Reactivity of 1,3-dimethylimidazolium-2-carboxylate with dimethylcarbonate at high temperature: Unexpected 2-ethyl-functionalisation of the imidazolium moiety and employment of the NHC-CO2/dimethylcarbonate system in a base promoted reaction

Article abstract of DOI:10.1016/j.catcom.2013.11.013

The reaction of 1,3-dimethylimidazolium-2-carboxylate and dimethylcarbonate (DMC) at high temperature yielded the new compounds 2-ethyl-1,3- dimethylimidazolium methyl carbonate salt and 2-ethyl-1,3-dimethylimidazolium-4- carboxylate zwitterion which were obtained as a mixture in approximately 4:1 molar ratio. The compounds were also isolated in pure form through alternative synthetic procedures and characterized by ESI-HRMS, ¹H, ¹³C NMR and FTIR spectroscopy. The 1,3-dimethylimidazolium-2- carboxylate/dimethylcarbonate system was employed in the synthesis of 1,7-heptanedioic acid dimethyl ester from cyclohexanone and DMC. The target compound was obtained in 49% yield and 66% selectivity.

Full text of DOI:10.1016/j.catcom.2013.11.013

Catalysis Communications 46 (2014) 94–97
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Short Communication
Reactivity of 1,3-dimethylimidazolium-2-carboxylate with
dimethylcarbonate at high temperature: Unexpected
2-ethyl-functionalisation of the imidazolium moiety and employment of
the NHC-CO2/dimethylcarbonate system in a base promoted reaction
Cosimo Annese a, Lucia D'Accolti a, Caterina Fusco b, Immacolata Tommasi a,
⁎
a
Dipartimento di Chimica, Università di Bari “A. Moro”, v. Orabona, 4, 70126 Bari, Italy
b
CNR-ICCOM, Dipartimento di Chimica, Università di Bari, v. Orabona, 4, 70126 Bari, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
The reaction of 1,3-dimethylimidazolium-2-carboxylate and dimethylcarbonate (DMC) at high tempera-
ture yielded the new compounds 2-ethyl-1,3-dimethylimidazolium methyl carbonate salt and 2-ethyl-
1,3-dimethylimidazolium-4-carboxylate zwitterion which were obtained as a mixture in approximately
4:1 molar ratio. The compounds were also isolated in pure form through alternative synthetic procedures
and characterized by ESI-HRMS, 1H, 13C NMR and FTIR spectroscopy. The 1,3-dimethylimidazolium-2-carboxylate/
dimethylcarbonate system was employed in the synthesis of 1,7-heptanedioic acid dimethyl ester from cyclohexanone
and DMC. The target compound was obtained in 49% yield and 66% selectivity.
Received 25 September 2013
Received in revised form 12 November 2013
Accepted 14 November 2013
Available online 26 November 2013
Keywords:
1,3-Dimethylimidazolium-2-carboxylate
Dimethylcarbonate
© 2013 Elsevier B.V. All rights reserved.
N-heterocyclic carbenes
2-Ethyl-1,3-dimethylimidazolium methyl
carbonate salt
1. Introduction
The mechanism proposed for the transcarboxylation reaction,
[12,13] is shown in Scheme 1 and involves CO2 dissociation from
N-heterocyclic carbenes (NHC) are nowadays well established as li-
gands for homogeneous catalysis and active organocatalysts for a varie-
ty of organic syntheses [1–8]. Some common routes to NHC include
deprotonation of an imidazolium salt by a strong base [1-2] and oxida-
tive addition of the C(2)–H bond to transition metal complexes [1,4–8].
N-heterocyclic carbenes–CO2 (NHC-CO2) adducts have also been syn-
thesized and used both in CO2 conversion chemistry [1] and as carbene
transfer agents [7]. In our previous work we reported the use of NHC–
CO2 as 1,3-dimethylimidazolium-2-carboxylate (IMeCO2) (1a) [9] and
1-n-butyl-3-methylimidazolium-2-carboxylate, (IMenBuCO2) (2a) in a
transcarboxylation reaction of acetophenone (and other activated C–H
compounds) and CH3OH to form benzoylacetate and methyl carbonate
salts respectively in the presence of MX (MX = NaBF4, KPF6, NaBPh4,
NaI) [10–12]. Expanding the scope of NHC–CO2, Louie et al. [13] report-
ed the transcarboxylation of acetophenone using 1,3-bis-(2,6-
diisopropylphenyl)imidazolium-2-carboxylate (IPrCO2) and 1,3-bis-
(2,4,6-trimethyphenyl)imidazolium-2-carboxylate, (IMesCO2) in the
presence of NaBPh4.
NHC–CO2 (1a, 2a) leading to a 1,3-dialkylimidazol-2-ylidene species.
The latter deprotonates the substrate R3–H, generating the R3-anion
which nucleophilically attacks CO2 affording carboxylates or alkyl
carbonates.
⁎
Corresponding author. Tel.: +39 080 544 2484.
E-mail address: immacolata.tommasi@uniba.it (I. Tommasi).
Scheme 1. Transcarboxylation of activated C–H substrates (R3–H) from IMeCO2 and
IMenBuCO2.
1566-7367/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.catcom.2013.11.013

C. Annese et al. / Catalysis Communications 46 (2014) 94–97
95
Considering the proposed intermediacy of the imidazolium carbene
in the above reported catalysis, we decided to investigate the reactivity
of IMeCO2 (1a) in the synthesis of 1,7-heptanedioic acid dimethyl ester
from cyclohexanone and dimethylcarbonate (DMC) under basic condi-
tions. In the course of our study we gained evidence that IMeCO2 (1a)
itself reacted with DMC at high temperature affording two unexpected
products i.e. 2-ethyl-1,3-dimethylimidazolium methyl carbonate salt
(3, Scheme 2) and 2-ethyl-1,3-dimethylimidazolium-4-carboxylate
zwitterion (4, Scheme 2) (not previously characterized) that were ob-
tained in mixture. For reliable products identification, 3 and 4 were
also synthetized as pure compounds through alternative synthetic
routes. We describe here the synthesis of compounds 3 and 4 and em-
ployment of the IMeCO2/DMC system in the reaction of cyclohexanone
with DMC affording 1,7-heptanedioic acid dimethyl ester.
FTIR spectroscopy. NMR data of the pure compounds 3 and 4 were in
perfect agreement with those obtained by analysis of the mixture pro-
duced from the reaction of IMeCO2 with DMC at high temperature
(Scheme 2).
ð1Þ
Compounds 3 and 4 are extremely hygroscopic. Unsatisfactory el-
emental analyses were obtained for product 3 [14] while elemental
analysis of compound 4 was in good agreement with the formula
C8H12N2O2·1/2H2O.
2. Experimental
A literature survey shows that the synthesis of 2-ethyl-1,3-
dimethylimidazolium moiety can be accomplished by use of conventional
methods that require the use of toxic alkylating agents [15,16]. To the best
of our knowledge the synthesis and characterization of compounds 3 and
4 was not previously reported. It is worth citing the vast employment of
DMC as a safe alkylating agent for the synthesis of ionic liquids
[14,17–19] and report of several zwitterionic imidazolium-derivatives
[20] and NHC with negative-charge tags [21] characterized by ESI-MS.
Experimental details for all reactions and characterization of com-
pounds are given in the Supporting Information.
3. Results and discussion
3.1. Reactivity of IMeCO2 (1a) with DMC at high temperature: obtainment
of compounds 3 and 4 in mixture
IMeCO2 [9] was reacted with DMC (as solvent and reactant) at differ-
ent temperatures ranging from 180 to 200 °C (3 h). NMR analysis of the
crude reaction mixture showed the quantitative conversion of the
imidazolium carboxylate and the formation of two major products: 2-
ethyl-1,3-dimethylimidazolium methyl carbonate salt (3, Scheme 2)
and 2-ethyl-1,3-dimethylimidazolium-4-carboxylate zwitterion (4,
Scheme 2) obtained in mixture besides other minor products.
The two products were identified by NMR spectroscopy (DEPT,
HMQC and HMBC) and by ESI-HRMS (see SI). Attempt to crystallize
compound 3 from CH3CN/Et2O lead to partial methyl carbonate decom-
position. The 3/4 molar ratio in the mixture was estimated by 1H NMR
spectroscopy (from the relative integrals of the N–CH3 signals) as ap-
proximately 4:1.
3.3. Proposed mechanism
The mechanistic pathway for formation of product 3 at high temper-
ature is tentatively proposed in Scheme 3. Product 3 may form upon
IMeCO2 (1a) decarboxylation followed by methylation of the 2-
ylidene intermediate. The C(2)-methyl substituted imidazolium cation
(5) can be deprotonated by CH3O− generating a zwitterionic species 6
which can be stabilized by resonance (structure 7). Our hypothesis is
corroborated from literature data [22] as a 1,2,3-trimethylimidazolium
salt was shown to undergo deprotonation by strong bases affording
the 2,3-dihydro-1,3-dimethyl-2-methyleneimidazole (7). In our sys-
tem, zwitterion 6 may further react with DMC affording the observed
imidazolium derivative 3. We also propose that CH3O− may
deprotonate at high temperature product 3 leading zwitterion 8. The
latter may be in resonance with a 2-ethylidene-2,3-dihydro-1,3-
dimethylimidazole species.
Varying the temperature over the range 180–200 °C did not affect
significantly the 3/4 molar ratio, while formation of the two products
was not observed after 3 h of reaction at 150 °C.
3.2. Synthesis of compounds 3 and 4 in pure form
According to the proposed reaction mechanism, DMC is involved in a
“double” alkylation reaction.
To obtain compound 3, 2-ethylimidazole was reacted with DMC at
85 °C during 6 days. Sampling and analyzing by 1H NMR spectroscopy
the reaction mixture allowed monitoring the conversion of 2-
ethylimidazole into a mixture of 2-ethyl-1-methylimidazole and 2-
ethyl-1,3-dimethylimidazolium methyl carbonate salt (3). Removing
part of DMC by rotary evaporation allowed precipitation of the pure
product 3 which was isolated as a white solid in low yield (7%). The
mother solution was heated again at 95 °C during 4 days and subjected
to usual work-up (see SI) to afford a mixture of 3 and 4 in 5:1 molar
ratio. Compound 4 was obtained in high yield (73%) by heating pure
product 3 at 200 °C (8 h) in toluene suspension (Eq. (1)). Pure com-
pounds 3 and 4 were characterized by ESI-HRMS, 1H, 13C NMR and
From literature it is known that DMC reacts as an ambivalent
electrophile that can function as either carboxymethylating or as
methylating agent depending on the experimental conditions [23].
Picquet, Plasseraud et al., by applying different reaction conditions,
have reported the use of IMenBuCO2 (2a) in transesterification of
DMC with glycerol (affording cyclic carbonates) [24] or with other
diols affording polycarbonates [25].
Concerning product 4, we have synthetic evidence (Eq. (1)) that the
methyl carbonate anion carboxylates the C(4)-imidazolium carbon.
Moreover, Crabtree et al. have reported a theoretical mechanistic inves-
tigation about the carboxylation at the C(2)-imidazolium position by
CH3OC(O)O− [7].
Scheme 2. Reactivity of IMeCO2 with DMC at high temperature.

96
C. Annese et al. / Catalysis Communications 46 (2014) 94–97
of the ketone followed by a retro-Dieckman condensation [23]. As far
as the nature of the base is concerned, the literature reports the use of
both organic and inorganic bases (i.e. sodium alkoxydes [29], inorganic
carbonates [28], aliphatic amines [30] and metal oxides [31]) that have
been employed in various experimental conditions to perform the tar-
get reaction. To facilitate the comparison, we have collected the most
relevant data concerning the reaction in Table S4 (see SI). On the basis
of data reported in the literature, sodium alkoxydes [29] promote the
targeted synthesis with satisfactory yield in the desired product 9b
(85%) but require a substrate/base molar ratio of 0.7. Other catalysts
[28,30] promote the synthesis of 9b with lower yield and selectivity
but with TON ranging over 4–20. Finally, the use of MgO [31] requires
very high temperatures (260 °C) and a substrate/base molar ratio of
0.5 to obtain 9b with 51% yield and 62% selectivity. In our experiments,
data collected in Table 1 (entries 1–5), show that 1,7-heptanedioic acid
dimethyl diester (9b) was obtained as the main reaction product
besides 2-methyl-1,7-heptanedioic acid dimethyl ester (10) and 2-(1-
cyclohexen-1-yl)cyclohexanone (11). The “one pot” procedure
(IMeCO2/DMC/cyclohexanone) was employed in experiments reported
in entries 1–3. By using 5 equivalents of cyclohexanone the reaction was
tested at 150 and 200 °C (entries 1–2). Obtained results show that the
higher temperature is necessary to achieve satisfactory substrate con-
version (66% versus 26%). At the temperature of 200 °C (entries 2–3)
lowering the substrate excess (1.5 eq. versus 5 eq.) allowed a better
yield (49% versus 28%) and a better selectivity in 9b (66% versus 42%).
Comparing entries 2 and 3, we explain the increased selectivity to-
wards 2-(1-cyclohexen-1-yl)cyclohexanone in entry 2 as due to the in-
creased amount of cyclohexanone available for the auto-condensation
reaction. Employing the pure compounds 3 or 4 in the synthetic tests
(entries 4 and 5 respectively) we obtained lower substrate conversion
(60% in entry 4, 58% in entry 5) with respect to entry 3 (74%), while
comparable products selectivity was observed. To rationalize these re-
sults, we sampled and analyzed by 1H NMR the reaction mixture of a
synthetic test performed according to conditions reported in entries 3.
We observed, thus, that during the first 1.5 h of reaction IMeCO2 and
1,3-dimethyl imidazolium cation were the most abundant imidazolium
species in the reaction mixture (N–CH3 signals observed at 3.99 and
3.87 ppm respectively), while, during the following 1.5 h, compound
3 increased (N–CH3 signal at 3.76 ppm). After 3 h of reaction, the
most abundant species was represented by compound 3 while com-
pound 4 was always formed in approximate 1:4 molar ratio with re-
spect to compound 3. NMR analysis of the reaction mixture gave also
evidence of minor components. Analogously, sampling and analyzing
(by 1H NMR) a reaction performed according to entry 4 showed the 2-
ethyl-1,3-dimethylimidazolium cation being the most abundant species
during the reaction besides other minor uncharacterized components.
In our effort to identify the nature of the base promoting the targeted re-
action, we observed, thus, a quite complex transformation of the
imidazolium species which still produced effectively the desired prod-
uct. By citing Maschmeyer [32], we consider doing the synthesis in the
presence of “a mixture of compounds” that, on the overall, convert the
substrate more effectively than the systems 3/DMC and 4/DMC. For
a more reliable comparison of the performance of our system (en-
tries 2–3, Table 1) with the activity of sodium alkoxydes [29] and ter-
tiary amines [30] we have tested these bases according to condition
reported in entries 6–8. In entries 7 and 8, respectively 69% and
67% substrate conversion and 49% and 28% yield in 9b were obtained.
By comparing entry 8 and 3, we observed that a lower yield (28% ver-
sus 49%) and selectivity (42% versus 66%) in 9b was obtained by
using the amine. In summary, when our system was charged with
1.5 eq. of substrate (entry 3) it seemed to promote a stoichiometric
reaction with a TON of 1.1 [33] that was slightly higher if compared
with a TON of 0.7 obtained in entry 7. In addition, when our system
was charged with 5 eq. of substrate, (entry 2) a TON of 3.3 was ob-
tained, showing that the system may work catalytically, although
with lower selectivity.
Scheme 3. Proposed mechanism for the synthesis of compound 3 at high temperature.
3.4. Synthesis of 1,7-heptanedioic acid dimethyl ester from cyclohexanone
and DMC
With compounds 3 and 4 in hand (either in mixture or as pure com-
pounds), we decided to test their reactivity as bases selecting cyclohex-
anone as target compound that was reacted with DMC to synthesize the
α,ω-diester of 1,7-heptanedioic acid (9b, Scheme 4).
We set out to implement in the targeted synthesis either a “one pot”
procedure (reacting IMeCO2 with DMC and cyclohexanone) or the pure
compounds (reacting pure 3 or 4 with DMC and cyclohexanone). The
interest for cyclohexanone as starting material to produce 9b is due to
its employment as intermediate in industrial manufacture of Nylon
7,7 and in formulation of adhesives, [26] and herbicidal mixtures [27].
Manufacture of 1,7-heptanedioic acid is carried out by cycloheptanone
oxidation with N2O4 or 1,5-pentanediol carbonylation over Ni(CO)4 cata-
lyst. However the synthesis shown in Scheme 4 is a green alternative
route [28] that proceeds through a base catalyzed α-carboxymethylation
Scheme 4. Mechanism for the synthesis of 1,6-hexanedioic acid dimethyl ester (9a) and
1,7-heptanedioic acid dimethyl ester (9b) from alicyclic ketones and dimethycarbonate
[23].

C. Annese et al. / Catalysis Communications 46 (2014) 94–97
97
Table 1
Distribution of products and yields obtained by reaction of cyclohexanone with DMC in the presence of various bases. Selectivity is reported in brackets.
Entry
Base
Substrate/base
molar ratio
T
(°C)
Substrate conversion
(%)a
9b Yield (selectivity)
10 Yield (selectivity)
11 Yield (selectivity)c
(%)b
(%)b
(%)b
1
2
3
4
5
6
7
8
IMeCO2/DMCd
″
5
5
1.5
1.5
1.5
5
150
200
200
200
200
200
200
200
26
66
74
60
58
27
69
67
11 (42)
28 (42)
49 (66)
37 (62)
35 (60)
15 (56)
49 (71)
28 (42)
4 (15)
8 (12)
11 (15)
8 (13)
8 (31)
27 (41)
12 (16)
8 (13)
″
3/DMC
4/DMC
CH3ONa
″
8 (14)
6 (10)
e
12 (44)
18 (26)
31 (46)
e
1
1.5
(C2H5)3N
3 (4)
a
Reaction time 9 h.
Chromatographic yields.
b
c
For product 11 the selectivity was calculated as: moles of substrate that undergo auto-condensation/total moles of substrate converted.
IMeCO2:DMC were used in 1:7 molar ratio.
Product detected in traces.
d
e
[7] A.M. Voutchkova, M. Feliz, E. Clot, O. Eisenstein, R.H. Crabtree, J. Am. Chem. Soc. 129
(2007) 12834–12846.
4. Conclusion
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Rogers, Chem. Commun. (2003) 28–29.
In the present work is disclosed the synthesis of the new compounds
3 and 4.
In addition, we describe a new unexpected reactivity of the IMeCO2/
dimethylcarbonate system at high temperature giving access to a
mixture of imidazolium compounds that can be used to promote the
synthesis of 1,7-heptanedioic acid dimethyl ester with 49% yield and
66% selectivity. By comparison with the catalysis promoted by other
bases, the IMeCO2/DMC system seems to conciliate the obtainment of
a 74% substrate conversion with a reasonable yield and selectivity in
1,7-heptanedioic acid dimethyl ester.
[10] I. Tommasi, F. Sorrentino, Tetrahedron Lett. 46 (2005) 2141–2145.
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[13] B.R. Van Ausdall, N.F. Poth, V.A. Kincaid, A.M. Arif, J. Louie, J. Org. Chem. 76 (2011)
8413–8420.
[14] In analogy to what reported by R.D. Rogers. D.J. Holbrey, R.D. Rogers, S.S. Shulka, C.D.
Wilfred, Green Chemistry 12 (2010) 407–413(for the 1-butyl-1-methylpyrrolidinium
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Acknowledgments
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Financial support by the Ministry of Education of Italy (MIUR, grant
PRIN 2008) and by the Italian National Research Council (CNR, Rome)
is gratefully acknowledged.
[19] S. Kazuji, N. Tomoharu, JP3504349, 2003.
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Appendix A. Supplementary data
Supplementary data to this article can be found online at http://dx.
doi.org/10.1016/j.catcom.2013.11.013.
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