Highly Efficient Synthesis of Hindered 3-Azoindoles via Metal-Free C-H Functionalization of Indoles

Article abstract of DOI:10.1055/s-0039-1690048

Although 3-azoindoles have recently emerged as an appealing family of photoswitch molecules, the synthesis of such compounds has been poorly covered in the literature. Herein a high-yielding and operationally simple protocol is reported allowing the synthesis of 3-azoindoles, featuring important steric hindrance around the azo motif. Remarkably, this C-H coupling is characterized by excellent atom economy and occurs under metal-free conditions, at room temperature, and within few minutes, delivering the expected products in excellent yields (quantitatively in most of the cases). Accordingly, a library of new molecules, with potential applications as photochromic compounds, is prepared.

Full text of DOI:10.1055/s-0039-1690048

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2020, 52, A–G
paper
A
en
N. Jacob et al.
Paper
Synthesis
Highly Efficient Synthesis of Hindered 3-Azoindoles via Metal-Free
C–H Functionalization of Indoles
Nicolas Jacob
Highly substituted
3-azoindoles
Lucas Guillemard
Joanna Wencel-Delord*
NO METAL
H
NO ADDITIVES
N
N
Laboratoire d’Innovation Moléculaire et Applications
(UMR CNRS 7042), Université de Strasbourg/Université de
Haute-Alsace, ECPM, 25 Rue Becquerel, 67087 Strasbourg,
France
+
N2
BF4
MILD REACTION
CONDITIONS
N
N
SHORT
REACTION TIME
wenceldelord@unistra.fr
19 examples
up to 99% yield
Published as part of the Bürgenstock Special Section 2019
Future Stars in Organic Chemistry
Received: 20.11.2019
Accepted after revision: 06.01.2020
Published online: 16.01.2020
es will be selected (long thermal lifetime) while compounds
characterized by short thermal lifetime are used in real-
time optical information transmitting materials,10 in me-
dicinal chemistry for neurons or ion channel stimulation
purposes.11 Accordingly, several families of molecular pho-
toswitches have been designed (Figure 1b) including spiro-
pyranes,12 stilbenes13 and diarylethenes,14 but the azoben-
zenes15 are, by far, the most commonly applied ones (Figure
1a). More recently, indigoids16 or Stenhouse adducts17 have
been disclosed. Considerable attention has also been fo-
cused on heteroazoswitches,18 including compounds featur-
ing pyridine, imidazole, pyrazole, and purine motifs.
In clear contrast, 3-arylazoindoles are relatively under-
explored molecules.19 Surprisingly, only few literature re-
ports disclose synthesis of indoles bearing a diazo moiety in
C3 position20 and the recent methodologies request use of
sophisticated coupling partners such as aryltriazenes21 in
ionic liquid medium or arylhydrazine hydrochlorides22 un-
der visible-light irradiation or heating at 90 °C.
Very recently, a unique potential of 3-arylazoindole
photoswitches has been demonstrated by König (Figure
1c)23 and thus development of truly efficient, sustainable
and straightforward protocols delivering such compounds
is timely. In particular, as the properties of azoswitches, and
especially their thermal lifetime, are impacted by the sub-
stitution pattern around the azo moiety, synthesis of a li-
brary of 3-arylazoindoles bearing various substituents in
proximity of N=N motif, on both C2 position of the indole
and ortho-, ortho′-positions of the aromatic ring, seems
very appealing (Figure 1d).24 Accordingly, we report herein
an extremely simple but highly efficient strategy to prepare
sterically hindered 2-substituted 3-arylazoindoles, the mol-
ecules with promising photochromic properties.
DOI: 10.1055/s-0039-1690048; Art ID: ss-2019-z0645-op
Abstract Although 3-azoindoles have recently emerged as an appeal-
ing family of photoswitch molecules, the synthesis of such compounds
has been poorly covered in the literature. Herein a high-yielding and op-
erationally simple protocol is reported allowing the synthesis of 3-azo-
indoles, featuring important steric hindrance around the azo motif. Re-
markably, this C–H coupling is characterized by excellent atom
economy and occurs under metal-free conditions, at room tempera-
ture, and within few minutes, delivering the expected products in excel-
lent yields (quantitatively in most of the cases). Accordingly, a library of
new molecules, with potential applications as photochromic com-
pounds, is prepared.
Key words azoindole, C–H functionalization of indoles, azoswitches,
diazenylation
Reversible modification of the key properties of a mole-
cule, such as geometry, rigidity, dielectric constant, or re-
fractive index under light irradiation is an intriguing feature
of photochromic compounds with great potential applica-
tions in different fields.1 Thus, not surprisingly, molecular
photoswitches have been attracting, over the last few de-
cades, a growing attention and consequently these mole-
cules have found numerous applications in light-triggered
materials and machines,2 3D data storage systems,3 light
driven molecular motors,4 polymers,5 drug delivery,6 and
control of cell death.7 Such a large range of applications can
be reached, because the physical properties of pho-
toswitches, and in particular the thermal lifetime of the
metastable Z-isomer (varying from nanosecond scale range
to days), can be controlled by carefully selecting the appro-
priate photochromic scaffolds (Figure 1a). For example, if
molecular storage,8 or biological applications in photomod-
ulation of protein expression systems or oligonucleotide
recognition applications are targeted,9 stable photoswitch-
Our investigations began by exploring the coupling be-
tween 2-(tert-butyl)-1H-indole (1a) and electron-rich para-
methoxyphenyldiazonium salt 2a. The reaction occurred
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G
Georg Thieme Verlag KG, Rüdigerstraße 14, 70469 Stuttgart, Germany

B
N. Jacob et al.
Paper
Synthesis
a)
c)
Emerging family of
diazoindole
photoswitches
azobenzene
UV light
N
N
N
N
N
N
visible light or
N
thermal equilibration
E-azobenzene
(trans)
Z-azobenzene
(cis)
Challenge
d)
Sustainable and efficient
synthesis of highly substituted
3-azoindoles
b)
diarylethenes
spiropyran
NO2
stilbene
R
R
O
N
N
N
R
R
R
R
R
S
S
N
Figure 1 Several families of common photoswitch compounds
smoothly in methanol medium and at room temperature,
delivering the expected (E)-2-(tert-butyl)-3-[(4-methoxy-
phenyl)diazenyl]-1H-indole (3a) in quantitative yield (Table
1, entry 1). Comparable results were obtained when using
2-(methyl)-1H-indole (1b) as substrate (entry 2). Besides,
the reaction is extremely fast as full conversion of 1b could
be achieved in less than 10 minutes (entry 3), even in the
presence of equimolar amounts of both coupling partners
(entry 4). Electron-poor Ac-substituted aryldiazonium salts
may also be converted into 3-arylazoindoles, but the reac-
tion generally requires a slight excess of the diazonium salts
coupling partners (entry 5). Accordingly, the general reac-
tion conditions have been determined, that is, use of 1.3
equivalents of diazonium salt in MeOH medium and 30
minutes as standard reaction time (entry 6). Of note is that
the desired products are isolated via simple filtration of the
crude mixture through silica gel pad, further demonstrating
the experimental simplicity and efficiency of this protocol.
This transformation hence perfectly follows the require-
ments of sustainable and green chemistry, as neither a cat-
alysts nor sophisticated additives or strong oxidants are re-
quired and this coupling is characterized by excellent atom
economy. Finally, the reaction performed in water is slug-
gish and the desired product 4a was formed in only 68%
NMR conversion after 4 days (entry 7).
The generality of this new protocol was subsequently
explored (Scheme 1). Rewardingly, indole 1a bearing a
highly hindering tert-butyl motif in C2 position could be
coupled very smoothly with diverse diazo coupling part-
ners, both electron-rich and electron-poor, affording the
expected products in excellent yields and in short reaction
time. Importantly, the presence of a substituent in the or-
tho-position of 2 is tolerated well, as 3b, 3c, and 3e could be
isolated in almost quantitative yields. In addition, very con-
gested azoindole 3g could also be synthesized following the
standard procedure in 93% yield. Interestingly, our protocol
also tolerates relatively well a halogen atom on the indole
scaffold, as 3h could be isolated in 70% yield, albeit excess of
Table 1 Optimization Studya
R2
N
+
-
N2
N
BF4
R2
MeOH (0.115 M)
rt, time
R1
+
R1
N
N
H
H
2
1a
1b
3a, 3e, 4a
x equiv.
Entry
R1
R2
3
x (equiv.)
Time
Yield (%)
1
2
3
4
5
6
7b
t-Bu
Me
4-OMe
4-OMe
4-OMe
4-OMe
2-Ac
3a
4a
4a
4a
3e
3e
4a
1.5
1.5
1.5
1.0
1.5
1.3
1.3
16 h
99
99
99
99
99
99
68
16 h
Me
10 min
10 min
16 h
Me
t-Bu
t-Bu
Me
2-Ac
30 min
96 h
4-OMe
a Standard reaction conditions: 1 (0.115 mmol, 1 equiv.), 2 (0.150 mmol,
1.3 equiv.), MeOH (1 mL), rt, under air, approx. 30 min; isolated yield.
b Reaction performed in H2O, conversion determined by 1H NMR analysis.
2 and prolonged reaction time were required in this case.
Also, the coupling using mesityldiazonium salt was more
sluggish; additional portion of the diazonium salt and lon-
ger reaction time (2 h) were needed to reach full conversion
but, rewardingly, under such a modified protocol 3d was af-
forded in high 87% yield. The reaction occurs with a compa-
rable outcome when using the less hindered 2-(methyl)-
1H-indole (1b), furnishing the coupling products 4a–c in
very high yields. The mesityl-derived azoindole 4d was ob-
tained in 85% yield using 2 equivalents of the diazo salt
partner. Functionalized indole substrates bearing F, Cl, and
Me motifs could also be converted into the expected prod-
ucts 4e–g in excellent yields. Of note is that this reaction is
not specific to 1H-indoles, and diazo-(N-methyl)indoles
5a–c were also synthesized successfully. In contrast, acyl-
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

C
N. Jacob et al.
Paper
Synthesis
protected indole turned out to be ineffective. Finally, under
the standard reaction conditions, 2-phenylindole was con-
verted into the corresponding diazo compound 7a in 96%
yield and pyrrole-derived substrate undergoes selective C2-
functionalization delivering 8a in quantitative yield.
Importantly, the reaction is also efficient even at 50
times larger scale (5.75 mmol, 754 mg of 1b) and appealing
product 4a could hence be isolated in quantitative yield
(Scheme 2). However, larger excess of 2a (2 equiv.) and
slightly longer reaction time (1 h) were critical to reach full
conversion.
R3
N
N
+
–
N2
BF4
R3
MeOH (0.115 M)
rt, 30 min
R1
R1
+
N
N
R2
R2
2
1
1,3 equiv.
OMe
Me
OMe
N
N
N
N
N
N
N
N
OMe
N
H
N
N
N
H
H
H
3d: 87%a
3b: 95%
3c: 99%
3a: 99%
–
N2+BF4
F
OMe
N
MeOH (0.115 M)
N
+
N
rt, 1 h
Cl
H
OMe
N
Me
Ac
N
N
N
N
N
N
H
N
N
4a: > 99%
1.52 g (5.73 mmol)
2a
2 equiv.
Br
1b
5.75 mmol
754 mg
N
H
N
H
N
H
N
H
3h: 70%b
3e: 98%
Scheme 2 Large-scale synthesis
3f: 82%
3g: 93%
OMe
F
Subsequently, in order to gather additional information
about the newly synthesized compounds, their UV/Vis ab-
sorption spectra were recorded (Figure 2). Interestingly, all
compounds present rather similar absorption patterns,
ranging from 353 nm (for 3-azaindoles bearing mesityl
Cl
Me
Me
N
N
N
N
N
N
N
N
Me
Me
Me
N
H
N
N
H
N
H
H
4d: 85%a
4a: 98%
4b: 99%
4c: 85%
OMe
Cl
N
N
N
O
N
N
N
Cl
F
Me
Me
Me
Me
N
N
N
H
H
H
4f: 84%c
4g: 99%
4e: 97%
F
OMe
OMe
Cl
Me
N
N
N
N
N
N
N
N
Me
Me
Me
Me
N
N
N
N
Me
Me
Me
O
5a: 90%
5b: 90%
5c: 47%
6a: 0%
Cl
Me
N
Cl
N
N
N
N
Me
N
8a: 99%c
H
7a: 96%
Scheme 1 Scope of C3-diazenylation of indoles. Isolated yields are
shown. a) an additional portion of 0.7 equiv. of 2 was added after 30
min, and stirred for 2 h; b) an additional portion of 0.7 equiv. of 2 was
added twice after 30 min, and stirred for 1 h; c) an additional portion of
0.7 equiv. of 2 was added after 30 min, and stirred for 30 min.
Figure 2 Examples of UV/Vis absorption spectra of the selected products
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

D
N. Jacob et al.
Paper
Synthesis
motif such as 3d and 4d) to 393 nm (for 3-azoindole featur-
ing 2-Ac phenyl motif such as 3e). Besides, the initial testes
of cis–trans photoisomerization indicate that this process is
relatively fast, inferior to the minute scale.
1H NMR (CDCl3, 400 MHz):  = 8.61–8.54 (m, 1 H), 8.28 (br s, 1 H),
7.86 (d, J = 8.9 Hz, 2 H), 7.37–7.30 (m, 1 H), 7.30–7.18 (m, 2 H), 7.01
(d, J = 9.0 Hz, 2 H), 3.89 (s, 3 H), 1.69 (s, 9 H).
13C NMR (CDCl3, 101 MHz):  = 160.21, 151.70, 148.76, 133.68,
123.33, 123.32, 123.31, 123.25, 122.96, 120.49, 114.20, 110.69, 55.67,
34.11, 31.01.
In conclusion, we have described herein a very efficient
synthesis of original, highly substituted 3-azoindoles. The
coupling occurs via metal-free C–H diazenylation of in-
doles, using aryldiazonium salts as coupling partners. Re-
markably, the reaction does not require addition of a cata-
lyst and performs smoothly at room temperature within
few minutes delivering the expected products in quantita-
tive yields in most of the cases. This sustainable, particular-
ly mild and atom-economical protocol is highly tolerant to-
wards various functionalities, furnishing a library of inter-
esting scaffolds. These unprecedented molecules appear as
privileged candidates for original photoswitch design. Be-
sides, the simplicity of this protocol renders it perfectly
suitable to be used in late-modification of sophisticated
indole-containing drugs.
HRMS (ESI): m/z [M + H]+ calcd for C19H22N3O: 308.1757; found:
308.1754.
(E)-2-(tert-Butyl)-3-(o-tolyldiazenyl)-1H-indole (3b)
Deep orange solid; yield: 32 mg (95%, 0.110 mmol).
1H NMR (CDCl3, 400 MHz):  = 8.51 (dd, J = 7.4, 1.8 Hz, 1 H), 8.33 (br s,
1 H), 7.70–7.63 (m, 1 H), 7.38–7.32 (m, 2 H), 7.31–7.26 (m, 3 H), 7.26–
7.22 (m, 1 H), 2.81 (s, 3 H), 1.71 (s, 9 H).
13C NMR (CDCl3, 101 MHz):  = 152.81, 152.34, 136.60, 133.71,
132.50, 131.13, 128.57, 126.41, 123.50, 123.33, 123.13, 120.25,
114.96, 110.78, 34.21, 31.05, 18.49.
HRMS (ESI): m/z [M + H]+ calcd for C19H22N3: 292.1808; found:
292.1801.
(E)-2-(tert-Butyl)-3-[(2-methoxyphenyl)diazenyl]-1H-indole (3c)
Deep red solid; yield: 35 mg (99%, 0.114 mmol).
All the reactions were performed under air atmosphere, using tube
reactors (10 mL). Chemicals and solvents (suppliers: Aldrich, Alfa Ae-
sar, Fluorochem, TCI) were directly used without further purification.
Technical grade solvents for purification were used without further
purification or distillation. 1H, 13C, and 19F NMR spectra were recorded
in CDCl3 or acetone-d6 at rt on Bruker, Avance 400 (400 MHz) or
Avance III-HD (500 MHz) spectrometers and FID was processed in
MestreNova software. Chemical shits were referenced to residual sol-
vent peaks and reported in ppm (i.e., CDCl3 referenced at 7.26 and
77.16 ppm respectively and acetone-d6 referenced at 2.05 ppm). Stan-
dard abbreviations were used for NMR spectra to represent the signal
multiplicity. The coupling constants were reported in hertz (Hz).
Thin-layer chromatography (TLC) were carried out on precoated alu-
minum sheets (Merck 60-F254 plates) and the components were visu-
alized by observation under UV light at 254 nm. Products were puri-
fied by column chromatography on 40–63 mesh silica gel, SiO2. HRMS
measurements were carried out by Service de Spectrométrie de
Masse de l’Institut de Chimie at the University of Strasbourg.
1H NMR (CDCl3, 400 MHz, 333 K):  = 8.59 (br s, 1 H), 8.50 (d, J = 7.4
Hz, 1 H), 7.68 (dd, J = 7.9, 1.7 Hz, 1 H), 7.38 (d, J = 7.6 Hz, 1 H), 7.29–
7.23 (m, 3 H), 7.08 (dd, J = 8.2, 1.2 Hz, 1 H), 7.03 (td, J = 7.6, 1.2 Hz, 1
H), 4.07 (s, 3 H), 1.69 (s, 9 H).
13C NMR (CDCl3, 101 MHz, 333 K):  = 155.66, 153.34, 143.87, 133.79,
132.55, 129.10, 124.36, 123.81, 123.34, 121.30, 120.79, 116.30,
113.38, 111.85, 56.99, 34.56, 31.01.
HRMS (ESI): m/z [M + H]+ calcd for C19H22N3O: 308.1757; found:
308.1748.
(E)-2-(tert-Butyl)-3-(mesityldiazenyl)-1H-indole (3d)
Prepared according to the general procedure, with a following modifi-
cation: an additional portion of 0.7 equiv of mesityldiazonium tetra-
fluoroborate was added after 30 min; stirred for 2 h; deep orange sol-
id; yield: 32 mg (87%, 0.100 mmol).
1H NMR (CDCl3, 400 MHz):  = 8.57–8.48 (m, 1 H), 8.29 (br s, 1 H),
7.40–7.33 (m, 1 H), 7.31–7.21 (m, 2 H), 6.96 (s, 2 H), 2.42 (s, 6 H), 2.35
(s, 3 H), 1.65 (s, 9 H).
13C NMR (CDCl3, 101 MHz):  = 152.00, 150.67, 136.14, 133.45,
132.31, 130.35, 129.69, 123.35, 123.25, 123.19, 120.32, 110.63, 34.07,
30.90, 21.11, 19.60.
The preparation of starting aryldiazonium tetrafluoroborates 2 and
indoles 1 are provided in the Supporting Information.
3-Azoindoles; General Procedure
A 10 mL reaction tube equipped with magnetic stir bar was filled
with indole derivative 1 (0.115 mmol, 1 equiv.) and diazonium tetra-
fluoroborate salt 2 (0.150 mmol, 1.3 equiv.) under air. Then, anhy-
drous MeOH (1 mL) was added, the reaction mixture turned immedi-
ately to a deep dark red color. The resulting mixture was stirred at rt
for 30 min. Afterwards, the reaction mixture was filtered through a
short pad of silica gel. The reaction tube and the pad of silica gel were
washed with DCM until the disappearance of color of the filtrate
(~100 mL). The solvent was removed under reduced pressure and the
resulting highly colored solid was dried under vacuum to give the ex-
pected pure product.
HRMS (ESI): m/z [M + H]+ calcd for C21H26N3: 320.2121; found:
320.2122.
(E)-1-(2-{[2-(tert-Butyl)-1H-indol-3-yl]diazenyl}phenyl)ethan-1-
one (3e)
Deep orange solid; yield: 36 mg (98%, 0.113 mmol).
1H NMR (CDCl3, 400 MHz):  = 12.87 (br s, 1 H), 8.35 (d, J = 6.9 Hz, 1
H), 7.97 (d, J = 8.5 Hz, 1 H), 7.93 (d, J = 7.9 Hz, 1 H), 7.64 (t, J = 7.8 Hz, 1
H), 7.59 (d, J = 6.5 Hz, 1 H), 7.45–7.38 (m, 2 H), 7.11 (t, J = 7.5 Hz, 1 H),
2.75 (s, 3 H), 1.60 (s, 9 H).
13C NMR (CDCl3, 101 MHz):  = 202.25, 179.13, 145.95, 141.96,
135.64, 132.13, 130.49, 126.41, 122.52, 121.72, 121.47, 120.90,
119.83, 114.96, 36.53, 30.53, 28.27 (1 C undetected due to overlap-
ping).
(E)-2-(tert-Butyl)-3-[(4-methoxyphenyl)diazenyl]-1H-indole (3a)
Deep orange solid; yield: 35 mg (99%, 0.114 mmol).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

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N. Jacob et al.
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Synthesis
HRMS (ESI): m/z [M + H]+ calcd for C20H22N3O: 320.1757; found:
320.1744.
1H NMR (CDCl3, 400 MHz):  = 8.54–8.48 (m, 1 H), 8.28 (br s, 1 H),
7.91–7.86 (m, 2 H), 7.33–7.24 (m, 3 H), 7.20–7.12 (m, 2 H), 2.82 (s,
3 H).
13C NMR (CDCl3, 126 MHz):  = 163.08 (d, J = 248.2 Hz), 150.75 (d, J =
1.8 Hz), 142.92, 135.14, 132.81, 123.75, 123.41 (d, J = 8.4 Hz), 123.03,
122.57, 119.70, 115.80 (d, J = 22.7 Hz), 110.65, 11.72.
19F NMR (CDCl3, 376 MHz):  = –113.55 (s, 1 F).
HRMS (ESI): m/z [M + H]+ calcd for C15H13FN3: 254.1088; found:
(E)-2-(tert-Butyl)-3-[(4-fluorophenyl)diazenyl]-1H-indole (3f)
Deep yellow solid; yield: 28 mg (82%, 0.095 mmol).
1H NMR (CDCl3, 400 MHz):  = 8.59–8.52 (m, 1 H), 8.34 (br s, 1 H),
7.88–7.83 (m, 2 H), 7.38–7.33 (m, 1 H), 7.31–7.22 (m, 2 H), 7.20–7.12
(m, 2 H), 1.69 (s, 9 H).
13C NMR (CDCl3, 126 MHz):  = 162.97 (d, J = 248.0 Hz), 152.87,
150.89 (d, J = 3.0 Hz), 133.70, 131.57, 123.59, 123.46 (d, J = 8.5 Hz),
123.27, 123.23, 120.33, 115.82 (d, J = 22.5 Hz), 110.80, 34.19, 31.03.
254.1076.
(E)-3-[(2-Chloro-6-methylphenyl)diazenyl]-2-methyl-1H-indole
19F NMR (CDCl3, 376 MHz):  = –113.73 (s, 1 F).
(4c)
Deep orange solid; yield: 28 mg (85%, 0.099 mmol).
HRMS (ESI): m/z [M + H]+ calcd for C18H19FN3: 296.1557; found:
296.1544.
1H NMR (CDCl3, 400 MHz):  = 8.50 (d, J = 7.4 Hz, 1 H), 8.31 (br s, 1 H),
7.35 (dd, J = 8.0, 0.7 Hz, 1 H), 7.33–7.24 (m, 3 H), 7.16 (d, J = 7.6 Hz, 1
H), 7.09 (t, J = 7.7 Hz, 1 H), 2.79 (s, 3 H), 2.42 (s, 3 H).
(E)-2-(tert-Butyl)-3-[(2-chloro-6-methylphenyl)diazenyl]-1H-
13C NMR (CDCl3, 126 MHz):  = 150.46, 143.72, 135.11, 133.74,
131.57, 130.05, 128.20, 127.05, 123.90, 123.89, 123.44, 122.62,
119.42, 110.61, 19.61, 11.64.
HRMS (ESI): m/z [M + H]+ calcd for C16H15ClN3: 284.0949; found:
284.0946.
indole (3g)
Deep orange solid; yield: 35 mg (93%, 0.107 mmol).
1H NMR (CDCl3, 500 MHz):  = 8.56 (dd, J = 6.5, 2.1 Hz, 1 H), 8.39 (br s,
1 H), 7.38–7.34 (m, 2 H), 7.30–7.24 (m, 2 H), 7.17 (ddd, J = 7.6, 1.5, 0.7
Hz, 1 H), 7.09 (t, J = 7.8 Hz, 1 H), 2.39 (s, 3 H), 1.65 (s, 9 H).
13C NMR (CDCl3, 126 MHz):  = 153.84, 150.84, 133.59, 132.55,
131.56, 129.71, 128.11, 127.33, 126.78, 123.75, 123.72, 123.40,
120.17, 110.73, 34.26, 30.92, 19.47.
HRMS (ESI): m/z [M + H]+ calcd for C19H21ClN3: 326.1419; found:
326.1408.
(E)-3-(Mesityldiazenyl)-2-methyl-1H-indole (4d)
Prepared according to the general procedure, with a following modifi-
cation: an additional portion of 0.7 equiv of mesityldiazonium tetra-
fluoroborate was added after 30 min; stirred for 2 h.
Deep yellow solid; yield: 27 mg (85%, 0.097 mmol).
1H NMR (CDCl3, 400 MHz):  = 8.47–8.41 (m, 1 H), 8.20 (br s, 1 H),
(E)-5-Bromo-2-(tert-butyl)-3-[(4-methoxyphenyl)diazenyl]-1H-
indole (3h)
7.33–7.23 (m, 3 H), 6.95 (s, 2 H), 2.77 (s, 3 H), 2.45 (s, 6 H), 2.33 (s, 3
H).
13C NMR (CDCl3, 126 MHz):  = 150.24, 142.10, 136.47, 135.06,
133.41, 130.79, 129.94, 123.47, 122.92, 122.37, 119.50, 110.56, 21.15,
19.68, 11.58.
Prepared according to the general procedure, with a following modifi-
cation: two additional portions of 0.7 equiv of mesityldiazonium
tetrafluoroborate were added after 30 min and 1h; stirred for 1 h;
deep orange solid; yield: 31 mg (70%, 0.0803 mmol).
1H NMR (CDCl3, 500 MHz):  = 8.72 (d, J = 1.9 Hz, 1 H), 8.30 (br s, 1 H),
7.86 (d, J = 9.0 Hz, 2 H), 7.31 (dd, J = 8.5, 2.0 Hz, 1 H), 7.20 (d, J =
8.5 Hz, 1 H), 7.01 (d, J = 8.9 Hz, 2 H), 3.89 (s, 3 H), 1.67 (s, 9 H).
HRMS (ESI): m/z [M + H]+ calcd for C18H20N3: 278.1652; found:
278.1648.
13C NMR (CDCl3, 126 MHz):  = 160.48, 152.42, 148.49, 132.29,
130.63, 126.07, 125.73, 123.49, 121.91, 116.10, 114.23, 112.13, 55.68,
34.15, 30.89.
HRMS (ESI): m/z [M + H]+ calcd for C19H21BrN3O: 386.0863; found:
386.0847.
(E)-3-[(2-Chlorophenyl)diazenyl]-5-fluoro-2-methyl-1H-indole
(4e)
Deep yellow solid; yield: 32 mg (97%, 0.111 mmol).
1H NMR (CDCl3, 500 MHz):  = 8.32 (dd, J = 9.7, 2.7 Hz, 1 H), 8.29 (br s,
1 H), 7.80 (dd, J = 7.9, 1.8 Hz, 1 H), 7.55 (dd, J = 7.8, 1.5 Hz, 1 H), 7.34–
7.30 (m, 1 H), 7.28 (dd, J = 7.7, 1.8 Hz, 1 H), 7.19 (dd, J = 8.7, 4.3 Hz, 1
H), 6.98 (td, J = 8.9, 2.6 Hz, 1 H), 2.82 (s, 3 H).
(E)-3-[(4-Methoxyphenyl)diazenyl]-2-methyl-1H-indole (4a)
13C NMR (CDCl3, 126 MHz):  = 160.30 (d, J = 237.9 Hz), 149.83,
145.08, 134.19 (d, J = 3.9 Hz), 134.10, 131.48, 130.56, 129.58, 127.19,
120.02 (d, J = 11.3 Hz), 116.95, 111.81 (d, J = 26.3 Hz), 111.23 (d, J =
9.5 Hz), 108.63 (d, J = 25.6 Hz), 11.81.
Deep red solid; yield: 30 mg (98%, 0.113 mmol).
1H NMR (CDCl3, 400 MHz):  = 8.57–8.50 (m, 1 H), 8.18 (br s, 1 H),
7.89 (d, J = 8.9 Hz, 2 H), 7.30–7.26 (m, 1 H), 7.26–7.20 (m, 2 H), 7.01
(d, J = 9.0 Hz, 2 H), 3.88 (s, 3 H), 2.80 (s, 3 H).
19F NMR (CDCl3, 376 MHz):  = –120.04 (s, 1 F).
HRMS (ESI): m/z [M + H]+ calcd for C15H12ClFN3: 288.0698; found:
13C NMR (CDCl3, 126 MHz):  = 160.33, 148.61, 141.70, 135.10,
132.66, 123.45, 123.26, 122.71, 122.57, 119.88, 114.18, 110.55, 55.66,
11.67.
288.0686.
HRMS (ESI): m/z [M + H]+ calcd for C16H16N3O: 266.1285; found:
266.1288.
(E)-5-Chloro-3-[(4-methoxyphenyl)diazenyl]-2-methyl-1H-indole
(4f)
(E)-3-[(4-Fluorophenyl)diazenyl]-2-methyl-1H-indole (4b)
Prepared according to the general procedure, but by using another 0.7
equiv of the corresponding aryldiazonium tetrafluoroborate after 30
min; stirred for 30 min.
Deep yellow solid; yield: 29 mg (99%, 0.115 mmol).
Deep orange solid; yield: 29 mg (84%, 0.097 mmol).
© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

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N. Jacob et al.
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Synthesis
1H NMR (CDCl3, 400 MHz):  = 8.51 (dd, J = 1.9, 0.8 Hz, 1 H), 8.26 (br s,
1 H), 7.88 (d, J = 9.0 Hz, 2 H), 7.19 (d, J = 0.8 Hz, 1 H), 7.18 (d, J = 1.9 Hz,
1 H), 7.00 (d, J = 9.0 Hz, 2 H), 3.89 (s, 3 H), 2.80 (s, 3 H).
13C NMR (CDCl3, 101 MHz):  = 160.60, 148.22, 142.74, 133.42,
132.03, 128.28, 123.62, 123.38, 122.14, 120.74, 114.23, 111.54, 55.68,
11.73.
1H NMR (CDCl3, 500 MHz):  = 8.67–8.63 (m, 1 H), 8.61 (br s, 1 H),
8.03–7.98 (m, 2 H), 7.53–7.47 (m, 2 H), 7.46–7.42 (m, 2 H), 7.39–7.30
(m, 3 H), 7.15 (ddd, J = 7.6, 1.5, 0.8 Hz, 1 H), 7.10 (t, J = 7.7 Hz, 1 H),
2.39 (s, 3 H).
13C NMR (CDCl3, 126 MHz):  = 150.58, 142.92, 135.46, 133.22,
131.66, 130.64, 129.94, 129.57, 129.18, 128.96, 128.24, 127.70,
127.33, 124.88, 123.99, 123.87, 119.87, 111.01, 19.66.
HRMS (ESI): m/z [M + H]+ calcd for C16H15ClN3O: 300.0898; found:
300.0888.
HRMS (ESI): m/z [M + H]+ calcd for C21H17ClN3: 346.1106; found:
346.1091.
(E)-1-{2-[(2,5-Dimethyl-1H-indol-3-yl)diazenyl]phenyl}ethan-1-
one (4g)
(E)-N-(2-Chloro-6-methylphenyl)-1-(1-phenyl-1H-pyrrol-2-
yl)methanimine (8a)
Deep orange solid; yield: 33 mg (quant, 0.115 mmol).
Prepared according to the general procedure, but by using another 0.7
equiv. of the corresponding aryldiazonium tetrafluoroborate after 30
min; stirred for 30 min; deep orange solid; yield: 34 mg (99%, 0.115
mmol).
1H NMR (CDCl3, 500 MHz):  = 8.15 (s, 1 H), 8.03 (d, J = 8.3 Hz, 1 H),
7.88 (d, J = 7.8 Hz, 1 H), 7.63 (ddd J = 8.5, 7.2, 1.5 Hz, 1 H), 7.39 (d, J =
7.9 Hz, 1 H), 7.22–7.18 (m, 2 H), 2.72 (s, 3 H), 2.65 (s, 3 H), 2.53 (s, 3 H)
(NH proton not detected).
1H NMR (CDCl3, 500 MHz):  = 7.53–7.48 (m, 2 H), 7.46–7.41 (m, 2 H),
7.38–7.34 (m, 1 H), 7.29–7.26 (m, 1 H), 7.23 (dd, J = 2.8, 1.6 Hz, 1 H),
7.08–7.03 (m, 2 H), 6.93 (dd, J = 4.2, 1.7 Hz, 1 H), 6.48 (dd, J = 4.1, 2.8
Hz, 1 H), 2.16 (s, 3 H).
13C NMR (CDCl3, 126 MHz):  = 149.50, 147.43, 138.66, 131.93,
129.93, 128.94, 128.22, 128.19, 127.81, 127.68, 127.27, 126.55,
111.24, 100.20, 19.43.
HRMS (ESI): m/z [M + H]+ calcd for C18H19N3O: 292.1444; found:
292.1439.
(E)-3-[(4-Methoxyphenyl)diazenyl]-1,2-dimethyl-1H-indole (5a)
Deep orange solid; yield: 29 mg (90%, 0.104 mmol).
1H NMR (CDCl3, 500 MHz):  = 8.59–8.54 (m, 1 H), 7.87 (d, J = 9.0 Hz, 2
H), 7.34–7.26 (m, 3 H), 7.00 (d, J = 8.9 Hz, 2 H), 3.88 (s, 3 H), 3.76 (s, 3
H), 2.82 (s, 3 H).
13C NMR (CDCl3, 126 MHz):  = 160.10, 148.72, 143.88, 136.96, 132.30
123.11, 122.69, 122.66, 119.27, 114.16, 108.85, 55.66, 29.98, 10.30 (1
C undetected due to overlapping).
HRMS (ESI): m/z [M + H]+ calcd for C17H15ClN3: 296.0949; found:
296.0940.
Funding Information
HRMS (ESI): m/z [M + H]+ calcd for C17H18N3O: 280.1444; found:
280.1433.
This work was carried out within ANR JCJC grant ‘2al-Vis-Phot-CH’
(ANR-15-CE29-0004-01).
A
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4-01)
(E)-3-[(4-Fluorophenyl)diazenyl]-1,2-dimethyl-1H-indole (5b)
Deep orange solid; yield: 33.5 mg (90%, 0.112 mmol).
1H NMR (CDCl3, 500 MHz):  = 8.58–8.52 (m, 1 H), 7.90–7.85 (m, 2 H),
7.34–7.27 (m, 3 H), 7.15 (t, J = 8.7 Hz, 2 H), 3.76 (s, 3 H), 2.82 (s, 3 H).
13C NMR (CDCl3, 126 MHz):  = 162.88 (d, J = 247.5 Hz), 150.81 (d, J =
2.4 Hz), 145.19, 137.08, 132.42, 123.43, 123.24 (d, J = 8.4 Hz), 123.07,
122.66, 119.11, 115.76 (d, J = 22.6 Hz), 109.00, 30.08, 10.34.
Acknowledgment
L.G. acknowledges Agence Nationale de la Recherche (ANR) for the
Ph.D. grant and N.J. acknowledges ANR for Master 2 fellowship. We
would like to thank Dr. A. Specht and Dr. S. Lakhdar for inspiring ini-
tial photophysical study discussions.
19F NMR (CDCl3, 376 MHz):  = –113.97 (s, 1 F).
HRMS (ESI): m/z [M + H]+ calcd for C16H15FN3: 268.1244; found:
268.1230.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0039-1690048.
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(E)-3-[(2-Chloro-6-methylphenyl)diazenyl]-1,2-dimethyl-1H-
indole (5c)
Deep orange solid; yield: 16 mg (47%, 0.054 mmol).
References
1H NMR (CDCl3, 500 MHz):  = 8.56–8.50 (m, 1 H), 7.37–7.27 (m, 4 H),
7.16 (ddd, J = 7.6, 1.5, 0.8 Hz, 1 H), 7.07 (t, J = 7.7 Hz, 1 H), 3.77 (s, 3 H),
2.79 (s, 3 H), 2.42 (s, 3 H).
13C NMR (CDCl3, 126 MHz):  = 150.60, 145.74, 137.05, 133.36,
131.65, 129.98, 128.19, 128.16, 126.81, 123.51, 123.41, 122.69,
118.84, 108.93, 30.04, 19.63, 10.19.
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G

G
N. Jacob et al.
Paper
Synthesis
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© 2020. Thieme. All rights reserved. Synthesis 2020, 52, A–G