Selective encapsulation of volatile and reactive methyl iodide

Article abstract of DOI:10.1039/c2cc34346k

A simple organic molecular container can selectively encapsulate the volatile and highly reactive MeI through hydrogen-bonding interactions in solution. The remarkable encapsulation of MeI without self-methylation of the container appears to be determined by the complementary binding sites and the rigidity of the hydrogen-bonding array constrained by the molecular framework.

Full text of DOI:10.1039/c2cc34346k

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Selective encapsulation of volatile and reactive methyl iodide†
Yih-Chern Horng,*a Pin-Shen Huang,a Chang-Chih Hsieh,a Chih-Hong Kuo,a and Ting-Shen Kuob
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
DOI: 10.1039/b000000x
considered a desirable method for MeI removal since this method
50 facilitates non-destructive removal and recovery of MeI, which
can then be used in various organic syntheses.
5
A simple organic molecular container can selectively
encapsulate the volatile and highly reactive MeI through
hydrogen-bonding interactions in solution. The remarkable
encapsulation of MeI without self-methylation of the
container appears to be determined by the complementary
Although fluorescent sensors for the detection of MeI through
methylation in solution have recently been developed,11 synthetic
receptors for the recognition and encapsulation of intact
55 molecular MeI have not been designed. Hydrogen bonding
mediated by amino or amido groups (hydrogen-bond donors) in
the host is, by far, the most common noncovalent interaction for
recognition processes in supramolecular and biological host-guest
chemistry.12 Such interactions are also effective in mediating
10 binding sites and the rigidity of the hydrogen-bonding array
constrained by the molecular framework.
Molecular recognition is the fundamental property of a synthetic
or biological host that aids the specific selection of guests and
plays an important role in a wide variety of functions such as
15 sensing, adsorption, complexation, drug delivery, catalysis, and
membrane transportation.1 In the past three decades, numerous
host-guest complexes have been reported, and the key factors
controlling host-guest binding interactions have been identified to
be (i) preorganization of the receptors and (ii)
20 complementary stereoelectronic arrangement of binding sites in
the host and guest molecules.2 For the encapsulation of unreactive
small neutral molecules in solution,3 many elegant containers
with defined small internal volumes have been constructed from
unimolecular containers of Cram4 and Collet5, to the more recent,
25 self-assembling systems of Rebek.6 Nevertheless, the recognition
and encapsulation of small, highly reactive and hazardous species
such as phosgene, PBr3, H2O2, and methyl iodide (MeI) have not
been achieved because these species tend to react with the
specific functional groups (SFGs) of the synthetic molecular host
30 and form irreversible adducts. One approach to overcome this
challenge involves designing a host that does not have SFGs but
allows for noncovalent bonding interactions within its
complementary cavity. While there are a few examples7 that
demonstrate this principle, this approach is not practical because
35 the host-guest interactions are dependent on the molecular
packing arrangement and specific selectivity is poor. Employing
host molecules with shape-persistent architectures and sterically
constrained SFGs is an alternative solution, but there are no
published reports in this regard. Despite their ability to react with
40 suitable guests, the SFGs may become inert if structurally rigid,
thereby facilitating encapsulation and significant stabilization of
the guest molecule through effective interactions such as
hydrogen bonding. In the present study, we employed this
principle for the recognition and encapsulation of the highly
45 reactive molecule MeI. MeI shows moderate-to-high acute
toxicity for inhalation and ingestion;8 further, it is an
environmental pollutant9 and is an important component of
radioactive nuclear waste.10 Molecular encapsulation is
13
60 binding with I2 or I− guests14 in artificial receptors. However,
special methods must be adopted to design a receptor with NH
functionalities for the specific selection of MeI, so that
methylation of the hydrogen-bonding donor atoms is prevented.
We demonstrate for the first time that the highly reactive MeI can
65 be trapped selectively and intact by a simple molecular container
in solution through NH⋅⋅⋅I interactions, under ambient conditions.
Methylation of the secondary amine is prevented by
delocalization of the lone pair of electrons on the nitrogen atom
and the rigidity of the molecular container. In addition, the ability
70 of the container to prevent the evaporation of MeI is
demonstrated.
HN
NH
NH
R
H
HN
N
S
NH
H
S
S
N
R
S
S
HN
NH
S
R
NH
N
•
3X
H
NH
-
a:
=
=
=
2
R
H X
F
3SO3
C
=
,
1
2
-
:
e
M
,
2b R
X
I
Scheme 1 Chemical structures of the compounds discussed here.
In our research, we focused on the self-assembly and
75 encapsulation performance of cage-type molecules with dynamic
covalent bonds.15 We report a cylindrical organic container 1,16
which is a dimer of tripodal trisulfide precursors linked by three
disulfide bonds, as shown in Scheme 1. The container, which is
insoluble in most organic solvents but shows high solubility in
80 benzene or toluene, can encapsulate I2 in solution or in
amorphous solid state through NH⋅⋅⋅I interactions.13a On the basis
of the crystal structure of the I2⊂1 adduct and the architectural
stability of the container, we state that the internal
microenvironment of 1 with the rigidified hydrogen-bonding
85 array is ideal for trapping a single molecule of MeI.
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Before performing experiments on MeI encapsulation, the
solution of 1 at -20°C. Comparison of the structures of different
stability of the container toward protonation was investigated,
since protons are smaller entities that are more susceptible to
1-adducts (i.e., 1 having various encapsulated guests) revealed no
notable change in the structural parameters of the container
nucleophilic attack than is MeI. The chemical nature of 1 50 (ESI†), thereby confirming the architectural rigidity of the
5
remained unaffected even after treatment for 3 days with excess
CF3SO3H (strong organic acid) in toluene or with H2SO4 (strong
inorganic acid) in a toluene/CH3CN mixture, indicating that this
molecular container is resistant to protonation and can
encapsulate MeI without undergoing self-methylation.
container. As shown in Fig. 3, a single molecule of MeI is
accommodated in the cavity of 1 through weak three-point NH⋅⋅⋅I
hydrogen-bonding interactions (van der Waals radii: H, 1.20 Å; I,
1.98 Å).19 The C-I bond distance in the trapped MeI was
55 comparable with that in crystalline MeI at high pressures.20
Besides,
a nonbonding (lone pair) I⋅⋅⋅Ph (aromatic base)
interaction21 was observed (van der Waals radii: C, 1.70 Å; I,
1.98 Å) in the crystal structure.
10
1
Fig. 1 H NMR spectra (300 MHz, 298 K, toluene-d8 (*)) of MeI⊂1 (a)
purified 1 (b). (c) partial 1H-1H NOESY spectrum of MeI⊂1.
60 Fig. 2 Partial solid-state IR spectra of 1 as synthesized (a), crystalline
I2⊂1 (b), crystalline MeI⊂1 (c), and soild MeI⊂1 after exposure to the
atmosphere for over 24 h under ambient conditions (d). The dashed gray
lines represent the N-H stretching frequencies at 3370 and 3390 cm-1.
Addition of 1 mol equiv of MeI to a stirred toluene solution of
15 1 at ambient temperature resulted in the formation of a large
amount of light-yellow precipitate within 2 min, confirming that
1 is capable of encapsulating MeI in solution. The 1H NMR
spectrum of the precipitate in toluene-d8 was recorded at room
temperature, although the precipitate was only sparingly soluble
20 in this solvent. The spectrum showed significant shift of the host
signals, especially the amino and aromatic proton signals (Fig. 1a
and b). The C3 symmetry of the container remained unchanged,
indicating that none of the nitrogen atoms was uniquely
methylated. Besides, NOESY spectrum (Fig. 1c) showed a cross
25 peak between the MeI and N-H resonances of 1, revealing the
weak spatial correlation between the protons of MeI and the
amino protons oriented toward the cavity. These observations
along with DOSY NMR experiments (ESI†) indicated that the
MeI molecules were well accommodated in the cavity of 1 in
30 solution. The packing coefficient (PC)17 of 0.57 for MeI (ESI†) is
in good agreement with the optimal packing in solution
postulated by Rebek. No chemical shift was observed in the
spectrum of 1 when iodides with larger molecular volume such as
EtI (ESI†) or iPrI were used, consistent with their larger PCs
35 (>75%). However, CH2Cl2 with similar volume to MeI showed
no evidence of encaptulation.13a Thus, more specific interactions
other than just molecular packing should be involved for the
encaptulation of MeI in solution, as compared to other similar C3
symmetric hosts.18 The solid-state IR spectrum of the precipitate
40 showed N-H stretching bands with equal intensities at 3370 and
3390 cm-1, which were identical to the stretching vibrations for
I2⊂1and 1, respectively, indicating that only three of the six NH
groups of 1 were involved in hydrogen bonding with MeI in the
solid state (Fig. 2a, b, and c).
Upon encapsulation in 1, MeI became less volatile, and the
65 amount of MeI⊂1 solid immersed in toluene remained unchanged
even after exposure to the atmosphere for over 4 months under
ambient conditions. This behavior was contradictory to that of the
naked MeI in toluene under the same concentration conditions: in
this case, MeI vaporized completely within 7 days. As the
70 temperature of the mixture increased to 80°C, the precipitates
dissolved within 2 h and the trapped MeI was released from the
1
cavity, with the concurrent regeneration of 1, as revealed by H
NMR analyses. In the IR spectrum of the solid MeI⊂1 exposed to
the atmosphere at ambient temperature for 24 h, the intensity of
75 the NH stretching band at 3370 cm-1 decreased by about 10%,
indicating that 1 efficiently retarded the evaporation of MeI even
under non-solvated conditions (Fig. 2d).
Fig. 3 Molecular structure of MeI⊂1: side view (left) and top view (right).
80 The thermal ellipsoids are drawn at a 35% probability level. The MeI
molecule is statically disordered with the two positions for carbon and
iodide atoms interchangeable. Hydrogen atoms bound to carbon atoms in
1 are omitted for clarity. The dashed lines represent NH···I hydrogen
bonding interactions. Selected distances [Å] and angles [°]: C-I 2.100,
85 NH···I 3.238, I···X 3.462 (X = centroid of the aromatic base); N-H-I
156.7, C-I-X 180.0.
45
MeI⊂1 crystals suitable for X-ray crystallographic analysis
were prepared by slow diffusion of neat MeI into a toluene
2
|
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a Department of Chemistry, National Changhua University of Education,
To assess whether MeI encapsulation occurred without the
1 Jin-De Road, Changhua 50058, Taiwan. Fax: 886 4721 1190; E-mail:
ychorng@cc.ncue.edu.tw
self-methylation of 1, we synthesized a modified receptor 2,
which does not have disulfide linkages, and investigated its
electronic and structural features after protonation and
methylation. The (Ph)C−N bond distances in 2 (ESI†) were
similar to those in the 1-adducts and the trimethylated product
obtained from the trisulfide precursor of 1 (ESI†) and were
typical of aniline-type C−N bonds with partial double-bond
character. The reaction of 2 with 3 equiv CF3SO3H in CH2Cl2
10 readily afforded the triprotonated salt in quantitative yield within
3 h. However, treatment of 2 with 6 equiv MeI in toluene under
ambient conditions afforded the methylated products in very low
yield (15%) after 12 h, presumably because delocalization of the
lone-pair of electrons weakened the nucleophilicity of the
15 nitrogen atoms toward MeI. Crystal structure analysis of the
b Instrumentation Center, Department of Chemistry, National Taiwan
55 Normal University, Taipei 11677, Taiwan.
5
† Electronic Supplementary Information (ESI) available: Experimetal
details and single-crystal data. CCDC 883531 (MeI⊂1), 883532 (2),
883533 (2a), and 883534 (2b). For ESI and crystallographic data in CIF
or other electronic format see DOI: 10.1039/b000000x/
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65
70
75
80
85
protonation and methylation products of
2 (2a and 2b,
respectively) revealed that the aminophenyl rings, which were
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(for 2b, Fig. 4; for 2a, ESI†). Such a structural adaptation was not
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Fig. 4 The molecular structure (left) and space-filled model (right) of the
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A promising strategy for the selective encapsulation of volatile
and reactive species on the basis of the steric hindrance of a
35 reactive functionality constrained by a simple, structurally rigid
organic capsule with a complementary cavity is proposed. This
method allows for the selective recognition and encapsulation of
the environmentally relevant and highly reactive MeI in solution.
The structurally rigidified reactive functional groups within the
40 host’s skeleton provide a stabilizing effect that aids the selective
recognition and encapsulation of reactive substances. Our
approach can be extended to other reactive and hazardous species
through appropriate design of the functional cavity and molecular
framework. Preparation of larger water-soluble analogs of 1 that
45 act as hosts for highly complicated reactive guest species and
have greater biological relevance is currently underway.
100
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effects of the trapped MeI molecule. This is further supported by the
fact that the stretching frequencies of the NH groups, which are
involved in hydrogen bonding with the I atoms, in I2⊂1 and MeI⊂1
are nearly identical in the solid-state IR spectra.
105
110
115
120
We are grateful to the National Science Council (Taiwan) for
their financial support of this work (NSC 99-2113-M-018-003-
MY3).
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50 Notes and references
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3