I2-Mediated 2: H -indazole synthesis via halogen-bond-assisted benzyl C-H functionalization

Article abstract of DOI:10.1039/c6ob01827k

I₂-Mediated benzyl C-H functionalization has been developed for the synthesis of 2H-indazoles, which features high efficiency, simple conditions and no need for metals. Mechanistic experiments and DFT calculations have revealed halogen bond assistance and a radical chain process for this reaction. The azo group and the bound iodine cooperate in the hydrogen abstraction step, which circumvents the thermodynamic disfavor of direct hydrogen abstraction by a simple iodine radical.

Full text of DOI:10.1039/c6ob01827k

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DOI: 10.1039/C6OB01827K
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Article
I2-mediated 2H-indazole synthesis via halogen-bond-assisted
benzyl C-H functionalization
Xiangli Yi,a Lei Jiaob and Chanjuan Xi*a,c
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
I2-mediated benzyl C-H functionalization has been developed for
synthesis of 2H-indazoles, which features high efficiency, simple
condition and no need for metals. Mechanistic experiments and
DFT calculations have revealed halogen bond assistance and a
radical chain process for this reaction. Azo group and the bound
iodine cooperate in hydrogen abstraction step, which circumvents
the themodynamic disfavor of direct hydrogen abstraction by
simple iodine radical.
Scheme 1 2H-indazole synthesis via C-H functionalization.
has been introduced to this field, converting azobenzenes (sp2
C-H activation) to the corresponding 2H-indazoles (Scheme 1,
left side).8 Many of these reactions have limitations in terms of
complicated procedures, difficult manipulation of reagents
or poorly controlled regioselectivity, and most of them require
the use of transition-metals. A few reactions of ortho-
alkylazobenzenes with NBS9 or base10 to form 2H-indazoles
have been reported, which are limited to several particular
substrates. Herein, we report an efficient I2-mediated synthesis
of 2H-indazole from ortho-alkylazobenzene via benzyl C-H
functionalization (Scheme 1, right side).
Introduction
C-H functionalization is a prevalent strategy in organic synthesis
because of its atom and step economy. Recently, many metal-
catalyzed C-H functionalization reactions have been developed
leading to efficient transformations of organic compounds.1 On
the other hand, metal-free C-H functionalization reactions are
also very important2 since they can avoid using costly metals
and are more desired in drug processing without removing
potentially toxic metals.
2H-indazole is the scaffold of many bioactive molecules and
is playing an increasingly important role in pharmaceutical
research.3 Over the years, several strategies have been
developed for 2H-indazole synthesis. Reductive cyclization of
N-(o-nitrobenzylidene)aniline mediated by triethyl phosphite
represents one of the first methods to synthesize 2H-indazoles.4
Later, the strategies of metal-catalyzed cyclization,5 cross
coupling6 and cycloaddition7 diversified the synthesis of 2H-
indazoles. More recently, metal-catalyzed C-H functionalization
Results and discussion
Initially, 1,2-dimesityldiazene 1a was found to react with
iodine to give 2-mesityl-5,7-dimethyl-2H-indazole 2a in DCE at
120 oC (71% yield, Table 1, entry 1). Then, reaction optimization
was carried out by the first changing the oxidant. Iodine
monocholoride gave 51% yield (entry 2), while bromine only
afforded trace amount of 2a (entry 3). Two peroxides (tBuOOtBu
t
and BuOOBz) were tried and the reaction didn’t proceed
(entries 4-5). The starting materials remained. Considering the
generation of two equivalents of HI which may deteriorate the
yield in entry 1, two equivalents of base were added. Addition
of NaOAc led to an increase in yield to 93% (entry 6), and
NaHCO3 led to a smaller increase (entry 7). Lowering reaction
temperature to 110 oC (entry 8) and shortening reaction time to
6 h (entry 9) both resulted in lower yield, 75% and 60%,
respectively. To simplify the condition, the reaction was carried
out under air instead of N2, and the yield was not affected (entry
10). Therefore, the optimal condition is shown in entry 10.
a.Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry
of Education), Department of Chemistry, Tsinghua University, Beijing 100084,
China. E-mail: cjxi@tsinghua.edu.cn.
b.Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua
University, Beijing 100084, China.Address here.
c. State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin
300071, China.
† Electronic Supplementary Information (ESI) available: [Experimental procedures,
full characterization including 1H NMR and 13C NMR data and spectra for all
compounds, mechanistic experiments and computational details]. See
DOI: 10.1039/x0xx00000x
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Table 1 Reaction optimization with 1,2-dimesityldiazene 1a a
.
Based on the optimized condition, investigationVoienw AsruticblestOrnalitnee
scope was conducted (Table 2). ReplacingDtOheI: 1b0u.1l0k3y9m/Ce6sOitBy0l1w82it7hK
phenyl provided product 5,7-dimethyl-2-phenyl-2H-indazole(2b
in good yield (87%). Substrates with electron-donating and
electron-withdrawing groups both gave excellent yields (92%
for 2c and 91% for 2d). Altering one ortho-methyl in 1b to other
substituents, such as methoxyl-carbonyl, bromo, iodo and
)
phenyl group, resulted in the corresponding products (2f
and 2i) in moderate to good yields. In the case of 1g, bromo
group was partially replaced by iodo group (2g 2h= 1:0.6) in the
, 2g, 2h
:
product. When the other substituent was benzyl or –CH2CO2Et,
the reaction happened completely on methylene instead of
methyl (2j, 92% yield; 2k 82% yield). In contrast, when the other
substituent is ethyl, the reaction selectivity of methylene over
methyl is about 6 times (2l, 73% yield; 2l’, 12%, yield). The
selectivity shown in 1j, 1k and 1l suggests that the reaction is
possibly a radical process. Interestingly, when mono-ortho-
substituted azobenzenes 1m and 1n were employed as
substrates, only trace amount of products were observed on gas
chromatography mass spectrometry (GC-MS) and the starting
materials remained. It indicates that di-ortho-substitution of
a
Reaction condition: 0.2 mmol of 1a, 0.21 mmol of oxidant, 1 mL of DCE,
under N2 in sealed tube for 12 h. b 1H-NMR yield. c Reaction time: 6 h. d Under
air. e Isolated yield.
Table 2 Substrate scope of stoichiometric I2 mediated C-H functionalization.a
b
a Reaction condition: 0.2 mmol of
1
, 0.21 mmol of I2, 0.4 mmol of NaOAc, 1 mL of DCE, 120 oC under air in a sealed tube for 12 h. 1H-NMR yields(%) and
isolated yields(%, in bracket) c Reaction time: 4 h. d Reaction time: 24 h. e Reaction time: 1 h.
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the substrate is necessary for this reaction.
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To understand the mechanism of this reaction, detailed
investigations were conducted. First, we noticed that one
salient difference between I2 and peroxide as oxidant in this
reaction is that I2 can form halogen bond with nitrogen atom,11
which might bind I2 close to ortho-methylene and thus the
reaction could be promoted. To verify this hypothesis, we first
used far-infrared (FIR) spectrometer to prove the existence of
halogen bond (Figure 1).12 Compared with the background
(solution of only 1c), a new absorption peak emerged around
192 cm-1 for solution of 1c and I2. Generally, Free I2 does not
show FIR absorption, while binding of basic N (sp2) with I2 can
DOI: 10.1039/C6OB01827K
polarize I-I bond to give FIR signal in the range of 200 - 180 cm-
1 12b
.
The FIR signal at 192 cm-1 clearly shows the halogen
bonding between azo group and iodine. Additionally, binding
of I2 with the distal N should be preferred over binding with
the nearer N because the distal N is less sterically hindered and
more electron-rich.
Figure 2 1H-NMR spectrum of the solution of azobenzene 1b and I2 in CDCl3.
Table 3 1H-NMR peak shift of ortho-methyl and corresponding reactivity of
azobenzenes.
In order to see the impact of halogen bond on the substrate,
1H NMR spectrum of the solution of 1b and I2 was recorded.
We noticed that when all other peaks remained unmoved, the
peak of hydrogen in ortho-methyl group clearly shifted to
upfield (Figure 2). The result suggests that, after binding to the
azo group, the iodine is situated close to the ortho-methyl so
that an obvious impact on its’ chemical shift can be observed.
In the similar experiments of 1c
obvious shift of peak of ortho-methyl could be observed in all
di-ortho-substituted azobenzenes ( ≥0.01 ppm, 1c 1g, and 1i),
, 1g, 1i, 1m, and 1n (Table 3),
,
while peak of ortho-methyl in 1m and 1n remained almost
unmoved (about 0.002 ppm). This phenomenon can be
rationalized by the conformation distribution analysis: It is
known that rotation of C-N bond of azobenzene is flexible in
solution,13 so the two main conformations of adduct (
form an equilibrium (eq. 1). When R is H, (methyl stays far
A and B)
good reactivity while unobvious peak shifts mean poor
reactivity. In combination with the conformation analysis
above, we can conclude that easy formation of conformation
A
from bound I2) will dominate, so the impact of bound I2 on the
1H NMR signal of ortho-methyl is very small. However, when R
is larger, the population of B (methyl stays close to bound I2)
will increase due to steric repulsion between R and bound I2,
and thus more obvious peak shift of ortho-methyl can be
observed.
B
where methyl stays close to iodine is crucial for this reaction.
To verify the radical assumption we inferred from the
substrate selectivity, substrate 1o with two ortho-isopropyls
was employed to react with iodine under electron
paramagnetic resonance (EPR) monitoring. Difficulty in
1
aromatization for
1o may enable us to observe the
By comparing the reactivity in Table 2 with H NMR shift
intermediate before aromatization. To our delight, EPR signal
emerged after 6 minutes’ heating of the reaction mixture in
EPR tube, which tremendously strengthened in the following
12 minutes, suggesting the piling up of radical species (Figure
3). The obtained signal at 18 min was well simulated mainly
considering the coupling of the two N (nuclear spin= 1) and
one H (nuclear spin= 1/2) with the single electron (Figure 4)
results (Table 3), we can see that obvious peak shifts promise
and thus is consistent with the assumed radical structure (3o
,
Figure 3). Notably, the EPR experiment was conducted in
darkness, so the radical should be generated in thermal
induced way.
Based on the above results and further DFT calculation14 for
model substrate 1e, a plausible radical chain mechanism is
proposed in Scheme 2. First, azo substrate
to form , which is exergonic by 2.9 kcal/mol. Then, the radical
chain reaction starts via assisted homolysis of I-I bond in (by
iodine radical) to afford bound radical , which could be
1 associates with I2
4
4
5
Figure 1 Far infrared spectrum of solution of 1c and I2 in cyclohexane.
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DOI: 10.1039/C6OB01827K
Figure 3 EPR monitoring of reaction of 1o and I2 in p-xylene at 120 oC.
Figure 4 Simulation of EPR signal obtained in reaction of 1o
.
regarded as a complex of
an iodine-assisted hydrogen transfer from the benzylic
position to nitrogen via TS-1 leads to intermediate with an
activation free energy barrier of 30.1 kcal/mol. Notably, unlike
C-H hydrogen abstraction by bromine radical,9 direct C-H
hydrogen abstraction by iodine radical is very disfavoured in
thermodynamics (ΔH=20-33 kcal/mol)15 and thus is considered
1
with iodine radical. Subsequently,
(Figure S1), which is consistent with the key C-H cleavage step.
6
Conclusions
We have presented an efficient synthesis of 2H-indazoles via
benzyl C-H functionalization without assistance of metals.
Representative substrates were examined, which proved the
reaction to be suitable for both electron-rich and - deficient
substrates and tolerate various functional groups. Mechanistic
studies show that the ease of combining I2 close to C-H of
ortho-alkyl is very important for this conversion. EPR and DFT
studies have rationalized a radical chain mechanism. Notably,
simple iodine radical has been reported to be unreactive for
alkanyl C-H (including benzyl C-H) hydrogen abstraction
because of thermodynamically disfavor.15 However, bound
not feasible in this reaction. Intermediate
6 then undergoes
intramolecular cyclization to afford N-centered radical species
≠
7
via TS-2 (∆Gsol = 24.9 kcal/mol), which is later converted to
a more stable intermediate via proton transfer. Finally,
abstraction of a second benzylic hydrogen by I2 furnishes the
protonated product and concomitantly regenerates iodine
3
8
radical. The overall activation free energy of this process is
around 30 kcal/mol, which is consistent with the reaction
conditions (120 oC, 12 h). A primary kinetic isotope effect (KIE)
of 9.0 was observed for the deuterated substrates 1b-d3
iodine
radical
successfully
realized
benzyl
C-H
functionalization with the assistance of azo group in this
reaction.
Scheme 2 Proposed mechanism for I2-mediated selective benzyl C-H functionalization and DFT computational for the reaction of 1e. The Gibbs free energies in solution
(∆Gsol, in kcal/mol) are given in parentheses.
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106.1, 17.0; GC-MS: 233; HRMS (ESI positive mode) calcd for
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C15H11N3+H+ 234.1026, found 234.1027.DOI: 10.1039/C6OB01827K
7-Methyl-2-phenyl-2H-indazole (2e): Synthesized via GP2;
colorless oil (33.3 mg, 80% isolated yield); Rf: 0.51 (PE:
EA=10:1); 1H NMR (400 MHz, CDCl3): δ 8.38 (s, 1H), 7.95 – 7.90
(m, 2H), 7.58 – 7.50 (m, 3H), 7.44 – 7.37 (m, 1H), 7.12 – 7.07
(m, 1H), 7.04 (dd, J = 8.2, 6.7 Hz, 1H), 2.71 (s, 3H); 13C NMR (100
MHz, CDCl3): δ 150.3, 140.8, 129.7, 128.2, 127.9, 125.8, 122.9,
122.7, 121.3, 120.9, 117.9, 17.3; GC-MS: 208; HRMS (ESI
positive mode) calcd for C14H12N2+H+ 209.2659, found
209.2661.
Methyl 5-methyl-2-phenyl-2H-indazole-7-carboxylate (2f):
Synthesized via modified GP2 (24 h); white crystal (21.3 mg,
40% isolated yield); Rf: 0.51 (PE: EA=4:1); M.p. 109-111 oC; 1H
NMR (400 MHz, CDCl3): δ 8.41 (s, 1H), 7.99 (d, J = 1.6 Hz, 1H),
7.97 – 7.93 (m, 2H), 7.69 – 7.66 (m, 1H), 7.54 – 7.47 (m, 2H),
7.42 – 7.36 (m, 1H), 4.04 (s, 3H), 2.46 (d, J = 0.8 Hz, 3H); 13C
NMR (100 MHz, CDCl3): δ 166.8, 146.0, 140.5, 134.6, 131.1,
129.6, 128.2, 124.9, 124.6, 121.2, 120.5, 119.4, 52.4, 21.5; GC-
MS: 266; HRMS (ESI positive mode) calcd for C16H14N2O2+H+
267.1128, found 267.1129.
Experimental Section
General procedure for azobenzene synthesis (GP1)16
2.2 mmol of aniline was added into a solution of nitroso-
benzene (2.0 mmol) in 20 mL acetic acid. The reaction mixture
o
was stirred at 30 C in darkness for 2 days. After the reaction
completion, the mixture was diluted with 20 mL water and
extracted 3 time with 20 mL petroleum ether (PE). The organic
phase was combined, washed with NaHCO3 solution, dried and
evaporated. The obtained residual was eluted over silica gel
column with PE-dichloromathane (DCM) to give the
corresponding azobenzenes. The characterization data for
azobenzenes are displayed in ESI.
General procedure for 2H-indazole synthesis (GP2)
A seal tube was charged with 0.2 mmol of azobenzene, 0.4
mmol of NaOAc (32.8 mg), 0.21 mmol of I2 (54 mg), 1 mL DCE
and then moved into an oil bath which was preheated to 120
oC. After 12 h, the reaction was cooled to room temperature
and quenched with 1 mL of saturated NaHCO3 solution and 3
drops of saturated Na2S2O3 solution. Then, the mixture was
extracted with ethyl acetate (EA) and the obtained organic
phase was dried and evaporated. The residual was eluted over
Silica gel column with PE-EA to give the corresponding 2H-
indazoles.
7-Bromo-5-methyl-2-phenyl-2H-indazole (2g) and 7-iodo-5-
methyl-2-phenyl-2H-indazole (2h): Synthesized using 1g via
modified GP2 (24 h); white crystal (42.7 mg, 70% isolated yield,
2g: 2h= 1:0.61); Rf: 0.41(PE: EA=10:1); HRMS (ESI positive
mode) calcd for C14H11N2Br+H+ 287.1078, found 287.1075;
HRMS (ESI positive mode) calcd for C14H11N2I+H+ 335.0040,
found 335.0039.
2-Mesityl-5,7-dimethyl-2H-indazole (2a): Synthesized via
GP2; white solid (44.9 mg, 85% isolated yield); Rf: 0.42 (PE:
7-Iodo-5-methyl-2-phenyl-2H-indazole (2h): Synthesized via
GP2; white solid (56.4 mg, 85% isolated yield); M.p. 108-110
oC; Rf: 0.41 (PE: EA=10:1); 1H NMR (400 MHz, CDCl3): δ 8.41 (d,
J = 6.7 Hz, 1H), 7.93 – 7.87 (m, 2H), 7.66 (s, 1H), 7.54 – 7.48 (m,
2H), 7.42 – 7.36 (m, 2H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 149.7, 140.4, 139.4, 133.4, 129.6, 128.2, 122.3, 121.2, 121.2,
119.0, 83.9, 21.4; GC-MS: 334; HRMS (ESI positive mode) calcd
for C14H11IN2+H+ 335.0040, found 335.0039.
o
1
EA=10:1); M.p. 114-116 C; H NMR (400 MHz, CDCl3): δ 7.83
(s, 1H), 7.34 (s, 1H), 6.98 (s, 2H), 6.97 (s, 1H), 2.65 (s, 3H), 2.43
(s, 3H), 2.36 (s, 3H), 1.97 (s, 6H); 13C NMR (100 MHz, CDCl3): δ
148.6, 139.2, 137.7, 135.5, 131.6, 128.9, 128.2, 127.9, 124.0,
122.0, 115.9, 21.9, 21.2, 17.4, 17.3; GC-MS: 264; HRMS (ESI
positive mode) calcd for C18H20N2+H+ 265.1699, found
265.1700.
5-Methyl-2,7-diphenyl-2H-indazole (2i): Synthesized via GP2;
colorless oil (29.0 mg, 51% isolated yield); Rf: 0.52 (PE:
EA=10:1); 1H NMR (400 MHz, CDCl3): δ 8.37 (s, 1H), 8.17 – 8.13
(m, 2H), 7.97 – 7.93 (m, 2H), 7.55 – 7.49 (m, 4H), 7.45 – 7.34
(m, 4H), 2.50 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 147.2, 140.8,
138.3, 132.3, 130.6, 129.6, 129.0, 128.5, 128.4, 127.7, 127.6,
124.3, 120.9, 119.5, 117.9, 22.0; GC-MS: 284; HRMS (ESI
positive mode) calcd for C20H16N2+H+ 285.1386, found
285.1384.
5,7-Dimethyl-2-phenyl-2H-indazole (2b): Synthesized via
GP2; white solid (35.5 mg, 80% isolated yield); Rf: 0.51 (PE:
EA=10:1); M.p. 62-64 oC; 1H NMR (400 MHz, CDCl3): δ 8.25 (s,
1H), 7.91 (d, J = 7.5 Hz, 2H), 7.52 (t, J = 7.9 Hz, 2H), 7.38 (t, J =
7.4 Hz, 1H), 7.28 (s, 1H), 6.95 (s, 1H), 2.68 (s, 3H), 2.41 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 149.3, 140.9, 132.2, 129.6, 128.9,
127.8, 127.6, 123.0, 121.1, 119.8, 115.8, 21.9, 17.2; GC-MS:
222; HRMS (ESI positive mode) calcd for C15H14N2+H+ 223.1230,
found 223.1232.
5,7-Dimethyl-2,3-diphenyl-2H-indazole (2j): Synthesized via
modified GP2 (1 h); colorless crystal (51.5 mg, 86% isolated
5-Methoxy-7-methyl-2-phenyl-2H-indazole (2c): Synthesized
via modified GP2 (4 h); white solid (40.4 mg, 85% isolated
o
1
yield); Rf: 0.44 (PE: EA=10:1); M.p. 120-122 C; H NMR (400
MHz, CDCl3): δ 7.50 – 7.44 (m, 2H), 7.42 – 7.30 (m, 9H), 7.01 (s,
1H), 2.70 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
148.4, 140.5, 134.9, 132.4, 130.4, 129.8, 129.8, 129.1, 128.8,
128.2, 128.1, 127.6, 126.3, 121.9, 116.0, 22.0, 17.2; GC-MS:
298; HRMS (ESI positive mode) calcd for C21H18N2+H+ 299.1543,
found 299.1541.
o
1
yield); Rf: 0.36 (PE: EA=10:1); M.p. 100-101 C; H NMR (400
MHz, CDCl3): δ 8.24 (s, 1H), 7.91 – 7.86 (m, 2H), 7.54 – 7.48 (m,
2H), 7.39 – 7.34 (m, 1H), 6.82 – 6.79 (m, 1H), 6.74 (d, J = 2.2 Hz,
1H), 3.84 (s, 3H), 2.64 (s, 3H); 13C NMR (100 MHz, CDCl3): δ
155.8, 147.4, 140.9, 129.9, 129.6, 127.6, 122.6, 120.9, 120.8,
119.7, 93.8, 55.4, 17.1; GC-MS: 238; HRMS (ESI positive mode)
calcd for C15H14N2O+H+ 239.1178, found 239.1179.
Ethyl 5,7-dimethyl-2-phenyl-2H-indazole-3-carboxylate (2k):
Synthesized via modified GP2 (1 h); colorless crystal (42.4 mg,
72% isolated yield); Rf: 0.34 (PE: EA=10:1); M.p. 122-124 oC; 1H
NMR (400 MHz, CDCl3): δ 7.69 (s, 1H), 7.51 (s, 5H), 7.02 (s, 1H),
4.34 (q, J = 7.1 Hz, 2H), 2.65 (s, 3H), 2.48 (s, 3H), 1.32 (t, J = 7.1
Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 159.9, 147.9, 141.4,
135.9, 129.3, 129.2, 128.7, 128.5, 126.6, 124.6, 124.5, 117.2,
7-Methyl-2-phenyl-2H-indazole-5-carbonitrile
(2d):
Synthesized via modified GP2 (24 h); white crystal (36.3 mg,
78% isolated yield); Rf: 0.15 (PE: EA=10:1); M.p. 181-183 oC; 1H
NMR (400 MHz, CDCl3): δ 8.51 (s, 1H), 8.01 (s, 1H), 7.91 (d, J =
7.7 Hz, 2H), 7.56 (t, J = 7.9 Hz, 2H), 7.45 (t, J = 7.4 Hz, 1H), 7.18
(s, 1H), 2.68 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 150.2, 140.1,
130.3, 129.9, 128.8, 126.1, 125.8, 122.6, 121.5, 121.4, 120.1,
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(a) B. Hag, Z. Peng and P. Knochel, Org. Lett., 20V0ie9w,A1rt1ic,le4O2n7lin0e;
6
61.0, 22.3, 17.0, 14.3; GC-MS: 294; HRMS (ESI positive mode)
calcd for C18H18N2O2+H+ 295.1441, found 295.1440.
(b) N. Halland, M. Nazaré, O. R'Kyek,DJO. IA: 1lo0.n10so39, /MC6.OUBr0m18a2n7nK
and A. Lindenschmidt, Angew. Chem. Int. Ed., 2009, 48, 6879;
(c) J. J. Song and N. K. Yee, Org. Lett., 2000, 2, 519.
3,7-Dimethyl-2-phenyl-2H-indazole (2l): Synthesized via GP2,
separated from its mixture with 2l’; yellowish oil (29.2 mg, 66%
isolated yield); Rf: 0.26 (PE: EA=10:1); 1H NMR (400 MHz,
CDCl3): δ 7.62 – 7.52 (m, 4H), 7.50 – 7.46 (m, 2H), 7.12 – 7.08
(m, 1H), 7.01 (dd, J = 8.4, 6.7 Hz, 1H), 2.67 (s, 1H), 2.63 (s, 1H);
13C NMR (100 MHz, CDCl3): δ 149.0, 140.2, 132.3, 129.3, 128.7,
127.7, 126.1, 125.8, 121.4, 121.3, 117.5, 17.3, 11.3; GC-MS:
222; HRMS (ESI positive mode) calcd for C15H14N2+H+ 223.1230,
found 223.1231.
7-Ethyl-2-phenyl-2H-indazole (2l’): Synthesized via GP2,
separated from its mixture with 2l; yellowish oil (4.4 mg, 10%
isolated yield); Rf: 0.48 (PE: EA=10:1); 1H NMR (400 MHz,
CDCl3): δ 8.39 (s, 1H), 7.92 (d, J = 7.7 Hz, 2H), 7.58 – 7.50 (m,
3H), 7.40 (t, J = 6.9 Hz, 1H), 7.13 – 7.03 (m, 2H), 3.14 (q, J = 7.5
Hz, 2H), 1.46 (t, J = 7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ
149.6, 140.9, 134.3, 129.7, 127.9, 123.7, 122.9, 121.3, 120.7,
117.9, 24.5, 14.0; GC-MS: 222; HRMS (ESI positive mode) calcd
for C15H14N2+H+ 223.1230, found 223.1231.
7
8
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This work was supported by the National Natural Science
Foundation of China (21272132 and 21472106) and the
National Key Basic Research Program of China (973 program)
(2012CB933402). We thank Tsinghua Xuetang Talents Program
for computational support. We also thank Prof. Yong Li and
Prof. Haijun Yang (in Tsinghua University) for EPR analysis, Prof.
Qun Zhou (in Tsinghua University) for help in FIR experiments
and Prof. Chao Chen (in Tsinghua University) for advices to this
work.
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