Silver(I) oxide nanoparticles as a catalyst in the azide-alkyne cycloaddition

Article abstract of DOI:10.1016/j.tetlet.2015.08.083

1,3-Dipolar cycloadditions between a number of azides and monosubstituted acetylenes have been carried out in the presence of catalytic amounts of silver(I) oxide nanoparticles. 4-Substituted 1,2,3-triazoles were usually the only products, while the prese

Full text of DOI:10.1016/j.tetlet.2015.08.083

Accepted Manuscript
Silver(I) oxide nanoparticles as a catalyst in the azide-alkyne cycloaddition
Anna M. Ferretti, Alessandro Ponti, Giorgio Molteni
PII:
S0040-4039(15)30037-X
DOI:
http://dx.doi.org/10.1016/j.tetlet.2015.08.083
TETL 46667
Reference:
Tetrahedron Letters
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2 August 2015
31 August 2015
Please cite this article as: Ferretti, A.M., Ponti, A., Molteni, G., Silver(I) oxide nanoparticles as a catalyst in the
azide-alkyne cycloaddition, Tetrahedron Letters (2015), doi: http://dx.doi.org/10.1016/j.tetlet.2015.08.083
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Silver(I) oxide nanoparticles as a catalyst in
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Anna M. Ferretti, Alessandro Ponti and Giorgio Molteni

1
Tetrahedron Letters
Silver(I) oxide nanoparticles as a catalyst in the azide-alkyne cycloaddition
Anna M. Ferretti,a Alessandro Ponti,a* and Giorgio Moltenibǂ
aIstituto di Scienze e Tecnologie Molecolari (ISTM), Consiglio Nazionale delle Ricerche, via Golgi 19, 20133 Milano, Italy. bUniversità degli Studi di Milano,
Dipartimento di Chimica, via Golgi 19, 20133 Milano, Italy
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
The 1,3-dipolar cycloadditions between a number of azides and monosubstituted acetylenes have
been carried out in the presence of catalytic amounts of silver(I) oxide nanoparticles. 4-
Substituted 1,2,3-triazoles were usually the only products, while the presence of electron-
withdrawing groups onto the azide moiety caused a loss of regioselectivity giving mixtures of 4-
and 5-substituted 1,2,3-triazoles. A novel catalytic cycle has been proposed to rationalise this
latter "non-click" behaviour.
Available online
Keywords:
2015 Elsevier Ltd. All rights reserved.
Silver oxide
Nanoparticle
Azide
Alkyne
1,3-Dipolar cycloadditions
1. Introduction
2. Results and discussion
Both metal1,2 and metal oxide3 inorganic nanoparticles (NPs)
have recently emerged as effective catalysts in a number of
synthetically useful transformations. For instance, the 1,3-dipolar
cycloaddition between azides and monosubstituted alkynes have
been successfully performed in the presence of Cu, Cu2O, and
CuO NPs.4-7 Within this framework, some of us described the use
of colloidal copper/copper oxide NPs as a valuable catalyst for
the azide-alkyne cycloaddition.8
Uncoated silver(I)oxide nanoparticles (NPs) were synthesized
by alkaline precipitation from aqueous silver nitrate solution.20
A
TEM image of the Ag2O NPs is shown in Figure 1. The
nanoparticles had approximately spherical shape and ranged in
size from 2 to 14 nm. The diameter distribution had mean
<d> = 5.3 nm and standard deviation σd = 1.3 nm (dispersion
σd/<d> = 25%).
Concerning the metal which follows copper in the 1B column
of the Periodic Table, Ag2O NPs have found application as
sensors9,10 and antimicrobial materials11 but most applications
exploited Ag2O NPs as catalysts. For instance, nanoscale Ag2O
was recognized as an active species in silver-titania
photocatalysis12-14 and Ag2O NPs have been used for the
oxidation of CO to CO2.15-17 Ag2O NPs were less studied as a
catalyst for synthetic organic chemistry. Just two reports are
known which describes the use of ≈10 nm18 and ≈1 μm19 Ag2O
NPs in the synthesis of propargylamines; a tentative reaction
mechanism was there proposed involving the formation of a
silver acetylide.18
Figure 1. TEM image of as-synthesized Ag2O NPs (left) and
the corresponding size distribution (right).
Due to the known chemical and crystallographic similarity of
Ag2O and Cu2O, we perceived that Ag2O NPs could be used as a
catalyst for the azide-alkyne cycloaddition, so we decided to
investigate colloidal Ag2O NPs under this respect. In the
following sections, we will show that Ag2O NPs coated with
oleic acid behave as an effective catalyst in the reaction between
azides and monosubstituted acetylenes
The powder X-ray diffractogram of the uncoated NPs is
displayed in Figure 2 confirming the occurrence of genuine
silver(I) oxide NPs.
___________
ǂCorresponding author. Tel./fax: +39 025031 4141/4139.
E-mail address: giorgio.molteni@unimi.it (G. Molteni).

2
Tetrahedron Letters
substituted 1,2,3-triazoles 3. However, longer reaction times and
lower product yields were experienced compared to the same
reactions carried out in the presence of air-protected Cu/Cu-oxide
nanoparticles as the catalyst.8
Figure 2. Powder X-ray diffractogram of uncoated Ag2O
nanoparticles.
Since we planned to use Ag2O NPs as a well-dispersed catalyst in
toluene, we coated the as-synthesized NPs with oleic acid. These
coated NPs showed good colloidal stability in toluene and were
used for all of the azide-alkyne cycloadditions described below.
We investigated the morphology of Ag2O NPs after they were
used as the catalyst (Figure 3).22 The nanoparticles maintained a
spherical shape and their size resulted somewhat reduced,
ranging from 1 to 12 nm. The diameter distribution had mean
<d> = 3.4 nm and standard deviation σd = 1.4 nm (dispersion
σd/<d> = 41%).
Scheme 1. Ag2O NPs catalysed arylazide-alkyne
cycloadditions in anhydrous toluene.
Table 1. Ag2O NPs catalysed arylazide-alkyne
cycloadditions in anhydrous toluene.a
______________________________________________________________________________
Entry
R1
R2
t(h)
3 (%)b
______________________________________________________________________________
H
H
MeO
COOMe
Ph
COOMe
16
12
12
9
54c
58
50
44
aa
ab
ba
bb
MeO
Ph
______________________________________________________________________________
b
c
aAt 30°C. Isolated yields. Yield of 3aa was 29% and 43%
after 4 and 8 h, respectively.
Next, Ag2O NPs-catalysed cycloadditions were performed in
non-anhydrous toluene at 20ºC (Scheme 2). Reaction times and
product yields are given in Table 2, while structures of
cycloadducts 3 and 4 were determined by analytical and
spectroscopic methods which matches literature data.25,26 Easy
filtration of the undissolved material allowed the recovering of
the Ag2O NPs which were reused without significant loss of
catalytic activity.
Figure 3. TEM image of Ag2O NPs coated with oleic acid
after use as a catalyst (left)22 and the corresponding size
distribution (right).
Catalysed azide-alkyne cycloadditions represent a fruitful
field which had grown dramatically in the last decade.4,23,24
Hence, we decided to investigate scope and limitations of the
reaction between arylazides 1 and alkynyl dipolarophiles 2
(Figure 4) in the presence of catalytic amounts of Ag2O NPs (1.9-
2.7% in weight with respect to 1).
Scheme 2. Ag2O NPs catalysed arylazide–alkyne
cycloadditions in toluene.
Figure 4. Reactants to be submitted to dipolar cycloaddition
in the presence of Ag2O NPs as the catalyst.
As can be inferred from comparison of the data in Table 1 and
2, the presence of small amounts of water27 produced significant
cycloaddition speed-up and product yield enhancement. It is also
worth noting the loss of regioselectivity of the reactions between
azides 1c,d and methyl propiolate (Table 2, entry ca and da),
First of all, we performed such reactions by stirring an
equimolecular mixture of the reactants at 30ºC under nitrogen in
anhydrous toluene as depicted in Scheme 1 and Table 1. Fully
regioselective cycloadditions provided only the 1-aryl-4-

3
which parallels previous results obtained by thermal
cycloadditions.25 A similar behaviour is not unprecedented, since
it was reported in the cycloadditions between 4-chloro-
phenylazide and phenylacetylenes catalysed by silver(I)-
electronic configuration, the silver (I) provided by the Ag2O
nanoparticle surface can coordinate two molecules of water and
the terminal alkyne 2 giving the labile 18 electron complex 6.
Water displacement by azides 1a,b can generate the reactive
intermediate 7, which leads to the corresponding 4-substituted
1,2,3-triazoles 3. The ability of electron poor 1c,d to act as a
ligand may be by far less effective than that of 1a,b on the basis
of the corresponding σ+ Hammett values.33 In the former cases
the upper part of the catalytic cycle would work providing
mixtures of the corresponding regioisomers 3 and 4.
complexed
N,N-diisopropyl(2-dicyclohexylphosphanyl)benza-
mide.28,29 It is well-known that the classic Huisgen cycloaddition
between arylazides and acetylenes30,31 can hardly occur at room
temperature. Accordingly, we observed that in the absence of
Ag2O NPs azide 1a and methyl propiolate did not react
appreciably after ten days at 20°C; the same fate occurred in the
presence of sparingly soluble silver(I) bulk salts capable of
Brønsted basic catalysis, namely Ag2O, Ag2CO3, AcOAg and
silver oleate. A further finding is related to the lack of reactivity
of the internal dipolarophiles 4-heptyn-2-ol and dimethyl
acetylenedicarboxy late (DMAD). The behaviour of propargyl
bromide (Table 2, entry bd) may appear prima facie
disappointing. However, this lack of reactivity is due to the
sensitivity of Ag2O NPs to the bromide ion present in the halide;
the NPs are thus destroyed and replaced by bulk silver bromide
which is unable to act as a catalyst.32
This behaviour is different compared to that of the substituent-
insensitive Cu(I) catalyzed cycloadditions and may be due to the
weaker interaction between the azide N1 and Ag(I) of
intermediate 7. The latter argument is corroborated by the known
fact that Cu(I) is more tenaciously bonded to N donors than Ag(I)
is.34 On the other hand, the formation of intermediate 6 is
reasonable since σ-acetylide complexes of both Cu(I) and Ag(I)
are known.35
Since azide 8 (Scheme 3) displays roughly the same electronic
features of 1d,36 as a further stage of our work we submitted 8 to
cycloaddition with methyl propiolate. The results summarised in
Scheme 3 speak again in favour of the lack of regioselectivity as
predicted by the above catalytic cycle.
Table 2. Ag2O NPs catalysed arylazide–alkyne cycloadditions in
toluene.a
__________________________________________________________________________________
Entry R1
R2
t (h)
3 (%)b
4 (%)b
__________________________________________________________________________________
__
H
MeO
Cl
NO2
H
MeO
MeO
MeO
COOMe
COOMe
COOMe
COOMe
Ph
Ph
CH2OH
CH2Br
4
4
6
16
4
3
7
7
90
95
70
50
90
aa
ba
ca
da
ab
bb
bc
bd
__
25
44
__
__
__
92
Scheme 3. Ag2O NPs catalysed cycloadditions between azide
8 and methyl propiolate in toluene.
90
< 2c,d
< 2c,d
__________________________________________________________________________________
aAt 20°C. bIsolated yields. Not fully characterised. d88% of
unreacted 1b was recovered.
c
2. Conclusions
The use of Ag2O NPs in the azide-alkyne cycloaddition
displayed several encouraging features, which can be
summarised as follows: (i) the catalyst was effective, reusable
after simple filtration and chemically robust, (ii) high product
yields and cycloaddition regioselectivity were usually observed;
(iii) the experimental procedure was simple, i.e. heating of the
reaction mixture was avoided; (iv) a pronounced substituent
effect was observed, whereas electron-withdrawing groups
placed onto the azide moiety gave mixtures of regioisomeric
cycloadducts. This latter feature resembles the behaviour of the
thermal Huisgen reaction and could be regarded as a limitation,
however the proposed catalytic cycle based onto the labile
bis(aquo)-silver(I) acetilyde intermediate 6 should represent a
novel and interesting insight in the growing field of metal-
catalysed azide-alkyne cycloaddition.
All the above observations may find a rationale provided that
the catalytic cycle depicted in Figure 5 does work.
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Figure 5. Proposed catalytic cycle of the cycloaddition
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4
Tetrahedron Letters
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