An alternative to nitromethane as solvent: The promoting influence of nitro-functionalized imidazolium salts for synthesis and catalysis

Article abstract of DOI:10.1002/adsc.201100530

Nitromethane, a volatile and toxic organic compound, is commonly used as solvent for organic and catalytic reactions. In order to find an alternative for this specific nitro-containing organic solvent, the performance of some nitro-functionalized imidazolium salts such as 1-methyl-3-(4-nitrobenzyl) imidazolium hexafluorophosphate, 1-methyl-3-(4-nitrobenzyl)imidazolium tetrafluoroborate, 1-methyl-3-(4-nitrobenzyl)imidazolium bis(trifluoromethanesulfonyl)amide and 1,2-dimethyl-3-(4- nitrobenzyl) imidazolium hexafluorophosphate, was examined in some reactions including trimethylsilylation of alcohols with hexamethyldisilazane, ring-opening reactions of 2-aryl-3,4-dihydropyrans with thiophenols or thiols, and a copper- mediated oxidative coupling of alkynes. As expected, these imidazolium salts can indeed replace nitromethane in these reactions. Particularly, the imidazolium salt along with the metal catalyst, if involved, can be easily recovered and reused without significant loss of activity. The use of these nitro-functionalized imidazolium salts as alternative solvents for nitromethane not only confers a green aspect to the reaction system, but also facilitates a rational design of a catalytic system with the concept of green chemistry. Copyright

Full text of DOI:10.1002/adsc.201100530

FULL PAPERS
DOI: 10.1002/adsc.201100530
An Alternative to Nitromethane as Solvent: The Promoting
Influence of Nitro-Functionalized Imidazolium Salts for Synthesis
and Catalysis
Yajun Ren,a Minghao Li,a Jie Yang,a Jiajian Peng,b,* and Yanlong Gua,*
a
Institute of Physical Chemistry and Industrial Catalysis, School of Chemistry and Chemical Engineering, Hubei Key
Laboratory of Material Chemistry and Service Failure, Huazhong University of Science and Technology (HUST), 1037
Luoyu road, Hongshan District, Wuhan 430074, Peopleꢀs Republic of China
Fax: (086)-(0)27-8754-4532; e-mail: klgyl@hust.edu.cn
b
Key Laboratory of Organosilicon Chemistry and Material Technology, Ministry of Education, Hangzhou Normal
University, Hanzhou, 310012, Peopleꢀs Republic of China
E-mail: jipeng@hznu.edu.cn
Received: July 4, 2011; Revised: August 30, 2011; Published online: December 13, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100530.
Abstract: Nitromethane, a volatile and toxic organic kynes. As expected, these imidazolium salts can
compound, is commonly used as solvent for organic indeed replace nitromethane in these reactions. Par-
and catalytic reactions. In order to find an alternative ticularly, the imidazolium salt along with the metal
for this specific nitro-containing organic solvent, the catalyst, if involved, can be easily recovered and
performance of some nitro-functionalized imidazoli- reused without significant loss of activity. The use of
um salts such as 1-methyl-3-(4-nitrobenzyl)imidazoli- these nitro-functionalized imidazolium salts as alter-
um hexafluorophosphate, 1-methyl-3-(4-nitrobenz- native solvents for nitromethane not only confers a
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
um hexafluorophosphate, was examined in some
reactions including trimethylsilylation of alcohols Keywords: nitro-functionalized imidazolium salts;
with hexamethyldisilazane, ring-opening reactions of oxidative coupling of alkynes; ring-opening of dihy-
2-aryl-3,4-dihydropyrans with thiophenols or thiols, dropyran with nucleophiles; trimethylsilylation of al-
and a copper- mediated oxidative coupling of al- cohols with hexamethyldisilazane
Introduction
environmentally benign one, has gained much atten-
tion.[2] In order to make the replacement acceptable
One of the biggest problems posed to the chemical in- for the industry, it has to be done in a way that does
dustry is to continuously deal with the fact that all not stifle the technological development and that can
chemical plants rely heavily on toxic, hazardous and be accomplished with moderate economical cost. Fur-
flammable organic solvents.[1] Organic solvents used thermore, new solvents should lead to the same, or
in most of the synthetic processes in the chemical in- even more benefits than the traditional ones. There-
dustry evaporate into the atmosphere with detrimen- fore, replacing a traditional solvent in an industrial
tal effects on the environment as well as human process with a new one is not a simple task, and many
health. Most of the time, these volatile organic sol- aspects as well as their relative importance must be
vents are expensive to purchase, difficult to recycle or considered and balanced.[3]
reuse, and impractical to dispose of without incurring
substantial costs and/or adversely affecting the envi- pound that has been widely used as a solvent in or-
ronment and/or personnel. ganic reactions, separations, and purifications. Today,
Nitromethane is the simplest organic nitro com-
In order to solve these problems, the replacement data concerning the hazardous properties of nitrome-
of organic solvents, which are volatile and toxic, with thane are easily available in many handbooks. Be-
Adv. Synth. Catal. 2011, 353, 3473 – 3484
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
3473

Yajun Ren et al.
FULL PAPERS
cause nitromethane can detonate and cause serious
harm to people, in order to handle this solvent un-
eventfully, some unsafe conditions should be avoided
during its uses.[4] In some cases, for example, when it
is mixed with a few percent of certain compounds
such as amines, acids, and bases, nitromethane is “sen-
sitized” and can be easily detonated. However, be-
cause of its specific effect exhibited in some organic
reactions,[5] the risk does not seem noticeable for
many researchers who are using this solvent in combi-
nation with strong acidic catalysts.[6]
In order to minimize the risk of using nitromethane
as solvent, it is necessary to develop alternative sol-
vents to such a nitro-containing compound. The par-
ticular properties of nitromethane are most likely re-
Figure 1. Functionalized 1,3-dialkylimidazolium salts.
lying on the nitro group present in its molecular struc- was directly attached to a phenyl ring, it is not unrea-
ture. To find an alternative solvent for nitromethane, sonable to expect that the potential of these imidazo-
we have to keep the nitro part in the new solvent lium salts to explosion should be much lower than
molecule, and strategically avoid all the negative ef- that of nitromethane. By a simple estimation on the
fects, such as volatility, toxic and risk problems. For basis of their molecular structures, data of the imida-
this purpose, we turned to one of the advantages of zolium salts concerning explosion should be close to
ionic liquid materials with tunable physical properties. that of nitrobenzene. In addition to these nitro-func-
By changing the anion and cation, ionic liquids can be tionalized salts, two tertiary amine-functionalized imi-
prepared varying in polarity, viscosity, density, melting dazolium ionic liquids, AFIL 1 and AFIL 2, were also
point, and miscibility/solubility properties. These con- used in a metal-catalyzed reaction (Figure 1). Having
siderations are driving our efforts in developing an al- these imidazolium salts in hand, we then focused our
ternative molten salt solvent for nitromethane, and attention on replacing nitromethane in organic and
now we wish to report the use of the title compounds catalytic reactions by using these nitro-functionalized
in organic synthesis and catalysis.
imidazolium salts as environmentally benign solvents.
A common method to prepare a functionalized
ionic liquid involves generally the use of a haloalkane
that contains a functional group as a quaternization Results and Discussion
reagent for the N-alkylimidazole. However, to find a
reagent that contains both a nitro group and an ali- Silylation of hydroxy-containing compounds with
phatic haloalkane fragment is not very easy. Fortu- hexamethyldisilazane (HMDS) is one of the most
nately, Liu and his co-workers have described the syn- popular methods for protecting alcohols and phe-
thesis of some nitro-functionalized imidazolium ionic nols.[8] Although various catalysts have been reported
liquids quite recently.[7] In Liuꢀs report, 4-nitro-(bro- to be effective for this reaction, for practical synthesis,
momethyl)benzene was used as a key quaternization researchers still prefer to use an old and toxic system,
reagent to react with 1-alkylimidazole to form some pyridine+chlorotrimethylsilane, in which pyridine is
1-alkyl-3-(4-nitrobenzyl)-1H-imidazolium
bromide the solvent and chlorotrimethylsilane acts as catalyst.
salts, which can then be used in the ion-exchange syn- In order to develop an environmentally benign
thesis as precursors of the nitro-functionalized imida- method for silylation with HMDS, Kim has recently
zolium salts. Inspired by this method, we were able to reported a catalyst-free method, in which nitrome-
synthesize four nitro-functionalized imidazolium salts, thane was found to be a key promoting medium for
including
hexafluorophosphate
nitrobenzyl)imidazolium tetrafluoroborate (NFIS 2), range of alcohols and phenols, owing to the fact that
1-methyl-3-(4-nitrobenzyl)imidazolium the silylation reaction.[9] Although Kimꢀs method
A
(NFIS 1),
1-methyl-3-(4- avoids the use of a catalyst and is effective for a wide
ACHTUNGTRENNUNG
1-methyl-3-(4-nitrobenzyl)imidazolium bis(trifluoro- the reaction was conducted in nitromethane that is a
methanesulfonyl)amide (NFIS 3), and 1,2-dimethyl-3- volatile and explosive reagent, silylation with HMDS
(4-nitrobenzyl)imidazolium
hexafluorophosphate still needs improvement from the viewpoint of green
(NFIS 4) (Figure 1). It should be noted that three of synthesis.
these imidazolium salts, NFIS 1, NFIS 2, and NFIS 4,
Table 1 shows the results of silylation of benzyl al-
are solid at room temperature, and their melting cohol with HMDS in the presence of the nitro-func-
points are higher than 808C (see Supporting Informa- tionalized imidazolium salts. The reaction was con-
tion). Therefore, these salts are not room temperature ducted at room temperature and under solvent-free
ionic liquids. In view of the fact that the nitro group conditions. Because all the nitro-functionalized imida-
3474
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3473 – 3484

An Alternative to Nitromethane as Solvent: The Promoting Influence of Nitro-Functionalized Imidazolium Salts
O-silyl ether.[9] Although the performances of nitro-
Table 1. Silylation of benzyl alcohol with HMDS in the pres-
ence of nitro-containing compounds.[a]
methane and nitrobenzene in the model silylation re-
action are comparable with those of our nitro-func-
tionalized salts, these systems are suffering from the
difficulty of recovering the nitro-containing com-
pounds. In this context, using the nitro-functionalized
imidazolium salts as alternative substance is of prime
Entry
Catalyst (10 mol%)
Yield [%]
significance because the imidazolium salt, which is a
solid under the reaction conditions, could be easily re-
covered and reused. When the reaction scale was in-
creased to 20 mmol, NFIS 1 could be recycled for at
least 4 runs without significant loss of its activity
(Table 1, entries 10 and 11). This result not only dem-
onstrates the good recycling ability of NFIS 1, but
also shows that our method is applicable for a practi-
cal synthesis. It should be noted that a blank reaction
without any catalyst gave no product even after 5 h
under identical conditions (entry 12). Thus, NFIS 1
was proved to be the best catalyst for the model sily-
lation reaction.
With the optimized conditions in hand, we probed
the scope of the reaction with respect to the alcoholic
compounds. As evidenced by the results in Table 2, al-
cohols with different substituents, such as benzyl, fur-
furyl, 2-naphthylmethyl, 2-thienylethyl, homoveratryl,
and a-cyanobenzyl, smoothly reacted with HMDS,
producing the corresponding trimethylsilyl ethers gen-
1
NFIS 1
NFIS 1
NFIS 2
NFIS 3
NFIS 4
99
73
92
96
89
21
32
94
90
99
98
0
2[b]
3
4
5
6
7
8
9
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
nitromethane
nitrobenzene
NFIS 1
10[c]
11[c,d]
12
NFIS 1
[e]
–
[a]
Benzyl alcohol: 0.5 mmol, HMDS: 0.5 mmol, nitro-con-
taining compound: 0.05 mmol, room temperature, 1 h.
Reaction time, 0.5 h.
Benzyl alcohol, 20.0 mmol.
The fifth run.
[b]
[c]
[d]
[e]
No catalyst was used.
zolium salts are solid at room temperature, and in- erally in good yields (entries 1 to 8). In the presence
soluble in the reaction mixture, the salt behaves like a of NFIS 1, cinnamyl alcohol and propargyl alcohols
solid catalyst in the model reaction. We thought that could be selectively converted to the silyl ethers with-
the incomplete dissolution of the ionic liquid might out affecting the double and triple bonds (entries 9 to
result in an insufficient reaction. To our surprise, as 11). Alcohols containing the indolyl group, such as 1-
shown in Table 1, a yield of 99% was obtained after (2-hydroxyethyl)indole and 2-(hydroxymethyl)indole,
1 h reaction time (entry 1). With a decrease of the re- which are generally unstable under acidic conditions,
action time, the yield also decreases (entry 2). It were also examined in our system, and the corre-
should be noted that, in our system, the imidazolium sponding products were obtained in excellent yields
salt NFIS 1 was used in catalytic amounts (10 mol%). (entries 12 and 13). 1-Ferrocenylethanol also readily
Under identical conditions, some other nitro-function- participated in the reaction (entry 14). Notably, none
alized imidazolium salts, such as NFIS 2, NFIS 3, and of these reactions involved the use of an added cata-
NFIS 4, also worked well, but the yields of 2a were lyst. A Baylis–Hillman alcohol, 1p, which was pre-
slightly inferior (entries 3 to 5). Common ionic liquids, pared from 4-methoxybenzaldehyde and ethyl acry-
such as [BMIm]BF4 and [BMIM]PF6, were also used late and has been proven to be an active Micheal ac-
in this reaction; however, the yields obtained are ceptor in the aza-Michael reaction,[10] can also be sily-
rather poor (entries 6 and 7). These results imply that lated without formation of the aza-Michael adduct
the nitro group might play a key role in promoting with ammonia (entry 15). However, a limitation was
the trimethylsilylation reaction. In order to confirm observed with 2-(benzylamino)ethanol, which failed
our hypothesis, reactions in the presence of nitrome- to participate in the silylation reaction (entry 16),
thane and nitrobenzene were also examined under likely due to a preferred interaction of the amine with
identical conditions. As we expected, high yields were the nitro group that deactivates the imidazolium salt
obtained in these cases (entries 8 and 9), indicating catalyst. It is noteworthy that hydroxylgroups of
that the nitro group is indeed capable of promoting phenol derivatives, such as 2,4-dimethylphenol, could
the model reaction. Kim and others have shown that also be protected with this method (entry 17), thus ex-
the silylation might start from a coordination of the tending the generality of our method further. It
oxygen atom in the nitro group to the silicon atom of should be noted that the yields obtained here are
HMDS, which activates the silylating reagent and competitive with Kimꢀs system,[9] but even NFIS 1 was
allows an easy formation of the nitro-alcohol inter- used in only catalytic amounts. Furthermore, the easy
mediate that can then eliminate ammonia to form the recovery of NFIS 1 as well as the robust activity en-
Adv. Synth. Catal. 2011, 353, 3473 – 3484
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3475

Yajun Ren et al.
FULL PAPERS
Table 2. Silylation of alcohols with HMDS in the presence
dowed our system with some attractive green parame-
ters.
of NFIS 1.[a]
Nitro-functionalized salts were demonstrated, by
means of the above-mentioned results, to be a promis-
ing alternative to nitromethane as solvent. In order to
extend the applicability of this concept, we then tried
to use the nitro-functionalized imidazolium salts in
some catalytic systems that also involve the use of ni-
tromethane as solvent. A literature survey showed
that nitromethane has been widely used in acid-cata-
lyzed reactions as solvent. Particularly, in the nucleo-
philic substitution of benzylic alcohols, nitromethane
exhibited an outstanding promoting effect on the cat-
alytic reactions.[6] Whilst the positive effect of nitro-
methane as solvent in acid-catalyzed organic reactions
has been recognized and an explosive growth in re-
search on acid catalysis in this solvent has been wit-
nessed in the past few years, the potential negative ef-
fects of this nitro-containing solvent on the environ-
ment and safety aspects have been ignored almost
completely. With the nitro-functionalized imidazolium
salts, we might have a chance to solve these problems.
In order to evaluate the value of these nitro-func-
tionalized imidazolium salts in assisting acid catalysis,
we have to find an appropriate model reaction that
not only allows a direct use of the imidazolium salt as
an alternative solvent for nitromethane, but is also ca-
pable of gaining, more or less, benefit from the ration-
al design of a new catalyst system. We have recently
reported some ring-opening reactions of 2-aryl-3,4-di-
hydropyran and 2-alkoxy-3,4-dihydropyran with nu-
cleophiles, such as indole and thiophenol or thiol.[11]
This type of reaction was performed in nitromethane
by using manganese(II) chloride or bromide as cata-
lyst. Particularly, for the reaction of 2-aryl-3,4-dihy-
dropyran, a mechanistic investigation revealed that an
acid-catalyzed formation of a benzylcarbenium is the
key to render the reaction possible.[11a] Thus, this ring-
opening reaction is an acid-catalyzed reaction. Al-
though the catalysis was found to be quite unique and
effective for the synthesis of the target compounds,
owing to the following drawbacks: (i) the use of nitro-
methane, which is toxic and explosive reagent, as a
solvent; and (ii) difficulty of recycling the manganese
halide catalyst; the catalytic system still needs im-
provement from the viewpoint of green chemistry.
We thus investigated the ring-opening reaction of
2-aryl-3,4-dihydropyran 3a with 3,5-dimethylthiophe-
nol, 4a. As shown in Table 3, in nitromethane, the re-
action proceeded selectively by using manganese(II)
chloride tetrahydrate as catalyst, however, the yield
of the desired product 5a reached only 63% after 11 h
of reaction at 808C (entry 1). The reactions in other
solvents, such as toluene, 1,4-dioxane, DCE, and the
ionic liquid [BMIm]PF6, proceeded also sluggishly
(entries 2 to 5). Surprisingly, when a combination of
NFIS 1 and [BMIm]PF6 was used as solvent, a yield
Entry Alcohol
Time
[h]
Product Yield
[%]
1
2
1b
1c
1
1
2b
2c
90
88
3
4
1d
1e
1
1
2d
2e
99
90
5
6
1f
1g
1
1
2f
2g
80
97
7
8
1h
1i
1
1
2h
2i
79
83
9
1j
1
2j
89
74
10
1k
1l
1
1
2k
11
12
2l
84
81
1m 1
2m
13
14
1n
1o
1
1
2n
2o
83
99
15
16
1p
1
2p
97
1q
1r
1
3
–
0
17
2q
84
[a]
Alcohols, 1.0 mmol; HMDS: 1.0 mmol; NFIS 1,
0.1 mmol; room temperature.
3476
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3473 – 3484

An Alternative to Nitromethane as Solvent: The Promoting Influence of Nitro-Functionalized Imidazolium Salts
Table 3. Ring-opening reaction of 3a with 4a catalyzed by acids.[a]
Entry
Catalyst
Solvent[b]
Co-solvent
Yield [%]
1
2
3
4
5
6
7
8
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
LiBr
CH3NO2
toluene
1,4-dioxane
DCE
–
–
–
–
A
N
E
ACHTUNGTRENNUNG
G
E
63
trace
trace
32
–
43
NFIS 1
NFIS 3
NFIS 1
NFIS 1
NFIS 1
NFIS 1
NFIS 1
NFIS 1
NFIS 1
NFIS 1
95
94[c]
40
9
H3BO3
MnBr2
ZnCl2
20
58
56
55
30
43
96
10
11
12
13
14
15[c]
E
T
E
R
Sc
N
FeCl3
InCl3
MnCl2·4H2O
A
[a]
3a: 0.25 mmol; 4a: 0.3 mmol; NFIS 1: 0.25 mmol; [BMIm]PF6: 100 mg; catalyst: 0.05 mmol.
When organic solvent was used, it was added in a volume of 0.5 mL.
Pure ethyl acetate was used for extracting the product.
Reused in third run.
[b]
[c]
[d]
of 95% was obtained under identical conditions place nitromethane in this acid-catalyzed reaction,
(entry 6). It should be noted that, because NFIS 1 is a but is also capable of enhancing, to some extent, the
solid at room temperature, in the absence of catalytic activity of MnCl2·4H2O, rendering eventually
[BMIm]PF6, the ionic phase tended to solidify during the model reaction to proceed toward completion.
the extraction of product, making thus the extraction
Because the ionic phase, NFIS 1+[BMIm]PF6, is
problematic. Therefore, small amount of immiscible with most of the non-polar organic sol-
a
[BMIm]PF6 was added for the purpose of facilitating vents, we are thus able to extract, at the end of the re-
isolation of the product. Because the PF6 anion is action, the formed organic products with a mixture of
rather unstable in the presence of water, therefore the n-heptane and ethyl acetate (v/v=5/1). This proce-
promoting effect might have resulted from the gener- dure not only allows an easy isolation of the products
ation of HF. To clarify this point, a combination of but also facilitates recycling of the ionic phase, where-
NFIS 3 and [BMIm]NTf2 was also examined, and in in the metal catalyst is immobilized. As shown in
this case, the reaction proceeded very well (entry 7). Table 3, the recovered ionic liquid as well as the man-
Because the NTf2 anion was considered as a stable ganese chloride catalyst can be reused at least three
species toward water, the possible influence of the hy- times without significant loss of activity (entry 15).
drolysis of PF6 anion on the reaction has thus been Table 4 gives also the results of manganese chloride
excluded. Under identical conditions, many other cat- tetrahydrate-catalyzed ring-opening reactions of 3a-
alysts, such as LiBr, H3BO3, MnBr2, ZnCl2, Sc
ACHTUNGTRENNUNG
FeCl3, and InCl3, were also examined. However, the NFIS 1/AHCTUNGTRENNUNG
yields obtained are much lower than that with manga- in order to improve the reaction yields. As expected,
nese chloride tetrahydrate (entries 8 to 14). There- this system has proved to be very effective for these
fore, MnCl2·4H2O/ACHTUNTGRNENUG(NFIS 1+CAHTUNGTERN[NUGN BMIm]PF6) was proven ring-opening reactions, and generally, good to excel-
to be an optimal system for the model reaction in lent yields could be obtained. Thus, with this type of
Table 3. All these results demonstrate that the nitro- ring-opening reaction, the capacity of the nitro-func-
functionalized imidazolium salt is not only able to re-
Adv. Synth. Catal. 2011, 353, 3473 – 3484
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3477

Yajun Ren et al.
FULL PAPERS
Table 4. Substrate scope of manganese(II) halide-catalyzed ring-opening reactions of dihydropyrane with thiols or thiophe-
nols.[a]
Entry
1
Catalyst
MnBr2
Dihydropyran
RSH
Product
Yield [%]
98
3a
4b
4c
5b
2
MnCl2·4H2O
3a
5c
95
3
4
5
MnCl2·4H2O
MnCl2·4H2O
MnCl2·4H2O
3a
3a
3a
4d
4e
4f
5d
5e
5f
85
83
84
6
7
MnBr2
3a
3a
4g
4h
5g
5h
98
71
MnCl2·4H2O
8
MnBr2
MnBr2
MnBr2
3b
3c
3d
4b
4b
4b
5i
5j
5k
77
84
76
9
10[b]
[a]
Dihydropyran: 0.25 mmol, thiols or thiophenols: 0.3 mmol, catalyst: 0.05 mmol, NFIS 1: 0.25 mmol, [BMIm]PF6: 100 mg.
1008C, 24 h.
[b]
tionalized imidazolium salt for assisting acid catalysis mogeneous and heterogeneous systems is appealingly
was successfully demonstrated.
needed.
A literature survey also stated that, for Glaser oxi-
The good capacity of the nitro-functionalized imi-
dazolium salts encourages us to further use them in dative homo-coupling reactions of alkynes, Cu(I) was
transition metal-catalyzed reactions. The Glaser oxi- used in the most cases, whereas Cu(II) has been
dative homo-coupling reaction of terminal alkynes is rarely investigated,[14] probably because of its low ac-
an important organic transformation that can pro- tivity. In view of the fact that: (i) Cu(II) salts are gen-
duce, in a direct way, diyne derivatives, which are erally cheaper than Cu(I) salts, and (ii) Cu(II) salts
very useful building blocks in organic synthesis.[12] In are more stable than the other salts, we focused our
the past five years, a plethora of methods has flourish- attention on investigating Glaser oxidative homo-cou-
ed around Glaser coupling reactions by using Cu spe- pling reactions of alkyne with Cu(II) salts.
cies as catalyst.[13] Generally, in this type of reaction,
solid catalysts showed not only a good performance nylacetylene (6a) was investigated using Cu
but also, in some cases, a robust activity during the catalyst in different solvent systems. In the absence of
catalyst recycling. Unfortunately, the costs of many Cu(OAc)2, no product was detected (entry 1). The
solid catalysts are generally high, and thus restrict its catalytic activities of Cu(OAc)2 are rather poor in
As shown in Table 5, the oxidative coupling of phe-
(OAc)2 as
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
application in practical synthesis. On the contrary, ionic liquids, such as [BMIm]PF6, [BMIm]BF4, and
many homogeneous Cu catalysts are very cheap, but [BMIm]Cl (entries 2 to 4). Interestingly, in
often suffer from inefficiency in recycling the catalyst [BMIm]PF6, when CuACTHNURGTNE(UNG OAc)2 was used in conjunction
and dealing with toxic bases or ligands. Therefore, a with a tertiary amine-functionalized ionic liquid,
new system that can combine both advantages of ho- AFIL 1, the yield of 7a could be increased to 47%
3478
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3473 – 3484

An Alternative to Nitromethane as Solvent: The Promoting Influence of Nitro-Functionalized Imidazolium Salts
Table 5. Glaser coupling of phenylacetylene in different conditions.[a]
Entry
Alkyne
Cu catalyst
–
Solvent
Additive (10 mol%)
Product
Yield [%]
1
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6a
6b
6c
6d
6e
A
–
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7a
7b
7c
7d
7e
0
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16[b]
17[c]
18[d]
19[e]
20
21
22
23
Cu
Cu
Cu
N
G
–
–
–
trace
trace
trace
47
trace
22
89
79
93
46
trace
71
51
63
20
31
50
99
99
Cu
A
AFIL 1
AFIL 2
Cu
Cu
Cu
triethylamine
AFIL 1+nitrobenzene
AFIL 1+nitromethane
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
AFIL 1+NFIS 1
Cu
A
Cu
A
CuCl2
CuSO4
CuCl
CuBr
CuI
Cu
Cu
Cu
Cu
N
Cu
Cu
Cu
Cu
N
97
93
98
[a]
Phenylacetylene, 1.0 mmol; Cu catalyst, 0.025 mmol; solvent, 0.5 mL; additive, 0.1 mmol for each component.
258C.
[b]
[c]
[d]
[e]
Cu
Reaction time, 3 h.
Cu(OAc)2, 10 mol%.
ACHTUNGTRENNUNG(OAc)2, 2.0 mol%.
ACHTUNGTRENNUNG
(entry 5). Interestingly, when AFIL 2, that has a yield of 7a could be increased to 89% and 79%, re-
methyl group in the C-2 position of the imidazolium spectively (entries 8 and 9). Inspired by these promis-
ring, was used instead of AFIL 1, only traces of 7a ing results, we then replaced the nitro-containing
were obtained (entry 6). Furthermore, a poor yield compounds by a nitro-functionalized imidazolium
was also obtained when triethylamine was used in salt, NFIS 1. As expected, the nitro-functionalized
conjunction with [BMIm]PF6 under identical condi- imidazolium salt showed a significant synergistic pro-
tions (entry 7). These results indicates that both the moting effect with the tertiary amine-functionalized
1,3-dialkyl-2H-imidazolium cation and the diethylami- ionic liquid, AFIL 1, in the model Glaser reaction,
no group are important for improving the catalytic ac- and finally, the reaction yield reached 93% (entry 10).
tivity of Cu
In order to further improve the catalytic acitivty of CuSO4, CuCl, CuBr, and CuI, were examined in the
Cu(OAc)2 in the model reaction of Table 5, we then optimal ternary ionic system composed of
A
In a later study, other Cu salts, such as CuCl2,
ACHTUNGTRENNUNG
turned to search for a suitable co-catalyst. We found [BMIm]PF6, AFIL 1, and NFIS 1, but the yields ob-
unexpectedly that nitro-containing compounds, such tained were rather poor (entries 11 to 15). These re-
as nitrobenzene and nitromethane, exhibited a signifi- sults imply that Cu
cant promoting effect on the Cu(OAc)2-catalyzed alyze the model reaction in this three-component
Glaser coupling reaction in this ionic phase, and the ionic phase system. Further investigations revealed
ACHTUNGERTN(NUNG OAc)2 has a unique ability to cat-
AHCTUNGTRENNUNG
Adv. Synth. Catal. 2011, 353, 3473 – 3484
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3479

Yajun Ren et al.
FULL PAPERS
that the reaction was also affected by the tempera-
ture, catalyst amount, and reaction time, and the opti-
mal condition are 608C, 5 mol% of catalyst, and 6 h
of reaction (entries 16 to 18).
The aim of this study is to develop a new catalyst
system that not only is capable of catalyzing Glaser
coupling reactions efficiently, but also could be recy-
cled easily and steadily. We therefore investigated the
recyclability of this system. During the condition opti-
mization, we found that the desired product, 7a, could
be formed quantitatively in the presence of 10 mol%
of CuACHTUNGTRENNUNG(OAc)2 (Table 5, entry 19). The quantitative
Figure 3. Reuse of the CuACTHNUTRGNE(UNG OAc)2/ionic liquid system.
transformation allowed us to isolate the product with
a very simple procedure. After the reaction, the
system was extracted repeatedly with n-heptane until and recyclable. By means of these promising results,
the upper organic phase showed no strong UV re- the nitro-functionalized imidazolium salt was demon-
sponse. The product could be obtained by following strated again to be a useful reagent for transition
distillation of the combined organic phases (Figure 2). metal-catalyzed organic reactions.
Further analysis of the product with 1H NMR re-
Although we cannot yet offer an explanation for
vealed that no detectable contamination of the imida- the high activity of Cu(OAc)2 in the ionic phase, the
AHCTUNGTRENNUNG
zolium salt could be observed, indicating the good good performance might be related to a synergistic in-
performance of this isolation method. This procedure teraction of AFIL 1, Cu(II), and NFIS 1. In view of
not only avoids the use of silica gel column chroma- the fact that replacing AFIL 1 by AFIL 2, which con-
tography for the product isolation, but also allows an tains a methyl group in the C-2 position of the imida-
easy recovery of n-heptane, thus minimizing the gen- zolium ring, resulted in a dramatic decrease of the re-
eration of waste. The recovered ionic phase as well as action yield, it is thus not unreasonable to expect that
the catalyst could be reused at least five times without a carbene fragment, which could be generated from
any significant loss of the catalytic activity (Figure 3). the 1,3-dialkyl-2H-imidazolium salt, might be in-
Furthermore, some other terminal alkynes can also be volved in the catalytic cycle. In addition, because of
converted to the corresponding dialkynes in excellent the following reasons: (i) Cu
yields by means of this system (Table 5, entries 20 to work in a normal ionic liquid, [BMIm]PF6 in the ab-
23). Therefore, the combination of Cu(OAc)2 with sence of AFIL 1; and (ii) the NFIS 1/AFIL 1 system
ACHTUNGRTEN(NUGN OAc)2 catalyst does not
AHCTUNGTRENNUNG
imidazolium salts offers a robust and efficient catalyst could be reused steadily although AFIL 1 was used in
system for Glaser coupling reactions. Particularly, the catalytic amounts, the diethylamino group in AFIL 1
use of a nitro-functionalized imidazolium salt is pivo- does not seem to work as a base that the conventional
tal for enhancing the catalyst system to be efficient CuACTHNUTRGNEUNG
(OAc)2 catalyst systems needed.[14] Therefore, we
suspect that the diethylamino group can play a key
role in constructing a catalytically active species.
Shreeve and co-workers have reported a catalyst
system for the oxidative coupling of terminal alkynes,
in which a tertiary amine-functionalized imidazolium
ionic liquid was used in conjunction with
a
PdCl2A
CTHUNGTRENNUNG
effect of the tertiary amine group and the imidazoli-
um ring was observed in Shreeveꢀs system. But, a pal-
ladium-carbene complex (I) that was prepared by
using a 1-butyl-3-methylimidazolium salt as precursor
and a triphenylphosphine as an additional ligand has
been reported by Ryu and Nokihara, to be catalytical-
À
ly active for many C C coupling reactions, such as
Suzuki, Stille, Sonogashira, and Heck reactions.[16] It
should be noted that preparation of (I) is quite easy,
and can be performed under mild conditions. An or-
ganic base, diisopropylamine, was sufficient for the re-
moval of the proton in the C-2 position of the imida-
zolium ring.16(a) Inspired by these results, and taking
into consideration the significant effect of both the
Figure 2. Recycling procedure of CuACTHNUTRGENUN(G OAc)2/ionic phase
system.
3480
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3473 – 3484

An Alternative to Nitromethane as Solvent: The Promoting Influence of Nitro-Functionalized Imidazolium Salts
tetrahydrate for the ring-opening of dihydropyran 3a
with thiophenol could be significantly improved in re-
lation to its counterpart deriving from the nitrome-
thane system. An unexpected subtle synergistic pro-
moting effect of NFIS 1 and AFIL 1 was also ob-
served in CuACTHUNRGTNEUNG(OAc)2-catalyzed oxidative coupling of
phenylacetylene. In all the reactions studied, the imi-
dazolium salt along with the metal catalyst, if in-
volved, could be easily recovered and reused without
significant loss of activity. The simple procedures for
Figure 4. Possible Cu species for catalyzing the Glaser cou-
pling of 6a.
1,3-dialkyl-2H-imidazolium ring and the diethylamino their preparation as well as the easy recovery and
group on the catalytic activity of Cu(OAc)2, we thus reuse of these novel materials are expected to con-
AHCTUNGTRENNUNG
proposed a possible structure of the catalytic active tribute to the development of more benign systems
species as shown in Figure 4. Under the reaction con- for organic synthesis and catalysis.
ditions, a carbene fragment might be somehow
formed. Because of the presence of a tertiary amino
group, the newly formed species might act as a chelat- Experimental Section
ing NHC-N donor hybrid ligand[17] to coordinate with
All chemicals were used as received. All reactions were con-
ducted in a 10-mL V-type flask equipped with triangle mag-
the copper ion center, generating the Cu-carbene
complex (II) that might possess a moderate activity
for catalyzing the model Glaser coupling reaction. It
should be noted that coordination of the diethylamino
group to a metal center can form a six-membered
ring that might allow an easy construction of the in-
termediate (II). In fact, such a coordination of a nitro-
gen donor-functionalized carbene to a metal center,
rhodium, has been reported to be possible by Herr-
mann.[18] It should be noted also that, although our
hypothesis seems to be viable for explaining the syn-
ergistic effect of 1,3-dialkyl-2H-imidazolium salt and
netic stirring. In
a typical silylation reaction, NFIS 1
(0.05 mmol) was mixed with benzyl alcohol (0.5 mmol) and
HMDS (0.5 mmol) under air. The mixture was stirred for
1 h at room temperature. After reaction, the mixture was
mixed with a mixture of ethyl acetate and n-heptane (v/v=
1/5, 2.0 mL). The upper organic solution was then loaded
onto a preparative TLC plate. The product 2a was obtained
in a yield of 99%.
The other reactions were performed as an analogous pro-
cedure, and the details are available in the electronic Sup-
porting Information.
the diethylamino group for the CuACTHNUTRGNEUNG(OAc)2 catalyst, the
For the reuse experiment, the reaction scale was increased
to 20.0-mmol. After the reaction, NFIS 1 was filtered off
and washed with n-heptane (4 mLꢂ3). The recovered
NFIS 1 was directly submitted to the next run after drying
at room temperature for 12 h. The product 2a was isolated
through silica column chromatography by using a solution
composed of ethyl acetate and n-heptane (v/v=1/10) as
eluting solvent.
exact reason of why NFIS 1 could significantly im-
prove the catalytic activity is still unclear. Futher-
more, because we are failed to obtain supportive data
by using ESI-MS, the mechanism still remains to be
delineated in detail. We are now actively pursuing on
investigating the mechanism of these catalysis.
Conclusions
Spectroscopic Data of the New Compounds
1,2-Dimethyl-3-(4-nitrobenzyl)imidazolium hexafluorophos-
phate (NFIS 4): Colorless solid; mp 170–1728C; 1H NMR
[(CD3)2SO]: d=2.57 (s, 3H), 3.77 (s, 3H), 5.60 (s, 2H), 7.56
(d, J=7.2 Hz, 2H), 7.72 (dd, Ja =2.0 Hz, Jb =14.0 Hz,2H),
8.26 (d, J=8.4 Hz, 2H); 13C NMR: d=9.5, 30.7, 35.0, 49.9,
121.4, 123.0, 124.0, 128.9, 142.1, 145.2, 147.5; IR: n=3164,
In conclusion, nitro-functionalized imidazolium salts
were proven to be environmentally benign alterna-
tives to nitromethane that is a volatile, explosive, and
widely used organic solvent. Three reactions including
the trimethylsilylation of alcohols with HMDS, the
ring-opening reaction of 2-aryl-3,4-dihydropyrans with 3084, 2995, 2972, 2859, 1601, 1523, 1450, 1418, 1388, 1349,
1293, 1275, 1190, 1168, 1115, 1083, 1046, 1017, 976, 951, 848,
833, 782, 736, 679, 646, 631, 558 cmÀ1; HR-MS (ESI): m/z=
232.1089, calcd. for C12H14N3O2 [M]+: 232.1086 (cation part
of salt).
thiophenols or thiols, and a copper-mediated oxida-
tive coupling of alkynes, were examined, and in all
these reactions, the nitro-functionalized imidazolium
salts proved to be not only capable of replacing nitro-
methane but are also profitable for the selected
model reactions. For example, the yields of the trime-
thylsilylation of alcohols with HMDS over NFIS 1 are
competitive with that obtained by using nitromethane
as solvent but NFIS 1 was used in only catalytic
(3,4-Dimethoxyphenethoxy)trimethylsilane (2e): Yellow
1
pale liquid; H NMR (CDCl3): d=0.15 (s, 9H), 2.84 (t, J=
6.8 Hz, 2H), 3.83 (t, J=7.2 Hz, 2H), 3.83 (s, 3H), 3.92 (s,
3H), 6.79–6.86 (m, 3H); 13C NMR: d=0.5, 39.0, 55.7, 55.8,
64.0, 111.1, 112.4, 120.9, 131.6, 147.4, 148.7; IR: n=3539,
2998, 2953, 2909, 2835, 2736, 1727, 1591, 1515, 1464, 1417,
amounts. The catalytic activity of manganese chloride 1334, 1261, 1156, 1141, 1091, 1031, 930, 876, 842, 807, 759,
Adv. Synth. Catal. 2011, 353, 3473 – 3484
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3481

Yajun Ren et al.
FULL PAPERS
759, 690, 632 cmÀ1 ; HR-MS (ESI): m/z=277.1228, calcd. for
C13H22NaO3Si [M+Na]+: 277.1236.
Methyl 2-acetyl-5-(4-methoxyphenyl)-5-(o-tolylthio)penta-
noate (5c): Mixture of diastereomers; yellow liquid;
1H NMR (CDCl3): d=1.82–1.94 (m, 4H), 2.13 (s, 1.5H),
2.14 (s, 1.5H), 2.29 (s, 3H), 3.38 (m, 1H), 3.68 (s, 1.5H),
3.68 (s, 1.5H), 3.76 (s, 3H), 4.02–4.06 (m, 1H), 6.78 (d, J=
8.8 Hz, 2H), 7.10–7.15 (m, 5H), 7.22–7.26 (m, 1H);
13C NMR: d=20.8, 26.3, 26.4, 28.9, 29.0, 33.9, 34.0, 51.9,
52.0, 52.5, 52.6, 55.3, 59.2, 59.3, 114.0, 126.3, 127.2, 127.3,
128.8, 130.3, 132.6, 132.7, 133.1, 133.2 ,134.1, 134.2, 140.0,
140.1, 158.9, 170.0, 170.1, 202.7; IR: n=3058, 3003, 2952,
2838, 1740, 1713, 1608, 1510, 1459, 1438, 1357, 1300, 1247,
1175, 1147, 1112, 1062, 1032, 989, 913, 835, 746, 680,
1-[2-(Trimethylsilyloxy)ethyl]-1H-indole (2m): Yellow
liquid; 1H NMR (CDCl3): d=0.15
ACTHNUTRGNE(NUG m, 9H), 4.02 (t, J=
5.6 Hz, 2H), 4.35 (t, J=5.2 Hz, 2H), 6.67 (d, J=2.0 Hz,
1H), 7.27–7.33 (m, 2H), 7.37–7.39 (m, 1H), 7.50 (t, J=
7.6 Hz, 1H), 7.80 (d, J=6.8 Hz, 1H); 13CNMR: d=À0.6,
48.6, 48.7, 61.8, 101.2, 101.6, 109.5, 119.4, 119.7, 121.0, 121.2,
121.5, 121.8, 128.7, 128.8, 136.3; IR: n=3407, 3054, 2957,
2870, 1612, 1512, 1463, 1399, 1359, 1334, 1315, 1252, 1200,
1111, 1077, 1013, 922, 843, 741, 718, 691, 612 cmÀ1; HR-MS
(ESI): m/z=256.1126, calcd. for C13H19NNaOSi [M+Na]+:
256.1134.
545 cmÀ1
;
HR-MS (ESI): m/z=409.1437, calcd. for
C22H26NaO4S [M+Na]+: 409.1449.
2-[(Trimethylsilyloxy)methyl]-1H-indole (2n): Brown
solid; mp 68–708C; 1H NMR (CDCl3): d=0.21 (s, 9H),
4.77–4.87 (m, 2H), 6.39 (s, 1H), 7.21–7.26 (m, 2H), 7.36 (d,
J=8.0 Hz, 1H), 7.61 (d, J=7.6 Hz, 1H), 8.46 (s, 1H);
13C NMR: d=À0.4, 58.6, 99.5, 100.5, 110.9, 119.8, 120.5,
121.8, 128.1, 128.4, 136.1, 136.4, 137.7, 137.8; IR: n=3394,
3375, 3056, 2959, 2937, 1456, 1428, 1369, 1342, 1290, 1250,
1219, 1136, 1052, 970, 926, 843, 796, 753, 736, 705, 630, 609,
Methyl 2-acetyl-5-[(2,4-dimethylphenyl)thio]-5-(4-meth-
oxyphenyl)pentanoate (5d): Mixture of diastereomers;
yellow liquid; 1H NMR (CDCl3): d=1.79–1.86 (m, 2H),
1.88–1.94 (m, 2H), 2.13 (s, 1.5H), 2.14 (s, 1.5H), 2.25 (s,
6H), 3.35–3.39 (m, 1H), 3.68 (s, 3H), 3.77 (s, 3H), 3.93–3.97
(m, 1H), 6.78 (d, J=8.4 Hz, 2H), 6.86 (d, J=8.0 Hz, 1H),
6.96 (s, 1H), 7.09–7.14 (m, 3H); 13C NMR: d=20.8, 21.2,
26.4, 26.5, 29.0, 33.7, 33.9, 52.4, 52.5, 52.6, 52.7, 55.4, 59.3,
59.4, 114.0, 127.2, 128.8, 130.4, 130.5, 131.2, 133.5, 133.8,
133.9, 137.5, 137.6, 140.6, 140.7, 158.9, 170.1, 170.2, 202.8;
IR: n=3000, 2952, 2932, 2837, 1741, 1715, 1647, 1608, 1510,
1438, 1357, 1301, 1248, 1176, 1145, 1112, 1033, 879, 814, 763,
722, 687, 664, 630 cmÀ1; HR-MS (ESI): m/z=423.1592,
calcd. for C23H28NaO4S [M+Na]+: 423.1606.
533 cmÀ1
C12H17NNaOSi [M+Na]+: 242.0977.
Ethyl 2-[(4-methoxyphenyl)(trimethylsilyloxy)methyl]-
;
HR-MS (ESI): m/z=242.0969, calcd. for
1
acrylate (2p): Yellow liquid; H NMR (CDCl3): d=0.15 (s,
9H), 1.29 (t, J=6.4 Hz, 3H), 3.84 (s, 3H), 4.20 (q, J=
6.8 Hz, 2H), 5.68 (s, 1H), 6.08 (t, J=1.6 Hz, 1H), 6.35 (s,
1H), 6.91 (d, J=8.8 Hz, 2H), 7.33–7.36ACTHNUTRGNEUNG
(m, 2H); 13C NMR:
Methyl 2-acetyl-5-(4-methoxyphenyl)-5-[(4-methoxyphe-
nyl)thio]pentanoate (5e): Mixture of diastereomers, yellow
liquid; 1H NMR (CDCl3): d=1.77–1.93 (m, 4H), 2.14 (s,
1.5H), 2.15 (s, 1.5H), 3.35–3.40 (m, 1H), 3.69 (s, 1.5H), 3.69
(s, 1.5H), 3.76 (s, 1.5H), 3.76 (s, 1.5H),3.77 (s, 1H), 3.88–
3.92 (m, 1H), 6.72 (d, J=0.8 Hz, 1H), 6.75 (d, J=0.8 Hz,
1H), 6.77 (s, 1H), 6.79 (d, J=0.8 Hz, 1H), 7.04 (d, J=
8.8 Hz, 2H), 7.14 (d, J=2.4 Hz, 1H), 7.16 (d, J=2.4 Hz,
1H); 13C NMR: d=26.3, 26.4, 28.8, 28.9, 33.3, 33.4, 52.5,
52.6, 53.8, 53.9, 55.3, 55.4, 59.2, 59.3, 113.8, 113.9, 114.3,
128.9, 136.2, 158.8, 159.7, 170.0, 170.1, 202.8; IR: n=3062,
3001, 2953, 2837, 1742, 1715, 1645, 1593, 1508, 1495, 1459,
1441, 1358, 1284, 1247, 1176, 1150, 1109, 1080, 991, 913, 888,
830, 800, 736, 698, 641, 609, 527, 503 cmÀ1; HR-MS (ESI):
m/z=425.1397, calcd. for C22H26NaO5S [M+Na]+: 425.1399.
Methyl 2-acetyl-5-(4-methoxyphenyl)-5-[(2-methoxyphe-
nyl)thio]pentanoate (5f): Mixture of diastereomers; yellow
liquid; 1H NMR (CDCl3): d=1.82–1.91 (m, 4H), 2.13 (s,
1.5H), 2.14 (s, 1.5H), 3.37–3.40 (m, 1H), 3.67 (s, 1.5H), 3.67
(s, 1.5H), 3.74 (s, 3H), 3.85 (s, 3H), 4.22–4.29 (m, 1H), 6.76–
6.81 (m, 4H), 7.14–7.18 (m, 4H); 13C NMR: d=26.3, 26.4,
28.8, 33.8, 33.9, 50.1, 50.2, 52.5, 55.3, 55.8, 59.2, 110.7, 113.8,
120.8, 122.7, 128.7, 128.8, 133.6, 133.7, 158.7, 169.9, 170.0,
202.8; IR: n=3061, 3002, 2953, 2837, 1742, 1715, 1647, 1609,
1580, 1511, 1472, 1435, 1358, 1300, 1272, 1246, 1177, 1149,
1111, 1071, 1026, 913, 836, 797, 753, 685, 648, 632, 611,
d=0.0, 14.1, 55.1, 60.5, 72.2, 76.8, 77.2, 77.5, 113.5, 123.5,
128.4, 134.5, 144.1, 159.0, 166.0; IR: n=2958, 2904, 2837,
1719, 1612, 1511, 1464, 1371, 1299, 1251, 1173, 1146, 1075,
1036, 960, 888, 960, 753, 688, 661, 615, 545 cmÀ1; HR-MS
(ESI): m/z=331.1338, calcd. for C16H24NaO4Si [M+Na]+:
331.1342.
Methyl 2-acetyl-5-[(3,5-dimethylphenyl)thio]-5-(4-meth-
oxyphenyl)pentanoate (5a): Mixture of diastereomers;
1
yellow liquid; H NMR (CDCl3): d=1.73–1.83 (m, 4H), 2.05
(s, 1.5H), 2.06 (s, 1.5H), 2.15 (s, 6H), 3.27–3.32 (m, 1H),
3.60 (s, 3H), 3.70 (s, 3H), 4.00–4.05 (m, 1H), 6.73 (d, J=
8.8 Hz, 3H), 6.79 (s, 2H), 7.06 (d, J=8.8 Hz, 2H);
13C NMR: d=21.3, 26.3, 26.4, 28.8, 28.9, 33.8, 33.9, 52.4,
52.5, 55.4, 59.2, 59.3, 114.0, 128.9, 129.0, 129.1 , 130.0 ,130.1,
133.3, 133.4, 134.3, 134.4, 138.3, 158.9, 170.0, 170.1, 202.8;
IR: n=3028, 2954, 2917, 2837, 1741, 1713, 1646, 1606, 1581,
1509, 1454, 1437, 1357, 1301,1247, 1174, 1144, 1110, 1088,
1031, 914, 884, 832, 799, 737, 687, 631, 580 cmÀ1; HR-MS
(ESI): m/z=423.1591, calcd. for C23H28NaO4S [M+Na]+
423.1606.
Methyl 2-acetyl-5-(4-methoxyphenyl)-5-(phenylthio)pen-
tanoate (5b): Mixture of diastereomers; yellow liquid;
1H NMR (CDCl3): d=1.85–1.91 (m, 4H), 2.13 (s, 1.5H),
2.14 (s, 1.5H), 3.35–3.40 (m, 1H), 3.67 (s, 1.5H), 3.67 (s,
1.5H), 3.76 (s, 3H), 4.06–4.10 (m, 1H), 6.79 (d, J=8.4 Hz,
2H), 7.13 (d, J=8.8 Hz, 2H), 7.18–7.26 (m, 5H); 13C NMR:
d=26.2, 26.3, 28.8, 28.9, 33.7, 33.9, 52.5, 52.6, 52.7, 55.3,
59.1, 59.2, 113.9, 127.2, 127.3, 128.7, 128.8, 132.5, 132.6,
133.1, 134.7, 158.8, 169.9, 167.0, 202.7; IR: n=3057, 3001,
2953, 2837, 1742, 1715, 1647, 1609, 1582, 1511, 1438, 1358,
1302, 1249, 1177, 1147, 1112, 1032, 892, 835, 743, 693, 611,
538 cmÀ1
;
HR-MS (ESI): m/z=425.1392, calcd. for
C22H26NaO5S [M+Na]+: 425.1399.
Methyl
2-acetyl-5-[(4-chlorophenyl)thio]-5-(4-methoxy-
phenyl)pentanoate (5g): Mixture of diastereomers; yellow
liquid; 1H NMR (CDCl3): d=1.81–1.92 (m, 4H), 2.15 (s,
1.5H), 2.16 (s, 1.5H), 3.35–3.40 (m, 1H),3.69 (s, 1.5H), 3.69
(s, 1.5H), 3.77 (s, 3H), 4.01–4.05 (m, 1H), 6.78 (d, J=
8.4 Hz, 2H), 7.09 (d, J=8.4 Hz, 2H), 7.11–7.17 (m, 4H);
558 cmÀ1
C21H24NaO4S [M+Na]+: 395.1293.
;
HR-MS (ESI): m/z=395.1288, calcd. for
3482
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3473 – 3484

An Alternative to Nitromethane as Solvent: The Promoting Influence of Nitro-Functionalized Imidazolium Salts
13C NMR: d=26.2, 26.3, 28.9, 29.0, 33.7, 33.8 ,52.6, 52.7,
53.0, 53.1, 55.4, 59.2, 59.3, 114.0, 128.9, 129.0, 132.8, 132.9,
Acknowledgements
133.1, 133.2, 133.5, 133.6, 134.1, 134.2, 159.0, 169.9, 170.0,
202.6; IR: n=3001, 2953, 2919, 1739, 1713, 1648, 1609, 1509,
1471, 1437, 1386, 1356, 1301, 1245, 1176, 1148, 1092, 1033,
1012, 960, 903, 881, 819, 775, 743, 678, 630, 595 cmÀ1; HR-
MS (ESI): m/z=429.0900, calcd. for C21H23ClNaO4S [M+
Na]+: 429.0903.
Methyl 2-acetyl-5-(cyclohexylthio)-5-(4-methoxyphenyl)-
pentanoate (5h): Mixture of diastereomers; yellow liquid;
1H NMR (CDCl3): d=1.67–1.71 (m, 5H), 1.72 (s, 1H), 1.74–
1.85 (m, 8H), 1.87 (s, 1.5H), 1.88 (s, 1.5H), 1.94–2.04 (m,
1H), 3.36–3.41 (m, 1H), 3.70 (s, 1.5H), 3.71 (s, 1.5H), 3.78
(m, 4H), 6.83 (d, J=8.8 Hz, 2H), 7.20 (d, J=8.4 Hz, 2H);
13C NMR: d=25.8, 25.9, 26.1, 26.4, 28.8, 28.9, 33.2, 33.3,
The authors thank for the National Natural Science Founda-
tion of China for financial support (20903042). The authors
are also grateful to all the staff members in the Analytical
and Testing Center of HUST, for their contributions to our
work. The authors also thank the Specialized Research Fund
for the Doctoral Program of Higher Education
(20090142120081). The Program for new Century Excellent
Talents in the University of China (NCET-10-0383) and the
Chutian Scholar Program of the Hubei provincial govern-
ment are also acknowledged.
33.9, 34.7, 34.8, 42.5, 42.6, 47.1, 47.2, 52.4, 52.5, 55.3, 59.3, References
59.4, 113.9, 128.6, 128.7, 134.6, 158.6, 170.0, 170.1, 202.8,
[1] a) J. Sherman, B. Chin, P. D. Huibers, R. Garcia-Valls,
202.9; IR: n=3027, 3000, 2929, 2852, 1743, 1716, 1610, 1510,
1446, 1358, 1302, 1248, 1176, 1148, 1110, 1035, 998, 834, 744,
694, 610, 592, 553, 539 cmÀ1; HR-MS (ESI): m/z=401.1757,
calcd. for C21H30NaO4S [M+Na]+: 401.1762.
T. A. Hatton, Environ. Health Perspect. 1998, 106, 253–
271; b) R. A. Sheldon, Green Chem. 2005, 7, 267–278;
c) T. Erdmenger, C. Guerrero-Sanchez, J. Vitz, R. Hoo-
genboom, U. S. Schubert, Chem. Soc. Rev. 2010, 39,
3317–3333; d) B. Schaffner, F. Schaffner, S. P. Verevkin,
A. Borner, Chem. Rev. 2010, 110, 4554–4581; e) H. L.
Yu, L. Ou, J. H. Xu, Curr. Org. Chem. 2010, 14, 1424–
1432; f) M. J. Hernaiz, A. R. Alcantara, J. I. Garcia,
J. V. Sinisterra, Chem. Eur. J. 2010, 16, 9422–9437.
[2] a) C. Reichardt, T. Welton, Solvents and Solvent Effects
in Organic Chemistry, 4th edn., Wiley-VCH, Wein-
heim/Germany, 2010, Chapter 8 (Solvents and Green
Chemistry) and Table A-14 on p 583; b) W. M. Nelson,
Art in science: utility of solvents in green chemistry.
Green Chem. 1998, 200–224; c) S. V. Dzyuba, R. A.
Bartsch, Angew. Chem. 2003, 115, 158–160; Angew.
Chem. Int. Ed. 2003, 42, 148–150; d) P. Lozano, Green
Chem. 2010, 12, 555–569; e) N. Yan, C. Xiao, Y. Kou,
Coord. Chem. Rev. 2010, 254, 1179–1218; f) P. Anastas,
N. Eghbali, Chem. Soc. Rev. 2010, 39, 301–312; g) B. W.
Cue, J. Zhang, Green Chem. Lett. Rev. 2009, 2, 193–
211.
[3] a) C. Estevez, Sustainable solutions - green solvents for
chemistry, RSC Green Chemistry Series 2009, 4 (Sus-
tainable Solutions for Modern Economies), 407–424;
b) R. T. Baker, S. Kobayashi, W. Leitner, Adv. Synth.
Catal. 2006, 348, 1337–1340; c) M. Lombardo, C. Trom-
bini, Catalysis in non-conventional reaction media, RSC
Green Chemistry Series, 2009, 3 (Eco-Friendly Synthe-
sis of Fine Chemicals), 1–79; d) M. Avalos, R. Babiano,
P. Cintas, J. L. Jimenez, J. C. Palacios, Angew. Chem.
2006, 118, 4008–4012; Angew. Chem. Int. Ed. 2006, 45,
3904–3908.
Ethyl
2-acetyl-5-(4-methoxyphenyl)-5-(phenylthio)pen-
tanoate (5i): Mixture of diastereomers; colorless liquid;
1H NMR (CDCl3): d=1.21 (dt, Ja =2.8 Hz, Jb =7.2 Hz, 3H),
1.72–1.97 (m, 4H), 2.12 (s, 1.5H), 2.13 (s, 1.5H), 3.34 (q, J=
6.0 Hz, 1H), 3.75 (s, 3H), 4.06–4.18 (m, 3H), 6.78 (td, Ja =
2.4 Hz, Jb =8.8 Hz, 2H), 7.13 (dd, Ja =1.6 Hz, Jb =8.8 Hz,
2H), 7.16–7.22 (m, 3H), 7.22–7.28 (m, 2H); 13C NMR
(CDCl3): d=14.1, 26.1, 26.2, 28.8, 28.8, 33.7, 33.8, 52.6, 52.6,
55.2, 59.3, 59.4, 61.5, 113.9, 127.2, 127.2, 128.7, 128.8, 132.5,
132.5, 133.1, 133.2, 134.7, 134.8, 158.8, 169.4, 169.5, 202.7;
IR: n=3060, 2960, 2937, 2837, 1738, 1716, 1608, 1510, 1454,
1360, 1303, 1249, 1176, 1035, 835, 744, 692 cmÀ1; HR-MS
(ESI): m/z=409.1444, calcd. for C22H26NaO4S [M+Na]+:
409.1449.
Ethyl 2-acetyl-5-(phenylthio)-5-(p-tolyl)pentanoate (5j):
Mixture of diastereomers; colorless liquid; 1H NMR
(CDCl3): d=1.22 (dt, Ja =2.0 Hz, Jb =7.2 Hz, 3H), 1.73–1.97
(m, 4H), 2.13 (s, 1.5H), 2.14 (s, 1.5H), 2.29 (s, 3H), 3.34 (q,
J=6.4 Hz, 1H), 4.06–4.18 (m, 3H), 7.06 (d, J=8.0 Hz, 2H),
7.11 (d, J=8.0 Hz, 2H), 7.15–7.22 (m, 3H), 7.23–7.28 (m,
2H); 13C NMR (CDCl3): d=14.1, 21.1, 26.1, 26.2, 28.7, 28.8,
33.7, 33.8, 52.9, 53.0, 59.4, 59.4, 61.5, 61.5, 127.1, 127.1, 127.6,
128.7, 129.2, 132.3, 132.4, 134.9, 134.9, 137.0, 138.1, 138.2,
169.4, 169.5, 202.7; IR: n=3053, 3020, 2980, 2925, 2866,
1738, 1716, 1642, 1583, 1512, 1443, 1359, 1243, 1145, 1023,
821, 742, 692 cmÀ1; HR-MS (ESI): m/z=393.1495, calcd. for
C22H26NaO3S [M+Na]+: 393.1500.
Ethyl 2-acetyl-5-[4-(tert-butyl)phenyl]-5-(phenylthio)pen-
tanoate (5k): Mixture of diastereomers; colorless liquid;
1H NMR (CDCl3): d=1.20 (t, J=7.2 Hz, 3H), 1.29 (s, 9H),
1.64–2.00 (m, 4H), 2.11 (s, 1.5H), 2.12 (s, 1.5H), 3.34 (q, J=
7.6 Hz, 1H), 4.12 (quint, J=6.8 Hz, 3H), 7.13–7.22 (m, 5H),
7.23–7.30 (m, 4H); 13C NMR (CDCl3): d=14.1, 26.1, 26.2,
28.7, 28.8, 31.4, 33.7, 33.8, 34.5, 52.8, 52.8, 59.4, 59.5, 61.4,
61.5, 125.5, 127.1, 127.1, 127.4, 128.7, 128.7, 132.0, 132.3,
132.3, 135.0, 135.0, 138.0, 138.0, 150.2, 169.5, 169.5, 202.8;
IR: n=3056, 2965, 2905, 2869, 1739, 1717, 1643, 1584, 1470,
1362, 1146, 1024, 842, 744, 692, 570 cmÀ1; HR-MS (ESI): m/
z=435.1964, calcd. for C25H23NaO3S [M+Na]+: 435.1970.
[4] S. Odiot, M. Blain, E. Vauthier, S. Fliszar, J. Mol. Struct
– THEOCHEM 1993, 98, 233–238.
[5] For metal catalysis in nitromethane, see: a) P. Kothan-
daraman, W. Rao, X. Zhang, P. W. H. Chan, Tetrahe-
dron 2009, 65, 1833–1838; b) P. Rubenbauer, T. Bach,
Adv. Synth. Catal. 2008, 350, 1125–1130; c) Y. Kunino-
bu, H. Ueda, K. Takai, Chem. Lett. 2008, 37, 878–879;
d) H.-H. Li, Y.-H. Jin, J.-Q. Wang, S.-K. Tian, Org.
Biomol. Chem. 2009, 7, 3219–3221; e) G. Li, L. Zhang,
Angew. Chem. 2007, 119, 5248–5251; Angew. Chem. Int.
Ed. 2007, 46, 5156–5159.
Adv. Synth. Catal. 2011, 353, 3473 – 3484
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
3483

Yajun Ren et al.
FULL PAPERS
[6] For acid catalysis in nitromethane, some researchers
have already mentioned the possibility of explosion,
e.g.: a) M. Noji, Y. Konno, K. Ishii, J. Org. Chem. 2007,
72, 5161–5167. But there are many users who did not
give any warning to the readers: b) U. Jana, S. Maiti, S.
Biswas, Tetrahedron Lett. 2007, 48, 7160–7163; c) J. J.
Kennedy-Smith, L. A. Young, F. D. Toste, Org. Lett.
2004, 6, 1325–1327; d) C. C. Silveira, S. R. Mendes, L.
Wolf, G. M. Martins, Tetrahedron Lett. 2010, 51, 4560–
4562; e) M. Rueping, B. J. Nachtsheim, A. Kuenkel,
Org. Lett. 2007, 9, 825–828; f) R. Sanz, D. Miguel, A.
Martinez, J. M. Alvarez-Gutierrez, F. Rodriguez, Org.
Lett. 2007, 9, 2027–2030; g) K. Motokura, N. Nakagiri,
T. Mizugaki, K. Ebitani, K. Kaneda, J. Org. Chem.
2007, 72, 6006–6015; h) M. Noji, T. Ohno, K. Fuji, N.
Futaba, H. Tajima, K. Ishii, J. Org. Chem. 2003, 68,
9340–9347; i) J. Kischel, K. Mertins, D. Michalik, A.
Zapf, M. Beller, Adv. Synth. Catal. 2007, 349, 865–870;
j) G. W. Wang, Y.-B. Shen, X.-L. Wu, Eur. J. Org.
Chem. 2008, 4999–5004.
[13] a) J. D. Crowley, S. M. Goldup, N. D. Gowans, D. A.
Leigh, V. E. Ronaldson, A. M. Z. Slawin, J. Am. Chem.
Soc. 2010, 132, 6243–6248; b) F. Nador, L. Fortunato, Y.
Moglie, C. Vitale, G. Radivoy, Synthesis 2009, 4027–
4031; c) T. Oishi, T. Katayama, K. Yamaguchi, N.
Mizuno, Chem. Eur. J. 2009, 15, 7539–7542; d) S. N.
Chen, W.-Y. Wu, F.-Y. Tsai, Green Chem. 2009, 11,
269–274; e) L. Li, J. Wang, G. Zhang, Q. Liu, Tetrahe-
dron Lett. 2009, 50, 4033–4036; f) P. Kuhn, P. Pale, J.
Sommer, B. Louis, J. Phys. Chem. C 2009, 113, 2903–
2910; g) S. Adimurthy, C. C. Malakar, U. Beifuss, J.
Org. Chem. 2009, 74, 5648–5651; h) P. Kuhn, A. Alix,
M. Kumarraja, B. Louis, P. Pale, J. Sommer, Eur. J.
Org. Chem. 2009, 423–429; i) D. Li, K. Yin, J. Li, X. Jia,
Tetrahedron Lett. 2008, 49, 5918–5919; j) K. Yamaguchi,
K. Kamata, S. Yamaguchi, M. Kotani, N. Mizuno, J.
Catal. 2008, 258, 121–130; k) K. Kamata, S. Yamaguchi,
M. Kotani, K. Yamaguchi, N. Mizuno, Angew. Chem.
2008, 120, 2441–2444 ; Angew. Chem. Int. Ed. 2008, 47,
2407–2410; l) A. Kusuda, X. H. Xu, X. Wang, E. Toku-
naga, N. Shibata, Green Chem. 2011, 13, 843–846;
m) K. Yin, C. Li, J. Li, X. Jia, Green Chem. 2011, 13,
591–593; n) S. Zhang, X. Liu, T. Wang, Adv. Synth.
Catal. 2011, 353, 1463–1466.
[14] a) H.-F. Jiang, J.-Y. Tang, A.-Z. Wang, G.-H. Deng, S.-
R. Yang, Synthesis 2006, 1155–1161; b) J. Li, H. Jiang,
Chem. Commun. 1999, 2369–2370; c) K. Balaraman, V.
Kesavan, Synthesis 2010, 3461–3466; d) G. Eglinton,
A. R. Galbraith, Chem. Ind. (London) 1956, 737; e) D.
Wang, J. Li, N. Li, T. Gao, S. Hou, B. Chen, Green
Chem. 2010, 12, 45–48; f) T.-M. Wu, S.-H. Huang, F.-Y.
Tsai, Appl. Organomet. Chem. 2011, 25, 395–399.
[15] C. Ye, J.-C. Xiao, B. Twamley, A. D. LaLonde, M. G.
Norton, J. M. Shreeve, Eur. J. Org. Chem. 2007, 5095–
5100.
[7] Z. Liu, J. Dou, Y. Zhao, Faming Zhuanli Shenqing
Gongkai Shuomingshu, CN 101698660 A 20100428,
2010.
[8] a) B. E. Cooper, Chem. Ind. 1978, 107, 794; b) C. A.
Bruynes, T. K. Jurriens, J. Org. Chem. 1982, 47, 3966;
c) D. Zareyeea, B. Karimi, Tetrahedron Lett. 2007, 48,
1277; d) J. S. Yadav, B. V. S. Reddy, A. K. Basak, G.
Baishya, A. V. Narsaiah, Synthesis 2006, 3831; e) B.
Karimi, B. Golshani, J. Org. Chem. 2000, 65, 7228;
f) M. M. Mojtahedi, H. Abbasi, M. S. Abaee, J. Mol.
Catal. A: Chem. 2006, 250, 6.
[9] S. T. Kadam, S. S. Kim, Green Chem. 2010, 12, 94–98.
[10] a) S. Nag, G. P. Yadav, P. R. Maulik, S. Batra, Synthesis
2007, 911–917; b) P. T. Kaye, M. A. Musa, Synth.
Commun. 2003, 33, 1755–1770; c) P. Perlmutter, M.
Tabone, Tetrahedron Lett. 1988, 29, 949–952.
[11] a) M. Li, C. Tang, J. Yang, Y. Gu, Chem. Commun.
2011, 47, 4529–4531; b) M. Li, H. Li, T. Li, Y. Gu, Org.
Lett. 2011, 13, 1064–1067; c) M. Li, J. Yang, Y. Gu,
Adv. Synth. Catal. 2011, 353, 1551–1564.
[12] a) G. W. Gribble, J. J. Li, (Eds.), Glaser Coupling, in:
Name Reactions for Homologations, Wiley, New York,
2009, pp 236–257; b) P. Siemsen, B. Felber, G. Dyker,
(Eds.), Glaser homocoupling and the Cadiot-Chodkie-
[16] a) S. Liu, T. Fukuyama, M. Sato, I. Ryu, Synlett 2004,
1814–1816; b) Md. T. Rahman, T. Fukuyama, I. Ryu, K.
Suzuki, K. Yonemura, P. F. Hughes, K. Nokihara, Tetra-
hedron Lett. 2006, 47, 2703–2706.
[17] Some analogous structures have been used as chelated
ligands for the synthesis of some organometallic com-
plexes: a) S. Warsink, S. Y. de Boer, L. M. Jongens, C.-
F. Fu, S.-T. Liu, J. T. Chen, M. Lutz, A. L. Spek, C. J.
Elsevier, Dalton Trans. 2009, 7080–7086; b) X. Hu, K.
Meyer, J. Am. Chem. Soc. 2004, 126, 16322–16323.
[18] W. A. Herrmann, C. Kocher, L. J. Gookn, G. R. J.
Artus, Chem. Eur. J. 1996, 2, 1627–1636.
À
wicz heterocoupling reaction, in: Handbook of C H
Transformations, Wiley-VCH, Weinheim/Germany,
2005, Vol. 1, pp 53–62, 83–84.
3484
asc.wiley-vch.de
ꢁ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2011, 353, 3473 – 3484