Visible-light-induced regioselective cross-dehydrogenative coupling of 2 H-indazoles with ethers

Article abstract of DOI:10.1021/acs.joc.9b00318

A visible-light-promoted regioselective C(sp²)-H/C(sp³)-H cross-dehydrogenative coupling between 2H-indazoles and ethers has been achieved using a catalytic amount of rose bengal as an organophotoredox-catalyst and tert-butyl hydroperoxide (TBHP) as an oxidant at ambient temperature under aerobic conditions. A variety of C-3 oxyalkylated 2H-indazoles have been synthesized in moderate to good yields. Mechanistic studies suggest a radical pathway of the present reaction.

Full text of DOI:10.1021/acs.joc.9b00318

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Note
Visible-Light-Induced Regioselective Cross-
Dehydrogenative Coupling of 2H-Indazoles with Ethers
Mukta Singsardar, Sudip Laru, Susmita Mondal, and Alakananda Hajra
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b00318 • Publication Date (Web): 15 Mar 2019
Downloaded from http://pubs.acs.org on March 15, 2019
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Visible-Light-Induced Regioselective Cross-Dehydrogenative Coupling of 2H-
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Indazoles with Ethers
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Mukta Singsardar, Sudip Laru, Susmita Mondal, and Alakananda Hajra*
Department of Chemistry, Visva-Bharati (A Central University), Santiniketan 731235, India
Email: alakananda.hajra@visva-bharati.ac.in
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rose bengal
X
H
organophotocatalysis
C(sp2)-H/C(sp3)-H coupling
room temperature
blue LED
R1
+
R
R1
N R
N
X
TBHP (1.0 equiv)
DABCO (1.0 equiv)
ambient air, rt, 24 h
H
N
N
X = O, S
26 examples
up to 95% yield
cost-effective
ABSTRACT
A visible-light-promoted regioselective C(sp2)-H/C(sp3)-H cross-dehydrogenative coupling
between 2H-indazoles and ethers has been achieved using a catalytic amount of rose bengal as an
organophotoredox-catalyst and tert-butyl hydroperoxide (TBHP) as an oxidant at ambient
temperature under aerobic conditions. A variety of C-3 oxyalkylated 2H-indazoles have been
synthesized in moderate to good yields. Mechanistic studies suggest a radical pathway of the
present reaction.
Indazole, a nitrogen-based fused heterocycle possesses a large number of biological
activities such as anti-tumour,1a anti-HIV,1b anti-microbial,1c anti-inflammatory,1d anti-
depressant,1e anti-cancer,1f anti-platelet,1g anti-contraceptive,1f and anti-malarial.1g In
pharmaceutical chemistry, indazoles are also known to be an efficient bioisostere of indoles and
benzimidazoles.1 There are several marketed drugs with indazole moeity such as MK-4827
(anticancer agent),2a pazopanib (votrient, tyrosine kinase inhibitor),2b bendazac (votrient, tyrosine
kinase inhibitor),2c and gamendazole (Fig 1.).1h Moreover it is used as bacterial gyrase β-
inhibitors3a and estrogen receptors.3b Considering the broad applications of indazole in
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pharmaceutical chemistry, several methodologies have been developed for the synthesis and
functionalization of this moiety.4 Recently phosphonylation,5a trifluoromethylation,5b and
thiocyanation5c on indazole moiety have been reported by our group also. Regardless the
significance of such functionalizations, there is still great demand to develop straightforward,
mild, and environmentally friendly method for synthesis of functionalized indazoles.
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O
OH
O
O2N
HO
N
N
O
N
Ph
N
OH
Antiparasitic drug
Bendazac
H2N
Ph
N
N
N
O
Cl
N
F3C
O2N
Ph
Gamendazole
Cl
N
N
Neuroprotective sodium channel modulator
Fig 1. 2H-Indazole-containing some biologically active molecules.
On the other hand, cyclic ethers are important in the field of pharmaceutical chemistry
and natural product.6 The synthesis of cyclic ether functionalized complex organic molecules
becomes a challenging task in synthetic organic chemistry due to the inertness of simple ethers.
Although a numerous methodologies have been developed for α-C-H functionalization of ethers,
most of these approaches require transition-metal catalysts, ligands, and harsh reaction
conditions.7
Recently, visible-light-mediated photoredox-catalyzed direct functionalization of C-H
bond has drawn a significant attention from the synthetic chemistry community.8 Inexpensive
organic dyes like rose bengal (RB), eosin Y, methylene blue, etc., have utilized as an alternatives
of transition-metal-containing photoredox catalysts due to their synthetic versatility,
inexpensiveness, nontoxicity, and better environmental perspective.9 In 2015, Wang and co-
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workers described a visible-light-mediated eosin Y-catalyzed vinylation of THF using alkyne as
vinylating agent.8g With our ongoing studies on organophotoredox catalysis,10 herein we
described an environmentally benign visible-light-promoted method for oxyalkylation of 2H-
indazole via cross-dehydrogenative coupling between 2H-indazoles and ethers using rose bengal
as photo-redox-catalyst under aerobic conditions at room temperature (Scheme 1).
Scheme 1. Visible-Light-Mediated Oxyalkylation of Indazoles
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O
rose bengal
R1
R1
+
H
N R
N R
air, rt
blue LED
O
N
N
Initially, the reaction was carried out using 2-phenyl-2H-indazole (1a) (0.25 mmol) as
model substrate and rose bengal (2 mol %) as a photocatalyst under irradiation with 34 W blue
LED lamp. Delightfully, 2-phenyl-3-(tetrahydrofuran-2-yl)-2H-indazole (3aa) was formed in
30% yield after 24 h using tetrahydrofuran (THF) as an oxyalkylating reagent and DABCO as an
additive under ambient air (Table 1, entry 1). Even, no improvement of the yield was observed
after 36 h. No desired product was obtained in the absence of photocatalyst (Table 1, entry 2).
After that, we screened the effect of different oxidants such as H2O2, TBHP, DTBP, K2S2O8, and
PhI(OAc)2 (Table 1, entries 3-7). Interestingly, 90% yield of the oxyalkylated product was
obtained in presence of TBHP (Table 1, entry 4). Other photo-redox-catalysts, such as eosin Y,
eosin B, and Rhodamine 6G were not effective like rose bengal (Table 1, entries 8-10). The
coupling product was formed in 37% yield in presence of eosin Y and molecular sieves 4 Å/
HCOOH (Table 1, entry 8). We also checked the effect of different bases like DBU, Et3N,
K2CO3, Na2CO3, and Cs2CO3 but these were not suitable for this protocol (Table 1, entries 11-
15). No formation of the product was found in absence of base (Table 1, entry 16). The yields of
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the product decreased with decreasing the loading of both rose bengal and DABCO but no
significant improvement of the reaction yield was found with increasing the amounts of both
catalyst and base (Table 1, entry 17 and 18). The yield of the reaction decreased with decreasing
as well as increasing the amount of TBHP (Table 1, entry 19). The desired product was formed
in 42% yield in presence of 1.0 mL THF (Table 1, entry 20). Other classical photoredox catalysts
like Ru(bpy)3Cl2·6H2O and Ir(ppy)3 were not suitable for this reaction (Table 1, entries 21 and
22). Furthermore, the desired coupling product was not observed under the irradiation with 5 W
blue LED and 10 W white LED (Table 1, entry 23). Thus the optimized yield (90%) was
achieved using 2 mol % rose bengal, 1.0 equiv DABCO, and 1.0 equiv TBHP (5.0-6.0 M in
dacane) under irradiation with 34 W blue LED for 24 h at room temperature under aerobic
condition (Table 1, entry 4).
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Table 1. Representative Results for Optimization of the Reactiona
O
photocatalyst
oxidant
N Ph
N Ph
+
additive, air
34 W blue LED
O
N
3aa
N
1a
2a
entry photocatalyst (mol %) oxidant (equiv) additive (equiv) yield (%)
1
2
rose bengal
-
O2
O2
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
30
NR
3
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
eosin Y
H2O2
trace
90
4
TBHP
DTBP
K2S2O8
PhI(OAc)2
TBHP
TBHP
TBHP
5
trace
35
6
7
30
8
trace, 37%b
9
eosin B
NR
10
Rhodamine 6G
NR
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rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
rose bengal
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DBU
Et3N
20
NR
K2CO3
Na2CO3
Cs2CO3
-
20
35
58
9
NR
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DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
DABCO
67c, 91d
52e, 88f
45g, 35h
42i
Ru(bpy)3Cl2·6H2O
Ir(ppy)3
TBHP
TBHP
TBHP
28
trace
NRj
rose bengal
aReaction conditions: 1a (0.25 mmol), 2a (2.0 mL), photocatalyst (2 mol %), base (1.0 equiv),
oxidant (1.0 equiv), 34 W blue LED, 24 h, air, room temperature. NR = no reaction. 4 Å MS/
HCOOH instead of DABCO. 1 mol % rose bengal, and 3 mol % rose bengal. 0.5 equiv
DABCO and f2.0 equiv DABCO. g0.5 equiv TBHP (5.0-6.0 M in dacane), and h2.0 equiv TBHP
(5.0-6.0 M in dacane), i1.0 mL THF, jIrradiation with 5 W blue LED and 10 W white LED.
b
c
d
e
After getting the optimized reaction conditions, we examined the substrate scope of this
cross-coupling reaction with various substituted 2H-indazoles. As shown in Scheme 2, we first
varied the substituent at N-2 position of 2H-indazoles. Electron-donating groups like –Me and –
OMe containing 2-phenyl-2H-indazole afforded the corresponding C-3 oxyalkylated products in
excellent yields (3ba-3da). Halogen (F, Cl, and Br)-containing 2H-indazoles also worked well
under the optimized reaction conditions (3ea-3ga). Pyridinyl substituted 2H-indazole also
underwent the reaction very smoothly (3ha). In addition, 4-methoxybenzyl and tert-butyl
substituted 2H-indazoles gave the oxyalkylated products in moderate yields (3ia and 3ja). Next
we investigated various substituents in the arene part of 2H-indazoles. Both electron-releasing
(Me and OMe) and halogen (F and Cl) containing 2H-indazole provided the desired products
(3ka-3oa) in good yields. 2-Phenyl-2H-[1,3]dioxolo[4,5-f]indazole derivatives (1p and 1q) were
also well tolerable in the present reaction (3pa and 3qa). Electron-withdrawing group containing
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2H-indazole in phenyl ring did not undergo the oxyalkylation. Ortho-substituted 2-phenyl-2H-
indazoles could not form the desired products. Next to validate the applicability of the present
protocol, a gram-scale reaction was carried out by taking 1a in 5 mmol scale under the optimized
conditions. To our delight 2-phenyl-3-(tetrahydrofuran-2-yl)-2H-indazole (3aa) was formed in
89% yield. However, 2H-indazole and 1H-indazole remained unreactive under the optimized
reaction conditions. An inseparable mixture of products was obtained in case of cbz-protected
2H-indazole.
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Scheme 2. Substrate Scope of 2H-Indazolesa
O
rose bengal (2 mol %)
blue LED
R1
N R
N R
R1
+
O
2a
DABCO (1.0 equiv)
TBHP (1.0 equiv)
24 h
N
O
N
1
3
O
O
N
Cl
N
F
N
R2
N
N
N
2
3ba
3ca
R = 4-Me,
, 95%
b
3ga
, 82%
3aa
, 90%, (89%)
2
R = 3-Me,
, 93%
OMe
2
3da
R = 4-OMe,
, 91%
O
O
2
3ea
R = 4-F,
, 84%
2
3fa
R = 4-Br,
, 76%
N
N
, 78%
N
N
N
3ia
3ha
, 88%
O
O
R5
O
O
R3
Me
Me
N
N
R4
3ka
N
O
N
N
5
3pa
, 64%
R = 4-H,
N
3
4
Me
R = 5-OMe, R = 4-Me,
, 83%
5
3qa
, 67%
R = 4-Me,
3
4
3la
3ja
R = 5-OMe, R = 4-OMe,
, 81%
, 45%
3
4
3ma
R = 5,6-OMe, R = 4-Me,
, 89%
3
4
3na
R = 5-F, R = 4-OMe,
, 85%
3
4
3oa
R = 5-Cl, R = 4-Me,
, 87%
aReaction conditions: 1 (0.25 mmol), 2a (2.0 mL), rose bengal (2 mol %), DABCO (1.0 equiv),
and TBHP (5.0-6.0 M in dacane, 1.0 equiv), 34 W blue LED, 24 h, ambient air, room
temperature. b5 mmol scale.
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Next, to show the general applicability of the present methodology, we investigated our
reaction taking different ethers (Scheme 3). 2-Phenyl-2H-indazole substituted with 4-Me and 3-
Me in the N-phenyl ring smoothly reacted with 1,3-dioxolane (2b) to provide the desired
products (3bb and 3cb) in good yields. Halogen substituted 2H-indazoles also worked well (3rb
and 3gb). 5-Fluoro-2-(p-tolyl)-2H-indazole also reacted with 1,3-dioxolane (3sb, 59%).
Moreover, 2-methyltetrahydrofuran, 1,4-dioxane furnished the coupling products (3bc and 3bd)
without any difficulties. Aliphatic ether like diethyl ether also participated in this coupling
reaction to afford the desired product with good yield (3bf, 80%). It is also notable that
tetrahydrothiophene reacted well under the present reaction condition to give the corresponding
product 3bg in 67% yield. 2-Phenyl-2H-indazole did not form the coupling products with
cycloalkanes like cyclopentane and cyclohexane. Other heterocycles such as indole and 1-methyl
indole did not couple with ethers under the present reaction conditions.
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Scheme 3. Substrate Scope of Ethersa
X
rose bengal (2 mol %)
blue LED
+
N Ar
N Ar
X
TBHP (1.0 equiv)
DABCO (1.0 equiv), 24 h
H
=
N
N
2
1
X
O, S
3
O
O
O
2
3bb
3cb
Me
R = 4-Me,
, 74%
2
R = 3-Me,
, 72%
R1
N
N
Me
Me
2
N
3rb
R = 4-Cl,
, 82%
3gb
R2
2
N
N
R = 3-Cl, 4-F,
, 61%
3sb
O
3bc
, 79%
2
1
R = 4-Me, R = 5-F,
, 59%
O
S
Me
O
Me
N
Me
N
N
Me
3bf
N
3bg
3bd
, 83%
, 67%
N
, 80%
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aReaction conditions: 1 (0.25 mmol), 2 (2.0 mL), rose bengal (2 mol %), DABCO (1.0 equiv),
3
4
and TBHP (5.0-6.0 M in dacane, 1.0 equiv), 34 W blue LED, 24 h, air, room temperature.
5
6
7
8
9
A few control experiments were carried out to get the mechanistic insights of the
current protocol (Scheme 4). The product was not obtained in absence of photocatalyst
(Scheme 4, eq A). 2-Phenyl-2H-indazole (1a) did not produce the corresponding α-
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oxyalkylated product (3aa) in the presence of radical scavengers like 2,2,6,6-
tetramethylpiperidine-1-oxyl (TEMPO), 2,6-di-tert-butyl-4-methyl phenol (BHT), and p-
benzoquinone (BQ) (Scheme 4, eq B). Moreover, with the addition of stoichiometric amount
1,1-diphenylethylene, the present reaction completely suppressed along with the
formation of 2-(2,2-diphenylvinyl)tetrahydrofuran (4a) in 75% yield (Scheme 4, eq C).
These observations clearly reveal the radical mechanistic pathway of the present reaction.
Scheme 4. Mechanistic Studies
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O
O
without rose bengal
N Ph
+
N Ph
(A)
DABCO (1.0 equiv)
N
N
TBHP (1.0 equiv)
2a
(2.0 mL)
1a
1a
(0.25 mmol)
3aa
, 0%
blue LED, 24 h
O
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O
standard conditions
N Ph
N
+
N Ph
(B)
radical scavenger
N
(2.0 equiv)
2a
(2.0 mL)
(0.25 mmol)
3aa
TEMPO,
3aa
, 0%
, trace
, 0%
BHT,
BQ,
3aa
O
O
O
standard conditions
N Ph
N
+
N Ph +
Ph
(C)
radical scavenger
(2.0 equiv)
N
Ph
2a
(2.0 mL)
1a
(0.25 mmol)
3aa
, 0%
Ph
4a
, 75%
Ph
Based on mechanistic studies and previous literature reports,4e,7a a radical
mechanism for the formation of 2-phenyl-3-(tetrahydrofuran-2-yl)-2H-indazole (3aa) is
presented in Scheme 5. Initially, RB is transformed to its excited-state RB* under blue LED
irradiation. Next, a hydroxide anion and tert-butyloxy radical are formed via a single electron-
transfer process (SET) between RB* and TBHP. Then, tert-butyloxy radical takes up a proton
from α -C(sp3)-H of THF (2a) to form an alkoxyalkyl radical intermediate A. After that the
alkoxyalkyl radical undergoes reaction at C-3 position of 2-phenyl-2H-indazole (1a) to produce
the radical intermediate (B). Subsequently intermediate B is oxidized by RB • + to generate
cationic intermediate C. Finally, 3-oxyalkylated 2H-indazole (3aa) is obtained via deprotonation
of intermediate C.
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Scheme 5. Proposed Mechanistic Pathway
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Cl
-
O
Cl
Cl
Cl
.
2a
THF (
)
OH
-
tBuO
tBuOOH
RB*
.
COONa
I
.
+
A
I
RB
1a
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O
NaO
O
O
I
I
RB
H
h
N Ph
N
RB
.
B
O
O
H
Base
-H+
N Ph
N Ph
N
+
N
3aa
C
In summary, we have disclosed a convenient route for the oxyalkylation of 2H-indazoles
via C−H/C−H cross-dehydrogenative coupling (CDC) between 2H-indazole and ethers under
irradiation of blue LED at room temperature. A wide range of functional groups on 2H-indazole
were well tolerant under the optimized reaction conditions. Metal-free and mild reaction
conditions, broad substrates scope, ambient air, and gram-scale synthesis are the attractive
features of this methodology. To the best of our knowledge we are not aware of any previous
literature reports for such visible-light-promoted oxyalkylation of 2H-indazoles. We believe that
the present methodology opens a new door in organic synthesis to synthesize oxyalkylated 2H-
indazoles.
EXPERIMENTAL SECTION
General Information: All reagents were bought from commercial sources and used as recieved
without further purification. All reactions involving moisture sensitive reactants were executed
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using oven dried glassware. All commercially available solvents were used after distillation. H
NMR spectra were determined on 400 MHz spectrometer as solutions in CDCl3 and 13C{1H}
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spectra were recorded at 100 MHz spectrometer in CDCl3 solution. Chemical shifts (δ) are
expressed in parts per million (ppm) and coupling constants (J) are given in Hz. Chemical shifts
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are referenced to CDCl3 (δ = 7.26 for 1H and δ = 77.16 for C{1H} NMR) as internal standard.
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NMR spectra uses the following abbreviations to describe the multiplicity: s (singlet), d
(doublet), t (triplet), and m (multiplet). The progress of reaction was checked by TLC plates
(silica gel coated glass slide) and the spots were visualized under UV light.
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General Procedure for the Preparation of 2H-indazoles (1)
A mixture of aryl aldehydes (3.0 mmol), the appropriate anilines (3.0 mmol), molecular sieves 4
Å MS (3 gm), and dichloromethane (15 mL) was taken in a dried round-bottom flask. Then the
mixture was stirred at room temperature under ambient air. After 24 h, the mixture was filtered
through Celite and the filtrate was concentrated under reduced pressure to provide the pure
imines without additional purification. The desired imine (3.0 mmol) was then dissolved in dry
DMSO (15 mL) and copper iodide (20 mol %, 114 mg), TMEDA (20 mol %, 69.7 mg), and
sodium azide (2.0 equiv, 390 mg) were added to it. After that the reaction mixture was stirred at
120 °C for 24 h. Next, the brown mixture was allowed to reach room temperature, diluted with
ethyl acetate (20 mL) and water (20 mL). The precipitate was filtered through a short pad of
Celite and the filtrates were extracted with ethyl acetate. The combined organic layers were
concentrated under reduced pressure and the crude mixtures were purified by column
chromatography using ethyl acetate in hexanes (3-5%) as an eluent to give pure indazoles.
Compounds 1a,4b 1b,4b 1d,4d 1f,4d 1h,4b 1j,4d 1o,4d 1p,4d 1r,4b and 1s4b are known, and the
spectroscopic and physical data are completely matched with those from the literature.
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2-(m-Tolyl)-2H-indazole (1c): Yellow Solid (525 mg, 84%); mp 63−65 °C; H NMR (CDCl3,
400 MHz): δ 8.25 (s, 1H), 7.70-7.68 (m, 1H), 7.64 (s, 1H), 7.57 (d, J = 8.8 Hz, 1H), 7.53 (d, J =
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8.0 Hz, 1H), 7.28-7.19 (m, 2H), 7.08 (d, J = 8.4 Hz, 1H), 7.01-6.97 (m, 1H), 2.33 (s, 3H);
13C{1H} NMR (CDCl3, 100 MHz): δ 149.7, 140.4, 139.8, 129.5, 129.3, 128.7, 126.8, 122.7,
122.4, 121.7, 120.5, 120.4, 117.9, 21.5; Anal. Calcd for C14H12N2: C, 80.74; H, 5.81; N, 13.45%;
Found C, 80.91; H, 5.78; N, 13.40%.
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2-(4-Fluorophenyl)-2H-indazole (1e): Yellow Solid (484 mg, 76%); mp 96−98 °C; H NMR
(CDCl3, 400 MHz): δ 8.31 (s, 1H), 7.86-7.83 (m, 2H), 7.78 (d, J = 8.4 Hz, 1H), 7.69 (d, J = 8.4
Hz, 1H), 7.35-7.31 (m, 1H), 7.20 (t, J = 8.8 Hz, 2H), 7.14-7.10 (m, 1H); 13C{1H} NMR (CDCl3,
100 MHz): δ 162.1 (JC-F = 247.0 Hz), 149.9, 136.9, 127.0, 122.9, 122.8 (JC-F = 9.0 Hz), 122.6,
120.5, 120.4, 117.9, 116.5 (JC-F = 22.0 Hz); Anal. Calcd for C13H9FN2: C, 73.57; H, 4.27; N,
13.20%; Found C, 73.78; H, 4.21; N, 13.30%.
2-(3-Chloro-4-fluorophenyl)-2H-indazole(1g): Yellow Solid (584.6 mg, 79%); mp 83−85 °C;
1H NMR (CDCl3, 400 MHz): δ 8.34 (s, 1H), 8.03-8.01 (m, 1H), 7.78-7.75 (m, 2H), 7.69 (d, J =
8.4 Hz, 1H), 7.35-7.27 (m, 2H), 7.14-7.11 (m, 1H); C{1H} NMR (CDCl3, 100 MHz): δ 157.5
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(JC-F = 249.0 Hz), 150.1, 137.2 (JC-F = 4.0 Hz), 127.5 (JC-F = 21.0 Hz), 123.4, 123.0, 122.4, 122.3,
120.56, 120.50, 120.4, 118.0, 117.6, 117.3; Anal. Calcd for C13H8ClFN2: C, 63.30; H, 3.27; N,
11.36%; Found C, 63.11; H, 3.24; N, 11.29%.
2-(4-Methoxybenzyl)-2H-indazole (1i): Yellowish Brown Solid (586 mg, 82%); mp 86−88 °C;
1H NMR (CDCl3, 400 MHz): δ 7.76 (s, 1H), 7.64 (d, J = 8.4 Hz, 1H), 7.52 (d, J = 8.4 Hz, 1H),
7.21-7.16 (m, 3H), 7.00-6.96 (m, 1H), 6.82-6.79 (m, 2H), 5.44 (s, 2H), 3.71 (s, 3H); C{1H}
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NMR (CDCl3, 100 MHz): δ 159.8, 149.0, 129.7, 127.8, 126.0, 122.6, 122.1, 121.7, 120.2, 117.6,
114.4, 57.1, 55.4; Anal. Calcd for C15H14N2O: C, 75.61; H, 5.92; N, 11.76%; Found C, 75.79; H,
5.97; N, 11.67%.
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5-Methoxy-2-(p-tolyl)-2H-indazole (1k): Brown Solid (622 mg, 87%); mp 95−97 °C; H NMR
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(CDCl3, 400 MHz): δ 8.07 (s, 1H), 7.62-7.56 (m, 3H), 7.16 (d, J = 8.4 Hz, 2H), 6.93-6.90 (m,
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1H), 6.75 (d, J = 2.4 Hz, 1H), 3.71 (s, 3H), 2.28 (s, 3H); C{1H} NMR (CDCl3, 100 MHz): δ
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155.4, 146.6, 138.3, 137.4, 130.0, 122.7, 121.8, 120.4, 119.28, 119.26, 96.3, 55.3, 21.0; Anal.
Calcd for C15H14N2O: C 75.61; H, 5.92; N, 11.76%; Found: C, 75.43; H, 5.98; N, 11.83%.
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5-Methoxy-2-(4-methoxyphenyl)-2H-indazole (1l): Brown Solid (587.5 mg, 77%); mp 133−135
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°C; H NMR (CDCl3, 400 MHz): δ 8.04 (s, 1H), 7.64 (d, J = 8.8 Hz, 2H), 7.58 (d, J = 9.2 Hz,
1H), 6.94-6.88 (m, 3H), 6.76 (d, J = 2.0 Hz, 1H), 3.74 (s, 3H), 3.73 (s, 3H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 159.0, 155.4, 146.5, 134.2, 122.7, 122.0, 121.6, 119.3, 119.1, 114.6, 96.3,
55.6, 55.4; Anal. Calcd for C15H14N2O2: C, 70.85; H, 5.55; N, 11.02%; Found C, 71.00; H, 5.51;
N, 11.13%.
5,6-Dimethoxy-2-(p-tolyl)-2H-indazole (1m): Yellowish Brown Solid (716.5 mg, 89%); mp
102−104 °C; 1H NMR (CDCl3, 400 MHz): δ 8.06 (s, 1H), 7.64 (d, J = 8.4 Hz, 2H ), 7.20 (d, J =
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8.4 Hz, 2H), 7.01 (s, 1H), 6.78 (s, 1H), 3.91 (s, 3H), 3.85 (s, 3H), 2.33 (s, 3H); C{1H} NMR
(CDCl3, 100 MHz): δ 151.8, 148.2, 146.3, 138.2, 136.8, 129.9, 119.8, 119.0, 117.2, 96.9, 95.7,
55.8, 20.9; Anal. Calcd for C16H16N2O2: C, 71.62; H, 6.01; N, 10.44%; Found C, 71.81; H, 6.06;
N, 10.52%.
5-Fluoro-2-(4-methoxyphenyl)-2H-indazole (1n): Yellowish Solid (523 mg, 72%); mp 128−130
°C; 1H NMR (CDCl3, 400 MHz): δ 8.26 (s, 1H), 7.78-7.73 (m, 3H), 7.27-7.24 (m, 1H), 7.13-7.08
(m, 1H), 7.04-7.00 (m, 2H), 3.86 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 159.5, 158.7 (JC-F
= 238.0 Hz), 147.0, 134.0, 122.4, 120.5 (JC-F = 8.0 Hz), 119.9, 119.8, 118.3, 118.0, 114.7, 102.7
(JC-F = 24.0 Hz), 55.7; Anal. Calcd for C14H11FN2O: C, 69.41; H, 4.58; N, 11.56%; Found C,
69.21; H, 4.53; N, 11.64%.
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2-(p-Tolyl)-2H-[1,3]dioxolo[4,5-f]indazole (1q): Yellowish solid (514.5 mg, 68%); mp 148−150
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°C; H NMR (CDCl3, 400 MHz): δ 8.12 (s, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.4 Hz,
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Calcd for C15H12N2O2: C, 71.42; H, 4.79; N, 11.10%; Found: C, 71.26; H, 4.83; N, 11.01%.
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General Experimental Procedure for the Synthesis of 3:
Indazoles (0.25 mmol), ether (2.0 mL), rose bengal (2 mol %, 5 mg), DABCO (1.0 equiv, 28 mg)
and TBHP (1.0 equiv, 5.0-6.0 M in dacane, 0.035 mL) were taken in an oven-dried reaction
vessel equipped with a magnetic stir bar. Then reaction mixture was irradiated using a Kessil 34
W blue LED at room temperature under open atmosphere for 24 h. The progress of the reaction
was monitored by TLC. After completion, the reaction mixture was quenched with 10 mL
water/ethyl acetate (1:3). Then the reaction mixture was extracted with ethyl acetate and the
organic phase was dried over anhydrous Na2SO4. After evaporating the solvent under reduced
pressure the crude residue was obtained. Finally it was purified by column chromatography on
silica gel (60-120 mesh) using petroleum ether/ethylacetate as an eluent to afford the pure
products.
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2-Phenyl-3-(tetrahydrofuran-2-yl)-2H-indazole (3aa): Colourless gummy (59 mg, 90%); H
NMR (CDCl3, 400 MHz): δ 7.82-7.80 (m, 1H), 7.75-7.72 (m, 1H), 7.60-7.56 (m, 2H), 7.55-7.49
(m, 3H), 7.34-7.30 (m, 1H), 7.12-7.08 (m, 1H), 5.20 (t, J = 7.6 Hz, 1H), 4.19-4.14 (m, 1H), 3.94-
3.89 (m, 1H), 2.31-2.22 (m, 2H), 2.21-2.13 (m, 1H), 2.10-2.01 (m, 1H); 13C{1H} NMR (CDCl3,
100 MHz): δ 149.0, 140.1, 136.2, 129.27, 129.21, 126.6, 126.5, 121.8, 120.8, 120.2, 118.0, 73.9,
68.9, 32.5, 26.8; Anal. Calcd for C17H16N2O: C, 77.25; H, 6.10; N, 10.60%; Found C, 77.41; H,
6.13; N, 10.69%.
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3-(Tetrahydrofuran-2-yl)-2-(p-tolyl)-2H-indazole (3ba): Colourless gummy (66 mg, 95%); H
NMR (CDCl3, 400 MHz): δ 7.80 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.46-7.44 (m,
2H), 7.32-7.29 (m, 3H), 7.10-7.07 (m, 1H), 5.18 (t, J = 7.6 Hz, 1H), 4.18-4.13 (m, 1H), 3.93-3.87
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(m, 1H), 2.44 (s, 3H), 2.28-2.21 (m, 2H), 2.20-2.12 (m, 1H), 2.08-1.99 (m, 1H); C{1H} NMR
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(CDCl3, 100 MHz): δ 148.8, 139.2, 137.5, 136.1, 129.7, 126.4, 126.1, 121.7, 120.8, 120.0, 117.9,
74.0, 68.9, 32.4, 26.7, 21.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H18N2O: 279.1491;
Found 279.1479.
3-(Tetrahydrofuran-2-yl)-2-(m-tolyl)-2H-indazole (3ca): Light yellow gummy (65 mg, 93%);
1H NMR (CDCl3, 400 MHz): δ 7.82-7.79 (m, 1H), 7.74-7.72 (m, 1H), 7.42-7.38 (m, 2H), 7.35-
7.29 (m, 3H), 7.11-7.07 (m, 1H), 5.20 (t, J = 7.6 Hz, 1H), 4.20-4.14 (m, 1H), 3.94-3.89 (m, 1H),
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2.44 (s, 3H), 2.29-2.23 (m, 2H), 2.20-2.16 (m, 1H), 2.08-2.03 (m, 1H); C{1H} NMR (CDCl3,
100 MHz): δ 148.9, 139.9, 139.5, 136.2, 129.9, 128.9, 127.1, 126.6, 123.4, 121.7, 120.8, 120.1,
117.9, 74.0, 68.9, 32.5, 26.8, 21.4; Anal. Calcd for C18H18N2O: C, 77.67; H, 6.52; N, 10.06%;
Found C, 77.49; H, 6.55; N, 9.99%.
2-(4-Methoxyphenyl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3da): Light yellow gummy (67
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mg, 91%); H NMR (CDCl3, 400 MHz): δ 7.80 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H),
7.50-7.47 (m, 2H), 7.32-7.28 (m, 1H), 7.11-7.07 (m, 1H), 7.03-7.01 (m, 2H), 5.16 (t, J = 7.6 Hz,
1H), 4.18-4.12 (m, 1H), 3.93-3.89 (m, 1H ), 3.87 (s, 3H), 2.28-2.22 (m, 2H), 2.20-2.12 (m, 1H),
2.09-2.00 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 160.1, 148.8, 136.2, 133.0, 127.6,
126.5, 121.7, 120.7, 120.0, 117.8, 114.3, 74.0, 68.9, 55.7, 32.4, 26.8; Anal. Calcd for
C18H18N2O2: C, 73.45; H, 6.16; N, 9.52%; Found C, 73.65; H, 6.10; N, 9.60%.
2-(4-Fluorophenyl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3ea): Light yellow gummy (59 mg,
84%); 1H NMR (CDCl3, 400 MHz): δ 7.80-7.78 (m, 1H), 7.73-7.71 (m, 1H), 7.59-7.56 (m, 2H),
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7.34-7.30 (m, 1H), 7.24-7.19 (m, 2H), 7.12-7.08 (m, 1H), 5.15 (t, J = 7.6 Hz, 1H), 4.17-4.11 (m,
1H), 3.94-3.88 (m, 1H), 2.30-2.22 (m, 2H), 2.21-2.13 (m, 1H), 2.11-2.02 (m, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 162.8 (JC-F = 252 Hz), 149.0, 136.2, 128.3 (JC-F = 8 Hz), 126.8, 122.0,
121.5, 120.7, 120.2, 117.9, 117.5, 116.2 (JC-F = 23 Hz), 73.7, 68.9, 32.3, 26.8; Anal. Calcd for
C17H15FN2O: C, 72.33; H, 5.36; N, 9.92%; Found C, 72.51; H, 5.31; N, 9.82%.
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2-(4-Bromophenyl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3fa): Colourless gummy (65 mg,
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76%); H NMR (CDCl3, 400 MHz): δ 7.79 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.68-
7.66 (m, 1H), 7.51-7.48 (m, 2H), 7.37-7.30 (m, 2H), 7.12-7.09 (m, 1H), 5.17 (t, J = 7.6 Hz, 1H),
4.18-4.12 (m, 1H), 3.95-3.89 (m, 1H), 2.32-2.25 (m, 2H), 2.21-2.16 (m, 1H), 2.12-2.03 (m, 1H);
13C{1H} NMR (CDCl3, 100 MHz): δ 143.4, 138.4, 132.4, 128.0, 127.6, 126.9, 122.2, 120.8,
120.4, 118.0, 103.0, 73.7, 68.9, 32.3, 26.8; Anal. Calcd for C17H15BrN2O: C, 59.49; H, 4.41; N,
8.16%; Found C, 59.34; H, 4.35; N, 8.05%.
2-(3-Chloro-4-fluorophenyl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3ga): Light yellow gummy
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(65 mg, 82%); H NMR (CDCl3, 400 MHz): δ 7.79-7.70 (m, 3H), 7.54-7.50 (m, 1H), 7.35-7.28
(m, 2H), 7.13-7.09 (m, 1H), 5.17 (t, J = 7.6 Hz, 1H), 4.17-4.11 (m, 1H), 3.96-3.90 (m, 1H), 2.32-
2.24 (m, 2H), 2.23-2.16 (m, 1H), 2.14-2.05 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 158.4
(JC-F = 251 Hz), 149.1, 136.6, 136.1, 128.9, 127.1, 126.3 (JC-F = 8 Hz), 122.3, 122.0, 120.7,
120.3, 118.0, 117.0 (JC-F = 22 Hz), 73.5, 68.9, 32.1, 26.8; Anal. Calcd for C17H14ClFN2O: C,
64.46; H, 4.46; N, 8.84%; Found C, 64.63; H, 4.50; N, 8.75%.
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2-(Pyridin-2-yl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3ha): yellow gummy (58 mg, 88%); H
NMR (CDCl3, 400 MHz): δ 8.52-8.51 (m, 1H), 8.11-8.09 (m, 1H), 7.93-7.87 (m, 2H), 7.68 (d, J
= 8.4 Hz, 1H), 7.33-7.27 (m, 2H), 7.05-7.01 (m, 1H), 6.08-6.04 (m, 1H), 4.29-4.23 (m, 1H),
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4.02-3.97 (m, 1H), 2.69-2.59 (m, 1H), 2.13-2.05 (m, 3H); C{1H} NMR (CDCl3, 100 MHz): δ
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153.5, 149.3, 147.7, 138.78, 138.72, 127.4, 122.8, 122.6, 121.7, 121.0, 118.6, 117.7, 76.5, 69.3,
34.1, 26.5; Anal. Calcd for C16H15N3O: C, 72.43; H, 5.70; N, 15.84%; Found C, 72.21; H, 5.67;
N, 15.90%.
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78%); H NMR (CDCl3, 400 MHz): δ 8.61-8.58 (m, 3H), 8.31 (d, J = 7.6 Hz, 1H), 8.04 (d, J =
8.4 Hz, 1H), 7.85-7.80 (m, 1H), 7.56-7.52 (m, 1H), 7.05-7.02 (m, 3H), 5.75-5.72 (m, 1H), 4.22-
4.16 (m, 1H), 4.11-4.06 (m, 1H), 3.89 (s, 3H), 2.75-2.70 (m, 1H), 2.44-2.39 (m, 1H), 2.25-2.20
(m, 1H), 2.17-2.12 (m, 1H); C{1H} NMR (CDCl3, 100 MHz): δ 168.8, 161.8, 159.7, 151.6,
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133.5, 131.1, 130.3, 129.2, 126.5, 125.2, 121.6, 114.0, 78.8, 69.4, 55.5, 30.1, 26.1; Anal. Calcd
for C19H20N2O2: C, 74.00; H, 6.54; N, 9.08%; Found C, 74.19; H, 6.50; N, 8.97%.
2-(Tert-butyl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3ja): Colourless gummy (27 mg, 45%); 1H
NMR (CDCl3, 400 MHz): δ 7.69 (t, J = 8.4 Hz, 2H), 7.23-7.19 (m, 1H), 7.01-6.98 (m, 1H), 5.66
(t, J = 7.2 Hz, 1H), 4.33-4.28 (m, 1H), 4.00-3.95 (m, 1H), 2.42-2.37 (m, 1H), 2.31-2.22 (m, 2H),
2.20-2.14 (m, 1H), 1.81 (s, 9H); 13C{1H} NMR (CDCl3, 100 MHz): δ 146.5, 135.0, 125.4, 121.4,
121.0, 120.9, 117.8, 75.1, 69.0, 61.9, 33.4, 31.3, 26.9; Anal. Calcd for C15H20N2O: C, 73.74; H,
8.25; N, 11.47%; Found C, 73.95; H, 8.31; N, 11.39%.
5-Methoxy-3-(tetrahydrofuran-2-yl)-2-(p-tolyl)-2H-indazole (3ka): Colourless gummy (64 mg,
83%); 1H NMR (CDCl3, 400 MHz): δ 7.64-7.61 (m, 1H), 7.44-7.41 (m, 2H), 7.30 (d, J = 8.0 Hz,
2H), 7.03-7.01 (m, 1H), 6.98 (d, J = 2.0 Hz, 1H), 5.15 (t, J = 7.6 Hz, 1H), 4.18-4.12 (m, 1H),
3.93-3.87 (m, 1H), 3.86 (s, 3H), 2.43 (s, 3H), 2.24-2.17 (m, 2H), 2.16-2.11 (m, 1H), 2.06-2.00
(m, 1H); C{1H} NMR (CDCl3, 100 MHz): δ 154.9, 154.7, 139.0, 137.7, 134.6, 129.7, 126.1,
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121.3, 120.0, 119.3, 97.1, 74.1, 68.8, 55.5, 32.1, 26.7, 21.3; Anal. Calcd for C19H20N2O2: C,
74.00; H, 6.54; N, 9.08%; Found: C, 73.84; H, 6.59; N, 9.01%.
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5-Methoxy-2-(4-methoxyphenyl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3la): Yellow gummy
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(65.5 mg, 81%); H NMR (CDCl3, 400 MHz): δ 7.62 (d, J = 8.8 Hz, 1H), 7.47-7.45 (m, 2H),
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7.03-6.97 (m, 4H), 5.13 (t, J = 7.6 Hz, 1H), 4.15-4.13 (m, 1H), 3.92-3.88 (m, 1H), 3.87 (s, 3H),
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3.86 (s, 3H), 2.23-2.17 (m, 2H), 2.15-2.08 (m, 1H), 2.06-1.99 (m, 1H); C{1H} NMR (CDCl3,
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100 MHz): δ 159.9, 154.9, 145.6, 134.7, 133.2, 127.5, 121.3, 119.9, 119.2, 114.3, 97.1, 74.1,
68.8, 55.7, 55.5, 32.0, 26.7; Anal. Calcd for C19H20N2O3: C, 70.35; H, 6.21; N, 8.64%; Found C,
70.50; H, 6.18; N, 8.58%.
5,6-Dimethoxy-3-(tetrahydrofuran-2-yl)-2-(p-tolyl)-2H-indazole (3ma): Light yellow gummy
(75 mg, 89%); 1H NMR (CDCl3, 400 MHz): δ 7.41-7.39 (m, 2H), 7.28 (d, J = 8.4 Hz, 2H), 6.98
(d, J = 2.0 Hz, 2H), 5.13 (t, J = 7.6 Hz, 1H), 4.16-4.11 (m, 1H), 3.936 (s, 6H), 3.933-3.86 (m,
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1H), 2.42 (s, 3H), 2.21-2.08 (m, 3H), 2.05-1.98 (m, 1H); C{1H} NMR (CDCl3, 100 MHz): δ
151.7, 147.6, 145.6, 138.7, 137.7, 134.8, 129.7, 126.0, 114.5, 97.8, 95.8, 74.2, 68.8, 56.0, 55.9,
32.3, 26.7, 21.3; Anal. Calcd for C20H22N2O3: C, 70.99; H, 6.55; N, 8.28%; Found C, 70.79; H,
6.51; N, 8.38%.
5-Fluoro-2-(4-methoxyphenyl)-3-(tetrahydrofuran-2-yl)-2H-indazole (3na): Yellow gummy
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(66 mg, 85%); H NMR (CDCl3, 400 MHz): δ 7.70-7.67 (m, 1H), 7.48-7.44 (m, 2H), 7.38-7.35
(m, 1H), 7.14-7.08 (m, 1H), 7.04-7.00 (m, 2H), 5.12 (t, J = 7.6 Hz, 1H), 4.17-4.12 (m, 1H), 3.92-
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3.89 (m, 1H), 3.88 (s, 3H), 2.24-2.12 (m, 3H), 2.07-2.01 (m, 1H); C{1H} NMR (CDCl3, 100
MHz): δ 160.2, 158.1 (JC-F = 238 Hz), 146.2, 136.4 (JC-F = 8 Hz), 132.8, 127.5, 119.9, 119.8,
119.2, 119.1, 118.2, 117.9, 114.4, 103.3 (JC-F = 24 Hz), 73.9, 68.9, 55.7, 32.4, 26.7; Anal. Calcd
for C18H17FN2O2: C, 69.22; H, 5.49; N, 8.97%; Found C, 69.05; H, 5.53; N, 9.06%.
5-Chloro-3-(tetrahydrofuran-2-yl)-2-(p-tolyl)-2H-indazole (3oa): Light yellow gummy (68 mg,
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87%); H NMR (CDCl3, 400 MHz): δ 7.78 (d, J = 1.2 Hz, 1H), 7.65 (d, J = 9.2 Hz, 1H), 7.43-
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7.41 (m, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.25-7.22 (m, 1H), 5.12 (t, J = 7.6 Hz, 1H), 4.20-4.15 (m,
1H), 3.93-3.87 (m, 1H), 2.45 (s, 3H), 2.25-2.14 (m, 3H), 2.09-2.01 (m, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 147.2, 139.6, 137.2, 136.1, 129.9, 127.9, 127.2, 126.0, 120.4, 119.7, 119.4,
74.0, 69.0, 32.7, 26.7, 21.3; Anal. Calcd for C18H17ClN2O: C, 69.12; H, 5.48; N, 8.96%; Found:
C, 68.93; H, 5.45; N, 8.88%.
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2-Phenyl-3-(tetrahydrofuran-2-yl)-2H-[1,3]dioxolo[4,5-f]indazole (3pa): Light yellow gummy
(49 mg, 64%); 1H NMR (CDCl3, 400 MHz): δ 7.54-7.45 (m, 5H), 6.99 (d, J = 10.4 Hz, 2H), 5.96
(d, J = 1.6 Hz, 2H), 5.11 (t, J = 7.6 Hz, 1H), 4.16-4.11 (m, 1H), 3.91-3.85 (m, 1H), 2.23-2.12 (m,
3H), 2.08-2.02 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 149.4, 146.5, 145.4, 140.0, 129.2,
128.8, 126.2, 115.7, 101.0, 95.6, 94.2, 73.9, 68.8, 32.4, 29.8, 26.7; HRMS (ESI-TOF) m/z: [M +
Na]+ Calcd for C18H16N2O3: 331.1053; Found 331.1049.
3-(Tetrahydrofuran-2-yl)-2-(p-tolyl)-2H-[1,3]dioxolo[4,5-f]indazole (3qa): Light yellow
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gummy (54 mg, 67%); H NMR (CDCl3, 400 MHz): δ 7.40-7.38 (m, 2H), 7.29 (d, J = 8.4 Hz,
2H), 6.99 (d, J = 11.2 Hz, 2H), 5.95 (d, J = 1.2 Hz, 2H), 5.09 (t, J = 7.6 Hz, 1H), 4.16-4.10 (m,
1H), 3.90-3.85 (m, 1H), 2.43 (s, 3H), 2.22-2.09 (m, 3H), 2.05-1.98 (m, 1H); 13C{1H} NMR
(CDCl3, 100 MHz): δ 149.3, 146.4, 145.3, 138.8, 137.6, 135.5, 129.7, 126.0, 120.0, 101.0, 95.7,
94.2, 74.0, 68.8, 32.4, 26.7, 21.3; Anal. Calcd for C19H18N2O3: C, 70.79; H, 5.63; N, 8.69%;
Found: C, 70.64; H, 5.66; N, 8.62%.
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3-(1,3-Dioxolan-2-yl)-2-(p-tolyl)-2H-indazole (3bb): Colourless gummy (52 mg, 74%); H
NMR (CDCl3, 400 MHz): δ 7.85 (d, J = 8.4 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.57-7.55 (m,
2H), 7.34-7.30 (m, 3H), 7.15-7.12 (m, 1H), 6.13 (s, 1H), 4.23-4.21 (m, 2H), 4.07-4.05 (m, 2H),
2.44 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.7, 139.3, 137.4, 131.2, 129.8, 126.6,
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126.0, 122.7, 121.0, 120.8, 117.9, 98.5, 65.8, 21.3; Anal. Calcd for C17H16N2O2: C, 72.84; H,
5.75; N, 9.99%; Found: C, 73.00; H, 5.70; N, 10.07%.
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3-(1,3-Dioxolan-2-yl)-2-(m-tolyl)-2H-indazole (3cb): Red gummy (50 mg, 72%); H NMR
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(CDCl3, 400 MHz): δ 7.85 (d, J = 8.8 Hz, 1H), 7.76 (d, J = 8.8 Hz, 1H), 7.51-7.47 (m, 2H), 7.40
(t, J = 8.0 Hz, 1H), 7.35-7.29 (m, 2H), 7.16-7.12 (m, 1H), 6.15 (s, 1H), 4.27-4.19 (m, 2H), 4.10-
4.02 (m, 2H), 2.45 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.7, 139.7, 139.5, 131.3,
130.0, 128.9, 126.8, 126.7, 123.2, 122.7, 121.0, 120.8, 117.9, 98.4, 65.8, 21.4; HRMS (ESI-
TOF) m/z: [M + H]+ Calcd for C17H16N2O2: 281.1284; Found 281.1279.
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2-(4-Chlorophenyl)-3-(1,3-dioxolan-2-yl)-2H-indazole (3rb): Brown gummy (61.5 mg, 82%);
1H NMR (CDCl3, 400 MHz): δ 7.86-7.84 (m, 1H), 7.75-7.73 (m, 1H), 7.67-7.65 (m, 2H), 7.52-
7.49 (m, 2H), 7.36-7.32 (m, 1H), 7.17-7.13 (m, 1H), 6.13 (s, 1H), 4.24-4.18 (m, 2H), 4.11-4.05
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(m, 2H); C{1H} NMR (CDCl3, 100 MHz): δ 148.9, 138.4, 135.2, 131.3, 129.4, 127.4, 127.0,
123.0, 121.3, 120.8, 117.9, 98.2, 65.8; Anal. Calcd for C16H13ClN2O2: C, 63.90; H, 4.36; N,
9.31%; Found: C, 64.08; H, 4.42; N, 9.22%.
2-(3-Chloro-4-fluorophenyl)-3-(1,3-dioxolan-2-yl)-2H-indazole (3gb): Light yellow gummy
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(48.5 mg, 61%); H NMR (CDCl3, 400 MHz): δ 7.85-7.83 (m, 2H), 7.73 (d, J = 8.8 Hz, 1H),
7.64-7.61 (m, 1H), 7.36-7.28 (m, 2H), 7.17-7.14 (m, 1H), 6.15 (s, 1H), 4.23-4.17 (m, 2H), 4.12-
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4.06 (m, 2H); C{1H} NMR (CDCl3, 100 MHz): δ 158.4 (JC-F = 251 Hz), 155.8, 150.8, 148.9,
128.6, 127.2, 126.0 (JC-F = 9 Hz), 123.2, 121.8, 121.4, 120.7, 117.9, 117.7, 116.9 (JC-F = 23 Hz),
98.1, 65.8; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C16H12ClFN2O2: 319.0644; Found
319.0644.
3-(1,3-Dioxolan-2-yl)-5-fluoro-2-(p-tolyl)-2H-indazole (3sb): Light yellow gummy (44 mg,
59%); 1H NMR (CDCl3, 400 MHz): δ 7.74-7.71 (m, 1H), 7.56-7.53 (m, 2H), 7.43-7.40 (m, 1H),
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7.32 (d, J = 8.0 Hz, 2H), 7.15-7.10 (m, 1H), 6.07 (s, 1H), 4.25-4.21 (m, 2H), 4.12-4.03 (m, 2H);
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2.45 (s, 3H); C{1H} NMR (CDCl3, 100 MHz): δ 146.1, 138.3 (JC-F = 230 Hz), 129.9 (JC-F = 5
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Hz), 125.8, 125.5, 120.5, 120.0 (JC-F = 10 Hz), 118.4, 118.2, 103.5 (JC-F = 24 Hz), 98.3, 65.8,
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21.3; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C17H15FN2O2: 299.1190; Found 299.1190.
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3-(2-Methyltetrahydrofuran-2-yl)-2-(p-tolyl)-2H-indazole (3bc): Light yellow liquid (58 mg,
79%); 1H NMR (CDCl3, 400 MHz): δ 7.96-7.93 (m, 1H), 7.68-7.65 (m, 1H), 7.33-7.26 (m, 5H),
7.08-7.04 (m, 1H), 3.89-3.85 (m, 1H), 3.66-3.61 (m, 1H), 2.45 (s, 3H), 2.35-2.29 (m, 1H), 1.94-
1.83 (m, 2H), 1.81-1.73 (m, 1H), 1.64 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.5, 141.7,
139.5, 139.3, 129.2, 127.0, 126.4, 122.4, 121.3, 119.7, 117.5, 82.7, 67.5, 39.5, 29.2, 25.9, 21.4;
HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C19H20N2O: 293.1648; Found 293.1648.
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3-(1,4-Dioxan-2-yl)-2-(p-tolyl)-2H-indazole (3bd): Yellow gummy (61 mg, 83%); H NMR
(CDCl3, 400 MHz): δ 7.97 (d, J = 8.4 Hz, 1H), 7.74 (d, J = 8.8 Hz, 1H), 7.44-7.42 (m, 2H), 7.35-
7.30 (m, 3H), 7.15-7.11 (m, 1H), 4.98-4.95 (m, 1H), 4.10-4.05 (m, 1H), 3.97-3.94 (m, 1H), 3.86-
3.79 (m, 4H), 2.46 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz): δ 148.8, 139.6, 137.2, 131.8,
129.9, 126.6, 126.0, 122.3, 121.2, 120.9, 118.0, 71.6, 69.5, 67.1, 66.5, 21.3; HRMS (ESI-TOF)
m/z: [M + H]+ Calcd for C18H18N2O2: 295.1441; Found 295.1441.
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3-(1-Ethoxyethyl)-2-(p-tolyl)-2H-indazole (3bf): Yellow gummy (56 mg, 80%); H NMR
(CDCl3, 400 MHz): δ 7.93 (d, J = 8.4 Hz, 1H), 7.73 (d, J = 8.8 Hz, 1H), 7.39-7.37 (m, 2H), 7.34-
7.30 (m, 3H), 7.12-7.08 (m, 1H), 4.83 (q, J = 6.8 Hz, 1H), 3.30 (q, J = 7.2 Hz, 2H), 2.45 (s, 3H),
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1.62 (d, J = 6.8 Hz, 3H), 1.12 (t, J = 7.2 Hz, 3H) ; C{1H} NMR (CDCl3, 100 MHz): δ 148.8,
139.4, 137.6, 137.5, 129.8, 126.7, 126.2, 121.6, 121.0, 120.0, 117.7, 70.4, 64.2, 22.0, 21.3, 15.3;
Anal. Calcd for C18H20N2O: C, 77.11; H, 7.19; N, 9.99%; Found C, 76.94; H, 7.13; N, 10.07%.
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3-(Tetrahydrothiophen-2-yl)-2-(p-tolyl)-2H-indazole (3bg): Colourless gummy (49 mg, 67%);
1H NMR (CDCl3, 400 MHz): δ 7.95 (d, J = 8.4 Hz, 1H), 7.72 (d, J = 8.8 Hz, 1H), 7.42-7.40 (m,
2H), 7.34-7.29 (m, 3H), 7.10-7.06 (m, 1H), 4.84-4.80 (m, 1H), 3.34-3.27 (m, 1H), 3.10-3.05 (m,
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1H), 2.45 (s, 3H), 2.43-2.35 (m, 3H), 2.00-1.92 (m, 1H); C{1H} NMR (CDCl3, 100 MHz): δ
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149.0, 139.4, 137.2, 135.8, 129.9, 126.5, 126.2, 121.2, 121.1, 119.6, 118.3, 44.0, 38.2, 34.0, 31.9,
21.4; Anal. Calcd for C18H18N2S: C, 73.43; H, 6.16; N, 9.52%; Found C, 73.58; H, 6.13; N,
9.42%.
2-(2,2-Diphenylvinyl)tetrahydrofuran (4a):7c Colourless liquid (94 mg, 75%); 1H NMR (CDCl3,
400 MHz): δ 7.32-7.27 (m, 5H), 7.24-7.19 (m, 5H), 3.79-3.73 (m, 1H), 3.69-3.65 (m, 1H), 3.55-
3.49 (m, 1H), 2.93-2.89 (m, 1H), 2.67-2.61 (m, 1H), 1.82-1.77 (m, 1H), 1.71-1.65 (m, 1H), 1.37-
1.32 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz): δ 127.9, 127.7, 127.4, 127.1, 127.0, 126.8,
85.6, 79.3, 76.5, 66.8, 42.4, 32.1, 26.6, 26.2.
ASSOCIATED CONTENT
Supporting information
Scanned copies of 1H, and 13C{1H} NMR spectra of the synthesized compounds are available as
supporting information. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: alakananda.hajra@visva-bharati.ac.in.
Notes
The authors declare no competing financial interest
ACKNOWLEDGMENT
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A.H. acknowledges the financial support from CSIR, New Delhi (Grant no. 02(0307)/17/EMR-
II). M. S. thanks UGC-New Delhi for NFHE and S.M. thanks CSIR for her fellowship.
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