Direct Arylations via C–H Bond Functionalization of 1,2,3-Triazoles by a Reusable Pd/C Catalyst Under Solvent-Free Conditions

Article abstract of DOI:10.1002/ejoc.201901305

Fully substituted triazoles are synthesized by a sustainable direct arylation reaction performed under solvent-free conditions and in the presence of a recyclable Pd/C heterogeneous catalyst. Exclusion of air as well as anhydrous conditions are not requir

Full text of DOI:10.1002/ejoc.201901305

A Journal of
Accepted Article
Title: Direct arylations via C−H bond functionalization of 1,2,3-triazoles
by reusable Pd/C catalyst in solvent-free conditions
Authors: Angela Punzi, Nicola Zappimbulso, and Gianluca M. Farinola
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Eur. J. Org. Chem. 10.1002/ejoc.201901305
Link to VoR: http://dx.doi.org/10.1002/ejoc.201901305
Supported by

10.1002/ejoc.201901305
European Journal of Organic Chemistry
FULL PAPER
Direct arylations via C−H bond functionalization of 1,2,3-triazoles
by reusable Pd/C catalyst in solvent-free conditions
Angela Punzi,[a,b] Nicola Zappimbulso,[a] and Gianluca M. Farinola*[a]
Abstract: Fully substituted triazoles are synthesized by a
sustainable direct arylation reaction performed in solvent-free
provide much more environmentally benign protocols for direct
arylation. In fact, such conditions enable to reduce reaction waste
(solvent constitute most of mass wasted in syntheses), avoid the
hazards and toxicity associated with some solvents, save energy
due to shorter reaction times and simpler workups. A limited
number of examples of direct arylation reactions in solvent free
conditions have been reported[9] and, to the best of our knowledge,
the direct arylation reaction of 1,4-disubstituted 1,2,3-triazoles in
solvent free conditions has not been reported in the literature so
far. In the frame of our studies on the synthesis of heteroaromatic-
based materials[10] as well as on development of innovative Pd-
catalyzed methodologies,[11] we report herein the first Pd-
catalyzed direct arylation protocol of 1,4-disubstituted 1,2,3-
triazoles that is performed in (i) solvent-free, (ii) non-anhydrous
conditions, (iii) without exclusion of air, and (iv) in the presence of
a reusable catalyst.
conditions and in the presence of
a
recyclable Pd/C
heterogeneous catalyst. Exclusion of air as well as anhydrous
conditions are not required, enabling a convenient synthesis of
1,4,5-trisubstituted 1,2,3-triazoles and 1,2,3-triazole-fused
isoindolines starting from 1,4-disubstituted 1,2,3-triazoles, easily
prepared via click chemistry, and functionalized aryl iodides.
Introduction
The 1,2,3-triazole ring represents a key structural motif of
manifold
interest
areas
including
drug
discovery,[1]
bioconjugation,[ 2,3] and materials science.[3] These compounds
are commonly synthesized by the copper(I)-catalyzed 1,3-dipolar
cycloaddition reaction of azides with alkynes (CuAAC), the most
prominent example of ‘click chemistry’, developed by the groups
of Sharpless[4] and Meldal.[5] The CuAAC approach is efficient and
highly regioselective with terminal alkynes affording 1,4-
disubstituted 1,2,3-triazoles in excellent yields.[6] On the contrary,
this methodology is found to be not generally useful for the
conversion of internal alkynes to fully substituted 1,2,3-triazoles.
Among the known methods for the regioselective synthesis of fully
substituted 1,2,3-triazoles, the Pd-catalyzed direct arylation of the
easy available 1,4-disubstituted 1,2,3-triazoles turns out to be the
most general approach.[7] The major drawback of this taste is still
represented by the use of toxic solvents (e.g., N,N-
dimethylformamide, N-methyl-2-pyrrolidone, toluene). The use of
toxic N,N-dimethylformamide also represents a disadvantage for
the one-pot multicomponent syntheses of fully decorated triazoles
based on use of inexpensive copper catalysts.[8] Only few
examples of direct arylation protocols of 1,4-disubstituted 1,2,3-
triazoles based on the use of more sustainable experimental
conditions have been reported in the literature. For example,
protocols for Pd-catalyzed direct arylations in environmentally-
benign reaction media, such as polyethylene glycol (PEG)[7d] or
biomass-derived -valerolactone,[7h,7l] in the presence of reusable
palladium catalysts, were developed by Ackermann and co-
workers. The development of solvent free conditions would
Results and Discussion
Our preliminary investigations focused on the direct arylation
reaction of 1a, chosen as a model substrate for the C–H activation,
with iodo- or bromobenzene yielding 3a (Table 1). Initially, we
carried out the solvent-free direct arylation reaction of 1a using
Pd2(dba)3 as the catalyst, Cs2CO3 as the base, P(o-MeOPh)3 as
the ligand and pivalic acid (PivOH) as the additive, in non-
anhydrous conditions and in the presence of air, according to our
previously reported conditions for the synthesis of extended
heteroaromatic conjugated molecules.[11a] The coupling product
3a was isolated in high yield (79%, entry 1). Then, with the aim of
making the reaction conditions more sustainable, we evaluated
the possibility of using only tetra-n-butylammonium acetate
(Bu4NOAc) as both the base and the reaction medium, in the
absence of any other additive. The effectiveness of using neat
Bu4NOAc as both the base and, together with the reaction by-
products Bu4NBr and CH3COOH, the reaction medium was
recently demonstrated by Kantchev[12] in Ru-catalyzed direct
arylation reactions of 2-phenylpyridine and other nitrogen-
containing substrates. In neat Bu4NOAc, a series of commercial
Pd complexes were evaluated as pre-catalysts. Moderate yields
of 3a were obtained in the presence of homogeneous catalysts,
such as Pd2(dba)3 (59%, entry 2), PdCl2(PPh3)2 (55%, entry 3) and
Pd(OAc)2 (54%, entry 4). An increase of the yield of 3a (70%,
entry 5) was obtained in the presence of Pd/C, a recyclable
heterogeneous catalyst. Using Pd/C (5 mol %) as the catalyst,
we examined the role of the halogen, reaction temperature and
catalyst loading. The use of bromobenzene instead of
iodobenzene (entry 6) as well as the increase of the reaction
temperature (entry 7) drastically reduces the reaction yields. The
increase in the catalyst amount from 5 to 10%mol (entry 8) does
not produce any enhancement of the reaction yield. A lower
catalysts loading (2% mol) causes a decrease in the reaction yield
(47% yield vs 70%).
[a]
[b]
Dr. A. Punzi, Dr. N. Zappimbulso, Prof. G. M. Farinola
Dipartimento di Chimica, Università degli Studi di Bari Aldo Moro,
Via Orabona 4, 70126 Bari, Italy
E-mail: gianlucamaria.farinola@uniba.it
http://www.chimica.uniba.it
Centro Interdipartimentale di Ricerca “Metodologie e tecnologie
ambientali (METEA)
c/o Villa La Rocca
via Celso Ulpiani 27, 70126 Bari, Italy
Supporting information for this article is given via a link at the end of
the document.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901305
European Journal of Organic Chemistry
FULL PAPER
Table 1. Optimization of Pd-catalyzed C-H arylations.[a]
Entry
ArX
catalyst
ligand
additive
base
Temperature
(°C)
Yield [b]
1[c]
2
3
4
5
2a
2a
2a
2a
2a
2b
2a
2a
2a
Pd2(dba)3
Pd2(dba)3
PdCl2(PPh3)2
Pd(OAc)2
Pd/C
P(o-MeOPh)3
PivOH
Cs2CO3
Bu4NOAc
Bu4NOAc
Bu4NOAc
Bu4NOAc
Bu4NOAc
Bu4NOAc
Bu4NOAc
Bu4NOAc
110
110
110
110
110
110
140
110
79%
59%
55%
54%
70%
8%
20%
67%
47%
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
6
Pd/C
Pd/C
Pd/C
Pd/C
7
8[d]
9[e]
110
[a] Unless specified, C−H arylation was carried out as follows: 1a (1 equiv), aryl halide (3 equiv), Pd catalyst (5 mol %), Bu4NOAc (2 equiv) at 110 °C for 24 h. [b]
Yields refer to isolated products. [c] Reaction conditions: 1a (1 equiv), aryl halide (3 equiv), Pd catalyst (5 mol %), phosphine (10mol %), PivOH (30 mol %), Cs2CO3
(2 equiv) at 110 °C for 24 h. [d] Reaction performed in the presence of Pd/C (10 mol %).[e] Reaction performed in the presence of Pd/C (2 mol %).
Although the yields obtained using Pd/C in the presence of neat
Bu4NOAc are slightly lower than those obtained with Pd2(dba)3 in
the presence of Cs2CO3, P(o-MeOPh)3 and pivalic acid (79% vs
70%), the use of Pd/C was preferred for subsequent
investigations because of more sustainable reaction conditions,
including the possibility of catalyst recycle. To probe the catalyst
reusability, we recovered the Pd/C by a modified literature
protocol[7h] and evaluated the catalytic activity of the recycled
material in the subsequent runs (Table 2). We observed an
obtained with meta and para methyl substituted iodides, suggests
that the reaction may be affected by steric effects. The triazole-
aryl coupling reactions also occurred in good yields using aryl
iodides functionalized with electron-withdrawing groups, such as
fluorine (3f: 61%, 3o: 66%), nitro (3g: 56%) and trifluoromethyl
(3k: 63%, 3n: 78%) groups, and pyridyl iodides (3j: 47%), while
yields lower than 30% were obtained with aryl iodides bearing
ketone and ester groups. No effective chemoselectivity was
observed in the reaction between triazole 1b and 3-
unchanged catalytic activity of the recycled Pd/C until the third run, iodobromobenzene. The low or moderate yields sometimes
while a halving of its activity is detected at the fourth run.
observed in triazole-aryl coupling reactions performed with our
protocol are mainly due to a low conversion of the starting triazole
and only minimally to the formation of by-products. A different ring
substitution pattern does not seem to influence the triazole-aryl
coupling reactions course since they runned both with N-alkyl (3a-
l) and with N-aryl (3m-o) triazoles. Our strategy was also proved
viable for the intramolecular C–H functionalization with substrates
4a-b leading to 1,2,3-triazole-fused isoindolines 5a-b.[7l] A good
yield was obtained in the presence of Pd/C (5 mol %) and neat
Bu4NOAc (4 equiv) at 120°C for 48h (Scheme 2).
Table 2. Reuse of palladium catalyst.[a]
Run
Yield[b]
1th
70%
2th
72%
3th
70%
4th[c]
35%
[a] C−H arylation was carried out as follows: 1a (1 equiv), aryl halide (3 equiv),
Pd catalyst (5 mol %), Bu4NOAc (2 equiv) at 110 °C for 24 h. [b] Yields refer to
isolated products. [c] After the 4th run, an overall decrease of 27% in catalyst
weight is observed.
Conclusions
In conclusion, we have reported here the first example of direct
arylation reaction of 1,4-disubstituted 1,2,3-triazoles in solvent
free conditions that allow both to reduce reaction waste and to
avoid the hazards and toxicity associated with some solvents.
Moreover, the use of Pd/C, a recyclable heterogeneous catalyst,
in non-anhydrous conditions and in presence of air, causes our
protocol to be an environmentally attractive procedure for the
synthesis of 1,4,5-trisubstituted 1,2,3-triazoles and 1,2,3-triazole-
fused isoindolines. Despite the solvent free conditions represent
an undoubted advantage of our methodology, further effort will
have to be made to reduce or eliminate the use of organic
Having selected Pd/C (5 mol %) in the presence of neat Bu4NOAc
as the reaction system of choice for this study, we investigated
the substrate versatility reacting the 1,2,3-triazoles 1a-d, bearing
a different ring substitution pattern, with various aryl iodides. The
results of this screening are shown in the Scheme 1.
The triazole-aryl coupling reactions occurred in moderate to good
yields using aryl iodides functionalized with electron-donating
functionalities, such as methyl (3b: 67%, 3c: 57%, 3d: 81%, 3h:
44%, 3l: 51%) and methoxy (3i: 61%) groups.The yield obtained
with 2-iodotoluene (3h: 44%), which is lower with respect to those
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901305
European Journal of Organic Chemistry
FULL PAPER
solvents in the product isolation (no workup is required in our
conditions), so increasing the protocol eco-sustainability.
Experimental Section
General remarks: Reagents were purchased at the highest commercial
quality from Sigma-Aldrich and used without further purification. 4-Hexyl-
1-(p-tolyl)-1H-1,2,3-triazole 1d[13] was synthesized according to literature
procedures. Unless specified, preparative column chromatography was
carried out using Macherey-Nagel silica gel (60, particle size 0.063-0.2
mm). Macherey-Nagel aluminum sheets with silica gel 60 F254 were used
for TLC analyses. All new com-pounds were characterized by 1H-NMR,
13C-NMR, FT-IR and LC-MS analysis. 1H-NMR and 13C-NMR spectra were
were acquired on an Agilent 500 spectrometer at 500 and at 126 MHz,
respectively, using the CDCl3 residual proton peak at δ = 7.26 ppm as
internal standard for 1H spectra and the signals of CDCl3 at δ = 77.16 ppm
as internal standard for 13C spectra. High-resolution mass spectra were
acquired with a Shimadzu high-performance liquid chromatography ion
trap time-of flight (LC-IT-TOF) mass spectrometer via direct infusion of the
samples (elution with 0.1% (v/v) formic acid in methanol). Melting points
were determined on a Stuart Scientific Melting point apparatus SMP3.
Scheme 1. Synthesis of compounds 3a-o[a,b]
Synthesis of triazoles 1a-d and 4.
1-Hexadecyl-4-phenyl-1H-1,2,3-triazole (1a). Phenyl acetylene (0.78 g,
7.64 mmol) and hexadecylazide (1.65 g, 6.37mmol) were added at room
.
temperature to a solution of Cu(OAc)2 H2O (0.25g, 1.27 mmol) in H2O (50
mL) in a capped flask. The reaction mixture was warmed at 100°C and
stirred at the same temperature for 5h. After cooling at room temperature,
the reaction mixture was quenched with a saturated aqueous solution of
NH4Cl and extracted with ethyl acetate. The organic extracts were washed
with an aqueous solution of brine, dried over Na2SO4 and concentrated
under vacuum. The crude product was purified by column chromatography
on silica gel (hexane:ethyl acetate = 9:1) affording 1.85 g of compound 1a
(79% yield) as a white solid. mp = 100-101 °C (after crystallization from
CH2Cl2). 1H NMR (500 MHz, CDCl3): 7.38 (d, J = 7.6 Hz, 2H), 7.41 (s,
1H), 7.42 (t like, J = 7.5 Hz, 2H), 7.32 (t, J = 7.3 Hz, 1H), 4.38 (t, J = 7.2
Hz, 2H), 1.98-1.90 (m, 2H), 1.37-1.21 (m, 26H), 0.88 (t, J = 6.8 Hz, 3H);
13C NMR (126 MHz, CDCl3):147.9, 130.9, 128.9, 128.2, 125.8, 119.5,
50.6, 32.1, 30.5, 29.8, 29.8, 29.8, 29.8, 29.8, 29.7, 29.6, 29.5, 29.5, 29.1,
26.6, 22.8, 14.3; HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd for C24H40N3
370.3217; Found 370.3195.
4-Pentyl-1-phenethyl-1H-1,2,3-triazole (1b). 1-Heptyne (0.55 g, 5.71
mmol) and 2-phenyethylazide (0.700 g, 4.76 mmol) were added at room
.
temperature to a solution of Cu(OAc)2 H2O (0.19g, 0.95 mmol) in H2O (20
mL) in a capped flask. The reaction mixture was warmed at 100°C and
stirred at the same temperature for 6h. After cooling at room temperature,
the reaction mixture was quenched with a saturated aqueous solution of
NH4Cl and extracted with ethyl acetate. The organic extracts were washed
with an aqueous solution of brine, dried over Na2SO4 and concentrated
under vacuum. The crude product was purified by column chromatography
on silica gel (hexane:ethyl acetate = 7:3) affording 1.01 g of compound 1b
(87 % yield) as a whitish low-melting solid. 1H NMR (500 MHz, CDCl3):
7.21-7.11 (m, 3H), 6.99 (d, J = 7.2 Hz, 2H), 6.98 (s, 1H), 4.43 (t, J = 7.3
Hz, 2H), 3.08 (t, J = 7.3 Hz, 2H), 2.57 (t, J = 7.7 Hz, 2H), 1.57-1.50 (m, 2H),
1.29-1.17 (m, 4H), 0.81 (t, J = 7.0 Hz, 3H); 13C NMR (126 MHz,
CDCl3):147.7, 137.1, 128.4, 126.7, 120.9, 51.1, 36.6, 31.1, 28.9, 25.3,
22.2, 13.8; HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd for C15H22N3 244.1808;
Found 244.1796.
[a]Unless specified, C−H arylation was carried out as follows: 1a-d (1 equiv),
aryl iodide (3 equiv), Pd/C (5 mol %), Bu4NOAc (2 equiv) at 110 °C for 24 h.
[b]Yields refer to isolated products. [c]Reaction performed on a 1-mmol scale of
1b. [d]Yield from NMR data.
Scheme 2. Synthesis of compounds 5[a,b]
1-Octyl-4-(p-tolyl)-1H-1,2,3-triazole (1c). 1-Ethynyl-4-methylbenzene
(0.342 g, 2.95 mmol) and octylazide (0.381 g, 2.45 mmol) were added at
room temperature to a solution of Cu(OAc)2 H2O (0.098 g, 0.49 mmol) in
H2O (15 mL) in a capped flask. The reaction mixture was warmed at 100°C
and stirred at the same temperature for 5h. After cooling at room
[a] C−H arylation was carried out as follows: 4 (1 equiv), Pd/C (5 mol %),
Bu4NOAc (4 equiv) at 120 °C for 48 h. [b] Yield refers to isolated product.
.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901305
European Journal of Organic Chemistry
FULL PAPER
temperature, the reaction mixture was quenched with a saturated aqueous
solution of NH4Cl and extracted with ethyl acetate. The organic extracts
were washed with an aqueous solution of brine, dried over Na2SO4 and
concentrated under vacuum. The crude product was purified by column
chromatography on silica gel (hexane:ethyl acetate = 7:3) affording 0.604
g of compound 1c (91% yield) as a white solid. mp = 75-76°C (after
29.6, 29.5, 29.4, 29.0, 26.5, 22.8, 14.3; HRMS (LC-IT-TOF) m/z: [M+H]+
Calcd for C30H44N3 446.3530; Found 446.3529.
1-Hexadecyl-4-phenyl-5-(m-tolyl)-1H-1,2,3-triazole (3b). Compound 3b
was synthesized from 1a (50 mg, 0.14 mmol) and 1-iodo-3-methylbenzene
(92 mg, 0.42 mmol) in accordance with the general procedure. Purification
by column chromatography (hexane:ethyl acetate = 8.5:1.5) afforded
compound 3b (43 mg, 67% yield) as a white solid, mp = 66-67°C (after
1
washing with hexane). H NMR (500 MHz, CDCl3):7.72 (d, J = 7.9 Hz,
2H), 7.71 (s, 1H), 7.23 (d, J = 7.9 Hz, 2H), 4.38 (t, J = 7.3 Hz, 2H), 2.38 (s,
3H), 1.97-1.90 (m, 2H), 1.39-1.22 (m, 10H), 0.87 (t, J = 7.0 Hz, 3H); 13C
NMR (126 MHz, CDCl3):147.9, 138.0, 129.6, 128.0, 125.7, 119.2, 50.6,
31.8, 30.5, 29.2, 29.1, 26.7, 22.7, 21.4, 14.2; HRMS (LC-IT-TOF) m/z:
[M+H]+ Calcd for C17H26N3 272.2121; Found 272.2102.
1
crystallization from hexane). H NMR (500 MHz, CDCl3): 7.58-7.54 (m,
2H), 7.39 (t, J = 7.7 Hz, 1H), 7.32 (d J = 7.7 Hz, 1H), 7.28-7.21 (m, 3H),
7.14-7.10 (m, 2H), 4.18 (t, J = 7.4 Hz, 2H), 2.40 (s, 3H), 1.82-1.75 (m, 2H),
1.32-1.16 (m, 26H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (126 MHz,
CDCl3):144.1, 139.3, 133.9, 131.3, 130.6, 130.5, 129.3, 128.5, 128.4,
127.6, 127.2, 126.8, 48.4, 32.1, 30.2, 29.8, 29.8, 29.7, 29.5, 29.5, 29.0,
26.5, 22.8, 21.6, 14.3; HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd for C31H46N3
460.3686; Found 460.3691.
4-Hexyl-1-(p-tolyl)-1H-1,2,3-triazole (1d).[13,14] Compound 1d was
synthesized from p-tolylboronic acid (408 mg, 3 mmol), NaN3 (234 mg, 3.6
mmol) and 1-octyne (364 mg, 3.3 mmol) in accordance with a literature
procedure (201 mg, 28% yield).[13] Spectroscopic data are in agreement
with those previously reported in the literature.[14]
1-Hexadecyl-4-phenyl-5-(p-tolyl)-1H-1,2,3-triazole (3c). Compound 3c
was synthesized from 1a (50 mg, 0.14 mmol) and 1-iodo-4-methylbenzene
(92 mg, 0.42 mmol) in accordance with the general procedure. Purification
by column chromatography (hexane:ethyl acetate = 8.5:1.5) afforded
compound 3c (37 mg, 57% yield) as a white solid, mp = 54-55°C (after
crystallization from hexane). 1H NMR (500 MHz, CDCl3):7.57-7.54 (m,
2H), 7.30 (d, J = 7.9 Hz, 2H), 7.28-7.21 (m, 3H), 7.20 (d, J = 7.9 Hz, 2H),
4.18 (t, J = 7.4 Hz, 2H), 2.45 (s, 3H), 1.81-1.74 (m, 2H), 1.32-1.17 (m, 26H),
0.88 (t, J = 6.9 Hz, 3H); 13C NMR (126 MHz, CDCl3):144.0, 139.6, 133.7,
131.2, 130.0, 129.8, 128.3, 127.5, 126.7, 125.1, 48.2, 31.9, 30.1, 29.7,
29.7, 29.7, 29.6, 29.6, 29.5, 29.3, 29.3, 28.9, 26.4, 22.7, 21.4, 14.1; HRMS
(LC-IT-TOF) m/z: [M+H]+ Calcd for C31H46N3 460.3686; Found 460.3692.
4-Hexyl-1-(2-iodobenzyl)-1H-1,2,3-triazole (4). 2-Iodobenzylazide (0.700
g, 2.70 mmol) and 1-octyne (0.356 g, 3.24 mmol) were added at room
.
temperature to a solution of Cu(OAc)2 H2O (0.108 g, 0.54 mmol) in H2O
(15 mL) in a capped flask. The reaction mixture was warmed at 100°C and
stirred at the same temperature for 2h. After cooling at room temperature,
the reaction mixture was quenched with a saturated aqueous solution of
NH4Cl and extracted with ethyl acetate. The organic extracts were washed
with an aqueous solution of brine, dried over Na2SO4 and concentrated
under vacuum. The crude product was purified by column chromatography
on silica gel (hexane:ethyl acetate = 7:3) affording 0.775 g of compound
4 (78% yield) as a white solid, mp = 65-66°C. 1H NMR (500 MHz,
CDCl3):7.88 (dd, J = 8.4, 1.2 Hz, 1H), 7.32 (td, J = 7.6, 1.1 Hz, 1H), 7.28
(br s, 1H), 7.06-7.01 (m, 2H), 5.58 (s, 2H), 2.70 (t, J = 7.8 Hz, 2H), 1.69-
1.61 (m, 2H), 1.38-1.25 (m, 6H), 0.87 (t, J = ,7.0 Hz, 3H); 13C NMR (126
MHz, CDCl3):149.1, 139.9, 137.9, 130.4, 129.6, 129.1, 121.0, 98.6, 58.4,
31.7, 29.5, 29.0, 25.9, 22.7, 14.2; HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd
for C15H21N3I 370.0775; Found 370.0752.
5-(3,5-Dimethylphenyl)-1-hexadecyl-4-phenyl-1H-1,2,3-triazole
(3d).
Compound 3d was synthesized from 1a (50 mg, 0.14 mmol) and 1-iodo-
3,5-dimethylbenzene (98 mg, 0.42 mmol) in accordance with the general
procedure. Purification by column chromatography (hexane:ethyl acetate
= 8.5:1.5) afforded compound 3d (54 mg, 81% yield) as a white solid, mp
= 69-70°C (after crystallization from hexane). 1H NMR (500 MHz,
CDCl3):7.59-7.56 (m, 2H), 7.28-7.20 (m, 3H), 7.13 (br s, 1H), 6.92 (br s,
2H), 4.16 (t, J = 7.4 Hz, 2H), 2.36 (s, 6H), 1.82-1.75 (m, 2H), 1.32-1.17 (m,
26H), 0.88 (t, J = 6.9 Hz, 3H); 13C NMR (126 MHz, CDCl3): 144.0, 139.1,
134.1, 131.4, 131.4, 128.5, 128.3, 127.7, 127.6, 126.7, 48.3, 32.1, 30.2,
29.8, 29.8, 29.8, 29.8, 29.7, 29.5, 29.5, 29.0, 26.5, 22.8, 21.4, 14.3; HRMS
(LC-IT-TOF) m/z: [M+H]+ Calcd for C32H48N3 474.3843; Found 474.3839.
Synthesis of triazoles 3a-o.
General Procedure: A round-bottom flask (10 mL) with a screw cap and
equipped with a magnetic stirrer was charged with 1,2,3-triazole (1 equiv),
aryl iodide (3 equiv), Pd/C (5% mol) and Bu4NOAc (2 equiv). The resulting
heterogeneous reaction mixture was reacted at 110 °C (sand bath) under
magnetic stirring. After 24 h, the mixture was cooled to room temperature,
diluted with ethyl acetate and the resulting suspension was centrifuged to
recover both the heterogeneous catalyst as a solid material and the
organic layer containing the crude product (2 times). The organic extracts
were concentrated under vacuum and the crude product was purified by
column chromatography on silica gel. Procedure for recovery of Pd/C:
to the solid material recovered by centrifugation, EtOH was added. The
resulting suspension was stirred for 10 min and the solvent was removed
after centrifugation (2 times). The residual Pd/C was dried in vacuum at
60 °C overnight and used for the subsequent run.
4-Pentyl-1-phenethyl-5-phenyl-1H-1,2,3-triazole (3e). Compound 3e was
synthesized from 1b (50 mg, 0.21 mmol) and iodobenzene (129 mg, 0.63
mmol) in accordance with the general procedure. Purification by column
chromatography (hexane:ethyl acetate = 8.5:1.5) afforded compound 3e
(40 mg, 60% yield) as a viscous dark yellow oil. 1H NMR (500 MHz,
CDCl3):7.44-7.37 (m, 3H), 7.21-7.18 (m, 3H), 6.95-6.92 (m, 2H), 6.92-
6.88 (m, 2H), 4.38 (t, J = 7.3 Hz, 2H), 3.11 (t, J = 7.3 Hz, 2H), 2.56 (t, J =
7.8 Hz, 2H), 1.64-1.56 (m, 2H), 1.28-1.18 (m, 4H), 0.82 (t, J = 7.0 Hz, 3H);
13C NMR (126 MHz, CDCl3): 145.7, 137.5, 134.7, 129.7, 129.2, 128.9,
128.9, 128.7, 127.8, 126.9, 49.5, 36.8, 31.5, 29.4, 25.0, 22.5, 14.1; HRMS
(LC-IT-TOF) m/z: [M+H]+ Calcd for C21H26N3 320.2121; Found 320.2121.
1-Hexadecyl-4,5-diphenyl-1H-1,2,3-triazole (3a). Compound 3a was
synthesized from 1a (50 mg, 0.14 mmol) and iodobenzene (86 mg, 0.42
mmol) in accordance with the general procedure. Purification by column
chromatography (hexane:ethyl acetate = 9:1) afforded compound 3a (44
mg, 70% yield) as a white solid, mp = 63-64°C (after crystallization from
hexane). 1H NMR (500 MHz, CDCl3):7.54 (dd, J = 8.1, 1.5 Hz, 2H), 7.53-
7.49 (m, 3H), 7.34-7.31 (m, 2H), 7.28-7.21 (m, 3H), 4.19 (t, J = 7.2 Hz, 2H),
1.82-1.74 (m, 2H), 1.28-1.17 (m, 26H), 0.88 (t, J = 6.9 Hz, 3H) ; 13C NMR
(126 MHz, CDCl3):144.3, 133.8, 131.2, 130.1, 129.7, 129.5, 128.5,
128.4, 127.7, 126.9, 48.4, 32.1, 30.2, 29.8, 29.8, 29.8, 29.8, 29.8, 29.7,
5-(4-Fluorophenyl)-4-pentyl-1-phenethyl-1H-1,2,3-triazole
(3f).
Compound 3f was synthesized from 1b (243 mg, 1.00 mmol) and 1-fluoro-
4-iodobenzene (666 mg, 3 mmol) in accordance with the general
procedure. Purification by column chromatography (hexane:diethyl ether:
dichloromethane = 4:3:3) afforded compound 3f (254 mg, 75% yield) as a
viscous pale yellow oil. 1H NMR (500 MHz, CDCl3):7.22-7.18 (m, 3H),
7.09-7.04 (m, 2H), 6.89-6.85 (m, 2H), 6.82-6.78 (m, 2H), 4.35 (t, J = 7.1
Hz, 2H), 3.13 (t, J = 7.1 Hz, 2H), 2.54 (t, J = 7.8 Hz, 2H), 1.62-1.54 (m, 2H),
1.27-1.16 (m, 4H), 0.82 (t, J = 7.0 Hz, 3H) ; 13C NMR (126 MHz, CDCl3):
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901305
European Journal of Organic Chemistry
FULL PAPER
163.2 (d, J = 250.7 Hz), 145.5, 137.3, 134.2, 131.7 (d, J = 8.7 Hz), 128.9
(d, J = 15.9 Hz), 127.1, 123.4, 116.2 (d, J = 21.8 Hz); HRMS (LC-IT-TOF)
m/z: [M+H]+ Calcd for C21H25FN3 338.2027; Found 338.2020.
(126 MHz, CDCl3):144.9, 137.9, 132.5, 132.0, 131.8 (q, J = 33.2 Hz),
130.6, 129.4, 127.8, 127.0, 126.4 (q, J = 3.7 Hz), 123.8 (q, J = 272.5 Hz),
48.6, 31.8, 30.3, 29.1, 29.0, 26.5, 22.7, 21.3, 14.2; HRMS (LC-IT-TOF)
m/z: [M+H]+ Calcd for C24H29F3N3 416.2308; Found 416.2307.
5-(4-Nitrophenyl)-4-pentyl-1-phenethyl-1H-1,2,3-triazole (3g). Compound
3g was synthesized from 1b (50 mg, 0.21 mmol) and 1-iodo-4-
nitrobenzene (153 mg, 0.63 mmol) in accordance with the general
procedure. Purification by column chromatography (silica gel, particle size
0.040-0.063 mm, from hexane:diethyl ether:dichloromethane = 4:1:5 to
hexane: ethyl acetate 7:3) afforded compound 3g (42 mg, 56% yield) as a
5-(3,5-Dimethylphenyl)-1-octyl-4-(p-tolyl)-1H-1,2,3-triazole
(3l).
Compound 3l was synthesized from 1c (50 mg, 0.18 mmol) and 1-iodo-
3,5-dimethylbenzene (127 mg, 0.55 mmol) in accordance with the general
procedure. Purification by column chromatography (hexane:ethyl acetate
= 4:1) afforded compound 3l (35 mg, 51% yield) as a white solid, mp = 77-
78 °C (after crystallization from hexane). 1H NMR (500 MHz, CDCl3):7.47
(d, J = 8.1 Hz, 2H), 7.13 (br s, 1H), 7.07 (d, J = 8.1 Hz, 2H), 6.92 (br s, 2H),
4.15 (t, J = 7.5 Hz, 2H), 2.35 (s, 6H), 2.31 (s, 3H), 1.82-1.74 (m, 2H), 1.28-
1.17 (m, 10H), 0.86 (t, J = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3):144.0,
139.0, 137.3, 133.7, 131.3, 129.2, 128.6, 128.4, 127.7, 126.6, 48.2, 31.8,
30.2, 29.1, 29.0, 26.5, 22.7, 21.4, 21.3, 14.2; HRMS (LC-IT-TOF) m/z:
[M+H]+ Calcd for C25H34N3 376.2747; Found 376.2726.
1
viscous yellow oil. H NMR (500 MHz, CDCl3):8.19 (d, J = 8.1 Hz, 2H),
7.23 (t, J = 7.2 Hz, 1H), 7.18 (t, J = 7.2 Hz, 2H), 6.92 (d, J = 8.3 Hz, 2H),
6.82 (d, J = 7.0 Hz, 2H) 4.39 (t, J = 6.6 Hz, 2H), 3.17 (t, J = 6.6 Hz, 2H),
2.53 (t, J = 7.5 Hz, 2H), 1.63-1.55 (m, 2H), 1.28-1.16 (m, 4H), 0.83 (t, J =
7.0 Hz, 3H); 13C NMR (126 MHz, CDCl3): 148.1, 146.1, 137.2, 134.3,
133.1, 130.7, 130.0, 128.9, 127.2, 124.0, 50.0, 36.9, 31.4, 29.4, 25.0, 22.4,
14.1; HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd for C21H25N4O2 365.1972;
Found 365.1957.
4-Hexyl-5-phenyl-1-(p-tolyl)-1H-1,2,3-triazole (3m). Compound 3m was
synthesized from 1d (50 mg, 0.21 mmol) and iodobenzene (127 mg, 0.62
mmol) in accordance with the general procedure. Purification by column
chromatography (hexane:ethyl acetate = 7.5:2.5) afforded compound 3m
and unreacted 1d as an inseparable mixture (1.5:1 ratio, 45% yield by
NMR data); HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd for C21H26N3 320.2121;
Found 320.2106.
4-Pentyl-1-phenethyl-5-(o-tolyl)-1H-1,2,3-triazole (3h). Compound 3h was
synthesized from 1b (50 mg, 0.21 mmol) and 1-iodo-2-methylbenzene
(137 mg, 0.63 mmol) in accordance with the general procedure.
Purification by column chromatography (hexane:ethyl acetate = 3:2)
afforded compound 3h (31 mg, 44% yield) as a viscous yellow oil. 1H NMR
(500 MHz, CDCl3):7.36 (t, J = 7.6 Hz, 1H), 7.29 (d, J = 7.6 Hz, 1H), 7.23-
7.16 (m, 4H), 6.89 (dd, J = 6.4, 2.8 Hz, 2H), 6.65 (d, J = 7.6 Hz, 1H), 4.37
(ddd, J = 13.7, 8.5, 5.6 Hz, 1H), 4.05 (dt, J = 13.7, 7.9 Hz, 1H), 3.14 (dt, J
= 13.7, 7.9 Hz, 1H), 3.05 (ddd, J = 13.7, 8.5, 5.6 Hz, 1H), 2.55 (td, J = 14.9,
7.6 Hz, 1H), 2.41 (td, J = 14.9, 7.6 Hz, 1H), 1.95 (s, 3H), 1.62-1.51 (m, 2H),
1.25- 1.17 (m, 4H), 0.81 (t, J = 6.8 Hz, 3H); 13C NMR (126 MHz, CDCl3):
145.6, 138.0, 137.4, 134.1, 130.8, 130.5, 129.9, 128.9, 128.8, 127.0, 126.8,
126.2, 49.5, 36.6, 31.5, 29.0, 25.1, 22.4, 19.5, 14.1; HRMS (LC-IT-TOF)
m/z: [M+H]+ Calcd for C22H28N3 334.2278; Found 334.2266.
4-Hexyl-1-(p-tolyl)-5-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole
(3n).
Compound 3n was synthesized from 1d (50 mg, 0.21 mmol) and 1-iodo-
4-(trifluoromethyl)benzene (168 mg, 0.62 mmol) in accordance with the
general procedure. Purification by column chromatography (hexane:ethyl
acetate:diethy ether = 8:1:1) afforded compound 3n (63 mg, 78% yield) as
a viscous pale yellow oil. 1H NMR (500 MHz, CDCl3):7.63 (d, J = 8.2 Hz,
2H), 7.28 (d, J = 8.2 Hz, 2H), 7.18 (d, J = 8.4 Hz, 2H), 7.15 (d, J = 8.4 Hz,
2H), 2.73 (t, J = 7.7 Hz, 2H), 2.38 (s, 3H), 1.77-1.69 (m, 2H), 1.37-1.30
(m, 2H), 1.29-1.23 (m, 4H), 0.85 (t, J = 6.9 Hz, 3H); 13C NMR (126 MHz,
CDCl3):146.6, 139.2, 134.0, 132.3, 131.6, 130.8 (q, J = 32.8 Hz), 129.9,
129.9, 125.7 (q, J = 3.7 Hz), 124.7, 123.7 (q, J = 272.2 Hz), 31.5, 29.6,
29.0, 25.1, 22.5, 21.1, 14.0; HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd for
C22H25F3N3 388.1995; Found 388.1983.
5-(3-Methoxyphenyl)-1-octyl-4-(p-tolyl)-1H-1,2,3-triazole (3i). Compound
3i was synthesized from 1c (50 mg, 0.18 mmol) and 1-iodo-3-
methoxybenzene (129 mg, 0.55 mmol) in accordance with the general
procedure. Purification by column chromatography (hexane:ethyl acetate
= 8.5:1.5) afforded compound 3j and unreacted 1c as an inseparable
mixture (2:1 ratio, 61% yield by NMR data). HRMS (LC-IT-TOF) m/z:
[M+H]+ Calcd for C24H32N3O 378.2540; Found 378.2523.
5-(4-Fluorophenyl)-4-hexyl-1-(p-tolyl)-1H-1,2,3-triazole (3o). Compound
3o was synthesized from 1d (50 mg, 0.21 mmol) and 1-fluoro-4-
iodobenzene (138 mg, 0.62 mmol) in accordance with the general
procedure. Purification by column chromatography (silica gel, particle size
0.040-0.063 mm, hexane:ethyl acetate:diethy ether = 8:1:1) afforded
compound 3o (46 mg, 66% yield) as a white solid, mp = 94-95°C (after
crystallization from hexane). 1H NMR (500 MHz, CDCl3):7.20-7.04 (m,
8H), 2.70 (t, J = 7.7 Hz, 2H), 2.36 (s, 3H), 1.75-1.67 (m, 2H), 1.36-1.22 (m,
6H), 0.85 (t, J = 6.9 Hz, 3H); 13C NMR (126 MHz, CDCl3):162.9 (d, J =
249.6 Hz), 164.3, 139.0, 134.4, 133.0, 131.6 (d, J = 8.3 Hz), 129.9, 124.8,
124.0 (d, J = 3.5 Hz), 116.2 (d, J = 21.9 Hz), 31.6, 29.7, 29.2, 25.3, 22.7,
21.3, 14.2; HRMS (LC-IT-TOF) m/z: [M+H]+ Calcd for C21H25FN3
338.2027; Found 338.2009.
3-(1-octyl-4-(p-tolyl)-1H-1,2,3-triazol-5-yl)pyridine (3j). Compound 3j was
synthesized from 1c (50 mg, 0.18 mmol) and 3-iodopyridine (113 mg, 0.55
mmol) in accordance with the general procedure. Purification by column
chromatography (hexane:ethyl acetate = 8.5:1.5) afforded compound 3j
(30 mg, 47% yield) as a viscous brownish oil. 1H NMR (500 MHz,
CDCl3):
J = 3.5 Hz, 1H), 8.63 (s, 1H), 7.71 (d, J = 7.8 Hz,
1H), 7.50 (dd, J = 7.8, 4.9 Hz, 1H), 7.36 (d, J = 8.0 Hz, 2H), 7.09 (d, J =
8.0 Hz, 2H), 4.21 (t, J = 7.5 Hz, 2H), 2.31 (s, 3H), 1.83-1.75 (m, 2H), 1.28-
1.17 (m, 10H), 0.85 (t, J = 7.1 Hz, 3H); 13C NMR (126 MHz, CDCl3): 150.2,
150.0, 145.6, 138.3, 138.1, 129.8, 129.5, 127.5, 127.0, 125.3, 124.3, 48.7,
31.8, 30.3, 29.1, 29.0, 26.6, 22.7, 21.3, 14.2; HRMS (LC-IT-TOF) m/z:
[M+H]+ Calcd for C22H29N4 349.2387; Found 349.2368.
Synthesis of 3-hexyl-8H-[1,2,3]triazolo[5,1-a]isoindole (5).[7l]
1-Octyl-4-(p-tolyl)-5-(4-(trifluoromethyl)phenyl)-1H-1,2,3-triazole
(3k).
Compound 3k was synthesized from 1c (50 mg, 0.18 mmol) and 1-iodo-4-
(trifluoromethyl)benzene (150 mg, 0.55 mmol) in accordance with the
general procedure. Purification by column chromatography (silica gel,
particle size 0.040-0.063 mm, hexane:ethyl acetate = 8:2) afforded
compound 3k (47 mg, 63% yield) as a viscous colorless oil. 1H NMR (500
MHz, CDCl3):7.77 (d, J = 8.1 Hz, 2H), 7.47 (d, J = 8.0 Hz, 2H),7.37 (d, J
= 8.1 Hz, 2H), 7.09 (d, J = 8.0 Hz, 2H), 4.20 (t, J = 7.3 Hz, 2H), 2.32 (s,3H),
1.82-1.74 (m, 2H), 1.27-1.16 (m, 10H), 0.85 (t, J = 7.1 Hz, 3H); 13C NMR
A round-bottom flask (10 mL) with a screw cap and equipped with a
magnetic stirrer was charged with 4 (100 mg, 0.27 mmol), Pd/C (5% mol)
and Bu4NOAc (4 equiv). The resulting heterogeneous reaction mixture was
reacted at 120 °C (sand bath) under magnetic stirring. After 48 h, the
mixture was cooled to room temperature and the crude was purified by
column chromatography (silica gel, particle size 0.040-0.063 mm,
hexane:ethyl acetate = 7:3) afforded compound 5 (35 mg, 53% yield) as a
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901305
European Journal of Organic Chemistry
FULL PAPER
1
pale brown solid. H NMR (500 MHz, CDCl3):7.61 (d, J = 7.6 Hz, 1H),
Marrocchi, D. Lanari, A. Bechtoldt, L. Ackermann, L. Vaccaro Green
Chem. 2018, 20, 2888-2893.
7.50 (d, J = 7.6 Hz, 1H), 7.46 (t, J = 7.6 Hz, 1H), 7.37 (t, J = 7.6 Hz, 1H),
5.30 (s, 2H), 2.94 (t, J = 7.6 Hz, 2H), 1.85-1.77 (m, 2H), 1.46-1.39 (m, 2H),
1.38-1.26 (m, 4H), 0.88 (7, J = 7.0 Hz, 3H).[7l]
[8]
[9]
a) R. Jeyachandran, H. Kumar Potukuchi, L. Ackermann Beilstein J. Org.
Chem. 2012, 8, 1771-1777; b) L. Ackermann, H. K. Potukuchi, D.
Landsberg, R. Vicente Org. Lett. 2008, 10, 3081-3084.
a) R. A. Jagtap, V. Soni, B. Punji ChemSusChem 2017, 10, 2242-2248;
b) S. Bensaid, H. Doucet ChemSusChem 2012, 5, 1559-1567; c) S.
Castro, J. J. Fernꢀndez, R. Vicente, F. J. Faꢁanꢀs, F. Rodríguez Chem.
Commun. 2012, 48, 9089-9091; d) R. B. Bedford, C. J. Mitchell, R. L.
Webster Chem. Commun. 2010, 46, 3095-3097.
Acknowledgments
This work was financially supported by “XF-actors 727987”. The
authors thank Dr. L. Amendolare and Dr. S. Ciola for preliminary
work on the optimization of Pd-catalyzed C-H arylations and Dr.
V. Triminì for preliminary work on the intramolecular C–H
functionalization.
[10] a) J. Veciana, A. Ardizzone, D. Blasi, N. Grimaldi, S. Sala, I. Ratera, D.
Vona, A. Rosspeintner, A. Punzi, E. Altamura, E. Vauthey, G. M. Farinola,
N. Ventosa Chem. Eur. J. 2018, 30, 2213-2217; b) M. A. M. Capozzi, A.
Punzi, F. Babudri, R. Musio, G. M. Farinola J. Org. Chem. 2018, 83,
14396-14405; c) A. Operamolla, A. Punzi, G. M. Farinola Asian J. Org.
Chem. 2017, 6, 120-138; d) A. Punzi, E. Maiorano, F. Nicoletta, D. Blasi,
A. Ardizzone, N. Ventosa, I. Ratera, J. Veciana, G. M. Farinola Eur. J.
Org. Chem. 2016, 15, 2617-2627; e) V. Fiandanese, I. Marino, A. Punzi
Tetrahedron, 2012, 68, 10310-10317; f) V. Fiandanese, S. Maurantonio,
A. Punzi, G. G. Rafaschieri Org. Biomol. Chem. 2012, 10, 1186-1195.
[11] a) A. Punzi, A. Operamolla, O. Hassan Omar, F. Brunetti, F.; A. D.
Scaccabarozzi, G. M. Farinola, N. Stingelin Chem. Mater., 2018, 30,
2213-2217; b) A. Punzi, M. A. M. Capozzi, S. Di Noja, R. Ragni, N.
Zappimbulso, G. M. Farinola J. Org. Chem. 2018, 83, 9312-9321; d) R.
Ragni, A. Punzi, F. Babudri, G. M. Farinola Eur. J. Org. Chem. 2018,
3500-3519; c) A. Punzi, D. I. Coppi, S. Matera, M. A. M. Capozzi, A.
Operamolla, R. Ragni, F. Babudri, G. M. Farinola Org. Lett. 2017, 19,
4754-4757; d) A. Punzi, F. Nicoletta, G. Marzano, C. G. Fortuna, J. Dagar,
T. M. Brown, G. M. Farinola Eur. J. Org. Chem. 2016, 3233-3242.
[12] Y.-L. Zou, Z.-Y. Wang, Y.-M. Feng, Y.-G. Li, E. A. B. Kantchev Eur. J.
Org. Chem. 2017, 6274–6282.
Keywords: C-H activation • solvent-free reactions • Pd-catalysis
• 1,2,3-triazoles • nitrogen-based heterocycles
[1]
a) E. Bonandi, M. S. Christodoulou, G. Fumagalli, D. Perdicchia, G.
Rastelli, D. Passarella Drug Discov. Today, 2017, 22, 1572-1581; b) D.
Dheer, V. Singh, R. Shankar Bioorg. Chem. 2017, 71, 30-54.
C. J. Pickens, S. N. Johnson, M. M. Pressnall, M. A. Leon, C. J. Berkland,
J. Cory Bioconjugate Chem. 2018, 29, 686-701.
[2]
[3]
[4]
a) J. E. Moses, A. D. Moorhouse Chem. Soc. Rev. 2007, 36, 1249-1262;
b) J-F. Lutz Angew. Chem. Int. Ed. 2007, 46, 1018-1025.
a) H. C. Kolb, M. G. Finn, K. B. Sharpless Angew. Chem., Int. Ed., 2001,
40, 2004-2021; b) V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B.
Sharpless Angew. Chem., Int. Ed., 2002, 41, 2596-2599.
[5]
C. W. Tornøe, C. Christensen, M. Meldal J. Org. Chem., 2002, 67, 3057-
3064.
[13] C.-Z. Tao, X. Cui, J. Li, A.-X. Liu, L, Liu, Q.-X. Guo Tetrahedron Lett.
2007, 48, 3525-3529.
[6]
[7]
J. E. Hein, V. V. Fokin Chem. Soc. Rev., 2010, 39, 1302-1315.
a) S. Chuprakov, N. Chernyak, A. S. Dudnik, V. Gevorgyan Org. Lett.,
2007, 9, 2333-2336; b) L. Ackermann, R. Vicente, R. Borna Adv. Synth.
Catal. 2008, 350, 741-748; c) L. Ackermann, A. Althammer, S. Fenner
Angew. Chem. Int. Ed. 2009, 48, 201-204; d) L. Ackermann, R. Vicente
Org. Lett., 2009, 11, 4922-4925; e) L. Ackermann, R. Jeyachandran, H.
K. Potukuchi, P. Novák, L. Büttner Org. Lett., 2010, 12, 2056-2059; f) K.
D. B. Yamajala, M. Patil, S. Banerjee J. Org. Chem., 2015, 80, 3003-
3011; g) C. Zhang, L. You, C. Chen Molecules 2016, 21, 1268; h) X. Tian,
F. Yang, D. Rasina, M. Bauer, S. Warratz, F. Ferlin, L. Vaccaro, L.
Ackermann Chem. Commun., 2016, 52, 9777-9780; i) S. V. Markandeya,
Ch. Renuka, P. K. Lakshm, A. Rajesh. C. Sridhar, K. R. Babu Synth.
Commun., 2018, 48, 135-145; l) F. Ferlin, L. Luciani, S. Santoro, A.
[14] G. A. Chesnokov, M. A. Topchiy, P. B. Dzhevakov, P. S. Gribanov, A. A.
Tukov, V. N. Khrustalev, A. F. Asachenko, M. S. Nechaev Dalton Trans.
2017, 46, 4331-4345.
This article is protected by copyright. All rights reserved.

10.1002/ejoc.201901305
European Journal of Organic Chemistry
FULL PAPER
Entry for the Table of Contents
FULL PAPER
Heterogeneous Pd-catalysis, solvent-
free conditions
Angela Punzi, Nicola Zappimbulso,
Gianluca M. Farinola*
Page No. – Page No.
1,4,5-Trisubstituted 1,2,3-triazoles and 1,2,3-triazole-fused isoindolines are
synthesized by a sustainable Pd-catalyzed direct arylation reaction performed in
solvent-free conditions and in the presence of a recyclable heterogeneous catalyst.
Direct arylations via C−H bond
functionalization of 1,2,3-triazoles by
reusable Pd/C catalyst in solvent-free
conditions
This article is protected by copyright. All rights reserved.