Bimolecular reaction via the successive introduction of two substrates into the crystals of networked molecular cages

Article abstract of DOI:10.1021/ja209290t

Two substrates, 4-hydroxydiphenylamine (3) and ethyl isocyanate (4), were successively introduced into the crystals of networked M₆L ₄ cages 1. Because of the encapsulation effect, most of the initially introduced substrate 3 remaine

Full text of DOI:10.1021/ja209290t

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Bimolecular Reaction via the Successive Introduction of Two
Substrates into the Crystals of Networked Molecular Cages
Yasuhide Inokuma, Nodoka Kojima, Tatsuhiko Arai, and Makoto Fujita*
Department of Applied Chemistry, School of Engineering, The University of Tokyo, and JST-CREST, 7-3-1 Hongo, Bunkyo-ku,
Tokyo 113-8656, Japan
S Supporting Information
b
The distinct features of the two compartments prompted us to
ABSTRACT: Two substrates, 4-hydroxydiphenylamine
(3) and ethyl isocyanate (4), were successively introduced
into the crystals of networked M6L4 cages 1. Because of the
encapsulation effect, most of the initially introduced sub-
strate 3 remained within the crystals during immersion in a
solution of 4. X-ray analysis revealed that before the reac-
tion, the nucleophilic NH group of 3 is effectively protected
by tight packing within the cage units while the OH group is
exposed to the incoming second substrate. Successive
introduction of 4 into the crystal results in the chemoselec-
tive acylation of 3 at the less nucleophilic OH group. The
observed chemoselectivity is consistent with that exhibited
by discrete M6L4 cage 2 in solution.
design a bimolecular reaction via the successive introduction of
two substrates into the crystal. Our idea was to firmly entrap the
first substrate in the M6L4 cages and subsequently introduce the
second substrate into the interstitial pores without leaching of
the first substrate from the cages. Accordingly, we examined the
acylation of 4-hydroxydiphenylamine (3) with ethyl isocyanate
(4) in the cavities of 1. We report that the bimolecular reaction
was successfully promoted by our strategy, and we unexpectedly
observed unusual chemoselective O-acylation in this reaction.
Network 1 was prepared from tris(4-pyridyl)triazine (TPT)
and Co(NCS)2 in a MeOH/o-dichlorobenzene mixture accord-
ing to the procedure reported previously.6 The introduction of
the first substrate 3 was easily accomplished simply by soaking
the crystals of 1 in a saturated toluene solution of 3, wherein
the orange crystals of 1 immediately turned reddish-black and
revealed broad charge-transfer (CT) bands at 500À700 nm in
the diffuse reflectance spectra [Figure S1 in the Supporting
Information (SI)]. The thermogravimetric analysis and extrac-
tion experiment showed that included guest 3 amounted to
∼35 wt %. On the basis of the elemental analysis, the inclusion
complex (hereafter denoted as 1⊃3) was best formulated as
remendous effort has been devoted to the design and
T
utilization of porous coordination networks1 as solid-state
reaction containers.2,3 Unlike solution reactions, however, the
successive introduction of two substrates into crystals is a
seemingly simple yet unexpectedly difficult task and has rarely
been examined because the in-diffusion of the second substrate
often induces out-diffusion of the first.4 Crystalline-state reac-
tions in the pores have therefore been typically examined by
covalently or noncovalently installing the first substrate on the
network framework and then introducing the second substrate
(reagent) by diffusion.5 We recently synthesized coordination
network 1 consisting of two structurally unique compartments:
infinitely arrayed octahedral M6L4 cages and the remaining
interstitial pores.6 Like their counterpart Pd6L4 discrete cages
(2),7 the M6L4 cage units of 1 strongly bind incoming substrates,
whereas the interstitial pores do not; in contrast, however,
the substrates have fluidity in the networked M6L4 crystal.
[(Co(NCS)2)3(TPT)4(3)m (solvent)]n (m = 8À9).
3
The guest inclusion occurred in a single-crystal-to-single-
crystal fashion, and because of the strong hostÀguest binding
in the cage, the guests were not disordered. The inclusion
geometry of 3 within the cage was clearly displayed by crystal-
lographic analysis (Figure 1).8 The X-ray structure revealed that
four guests 3 are fixed in the M6L4 cage unit along the cage’s S4
symmetry axis. The OH groups of the molecules of 3 are exposed
toward the interstitial pores at every portal of the cage, while the
NH groups are fully shielded by the TPT ligands (Figure 1b).
The large interstitial pores also included guests 3, which were
crystallographically located at two different positions. The larger
thermal ellipsoids and lower occupancies suggested weak binding
of the guest molecules in the pores. Importantly, the environ-
ment of 3 in the M6L4 cages differs considerably from that in the
interstitial pores.
Subsequently, the second substrate 4 was introduced into the
crystal by immersing the crystals of 1⊃3 in a decane solution
containing a large excess of 4. After 12 h, the crystals were filtered
and decomposed using HCl. The products formed in the crystal
were then extracted with CH2Cl2 and analyzed by NMR
spectroscopy, which showed the formation of the O-acylated
Received: October 2, 2011
Published: November 09, 2011
r
2011 American Chemical Society
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Figure 1. X-ray crystal structures of the inclusion complex 1⊃3:
(a) network structure; (b) one M6L4 cage. Guests 3 are represented as
CPK models. Other guests 3 in the interstitial pores have been omitted
for clarity.
Figure 2. Plot showing the relationship between the NMR yield of each
component 3À6 and the time of exposure of inclusion complex 1⊃3 to
vaporous EtNCO.
Scheme 1. Acylation of 4-Hydroxydiphenylamine (3) with
Ethyl Isocyanate (4) in Crystals of 1⊃3 and in Toluene
Solution
Scheme 2. Chemoselective Acylation of 3 with Pd6L4 Cage 2
in Solution
a Inclusion complex 1⊃3 was soaked in a decane solution containing a
large excess of 4 for 12 h. b A toluene solution of 3 was treated with excess
4 (added using a syringe pump) for 12 h.
4, in situ-formed 6 was not converted into 7. These results led
us to conclude that there are two competing reaction pathways
in the network crystals 1: (1) N-acylation of 3 followed by
O-acylation (3 f 5 f 7) and (2) O-acylation of 3 without
further reaction (3 f 6). On the basis of the crystal structure of
1⊃3, we reasoned that path (1) occurs in the large interstitial
pores, where the substrates are mobile, and path (2) takes place
in the cavity of the M6L4 cage, where N-acylation is completely
suppressed by the protection effect of the cage.
To confirm the inhibition of N-acylation by the cage, a control
experiment with discrete Pd6L4 cage 2 was examined in solution.
When powdered 3 was suspended in an aqueous solution of host
2, the solution color turned dark-red, and the encapsulation of 3
was clearly indicated by the upfield shift of the guest signals in
the 1H NMR spectrum (Scheme 2; alsosee theSI). The protons of
the unsubstituted phenyl ring of 3 were shifted more than those
of the 4-hydroxyphenyl group (see the SI), consistent with the
inclusion geometry of 3 in the 1⊃3 complex, where the N site is
shielded but the O site is exposed. When the solution of 2⊃3 was
treated with 5 equiv of 4, O-acylated product 6 was selectively
formed. The product was no longer a suitable guest for the cage
and precipitated as a colorless solid. This result strongly supports
the conclusion that N-site protection and O-selective acylation
occur within the networked M6L4 cages of 1.
and N,O-diacylated compounds 6 and 7 in yields of 38 and 55%,
respectively (Scheme 1).9 It is worthy of note that a total of 93%
of the originally introduced substrate 3 was acylated in the crystal
without leaching out. Analysis of the supernatant consistently
showed the leaching of only a small amount of the products
(7%). Practically, this small amount of product leaching was
completely avoided by introducing 4 into the crystals using a
vapor diffusion method. The crystallinity of network 1 remained
intact throughout the reaction, and leaching of free TPT ligand or
Co(II) ions was not detected by an elution test.
In this reaction, we unexpectedly observed unusual chemos-
electivity. As mentioned above, only O-acylated product 6 and N,
O-diacylated product 7 were formed, and N-acylated product 5
was not detected in the reaction mixture. In other words, the
acylation predominantly occurred at the less nucleophilic O site,
in striking contrast to the selective N-acylation of free 3 in
solution under standard conditions (Scheme 1). Despite the
presence of the unreacted amino group in 6, prolonged treatment
with 4 for 24 h did not cause any change in the product ratio.
Thus, the chemoselective formation of 6 is ascribed to the
protection of the N site by the cage, as clearly revealed by
X-ray structure.
In conclusion, the unique structural feature of networked
M6L4 cages 1 has facilitated the design of a bimolecular reaction
via the successive introduction of two substrates into the cavities
of a crystalline coordination network. Highly efficient hostÀ
guest interactions in the cages control the substrate geometry
in the crystal, resulting in high reaction selectivities (here,
chemoselectivity in the acylation of an aminophenol). We note
that the events observed in the M6L4 cage units are exactly the
To understand the unusual chemoselectivity, we traced the
product ratio during the reaction (Figure 2) by quenching the
reaction at various points and analyzing the products by NMR
spectroscopy. The product distribution at 0À4 h clearly revealed
that N-acylated product 5 was involved at the early stage of the
reaction and clearly served as an intermediate for the N,O-
diacylated product 7. Interestingly, the yield of 6 slowly but
monotonically increased over 8 h. Even in the presence of excess
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same as those in discrete Pd6L4 cage 2. Hence, the rich hostÀ
guest chemistry of 2 in solution10 can in principle be translated
into solid-state chemistry, offering various potential applications
of coordination network materials.
’ ASSOCIATED CONTENT
S
Supporting Information. Experimental details, charac-
b
terization data, and crystallographic data (CIF). This material is
available free of charge via the Internet at http://pubs.acs.org.
’ AUTHOR INFORMATION
Corresponding Author
mfujita@appchem.t.u-tokyo.ac.jp
’ ACKNOWLEDGMENT
This work was supported by KAKENHI, Japan Society for the
Promotion of Science.
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