A novel method for the synthesis of haloisoquinolines involving an electrophile-exchange process

Article abstract of DOI:10.3184/174751914X14140703941872

A synthesis of haloisoquinolines through electrophilic cyclisation involving an electrophilic-exchange process has been developed. A variety of 2-alkynyl benzyl azides are cyclised in the presence of KX (X = I, Br, Cl) and electrophilic fluoride reagents,

Full text of DOI:10.3184/174751914X14140703941872

682 RESEARCH PAPER
VOL. 38 NOVEMBER, 682–685
JOURNAL OF CHEMICAL RESEARCH 2014
A novel method for the synthesis of haloisoquinolines involving an
electrophile-exchange process
Hong-Ping Zhang* and Hong-Yan Li
Department of Biology and Chemistry Engineering, Shaoyang University, Shaoyang 422000, P.R. China
A synthesis of haloisoquinolines through electrophilic cyclisation involving an electrophilic-exchange process has been
developed. A variety of 2-alkynyl benzyl azides are cyclised in the presence of KX (X=I, Br, Cl) and electrophilic fluoride reagents,
to afford the corresponding haloisoquinolines in moderate to good yields. Reagents for electrophilic halogenation have been
generated from their inorganic salts (M+X–) by oxidation with a Selectfluor reagent and reacted in situ with the substrates.
Keywords: haloisoquinolines; electrophilic-exchange process; electrophilic cyclisation; 2-alkynyl benzyl azides
Isoquinolines are present in a wide variety of biologically active
compounds and pharmaceutical agents. Haloisoquinolins have
recently attracted considerable attention from both industry and
academia due to their therapeutic value in a variety of diseases,
showing anti-HIV-1, anticancer, antimicrobial, and antifungal
properties. Furthermore, functionalised isoquinolines have
been shown to be organocatalysts and are recognised as
useful tools for the highly enantioselective syntheses of chiral
molecules. Because of their importance, the development of new
synthetic approaches for their preparation remains an active
research area. Among these methods, electrophilic cyclisation
for accessing the haloisoquinoline skeleton has aroused
considerable interest. For example, the Yamamto group1,2
employed 2-alkynyl benzyl azides as the starting materials
for haloisoquinolines using an electrophilic iodocyclisation
process. Wu3,4 prepared 4-haloisoquinolines via CuX2-mediated
cyclisation of 2-alkynylbenzaldehyde O-methyl oximes, and
a three component reaction of 2-alkynylbenzaldoxime and
carbodiimide with electrophile.3,4 Another report by Li and
co-workers5 described the synthesis of iodoisoquinoline-fused
benzimidazoles by a copper-promoted tandem cyclisation
of 2-ethynylbenzaldehydes with o-benzenediamines and
iodine.5 Generally, all these procedures have focused on direct
halogenation of the isoquinoline skeleton by using different
halogenating species. Reagents for electrophilic halogenation
are available in different forms varying from the diatomic
elements to some fairly exotic halogen delivery reagents.
Although most of these reagents can be prepared and isolated
prior to use, the electrophiles are limited to halogens, such as
ICl,6,7 I2,8–10 NBS (N-bromo-succinimide),11,12 and Br2.13,14 Some
of these are relatively expensive, highly corrosive and toxic.
Therefore, there is considerable interest in developing more
efficient methods for electrophilic halogenation. Recently, it
has been shown that Selectfluor reagent could not only be used
as an electrophilic fluorination agent but also as an oxidising
agent. A variety of Selectfluor reagents as new oxidisers have
been used for the conversion of inorganic salts bearing halogen
anions to active electrophilic halogenation species and have
been successfully applied in introducing electrophiles into
aromatic systems.15,16 The results show that Cl+ and Br+ have
been generated from their respective inorganic salts (M+X–) by
oxidation with Selectfluor reagent, and then reacted in situ with
aromatic substrates.
suitable for constructing the 4-haloisoquinoline skeleton.17
A
novel synthesis of spiro[4.5]decenones via electrophilic ipso-
cyclisation involving an electrophile-exchange process was
reported by Li and co-workers.18 Accordingly, it occurred
to us that alternative electrophilic cyclisation of 2-alkynyl
benzyl azides including new electrophiles generated through
the process involving electrophile-exchange with Selectfluor
would give haloisoquinolines. Herein, we reported a new
method for the synthesis of 4-haloisoquinolines from 2-alkynyl
benzyl azides in the presence of KX and Selectfluor in DMF at
80 °C (Scheme 1).
N
N3
selectfluor, KX
R
R1
solvent
R1
X
R
X = I, Cl, Br
Scheme 1 Synthesis of haloisoquinolines promoted by Selectfluor
involving an electrophile-exchange process.
Results and discussion
As shown in Table 1, 2-phenylethynyl benzyl azide (1a) was
used as the model substrate to identify the optimal conditions.
Initially, the effect of solvents on the reaction of azide 1a was
examined in the presence of 1.5 equiv. F1, 1-fluoro-2,4,6-
trimethylpyridinium tetrafluoroborate, 3 equiv. KI (entries
1–5). DMF was superior to all the other solvents. The results
revealed that solvent polarity played a significant role in the
formation of haloisoquinoline. For example, the reactions
proceeded in highly polar solvents such as MeCN and THF,
although moderate yields of 68% and 66% were observed,
respectively (entries 2 and 3), and a significantly lower yield
was observed in 1,2-dichloroethane and toluene (entries 1 and
4). In addition, in the case of the electrophilic cyclisation of
2-phenylethynyl benzyl azide (1a), the cyclisation of 1a afforded
the corresponding product along with the 1,3-dipolar adduct 5
as a minor product in MeCN solvent. However, iodocyclisation
via I–/F+ electrophile exchange procedure did not produce 5 at all
(entry 2). The temperature also was evaluated, and the preferred
temperature for the reaction was 80 °C (entries 5–8). Another
electrophilic fluoride reagent F2, N-Fluoro-N′-(chloromethyl)
triethylenediamine bis(tetrafluoroborate), was examined, but
it was less effective than F1 (entry 9). It was noteworthy that
no reaction was observed without any electrophilic fluoride
reagents (entry 10). Subsequently, the amount of both KI and
F1 was investigated. The results revealed that 3 equiv. of KI
and 1.5 equiv. of F1 provided the best results, and produced
4-iodo-3-phenylisoquinoline in 88% yield (entries 6, 11, and
12). Finally, a series of salts including KBr, KCl, NaCl and
NH4Cl were also examined by reacting with 1a in the presence
Recently, we reported the synthesis of 4-haloisoquinolines
through the halopalladation cyclisation of alkynes with azides,
and the results showed that 2-alkynyl benzyl azides were
* Correspondent. E-mail: zhp4901@163.com
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JOURNAL OF CHEMICAL RESEARCH 2014 683
Table 1 Screening optimal conditionsa
N
N
N
5
F+
N3
N
MX
Ph
solvent
X
Ph
Ph
1a
2a-4a
M = K, Na, NH4
X = I, Cl, Br
CH2Cl
N+
N+
-
F+
=
2BF4
N+
F
-
BF4
F
F1
F2
Entry
KX
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KI
KBr
KCl
NaCl
NH4Cl
Solvent
Selectfluor
Temperature/oC
Time /h
Yield /%b
1
2c
3
4
5
6
7
8
9
10
11d
12e
13
14
15
16
CH2ClCH2Cl
MeCN
THF
Toluene
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
F1
F1
F1
F1
F1
F1
F1
F1
F2
–
F1
F1
F1
F1
F1
F1
80
80
80
80
80
100
60
r.t.
80
80
80
80
80
80
80
80
22
22
22
24
22
20
26
30
22
22
22
22
23
36
36
36
22
68
66
18
88
76
54
trace
68
0
81
79
80
72
65
60
aReaction conditions: 1 (0.3 mmol), KX (3 equiv.), F+ (1.5 equiv.), and DMF (3 mL).
bIsolated yield.
c1,3-dipolar adduct 5 in 15% yield was observed.
dF+ (1.0 equiv.).
eKI (2 equiv.).
of the Selectfluor F1 (entries 13–16). We observed that both
KBr (2b) and KCl (2c) were highly reactive. The reactivity
of the electrophiles generated from various potassium salts
decreased in the order I+ >Br+ >Cl+. It was found that using KCl
was marginally more effective than that for NaCl and NH4Cl.
Thus, we chose the following reaction conditions as optimum
for all subsequent cyclisations: 0.3 mmol of 2-alkynyl benzyl
azides, 1.5 equiv. F1, and 3 equiv. KX in DMF stirred at 80 °C
for an appropriate amount of time.
With the standard reaction conditions in hand, we then used
the KX/F1 system to explore the scope of azides (Table 2).
The results showed that azides attached to various aryl group
at the terminal alkyne were tolerated well in the presence of
3 equiv. KX and 1.5 equiv. F1 and afforded the corresponding
haloisoquinolines in moderate to good yield, respectively
(entries 1–9). Substrates with an electron-withdrawing
group also reacted (entries 1, 2, 3, 7, 8 and 9). The standard
conditions were also compatible with both aliphatic and vinyl
alkynes 1e–g (entries 10–18). Substrate 1g with a cyclohexenyl
group, for instance, gave the desired product 4g in 88% yield
(entry 16). However, the annulation of aliphatic alkynes 1e–g
afforded 4-bromo-1,2-dihydro-isoquinolines 3e–g using KBr/
F1 system (entries 11, 14 and 17). A thiophen-2-yl substrate
1h was perfectly tolerated. For example, in the presence
of 3 equiv. KX (X=I, Br) and 1.5 equiv. F1, treatment of
gave the corresponding haloisoquinolines 3h and 4h in 82% and
84% yield, respectively. It was interesting that an unexpected
dichloro-addition product 2h was obtained in KCl/F1 system.
The result was in accordance with our previous reports on
halopalladation of 2-alkynyl benzyl azides.17
In conclusion, we have developed a novel and flexible
approach to highly haloisoquinolines through electrophilic
cyclisation involving an electrophile-exchange procedure. In
the presence of KX (X=I, Br, Cl) and electrophilic fluoride
reagents, a variety of 2-alkynyl benzyl azides were cyclised
to afford the corresponding haloisoquinolines in moderate to
excellent yields. Importantly, a halide is introduced into the
products, which can then be further functionalised, making the
methodology more attractive for organic synthesis.
Experimental
NMR spectroscopy was performed on AMX-500 (Bruker)
spectrometer, operating at 500 MHz (1H NMR) and 125 MHz
(13C NMR). TMS was used an internal standard and CDCl3 was used as
the solvent. Mass spectrometric analysis was performed on a GC-MS
instrument (Shimadzu GCMS-QP2010 plus). Melting points were
recorded on an Electrothermal type 9100 melting point apparatus.
All melting points are uncorrected. Benzyl azides were prepared
according to the published method.20 Other reagents which were
commercially available were obtained from the Alfa Aesar and TCI
companies.
2-((2-(azidomethyl)phenyl)ethynyl)-5-methylthiophene
(1h)
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684 JOURNAL OF CHEMICAL RESEARCH 2014
Table 2 Synthesis of haloisoquinolines with azides and electrophilesa
N
N3
F1, KX
DMF, 80 o
C
R
X
R
X = I, Br, Cl
1
2–4
M.p./oC
Entry
R
KX
Time /h
Yield/%b,f
Found
Reported [ref.]
1
2
3
KCl
KBr
KI
24
22
22
70 (2b)
79 (3b)
80 (4b)
140.2–141.1
142.8–143.6
145.5–146.4
4-Chlorophenyl (1b)
4
5
6
KCl
KBr
KI
24
22
20
74 (2c)
82 (3c)
86 (4c)
77.5–77.8
109.6–110.8
113.6–114.4
77.6–77.8[17]
109.8–110.9[17]
113–115[19]
4-Methoxyphenyl (1c)
4-Nitrophenyl (1d)
Pentyl (1e)
7
8
9
KCl
KBr
KI
36
30
26
35 (2d)
44 (3d)
56 (4d)
154.4–155.7
158.6–159.4
154.6–155.8
154.6–155.8[17]
10
11
12
KCl
KBr
KI
24
22
22
77 (2e)
87 (3e)c
90 (4e)
13
14
15
KCl
KBr
KI
24
22
22
66 (2f)
81 (3f)d
85 (4f)
Octyl (1f)
16
17
18
KCl
KBr
KI
30
24
24
73 (2g)
82 (3g)e
88 (4g)
1-Cyclohexenyl (1g)
5-Methylthiophen-2-yl (1h)
19
20
21
KCl
KBr
KI
34
22
22
71 (2h)f
82 (3h)
84 (4h)
77.6–78.8
80.5–81.2
89.6–90.9
aReaction conditions: 1 (0.3 mmol), KX (3 equiv.), F1 (1.5 equiv.), and DMF (3 mL) at 80 °C.
bIsolated yield.
c3e is 4-bromo-3-pentyl-1,2-dihydroisoquinoline.
d3f is 4-bromo-3-octyl-1,2-dihydroisoquinoline.
e3g is 4-bromo-3-cyclohexenyl-1,2-dihydroisoquinoline.
f2h is 4-chloro-3-(3-chloro-5-methylthiophen-2-yl)isoquinoline.
gProducts were characterised by 1H NMR and 13C NMR spectroscopy.
Synthesis of haloisoquinolines; general procedure
(M+ +4, 52), 295 (M+ +2, 100), 293 (M+, 13), 258 (–Cl, 11), 223 (–2Cl,
20); HRMS (EI) for C14H9Cl2NS (M+): calcd 292.9833, found 292.9828.
4-Bromo-3-(4-chlorophenyl)isoquinoline (3b): yield 79%; orange
A flame-dried Schlenk tube with a magnetic stirring bar containing
the azide 1 (0.3 mmol), Selectfluor (1.5 equiv.), KX (3 equiv.) and
DMF (3 mL) was stirred at 80 °C until the complete consumption of
the starting material was observed (monitored by TLC and GC-MS
analysis). After the reaction was finished, the mixture was poured into
ethyl acetate, washed with brine (3×10 mL). The combined organic
layers were dried by anhydrous Na2SO4 and evaporated under vacuum.
The residue was purified by flash column chromatography on silica gel
(hexane/ethyl acetate) to afford the desired product.
1
solid, m.p. 142.8–143.6 °C (uncorrected); H NMR (500 MHz, CDCl3)
δ 9.21 (s, 1H), 8.32 (d, J=8.5 Hz, 1H), 8.00 (d, J=8.5 Hz, 1H), 7.84 (t,
J=7.5 Hz, 1H), 7.70–7.67 (m, 3H), 7.46 (d, J=8.5 Hz, 2H); 13C NMR
(125 MHz, CDCl3) δ 151.2, 151.1, 139.1, 136.0, 134.4, 132.0, 131.4,
128.7, 128.2, 128.1, 127.7, 127.0, 118.3; LRMS (EI, 70 eV) m/z (%): 319
(M+ +2, 45), 317 (M+, 47), 238 (–Br, 62), 203 (–(Br+Cl), 41); HRMS
(EI) for C15H979BrClN (M+): calcd 316.9607, found 316.9604.
4-Chloro-3-(4-chlorophenyl)isoquinoline (2b): Yield 70%; white
solid, m.p. 140.2–141.1 °C. (uncorrected); 1H NMR (500 MHz, CDCl3)
δ 9.21 (s, 1H), 8.34 (d, J=8.5 Hz, 1H), 8.03 (d, J=8.0 Hz, 1H), 7.86 (t,
J=8.5 Hz, 1H), 7.77 (t, J=8.0 Hz, 2H), 7.70 (t, J=8.5 Hz, 1H), 7.48
(d, J=8.5 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 150.5, 148.7, 137.4,
134.6, 131.8, 131.4, 128.6, 128.3, 128.1, 127.7, 125.9, 124.1; LRMS (EI,
70 eV) m/z (%): 275 (M+ +2, 5), 273 (M+, 15), 238 (–Cl, 69), 203 (–2Cl,
34); HRMS (EI) for C15H9Cl2N (M+): calcd 273.0112, found 273.0110.
4-Chloro-3-(3-chloro-5-methylthiophen-2-yl)isoquinoline (2h):
4-Bromo-3-(4-nitrophenyl)isoquinoline (3d): Yield 44%; yellow
solid, m.p. 158.6–159.4 °C (uncorrected); H NMR (500 MHz, CDCl3)
1
δ 8.64 (s, 1H), 8.33 (d, J=8.5 Hz, 2H), 7.90 (d, J=8.0 Hz, 1H), 7.76 (d,
J=8.0 Hz, 2H), 7.48 (t, J=7.5 Hz, 1H), 7.32 (d, J=7.5 Hz, 1H), 7.07
(d, J=8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 142.9, 135.1, 132.9,
131.3, 131.2, 131.0, 129.5, 129.2, 127.3, 124.5, 124.1, 122.5, 100.0,
29.7; LRMS (EI, 70 eV) m/z (%): 329 (M+ +2, 33), 327 (M+, 100), 249
(–Br, 25); HRMS (EI) for C15H979BrN2O2 (M+): calcd 327.9843, found
327.9840.
1
Yield 71%; orange solid, m.p. 77.6–78.8 °C (uncorrected); H NMR
4-Bromo-3-(5-methylthiophen-2-yl)isoquinoline (3h): Yield 82%;
1
(500 MHz, CDCl3) δ 9.10 (s, 1H), 8.35 (d, J=8.5 Hz, 1H), 7.99 (s, 1H),
7.96 (d, J=8.0 Hz, 1H), 7.82 (t, J=7.5 Hz, 1H), 7.63 (t, J=7.5 Hz, 1H),
2.47 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 150.2, 135.7, 135.0, 131.9,
129.0, 128.1, 127.8, 127.7, 124.0, 13.1; LRMS (EI, 70 eV) m/z (%): 297
orange solid, m.p. 80.5–81.2 °C (uncorrected); H NMR (500 MHz,
CDCl3) δ 9.12 (s, 1H), 8.31 (d, J=8.0 Hz, 1H), 8.02 (d, J=8.5 Hz, 1H,),
7.93 (d, J=7.5 Hz, 1H), 7.79 (t, J=7.5 Hz, 1H), 7.61 (t, J=7.5 Hz, 1H),
6.85–6.84 (m 1H), 2.56 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 150.8,
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JOURNAL OF CHEMICAL RESEARCH 2014 685
143.4, 141.3, 136.5, 131.9, 129.7, 128.0, 127.8, 127.5, 126.0, 115.3, 15.4;
LRMS (EI, 70 eV) m/z (%): 307 (M+ +4, 52), 305 (M+ +2, 100), 303 (M+,
23), 224 (–Br, 31); HRMS (EI) for C14H10BrNS (M+): calcd 302.9721,
found 302.9718.
CAUTION: Many low-molecular-weight azides are known to
be explosive. In this lab, no problems have been encountered in
this work, but great caution should be exercised when heating
compounds of this type, especially neat. The reactions described
here were run on only a few grams; but an increase in the scale of
these reactions will decrease the efficiency of heat dissipation and
explosions may result.
4-Iodo-3-(4-chlorophenyl)isoquinoline (4b): Yield 80%; yellow
1
solid, m.p. 145.5–146.4 °C (uncorrected); H NMR (500 MHz, CDCl3)
δ 9.14 (s, 1H), 8.20 (d, J=8.5 Hz, 1H), 7.94 (d, J=8.0 Hz, 1H), 7.83 (d,
J=8.5 Hz, 1H), 7.81 (d, J=6.5 Hz, 1H), 7.68 (t, J=7.5 Hz, 2H), 7.47
(t, J=6.0 Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 155.8, 152.1, 142.0,
138.5, 134.3, 132.3, 131.3, 128.2, 128.1, 128.0, 127.9, 98.0; LRMS (EI,
70 eV) m/z (%): 367 (M+ +2, 5), 365 (M+, 25), 238 (–I, 60), 203 (–(Cl+I),
31); HRMS (EI) for C15H9ClIN (M+): calcd 364.9468, found 364.9463.
4-Iodo-3-(4-nitrophenyl)isoquinoline (4d): Yield 56%; yellow solid,
m.p. 154.6–155.8 °C (uncorrected); 1H NMR (500 MHz, CDCl3) δ
9.20 (s, 1H), 8.36 (d, J=6.0 Hz, 2H), 8.24 (d, J=8.5 Hz, 1H), 8.00 (d,
J=8.0 Hz, 1H), 7.89 (t, J=8.0 Hz, 1H), 7.82 (d, J=8.5 Hz, 2H), 7.75 (t,
J=7.5 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 154.7, 152.3, 149.7, 147.5,
138.3, 132.7, 132.4, 131.1, 128.8, 128.3, 128.1, 123.2, 98.0; LRMS (EI,
70 eV) m/z (%): 378 (M+ +2, 33), 376 (M+, 100), 249 (–I, 25); HRMS (EI)
for C15H9IN2O2 (M+): calcd 375.9704, found 375.9701.
The authors thank the major project in institutions of higher
education of Hunan province (No. 14A133), Hunan provincial
natural Science Foundation (No. 14JJ7076), and Scientific and
Technological Innovative team of Shaoyang University (2012)
for financial support.
Received 17 August 2014; accepted 20 October 2014
Paper 1402836 doi: 10.3184/174751914X14140703941872
Published online: 13 November 2014
4-Iodo-3-pentylisoquinoline (4e): Yield 90%; pale yellow oil;
1H NMR (500 MHz, CDCl3) δ 9.05 (s, 1H), 8.10 (d, J=8.5 Hz, 1H), 7.87
(d, J=8.0 Hz, 1H), 7.75 (t, J=7.5 Hz, 1H), 7.59 (t, J=7.5 Hz, 1H), 3.25 (t,
J=8.0 Hz, 2H), 1.83–1.77 (m, 2H), 1.49–1.37 (m, 4H), 0.93 (t, J=7.5 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 158.3, 152.0, 138.3, 131.8, 131.4,
127.8, 127.7, 127.1, 98.8, 42.5, 31.8, 29.2, 22.6, 14.1; LRMS (EI, 70 eV)
m/z (%): 327 (M+ +2, 9), 325 (M+, 7), 254 (23), 177 (100); HRMS (EI) for
C14H16IN (M+): calcd 325.0327, found 325.0323.
4-Iodo-3-octylisoquinoline (4f): Yield 85%; pale yellow oil; 1H NMR
(500 MHz, CDCl3) δ 9.04 (s, 1H), 8.09 (d, J=8.5 Hz, 1H), 7.86 (d,
J=8.0 Hz, 1H), 7.74 (t, J=7.5 Hz, 1H), 7.58 (t, J=7.5 Hz, 1H), 3.25 (t,
J=8.0 Hz, 2H), 1.82–1.76 (m, 2H), 1.48–1.43 (m, 2H), 1.30–1.27 (m,
6H), 0.87 (t, J=7.0 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 158.3,
152.0, 138.3, 131.7, 131.4, 127.8, 127.7, 127.1, 98.8, 42.5, 31.9, 29.6, 29.5,
29.4, 29.3, 22.7, 14.1; LRMS (EI, 70 eV) m/z (%): 369 (M+ +2, 4), 367
(M+, 10), 240 (–I, 28), 177 (100); HRMS (EI) for C17H22IN (M+): calcd
367.0797, found 367.0793.
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Org. Lett., 2011, 13, 272.
14 F. Manarin, J.A. Roehrs, R.M. Gay, R. Brandao, P.H. Menezes, C.W.
Nogueira and G. Zeni. J. Org. Chem., 2009, 74, 2153.
15 R.G. Syvret, K.M. Butt, T.P. Nguyen, V.L. Bulleck and R.D. Rieth, J. Org.
Chem., 2002, 67, 4487.
4-Iodo-3-(5-methylthiophen-2-yl)isoquinoline (4h): Yield 84%;
1
orange solid, m.p. 89.6–90.9 °C (uncorrected); H NMR (500 MHz,
CDCl3) δ 9.05 (s, 1H), 8.21 (d, J=9.0 Hz, 1H), 7.87 (d, J=8.0 Hz, 1H),
7.82 (t, J=11.5 Hz, 1H), 7.78–7.73 (m, 1H), 7.61 (t, J=7.5 Hz, 1H), 6.86
(t, J=2.0 Hz, 1H), 2.47 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 151.7,
150.0, 143.1, 139.0, 133.7, 132.2, 129.9, 127.7, 126.4, 15.4; LRMS (EI,
70 eV) m/z (%): 353 (M+ +2, 32), 351 (M+, 16), 224 (–I, 21), 127 (20);
HRMS (EI) for C14H10INS (M+): calcd 350.9579, found 350.9576.
3-Phenyl-8H-[1,2,3]triazolo[5,1-a]isoindole (5):21 White solid,
16 M. Ztspan, J. Iskra and S. Stavber, Tetrahedron Lett., 1997, 38, 6305.
17 H.-P. Zhang, S.-C. Yu, Y. Liang, P. Peng, B.-X. Tang and J.-H. Li, Synlett,
2011, 7, 982.
1
151.6–152.9 °C (lit.21 152–154 °C)(uncorrected); H NMR (500 MHz,
CDCl3) δ 7.94 (d, J=8.0 Hz, 2H), 7.90 (d, J=7.5 Hz, 1H), 7.53 (t,
J=7.5 Hz, 3H), 7.48 (t, J=7.5 Hz, 1H), 7.44–7.40 (m, 2H), 5.37 (s, 2H);
13C NMR (125 MHz, CDCl3) δ 141.1, 139.3, 139.0, 131.2, 128.9, 128.8,
128.4, 128.2, 128.1, 127.0, 124.1, 121.2; LRMS (EI, 70 eV) m/z (%): 235
(M+ +2, 28), 233 (M+, 16), 126 (24).
18 B.-X. Tang, Q. Yin, R.-Y. Tang and J.-H. Li, J. Org. Chem., 2008, 73, 9008.
19 Q. Huang, J.A. Hunter and R.C. Larock, J. Org. Chem., 2002, 67, 3437.
20 H.-P. Zhang, H.-Y. Li and H.-F. Xiao, J. Chem. Res., 2013, 37, 556.
21 C. Chowdhury, S.B. Mandal and B. Achari, Tetrahedron Lett., 2005, 46,
8531.
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