Can the absence of solvation of neutral reagents by ionic liquids be responsible for the high reactivity in base-assisted intramolecular nucleophilic substitutions in these solvents?

Article abstract of DOI:10.1021/jo048485n

The kinetics of the rearrangement of the Z-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (1a) into the relevant 4-benzoylamino-2,5- diphenyl-1,2,3-triazole (2a) induced by amines have been studied in two room-temperature ionic liquids (IL-1, [BMI

Full text of DOI:10.1021/jo048485n

Can the Absence of Solvation of Neutral
Reagents by Ionic Liquids Be Responsible
for the High Reactivity in Base-Assisted
uids: 1-butyl-3-methylimidazolium tetrafluoroborate
[
BMIM][BF
4
] (IL-1) and hexafluorophosphate [BMIM]-
[
PF ] (IL-2). IL-1 and IL-2 are among the ionic liquids
6
most widely employed and could provide some informa-
tion on the effect of the present anion. As a matter of
fact, the presumably unlike cation-anion of different size
interactions between BMIM and two anions [a larger
Intramolecular Nucleophilic Substitutions
in These Solvents?†
Francesca D’Anna,*,‡ Vincenzo Frenna, Renato Noto,
‡
‡
-
-
4
‡
§
6 4
(PF ) and a smaller (BF )] could in turn affect the
Vitalba Pace, and Domenico Spinelli
interaction between the transition state and the solvent.
We have chosen the reaction in Scheme 1 because, at
least to our knowledge, no study of an intramolecular
ring-to-ring rearrangement in I Ls has been so far
reported in the literature. As a matter of fact, the
mechanism [intramolecular (internal) nucleophilic dis-
placement (SNi) of nitrogen onto nitrogen], transition-
state structure, and kinetic details of this BKR have been
deeply investigated experimentally both in several con-
Dipartimento di Chimica Organica “E. Patern o` ”, Universit a`
degli Studi di Palermo, Viale delle Scienze,
Parco d’Orleans 2, 90128 Palermo, Italy, and Dipartimento
di Chimica Organica “A. Mangini”, Universit a` degli Studi
di Bologna, Via San Giacomo 11, 40126 Bologna, Italy
fdanna@unipa.it
Received August 30, 2004
3g-h,5
ventional solvents6
and in organized systems such as
nonionic micelles and â-cyclodextrin.7
(
1) (a) Zim, D.; de Souza, R. F.; Dupont, J.; Monteiro, A. L.
Tetrahedron Lett. 1998, 39, 7071-7074. (b) Suarez, P. A. Z.; de Souza,
R. F.; Dupont, J. J. Polym. Bull. 1998, 40, 401-405. (c) Welton, T.
Chem. Rev. 1999, 99, 2071-2083. (d) Adams, C. J.; Seddon, K. R. Green
Chem. 2000, 2, 21-23. (e) Green, L.; Hemeon, I.; Singer, R. D.
Tetrahedron Lett. 2000, 41, 1343-1346. (f) Morrison, D. W.; Forbes,
D. C.; Davis, J. H. Tetrahedron Lett. 2001, 42, 6053-6055. (g) Pagni,
R. M.; Kabalka, G. W.; Lee, C.; Malladi, R. R.; Collins, B.; Conley, N.
Industrial Applications for Green Chemistry; Rogers, R. D., Seddon,
K. R., Eds.; American Chemical Society: Washington, DC, 2002; pp
42-55. (h) Dupont, J.; Fonseca, G. S.; Umpierre, A. P.; Fichtner, P. F.
P.; Teixera, S. R. J. Am. Chem. Soc. 2002, 124, 4228-4229. (i) Earle,
R. M.; Forestier, A.; Olivier-Bourbigou, H.; Wassercheid, P. Ionic Liquid
in Synthesis; Wassercheid, P., Welton, T., Eds.; Wiley-VCH Verlag:
New York, 2003; pp 174-213. (j) Sethi, A. R.; Smith, P.; Srinivasan,
N.; Welton, T. Green Industrial Application of Ionic Liquids; Rogers,
R. D., Seddon, K. R., Volkov, S., Eds.; Kluwer Academic Publishers:
Norwell, 2003; pp 457-464. (k) Gmouh, S.; Yang, H.; Vaultier, M. Org.
Lett. 2003, 5, 2219-2222. (l) Louen c¸ o, N. M. T.; Alfonso, C. A. M.
Tetrahedron 2003, 59, 789-794. (m) Rajagopal, R.; Srinivasan, K. V.
Ultrason. Sonochem. 2003, 10, 41-43. (n) Miao, W.; Chan, T. H. Org.
Lett. 2003, 5, 5003-5005. (o) Baudequin, C.; Baudoux, J.; Levillaine,
J.; Cahard, D.; Gaumont, A.-C.; Plaquevent, J.-C. Tetrahedron: Asym-
metry 2003, 14, 3081-3093. (p) Anjaiah, S.; Chandrasekhar, S.; Gr e´ e,
R. Tetrahedron Lett. 2004, 45, 569-571. (q) Shen, H.-Y.; Judeh, Z. M.
A.; Ching, C. B.; Xia, Q.-H. J. Mol. Catal. A 2004, 212, 301-308. (r)
Baleiz a˜ o, C.; Pires, N.; Gigante, B.; Curto, M. J. M. Tetrahedron Lett.
The kinetics of the rearrangement of the Z-phenylhydrazone
of 3-benzoyl-5-phenyl-1,2,4-oxadiazole (1a) into the relevant
4
-benzoylamino-2,5-diphenyl-1,2,3-triazole (2a) induced by
amines have been studied in two room-temperature ionic
liquids (IL-1, [BMIM][BF4] and IL-2, [BMIM][PF6]). The
data collected show that the reaction occurs faster in ionic
liquids than in other conventional solvents previously
studied (both polar or apolar, protic or aprotic). Presumably,
this could depend on their peculiar ability to minimize the
strong substrate-solvent, amine-solvent and amine-amine
interactions occurring in conventional solvents.
Room-temperature ionic liquids (I Ls) have been pro-
posed as environmentally benign solvents for their non-
detectable vapor pressure and for their easy recyclability.
2004, 45, 4375-4377. (s) Boovanahalli, S. K.; Kim, D. W.; Chi, D. Y.
J. Org. Chem. 2004, 69, 3340-3344. (t) Branco, L. C.; Alfonso, C. A.
M. J. Org. Chem. 2004, 69, 4381-4389.
1
I Ls promise several advantages in organic synthesis,
(2) (a) Lancaster, N. L.; Welton, T.; Young, J. B. J. Chem. Soc.,
Perkin Trans. 2 2001, 2267-2270. (b) Lancaster, L. N.; Salter, P. A.;
Welton, T.; Young, J. B. J. Org. Chem. 2002, 67, 8855-8861. (c)
McLean, A. J.; Muldoon, M. J.; Gordon, C. M.; Dunkin, I. R. Chem.
Commun. 2002, 1880-1881. (d) Chiappe, C.; Conte, V.; Pieraccini, D.
Eur. J. Org. Chem. 2002, 2831-2837. (e) Kim, D. W.; Song, C. E.; Chin,
D. Y. J. Org. Chem. 2003, 68, 4281-4288. (f) Chiappe, C.; Pieraccini,
D.; Saullo, P. J. Org. Chem. 2003, 63, 6710-6715. (g) Skrzjpczak, A.;
Neta, P. Int. J. Chem. Kinet. 2004, 36, 253-258. (h) Lancaster, N. L.;
Welton, T. J. Org. Chem. 2004, 69, 5986-5992. (i) Chiappe, C.;
Pieraccini, D. J. Org. Chem. 2004, 69, 6059-6064.
both increasing the effectiveness of the process and
lowering the usage of raw materials. Several organic
reactions were performed in I Ls with success but, to the
best of our knowledge, quantitative aspects of reactions
in I Ls have been much less investigated.2
To widen the applicability field of I Ls to new organic
reactions, we have undertaken a kinetic study of the
rearrangement (monocyclic rearrangement of hetero-
(3) (a) Boulton, A. J.; Katritzky, A. R.; Hamid, A. J. Chem. Soc. C
1967, 2005-2007. (b) Boulton, A. J. Lectures in Heterocyclic Chemistry;
Hetero Corporation: Provo, Utah, July 1973. (c) Afridi, A. S.; Katritzky,
A. R.; Ramsden, C. A. J. Chem. Soc., Perkin Trans. 1 1976, 315-320.
(d) Katritzky, A. R.; Gordev, M. F. Heterocycles 1993, 35, 483-518. (e)
Van der Plas, H. C. Ring Transformations of Heterocycles; Academic
Press: London, 1973; Vols. 1 and 2. (f) L’abb e´ , G. J. Heterocycl. Chem.
3
cycles, MRH, or Boulton-Katritzky reaction, BKR) of
the Z-phenylhydrazone of 3-benzoyl-5-phenyl-1,2,4-oxa-
diazole (1a) into the relevant 4-benzoylamino-2,5-diphen-
yl-1,2,3-triazole (2a) in two room-temperature ionic liq-
1984, 21, 621-638. (g) Ruccia, M.; Vivona, N.; Spinelli, D. Adv.
*
To whom correspondence should be addressed. Ph: +39.091.596919.
Heterocycl. Chem. 1981, 29, 141-169. (h) Vivona, N.; Buscemi, S.;
Frenna, V.; Cusmano, G. Adv. Heterocycl. Chem. 1993, 56, 49-154.
(4) Anthony, L. J.; Brennecke, J. F.; Holbrey, J. D.; Maginn, E. J.;
Mantz, R. A.; Rogers, R. D.; Trulove, P. C.; Visser, A. E.; Welton, T.
Ionic Liquids in Synthesis; Wasserscheid, P., Welton, T., Eds.; Wiley-
VCH Verlag: New York, 2003; pp 41-126.
Fax: +39.091.596825.
†
Dedicated to Professor Giorgio Modena on the occasion of his 80th
birthday.
‡
University of Palermo.
University of Bologna.
§
10.1021/jo048485n CCC: $30.25 © 2005 American Chemical Society
2828
J. Org. Chem. 2005, 70, 2828-2831
Published on Web 02/25/2005

TABLE 1. Apparent First-Order Rate Constants (kA,R)a
SCHEME 1
at 298.1 K and Calculated Second-Order Rate Constants
b
(
kII) for the Rearrangement of 1a into 2a in IL-1 and
IL-2 in the Presence of Amines
Solvent: IL-1
1
02 [BuA], M
0
.217
0.435
0.203
0.869
1.30
1.52
1.60
1.74
1.87
1
03 (kA,R
)
BuA, s-1
-1
0.0127
0.711
1.33
-
1
-4
kII (M
s
): (0.125 ( 0.004), i [(-3.07 ( 0.41) 10 ], n 6, r 0.998
1
02 [PIP], M
0
.210
0.436
0.843
0.874
3.02
1.33
5.06
1.50
6.30
1.74
8.14
1
03 (kA,R
)
PIP, s-1
0.0138
1
-1
-3
k
II (M s ): (0.517 ( 0.028), i [(-1.35 ( 0.32) 10 ], n 6, r 0.994
1
02 [TEA], M
Moreover an accurate theoretical DFT study has
recently furnished results convergent with experimental
data strongly supporting the proposed transition-state
structure for the reaction in the uncatalyzed range. As
a matter of fact, by measuring the rate constants for the
0
.217
0.436
0.327
0.874
1.10
1.31
1.52
1.54
2.05
1.74
2.48
1
03 (kA,R
)
TEA, s-1
1
0.0102
-
-4
k
II (M s-1): (0.156 ( 0.008), i [(-3.44 ( 0.96) 10 ], n 6, r 0.994
8
Solvent: IL-2
rearrangement of 1a into 2a in dioxane/water at different
10
2
[PIP], M
1.55
proton concentrations it has been observed that in the
0
.877
1.33
1.77
2.18
+
3
.8-7.0 pS range the reaction occurs via an uncatalyzed
1
03 (kA,R
)
PIP, s-1
0.0246
0.133
0.186
0.264
0.360
+
+
process (the pS -independent range), while at pS g 8.0
a (general) base-catalyzed pathway (the pS -dependent
1
-1
-4
k
II (M s ): (0.0261 ( 0.0010), i [(-2.09 ( 0.15) 10 ], n 5, r 0.998
+
a
The rate constants were reproducible to within (3%. [1a] 1.7
range) is operating.
-
4
b
×
10 M (at λ 366 nm, log ꢀ 4.28). See text.
In other solvents (benzene, toluene, dioxane, ethyl
acetate, acetonitrile and methanol) the rearrangement
of 1a has been studied in the presence of piperidine,
always observing one or more piperidine-catalyzed path-
ways and, in some occasions (in acetonitrile as well as
in methanol), a significant contribution of the uncata-
presence of organic bases,5
c-e,9
we planned to measure
the reactivity at 298.1 K in the presence of six different
molar concentrations (0.0020-0.0174 M, see data in the
Table 1) of the following bases: butylamine (BuA, a
primary amine), piperidine (PIP, a secondary cyclic
amine). and triethylamine (TEA, a tertiary amine),
showing different structure, basicity and steric require-
ments.
An excellent linear dependence of kA,R on amine
concentration has been found for each amine according
to eq 1 and the following, strictly comparable kII values
5
c-e
lyzed pathway.
The reactivity of some other Z-arylhydrazones has been
also investigated. In particular, the rearrangement of the
Z-4-nitrophenylhydrazone of 3-benzoyl-1,2,4-oxadiazole
1
b into the relevant triazole 2b has been extensively
studied in benzene (as well as in other solvents) in the
presence of several primary, secondary, and tertiary
amines with different basicity and steric requirements.5
First we checked that 1a does not rearrange signifi-
cantly into 2a in IL-1 within 10 days (i.e., if a reaction
-
1
-1
(
M
s ) have been calculated for BuA (0.125 ( 0.004, r
e,9
0
0
.998), PIP (0.517 ( 0.028, r 0.994), and TEA (0.156 (
.008, r 0.994), respectively. Significant “negative” in-
-
4
-3
tercept values (i ) -3.07 × 10 , -1.35 × 10 , and -3.44
-
8
-1
occurs, kA,R = 10 s ). However, remembering the
results obtained in conventional organic solvents in the
-
4
×
10 , for BuA, PIP and TEA, respectively) have also
1
0
been calculated.
(
5) (a) Spinelli, D.; Corrao, A.; Frenna, V.; Vivona, N.; Ruccia, M.;
kA,R ) i + (k )
[amine]
(1)
II amine
Cusmano, G. J. Heterocycl. Chem. 1976, 13, 357-360. (b) Frenna, V.;
Vivona, N.; Consiglio, G.; Corrao, A.; Spinelli, D. J. Chem. Soc., Perkin
Trans. 2 1981, 1325-1328. (c) Frenna, V.; Vivona, N.; Spinelli, D.;
Consiglio, G. J. Heterocycl. Chem. 1980, 17, 861-864. (d) Frenna, V.;
Vivona, N.; Consiglio, G.; Spinelli, D. J. Chem. Soc., Perkin Trans. 2
The behavior above could be related to an acid-base
interaction between the acidic imidazolium ion and the
amine, as confirmed by the observation that, when
recording the UV-vis spectra of IL-1 in the presence of
1
983, 1199-1202. (e) Frenna, V.; Vivona, N.; Consiglio, G.; Spinelli,
D. J. Chem. Soc., Perkin Trans. 2 1986, 1183-1187. (f) Frenna, V.;
Buscemi, S.; Arnone, C. J. Chem. Soc., Perkin Trans. 2 1988, 1683-
-4
-1
increasing piperidine concentrations (1 × 10 to 1 × 10
1
686. (g) D’Anna, F.; Ferroni, F.; Frenna, V.; Guernelli, S.; Lanza, C.
M), a decrease of the absorption maximum (λ ) 283 nm)
and an increase of the absorption at λ ) 400 nm could
be evidenced. This behavior is in line with the peculiar
acidic character of H-2 of IL-1, recently pointed out by
Z.; Macaluso, G.; Pace, V.; Petrillo, G.; Spinelli, D.; Spisani, R.
Tetrahedron 2005, 61, 167-168. (h) Cosimelli, B.; Guernelli, S.;
Buscemi, S.; Frenna, V.; Macaluso, G. J. Org. Chem. 2001, 66, 6124-
6
129. (i) Cosimelli, B.; Frenna, V.; Guernelli, S.; Lanza, C. Z.; Macaluso,
G.; Petrillo, G.; Spinelli, D. J. Org. Chem. 2002, 67, 8010-8018.
6) Guernelli, S.; Noto, R.; Sbriziolo, C.; Spinelli, D.; Turco Liveri,
M. L. J. Colloid Interface Sci. 2002, 239, 217-221.
7) Guernelli, S.; Lagan a` , M. F.; Spinelli, D.; Lo Meo, P.; Noto, R.;
Riela, S. J. Org. Chem. 2002, 67, 2948-2953.
8) Bottoni, A.; Frenna, V.; Lanza, C. Z.; Macaluso, G.; Spinelli, D.
J. Phys. Chem. A 2004, 108, 1731-1740.
1
(
means of H NMR measurements in different solvents
11
by Headley and Jackson. In agreement with the hy-
(
(
(10) This fact is not new in the literature, although it has never
been discussed before. Thus, for example, by using literature data we
calculated negative intercept values in the case of the reaction of
methyl p-nitrobenzenesulfonate with halide ions.
(11) Headley, D.; Jackson, N. M. J. Phys. Org. Chem. 2002, 15, 52-
55.
(
9) (a) Frenna, V.; Vivona, N.; Spinelli, D.; Consiglio, G. J. Heterocycl.
2
b
Chem. 1981, 18, 723-725. (b) Frenna, V.; Vivona, N.; Caronia, A.;
Consiglio, G.; Spinelli, D. J. Chem. Soc., Perkin Trans. 2 1983, 1203-
1
207.
J. Org. Chem, Vol. 70, No. 7, 2005 2829

pothesis advanced, the calculation of the [amine] value
corresponding to kA,R ) 0 in eq 1 (i.e., [amine] ) -i/kII
furnished three strictly comparable concentration val-
it a very effective solvent for the rearrangement herein.
As a matter of fact, the PIP-catalyzed reaction rate of
the rearrangement of 1a in IL-1 is higher than those
measured in any of the solvents previously tested, also
including ACN, which together with DMSO has been so
)
-
3
-3
-3
ues: 2.5 × 10 , 2.6 × 10 , and 2.2 × 10 M for BuA,
PIP, and TEA, respectively. Therefore the “true” effective
amine concentrations are lower than the stoichiometric
13
N
far considered the favorite solvent for S 2 and then for
-
3
5d-f,13
ones by ca. 2.4 × 10 M; of course, this correction does
S
N
i reactions.
The peculiar behavior of ACN was
5
d-f
not affect the amine-dependent slope values (kII).
related
not only to its HBD acidity and solvatochromic
N
The simple (first-order) dependence of the reactivity
on the amine concentration (whichever the amine) evi-
dences in IL-1 a behavior largely different from the more
complex one observed in conventional organic solvents
where, in the presence of piperidine, the rearrangement
constants (R 0.19, ET 0.460) but also to its HBA basicity
(â 0.40) which in the whole makes it able to provide
assistance to the reaction.13
However, in the case of IL-1 we think that its efficiency
as a solvent able to promote MRH cannot be ascribed only
to its high polarity. Probably, acting as an organizing
medium because of π-π interactions, it could help the
Z-phenylhydrazone 1a to assume the suitable geometry
for the occurrence of the intramolecular reaction, accord-
ing to the hypothesis that the high solubility of aromatic
compounds in I Ls could be related to some kind of
clathrate formation.14
5
c-f
of 1a
occurred with different kinetic laws depending
on the solvent polarity. In highly polar solvents (such as
acetonitrile and methanol, where also a significant
contribution of the uncatalyzed pathway could be evi-
denced) and, in contrast, in low polarity solvents (such
as benzene, toluene, dioxane and ethyl acetate) a first-
and a second-order dependence on the amine concentra-
5
c-g
tion were observed, respectively.
Moreover in the
As the properties of I Ls are largely controlled by the
5e,9
4
instance of 1b, the substrate most deeply investigated
in benzene, it was observed that in the presence of
amines of different basicities and steric requirements the
rearrangement follows a first-order dependence with
tertiary amines (or with highly hindered secondary
amines), but a second- and a third-order dependence with
secondary and primary amines, respectively.
nature of both the cation and the anion, in order to gain
further information concerning the anion influence we
have studied the rearrangement at 298.1 K of 1a in
another room-temperature ionic liquid, namely, 1-butyl-
3-methylimidazolium hexafluorophosphate (IL-2), in the
presence of PIP at five concentrations of amine (0.009-
0.022 M). Once more an excellent linear dependence of
To gain information about the base and solvent effects
a comparison with data in conventional solvents is
appropriate. For this we chose benzene (PhH) and
acetonitrile (ACN) as good examples of solvents with
completely different properties. In PhH and in ACN
different kinetic laws were observed depending on the
amine used; thus, to compare data in ionic liquid with
those for 1a and 1b in the two abovementioned solvents,
we calculated rate constant values at 0.01 M amine
concentration.
kA,R versus [PIP] with a negative intercept value (i )
-
4
-1 -1
-2.09 × 10 ) was found and a kII (M s ) of 0.0261
((0.0010, r 0.998) was calculated. In this case an amine
concentration value corresponding to kA,R ) 0 was
-
3
calculated (8 × 10 M), well in agreement with the
observation11 that IL-2 is more acidic than IL-1.
The reactivity of 1a in IL-2 is lower than in IL-1 by a
factor of ∼20. A similar reactivity trend in tetrafluorobo-
rate and in hexafluorophosphate salts was recently
observed in the nucleophilic substitution of 2-(3-bro-
2e
As far as base effects are concerned, for the rearrange-
ment of 1a in IL-1 (see data in Table 1) only a small
mopropyl)naphthalene with potassium acetate and the
outcome was attributed to a low solubility of the nucleo-
philic reagent. Also in the triplet energy transfer from
benzophenone to naphthalene a large reactivity variation
was observed by changing the solvent anion from hexaflu-
reactivity variation [at 298.1 K, (kII
)
BuA:(kII
)
TEA:(kII
)
PIP
)
1
:1.2:4.1] has been observed. In contrast, a much larger
and a similar reactivity range were observed for 1b in
9b
2c
PhH (at 313.1 K, 1:66:188) and in ACN (at 283.1 K,
orophosphate to bis(trifluoromethanesulfonyl)imide, at-
5
f
1
:1.1:8.1), respectively. The effect of the reactivity-
tributed to different charge distributions in the anions.
A comparison between the reactivity in the two I Ls is
surely of interest, considering that we have pointed out
that the 1 to 2 rearrangement is largely affected by the
very nature of the solvent: thus we think that differences
in solvent properties of the two I Ls could cause signifi-
cant reactivity differences.
selectivity principle could, at least in part, account for
the different behavior observed in the three solvents
(PhH, ACN, and IL-1), but it must be remembered that
in benzene, as well as in other conventional solvents,
amine-solvent and amine-amine interactions could
strongly differentiate the amines on the basis of their
nature and of their steric requirements (both intrinsic,
that is, structure-dependent and external, that is, de-
pendent on amine-solvent interactions) unlike what
probably occurs in IL-1 and ACN (see following).
Unfortunately, measurements of dielectric constants
of I Ls appear at present not available, and thus other
parameters useful to determine their “polarities” must
N
T
be used. E , R, and â parameters appear particularly
Looking now at the solvent effect on the reactivity of
a in the presence of piperidine, always comparing data
promising for discussing solvent effects in our case. As
N
1
matter of fact ET and R, as expected, are quite similar
N
at amine concentration 0.01 M, we observed a very large
increase of the reactivity on going from PhH to ACN or
for IL-1 and IL-2 (ET 0.673 and 0.667; R 0.73 and 0.77,
1
2
5
5
IL-1: (kA,R
)
PhH:(kA,R
)
ACN:(kA,R
)
IL-1 ) 1:1.2 × 10 :3.5 × 10 .
(
13) Reichardt, C. Solvents and Solvent Effect in Organic Chemistry,
Certainly the polar nature of IL-1 plays a role in making
3rd ed.; Wiley-VCH: Weinheim, Germany, 2003.
(14) Atwood, J. L. Liquid Clathrates, Inclusion Compounds; Atwood,
J. L., Davies, J. E. D., MacNicol, D. D., Eds.; Academic Press: London,
1984; Vol. 1.
(12) This value was referred at 313.1 K.
2830 J. Org. Chem., Vol. 70, No. 7, 2005

respectively) while â are significantly different (â 0.72
and 0.41, respectively)13 and could be related to the
higher negative charge concentration and then to a
higher basic efficiency for IL-1 with respect to IL-2.
Considering the role exerted by the solvent in MRH
because of its ability to assist proton abstraction in the
transition state the large decrease of HBA basicity (i.e.,
the decrease of â, see above) on going from tetrafluorobo-
rate to hexafluorophosphate well accounts for the de-
in IL-2 at a similar rate as observed in DMSO or DMF
but with the large advantage of an easy separation of
the reaction products).17 Moreover, ionic liquids do not
solvate the reagents but can largely affect the formation
of polar transition states, a fact that can be particularly
interesting for mechanistic studies.
Experimental Section
Materials. The Z-phenylhydrazone of 3-benzoyl-5-phenyl-
1
,2,4-oxadiazole and the relevant triazole were prepared accord-
crease observed in the reactivity (kII)IL-1/(kII)IL-2 = 20.
1
8
ing to a procedure reported. All other products were commer-
cial. BMIMBF and BMIMPF were dried on a vacuum line at
0 °C at least for 2 h and stored in a dryer under argon and
Anyway, the differences in the â values cannot completely
explain the observed “solvent” effect: indeed, ACN and
IL-2 have very similar â values (0.4013 and 0.41,
4
6
6
13
over calcium chloride. 1,4-Dioxane (for fluorescence) was used
without further purification. Amines were freshly distilled before
use.
respectively) but significantly different effects on the
N
reactivity of 1a [(kII
)
ACN/(kII
)
IL-2 ) 6.5, with ET values
UV-vis spectra and kinetic measurements were carried out
by using a spectrophotometer equipped with a peltier temper-
ature controller, able to keep the temperature within (0.1 K.
Kinetic Measurements and Calculations. Kinetic runs
were carried out at 298.1 K. The sample for a typical kinetic
run was prepared by injecting into a quartz cuvette (optical path
0.2 cm) 500 µL of IL, 50 µL of a solution of 1a in 1,4-dioxane,
and then 25 µL of a concentrated solution of amine in 1,4-
dioxane, previously thermostated. The concentration of 1a was
constant and equal to 0.00017 M, and the amine concentration
ranging from 0.0021 up to 0.0218 M. The absorbance at λ ) 360
nm was plotted versus time and showed a simple exponential
dependence. The reactions were all studied over six half-lives
or more. In all cases the correlation coefficient was higher than
moreover disfavoring ACN]. On the other hand it is well-
known that it is questionable whether the empirically
derived measurements of solvent properties could be
exclusively referred to room-temperature ionic liquids or
whether the different polarity of ionic liquids is also
affected by the nature of the tested compounds. For the
reasons above, we believe that the difference in reactivity
could be a consequence of the fact that, as reported, “there
is no single ionic liquid behavior; rather there are a range
of properties possible across the ever growing range of
ionic liquids discovered and yet to be discovered”.16
In conclusion, the data collected seem to indicate that
I Ls, besides the properties that make them very promis-
ing green solvents, can be useful for mechanistic studies.
Indeed, with the exception of an acid-base equilibrium
between imidazolium ion and amine, other interactions
15
0
.9998.
To evaluate the possibility of reusing I Ls, we tried a fast and
simple treatment of the solvent used. Thus, 5 mL of used IL-1
2
was extracted four times with 3 mL of Et O. The IL layer was
kept under vacuum at 60 °C for 2 h and reused. The apparent
first-order rate constants then obtained were reproducible within
(
such as substrate-IL, amine-IL, and amine-amine)
(
15% with respect to values determined in fresh IL-1.
seem to be absent or to have scarce relevance; thus,
solvent effects that often make difficult the mechanistic
interpretations for a reaction can be avoided. Therefore
the use of room-temperature ionic liquids as reaction
solvents appears a very useful tool both from a synthetic
and a mechanistic point of view. As a matter of fact they
show an effect on the reactivity similar to that exerted
by dipolar aprotic solvents such as ACN, DMSO, or DMF
All kinetic data were analyzed by means of the KALEIDA-
GRAPH 3.0.1 software.
Acknowledgment. We thank MIUR (PRIN 2004)
for financial support. Investigations were supported also
by the Universities of Bologna and Palermo (funds for
selected research topics).
JO048485N
(e.g., potassium 2-naphtholate reacts with 1-bromobutane
(
17) Earle, M. J.; MacCornac, P. B.; Seddon, K. R. Chem. Commun.
(
15) Armstrong, D. W.; He, L.; Liu, Y.-S. Anal. Chem. 1999, 71,
873-3876.
16) MacFarlane, D. R.; Forsyth, S. A. ACS Symp. Ser. 2003, 856,
64-272.
1998, 2245-2246.
3
2
(18) (a) Ruccia, M.; Spinelli, D. Gazz. Chim. Ital. 1959, 89, 1654-
1669. (b) Vivona, N.; Ruccia, M.; Frenna, V.; Spinelli, D. J. Heterocycl.
Chem. 1980, 17, 401-402.
(
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