finally, we wanted to see the possibility of the intramolecular
regioselective cyclization of 1a with the Ca(II) to yield the
quinoline 5a. Previously, this approach was reported by three
groups using different transition metal/Bronsted acid catalysts,
Me
3j
Me
62%, 14 h
O2N
Ph
Suzuki
coupling
N
Ph
N
[9]
such as CuCl2 in methanol[10] 1.5 equiv. of FeCl3 in CH2Cl2,
N
and PPTS in MeOH.[7] Hence we felt that it would be useful to
develop a catalytic intramolecular cyclization under solvent free
conditions from readily available ketones and terminal alkynes
instead of 2-aminoaryl propargyl alcohols. Therefore 2-aminoaryl
ketones were treated with terminal alkynes and KOtBu at rt
under neat conditions for 2 h, then the crude product was further
treated with 10 mol% of Ca(OTf)2/Bu4NPF6 for the specified time
8
,
Me
66%, 10 h
Scheme 3. Cross coupling reactions of iodide 3j: Conditions: Heck= ethyl
acrylate (3 equiv.), Pd(OAc)2 (5 mol%), Bu4NBr (1 equiv.), Na2CO3 (1 equiv.),
DMF, 80 oC; Sonogashira= Phenylacetylene (2 equiv.), Pd(OAc)2 (2 mol%),
DABCO (3 equiv.), MeCN, rt; Suzuki= PhB(OH)2 (1.3 equiv.), Pd(OAc)2 (5
mol%), Na2CO3 (1 equiv.), DMF/H2O (2:1), 100 oC.
o
Control experiments were conducted to look at the
sequence of the reaction mechanism as shown in the Scheme 4.
Under the standard conditions, 1a and 2a reacted to give 3a
(equn-i). It is well known that aniline reacts with diazonium salts
to give the corresponding azo dyes, so we treated 1a with 2a in
DCE and surprisingly 35% of 6-diazo arylquinoline 4a was
at 70 C under neat conditions to obtain the quinolines 5a-5l in
good to excellent yields (Table 4).
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10.1002/ejoc.201800248
European Journal of Organic Chemistry
formed along with unreacted 1a. Probably this could be due to
the presence of Lewis acidic boron in the form of ArN2BF4.
When we, blocked the para-position with chloro substitution (1f),
under standard conditions, reaction yielded 3-iodoquinoline (9)
without diazotization (equation-iii). Diazotization taking place
before cyclization was proved by the condition (iv & v). Quinoline
5a could not react with either I2 or ArN2BF4 under standard
conditions, similar result observed, when 3-iodoquinoline 10 was
treated with ArN2BF4.
Conclusion
In conclusion, we have developed a diversity-oriented comprehensive
approach for the synthesis of quinoline derivatives from 2-aminoaryl
propargyl alcohols. We described the first one-pot, synthesis of 6-aryl
diazo-3-iodoquinolines using
a sequential azo-coupling followed by
electrophilic cyclization. We further extended this study to the synthesis
of 6-aryl diazo quinolines and simple quinolines. New structures were
confirmed by single-crystal X-ray data. Control experiments
authenticated the sequence of the reaction mechanism. The synthetic
utility of these compounds in cross-coupling reactions is also
demonstrated.
Ph
N2BF4
O2N
OH
Ph
Ph
N
I
N
N
I
2, 1,2-DCE, rt
(i)
+
NH2
N
Ph
NO2
2a
Experimental Section
1a
3a, 67%, 3 h
O2N
Ph
1,2-DCE, rt
N
(ii)
1a
+
General information: Unless otherwise noted, all reagents were used as
received from commercial suppliers. Ca(OTf)2 and Bu4NPF6 were
obtained from Sigma-Aldrich and used without further purification.
Reactions were performed in flame-dried or oven-dried glassware with
magnetic stirring. Reactions were monitored using thin-layer
chromatography (TLC) with aluminium sheets silica gel 60 F254 from
Merck. TLC plates were visualized with UV light (254 nm), iodine
treatment or using ninhydrin stain. Column chromatography was carried
out using silica gel 60-120 mesh as the stationary phase. NMR spectra
were recorded at 500 MHz and 400 MHz (H) and at 125 MHz and 100
MHz (C), respectively on Avance Bruker spectrometer. Chemical shifts
(δ) are reported in ppm, using the residual solvent peak in CDCl3 (H: δ =
7.26 and C: δ = 77.0 ppm) as internal standard, and coupling constants
(J) are given in Hz. Melting points were measured with LABINDIA mepa
melting apparatus.
2a
+
1a
N
Ph
4a,
35%, 12 h
OH
Ph
Ph
Cl
Cl
I
(iii)
I
2, 1,2-DCE, rt
2a
+
Ph
NH2
N
Ph
1f
para-position blocked
9, 62%, 3 h
Ph
I
2, 1,2-DCE, rt
no reaction
(s.m.recoverd)
(iv)
(v)
2a
+
N
Ph
5a
10
Ph
1,2-DCE, rt
I
no reaction
(s.m.recoverd)
2a
+
N
Ph
Scheme 4. Control experiments
General experimental procedure for the synthesis of 3-iodo-2,4-
diphenyl-6-(phenyldiazenyl) quinoline (3a):
A mixture of 1-(2-
Based on the observations resulted from the control experiments
(Scheme 4), the reaction mechanism for the synthesis of 6-
diazoaryl-3-iodo quinoline derivatives (3) is described in the
Scheme 5. The mechanism starts with the azo-coupling of 1 and
2 followed by the iodocyclization and aromatization sequence as
shown in the Scheme 5.
aminophenyl)-1,3-diphenylprop-2-yn-1-ol 1a (150 mg, 0.50 mmol) and
(E)-1-(4-nitrophenyl)-2-(tetrafluoro-l5-boranyl) diazene 2a (175 mg, 0.75
mmol) stirred in 1,2-dichloroethane (1.5 mL) at room temperature for 15
min then I2 (194 mg, 0.75 mmol) was added to the reaction mixture and
stirred till completion of the reaction (monitored by TLC). After completion
of the reaction, the resulting mixture was quenched with aq. saturated
solution of Na2S2O3 (10 mL) and extracted into dichloromethane (15 mL,
thrice). Combined organic layers were washed with brine solution and
dried over anhydrous Na2SO4, and the solvent was evaporated under
reduced pressure, and the residue was purified by column
chromatography using EA/PE (5:95, v/v) to obtain the desired product 3a
in 67% yield.
HO
HO
H
Ar
Ar
BF4
N
azo-coupling
Ph
N
Ar1
N
N
Ar1
Ph
NH2
NH2
2
1
I1
aromatization
Ar OH
-
I2
+
Ar OH
I
I
N
N
N
N
Ar1
Ar1
Ph
Ph
6-endo dig
NH2
NH2
I3
I2
General experimental procedure for the synthesis of 2,4-diphenyl-6-
(phenyldiazenyl)quinoline (4a): A mixture of 1-(2-aminophenyl)-1,3-
diphenylprop-2-yn-1-ol 1a (150 mg, 0.50 mmol) and (E)-1-(4-nitrophenyl)-
2-(tetrafluoro-l5-boranyl)diazene 2a (175 mg, 0.75 mmol) stirred in 1,2-
dichloroethane (1.5 mL) at room temperature for 30 min then 10 mol% of
Ca(OTf)2 and Bu4NPF6 were added to the reaction mixture and stirred till
completion of the reaction (monitored by TLC). After completion of the
reaction, the resulting mixture was quenched with water (10 mL) and
extracted into dichloromethane (15 mL, thrice). Combined organic layers
were washed with brine solution and dried over anhydrous Na2SO4 and
the solvent was evaporated under reduced pressure and the residue was
iodocyclization
-HI
Ar
OH
Ar
I
N
I
aromatization
-H2O
N
N
N
Ar1
Ar1
N
Ph
N
H
Ph
b
I4
3
Scheme 5. Mechanism
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10.1002/ejoc.201800248
European Journal of Organic Chemistry
purified by column chromatography using EA/PE (5:95, v/v) to obtain the
was evaporated under reduced pressure, and the residue was purified by
column chromatography with silica gel using EA/PE (7:93, v/v) to give of
product 8 in 66% yield.
desired product 4a in 71 % yield.
General experimental procedure for the synthesis of 2,4-
diphenylquinoline (5a): Propargylic alcohol 1-(2-aminophenyl)-1,3-
diphenylprop-2-yn-1-ol 1a (150 mg, 0.50 mmol) and 10 mol% of Ca(OTf)2
and Bu4NPF6 were stirred at 70 oC under solvent-free condition till
completion of the reaction (monitored by TLC). After completion of the
reaction, the resulting mixture was quenched with water (10 mL) and
extracted into ethyl acetate (15 mL, thrice). Combined organic layers
were washed with brine solution and dried over anhydrous Na2SO4, and
the solvent was evaporated under reduced pressure, and the residue
was purified by column chromatography using EA/PE (5:95, v/v) to obtain
the desired product 5a in 92% yield.
E)-3-iodo-6-((4-nitrophenyl)diazenyl)-2,4-diphenylquinoline
(3a):
o
Orange solid; (67%); mp 212-214 C; 1H NMR (400 MHz, CDCl3):8.41
(d, J = 8.8 Hz, 2H), 8.35-8.27 (m, 2H), 8.17 (d, J = 5.2 Hz, 1H), 8.05 (d, J
= 8.4 Hz, 2H), 7.74-7.64 (m, 5H), 7.59-7.53 (m, 3H), 7.43 (d, J = 6 Hz,
2H) ppm; 13C NMR (100 MHz, CDCl3): δ 163.8, 156.2, 155.5, 150.3,
148.9, 143.3, 141.5, 131.1, 129.9, 129.8, 129.3, 129.2, 129, 128.1, 127.8,
127.5, 124.8, 124.1, 123.6, 119.9, 99.9 ppm; ESI m/z [M + H]+ 557;
HRMS (ESI) m/z calcd for C27H17IN4O2 [ M + H]+ 557.0474; found
557.0481
(E)-6-((4-fluorophenyl)diazenyl)-3-iodo-2,4-diphenylquinoline
(3b):
o
1
Orange solid; (68%); mp 222-224 C; H NMR (400 MHz, CDCl3):
m, 2H), 8.05 (d, J = 2 Hz, 1H), 7.96-7.92 (m, 2H), 7.72-7.70 (m, 2H),
7.64-7.62 (m, 3H), 7.54-7.50 (m, 3H), 7.41-7.39 (m, 2H), 7.20 (t, J = 8 Hz,
2H) ppm; 13C NMR (100 MHz, CDCl3): δ 165.9, 163.4, 163.1, 155.8,
150.4, 148.3, 143.5, 141.7, 130.8, 129.3, 129.2, 129.1, 128.9, 128.8,
128.8, 128.6, 128, 127.9, 127.6, 127.5, 125, 120.4, 116.3, 99.5 ppm; ESI
m/z [M + H]+ 530; HRMS (ESI) m/z calcd for C27H17FIN3 [ M + H]+
530.0529; found 530.0545
Synthesis of ethyl (E)-3-(6-((E)-(4-nitrophenyl)diazenyl)-4-phenyl-2-
(p-tolyl)quinolin -3-yl)acrylate (6)[8]: Ethyl acrylate (47 mg, 0.47 mmol),
was added to
a solution of (E)-3-iodo-6-((4-nitrophenyl)diazenyl)-4-
phenyl-2-(p-tolyl)quinoline 3j (115 mg, 0.23 mmol) in DMF (1.8 mL)
containing K2CO3 (53 mg, 2.5 eq) and Bu4NBr (50 mg, 1 equiv) and
stirred at room temperature for 5 min. Pd(OAc)2 (5 mol %) was then
added, and the flask was flushed with N2, sealed and allowed to stir at
80 °C for 18 h. The resulting mixture was filtered off, washed and
extracted with diethyl ether. The combined organics were washed with
water and then with brine solution and dried over anhydrous Na2SO4.
The solvent was evaporated under reduced pressure, and the residue
was purified by column chromatography with silica gel using EA/PE (7:93,
v/v) to give of product 6 in 82% yield.
(E)-6-((4-chlorophenyl)diazenyl)-3-iodo-2,4-diphenylquinoline (3c):
Orange solid; (65%); mp 232-233 oC; 1H NMR (400 MHz, CDCl3):
-
8.26 (m, 1H), 8.22-8.20 (m, 1H), 8.04 (d, J = 2 Hz, 1H), 7.85-7.83 (m, 2H),
7.70-7.68 (m, 2H), 7.64-7.58 (m, 3H), 7.52-7.45 (m, 5H), 7.39-7.36 (m,
2H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.2, 155.9, 150.9, 150.4,
148.4, 143.5, 141.7, 137.4, 130.8, 129.4, 129.3, 129.2, 129.1, 128.9,
128.8, 128.8, 128, 127.6, 124.3, 120.4, 99.6 ppm; ESI m/z [M + H]+ 547;
Anal. calcd: for C27H17ClIN3: C:59.42; H: 3.14; N: 7.70; found C: 59.48; H:
3.18; N: 7.65.
General
experimental
procedure
synthesis
of
(E)-6-((4-
nitrophenyl)diazenyl)
-4-phenyl-3-phenylethynyl)
-2-(p-tolyl)
quinoline (7)[8]: First Pd(OAc)2 (2 mol%) was dissolved in MeCN (1 mL).
Then, the indicated amount of Pd(OAc)2 acetonitrile solution was added
to a mixture of alkyne (44.5 mg, 0.45 mmol), aryl halide 3j (115 mg, 0.22
mmol), DABCO (76 mg, 3 equiv), and MeCN (4 mL). Then the mixture
was stirred under N2 at room temperature for 14 h. The resulting mixture
was filtered off, washed and extracted with diethyl ether. The combined
organics were washed with water and then with brine solution and dried
over anhydrous Na2SO4. The solvent was evaporated under reduced
pressure, and the residue was purified by column chromatography with
silica gel using EA/PE (7:93, v/v) to give of product 7 in 62% yield.
(E)-6-((4-bromophenyl)diazenyl)-3-iodo-2,4-diphenylquinoline (3d):
1
Orange solid; (61%); mp 198-200 oC; H NMR (400 MHz, CDCl3): 8.31-
8.23 (m, 2H), 8.08 (s, 1H), 7.81-7.79 (m, 2H), 7.73-7.53 (m, 10 H), 7.40
(d, J = 6.4 Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3): δ 163.2, 155.9,
151.2, 150.4, 148.4, 143.4, 141.7, 132.4, 130.8, 130.1, 129.3, 129.2,
128.9, 128.7, 128.2, 128.1, 128, 127.6, 127.3, 125.9, 124.5, 120.3, 99.6
ppm; ESI m/z [M + H]+ 590; HRMS (ESI) m/z calcd for C27H17BrIN3 [ M +
H]+ 589.9728; found 589.9731
(E)-3-iodo-6-((2-iodophenyl)diazenyl)-2,4-diphenylquinoline
(3e):
o
1
Orange solid; (71%); mp 206-208 C; H NMR (400 MHz, CDCl3):8.37
(d, J = 4 Hz, 1H), 8.24 (d, J = 8.8 Hz, 1H), 8.01 (s, 1H), 7.69 (d, J = 6.8
Hz, 2H), 7.61-7.50 (m, 7H), 7.40-7.29 (m, 4H), 7.17-7.14 (m, 1H) ppm;
13C NMR (125 MHz, CDCl3): δ163.2, 155.7, 148.4, 141.7, 140.6, 138.8,
137.3, 130.8, 130, 129.4, 129.2, 129.1, 129.1, 128.8, 128.7, 128.6, 128,
127.1, 126.8, 124.2, 120.2, 99.7, 98.7 ppm; ESI m/z [M + H]+ 638; Anal.
calcd. for C27H17I2N3: C: 50.89; H: 2.69; N, 6.59; found C, 50.84; H, 2.68;
N, 6.61.
General
experimental
procedure
synthesis
of
(E)-6-((4-
(8)[8]:
nitrophenyl)diazenyl)-3,4-diphenyl-2-(p-tolyl)quinoline
PhB(OH)2 (41.1 mg, 0.33 mmol) was added to a solution of (E)-3-iodo-6-
((4-nitrophenyl) diazenyl)-4-phenyl-2-(p-tolyl) quinoline 3j (140 mg, 0.27
mmol) in 3.0 mL of DMF/H2O (2:1) containing Na2CO3 (27.4 mg, 1 equiv)
and stirred at room temperature for 5 min. Pd(OAc)2 (5 mol %) was then
added, and the flask was flushed with N2, sealed and allowed to stir at
100 °C for 10 h. The resulting mixture was filtered off, washed and
extracted with diethyl ether. The combined organics were washed with
water and then with brine and dried over anhydrous Na2SO4. The solvent
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800248
European Journal of Organic Chemistry
(E)-6-((4-fluorophenyl)diazenyl)-3-iodo-4-phenyl-2-(p-tolyl)quinoline
(3f): Orange solid; (58%); mp 230-231 oC; 1H NMR (400 MHz,
CDCl3):-(m, (d, J = 8.8 Hz, 2H), 8.07 (d, J = 1.6 Hz,
2H), 7.79 (d, J = 8.4 Hz, 2H), 7.73-7.62 (m, 5H), 7.55-7.52 (m, 2H), 7.41-
7.39 (m, 2H), 2.50 (s, 3H) ppm;13C NMR (100 MHz, CDCl3):δ 163.2,
155.9, 151.2, 150.4, 148.4, 143.5, 141.7, 132.4, 130.8, 129.3, 129.2,
129.1, 128.9, 128.8, 128.6, 128.1, 128, 127.9, 127.6, 125.9, 124.5, 120.3,
99.6, 21.5 ppm; HRMS (ESI) m/z calcd for C28H19FIN3 [M + H]+
544.0685; found 544.0691
J = 7.8 Hz, 2H), 1.94-1.89 (m, 2H), 1.54-1.44 (m, 4H), 0.98-0.94 (m, 3H)
ppm;13C NMR (125 MHz, CDCl3): δ164.5, 154.9, 150.8, 149.9, 148.4,
141.7, 137.2, 130.1, 129.3, 129.1, 128.7, 128.7, 127.1, 124.2, 119.8, 101,
43.4, 31.8, 28.8, 22.5, 14.1 ppm; ESI m/z [M + H]+ 540; HRMS (ESI) m/z
calcd for C26H23ClIN3 [M + H]+ 540.0703; found 540.0699
(E)-3-iodo-6-((4-nitrophenyl)diazenyl)-2-pentyl-4-phenylquinoline
(3l): Orange solid; (71%); mp 190-192 oC; 1H NMR (400 MHz,
CDCl3):8.37 (d, J = 9.2 Hz, 2H), 8.28-8.25 (m, 1H), 8.16 (d, J = 9.2 Hz,
1H), 8.07 (d, J = 2 Hz, 1H), 8.01 (d, J = 9.2 Hz, 2H), 7.64-7.61 (m, 3H),
7.34-7.32 (m, 2H), 3.33 (t, J = 7.6 Hz, 2H), 1.95-1.89 (m, 2H), 1.57-1.45
(m, 4H), 1.0-0.97 (m, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ 165.3,
155.6, 155.2, 149.9, 148.8, 148.7, 141.6, 130.4, 129.8, 129.1, 128.9,
128.8, 127.1, 124.7, 123.5, 119.4, 101.7, 43.5, 31.9, 28.8, 22.6, 14.1
ppm; ESI m/z [M + H]+ 551; Anal. calcd. for C26H23IN4O2: C: 56.74; H:
4.21; N: 10.18; found C, 56.68; H, 4.94; N, 10.09
(E)-6-((4-chlorophenyl)diazenyl)-3-iodo-4-phenyl-2-(p-tolyl)quinoline
o
1
(g): Orange solid; (69%); mp 227-229 C; H NMR (500 MHz, CDCl3): δ
8.30-8.28 (m, 1H), 8.23 (d, J = 8.5 Hz, 1H), 8.05 (d, J = 2 Hz, 1H), 7.87
(d, J = 9 Hz, 2H), 7.64-7.62 (m, 4H), 7.58 (s, 1H), 7.49 (d, J = 9 Hz, 2H),
7.41-7.39 (m, 2H), 7.33-7.31 (m, 2H), 2.48 (s, 3H) ppm; 13C NMR (125
MHz, CDCl3): δ 163.3, 155.8, 150.9, 150.3, 148.4, 141.8, 140.6, 138.8,
137.3, 130.8, 129.4, 129.3, 129.2, 128.9, 128.7, 128.6, 128, 127.5, 127.1,
126.8, 124.3, 120.3, 99.8, 21.5 ppm; ESI m/z [M + H]+ 560; HRMS (ESI)
m/z calcd for C28H19ClIN3 [ M + H]+ 560.0390; found 560.0379
(E)-2-butyl-6-((4-chlorophenyl)diazenyl)-3-iodo-4-phenylquinoline
(3m): Orange solid; (68%); mp 183-184 oC; 1H NMR (400 MHz,
CDCl3):8.27-8.24 (m, 1H), 8.14 (d, J = 9.2 Hz, 1H), 7.98 (d, J = 2 Hz,
1H), 7.85 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 7.2 Hz, 3H), 7.48 (d, J = 8.6 Hz,
2H), 7.31 (d, J = 6 Hz, 2H), 3.34 (t, J = 8.4 Hz, 2H), 1.93-1.88 (m, 2H),
1.62-1.57 (m, 2H), 1.06 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz,
CDCl3): δ 164.6, 155, 150.8, 149.9, 148.4, 141.7, 137.2, 130.1, 129.4,
129.1, 128.8, 128.7, 128.3, 127.1, 124.2, 119.8, 101.5, 43.3, 31.3, 22.9,
14.1 ppm; ESI m/z [M + H]+ 540; HRMS (ESI) m/z calcd for C26H23ClIN3
[M + H]+ 540.0703; found 540.0699
(E)-6-((4-bromophenyl)diazenyl)-3-iodo-4-phenyl-2-(p-tolyl) quinoline
(h): Orange solid; (62%); mp 218-220 oC; 1H NMR (500 MHz,
CDCl3):- (m, 1H), 8.23 (d, J = 8.5 Hz, 1H), 8.06 (d, J = 2 Hz,
1H), 7.79 (d, J = 9 Hz, 1H), 7.65-7.61 (m, 7H), 7.40-7.34 (m, 5H), 2.47 (s,
3H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.3, 155.8, 151.2, 150.4,
148.4, 141.8, 140.6, 138.8, 132.4, 130.8, 130, 129.3, 129.2, 128.9, 128.7,
128.6, 128.4, 128.1, 127.5, 127.1, 124.5, 120.2, 99.8, 21.5 ppm; ESI m/z
[M + H]+ 604; HRMS (ESI) m/z calcd for C28H19BrIN3 [M + H]+ 603.9885;
found 603.9878
(E)-6-((4-bromophenyl)diazenyl)-2-butyl-3-iodo-4-phenylquinoline
(3n): Orange solid; (62%); mp 180-182 oC; 1H NMR (400 MHz, CDCl3):
8.27-8.24 (m, 1H), 8.13 (d, J = 5.2 Hz, 1H), 7.98 (d, J = 2 Hz, 1H), 7.77 (d,
J = 8.8 Hz, 2H), 7.64-7.60 (m, 5H), 7.33-7.31 (m, 2H), 3.33 (t, J = 8 Hz,
2H), 1.93-1.89 (m, 2H), 1.65-1.56 (m, 2H), 1.05 (t, J = 7.6 Hz, 3H) ppm;
13C NMR (125 MHz, CDCl3): δ 164.3, 154.7, 150.9, 149.6, 148.1, 141.4,
132.1, 129.8, 128.8, 128.5, 128.4, 128, 126.8, 125.4, 124.1, 119.5, 101.2,
42.9, 31, 22.6, 13.8 ppm; ESI m/z [M + NH4]+ 587; HRMS (ESI) m/z calcd
for C25H21BrIN3 [M + H]+ 570.0041; found 570.0049
(E)-3-iodo-6-((2-iodophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline
(i): Orange solid; (62%); mp 229-231 oC; 1H NMR (400 MHz,
CDCl3):8.36-8.33 (m, 1H), 8.22 (d, J = 4.8 Hz, 1H), 8.08 (s, 1H), 8 (d, J
= 8 Hz, 1H), 7.61-7.58 (m, 6H), 7.39-7.31 (m, 5H), 7.14 (d, 6.8 Hz, 1H),
2.43 (s, 3H)13C NMR (100 MHz, CDCl3): δ 163.2, 155.8, 150.9, 150.2,
148.4, 141.7, 140.5, 139.9, 138.7, 132.5, 130.8, 129.9, 129.2, 129.1,
128.8, 128.6, 128.5, 127.8, 127.4, 121.3, 117.1, 103.3, 99.6, 21.4 ppm;
ESI m/z [M + H]+ 638 Anal. calcd. for C28H19I2N3: C: 51.64; H: 2.94; N:
6.45; found C, 51.72; H, 2.91; N, 6.39.
(E)-2-butyl-3-iodo-6-((4-nitrophenyl)diazenyl)-4-phenylquinoline (3o):
Orange solid; (63%); mp 191-193 oC; 1H NMR (400 MHz,
CDCl3):d, J = 8.8 Hz, 2H), 8.28-8.26 (m, 1H), 8.16 (d, J = 9.2 Hz,
1H), 8.07 (s, 1H), 8.02 (d, J = 8.8 Hz, 2H), 7.63 (d, J = 6.4 Hz, 3H), 7.33
(d, J = 6.8 Hz, 2H), 3.34 (d, J = 7.6 Hz, 2H), 1.94-1.90 (m, 2H), 1.64-1.57
(m, 2H), 1.06 (t, J = 7.2 Hz, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ
165.3, 155.6, 149.9, 148.8, 148.7, 141.6, 130.4, 129.8, 129.1, 129, 128.9,
128.8, 127.1, 124.7, 123.5, 119.4, 101.7, 43.3, 31.2, 22.8, 14 ppm;
HRMS (ESI) m/z calcd for C25H21IN4O2 [M + H]+ 537.0787; found
537.0793
(E)
3-iodo-6-((4-nitrophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline
(j): Orange solid; (67%); mp 208-210 oC; 1H NMR (500 MHz,
CDCl3):8.39-8.38 (m, 2H), 8.32-8.29 (m, 1H), 8.25 (d, J = 9 Hz, 1H),
8.15 (d, J = 2 Hz, 1H), 8.04 (d, J = 9 Hz, 2H), 7.65-7.62 (m, 5H), 7.41-
7.35 (m, 4H), 2.48 (s, 3H) ppm;13C NMR (100 MHz, CDCl3): δ 163.9,
156.1, 155.5, 150.3, 148.9, 141.6, 140.5, 139, 131.1, 129.7, 129.7, 129.6,
129.2, 129.1, 128.9, 128.8, 128.7, 124.7, 123.6, 119.8, 100, 21.5 ppm;
ESI m/z [M + NH4]+ 588; HRMS (ESI) m/z calcd for C28H19IN4O2 [M + H]+
571.0630; found 571.0619
(E)-6-((4-nitrophenyl)diazenyl)-2,4-diphenylquinoline (4a): Orange
(E)-((4-chlorophenyl)diazenyl)-3-iodo-2-pentyl-4-phenylquinoline (k):
solid;
(71%);
mp
175-176
oC;
1H
NMR
(500
MHz,
1
Orange solid; (67%); mp 178-180 oC; H NMR (400 MHz, CDCl3):8.23-
CDCl3):s (d, J = 8 Hz, 2H), 8.33 (d, J = 0.5 Hz, 2H, 8.27
(d, J = 7.5 Hz, 2H), 8.07 (d, J = 9 Hz, 2H), 7.96 (s, 1H), 7.69-7.52 (m, 8H)
ppm; 13C NMR (125 MHz, CDCl3): δ 158.6, 155.7, 150.9, 150.7, 150,
8.20 (m, 1H), 8.11 (d, J = 4.8 Hz, 1H), 7.94 (d, J = 2.4 Hz, 1H), 7.82-7.80
(m, 2H), 7.62-7.58 (m, 3H), 7.45-7.43 (m, 2H), 7.30-7.28 (m, 2H), 3.30 (d,
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201800248
European Journal of Organic Chemistry
148.8, 139.1, 137.8, 131.7, 130, 129.6, 129, 128.9, 128.9, 128.7, 127.7,
126, 124.7, 123.5, 120.1, 119.5 ppm; HRMS (ESI) m/z calcd for
C27H18N4O2 [M+H]+ 431.1507; found 431.1512
(E)-6-((4-methoxyphenyl)diazenyl)-2,4-diphenylquinoline
(4h):
Orange solid; (59%); mp 180-182 oC; 1H NMR (400 MHz,
CDCl3):s, 1H), 8.42-8.28 (m, 2H), 7.91-7.97 (m, 2H), 7.64-7.69 (m,
3H), 7.51-7.58 (m, 8H), 7.03 (d, J = 9.2 Hz, 2H), 3.92 (s, 3H) ppm; 13C
NMR (100 MHz, CDCl3): δ 157.7, 151.9, 150.3, 150.2, 150.1, 147.1,
139.4, 138.1, 131.3, 129.6, 129.3, 128.9, 128.8, 128.7, 127.6, 126.1,
125.7, 124.9, 120.2, 119.9, 114.3, 55.6 ppm; HRMS (ESI) m/z calcd for
C28H21N3O [M + H]+416. 1778; found 416.1748
(E)-6-((4-fluorophenyl)diazenyl)-2,4-diphenylquinoline (4b): Orange
solid; (66%); mp 178-181 oC; 1H NMR (500 MHz, CDCl3):t, J = 1.5
Hz, 2H), 8.26-8.25 (m, 2H), 7.93-7.89 (m, 3H), 7.68-7.49 (m, 11H) ppm;
13C NMR (125 MHz, CDCl3): δ 158.1, 151, 150.4, 150.1, 139.2, 137.9,
137.1, 131.5, 129.8, 129.7, 129.6, 129.4, 128.9, 128.8, 128.7, 127.6,
126.9, 126, 124.2, 121.9, 119.9 ppm; HRMS (ESI) m/z calcd for
C27H18FN3 [ M + H]+ 404.1562; found 404.1568
(E)-2,4-diphenyl-6-(phenyldiazenyl)quinoline (4i): Orange solid;
(67%); mp 178-179 oC; 1H NMR (500 MHz, CDCl3):8.57 (d, J =1 Hz,
1H), 8.33 (d, J = 2.5 Hz, 2H), 8.27-8.25 (m, 2H), 7.96-7.94 (m, 2H), 7.69-
7.49 (m, 12H) ppm; 13C NMR (125 MHz, CDCl3): δ 157.9, 152.7, 150.4,
150.4, 150.2, 139.3, 138, 131.4, 131.1, 129.7, 129.6, 129.1, 128.9, 128.8,
128.7, 127.7, 126.6, 126, 122.9, 120.1, 119.9 ppm; HRMS (ESI) m/z
calcd. for C27H19N3 [M + H]+ 386.1657; found 386.1666
(E)-6-((4-chlorophenyl)diazenyl)-2,4-diphenylquinoline (4c): Pale
orange solid; (69%); mp 214-215 oC; 1H NMR (500 MHz, CDCl3): 8.55 (s,
1H), 8.25-8.31 (m, 1H), 7.89-7.93 (m, 2H), 7.59-7.68 (m, 3H), 7.49-7.57
(m, 11H) ppm; 13C NMR (125 MHz, CDCl3): δ 158.1, 151, 150.5, 150.4,
150, 139.2, 137.9, 137, 131.4, 129.8, 129.6, 129.4, 129.2, 128.9, 128.8,
128.7, 127.7, 126.9, 126, 124.2, 120 ppm; HRMS (ESI) m/z calcd for
C27H18ClN3 [M + H]+ 420.1278; found 420.1230
(E)-6-((4-nitrophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline
(4j):
o
1
Orange solid; (68%); mp 188-190 C; H NMR (400 MHz, CDCl3):
(s, 1H), 8.41-8.38 (m, 2H), 8.31 (d,J = 0.8 Hz, 2H), 8.17 (d, J= 8.4 Hz,
2H), 8.08-8.05 (m, 2H), 7.94 (s, 1H), 7.68-7.60 (m, 5H), 7.38 (d, J = 8 Hz,
2H), 2.48 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 158.1, 151.1, 150.5,
150.3, 149.9, 140, 138.1, 137, 136.4, 131.4, 129.7, 129.6, 129.4, 128.8,
128.7, 127.5, 126.9, 125.9, 124.2, 119.9, 119.8, 21.4 ppm; HRMS (ESI)
m/z calcd for C28H20N4O2 [M + H]+ 445.1664; found 445.1676
(E)-6-((4-bromophenyl)diazenyl)-2,4-diphenylquinoline (4d): Orange
solid;
(67%);
mp
195-196
oC;
1H
NMR
(500
MHz,
CDCl3):s(d, J =1.5 Hz, 2H), 8.27-8.25 (m, 2H), 7.93 (s,
1H), 7.83 (d, J = 8.8 Hz, 2H), 7.68-7.50 (m, 10H) ppm; 13C NMR (100
MHz, CDCl3): δ 158.1, 151.3, 150.5, 150.4, 150, 139.2, 137.9, 132.4,
131.5, 129.8, 129.6, 129, 128.9, 128.8, 127.7, 127.2, 126, 125.6, 124.4,
120, 119.9 ppm; HRMS (ESI) m/z calcd for C27H18BrN3 [M + H]+
464.0762; found 464.0780
(E)-6-((4-fluorophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline
(4k):
Orange solid; (66%); mp 199-201 oC; 1H NMR (500 MHz,
CDCl3):s8.29 (d, J = 1.6 Hz, 2H), 7.16 (d, J = 8.4 Hz, 2H),
7.98-7.95 (m, 2H), 7.90 (s, 1H), 7.68-7.58 (m, 6H), 7.37 (t, J = 8.8 Hz,
2H), 7.36 (s, 2H), 2.47 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ 157.9,
150.3, 150.2, 149.9, 149.2, 149.1, 140, 138.1, 136.4, 131.3, 129.7, 129.7,
129.6, 128.8, 128.7, 127.5, 126.7, 125.9, 125, 124.9, 119.9, 119.7, 116.2,
115.9, 21.4 ppm; HRMS (ESI) m/z calcd for C28H20FN3 [M + H]+
418.1719; found 418.1728
(E)-6-((2-iodophenyl)diazenyl)-2,4-diphenylquinoline (4e): Orange
solid; (61%); mp 178-179 oC; 1H NMR (400 MHz, CDCl3):8.40 (d, J = 2
Hz, 1H), 8.35 (s, 1H), 8.32-7.94 (m, 1H), 7.69-7.63 (m, 2H), 7.61-7.59 (m,
1H), 7.58-7.52 (m, 1H), 7.45-7.41(m, 9H), 7.28 (s, 1H), 7.20-7.16 (m, 1H)
ppm; 13C NMR (100 MHz, CDCl3): δ158.2, 151.2, 150.5, 150.5, 149.9,
139.9, 139.2, 137.8, 132.4, 131.5, 129.8, 129.6, 128.9, 128.9, 128.8,
128.7, 127.7, 127.2, 125.9, 120.8, 119.9, 117.2, 103.1 ppm; HRMS (ESI)
m/z calcd for C28H18IN3 [M + H]+ 512.0578; found 512.0602
(E)-6-((4-chlorophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline
(4l):
Pale orange solid; (63%); mp 191-192 oC; 1H NMR (500 MHz,
CDCl3):8.54 (s, 1H), 8.30 (d, J = 1Hz, 2H), 7.89-8.17 (m, 2H), 7.67-7.64
(m, 3H), 7.62-7.58 (m, 5H), 7.51-7.41 (m, 2H), 7.38-7.28 (m, 2H), 2.47 (s,
3H) ppm; 13C NMR (125 MHz, CDCl3): δ 158.1, 151.1, 150.4, 150.3,
149.9, 139.9, 138.1, 137, 136.4, 131.4, 129.6, 129.6, 129.3, 128.8, 128.7,
127.5, 126.9, 125.9, 124.1, 119.8, 119.7, 21.4 ppm; HRMS (ESI) m/z
calcd for C28H20ClN3 [M + H]+ 434.1778; found 434.1382
(E)-6-((2-bromophenyl)diazenyl)-2,4-diphenylquinoline (4f): Orange
o
1
solid; (66%); mp 177-179 C; H NMR (500 MHz, CDCl3):8.55 (s, 1H),
8.31 (d, J = 0.5 Hz, 2H), 8.25 (d, J = 7 Hz, 2H), 7.91 (t, J = 9.5 Hz, 3H),
7.68-7.56 (m, 7H), 7.52-7.49 (m, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ
158.1, 151, 150.5, 150.4, 150.1, 139.2, 138, 137.1, 137, 131.5, 129.8,
129.6, 129.4, 128.9, 128.8, 128.7, 127.7, 126.9, 126, 124.2, 120 ppm;
HRMS (ESI) m/z calcd for C27H18BrN3 [M + H]+ 464.0762; found 464.0750
(E)-6-((4-bromophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline (4m):
Orange solid; (63%); mp 215-216 oC; 1H NMR (400 MHz,
CDCl3):s, 1H), 8.29 (s, 2H), 8.16 (d, J = 8 Hz, 2H), 7.9 (s, 1H),
7.82 (d, J = 8.8 Hz, 2H), 7.66-7.58 (m, 7H), 7.37 (d, J = 8 Hz, 2H), 2.47 (s,
3H) ppm; 13C NMR (100 MHz, CDCl3): δ 158.1, 151.4, 150.5, 150.3,
149.9, 140, 138, 136.4, 132.4, 131.4, 129.7, 129.6, 128.9, 128.7, 127.6,
127.2, 125.9, 125.5, 124.4, 119.8, 119.7, 21.4 ppm; HRMS (ESI) m/z
calcd for C28H20BrN3 [ M + H]+ 478.0918; found 478.0927
(E)-2,4-diphenyl-6-(p-tolyldiazenyl)quinoline (4g): Orange solid;
(56%); mp 187-189 oC; 1H NMR (500 MHz, CDCl3):s, 1H), 8.33 (d,
J = 1.5 Hz, 2H), 8.27-8.25 (m, 2H), 7.93 (s, 1H), 7.65-7.52 (m, 11H),
7.37 (s, 1H), 2.77 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ 150.6,
148.3, 147.7, 143.9, 138.5, 131.3, 131.2, 129.8, 129.6, 128.9, 128.8,
128.7, 127.7, 127, 126.6, 126.5, 126.4, 126, 120.3, 119.9, 115.3, 17.5
ppm; HRMS (ESI) m/z calcd. for C28H21N3 [M + H]+ 400.1813; found
400.1778
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10.1002/ejoc.201800248
European Journal of Organic Chemistry
(E)-6-((2-iodophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline
(4n):
128.8, 128, 127.8, 127.5, 124.8, 124.1, 123.6, 119.9, 53.6 ppm; HRMS
(ESI) m/z calcd for C28H21N3O [ M + H]+ 416. 1778; found 416.1737
o
1
Orange solid; (68%); mp 290-291 C; H NMR (400 MHz, CDCl3):8.30
(s, 1H), 8.17 (d, J = 8.4 Hz, 1H), 8.07-8.04 (m, 1H), 7.92 (s, 2H), 7.69-
7.65 (m, 1H), 7.64 (d, J = 1.6 Hz, 1H), 7.62-7.57 (m, 6H), 7.45-7.37 (m,
3H), 7.20-7.16 (m, 1H), 2.47 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ
158.1, 151.2, 150.5, 150.4, 149.8, 140.1, 139.9, 137.9, 136.3, 132.3,
131.4, 129.7, 129.6, 128.9, 128.8, 128.7, 127.5, 127.2, 125.8, 120.7,
119.7, 117.2, 103.1, 21.4 ppm; HRMS (ESI) m/z calcd for C28H20IN3 [M +
H]+ 526.0778; found 526.0785
(E)-2-butyl-6-((4-nitrophenyl)diazenyl)-4-phenylquinoline (4t): Orange
solid; (77%); mp 160-162 oC; 1H NMR (500 MHz, CDCl3):8.62 (d, J =
2Hz, 1H), 8.39 (d, J = 9 Hz, 2H), 8.30-8.27 (m, 1H), 8.20 (d, J = 9 Hz,
1H), 8.05 (d, J = 9 Hz, 2H), 7.62-7.58 (m, 5H), 7.38 (s, 1H), 3.07 (t, J =
7.8 Hz, 2H), 1.92-7.86 (m, 2H), 1.54-1.50 (m, 2H), 1.01 (t, J = 8.8 Hz, 3H)
ppm; 13C NMR (125 MHz, CDCl3): δ 165, 155.7, 150.5, 150, 149.7, 148.7,
137.6, 130.9, 129.6, 128.8, 128.7, 125.5, 124.7, 123.5, 122.6, 119.2,
39.3, 32.1, 22.8, 14 ppm; HRMS (ESI) m/z calcd for C25H22N4O2 [ M + H]+
411.1820; found 411.1828
(E)-6-((2-bromophenyl)diazenyl)-4-phenyl-2-(p-tolyl)quinoline (4o):
Pale orange solid; (63%); mp 155-156 oC; 1H NMR (500 MHz,
CDCl3):8.61 (d, J = 2 Hz, 1H), 8.38-8.36 (m, 1H), 8.30 (d, J = 9 Hz, 1H),
8.17 (d, J = 3.5 Hz, 2H), 7.91-7.77 (m, 1H), 7.71-7.68 (m, 1H), 7.67-7.58
( m, 7H ), 7.37 (d, J = 8 Hz, 3H), 2.47 (s, 3H) ppm;13C NMR (125 MHz,
CDCl3): δ 158.1, 150.6, 150.3, 150.2, 149.6, 140, 137.9, 136.4, 133.8,
131.9, 131.4, 129.6, 129.6, 129.6, 129.6, 128.8, 128.7, 128.6, 127.9,
127.6, 127.5, 127.5, 126.1, 125.8, 120.2, 119.7, 117.6, 21.4 ppm; HRMS
(ESI) m/z calcd for C28H20BrN3 [M + H]+ 478.0878 ; found 478.0919
4-phenyl-2-propylquinoline (5d): Colourless liquid; (80%); 1H NMR
(500 MHz, CDCl3):d, J = 8.5 Hz, 1H), 7.90-7.89 (m, 1H), 7.73-7.69
(m, 1H), 7.55-7.49 (m, 5H), 7.47-7.44 (m, 1H), 7.27 (s, 1H), 3.03-3.00 (m,
2H), 1.94-1.90 (m, 2H), 1.08 (t, J = 7 Hz, 3H) ppm; 13C NMR (125 MHz,
CDCl3): δ 162.4, 148.5, 148.4, 138.3, 129.2, 129.2, 129.1, 128.3, 128.1,
125.7, 125.6, 125.3, 121.6, 41.3, 23.3, 14.1 ppm; HRMS (ESI) m/z calcd
for C18H17N [M + H]+ 248.1439; found 248.1451
(E)-4-phenyl-2-(p-tolyl)-6-(p-tolyldiazenyl)quinoline (4p): Orange
solid; (60%); mp 165-166 oC; 1H NMR (500 MHz, CDCl3):8.58-8.57 (m,
1H), 8.31 (d, J = 1.2 Hz, 2H), 8.18-8.16 (m, 2H), 7.91 (s, 1H), 7.68-7.58
(m, 7H), 7.39-7.37 (m, 4H), 2.77 (s, 3H), 2.47 (s, 3H) ppm; 13C NMR (125
MHz, CDCl3): δ 157.8, 150.7, 150.5, 150.4, 150.1, 140, 138.5, 138, 136.3,
131.3, 131.1, 129.7, 129.6, 128.8, 128.7, 128.6, 127.5, 126.8, 126.4,
125.9, 120.1, 119.7, 115.2, 21.4, 17.6 ppm; HRMS (ESI) m/z calcd for
C29H23N3 [M + H]+ 414.1970; found 414.1961
Ethyl
(E)-3-(6-((E)-(4-nitrophenyl)diazenyl)-4-phenyl-2-(p-
tolyl)quinolin-3-yl)acrylate (6): Orange solid; (82%); mp 256-258 oC; 1H
NMR (500 MHz, CDCl3): (d, J = 8.4 Hz, 2H), 8.27 (d, J = 6.8 Hz,
2H), 8.02 (d, J = 8.4 Hz, 2H), 7.60-7.58 (m, 6H), 7.38 (d, J = 6.8 Hz, 2H),
7.30 (d, J = 7.6 Hz, 2H), 4.48 (d, J = 16 Hz, 1H), 4.10-4.05 (m, 2H), 2.43
(s, 3H), 1.18 (t, J = 7.2 Hz, 3H) ppm;13C NMR (125 MHz, CDCl3): δ 166,
160.9, 155.6, 150.1, 149.8, 149.2, 148.8, 141.3, 139.2, 137.1, 135.7,
131.2, 129.8, 129.7, 129.2, 129, 128.8, 126.8, 126.6, 126, 124.7, 123.5,
119.8, 60.4, 21.4, 14.1 ppm; HRMS (ESI) m/z calcd for C33H26N4O4 [ M +
H]+ 543.2032; found 543.2022
(E)-4-phenyl-6-(4-methoxyphenyldiazenyl)-2-(p-tolyl)quinoline (4q) :
o
1
Orange solid; (62%); mp 181-182 C; H NMR (500 MHz, CDCl3):8.48
(d, J = 1 Hz, 1H), 8.31-8.30 (m, 2H), 8.16 (d, J = 8.5 Hz, 2H), 7.96-7.89
(m, 2H), 7.67-7.62 (m, 1H), 7.60-7.57 (m, 5H), 7.38-7.37 (m, J = 8 Hz,
2H), 7.03 (m, J = 9 Hz, 2H), 3.91 (s, 3H), 2.47 (s, 3H) ppm; 13C NMR
(125 MHz, CDCl3): δ 162.2, 157.5, 150.3, 147.1, 139.9, 138.9, 138.2,
131.1, 129.7, 129.6, 128.8, 128.7, 128.6, 128.6, 127.5, 126, 125.6, 124.8,
120.3, 119.6, 114.3, 55.6, 21.4 ppm; HRMS (ESI) m/z calcd for
C29H23N3O [M + H]+ 430.1878; found 430.1900
(E)-6-((4-nitrophenyl)diazenyl)-4-phenyl-3-(phenylethynyl)-2-(p-
o
1
tolyl)quinoline (7): Orange solid; (62%); mp 261-263 C; H NMR (500
MHz, CDCl3):-7.28 (m, 2H), 7.24 (d, J = 9.2Hz, 1H), 8.15-8.13 (m,
1H), 8.02-7.92 (m, 1H), 7.80 (d, J = 7.6 Hz, 2H), 7.71-7.49 (m, 11H),
7.40-7.34 (m, 3H), 2.48 (s, 3H) ppm;13C NMR (125 MHz, CDCl3): δ 156.1,
155.5, 15.4, 148.9, 148.8, 143.3, 141.5, 131.3, 131.1, 129.9, 129.6,
129.1, 128.9, 128.8, 128.7, 128.1, 127.8, 127.5, 127, 124.8, 124.7, 124,
123.6, 120, 116.6, 85.9, 77.5, 21.4 ppm; HRMS (ESI) m/z calcd for
C36H24N4O2 [ M + H]+ 545.1977 found 545.1971
(E)-4-phenyl-6-(phenyldiazenyl)-2-(p-tolyl)quinoline
(4r):
Orange
solid; (62%); mp 191-192 oC; 1H NMR (500 MHz, CDCl3):8.32 (s, 1H),
8.17 (d, J = 8 Hz, 2H), 7.96-7.91 (m, 2H), 7.68-7.58 (m, 3H), 7.55-7.49
(m, 8H), 7.38 (d, J = 8Hz, 2H), 2.47 (s, 3H) ppm; 13C NMR (125 MHz,
CDCl3): δ157.9, 152.7, 150.3, 150.3, 150.1, 139.9, 138.1, 136.4, 131.3,
131.1, 129.6, 129.1, 129, 128.8, 128.6, 127.5, 127.4, 126.5, 125.9, 122.8,
120.4, 120.1, 119.7, 21.4 ppm; HRMS (ESI) m/z calcd for C28H21N3
[M+H]+ 400.1778; found 400.1789
(E)-6-((4-nitrophenyl)diazenyl)-3,4-diphenyl-2-(p-tolyl)quinoline (8):
Orange solid; (66%); mp 230-232 oC; H NMR (500 MHz, CDCl3):-
1
m, 1H), 8.39-8.32 (m, 4H), 8.22 (d, J = 8 Hz, 4H), 8.12-8.10 (m, 4H),
7.99 (d, J = 3.2 Hz, 1H), 7.71-7.65 (m, 5H), 7.44-7.38 (m, 3H), 7.32-7.28
(m, 3H), 2.53 (s, 3H) ppm;13C NMR (125 MHz, CDCl3): δ 158.6, 155.8,
150.9, 150.6, 149.9, 148.7, 147.9, 147.3, 140.3, 137.8, 136.2, 131.6,
129.7, 129.6, 128.9, 128.8, 128.4, 127.6, 126.9, 126, 125.9, 124.8, 123.5,
120, 119.4, 21.5 ppm; ESI m/z [M + H]+ 521; HRMS (ESI) m/z calcd for
C34H24N4O2 [ M + H]+ 521.1977 found 521.1991
(E)-2-(4-methoxyphenyl)-4-phenyl-6-(phenyldiazenyl)quinoline (4s):
Orange solid; (66%); mp 187-189 oC; 1H NMR (400 MHz,
CDCl3):d, J = 4.8 Hz, 2H), 8.35-8.31 (m, 2H), 8.28 (d, J = 6.8 Hz,
2H), 8.18-8.05 (m, 2H), 7.74-7.65 (m, 5H), 7.59-7.53 (m, 3H), 7.43 (d, J =
6 Hz, 2H), 3.88 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.8, 156.1,
155.5, 150.3, 148.9, 148.8, 143.3, 141.5, 131, 129.9, 129.6, 129.2, 129,
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10.1002/ejoc.201800248
European Journal of Organic Chemistry
Crisp, Chem. Soc. Rev.1998, 27, 427; c) S. Brase, A. D. Meijere, Metal-
Catalyzed Cross-Coupling Reactions; Diederich, F., Stang, P. J., Eds.;
Wiley-VCH: Weinheim, Germany, 1998; p 99.
Acknowledgements
This work is partially supported by CSIR (02/200/14/EMR-II) India. AP
thank Central University of Rajasthan for the fellowships.
17. Sonogashira coupling see: K. Sonogashira, Y. Tohda, N. Hagihara,
Tetrahedron Lett. 1975, 16, 4467.
18. Suzuki coupling see: a) A. Suzuki, J. Organomet. Chem. 1999, 576, 147;
b) A. Suzuki, Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, Germany, 1998; 49; c) N.
Miyaura, Chem. Rev. 1995, 95, 2457.
Keywords: propargyl alcohols; iodocyclization; iodo-quinolines,
azo-coupling; regioselectivity, one-pot reactions
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FULL PAPER
Srinivasarao Yaragorla* and Abhishek
Pareek
Page No. – Page No.
Electrophilic cyclization of 2-
Aminophenylprop-1-yn-3-ols to 3-
Iodo-6-(aryldiazenyl)quinolines in a
one-pot, Azo-coupling and Iodo-
cyclization sequence
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