Synthesis of aryl azides: A probe reaction to study the synergetic action of ultrasounds and ionic liquids

Article abstract of DOI:10.1016/j.ultsonch.2011.06.010

The combined effect of ultrasounds and ionic liquids was used to perform the synthesis of aryl azides by nucleophilic aromatic substitution in ionic liquid/[1-butyl-3-methylimidazolium][N₃] binary mixtures. The ultrasounds efficiency was analyz

Full text of DOI:10.1016/j.ultsonch.2011.06.010

Ultrasonics Sonochemistry 19 (2012) 136–142
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Ultrasonics Sonochemistry
journal homepage: www.elsevier.com/locate/ultsonch
Synthesis of aryl azides: A probe reaction to study the synergetic action
of ultrasounds and ionic liquids
⇑
⇑
Francesca D’Anna , Salvatore Marullo, Paola Vitale, Renato Noto
Dipartimento STEMBIO, Sezione di Chimica Organica ‘‘E. Paternò’’, Università degli Studi di Palermo, Viale delle Scienze-Parco d’Orleans II, 90128 Palermo, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 14 April 2011
Received in revised form 13 June 2011
Accepted 16 June 2011
Available online 25 June 2011
The combined effect of ultrasounds and ionic liquids was used to perform the synthesis of aryl azides by
nucleophilic aromatic substitution in ionic liquid/[1-butyl-3-methylimidazolium][N3] binary mixtures.
The ultrasounds efficiency was analyzed as a function of the substrate and of the ionic liquid structure.
In the first case, both 6
ture is concerned, both aromatic and aliphatic ionic liquids were taken into account. Among aromatic cat-
ions, the effects due to different ability in giving hydrogen bond or interactions were considered. The
p and 10p electrons aryl halides were considered. As far as the ionic liquid struc-
p–p
Keywords:
Ionic liquids
Ultrasounds
Aryl azides
use of a geminal ionic liquid having an aromatic spacer was examined too.
On the whole, collected data evidence an activating effect on the target reaction by the combined use of
ultrasounds and ionic liquids. The structural order degree of the ionic liquid seems to be the main factor
affecting the ultrasounds efficiency. Furthermore, the effects due to changes in the anion structure seem
to be more significant than those due to changes in the cation structure.
Nucleophilic aromatic substitution
Ó 2011 Elsevier B.V. All rights reserved.
1. Introduction
pressure, low flammability and a certain structural order degree,
which markedly determine the aforementioned effects. Among
Since their enunciation, the fifth and the sixth principle of Green
Chemistry represented a clear request for the scientific community
to tune up new processes having low energetic requirements and to
use, when possible, solvents or any other auxiliary substances hav-
ing low environmental impact [1]. The significant ferment that such
a request has generated is testified by the large number of papers
focused on the use of alternative reaction media, such as water
[2–4], supercritical fluids [5] and ionic liquids [6,7]. In addition,
the use of alternative catalytic methods of irradiation such as
microwaves [8] and ultrasounds [9,10] has been investigated.
During the years, further development of research activity in
this field has been geared to identify the right combination of sol-
vent medium and catalytic methodology in order to achieve the
best results of synthetic processes with the full environmental
care. In this context, during the last few years interesting data have
been obtained by the combined use of ultrasounds (US) and ionic
liquids (ILs).
these properties, the negligible vapor pressure is the one that
makes them suitable reaction media for US irradiation. Although
a precise correlation between cavitation energy and vapor pressure
has not been reported, it is well known that rates of sonochemical
reaction can be increased by lowering the vapor pressure of the
solvent [15,16]. Under this light, the synergetic action of ILs and
US has been used in the study of the Suzuky [17] and the Heck
[18] reactions, alcohols acetylation [19], the synthesis of xanthene
derivatives [20], 2,4-diaryltriazoles [21], oximes [22], quinoline
derivatives [23] and so on.
In order to have a deeper understanding of such a synergetic ac-
tion, we studied the aryl azides formation by SNAr under US activa-
tion, using IL/[bmim][N3] binary mixtures as solvent media. This
reaction was chosen because in conventional organic solvents aryl
azides are not generally obtained by SNAr from corresponding aryl
halides. On the other hand, satisfactory results were obtained in IL
solution and using [bmim][N3] as the nucleophile source [24,25].
Previous literature reports have outlined the positive effect of US
irradiation on the SNAr reaction [26,27]; thus, in our opinion, the
above reaction could be a suitable probe to verify whether the
combined action of US and ILs has a further favorable effect.
Obviously, the interest in this investigation is also due to the
fact that the obtained products are key intermediates in organic
synthesis. Indeed, it is well known that aryl azides are useful synt-
hones in order to obtain various heterocycles having applications
in pharmaceutical, agricultural and materials chemistry [28,29].
As far as ILs are concerned as reaction media, the results ob-
tained allowed to outline the positive effects they may exert on a
given reaction in terms of rate, selectivity and yield [11,12]. It
has been frequently reasserted that ILs cannot be considered as
continuous media, such as conventional organic solvents [13,14].
As matter of fact, they show peculiar properties such as low vapor
⇑
Corresponding authors. Tel.: +39 091596919; fax: +39 091596825.
E-mail addresses: fdanna@unipa.it (F. D’Anna), rnoto@unipa.it (R. Noto).
1350-4177/$ - see front matter Ó 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.ultsonch.2011.06.010

F. D’Anna et al. / Ultrasonics Sonochemistry 19 (2012) 136–142
137
The substrates chosen for this work (see Fig. 1) differ for the
aromatic ring structure. In particular, 6 electrons (five- and six-
membered ring) and 10 electrons (bicyclic ring) derivatives were
As a matter of fact, it has been recently reported that this IL of
third generation has a higher structural order degree than the corre-
sponding monocationic [bmim][NTf2], as a consequence of the more
extensive cation–cation interaction [30]. The use of geminal ionic
liquids could be quite interesting. Indeed, despite some recent pa-
pers have had their synthesis and the study of their properties as
main subject [31,32], only few examples have been reported about
their use as reaction media [33,34]. Furthermore, in order to opti-
mize their applications, it could be rather interesting to have a better
knowledge of the relationships existing between their structure and
the effect they exert on the outcome of a given reaction. Under this
perspective, the comparison with data collected in [Bzmim][NTf2]
and [Bzbim][NTf2] solution could give useful information.
p
p
considered. In order to have information about the effect of IL nat-
ure on the US activation, the 2-bromo-5-nitrothiophene was cho-
sen as model substrate and the formation of the relevant azide
was studied at 298 K in different IL/[bmim][N3] binary mixtures
(see Fig. 1). This investigation allowed us to achieve a better
knowledge of the relationships between the IL nature and the US
action. This could impart to the study a predictive and, if possible,
a practical value, helping to choose the suitable IL media to carry
out a reaction under US irradiation.
In particular, ILs differing for the cation ability in giving
hydrogen bond or
p
–
p
interactions such as [bmim][NTf2] and
It is well known that both cohesive forces and structural order
degree are markedly affected by the size, shape and coordination
ability of the anion [35]. This is the reason why ILs differing for
the anion nature, such as [bmim][BF4], [bmim][PF6], [bmim][NTf2]
and [bmim][SbF6] were also used.
[bm2im] [NTf2] [where bm2im = 1-butyl-2,3-dimethylimidazolium
and NTf2 = bis(trifluoromethansulfonyl)imide] or [bmim][NTf2]
and [bmpyrr][NTf2] (where bmpyrr = N-butyl-N-methylpyrrolidi-
nium) were used. In addition, the effect due to a different extent
of
p
contact surface area for the cation was also evaluated, by using
Finally, in order to have a comparison with conventional organ-
ic solvents, the synthesis of the 2-azido-5-nitrothiophene, both un-
der silent and US activation, was studied also in MeOH solution
using [bmim][N3] as nucleophile source.
the [Bzmim][NTf2] and the [Bzbim][NTf2] as solvent media (where
Bzmim = 1-benzyl-3-methylimidazolium and Bzbim = 1-benzyl-3-
butylimidazolium).
The latter ILs differ for the length of the alkyl chain, which is a
further parameter able to affect both the nature of the cation–cat-
ion interactions and the structural order degree of IL. The influence
due to a different nature of the cation structure was also analyzed
by using a geminal IL, namely the 3,30-di-n-butyl-1,10-(1,3-phenyl-
enedimethylene)diimidazolium bis[bis(trifluoromethansulfonyl)
imide] [m-Xyl-(bim)2][NTf2]2.
2. Experimental details
2.1. Materials
[bmim][BF4], [bmim][PF6], 1,4-dioxane, NaN3 and aryl halides
were purchased and used without further purification. [bmim]
Fig. 1. Structure of the used substrates and ionic liquids.

138
F. D’Anna et al. / Ultrasonics Sonochemistry 19 (2012) 136–142
[NTf2], [bm2im][NTf2], [bmpyrr][NTf2], [bmim][SbF6], [Bzmim]
[NTf2], [Bzbim][NTf2], [m-Xyl-(bim)2][NTf2]2 were prepared accord-
ing to previously reported procedures [30,36,37]. All ionic liquids
were dried before use on a vacuum line at 70 °C for at least 2 h,
stored in a dryer under argon and over calcium chloride. The 2-bro-
mo-5-nitrofurane (2) [38] and the 2-bromo-3-nitrothiophene (4)
[39] were prepared according to previous reports.
Pale yellow oil (yield 80%). dH (300 MHz; CDCl3) 8.97 (s, 1H, H-
2), 7.47 (m, 5H, Ph), 7.33 (d, 3J 19.5, 2H, H4–H5), 5.40 (s, 2H, CH2-
Ph), 4.25 (t, 3J 7.5, 2H, CH2CH2CH2CH3), 1.91 (m, 2H,
CH2CH2CH2CH3), 1.43 (m, 2H, CH2CH2CH2CH3), 1.02 (t, 3J 7.2, 3H,
CH2CH2CH2CH3).
dC (300 MHz; CDCl3) 135.53 (C2 im), 132.21 (C1 Ph), 129.74
(C2–C4 Ph), 129.57 (C3–C5 Ph), 128.82 (C4 Ph), 122.32 (C5 im),
122.26 (C4 im), 120.02 (CF3SO2N), 53.62 (CH2-Ph), 50.06
(CH2CH2CH2CH3), 31.87 (CH2CH2 CH2CH3), 19.31 (CH2CH2CH2CH3),
13.17 (CH2CH2CH2CH3).
1H NMR spectra were collected on a 300 MHz spectrometer. All
spectra were recorded in CDCl3 solution.
2.1.1. 1-Benzyl-3-butylimidazolium bromide
Butylimidazole (3.68 g, 29.6 mmol) was dissolved in 2-propanol
(50 mL). The obtained solution was placed in an oil bath at 85 °C.
Benzylbromide (5.08 g, 29.6 mmol) was dissolved in 2-propanol
(50 mL) and the solution was added, dropwise, to the butylimidaz-
ole solution. The reaction mixture was stored at 85 °C for 24 h.
After cooling, the solution was concentrated in vacuo and the ob-
tained yellow oil was washed several times with diethyl ether.
The obtained bromide salt was dissolved in anhydrous dichloro-
methane (100 mL) and stirred overnight at room temperature, in
the presence of active charcoal (1% in weight). After filtration on
neutral alumina and concentration in vacuo, the corresponding
bromide was obtained.
2.2. Reaction conditions
The reactions were carried out in a thermostated ultrasonic
cleaning bath (VWR International USC-900) operating at a fre-
quency of 45 kHz. The tank dimensions were 495 ꢀ 130 ꢀ
150 mm, with a liquid holding capacity of 8.6 L. The ultrasonic clea-
ner had an output power of 0–200 W through digital adjustment.
The reactions were carried out in a round-bottomed flask of 20 mL
capacity suspended at the center of the cleaning bath, 5 cm below
the surface of the liquid.
Yellow oil (yield 91%). dH (300 MHz; CDCl3) 10.70 (s, 1H, H-2),
7.56 (m, 2H, H4–H5), 7.39 (m, 5H, Ph), 5.67 (s, 2H, CH2-Ph), 4.36
(t, 3J 7.5, 2H, CH2CH2CH2CH3), 1.93 (m, 2H, CH2CH2CH2CH3), 1.42
(m, 2H, CH2 CH2CH2CH3), 0.99 (t, 3J 7.5, 3H, CH2CH2CH2CH3).
dC (300 MHz; CDCl3) 137.45 (C2 im), 133.47 (C1 Ph), 129.87 (C2-
C6 Ph), 129.82 (C3-C5 Ph), 129.45 (C4 Ph), 122.43 (C5 im), 122.27
(C4 im), 53.67 (CH2-Ph), 50.37 (CH2CH2CH2CH3), 32.46 (CH2CH2CH2
CH3), 19.81 (CH2CH2CH2CH3), 13.83 (CH2CH2CH2CH3).
2.2.1. General procedure for aryl azides synthesis
An amount of 1.44 mmol of aryl halide was dissolved in
0.3 mL of 1,4-dioxane. The obtained solution was added drop-
wise to a thermostated mixture of 1.8 mmol of [bmim][N3] in
IL solution (1.2 mL). In all cases the reaction mixture was irradi-
ated in the water bath of the ultrasonic cleaner at the tempera-
ture and for the time indicated in Tables 1–3. The composition of
the reaction mixture was examined time by time by TLC. In
some cases, the reaction was quenched at a suitable time to
avoid the formation of overwhelming by-products. Then, the
reaction mixture was extracted several times with diethyl ether.
After solvent elimination, the residues were separated by flash
chromatography on neutral alumina. The pure aryl azides ob-
tained were characterized by IR, 1H NMR spectra and melting
points. In the case of 4-halopyridines, an equimolar amount of
hydrochloric acid was added to the reaction mixture in diethyl
ether solution. After solvent elimination, the composition of
the mixture was determined by 1H NMR.
2.1.2. 1-Benzyl-3-butylimidazolium bis(trifluoromethansulfonyl)imide
The 1-benzyl-3-butylimidazolium bromide (7.59 g, 25.7 mmol)
was dissolved in dichloromethane (40 mL). The obtained solution
was placed in an ice bath and lithium bis(trifluoromethansulfo-
nyl)imide (7.52 g, 26.2 mmol) was added. The reaction mixture
was stirred at room temperature for 48 h. Then, it was filtered to
remove the LiBr salt and the organic solution was washed with
water, until the aqueous phase was halide free (by means of a sil-
ver nitrate test). The ionic liquid, obtained after concentration in
vacuo, was dissolved in dichloromethane (100 mL) and treated
with active charcoal (1% in weight) overnight. Then, the solution
was filtered through a pad of neutral alumina and concentrated
in vacuo to give the ionic liquid.
Table 2
Yields in azido derivatives of Aryl Halides obtained through nucleophilic aromatic
substitution in [bmim][BF4]/[bmim][N3] binary mixtures under ultrasounds irradia-
tion or under silent conditions.a
Entry Substrate Temperature US yield
Silent yield
Silent yield
Table 1
b
b
b,c
(K)
%
(Time)
74 (20 min) 54 (20 min) 62 (2 h)
67 (5 min) 61 (5 min) 73 (30 min)
%
(Time)
%
(Time)
Yields in azido derivatives of (1) and (8) obtained through nucleophilic aromatic
substitution at different volumes of [bmim][BF4]/1,4-dioxane binary mixture at 298 K
under ultrasounds irradiation.a
1
2
3
4
5
6
7
8
9
1
2
3
4
5
6
7
8
9
298
298
298
298
313
323
298
298
323
54 (30 min) 83 (30 min) 83 (30 min)
73 (20 min) 54 (20 min) 58 (2 h)
Entry
Substrate
Vsolvent
(lL)
Co-solvent (%, v:v)
Yield %b
mixture
1
2
3
4
5
6
7
8
1c
1c
1c
1c
8d
8d
8d
8d
600
130
100
65
600
130
100
65
25
23
0
23
25
23
0
76
78
73
75
71
78
69
70
6 (16 h)
22 (6 h)
9e (12 h)
71 (4 h)
7f (8 h)
<2 (16 h)
13 (6 h)
<2 (12 h)
16 (4 h)
<2 (8 h)
13 (72 h)
19d (24 h)
20e (24 h)
86 (24 h)
52f (72 h)
a
All reaction were carried out by using 1.44 mmol of substrate and 1.8 mmol of
[bmim][N3].
23
b
Isolated yield after column chromatography. Yields were reproducible within
a
All reaction were carried out by using 1.44 mmol of substrate and 1.8 mmol of
[bmim][N3].
2%.
c
See Ref. [24].
Reaction temperature = 333 K.
b
d
e
f
Isolated yield after column chromatography. Yields were reproducible within
Yields calculated in the reaction mixture by 1H NMR (see Section 2).
In the case of 2-chloroquinoline, according to Ref. [24], the tetrazole derivative
2%.
c
Reaction time = 20 min.
Reaction time = 4 h.
d
of 2-azidoquinoline was obtained.

F. D’Anna et al. / Ultrasonics Sonochemistry 19 (2012) 136–142
139
Table 3
Under this perspective, in order to verify if the combined sys-
tem now used (ILs and US) may follow this tendency, we used
the [bmim][BF4] as solvent medium and we tried to decrease the
volume used in each experiment. Because all experiments in this
work were carried out using 1,4-dioxane as cosolvent (see Section
2), we decreased the volume of the solvent mixture used, keeping
constant the nucleophile:substrate molar ratio. We used two mod-
el substrates, namely the 2-bromo-5-nitrothiophene (1) and the
4-chloroquinoline (8), which were chosen for their significantly
different solubilities in our solvent media. Data collected are re-
ported in Table 1.
Yields in 2-azido-5-nitrothiophene obtained through nucleophilic aromatic substitu-
tion in different binary mixtures IL/[bmim][N3] at 298 K under ultrasounds irradiation
(20 min) or silent conditions (2 h).a
Entry
Solvent
US yield %b
Silent yield %b
1
2
3
4
5
6
7
8
9
MeOH
[bmim][BF4]
[bmim][PF6]
[bmim][SbF6]
[bmim][NTf2]
[bm2im][NTf2]
[bmpyrr][NTf2]
[Bzmim][NTf2]
[Bzbim][NTf2]
[m-Xyl-(bim)2][NTf2]2
11 (25)c
76
20
62d
63
84
63
70
74
75
74
64
74
69
57d
55d
69d
72
Also in this case the US activation positively affects our reaction
system. Indeed, irrespective of the substrate used, the decrease in
solvent volume does not induce any significant decrease in yields.
In both cases it seems that the best experimental conditions are
65
71
10
a
All reaction were carried out by using 1.44 mmol of substrate and 1.8 mmol of
[bmim][N3].
fulfilled using a solvent volume as large as 130 lL (entries 2 and
b
Isolated yield after column chromatography. Yields were reproducible within
6, Table 1). Once again, according to previously collected data
[24], the cosolvent plays a favorable role. Indeed, the absence of
cosolvent (entries 3 and 7, Table 1) induces a decrease in yields
[40]. This result perfectly agrees with report by Srinivasan et al.
[17] about the favorable effect exerted by MeOH in the US pro-
moted Suzuki cross-coupling reaction in IL, which was ascribed
to the homogeneity of the reaction mixture.
2%.
c
Reaction time = 2 h.
See Ref. [24].
d
3. Results and discussion
3.1. Optimization of experimental conditions
Under magnetic stirring, by using the best experimental condi-
tions found out for US irradiation (Vsolvent = 130 lL) and 1 as
Our primary goal was the optimization of the experimental con-
ditions. Preliminary runs were carried out using the 2-bromo-5-
nitrothiophene as the model substrate. The choice of this substrate
was due to its high reactivity, which was previously verified on
studying the formation of aryl azides in IL/[bmim][N3] binary mix-
tures at 298 K [24].
substrate, yield was lower despite a higher reaction time (yield =
62%, 2 h). However, since a meaningful comparison with results
previously obtained has to be made, all reactions mentioned in
the subsequent sections were conducted by using the same solvent
composition described elsewhere [24].
We first tried to work with an output power of 100 W. Data col-
lected in [bmim][BF4] solution show that the better yield in the 2-
azido-5-nitrothiophene was obtained after 40 min of irradiation
(yield = 76%). Further increases in irradiation time resulted in no
improvement. By irradiating with an output power of 200 W for
20 min a similar result was obtained (yield = 76%). In order to ver-
ify if the obtained yield was the limit value, we carried out the US
irradiation for 40 min and 2 h (the reaction time under silent con-
ditions) [24]. In both cases no significant changes in yield were ob-
tained (yield = 76% for 40 min and 77% for 2 h). Similarly, under
silent conditions, yield did not improve significantly after 2 h
[24]. Good reproducibility of experimental results was verified. In
particular, the 2-azido-5-nitrothiophene was obtained with small
differences in yield (2% in yield).
The first comparison between these data and those previously
collected under silent conditions, evidences two important fea-
tures. In agreement with the frequently claimed ultrasounds acti-
vation of organic reactions, [9,10,17–23] the target reaction
proceeded in a shorter reaction time (20 min versus 2 h) and with
significantly higher yield (76% for US; 62% for silent). Furthermore,
bearing in mind what previously sanctioned by the Green Chemis-
try principles, the ultrasounds activation seems to be quite advan-
tageous from an environmental point of view, as testified by a
lower waste of energy [E = 57.3 kcal for US irradiation (P = 200
W; t = 20 min) and 722 kcal for silent (P = 420 W, (output power
of the magnetic stirrer); t = 2 h)].
3.3. The effect of the substrate nature
In Table 2 yields collected for different substrates, under US
irradiation in [bmim][BF4] solution, are reported. For a useful com-
parison, we reported data collected at silent conditions by using
two different reaction times. In particular, together with data pre-
viously reported [24], the ones collected by using the same reac-
tion times used under US irradiation are also showed.
These data must be analyzed as a function of the nature of the
substrate and the reaction temperature. Under US irradiation we
used the lowest temperature that allowed to achieve a higher yield
compared to that obtained under silent conditions; moreover, we
used the lowest reaction time allowing the completion or limiting
yield to be reached. A maximum temperature value of 323 K was
used.
The comparison between data collected, at the same reaction
time, under US and silent conditions, shows that in all cases con-
sidered the US irradiation exerts a positive effect. Indeed, indepen-
dently of the used substrate an increase in yields can be detected
and this trend results more significant in the case of the 2-bro-
mo-5-nitrothiophene (1), 2-bromo-3-nitrothiophene (4) and 4-
chloropyridine (8).
As far as the comparison with data previously collected at silent
conditions [24] is concerned, shorter reaction times were used.
Furthermore, in some cases yields were comparable to those ob-
tained under silent conditions [24]. For instance, positive effects
of the combined action IL/US were detected in the case of the 2-
bromo-5-nitrothiophene (1), 2-bromo-3-nitrothiophene (4) and
1-bromo-2-nitrobenzene (6) (see entries 1, 4 and 6, Table 2). In-
deed, in these cases the US activation allowed to obtain compara-
ble or higher yields than the ones previously collected [24], using
shorter reaction times (1, 4 and 6) or also a lower reaction temper-
ature (6). By contrast, in the case of 2-bromo-5-nitrofurane (2), 2-
bromo-5-nitrothiazole (3), 4-bromopyridine (7) and 4-chloroquin-
oline (8) (see entries 2, 3, 7 and 8, Table 2) significantly lower
3.2. Solvent composition
Among the factors that must be taken into account in tuning up
a synthetic strategy, the amount of solvent used as well as its nat-
ure plays an important role. In order to respect the Green Chemis-
try principles, both modern industry and academy are trying to
decrease the amount of solvent used, promoting a sort of ‘‘solvent
economy’’ tendency.

140
F. D’Anna et al. / Ultrasonics Sonochemistry 19 (2012) 136–142
yields were obtained with respect to the ones previously collected
under silent conditions [24]. In order to explain these results, we
tested the stability of the starting materials and of the correspond-
ing azides to US irradiation. The US irradiation of 2 and 3, in the ab-
sence of [bmim][N3], for 5 min and 30 min, respectively, allowed to
recover only 73% and 69% of the substrate, respectively. On the
grounds of these results, a certain sensitivity of the starting mate-
rials to US irradiation may be hypothesized. This should induce a
decrease in the amount of substrate available for the reaction,
and consequently in the reaction yield. By contrast, in the case of
(7), the low yield in 4-azidopyridine could be ascribed to the high
vapor pressure of both substrate and product.
As far as the reaction temperature is concerned, comparison
with data previously obtained [24] indicates that in some cases
the synergetic favorable effect of US/IL becomes less significant
when a higher reaction temperature is needed. As a matter of fact,
both the 1-bromo-4-nitrobenzene (5) and the 2-chloroquinoline
(9) (see entries 5 and 9, Table 2) give significantly lower yields un-
der US irradiation. Different literature reports have evidenced the
unfavorable effect on the outcome of US irradiation deriving from
a temperature increase [41–42]. On this purpose, even Khosropour
et al. evidenced no improvement in yields, as a consequence of the
temperature increase, on studying the US promoted synthesis of
2,4-diarylthiazoles in [bmim][BF4] solution [21]. Probably, a higher
reaction temperature might induce a decrease in the order degree
of the IL supramolecular structure [43]. As a consequence, weaker
interactions should occur and, on the whole, a less efficient cavita-
tion process takes place (see later).
a less relevant IL anion effect had been detected. Indeed, yields var-
ied in a narrower range.
Data collected herein cannot be explained on the grounds of
the IL anion symmetry. Indeed, the two anions having the highest
symmetry ([PF6ꢁ] and [SbF6ꢁ]) give rise to the highest and the
lowest yield, respectively. We have previously obtained a similar
result, on studying the copper(II) catalyzed mononuclear rear-
rangement of heterocycles [44], and the obtained result was as-
cribed to the highest structural organization of [bmim][PF6].
This might be invoked also in the present study to explain our
experimental results.
In order to verify this hypothesis, all parameters accounting for
cation–anion, cation–cation and ion pairs interactions, such as b,
the cohesive pressure and the extent of IL aggregation degree
should be taken into account. Firstly, we analyzed the cohesive
pressure of the different ILs used in this work. This parameter
has been defined as a measure of the strength of the interactions
among solvent molecules. In some cases it has been invoked to
rationalize the ILs effect on the reaction course or on the ion pairs
stabilities in IL solution [45–47]. In our case, the cohesive pressure
significantly decreases on going from [bmim][PF6] to [bmim][NTf2]
(ced = 6774, 6632 and 4523 atm for [bmim][PF6], [bmim][BF4] and
[bmim][NTf2])[48] and this trend perfectly parallels the one de-
tected for yields. On the other hand, the b values (as a measure
hydrogen bond acceptor ability of the anion) for the ILs used in this
work change along the series: [bmim][BF4] > [bmim][PF6] > [b-
mim][NTf2] > [bmim][SbF6] [49]. Therefore, with the only excep-
tion of [bmim][PF6], changes in this parameter reflect the ones
observed for yields. In the case of [bmim][PF6], a significant contri-
bution to the activating effect of the US irradiation might also de-
rive from its largest viscosity. Indeed, Fuchigami et al. underlined
in a recent paper that the synergetic action of US and IL may be
a consequence of the favored mass transport in these viscous sol-
vent media [50].
3.4. The IL effect
In order to get further information about the effect of IL nature
on the US activation, the formation of 2-azido-5-nitrothiophene, at
298 K, was studied in different IL solutions. As we mentioned pre-
viously, in order to have a comparison with conventional organic
solvents, the target reaction was also studied in MeOH solution.
Moreover, for drawing a meaningful comparison with results pre-
viously collected, all silent reactions were conducted for 2 h, a time
after which no significant increase in yields had been detected for
the synthesis of 2-azido-5-nitrothiophene in the same reacting
system [24].
Taking into account the cation-anion interaction, it should be
hypothesized that a stronger interaction should induce a higher
structural order degree for the solvent system. This, in turn, favors
the occurrence of those supramolecular interactions which overall
allow to assimilate aromatic ILs to supramolecular fluids [51,52].
As far as the extent of IL aggregation degree is concerned, by using
resonance light scattering investigation we have previously evi-
denced a decrease in the aggregation degree of bmim+-ILs that par-
allels the changes in yields obtained in this work [53].
Data collected are reported in Table 3, together with data previ-
ously obtained under silent conditions at 298 K.
Analysis of data collected in MeOH solution shows that US irra-
diation induces no significant improvement on the studied reac-
tion. Indeed, the obtained yields under ultrasounds irradiation, at
two different reaction times (20 min and 2 h) resulted lower or
comparable to the one collected under silent conditions.
A different behavior was observed in IL solutions. In all the
cases considered, indeed yields were higher than those collected
in MeOH solution. Furthermore, with the only exception of
[bmim][SbF6] solution, yields collected in different IL solutions un-
der US activation resulted higher than those previously collected
under silent conditions [24]. However, also in [bmim][SbF6], a
comparable yield was obtained in a significantly lower reaction
time.
As we stated previously, the effectiveness of US irradiation in
conventional organic solvents increases on decreasing the solvent
vapor pressure, as a consequence of an easier cavitation process
[54]. The vapor pressure of a solvent accounts for the strength of
its intermolecular interactions. Therefore, an IL having strong
interactions could be compared to a conventional solvent having
a low vapor pressure, and consequently, it should be a solvent sys-
tem more efficient in promoting the US irradiation. As a confirma-
tion, the efficiency of US irradiation, evaluated as the difference
between the yields obtained under US activation and silent condi-
tions (Dyield), decreases on decreasing the structural order degree
of the solvent system (Dyield = 21, 14 and 13% for [bmim][PF6],
[bmim][BF4], [bmim][NTf2]).
For a better understanding of the obtained results in IL solution,
data collected in Table 3 must be analyzed both as a function of the
IL anion and cation structure.
3.4.2. The IL cation effect
The analysis of data collected as a function of IL cation structure
shows that, in all cases considered, comparable or higher yields
were obtained under US irradiation than under silent condition
[24]. As a consequence of the significant structural changes in
the used IL cations, quite articulate trends were observed in both
conditions. However, there are two important differences with re-
sults previously discussed about IL anion structure, that have to be
taken into account. First, under US irradiation the range of yields is
3.4.1. The IL anion effect
Analysis of collected data as a function of the IL anion structure
shows that yields decrease along the series: [bmim][PF6] > [b-
mim][BF4] > [bmim][NTf2] > [bmim][SbF6]. This trend, with the
exception of [bmim][SbF6], is quite similar to the one previously
obtained under silent conditions [24]. However, in the latter case

F. D’Anna et al. / Ultrasonics Sonochemistry 19 (2012) 136–142
141
narrower than that under silent conditions (Dyield = 17% and 11%
Acknowledgements
for silent and US, respectively). Second, under US irradiation the
decrease in reaction time does not correspond to an increase in
yield (see entry 9 of Table 3) in some cases. On the whole, these
data seem to indicate a less significant influence of change in IL
cation structure on the effectiveness of cavitation process.
We thank University of Palermo and MIUR (Prin 2008KRBX3B)
for financial support. We would also thank Dr. J.B. Harper for his
useful suggestions.
Comparison between data collected under silent conditions and
US irradiation, for butyl-methyl-substituted cations (namely
bmim+, bm2im+ and bmpyrr+, see entries 5–7 of Table 3), indicates
that the positive effect of US irradiation increases along the series
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