Elimination of Ethene from 1,2-Diiodoethane Induced by N-Heterocyclic Carbene Halogen Bonding

Article abstract of DOI:10.1071/CH19237

The attempted synthesis of N-heterocyclic carbene (NHC)-stabilised dicarbon (C₂) fragments via nucleophilic substitution at 1,2-diiodoethane is reported. Rather than the expected S_N2 pathway, clean elimination of ethene and formation of an iodoimidazolium cation was observed. The resistance towards nucleophilic substitution piqued interest, and subsequent investigation determined NHC-halogen bonding as the source. This is in contrast to reactions between NHCs and other alkyl halides, where substitution or elimination pathways are reported. A detailed theoretical study between these cases highlights the importance of iodine as a halogen bond donor compared with other halogens, and shows that NHCs are excellent halogen bond acceptors. This reactivity suggests potential for application of the halogen bonding interaction between NHCs and organic compounds.

Full text of DOI:10.1071/CH19237

RESEARCH FRONT
CSIRO PUBLISHING
Aust. J. Chem. 2019, 72, 614–619
Full Paper
https://doi.org/10.1071/CH19237
Elimination of Ethene from 1,2-Diiodoethane Induced
by N-Heterocyclic Carbene Halogen Bonding*
A B
,
A B
,
Tiffany B. Poynder,
Andrew Molino,
Dharmeshkumar P. Savaliya,
A B
,
A C
,
A C
,
David J. D. Wilson,
and Jason L. Dutton
A
Department of Chemistry and Physics, La Trobe Institute for Molecular Science,
La Trobe University, Melbourne, Vic. 3086, Australia.
B
These authors contributed equally to this work.
C
Corresponding authors. Email: david.wilson@latrobe.edu.au; j.dutton@latrobe.edu.au
The attempted synthesis of N-heterocyclic carbene (NHC)-stabilised dicarbon (C2) fragments via nucleophilic substitu-
tion at 1,2-diiodoethane is reported. Rather than the expected SN2 pathway, clean elimination of ethene and formation of an
iodoimidazolium cation was observed. The resistance towards nucleophilic substitution piqued interest, and subsequent
investigation determined NHC-halogen bonding as the source. This is in contrast to reactions between NHCs and other
alkyl halides, where substitution or elimination pathways are reported. A detailed theoretical study between these cases
highlights the importance of iodine as a halogen bond donor compared with other halogens, and shows that NHCs are
excellent halogen bond acceptors. This reactivity suggests potential for application of the halogen bonding interaction
between NHCs and organic compounds.
Manuscript received: 27 May 2019.
Manuscript accepted: 27 June 2019.
Published online: 24 July 2019.
Introduction
To find a more efficient route, while also expanding the
classes of NHCs that could potentially be used, we intended to
access NHC-stabilised C2 compounds via direct reaction of the
free carbene with a suitable C2 precursor. As an initial attempt
we intended to form dication 3 via an SN2 reaction between
Et2NHC (the nucleophile) and 1,2-diiodoethane (Scheme 2).
Dication 3 could then simply be deprotonated, furnishing a
derivative of 2 in only two steps. However, rather than the
desired SN2 reactivity, we discovered that the NHC reacts
cleanly with the alkyl halide to eliminate ethene.
Here we report a combined synthetic and theoretical investi-
gation of the unexpected reactivity of NHCs with alkyl halides,
in order to characterise and assess the wider applicability of this
new reactivity. In particular, reactivity based on a consideration
of halogen bonding offers the potential for new perspectives in
the interaction of NHCs with organic compounds.
The isolation of molecules with C2 fragments in a zero oxidation
state is a topic of current interest.[1–3] Our laboratory is partic-
ularly interested in the coordination chemistry of carbene
ligands with C2 fragments.[4–6] Recently, we discovered that
reduction of dication 1 generated a bis-N-heterocyclic olefin 2
(Scheme 1),[7] which demonstrated unique reactivity, such as
the first example of atmospheric O2 cleaving a C=C bond.[8] It is
of interest to extend the chemistry of this system, however,
reported methods to access the starting compounds are limited to
benzimidazolium fused N-heterocyclic carbene (NHC) deriva-
tives, as the syntheses start with 1,2-phenylenediamine to
generate benzimidazoles via two subsequent condensations
with maleic anhydride.[9] The reported method is also a rather
onerous synthesis, with the second condensation using poly-
phosphoric acid as a solvent at high temperatures.
Scheme 1. Reduction of 1 to give bis-N-heterocyclic olefin 2.
*Jason Dutton is the winner of the 2018 RACI Organometallic Award.
Journal compilation Ó CSIRO 2019
www.publish.csiro.au/journals/ajc

N-Heterocyclic Chemistry Halogen Bonding
615
2
Et
N
N
Et
Et
N
N
Et
3
I
Et
N
Et
H
H
H
H
I
I
N
N
Et
N
Et
I
4
5
Scheme 2. Reaction of NHC 4 with 1,2-diiodoethane.
H
X
X
X
X
R
R
R
R
N
N
N
N
R
N
R
R
N
N
X
X
X = Cl, Br
R
R
R
CX4
N
N
N
X
X
Scheme 3. Reported reactions of NHCs with haloalkanes.
Results and Discussion
Early reports from Arduengo shortly after the isolation of
the first N-heterocyclic carbene involving C1 perchloroalkanes
indicate that the reactions with NHCs primarily result in
halogenation of the NHC backbone,[14] with the same observed
by Jones and Junk in reactions of NHC with CBr4.[12]
The elimination of ethene and intermediacy of [Ph3P–I]þ has
been recently reported in a version of the Appel reaction
between triphenylphosphine and 1,2-diiodoethane at elevated
temperatures (60–1008C, 2 h), giving alkyl iodides from alco-
hols. Direct attack on the I by PPh3 was hypothesised but not
analysed in detail, nor was the [Ph3P–I]þ intermediate observed
or isolated.[15]
In our system, nucleophilic substitution reactions should give
a product with NHC bound to the C2 fragment, whereas
elimination pathways should generate protonated carbene as
the main NHC-containing product together with vinyl iodide. In
light of the report from Jones and Junk discussed above, the
exclusive and clean formation of 3 and ethylene thus merits
attention. We hypothesised that the mechanism might be direct
attack by the NHC onto an iodine atom via a halogen bonding
mechanism. Halogen bonding is a topic of increasing interest,
primarily for supramolecular applications, but also in organic
synthesis.[16] NHCs are considered good halogen bond accep-
tors,[17] however, a transformation of this type induced by
halogen bonding with NHCs has not been proposed before.
The energy profiles of two possible pathways, one involving
direct interaction with iodine and the other a standard SN2 attack
on the carbon atom were modelled at the B3LYP-D3(BJ)/
def2-TZVP (SMD,MeCN)//DSDPBEP86/def2-TZVPP (SMD,
MeCN) level of theory, using an N-Me substituted NHC as a
model system. The reaction energy profile is plotted in Fig. 1,
including the expected SN2 reaction, direct attack of the NHC on
The reaction of NHC 4 (generated in situ from the imidizao-
lium and potassium bis(trimethylsilyl)amide (KHMDS)) and
1,2-diiodoethane in C6D6 solvent in a 1 : 1 stoichiometric ratio
at room temperature resulted in the immediate visible evolu-
tion of a gas and precipitation of an orange solid. H and 13
1
C
NMR studies of the in situ reaction mixture revealed the
presence of a signal at 5.26 ppm in the 1H NMR spectrum. This
was consistent with the presence of ethylene, which was con-
firmed in the 13C NMR spectrum by a resonance at 123 ppm. A
sample of the solid that precipitated from the reaction was
dissolved in CDCl3, for which the 1H NMR spectrum showed a
single NHC-containing compound, missing the imidazolium
proton. The ESI mass spectrum gave signals at m/z 251 and
127.1 in positive and negative ion mode, respectively, con-
sistent with the iodoimidazolium cation being present as an
iodide salt (5). The isolated yield of the salt was 87 %, indi-
cating the reaction primarily generates 3 and ethylene. The
products, while not the goal of the reaction, caught our atten-
tion as it was not the expected result of a reaction between these
two species. In effect, the product requires a reduction of the
1,2-diiodoethane and oxidation of the NHC.
Denk and co-workers have described the reduction of haloalk-
anes with folates and imidazolidine derivatives,[10,11] but not with
free carbenes. Jones and Junk have reported reactions between
NHC and 1,2-dibromoethane to give a mixture of protonated
NHC, bromoimidazolium cations, and vinyl bromide as the
primary fate of the bromoethane.[12] Reactions of NHCs with
1,2-dichloroethane reported by Kuhn gives chloroimidazo-
lium;[13] however, Jones and Junk indicate in their study that
the reaction gives a substantial fraction of protonated carbene and
vinyl chloride from an elimination pathway as well (Scheme 3).

616
T. B. Poynder et al.
+
–
+
+
+
–
+
–
+
–
+
+
–
–
+
Fig. 1. Reaction profile for SN2 (red), elimination (green), and attack via halogen bonding (blue) for the reaction between Me2NHC and
1,2-diiodoethane. All values are calculated relative free energies (kJ molꢀ1).
Fig. 2. Calculated HOMO (left) and LUMO (right) of 1,2-diiodoethane.
iodine via a halogen-bonding mechanism, and a reaction
between Me2NHC and 1,2-diiodoethane.
An examination of the lowest unoccupied molecular orbital
(LUMO) of 1,2-diiodoethane is consistent with the proposed
halogen bond induced pathway (Fig. 2). The LUMO is of s
antibonding character with respect to the I–C bonds, but p
bonding with respect to the C–C bond. Population of the LUMO
on 1,2-diiodoethane by the lone pair of electrons from the
electron-donating NHC along the I–C bond axis would then
promote the observed transformation involving rupture of the
I–C bonds, formation of the C=C bond, and release of ethene.
Examination of the analogous reaction for 1,2-dibro-
moethane and NHC (Fig. 3) yields a barrier for halogen bonding
In the typical SN2 pathway, the initial transition state
barrier is calculated to be 110.4 kJ molꢀ1, with the products
206.5 kJ molꢀ1 below that of the reactants. To reach the final
observed products, attack on the carbenic carbon by iodide is
required together with rupture of the NHC C–C bond to yield the
ethylene and iodoimidazolium products. This second step is
calculated to be endergonic by ,100 kJ molꢀ1. This suggests the
reaction should stop after formation of the cation arising from
displacement of iodide if one equivalent of NHC is used and the
mechanism is of a classic SN2 reaction.
attack on the bromine atom that is much higher at 123 kJ molꢀ1
.
Deprotonation and elimination for 1,2-diiodoethane gives a
similarly high barrier at 106 kJ molꢀ1. However, direct attack of
the NHC on the iodine atom, breaking the C–I bonds and
forming ethene in a single step, has a much lower transition
state barrier of 65.5 kJ molꢀ1, leading directly to the observed
products, and consistent with the rapid room temperature reac-
tion. The requirement for elevated temperatures in the analo-
gous reaction with PPh3 and 1,2-diiodoethane[15] suggests that
NHCs have a superior propensity for halogen bonding to alkyl
iodides than do phosphines.
That is consistent with a C–Br bond being a worse halogen bond
acceptor than a C–I bond. The calculated energy of the LUMO
for 1,2-dibromoethane is 0.4 eV higher in energy than the
LUMO for 1,2-diiodoethane and is thus less accessible for
halogen bonding. For 1,2-dibromoethane the pathway with the
lowest barrier is the elimination reaction (113 kJ molꢀ1), con-
sistent with Jones’ observations.[12] The barrier for direct attack
on the bromine is very similar in energy (123 kJ molꢀ1),
accounting for the observation of bromoimidazolium as a
competing product in Jones’ work.

N-Heterocyclic Chemistry Halogen Bonding
617
+
–
+
+
+
–
+
–
+
+
–
+
+
–
–
Fig. 3. Reaction profile for SN2 (red), elimination (green), and attack via halogen bonding (blue) for the reaction between Me2NHC and 1,2-dibromoethane.
All values are calculated relative free energies (kJ molꢀ1).
+
–
+
+
–
+
–
+
Fig. 4. Calculated reaction profile for SN2 (red) for the reaction between 4-DMAP and 1,2-diiodoethane. No transition states were located for the
attack via halogen bonding.
Pyridine derivatives have been reported to undergo SN2
reactions with 1,2-haloalkanes, rather than elimination or the
halogen bonding based attack observed for phosphine/NHC.[18]
Modelling of this process using 4-DMAP (4-dimethylamino-
pyridine) as the pyridine indicates that the transition state barrier
for the SN2 is significantly lowered in comparison with NHCs,
with a barrier of 73 kJ molꢀ1 for 4-DMAP (Fig. 4). For the
pathway associated with halogen bonding attack on iodine, a
transition state was not able to be located, however the overall
reaction is thermodynamically unfavourable. The inability to
locate a transition state may also indicate that pyridines are less
prone to engaging in halogen bonding interactions than NHCs.

618
T. B. Poynder et al.
The lack of experimental observation of elimination/deprotona-
tion as a pathway can be rationalised by the lowered basicity of
pyridines as compared with NHCs.
Supplementary Material
NMR and mass spectra as well as calculated Cartesian coordi-
nates are available on the Journal’s website.
Conclusions
Conflicts of Interest
The attempted synthesis of NHC-stabilised dicarbon fragments
via nucleophilic substitution at 1,2-diiodoethane resulted in a
clean reaction via an NHC–halogen bonding interaction, elim-
inating ethene. The resistance to the substitution pathway
inspired an in-depth theoretical study comparing the reaction
pathways between other nucleophiles and alkyl halides. The
results highlight the importance of the halogen bonding capacity
between NHCs and iodine compared with other systems, sug-
gesting potential applications for halogen bonding interactions
between NHCs and organic compounds.
The authors declare no conflicts of interest.
Acknowledgements
The authors thank The La Trobe Institute for Molecular Science for their
generous funding of this project. This work was also supported by an ARC
Future Fellowship (JLD, FT16010007). Generous allocation of computing
resources from National Computational Infrastructure (NCI), Intersect, and
La Trobe University are acknowledged.
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