Microwave-Assisted Cascade Strategy for the Synthesis of Indolo[2,3-b]quinolines from 2-(Phenylethynyl)anilines and Aryl Isothiocynates

Article abstract of DOI:10.1021/acs.joc.6b02912

The in situ generated o-alkynylthioureas obtain by reacting 2-(phenylethynyl)anilines and aryl isothiocynates undergo efficient cascade cyclization in the presence of Ag₂CO₃ to form indoloquinolines under microwave heating. The prese

Full text of DOI:10.1021/acs.joc.6b02912

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Article
Microwave Assisted Cascade Strategy for the Synthesis of Indolo[2,3-
b]quinolines from 2-(Phenylethynyl)anilines and Aryl Isothiocynates
Wajid Ali, Anjali Dahiya, Ramdhari Pandey, Tipu Alam, and Bhisma K. Patel
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02912 • Publication Date (Web): 03 Feb 2017
Downloaded from http://pubs.acs.org on February 3, 2017
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Microwave Assisted Cascade Strategy for the Synthesis of Indolo[2,3-
b]quinolines from 2-(Phenylethynyl)anilines and Aryl Isothiocynates
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Wajid Ali,a Anjali Dahiya,a Ramdhari Pandey,a Tipu Alam,b Bhisma K. Patel*a
aDepartment of Chemistry, Indian Institute of Technology Guwahati, Guwahatiꢀ781039, India
bDepartment of Chemistry, Aligarh Muslim University, Aligarhꢀ202002, India
Fax: (+91)361ꢀ26909762.
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Eꢀmail: patel@iitg.ernet.in
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
Abstract: The in situ generated oꢀalkynyl thioureas obtain by reacting 2ꢀ(phenylethynyl)anilines
and aryl isothiocynates undergo efficient cascade cyclization in the presence of Ag2CO3 forming
indoloquinolines under microwave heating. The present tandem process allows the generation of
a variety of indolo[2,3ꢀb]quinolines derivatives in good to moderate yields with a wide
functional group tolerance.
INTRODUCTION
There have been continuous interests to synthesized natural product like compounds with
privileged scaffolds which are likely to have potential biological activities. Among these
privilege scaffolds, indoloquinoline alkaloids represent one of the important class of heterocycle
due to their immense biological activity1 (Figure 1) including the ability to interact with DNA as
an intercalator to inhibit topoisomerase II activity.2 Recent results reveals that some new
indolo[2,3ꢀb]quinoline (norcryptotackieine) type of natural product isolated from the leaves of
Justicia betonica3 exhibits exceptional pharmacological properties such as potent antiplasmodial,
antiproliferative, and antitumor.4 For example 2ꢀhalosubstituted norcryptotackieine are more
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active against plasmodium falciparum than neocryptolepine and are less cytotoxic. Besides,
indoloquinoline alkaloids are an integral part of the design, development and synthesis of various
modern commercial drugs.5 For these reasons, over the past several years tremendous efforts
have been devoted for the synthesis of such tetracyclicꢀfused quinoline alkaloids both by organic
and medicinal chemists with an aim to enhance the potency of indolo[2,3ꢀb]quinoline and a
variety of approaches have been successfully developed.6 Most of the available synthetic
strategies rely on the use of indole and its derivative as one of the coupling partner.6d,7 The
indoloquinoline system have also been assembled through a thermal cyclization of an enyneꢀ
carbodiimide.8 In 2003 Curran et al reported the synthesis of indolo[2,3ꢀb]quinoline via a
cascade radical annulation of oꢀalkynyl thiourea that involves irradiation of UV light (with
medium pressure Hg lamp) in a pyrex glass tube requiring a large excess of tris(trimethylsilyl)
silane (TTMSS) (4 equiv.), AIBN (1 equiv.) in anhydrous benzene (Scheme 1a).9 Although, this
method provides fruitful access to indoloquinolines, but the use of certain carcinogen (benzene),
expensive and excess amount of reagents and requirements of specialized setup giving moderate
yields and lesser substrate scope limits their applications. Therefore, developing strategy for the
synthesis of indoloꢀfused quinolines that are more efficient, cost effective, atom economical and
practical are well sought (Scheme 1b).
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Figure 1. Selected Indoloquinoline Possessing Biological Activity
Currently, cascade reactions are one of the most promising approaches in organic
synthesis due to their high atom economy, better efficiency and easy handling during the
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assembly of complex molecular structures.10 Such reactions have been adopted and emerged as
powerful synthetic tools for the conversion of internal alkynes into biologically active polycyclic
heterocycles.11 Furthermore, microwave assisted organic synthesis have the advantage of greater
reactivity, mild reaction conditions, high selectivity and shorter reaction times.12 Therefore
cascade reaction carried out under a microwave conditions are further advantageous to
conventional heating.
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Scheme 1. Strategy for the Synthesis of Indolo[2,3-b]quinolines
RESULT AND DISCUSSION
Our group has reported the synthesis of various heterocyclic scaffold through C−H bond
functionalization and cascade/tandem reactions.13 Owing to promising applications of
indolo[2,3ꢀb]quinolines as biologically active molecules, we plan to develop an alternative and
straight forward method for the synthesis of various functionalized indolo[2,3ꢀb]quinolines from
2ꢀ(phenylethynyl)anilines and aryl isothiocynates. We envisaged that the oꢀalkynyl thiourea
formed from 2ꢀ(phenylethynyl)aniline (1) and phenyl isothiocynate (a) may undergo
desulfurization in the presence of thiophilic reagents to produce a carbodiimide intermediate.14
The enyneꢀcarbodiimide intermediate so generated may undergo a thermal cyclization to produce
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the expected product indoloquinolines via a subsequent cyclization step. We first treated 2ꢀ
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(phenylethynyl)anilines (1) (1 equiv.) with phenyl isothiocynate (a) (2 equiv.) in the presence of
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Cu(OAc)2 (0.2 equiv.) as the catalyst in DMSO at 110 C for 24 h, but no desired product could
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be observed (Table 1, entry 1). However, the 2ꢀ(phenylethynyl)aniline (1) reacted with phenyl
isothiocynate (a) to form corresponding thiourea, which did not undergo any further change.
This result prompted us to investigate other thiophilic metal such as silver so as to facilitate
simultaneous desulfurization as well as activation of the internal alkyne for effective cyclization.
Superior alkynophilicity of silver is due to πꢀcoordination with carbon−carbon multiple bond
making it an ideal catalyst for alkyne based organic reactions. Based on these facts, we carried
out the same reaction under an identical condition but using Ag2CO3 (20 mol%) in lieu of
Cu(OAc)2. Gratifyingly, formation of a new product was observed in 21% yield (Table 1, entry
2). Characterization of the newly formed product through spectroscopic analysis (1HNMR,
13CNMR and HRMS) reveals the formation of our expected product 11ꢀphenylꢀ6Hꢀindolo[2,3ꢀ
b]quinoline (1a). Further optimizations were carried out to enhance the product yield using
various silver salts [Ag2SO4 (12%), AgOAc (09%), AgNO3 (13%), Ag(SO3CF3) (10%)] (Table
1, entries 3ꢀ6), but none were found to be superior to Ag2CO3. Replacement of silver salt with
other metal salt like Mn(OAc)2 (Table 1, entry 7) did not serve the purpose and the product was
obtained in a mere yield of 08%. The yield of the product was enhanced up to 36% (Table 1,
entry 8), when the loading of Ag2CO3 was increased to 1 equivalent. Further increase in the
Ag2CO3 (1.5 equiv.) loading had no substantial improvement in the product yield (38%) (Table
1, entry 9). Subsequently, we explored the possibility of using non metallic thiophilic reagents
such as DIB (diacetoxy benzene) (19%) and molecular iodine (21%) (Table 1, entry 10 and 11)
in combination with Ag2CO3 (20 mol%). However, the results suggest none of these
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combinations are suitable for this transformation. To our delight, increasing the reaction
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temperature to 130 C from 110 C improved the yield up to 47% (Table 1, entry 12). Further
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increasing the reaction temperature to 150 C had no substantial effect on the product yield
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(46%) (Table 1, entry 13). The reaction in other solvents such as DMF, mesitylene,
chlorobenzene, and 1,4ꢀdioxane tested did not give any satisfactory result compared to that of
DMSO (Table 1, entries 14ꢀ17). Formation of a trace of the product in absence of Ag2CO3 (Table
1, entry 14) suggests its essential role in this overall transformation.
Table 1. Optimization of Experimental Conditionsa
entry
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metal salt
Cu(OAc)2 (20%)
Ag2CO3 (20%)
Ag2SO4 (20%)
AgOAc (20%)
AgNO3 (20%)
Ag(SO3CF3) (20%)
Mn(OAc)2 (20%)
Ag2CO3 (100%)
Ag2CO3 (150%)
Ag2CO3 (20%)
Ag2CO3 (20%)
Ag2CO3 (100%)
Ag2CO3 (100%)
Ag2CO3 (100%)
Ag2CO3 (100%)
Ag2CO3 (100%)
Ag2CO3 (100%)
ꢀ
solvent
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
temp. (oC) yield %b
110
110
110
110
110
110
110
110
110
110
110
130
150
130
130
130
130
130
n.d.
21
12
09
13
10
08
36
38
19c
21d
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14
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15
trace
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DMF
Mesitylene
Chlorobenzene
1,4ꢀdioxane
DMSO
aReaction condition: 1 (0.25 mmol), a (0.50 mmol), Ag salts, solvent (3 mL), 24
h. bIsolated pure product. c1 eq. DIB. d1 eq. iodine. n. d. = not detected.
Recently microwave assisted organic synthesis have been widely employed, as reaction
under microwave improve the product yields and shorten the reaction time. So, we thought of
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performing the above reaction under a microwave condition. Under microwave condition [(10
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min. reaction time at 130 C (150 W, closed vial)] the desired product was obtain in an improve
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yield of 58% (Table 2, entry 1) under otherwise identical condition. Increasing the reaction time
from 10 min. to 30 min. enhance the product yield up to 70%. (Table 2, entry 2). However, any
further increase in the reaction time (60 min.) had slightly negative effect on the product yield
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(Table 2, entry 3). An elevated temperature 150 C of the microwave did not serve the purpose
(Table 2, entry 4). Here again reaction in the absence of Ag2CO3 gave the desired product in
trace, suggesting its essential requirement (Table 2, entry 5). Reduction in the quantity of phenyl
isothiocynate (a) from 2 to 1.5 equivalent has no substantial effect on the overall product yield
(Table 2, entry 6) under the present reaction condition. When the molar ratio of 1 and a was 1:1
the yield of product dropped to 62% (Table 2, entry 7).
Table 2. Effect of Microwave Heating on Optimization Reactiona
entry
metal salt
temp. (oC)
130
130
130
150
130
130
130
yield %b
58
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Ag2CO3 (100%)
Ag2CO3 (100%)
Ag2CO3 (100%)
Ag2CO3 (100%)
ꢀ
70c
66d
69
trace
71e
Ag2CO3 (100%)
Ag2CO3 (100%)
62f
aReaction condition: 1 (0.25 mmol), a (0.5 mmol), Ag2CO3 (0.25 mmol),
b
c
d
e
DMSO (3 mL), MW 10 min. Isolated pure product. 30 min.. 1 h. a
(0.375 mmol). fa (0.25 mmol).
Under the optimized condition (Table 2, entry 6), various 2ꢀ(phenylethynyl)anilines and
aryl isothiocynates were subjected to the reaction condition to explore the scope of this cascade
protocol. First of all the electronic effect of substituents R3 on the aryl isothiocynate was
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evaluated (Scheme 2, 1aꢀ1f) and the results are summarized in Scheme 2. The structure of the
product (1a) has been unequivocally established by single crystal Xꢀray crystallography (Figure
S1, see Supporting Information). Phenyl isothiocynates possessing electronꢀdonating (EDG)
substituents (bꢀd) at para position afforded the corresponding products in better yields compared
to unꢀsubstituted (a) and electronꢀwithdrawing (EWG) substituents (eꢀf). Phenyl isothiocynates
having substituent such as –Me (b), –tBu (c) and –OMe (d) at their para position provided their
corresponding products (1b, 78%), (1c, 76%) and (1d, 80%) (Scheme 2) respectively.
Comparatively lower yield of the indolo[2,3ꢀb]quinolines (1eꢀ1f, Scheme 2) were obtained when
moderately electronꢀwithdrawing groups [–Cl (e) (67%) and –F (f) (64%)] were present on the
phenyl isothiocynate. We also examine the effect of substituents R2 present on the other phenyl
ring of 2ꢀ(phenylethynyl)aniline on the product yield and found similar effect to that of R3
substituents on the phenyl isothiocynate i.e. substrates bearing electron releasing groups such as
–Me (2) and –OMe (3) furnished better yields [(2a, 77%), (3a, 81%)] of their product compared
to electronꢀwithdrawing substituents –F (4) giving product (4a, 66%) when reacted with phenyl
isothiocynate (a) (Scheme 2).
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Scheme 2. Substrate Scope for the Synthesis of Indolo[2,3-b]quinolinesa,b
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aReaction conditions: 1−8 (0.25 mmol), a−f (0.375 mmol), Ag2CO3 (0.25 mmol),
MW, 130 oC, time 20−30 min. bYields of the pure product reported.
Next, the effect of R1 substituents present on the amine bearing ring of 2ꢀ
(phenylethynyl)anilines (5, 6 and 7) on the reaction shows opposite trend on the product yields to
that of substituents R2 and R3. When substituent R1 is an electronꢀdonating group such as –Me
(5) the product (5a) was obtained in 67% yield. Whereas, presence of electronꢀwithdrawing
substituents such as –F (6), –Br (7) afford their corresponding products (6a) and (7a) in 76% and
69% yield respectively. 2ꢀ(Naphthalenꢀ1ꢀylethynyl)aniline (8) also reacted efficiently with
phenyl isothiocynate (a) to provide the indoloquinoline (8a) in 70% yield (Scheme 2). To
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demonstrate the scalability of the present methodology a reaction was carried out with 2ꢀ
(phenylethynyl)anilines (1) (4.15 mmol, 800 mg) with phenyl isothiocynate (a) (6.23 mmol, 841
mg) under the optimized reaction conditions giving 51% yield of the product.
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Scheme 3. Reaction of Substituted 2-(Phenylethynyl)anilines and Phenyl Isothiocynatesa,b
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aReaction conditions: 2−10 (0.25 mmol), a−f (0.0375 mmol), Ag2CO3 (0.25
mmol), MW, 130 oC, time 20−30 min. bYields of the pure product reported
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The present strategy was equally successful to any type of substituents (R1, R2 and R3)
present anywhere in the aryl ring of the substrates (Scheme 3). When both the substituents R2
and R3 are electronꢀdonating such as pꢀMe (2)/pꢀMe (b), pꢀOMe (3)/pꢀMe (b) good yields (81%
and 83%) of their respective products (2b) and (3b) were obtained. On the other hand, when R2
is electronꢀdonating and R3 is electronꢀwithdrawing substituents such as pꢀMe (2)/pꢀF (f), pꢀOMe
(3)/pꢀF (f), the yields of the isolated products were slightly lower [(2f, 74%), (3f, 76%)]. When
the substituents positions are reversed i.e. R2 is substituted with an electronꢀwithdrawing group
4ꢀF (4) and R3 with an electronꢀdonating group 4ꢀMe (b), the cascade product (4b) was obtained
in 73% yield. Substitution of R2 and R3 with an electronꢀwithdrawing group 4ꢀF (4) leads to
further drop in the product yield (4f, 62%). Next, when substituents R1 and R3 are EDG and
EWG or R1 with an EDG and R3 with EWG group or vice versa moderate yields ranges between
59%−74% of their corresponding products (5bꢀ6f) were obtained. Further, when both R1 and R2
are either electronꢀdonating 4ꢀMe (9) or electronꢀwithdrawing 4ꢀF (10) groups, products (9a) and
(10a) were obtained in 67% and 70% yields respectively. When all the substituent R1, R2 and R3
are either 4ꢀMe or 4ꢀF the products (9b and 10f) were isolated in 72% and 63% yields
respectively. Although, in this multistep process it is difficult to determine the exact rate
determining steps, however from Scheme 2 and Scheme 3 it is evident that the electronic effect
of substituent R1 on the product yield is more significant compared to substituents R2 and R3.
When strongly electron withdrawing substituent such as –NO2, –CN and –CF3 are present on the
R1 ring (amine bearing ring), the starting materials remained unreacted (even thiourea
intermediate was not formed). Nevertheless, when the same electronꢀwithdrawing substituents
are present on the R3 ring (i.e aryl isothiocyanate) both reacted to form the intermediate thiourea,
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but failed to undergo any further transformation. However, using preformed carbodiimide
intermediates, similar annulated products were successfully obtained even for substrates bearing
strong electronꢀwithdrawing groups as reported.8b
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To understand the mechanism of this process, few control experiments were conducted
(Scheme 4). When a presynthesized 1ꢀphenylꢀ3ꢀ(2ꢀ(phenylethynyl)phenyl)thiourea (A) was
subjected to the standard reaction condition, formation of the expected product (1a) in 73% yield
suggests the possible formation of a thiourea intermediate (A) in the present transformation
(Scheme 4, pathꢀa). However, in the absence of Ag2CO3 the reaction was completely
unproductive revealing the essential requirements of Ag2CO3 in the overall transformation
(Scheme 4, pathꢀb). Furthermore, 2ꢀ(phenylethynyl)ꢀNꢀ((phenylimino)methylene)aniline (B)
afforded the desired product in the presence of Ag2CO3 (77%) (Scheme 4, pathꢀc) and in its
absence (61%) (Scheme 4, pathꢀd). Thus the major role of the Ag2CO3 is the generation of
carbodiimide intermediate (B) from thiourea (A).
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Scheme 4. Control Experiments
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Formation of Ag2S via desulfurization of thiourea has been confirmed by the powder
XRD and EDX analysis as shown in Figure 2. The powder Xꢀray diffraction (PXRD) patterns
showed the phase purity and crystal structure of the formed Ag2S, as shown in Figure 2(i).
PXRD pattern of Ag2S is defined to be monoclinic acanthite phase with (121), (102), (012),
(043), (025), (ꢀ102), (411), (ꢀ103), (ꢀ123), (031), (102), (112), (004), (014), (ꢀ133), (ꢀ215), (041),
(ꢀ225), (ꢀ105), (ꢀ116) and (141) crystal planes according to the JCPDS Card No. 24ꢀ0715. To
further confirm the elemental composition and distribution in Ag2S, selected area elemental
mapping was carried out by energy dispersive Xꢀray (EDX) spectroscopic technique which is
depicted in the Figure 2(ii). EDX pattern in Figure 2(ii) shows the elemental compositions (At
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%) contained in the Ag2S. It displays that Ag2S contain a weight ratio of silver to sulphur 2.3:1,
which is very close to the expected ratio of Ag2S (2:1).
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Ag2S
(025)
JCPDS # 24-0715
(-103)
(-123)
(043)
(031)
(102)
(-215)
(014)
(141)
(121)
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2θ (Degree)
Figure 2. (i) Powder X-ray diffraction (PXRD) and (ii) Energy-dispersive X-ray
spectroscopy (EDS) pattern of the formed Ag2S
On the basis of our experimental findings and previous literature,8 a plausible reaction
mechanism has been proposed as depicted in Scheme 5. Reaction of 2ꢀ(phenylethynyl)anilines
(1) and phenyl isothiocynate (a) forms intermediate thiourea (A), which is desulfurized in the
presence of Ag2CO3 to a carbodiimide intermediate (B).14 Intramolecular thermal cyclization of
(B) generated a carbene type intermediate (C). The intermediate (C) undergo further cyclization
via carbene C−H insertion to form a non aromatic cyclize species (D), which is aromatized to
give the desired product (1a) (Scheme 5).
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Scheme 5. Proposed Mechanistic Pathway
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In conclusion, we have developed an elegant cascade approach for the synthesis of
indoloquinolines. This protocol allows the practical synthesis of many valuable indolquinoline
alkaloids through Ag2CO3 mediated cascade annulation of internal alkynes under microwave
heating. This methodology has the advantage of good functional group tolerance, mild
microwave reaction and shorter reaction time.
EXPERIMENTAL SECTION
General information:
All the reagents were commercial grade and used without purification. Organic extracts were
dried over anhydrous sodium sulphate. Solvents were removed in a rotary evaporator under
reduced pressure. Silica gel (60ꢀ120 mesh size) was used for the column chromatography. The
microwave reactions were carried out on the CEM Discover system (Model No. 908010,
manufactured by CEM Company in USA, with vertically focused infrared [IR] temperature
control system. Reactions were monitored by TLC on silica gel 60 F254 (0.25mm). NMR spectra
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were recorded in DMSOꢀd6, CDCl3 with tetramethylsilane as the internal standard for H NMR
(400 MHz and 600 MHz), DMSOꢀd6 or CDCl3 solvent as the internal standard for 13C NMR (100
MHz and 150 MHz). HRMS spectra were recorded using ESI mode (QꢀTOF MS Analyzer).
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General Procedure for the Synthesis of 11-Phenyl-6H-indolo[2,3-b]quinolone (1a).
2ꢀ(Phenylethynyl)aniline (1) (0.25 mmol, 48 mg) and phenyl isothiocynate (a) (0.375 mmol,
51 mg), and Ag2CO3 (0.25 mmol, 69 mg) in DMSO (1 mL) were taken in an oven dried
microwave reaction tube. The reaction vial was then sealed with a cap and stirred at 130 oC [150
W] under microwave irradiation for 0.5h. The reaction mixture was then cooled to room
temperature and admixed with ethyl acetate (25 mL). The organic layer was washed sequentially
with a saturated solution of sodium bicarbonate (2 x 5 mL). The organic layer was dried over
anhydrous Na2SO4 and evaporated under vacuum. The crude product so obtained was then
purified by silica gel column chromatography using EtOAc and hexane as eluent to give product
1a (52 mg, 71%).
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11-Phenyl-6H-indolo[2,3-b]quinoline (1a).9 Brown solid (52 mg, 71%); m.p. 251−253 C; H
NMR (400 MHz, DMSOꢀd6): δ (ppm) 6.92−6.93 (m, 2H), 7.34−7.43 (m, 2H), 7.47 (dd, 1H, J =
6.8 Hz), 7.53 (dd, 2H, J = 8.0 Hz), 7.62−7.71 (m, 5H), 8.04 (d, 1H, J = 8.4 Hz), 11.81 (s, 1H);
13C NMR (100 MHz, DMSOꢀd6): δ (ppm) 110.8, 115.4, 119.2, 120.2, 122.3, 122.7, 122.9, 125.7,
127.2, 127.8, 128.4, 128.6, 128.98, 129.02, 136.0, 141.4, 141.6, 146.3, 152.5; HRMS (ESI):
calcd. for C21H15N2 [M + H+] 295.1230; found 295.1224.
2-Methyl-11-phenyl-6H-indolo[2,3-b]quinoline (1b).6e Yellow solid (60 mg, 78%); m.p.
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253−255 C; 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.37 (s, 3H), 6.86 (d, 1H, J = 7.6 Hz),
6.92 (t, 1H, J = 7.6 Hz), 7.38 (s, 1H), 7.41 (t, 1H, J = 6.8 Hz), 7.47 (d, 1H, J = 8.0 Hz),
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7.51−7.55 (m, 3H), 7.64−7.72 (m, 3H), 7.95 (d, 1H, J = 8.8 Hz), 11.78 (s, 1H); C NMR (100
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MHz, DMSOꢀd6): δ (ppm) 21.3, 110.9, 115.4, 119.2, 120.3, 122.5, 122.8, 124.3, 127.2, 127.8,
128.7, 129.1, 129.2, 130.8, 131.8, 136.2, 140.8, 141.6, 144.9, 152.1; HRMS (ESI): calcd. for
C22H17N2 [M + H+] 309.1386; found 309.1382.
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2-(Tert-butyl)-11-phenyl-6H-indolo[2,3-b]quinoline (1c). Yellow solid (66.5 mg, 76%); m.p.
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259−261 C; H NMR (400 MHz, DMSOꢀd6): δ (ppm) 1.25 (s, 9H), 6.90−6.96 (m, 2H),
7.40−7.44 (m, 1H), 7.47 (d, 1H, J = 8.0 Hz), 7.56 (d, 3H, J = 6.8 Hz), 7.66−7.74 (m, 3H), 7.84
(dd, 1H, J = 8.8 Hz), 7.99 (d, 1H, J = 8.8 Hz) 11.76 (s, 1H); 13C NMR (100 MHz, DMSOꢀd6): δ
(ppm) 30.9, 34.5, 110.9, 115.3, 119.2, 120.2, 120.3, 122.2, 122.3, 127.0, 127.5, 127.8, 128.7,
129.1, 136.1, 141.5, 141.6, 144.8, 144.9, 152.3; HRMS (ESI): calcd. for C25H23N2 [M + H+]
351.1856; found 351.1852.
2-Methoxy-11-phenyl-6H-indolo[2,3-b]quinoline (1d).6e Black solid (65 mg, 80%); m.p.
257−259 oC; 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 3.78 (s, 3H), 6.96 (t, 1H, J = 8.4 Hz), 7.03
(d, 1H, J = 7.6 Hz), 7.07 (d, 1H, J = 7.8 Hz), 7.38 (d, 2H, J = 7.6 Hz), 7.48 (d, 1H, J = 8.0 Hz),
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7.53−7.55 (m, 2H), 7.63−7.70 (m, 3H), 8.11 (d, 1H, J = 9.2 Hz), 12.18 (s, 1H); C NMR (100
MHz, DMSOꢀd6): δ (ppm) 55.7, 105.0, 110.9, 117.0, 119.7, 121.1, 121.2, 123.2, 124.3, 127.9,
128.0, 128.7, 129.3, 129.5, 136.8, 141.6, 141.8, 142.2, 152.3, 155.4; HRMS (ESI): calcd. for
C22H17N2O [M + H+] 325.1335; found 325.1337.
2-Chloro-11-phenyl-6H-indolo[2,3-b]quinoline (1e). White solid (55 mg, 67%); m.p. 207−209
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oC; H NMR (400 MHz, DMSOꢀd6): δ (ppm) 6.90−6.97 (m, 2H), 7.42−7.46 (m, 1H), 7.49 (d,
1H, J = 8.0 Hz), 7.52−7.55 (m, 3H), 7.66−7.73 (m, 4H), 8.04 (d, 1H, J = 8.8 Hz), 11.94 (s, 1H);
13C NMR (100 MHz, DMSOꢀd6): δ (ppm) 111.0, 116.2, 119.5, 119.9, 122.5, 123.5, 124.0, 127.0,
128.3, 128.8, 128.9, 129.0, 129.2, 129.3, 135.2, 140.5, 141.8, 144.7, 152.6; HRMS (ESI): calcd.
for C21H14ClN2 [M + H+] 329.0840; found 329.0828.
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2-Fluoro-11-phenyl-6H-indolo[2,3-b]quinoline (1f).6e Yellow solid (50 mg, 64%); m.p.
266−268 oC; 1H NMR (400 MHz, CDCl3): δ (ppm) 6.91 (t, 1H, J = 8.0 Hz), 6.99 (d, 1H, J = 8.0
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(100 MHz, CDCl3): δ (ppm) 109.6, 109.9, 111.0, 117.3, 118.7, 118.9, 119.9, 120.5, 123.2, 124.0,
124.1, 128.1, 128.2, 128.3, 129.0, 129.3, 129.5, 136.0, 141.9, 142.05, 142.1, 143.0, 152.9, 157.3,
159.7; HRMS (ESI): calcd. for C21H14FN2 [M + H+] 313.1136; found 313.1147.
11-(p-Tolyl)-6H-indolo[2,3-b]quinoline (2a). Yellowish solid (59.5 mg, 77%); m.p. 221−223
oC ;1H NMR (400 MHz, CDCl3): δ (ppm) 2.60 (s, 3H), 7.01 (t, 1H, J = 8.0 Hz), 7.16 (d, 1H, J =
8.0 Hz), 7.38−7.45 (m, 4H), 7.46 (d, 2H, J = 8.0 Hz), 7.53 (t, 1H, J = 8.0 Hz), 7.74 (dd, 1H, J =
6.8 Hz), 7.83 (dd, 1H, J = 8.8 Hz), 8.23 (d, 1H, J = 8.0 Hz), 12.34 (s, 1H); 13C NMR (100 MHz,
CDCl3): δ (ppm) 21.7, 111.0, 117.1, 119.9, 121.4, 123.0, 123.3, 124.1, 125.6, 126.5, 126.9,
128.0, 129.0, 129.5, 129.8, 133.5, 138.5, 141.8, 143.3, 146.3, 153.6; HRMS (ESI): calcd. for
C22H17N2 [M + H+] 309.1386; found 309.1394.
11-(4-Methoxyphenyl)-6H-indolo[2,3-b]quinoline (3a). Brown solid (65.5 mg, 81%); m.p.
243−245 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 3.91 (s, 3H), 6.98 (t, 1H, J = 7.8 Hz), 7.06
(d, 1H, J = 7.8 Hz), 7.24 (d, 2H, J = 9.2 Hz), 7.38 (t, 1H, J = 7.8 Hz), 7.43 (dd, 1H, J = 7.8 Hz),
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7.44−7.49 (m, 3H), 7.67−7.72 (m, 2H), 8.04 (d, 1H, J = 8.4 Hz) 11.83 (s, 1H); C NMR (150
MHz, DMSOꢀd6): δ (ppm) 55.3, 110.9, 114.5, 115.7, 119.3, 120.4, 122.4, 122.8, 123.3, 125.9,
127.3, 127.8, 127.9, 128.5, 130.5, 141.5, 141.6, 146.4, 152.5, 159.5; HRMS (ESI): calcd. for
C22H17N2O [M + H+] 325.1335; found 325.1334.
11-(4-Fluorophenyl)-6H-indolo[2,3-b]quinoline (4a). Brown solid (51.5 mg, 66%); m.p.
297−299 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 6.95 (d, 1H, J = 7.8 Hz), 7.00 (t, 1H, J =
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7.2 Hz), 7.40 (t, 1H, J = 7.8 Hz), 7.44−7.47 (m, 1H), 7.50 (d, 1H, J = 7.8 Hz), 7.54 (t, 2H, J = 8.4
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NMR (150 MHz, DMSOꢀd6): δ (ppm) 111.0, 115.7, 116.2, 116.3, 118.2, 119.5, 120.1, 122.3,
123.0, 125.6, 127.3, 128.1, 128.7, 128.8, 131.35, 131.41, 132.2, 140.5, 141.7, 146.3, 152.4,
161.5, 163.2; HRMS (ESI): calcd. for C21H14FN2 [M + H+] 313.1136; found 313.1150.
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9-Methyl-11-phenyl-6H-indolo[2,3-b]quinoline (5a).8b Pale yellow solid (51.5 mg, 67%); m.p.
193−195 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 2.17 (s, 3H), 6.70 (s, 1H), 7.26 (d, 1H, J =
7.6 Hz), 7.37 (dd, 2H, J = 9.6 Hz), 7.47 (d, 1H, J = 7.8 Hz), 7.53 (d, 2H, J = 7.8 Hz), 7.61 (d, 1H,
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J = 7.8 Hz), 7.68−7.71 (m, 3H), 8.03 (d, 1H, J = 8.4 Hz), 11.73 (s, 1H); C NMR (150 MHz,
DMSOꢀd6): δ (ppm) 21.1, 110.7, 115.4, 118.2, 120.3, 121.8, 122.4, 122.7, 125.7, 127.2, 127.8,
128.5, 128.7, 128.8, 129.1, 136.0, 139.8, 141.4, 146.3, 152.7; HRMS (ESI): calcd. for C22H17N2
[M + H+] 309.1386; found 309.1392.
9-Fluoro-11-phenyl-6H-indolo[2,3-b]quinoline (6a). Light yellow solid (60 mg, 76%); m.p.
276−278 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 6.51 (dd, 1H, J = 9.6 Hz), 7.30 (td, 1H, J
= 9.6 Hz), 7.39 (t, 1H, J = 7.8 Hz), 7.48 (dd, 1H, J = 8.4 Hz), 7.54 (d, 2H, J = 6.0 Hz), 7.63 (d,
1H, J = 7.8 Hz), 7.68−7.44 (m, 4H), 8.05 (d, 1H, J = 8.4 Hz), 11.89 (s, 1H); 13C NMR (150
MHz, DMSOꢀd6): δ (ppm) 107.8, 108.0, 111.9, 112.0, 115.1, 115.3, 115.4, 120.6, 120.7, 122.6,
123.0, 125.9, 127.4, 128.9, 128.98, 129.03, 129.2, 135.5, 138.1, 142.3, 146.7, 153.0, 155.4,
157.0; HRMS (ESI): calcd. for C21H14FN2 [M + H+] 313.1136; found 313.1150.
9-Bromo-11-phenyl-6H-indolo[2,3-b]quinoline (7a).6d Brown solid (64 mg, 69%); m.p.
229−231 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 6.93 (s, 1H), 7.27 (t, 2H, J = 7.2 Hz), 7.45
(d, 2H, J = 8.4 Hz), 7.55 (d, 1H, J = 6.0 Hz), 7.63 (d, 1H, J = 8.4 Hz), 7.70−7.76 (m, 4H), 8.06
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(d, 1H, J = 8.4 Hz), 12.01 (s, 1H); 13C NMR (150 MHz, DMSOꢀd6): δ (ppm) 111.1, 113.0, 114.5,
118.2, 121.8, 123.3, 124.5, 125.9, 127.4, 128.8, 129.0, 129.3, 130.3, 135.5, 139.7, 140.5, 142.4,
146.8, 152.4; HRMS (ESI): calcd. for C21H14BrN2 [M + H+] 373.0335; found 373.0350.
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11-(Naphthalen-1-yl)-6H-indolo[2,3-b]quinoline (8a). Brown solid (60mg, 70%); m.p.
256−259 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 6.35 (d, 1H, J = 7.8 Hz), 6.73 (t, 1H, J =
7.8 Hz), 7.09 (d, 1H, J = 8.4 Hz), 7.22 (t, 1H, J = 7.8 Hz), 7.26 (t, 1H, J = 7.2 Hz), 7.33−7.38 (m,
2H), 7.48 (d, 1H, J = 8.4 Hz), 7.52 (t, 1H, J = 7.8 Hz), 764 (d, 1H, J = 6.6 Hz), 7.70 (t, 1H, J =
7.8 Hz), 7.79 (t, 1H, J = 7.8 Hz), 8.12 (d, 2H, J = 8.4 Hz), 8.23 (d, 1H, J = 8.4 Hz), 11.93 (s,
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1H); C NMR (150 MHz, DMSOꢀd6): δ (ppm) 110.9, 116.5, 119.3, 120.0, 122.2, 123.0, 123.5,
124.9, 125.8, 126.0, 126.5, 126.9, 127.1, 127.4, 128.0, 128.6, 128.7, 129.0, 131.0, 133.4, 133.5,
139.5, 141.7, 146.4, 152.6; HRMS (ESI): calcd. for C25H17N2 [M + H+] 345.1386; found
345.1373.
2-Methyl-11-(p-tolyl)-6H-indolo[2,3-b]quinoline (2b). Light Yellow solid (65 mg, 81%); m.p.
303−305 oC; 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.16 (s, 3H), 2.29 (s, 3H), 6.69−6.74 (m,
2H), 7.18 (d, 4H, J = 7.6 Hz), 7.26 (t, 3H, J = 7.6 Hz), 7.31 (dd, 1H, J = 8.8 Hz), 7.72 (d, 1H, J =
8.4 Hz) 11.51 (s, 1H); 13C NMR (100 MHz, DMSOꢀd6): δ (ppm) 21.1, 21.2, 110.7, 115.5, 118.2,
119.1, 120.3, 122.3, 123.0, 124.4, 127.1, 127.7, 128.9, 129.7, 131.5, 133.1, 137.8, 140.9, 141.6,
144.9, 152.1; HRMS (ESI): calcd. for C23H19N2 [M + H+] 323.1543; found 323.1552.
11-(4-Methoxyphenyl)-2-methyl-6H-indolo[2,3-b]quinoline (3b). Yellow solid (70 mg, 83%);
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m.p. 275−278 C; H NMR (600 MHz, DMSOꢀd6): δ (ppm) 2.38 (s, 3H), 3.91 (s, 3H), 6.96 (t,
1H, J = 7.2 Hz), 7.00 (d, 1H, J = 7.8 Hz), 7.24 (d, 2H, J = 8.4 Hz), 7.40−7.45 (m, 5H), 7.53 (d,
1H, J = 9.0 Hz), 7.94 (d, 1H, J = 8.4 Hz), 11.75 (s, 1H); 13C NMR (150 MHz, DMSOꢀd6): δ
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(ppm) 21.2, 55.2, 110.8, 114.5, 115.7, 119.2, 120.4, 122.3, 123.2, 124.5, 127.1, 127.8, 128.0,
130.4, 130.7, 131.7, 140.9, 141.6, 145.0, 152.1, 159.4; HRMS (ESI): calcd. for C23H19N2O [M +
H+] 339.1492; found 339.1482.
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2-Fluoro-11-(p-tolyl)-6H-indolo[2,3-b]quinoline (2f). Pale brown solid (60 mg, 74%); m.p.
280−282 oC; 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.49 (s, 3H), 6.94−7.01 (m, 2H), 7.22 (dd,
1H, J = 10.6 Hz), 7.40−7.51 (m, 6H), 7.58−7.65 (m, 1H), 8.08 (dd, 1H, J = 9.2 Hz), 11.86 (s,
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1H); C NMR (100 MHz, DMSOꢀd6): δ (ppm) 21.1, 108.4, 108.7, 111.0, 116.1, 118.2, 118.5,
119.5, 119.8, 122.5, 123.2, 123.3, 128.3, 128.9, 129.7, 129.8, 129.9, 132.4, 138.3, 140.88,
140.93, 141.8, 143.4, 152.3, 156.4, 158.8; HRMS (ESI): calcd. for C22H16FN2 [M + H+]
327.1292; found 327.1285.
2-Fluoro-11-(4-methoxyphenyl)-6H-indolo[2,3-b]quinoline (3f). Black solid (65 mg, 76%);
o
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m.p. 238−240 C; H NMR (600 MHz, DMSOꢀd6): δ (ppm) 3.92 (s, 3H), 7.00 (t, 1H, J = 7.2
Hz), 7.07 (t, 2H, J = 7.8 Hz), 7.26 (d, 2H, J = 8.4 Hz), 7.45−7.50 (m, 3H), 7.64 (td, 1H, J = 9.6
13
Hz), 7.81 (d, 1H, J = 9.0 Hz), 8.09 (dd, 1H, J = 9.6 Hz), 11.85 (s, 1H); C NMR (150 MHz,
DMSOꢀd6): δ (ppm) 55.3, 108.5, 108.7, 111.0, 112.4, 112.5, 114.5, 114.7, 116.3, 118.3, 118.5,
119.5, 119.9, 122.6, 123.47, 123.52, 127.3, 128.3, 129.5, 130.5, 141.8, 143.8, 143.4, 152.3,
156.8, 159.57, 159.63; HRMS (ESI): calcd. for C22H16FN2O [M + H+] 343.1241; found
343.1231.
11-(4-Fluorophenyl)-2-methyl-6H-indolo[2,3-b]quinoline (4b). Pale brown solid (59.5 mg,
73%); m.p. 288−289 oC; 1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.39 (s, 3H), 6.89 (d, 1H, J =
7.6 Hz), 6.97 (t, 1H, J = 7.6 Hz), 7.36 (s, 1H), 7.41−7.48 (m, 2H), 7.52−7.61 (m, 5H), 7.95 (d,
1H, J = 8.4 Hz), 11.78 (s, 1H); 13C NMR (150 MHz, DMSOꢀd6): δ (ppm) 21.4, 111.2, 115.9,
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116.4, 116.5, 119.6, 120.3, 122.4, 123.1, 124.4, 127.3, 128.2, 131.2, 131.5, 131.6, 132.3, 132.47,
132.49, 140.1, 141.8, 144.9, 152.1, 161.7, 163.3; HRMS (ESI): calcd. for C22H16FN2 [M + H+]
327.1292; found 327.1274.
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2-Fluoro-11-(4-fluorophenyl)-6H-indolo[2,3-b]quinoline (4f). Pale brown solid (51 mg, 62%);
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m.p. 308−310 C; H NMR (400 MHz, DMSOꢀd6): δ (ppm) 6.96 (d, 1H, J = 7.6 Hz), 7.01 (dd,
1H, J = 8.0 Hz), 7.22 (dd, 1H, J = 7.6 Hz), 7.43−7.51 (m, 2H), 7.56 (t, 2H, J = 4.8 Hz),
7.62−7.69 (m, 3H), 8.11 (dd, 1H, J = 9.2 Hz), 11.90 (s, 1H); 13C NMR (150 MHz, DMSOꢀd6): δ
(ppm) 108.7, 108.9, 111.5, 115.5, 115.7, 116.67, 116.72, 116.8, 118.9, 119.1, 119.9, 120.0,
120.5, 120.6, 122.7, 123.4, 123.5, 128.9, 129.86, 129.92, 131.59, 131.64, 140.4, 142.2, 143.3,
152.3, 157.3, 158.9, 161.9, 163.6; HRMS (ESI): calcd. for C21H13F2N2 [M + H+] 331.1041;
found 331.1058.
2,9-Dimethyl-11-phenyl-6H-indolo[2,3-b]quinoline (5b). Brown solid (53 mg, 66%); m.p.
o
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233−236 C; H NMR (600 MHz, DMSOꢀd6): δ (ppm) 2.16 (s, 3H), 2.37 (s, 3H), 6.64 (s, 1H),
7.23 (d, 1H, J = 7.8 Hz), 7.36 (d, 2H, J = 7.8 Hz), 7.52 (dd, 3H, J = 9.6 Hz), 7.66−7.71 (m, 3H),
13
7.93 (d, 1H, J = 9.0 Hz), 11.64 (s, 1H); C NMR (150 MHz, DMSOꢀd6): δ (ppm) 21.1, 21.2,
110.6, 115.4, 120.4, 122.4, 122.7, 124.3, 127.1, 127.7, 128.6, 128.9, 129.08, 129.13, 130.7,
131.7, 136.2, 139.7, 140.7, 144.9, 152.3; HRMS (ESI): calcd. for C23H19N2 [M + H+] 323.1543;
found 323.1548.
2-Fluoro-9-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (5f). Yellow solid (48 mg, 59%);
m.p. 211−213 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 2.17 (s, 3H), 6.70 (s, 1H), 7.19 (dd,
1H, J = 8.4 Hz), 7.28 (d, 1H, J = 7.8 Hz), 7.38 (d, 1H, J = 8.4 Hz), 7.55 (d, 2H, J = 6.6 Hz), 7.63
(td, 1H, J = 9.0 Hz), 7.69−7.74 (m, 3H), 8.08 (dd, 1H, J = 9.6 Hz), 11.76 (s, 1H); 13C NMR (100
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MHz, DMSOꢀd6): δ (ppm) 21.1, 108.4, 108.6, 110.8, 116.0, 118.3, 118.5, 119.9, 122.6, 122.97,
123.03, 128.0, 128.98, 129.04, 129.3, 129.5, 129.7, 129.8, 135.5, 140.0, 140.7, 143.3, 152.5,
156.8, 158.4; HRMS (ESI): calcd. for C22H16FN2 [M + H+] 327.1292; found 327.1278.
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9-Fluoro-2-methyl-11-phenyl-6H-indolo[2,3-b]quinoline (6b). Yellow solid (60 mg, 74%);
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m.p. 248−250 C; H NMR (600 MHz, DMSOꢀd6): δ (ppm) 2.36 (s, 3H), 6.46 (dd, 1H, J = 9.0
Hz), 7.27 (td, 1H, J = 9.0 Hz), 7.37 (s, 1H), 7.46 (dd, 1H, J = 7.8 Hz), 7.51−7.54 (m, 3H),
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7.66−7.71 (m, 3H), 7.93 (d, 1H, J = 8.4 Hz), 11.93 (s, 1H); C NMR (150 MHz, DMSOꢀd6): δ
(ppm) 21.2, 107.7, 107.9, 111.8, 111.9, 115.0, 115.07, 115.09, 115.3, 120.68, 120.74, 122.5,
124.4, 127.2, 128.9, 129.0, 129.2, 131.2, 132.0, 135.7, 138.0, 141.6, 145.3, 152.6, 155.3, 156.9;
HRMS (ESI): calcd. for C22H16FN2 [M + H+] 327.1292; found 327.1303.
2,9-Difluoro-11-phenyl-6H-indolo[2,3-b]quinoline (6f). Yellow solid (58.5 mg, 71%); m.p.
296−298 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 6.52 (dd, 1H, J = 9.0 Hz), 7.20 (dd, 1H, J
= 10.2 Hz), 7.31 (td, 1H, J = 9.0 Hz), 7.48 (dd, 1H, J = 9.0 Hz), 7.54 (d, 2H, J = 7.2 Hz), 7.63
13
(td, 1H, J = 9.6 Hz), 7.00−7.74 (m, 3H), 8.08 (d, 1H, J = 9.0 Hz),11.91 (s, 1H); C NMR (150
MHz, DMSOꢀd6): δ (ppm) 107.9, 108.1, 108.5, 108.6, 112.0, 112.1, 115.2, 115.3, 115.7, 115.9,
118.9, 119.0, 120.0, 120.07, 120.13, 120.2, 122.75, 122.81, 128.9, 129.2, 129.4, 129.8, 129.9,
135.0, 138.3, 141.5, 141.6, 143.7, 152.7, 155.4, 156.90, 156.94, 158.5; HRMS (ESI): calcd. for
C21H13F2N2 [M + H+] 331.1041; found 331.1058.
9-Methyl-11-(p-tolyl)-6H-indolo[2,3-b]quinoline (9a). Brown solid (54 mg, 67%); m.p.
o
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258−260 C; H NMR (600 MHz, DMSOꢀd6): δ (ppm) 2.18 (s, 3H), 250 (s, 3H), 6.81 (s, 1H),
7.25 (d, 1H, J = 7.8 Hz), 7.34−7.38 (m, 2H), 7.41 (d, 2H, J = 7.8 Hz), 7.49 (d, 2H, J = 7.8 Hz),
13
7.62 (d, 1H, J = 8.4 Hz), 7.69 (t, 1H, J = 7.8 Hz), 8.02 (d, 1H, J = 8.4 Hz), 11.70 (s, 1H); C
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NMR (150 MHz, DMSOꢀd6): δ (ppm) 21.1, 21.2, 110.6, 115.4, 118.2, 120.4, 122.5, 122.6, 123.0,
125.8, 127.2, 128.5, 128.8, 129.0, 129.6, 133.0, 138.0, 139.7, 141.5, 146.4, 152.7; HRMS (ESI):
calcd. for C23H19N2 [M + H+] 323.1543; found 323.1541.
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9-Fluoro-11-(4-fluorophenyl)-6H-indolo[2,3-b]quinoline (10a). Yellow solid (58 mg, 70%);
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m.p. 314−316 C; H NMR (600 MHz, DMSOꢀd6): δ (ppm) 6.56 (dd, 1H, J = 9.0 Hz), 7.32 (t,
1H, J = 9.0 Hz), 7.41 (t, 1H, J = 7.8 Hz), 7.49 (dd, 1H, J = 9.0 Hz), 7.56 (t, 2H, J = 8.4 Hz), 7.62
13
(d, 3H, J = 7.8 Hz), 7.74 (t, 1H, J = 7.8 Hz), 8.05 (d, 1H, J = 8.4 Hz), 11.90 (s, 1H); C NMR
(150 MHz, DMSOꢀd6): δ (ppm) 107.8, 107.9, 111.97, 112.03, 114.1, 115.3, 115.4, 115.6, 116.2,
116.4, 120.5, 120.6, 122.7, 123.1, 125.7, 127.4, 128.3, 129.1, 131.3, 131.4, 131.7, 138.1, 141.2,
146.7, 152.9, 155.4, 157.0, 161.6, 163.6; HRMS (ESI): calcd. for C21H13F2N2 [M + H+]
331.1041; found 331.1040.
2,9-Dimethyl-11-(p-tolyl)-6H-indolo[2,3-b]quinoline (9b). Pale brown solid (60.5 mg, 72%);
o
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m.p. 308−310 C; H NMR (600 MHz, DMSOꢀd6): δ (ppm) 2.18 (s, 3H), 2.38 (s, 3H), 2.52 (s,
3H), 6.74 (s, 1H), 7.24 (d, 1H, J = 7.8 Hz), 7.34−7.40 (m, 4H), 7.51−7.54 (m, 3H), 7.92 (d, 1H, J
13
= 9.0 Hz), 11.58 (s, 1H); C NMR (150 MHz, DMSOꢀd6): δ (ppm) 21.1, 21.18, 21.23, 110.6,
115.4, 120.5, 122.4, 122.9, 124.4, 127.1, 127.6, 128.9, 129.0, 129.7, 130.7, 131.6, 133.1, 137.9,
139.7, 140.9, 144.9, 152.3; HRMS (ESI): calcd. for C24H21N2 [M + H+] 337.1699; found
337.1693.
2,9-Difluoro-11-(4-fluorophenyl)-6H-indolo[2,3-b]quinoline (10f). Greenish brown solid (55
mg, 63%); m.p. 316−318 oC; 1H NMR (600 MHz, DMSOꢀd6): δ (ppm) 6.57 (dd, 1H, J = 9.0 Hz),
7.21 (dd, 1H, J = 10.2 Hz), 7.32 (td, 1H, J = 9.0 Hz), 7.46−7.48 (m, 1H), 7.56 (t, 2H, J = 8.4 Hz),
7.63 (dd, 3H, J = 5.4 Hz), 8.07 (dd, 1H, J = 8.4 Hz), 11.90 (s, 1H); 13C NMR (150 MHz, DMSOꢀ
d6): δ (ppm) 108.5, 108.7, 109.0, 109.2, 112.68, 112.74, 115.8, 116.0, 116.4, 116.6, 117.0, 117.2,
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119.5, 119.6, 120.67, 120.71, 123.48, 123.54, 130.46, 130.52, 131.9, 131.95, 132.01, 138.9,
141.08, 141.12, 144.3, 153.3, 156.0, 157.57, 157.59, 159.2, 162.4, 164.0; HRMS (ESI): calcd.
for C21H12F3N2 [M + H+] 349.0947; found 349.0939.
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AUTHOR INFORMATION
Corresponding Author
*E mail: patel@iitg.ernet.in
ACKNOWLEDGMENT
B. K. P acknowledges the support of this research by the Department of Science and
Technology (DST) (SB/S1/OCꢀ53/2013), New Delhi, and the Council of Scientific and Industrial
Research (CSIR) (02(0096)/12/EMRꢀII). WA thanks CSIR for fellowship. Author acknowledges
M. Shaad Ansari and M. Adil Afroz for carrying out the powder XRD and EDX experiment.
Supporting Information Available
Spectral data for all compounds, Xꢀray diffraction data (CIF file) of compound 1a, this material
is available free of charge via the Internet at http://pubs.acs.org.
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Microwave Assisted Cascade Strategy for the Synthesis of Indolo[2,3-b]quinolines from 2-
(Phenylethynyl)anilines and Aryl Isothiocynates
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Wajid Ali, Anjali Dahiya, Ramdhari Pandey, Tipu Alam, Bhisma K. Patel*
ACS Paragon Plus Environment