Regioselective control of aromatic halogenation reactions in carbon nanotube nanoreactors

Article abstract of DOI:10.1039/c3cc42414f

The use of single-walled carbon nanotubes as effective nanoreactors for preparative chemical reactions has been demonstrated for the first time. Extreme spatial confinement of reactant molecules inside nanotubes has been shown to drastically affect both the regioselectivity and kinetics of aromatic halogenation reactions.

Full text of DOI:10.1039/c3cc42414f

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Regioselective control of aromatic halogenation
reactions in carbon nanotube nanoreactors†
Cite this: Chem. Commun., 2013,
49, 5586
Scott A. Miners, Graham A. Rance and Andrei N. Khlobystov*
Received 3rd April 2013,
Accepted 8th May 2013
DOI: 10.1039/c3cc42414f
www.rsc.org/chemcomm
The use of single-walled carbon nanotubes as effective nanoreactors however, that due to the significant van der Waals attraction between
for preparative chemical reactions has been demonstrated for the first the one-dimensional host and high molecular weight incarcerated
time. Extreme spatial confinement of reactant molecules inside nano- guests, such as those formed in the oligomerisation reactions, extrac-
tubes has been shown to drastically affect both the regioselectivity and tionandrecoveryoftheformedproductisnotpossibleandassuchno
kinetics of aromatic halogenation reactions.
preparative reactions using SWNT have been performed so far. A more
attractive approach would be to probe well-known transformations of
small molecules, where inherently weaker intermolecular forces are
present, thus minimising the detrimental issue of product recovery. In
this study, we have investigated the influence of confinement in
narrow carbon nanotubes on aromatic halogenation reactions and
demonstrate for the first time regioselective control of preparative
chemical reactions using single-walled carbon nanoreactors.
The bromination of N-phenylacetamide by pyridiniumdichloro-
bromate (PyHCl2Br)13 in solution reliably and reproducibly forms an
unselective (68 : 32) mixture of N-(4-bromophenyl)acetamide ( para-
regioisomer) and N-(2-bromophenyl)acetamide (ortho-regioisomer)
respectively. This reaction is therefore an ideal probe to study
the effect of confinement on regioselectivity. The para-selective
bromination of N-phenylacetamide due to spatial confinement
within cyclodextrin cavities14 has been previously demonstrated
and attributed to the site selective electrophilic attack of the
incarcerated aromatic guest directed by the truncated conical
shape of the cyclodextrin host. As SWNT have cylindrical cavities
analogous to cyclodextrins, a similar effect of confinement is
expected to be possible in carbon nanotubes.
However, in order to demonstrate selectivity, it is integral
that a nanotube of suitable diameter be used which can
successfully discriminate between the formation of para- and
ortho-products. Geometric considerations showed single-walled
carbon nanotubes produced by the HiPCO15 process to have the
most suitable diameters for this purpose (Fig. 1b).
In order to ensure that the bromination reaction, known to
readily occur in the absence of nanotubes, was conducted within
the SWNT hollow interior, it was essential that one of the reactants
be encapsulated prior to the reaction. After extensively testing
possible methods of reactant encapsulation the most effective
method was found to be immersion of open nanotubes in molten
N-phenylacetamide; the nanotubes becoming spontaneously filled
with the reactant due to capillary forces. This has proven to be an
The confinement of guest molecules within host containers provides
a novel way to control the properties of the guest, manipulate
reaction pathways and govern the outcome of chemical reactions.
In recent decades, the reactions of molecules encapsulated within
various nanoreactors, such as cyclodextrins, cavitands, calixarenes,
supramolecular/coordination cages and zeolites, have been shown to
be drastically altered by confinement, where concentration, pressure,
reactant alignment and thus activation energy barriers become
critically influenced by the host.1 However, the use of hollow carbon
nanostructures, such as single-walled carbon nanotubes (SWNT), as
containers for confined reactions has yet to be explored; these
structures, which possess two nanoscopic and one macroscopic
dimensions (1D), bridge the gap between previously studied mole-
cular containers (0D) and porous solids (3D).
SWNT possess a cylindrical cavity of tunable size which permits the
encapsulation of a wide range of guest molecules through ubiquitous
van der Waals forces. Furthermore, as SWNT exhibit high mechanical,
chemical and thermal stability, reactions inside carbon nanotubes
can be carried out under a wider range of conditions than is possible
with existing nanoreactor systems.2 Previous studies have shown that
the regioselectivity and activity of metal-catalysed reactions are
affected by confinement inside carbon nanostructures,3–7 however
metal-free reactions represent a more direct way to study the confine-
ment effects induced by the nanotube itself. Few such reactions have
been carried out within carbon nanotubes to date, but notable
examples include the formation of linear structures, such as fullerene8
and fullerene epoxide oligomers,9 graphene nanoribbons10,11 and the
transformation of Fe(C60Me5)Cp into C70.12 It is important to note,
School of Chemistry, The University of Nottingham, University Park, Nottingham,
NG7 2RD, UK. E-mail: Andrei.Khlobystov@Nottingham.ac.uk;
Fax: +44 (0)115 9513563; Tel: +44 (0)115 9513917
† Electronic supplementary information (ESI) available: Experimental detail and
theoretical calculations. See DOI: 10.1039/c3cc42414f
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5586 Chem. Commun., 2013, 49, 5586--5588
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Fig. 1 Comparison of the van der Waals diameter of the internal cavity (dNT) of three
types of nanotubes to the critical van der Waals diameter (dcritical) of reactant and
product molecules. (a) CoMoCAT SWNT (dNT = 4.3 Å), too narrow to allow confine-
ment of the reactant (dcritical = 6.9 Å); (b) HiPCO SWNT (dNT = 6.9 Å), allowing the
formation of para- but not ortho-product and (c) wider AD SWNT (arc discharge)
(dNT = 9.6 Å) freely allowing the formation of both products. (S1, ESI†)
Fig. 2 Schematic representation of the molten encapsulation and fractional distillation
procedure to remove excess external molecules leaving N-phenylacetamide@SWNT.
dependent on their method of production, we conducted a series of
experiments with nanotubes produced by arc discharge (AD) and
CoMoCAT techniques whose average diameters are respectively wider
and narrower than that of HiPCO SWNT. The use of narrower
CoMoCAT SWNT (average van der Waals diameter of nanotube
internal cavity dNT = 4.3 Å, entry 4, Table 1) resulted in no change in
para-selectivity relative to the reaction in solution (entry 1), consistent
with the insufficient diameters of these nanotubes to encapsulate N-
phenylacetamide reactant molecules (Fig. 1a). Using wider AD SWNT
(dNT = 9.6 Å, entry 5) also gave no change in selectivity as the nanotube
diameter is large enough for both products to form with no size
discrimination (Fig. 1c). This comparison of different nanotubes
proves that the significant improvement in para-selectivity observed
in HiPCO SWNT is not due to any interaction with the nanotube
exterior, but instead a result of extreme and precise confinement
controlled by matching the size and shape of the reaction products
with the nanotube.
effective method as virtually all molecular liquids have a surface
tension below the 200 mN mÀ1 threshold for efficient encapsula-
tion.16 However, as immersion requires a significant excess of
molten N-phenylacetamide, this method, although highly effective
in filling nanotubes, unfortunately produces an excess of N-phenyl-
acetamide adsorbed on SWNT which must be removed prior to the
reaction. Several studies of the dynamics of molecules, particularly
water, confined within narrow SWNT have predicted that encapsu-
lated guests would exhibit drastically different behaviour to that of
the bulk phase due to arrangement in pseudo-1D arrays. For
example, both the melting17 and boiling point18 of water have been
calculated to be significantly elevated by confinement in narrow
SWNT. We therefore exploited this principle and developed a novel
fractional distillation procedure (Fig. 2) to separate the excess
external N-phenylacetamide from the confined molecules.
As the fractional distillation proceeds, the proportion of
external N-phenylacetamide decreases relative to the confined
molecules. By sampling the N-phenylacetamide@SWNT at dif-
ferent stages of fractional distillation, we are able to study
confinement effects by measuring the para-selectivity of the
subsequent bromination reaction (Fig. 3).
The plot demonstrates a clear increase in selectivity towards
the para-product as the excess N-phenylacetamide is removed
from the SWNT surface (up to 97% para-selectivity), confirming
that confinement in SWNT, similarly to cyclodextrins, promotes
the formation of the para-product. A control experiment with
closed nanotubes, where the reactant is not able to enter the
SWNT cavities, showed no increased yield of the para-product
(entry 2, Table 1) compared to solution (entry 1) confirming
that the open SWNT do act as nanoreactors (entry 3).
The regioselective outcome of the reaction is determined by the
precise match between the nanotube diameter and the diameters of
reactants/products. Since the diameters of SWNT are largely
Fig. 3 Plot of para-selectivity against N-phenylacetamide/SWNT mass ratio
showing the onset of confinement effects as the mass ratio of N-phenylaceta-
mide to SWNT decreases.
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Table 1 Effect of confinement in nanotubes on the regioselective halogenation
of N-phenylacetamide
Product ratio/%
Carbon nanotube
None
Halogenation agent Para
Ortho
1
2
3
4
5
6
7
PyCl2Bra
68
69
97
70
69
15
42
32
31
3
30
31
85
58
HiPCO SWNT (closed) PyCl2Br
Fig. 4 Schematic representation of the bromination reaction mechanism in a
HiPCO SWNT
CoMoCAT SWNT
AD SWNT
None
HiPCO SWNT
PyCl2Br
PyCl2Br
PyCl2Br
SWNT showing the formation of an intermediate with a large dipole moment
which is stabilised by
a highly polarisable nanoreactor, thus lowering the
b
Cl2
activation barrier and accelerating the reaction in nanotubes.
Cl2
a
Standard conditions: N-phenylacetamide (1.0 eq.), PyCl2Br (0.6 eq.
1.5 mmol dmÀ3), H2O, RT, 24 h. Standard conditions: N-phenyl- molecules from solution,21,22 can be employed for carbon nano-
acetamide (1.0 eq.), Cl2 (1000-fold excess), H2O, RT, 90 min (S2, ESI†).
b
reactors. Furthermore the enhanced thermal and chemical stability
of the SWNT interior surface combined with the rich reactivity of the
SWNT outer surface23–25 open up opportunities for constructing
Similarly to the bromination, we have shown that selectivity of the
chlorination reaction19 increases from 15% of para-product in
solution (entry 6, Table 1) to 42% due to confinement inside HiPCO
bespoke recyclable nanoreactors26 tailored for chemical processes
leading to products unattainable by other means.2
SWNT (entry 7). Furthermore, conversion rates of N-phenylacetamide
halogenation reach 100% in the optimum cases thus suggesting
facile diffusion of products from nanoreactors.
Notes and references
Para-selectivity is expected to rise sharply as surface adsorbed N-
phenylacetamide excess is removed by the fractional distillation.
However, our measurements indicate a much more gradual increase
in para-selectivity (Fig. 3) suggesting that not all N-phenylacetamide
reactant molecules could possibly be encapsulated at any one time.
Surprisingly, the measured selectivity for the para-product is higher
than is expected from the calculated proportion of encapsulated
N-phenylacetamide molecules at the start of the reaction, already
reaching 97% when just a minority of reactant molecules are encap-
sulated (S3, ESI†). This observation suggests that the rate of the
confined reaction is significantly accelerated compared to that of
the bulk and reactant molecules are diffusing into the nanotube
during the reaction. The theoretical simulations of Halls and
Schlegel20 predicted that nanotube confinement would substantially
affect the Menshutkin SN2 reaction and showed that the highly
polarisable nanotube stabilised the charge separation in the transition
state which significantly lowered the activation energy and endo-
thermicity compared to the reaction in the gas phase. The aromatic
bromination reaction mechanism (Fig. 4) also forms an intermediate
with a large charge separation (i.e. high dipole moment) and it is
therefore reasonable to surmise that the highly polarisable nanotube
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