Amine-Linked Covalent Organic Frameworks as a Platform for Postsynthetic Structure Interconversion and Pore-Wall Modification

Article abstract of DOI:10.1021/jacs.0c12249

Covalent organic frameworks have emerged as a powerful synthetic platform for installing and interconverting dedicated molecular functions on a crystalline polymeric backbone with atomic precision. Here, we present a novel strategy to directly access amine-linked covalent organic frameworks, which serve as a scaffold enabling pore-wall modification and linkage-interconversion by new synthetic methods based on Leuckart-Wallach reduction with formic acid and ammonium formate. Frameworks connected entirely by secondary amine linkages, mixed amine/imine bonds, and partially formylated amine linkages are obtained in a single step from imine-linked frameworks or directly from corresponding linkers in a one-pot crystallization-reduction approach. The new, 2D amine-linked covalent organic frameworks, rPI-3-COF, rTTI-COF, and rPy1P-COF, are obtained with high crystallinity and large surface areas. Secondary amines, installed as reactive sites on the pore wall, enable further postsynthetic functionalization to access tailored covalent organic frameworks, with increased hydrolytic stability, as potential heterogeneous catalysts.

Full text of DOI:10.1021/jacs.0c12249

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Article
Amine-Linked Covalent Organic Frameworks as a Platform for
Postsynthetic Structure Interconversion and Pore-Wall Modification
Lars Grunenberg, Gökcen Savasci, Maxwell W. Terban, Viola Duppel, Igor Moudrakovski, Martin Etter,
Robert E. Dinnebier, Christian Ochsenfeld, and Bettina V. Lotsch*
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ABSTRACT: Covalent organic frameworks have emerged as a
powerful synthetic platform for installing and interconverting
dedicated molecular functions on a crystalline polymeric backbone
with atomic precision. Here, we present a novel strategy to directly
access amine-linked covalent organic frameworks, which serve as a
scaffold enabling pore-wall modification and linkage-interconver-
sion by new synthetic methods based on Leuckart−Wallach
reduction with formic acid and ammonium formate. Frameworks
connected entirely by secondary amine linkages, mixed amine/
imine bonds, and partially formylated amine linkages are obtained
in a single step from imine-linked frameworks or directly from
corresponding linkers in a one-pot crystallization-reduction
approach. The new, 2D amine-linked covalent organic frameworks, rPI-3-COF, rTTI-COF, and rPy1P-COF, are obtained with
high crystallinity and large surface areas. Secondary amines, installed as reactive sites on the pore wall, enable further postsynthetic
functionalization to access tailored covalent organic frameworks, with increased hydrolytic stability, as potential heterogeneous
catalysts.
requires an additional pore-wall activation step, e.g., the
reduction of nitro groups to amines14 or the deprotection of
ethers to alcohols.15 In essence, a typical synthetic route would
consist of at least four sequential steps, including (a)
framework crystallization, (b) linkage transformation, (c)
pore-wall activation, and (d) pore-wall functionalization, to
obtain both stable and decorated frameworks. Being faced with
varying conversion yields and a loss of material between each
step, innovative synthetic methods condensing these trans-
formations into fewer steps, or even a single synthetic step, are
highly desirable.
As a solution to the challenges discussed, we here
demonstrate amine-linked covalent organic frameworks as a
powerful platform for facile pore-wall modification and linkage
interconversion enabled by new synthetic methods based on
Leuckart−Wallach16,17 reduction with formic acid and
ammonium formate. By fine-tuning reaction conditions,
frameworks connected entirely by secondary amine linkages,
mixed amine/imine bonds, and partially formylated amine-
INTRODUCTION
■
In recent years, covalent organic frameworks (COFs) have
emerged as a versatile class of crystalline porous polymers,
which have been pushing the frontiers of single-site
heterogeneous catalysis ever since. The unique combination
of ordered and tunable pore structures, with high surface areas
and versatile (opto-)electronic properties, offers great oppor-
tunities beyond gas storage and separation, including sensing,
electrochemical energy storage, optoelectronics, and heteroge-
neous (photo)catalysis.1−4
Imine-linked COFs constitute the most widely studied
subclass of COFs owing to their broad synthetic scope and
facile building block synthesis. The dichotomy of dynamic
covalent chemistry in COF synthesis implies that, while
reversible bond formation is critical for crystallization, the
reversibility of imine bond formation also causes its limited
stability against hydrolysis. To address this issue, several
postsynthetic locking strategies have been developed in the
past, e.g., converting labile imine-linked COFs into stable
benzothiazole-,5,6 amide-,7 or quinoline-linked frame-
works.4,8−13 Although these methods significantly increase
the material’s hydrolytic stability, most do not activate but
rather deactivate potential reactivity of the linkages for further
pore-wall modification. To achieve the latter, reactive centers
have to be installed into the linker moieties, which are often
incompatible with synthesis conditions. This incompatibility
Received: November 23, 2020
Published: February 24, 2021
© 2021 The Authors. Published by
American Chemical Society
https://dx.doi.org/10.1021/jacs.0c12249
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Figure 1. (a) Synthesis of amine-linked covalent organic frameworks. (b) FT-IR spectra, (c) 13C CP-MAS ssNMR spectra, and (d) XRPD pattern
comparison of PI-3-COF (green) and rPI-3-COF (blue). (e and f) Chemical structure of a single pore of (e) rPI-3, (f) rTTI, and (g) rPy1P-COF.
(h−j) Rietveld refinements for (h) rPI-3, (i) rTTI, and (j) rPy1P-COF.
linkages are accessible in a single step from imine-linked
frameworks or directly from the corresponding linkers in a
one-pot crystallization-reduction approach. We thus present a
novel strategy enabling direct access to amine-linked covalent
organic frameworks. In addition, we reveal correlations
between topologically equivalent disordered and crystalline
frameworks, which are not accessible by typical X-ray powder
diffraction (XRPD) analysis, using pair distribution function
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(PDF) analysis, solid-state nuclear magnetic resonance spec-
troscopy (ssNMR), and quantum-chemical calculations. These
findings enable us to identify unique pH-dependent amorph-
ization pathways and hence expand our fundamental under-
standing of amine-linked covalent organic frameworks as an
important yet underexplored class of heterogeneous catalysts.
Structural analysis of rPI-3-COF via XRPD reveals high
crystallinity (Table S3), represented by four narrow reflections
at 2θ = 5.6°, 9.7°, 11.2°, and 14.9°, indexed as 100, 110, 200,
and 210 reflections (space group P6̅), and a broad stacking
reflection at 2θ = 25.3°. Compared to its parent imine
structure (PI-3-COF), the apparent hexagonal symmetry and
crystallinity are retained, while a significant shift of the broad
stacking reflection at 2θ = 25.6° (PI-3-COF) toward smaller
angles appears. Rietveld24 refinement gives a larger in-plane
unit cell parameter of a = 18.090(7) Å and an increased
stacking distance of c = 3.5425(12) Å in rPI-3-COF (a =
18.034(7) Å and c = 3.5058(12) Å for PI-3-COF) (Table S1).
While the cell parameter a is affected by increased CN
(149 pm) vs CN (127 pm)25 bond lengths, the stacking
distance (c parameter) is also influenced by both enhanced
steric repulsion of the benzylic (CH2) protons of adjacent
layers and higher flexibility of the secondary amine bond in
rPI-3-COF. Notably, sorption isotherms reveal the complete
retention of porosity and pore-size distributions (Figure S54,
S64) of the materials with Brunauer−Emmett−Teller (BET)
surface areas of 1395 m2g−1 for rPI-3-COF (Figure S74) and
1404 m2g−1 for PI-3-COF (Figure S71), even exceeding those
previously published for PI-3-COF (∼1000 m2g−1).23 It must
be noted, however, that the porosity of rPI-3-COF is strongly
influenced by the drying procedure: Simple vacuum-drying
from dichloromethane resulted in a reduced BET surface area
of 966 m2g−1 (Figure S77), while solvent exchange to
methanol (Soxhlet extractor) and subsequent activation with
supercritical CO2 (scCO2) gave the best results for rPI-3-COF
with 1395 m2g−1 (Figures S69 and S74). While this effect was
not observed for the rigid imine PI-3 framework, an increased
flexibility in rPI-3-COF and a modulated pore-wall polarity
upon reduction are expected to enhance solvent interactions
and capillary effects, potentially intensifying drying-induced
disorder and pore collapse.26,27 Scanning electron microscopy
(SEM) and transmission electron microscopy (TEM) images
reveal intergrown, coral-shaped particle morphologies with
sizes between 600 to 1000 nm, decorated with 200 nm long
and 60 nm wide stings, for both imine-linked and reduced
PI-3-COF (Figures S82 and S85). The similarity of the
morphology before and after reduction renders intermediate
recrystallization processes unlikely to be at play. TEM images
show uniformly distributed crystallinity and extended porous
channels of hexagonal symmetry in the materials, which are
consistent with the structural model derived from XRPD data
and Rietveld refinement (Figures S91 and S96).
To demonstrate the general applicability of this protocol, we
applied it to two additional imine COFs with larger pores,
different linker compositions, and pore geometry. Both
TTI-COF and Py1P-COF were successfully reduced to their
new amine-linked derivatives rTTI-COF and rPy1P-COF with
high crystallinity as evident from sharp reflections at 2θ = 4.0°
(100), 6.9° (110), 8.1° (200), and 25.6° (stacking) for rTTI
and 2θ = 3.7° (110), 5.4° (020), 7.5° (220), 8.5° (130), 11.3°
(330), and 23.2° (stacking) for rPy1P-COF, respectively.
During our screenings to find the optimum reduction
conditions for rPy1P-COF, we noticed palladium contami-
nation in both the building blocks and the framework,
introduced by palladium-based cross-coupling reactions during
linker synthesis. The TEM images of an initial sample of
Py1P-COF (Pd contaminated) show unevenly distributed
palladium nanoparticles in the material (Figures S94 and
S95).28 While this contaminant did not affect the crystal-
RESULTS
■
Previous Strategies and Drawbacks. During our studies,
we found that a reduction of imine-linkages would both
increase the hydrolytic stability of the framework and
introduce secondary amine-linkages as reactive centers for
further functionalization of the pore wall. This transformation,
familiar from small organic molecules as well as molecular
cages, is usually achieved using borohydride-based reducing
agents, such as sodium borohydride or sodium cyanoborohy-
dride.18−20 Borohydride-based reduction has successfully been
used for robust and rigid 3D systems, while 2D frameworks
have only been obtained with diminished crystallinity and low
surface areas at best.11,15,21 While highly reactive, reactions
with sodium borohydride, in particular, suffer from limited
selectivity and low functional group tolerance.5,22 With these
shortcomings in mind, we sought an alternative, mild reduction
procedure affording crystalline and porous amine-linked
covalent organic frameworks. To this end, we identified the
Leuckart−Wallach reduction with formic acid, reported for
small organic molecules by Leuckart in 1885 and further
developed by Wallach, as a suitable reduction strategy.16,17
Synthesis of Amine-Linked COFs. As a model system,
we first synthesized the imine-linked PI-3-COF from 1,3,5-
triformyl benzene (TFB) and 4,4′,4″-(1,3,5-triazine-2,4,6-
triyl)trianiline (TTA) under solvothermal conditions in a 2:1
mesitylene/1,4-dioxane mixture with aqueous 6 M AcOH at
120 °C for 72 h, according to a modified literature
procedure.23 Upon reacting the imine-linked PI-3 framework
in a sequential step with 19 equiv of formic acid in the same
solvent, a new vibration appeared at 3405 cm−1 as probed by
Fourier transform infrared spectroscopy (FT-IR), attributed to
a secondary amine (vNH) stretching mode. The intensity of
the imine vibration (vCN) at 1630 cm−1 gradually decreased
over prolonged reaction time at 120 °C (Figures S1 and S2).
Extensive screening for the highest relative intensities of the
secondary amine vibrations in the IR spectrum yielded optimal
synthetic conditions at 21 equiv of formic acid in a 2:1
mesitylene/1,4-dioxane mixture and a reaction time of 24 h at
120 °C. Under these conditions, the samples did not show any
residual imine stretch vibration (vCN), hinting at the
complete transformation of the parent PI-3-COF structure
(Figure 1b). 13C cross-polarization magic angle spinning (CP-
MAS) solid-state NMR (ssNMR) spectroscopy similarly shows
the disappearance of the characteristic imine carbon signal at
155.3 ppm, while a new aliphatic carbon signal at 45.4 ppm is
visible for the reduced PI-3-COF (rPI-3-COF). Besides that,
new signals at 119 and 114 ppm become visible for rPI-3-COF,
assigned to the aromatic carbons next to the amine bond
(Figure 1c). 15N ssNMR of rPI-3-COF shows distinct signals
at −313.3 ppm for the secondary amine nitrogen and at
−141.4 ppm for the triazine (Figure S30). The absence of the
imine nitrogen at −59.0 ppm further suggests a quantitative
reduction of imine into amine linkages in rPI-3-COF. The
measured ssNMR chemical shifts are in good agreement with
values obtained by quantum-chemical calculations of repre-
sentative molecular and single-pore models (Table S5).
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lization step of Py1P-COF, the metal particles “overcatalyzed”
the reduction with formic acid, causing a partial digestion of
the framework. To avoid this contamination, the 4,4′,4″,4″′-
(pyrene-1,3,6,8-tetrayl)tetraaniline linker was further purified
on a metal scavenger (Biotage Isolute Si-TMT). A purified
imine-linked Py1P-COF was then crystallized and reduced
with formic acid to form rPy1P-COF without any noticeable
decomposition. The SEM and TEM images of rTTI and
rPy1P-COF thus show full retention of the porous, crystalline
features of their parent frameworks (Figures S84, S89, S93, and
S100).
Similar to the rPI-3-COF model system, new N−H
vibrations at 3407 (rTTI) or 3398 cm−1 (rPy1P) in the FT-
IR spectra and secondary amine nitrogen signals at −314.9
(rTTI) and −317.6 ppm (rPy1P) in the 15N-ssNMR spectra
prove the conversion into amine-linked frameworks (Figures
S3, S4, S35, and S38). Although both samples show good
porosity (1419 m2g−1 rTTI, 1042 m2g−1 rPy1P), the BET
surface area of rPy1P is reduced, compared to 1883 m2g−1 in
Py1P-COF (Figures S72, S73, S75, and S76). By comparing
linker geometries in small-pore hexagonal rPI-3, large-pore
hexagonal rTTI, and square-net rPy1P-COF, those frameworks
consisting of more rigid tritopic + tritopic [3 + 3] linker
combinations (rPI-3 and rTTI-COF) show full retention of the
BET surface area, while the tetratopic + bitopic [4 + 2] linker
combination in rPy1P-COF was obtained with a slightly
reduced surface area. This is in line with the expected
additional flexibility around the molecular axis of the bitopic
terepthalaldehyde linker, which facilitates local distortions in
the network, causing reduced accessibility of the pores and
thus a smaller surface area in rPy1P-COF.
Upon reduction, the in-plane cell parameters of larger-pore
square-net rPy1P-COF were barely influenced, with C−N
bond lengths contributing only a small percentage to the
overall pore-to-pore distance. On the contrary, the increased
stacking distance caused an expansion of the unit cell from
c = 3.818(4) Å to c = 4.069(9) Å, similar to the small-pore rPI-
3-COF. At first sight, these trends cannot be found for the
rTTI framework in direct comparison to TTI-COF. Apparent
symmetry29 changes (peak splitting) in the XRPD pattern,
however, show that upon reduction the stacking behavior of
TTI-COF changes from antiparallel slip-stacked TTI (P1) to
more eclipsed-like stacking in rTTI with an average crystallo-
graphic symmetry of P63/m (Figures S9 and S13 and Tables S1
and S2). Similar symmetry correlations have been described
for the TTI-COF system by Haase et al. in comparison to its
randomly stacked TTI (rsTTI) framework, resulting in both
in-plane and interlayer contractions.29,30 This trend is also
observed with rTTI-COF: The increase in symmetry is
accompanied by a pore contraction (a = 25.786(12) Å
(TTI) vs a = 25.147(9) Å (rTTI)), caused by changed bond
angles of antiparallel amine bonds, resulting in overall reduced
intralayer cell parameters for rTTI. Furthermore, enhanced
interlayer interactions in the eclipsed-stacked rTTI-COF
compensate repulsive steric effects of benzylic protons, and
thus, stacking distances decrease from 3.578(9) Å in TTI to
3.504(2) Å in the reduced framework (Tables S1 and S2).
One-Pot Procedure: Reductive Crystallization. When
comparing the conditions needed for the synthesis of the imine
framework and the following reduction, acids and the same
solvent mixture are used in both cases and only the amount
and type of acid changes. Thus, we expected that formic acid
could act as a catalyst for both the formation and reduction of
the framework, condensing the individual steps into a single
one-pot crystallization-reduction approach.
Indeed, with 21 equiv of formic acid in a 2:1 mixture of
mesitylene/1,4-dioxane at 120 °C for 72 h, a crystalline sample
of rPI3-COF was obtained directly from its corresponding
aldehyde and amine building blocks (Figure S15). Compared
to its two-step analogue, it was obtained in a different,
spherical morphology (Figure S87). As visible from broadened
signals in the 13C ssNMR and FT-IR spectra (Figures S7 and
S49), this sample is structurally less well-defined with a major
impact on the resulting porosity (BET area of 174 m2g−1,
Figure S79), which may also be reduced by trapped oligomers
in the pores of the framework, besides structural defects.
During our studies, we noticed a significant impact of the
reaction temperature on the obtained product. While formic
acid catalyzes the imine condensation both at high (120 °C)
and already at low (60 °C) temperatures, the subsequent
reduction is fast only at an elevated temperature (Figure S16).
As such, the one-pot protocol can be used to thermally switch
between the reversible synthesis of an imine-linked COF at a
low temperature or the irreversible “locking” of the framework
structure by simultaneous reduction to the amine-linked COF
using otherwise identical reaction conditions. We expect this
unique property to be key for the adaptation to other covalent
organic frameworks. Besides this “thermo-switchability”, it
highlights formic acid as a versatile yet underexplored catalyst
for the synthesis of imine-linked COFs at a reduced
temperature.
Reductive Formylation: Combined Reduction and
Protection. Solid ammonium formate as a green, less toxic,
and less corrosive alternative to formic acid was also effective
for the reduction of imine bonds under solvent-free conditions.
Reacting a salt-melt of ammonium formate and PI-3-COF for
3 h at 170 °C in a closed vessel afforded a product with
broadened secondary amine vibrations at vNH = 3370 cm−1
and carbonyl stretching modes at vCO = 1669 cm−1 in the
FT-IR spectrum (Figure S6). An additional signal at 162.8 ppm
in the 13C ssNMR spectrum, referring to an N-formyl-carbon
(Figures S43 and S46), shows that, besides the reduction, a
subsequent N-formylation resulted in a partially formylated,
reduced PI-3 framework (pfrPI-3-COF). A comparison of FT-
IR and ssNMR spectra excludes a degradation of the chemical
connectivity. The XRPD pattern shows a substantial reduction
in the long-range order reminiscent of an amorphous solid,
although a small feature corresponding to the 100 peak further
suggests that the intralayer connectivity is maintained (Figure
S17). When reacting pfrPI-3-COF with 2,3-dichloro-5,6-
dicyano-1,4-benzoquinone (DDQ) in dichloromethane, the
secondary amine linkages are oxidized back to the imine
linkages, affording reoxidized, partially formylated reduced PI-
3-COF (opfrPI-3-COF).15 Remarkably, after this treatment,
sharp signals in the XRPD pattern similar to the parent PI-3
framework become visible (Figures S11 and S17). The
feasibility of this amorphous-to-crystalline conversion suggests
a significant topological and structural similarity of the
reduced, amorphous COF to the crystalline compound and
led us to further investigate the correlations between the
crystalline and non-crystalline amine-linked frameworks.
Crystalline vs Disordered. During our screenings to find
optimal reduction conditions for the imine-linked frameworks,
we noticed that a large excess of formic acid can decrease the
crystallinity of the product, suggesting a profound role of
protonation on the layer structure. Using 59.5 equiv of formic
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Figure 2. (a) Energy surface plot for different values of dihedral angles U and Z in the molecular model PI-3 M. The blue crosses highlight the
lowest energy conformation for the single-pore model PI-3 SP. (b) Energy surface plot for the molecular model rPI-3 M. The blue crosses highlight
the lowest energy conformation for the single-pore model rPI-3 SP. As a comparison, the conformation of a protonated molecular model H+rPI-3
M is shown on the surface (red cross). Notably, in this simple molecular model, the effect of the anion and charge repulsion, occurring in the
layered real structure, are neglected. (c) Dihedral angles U and Z shown in a section of PI-3 M. (d) Reduced total scattering patterns and (e) pair
distribution functions for crystalline and disordered materials are overlaid. (f and g) Sixteen-layer structure models derived from PDF analysis for
disordered rPI-3-COF (left) and rPI-3-COF (right) considering random translational disorder in 1−10 directions are shown.
acid with PI-3-COF under the same conditions as above leads
to a practically X-ray amorphous structure with slightly
broadened but otherwise essentially identical signals as
rPI-3-COF in the FT-IR and ssNMR spectra (Figures S5
and S48). SEM and TEM did not show any morphological
changes of the particles (Figures S86 and S97). Stability tests
of rPI-3-COF, e.g., under acidic conditions, show similar
effects on the reflections in the XRPD patterns. In contrast to
the imine-linked PI-3-COF, the amine-linked rPI-3-COF does
not show any hydrolytic decomposition, though sharp
reflections in the XRPD pattern broaden or disappear
completely upon treatment with excess acidillustrating
local structural changes and distortion of the stacked 2D
layers (Figures S101 and S102).
To elucidate conformational changes in the structure of
PI-3-COF upon reduction, quantum-chemical calculations on
the PBE0-D3/def2-TZVP level of theory were performed to
obtain optimized structures for model compounds.31−34 The
surface plot for combined rotations around dihedral angles U
and Z in molecular models PI-3 M and rPI-3 M (Figures
S103−S105) shows an increased flexibility for the amine-
linked molecular model, apparent from a broad range of low
energy conformations (Figure 2a−c). Optimized single-pore
models PI-3 SP and rPI-3 SP (Figures S106 and S107) depict
discrete points on the surface close to the lowest energy
conformations of their molecular models with dihedral angles
(U) of 27.4° (PI-3 SP) and 6.46° (rPI-3 SP). Although
interlayer steric repulsion in the amine framework is increased
due to additional benzylic protons (C-10, Figure 1c) that align
perpendicular to the 2D surface, reduced 1,4-repulsion
between protons at C-9 and C-10 causes a flattening of the
dihedral angle U, albeit combined with increased flexibility of
the structure. These results corroborate the cell parameter
changes upon reduction as observed by Rietveld analysis of the
crystalline rPI-3-COF. To elucidate possible amorphization
pathways, resulting in a disordered structure of rPI-3 if
synthesized with an excess of formic acid, additional
protonation must be considered. When protonated at the
amine nitrogen, the dihedral angle U undergoes a significant
widening to 86.6° in the molecular model H+rPI-3 M (Figure
S105)a rotation associated with an energy barrier of
approximately 50 kJ/mol in the molecular model rPI-3 M
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Figure 3. (a) Reaction sequence for postsynthetic functionalization of amine-linked covalent organic frameworks. Frameworks entirely connected
by secondary amine linkages (rCOF) or hybrid materials with mixed amine/imine bonds (prCOF) and partially formylated amine-linkages
(pfrCOF) are accessible in a single step from imine COFs. As experimentally shown with pfrPI-3-COF (middle), N-formyl groups in pfrCOFs can
be deprotected under acidic conditions. Released secondary amine linkages may allow two-step functionalization to afford bifunctionalized
frameworks. The amine/N-formyl amine ratio is arbitrary. (b and c) FT-IR spectra of rTTI-COF samples functionalized with (b) benzoyl chloride
(BzCl) and (c) toluenediisocyanate (TDI) are shown and compared to rTTI-COF. Gray areas in (b) highlight reduced NH, emerging CO,
and characteristic CC vibrations in BzCl-rTTI-COF. For TDI-rTTI-COF, vibrations of dangling -NCO and emerging CO vibrations are
highlighted (gray).
(without protonation). Considering conformational restric-
tions in the layer geometry of the rPI-3-COF, less pronounced
but still substantial conformational changes, combined with
interlayer charge repulsion, are expected, leading to a
significant disruption of the periodicity of the stacked layers
as a function of the pH. This effect is further supported by a
vast signal broadening at 119 ppm (C-7) in the 13C ssNMR
spectrum with increasing disorder in rPI-3-COF (Figure S48),
whereas in the actual, well-ordered rPI-3-COF structure, a
narrow statistical distribution of dihedral angles indicates a
preferred conformation and thus a fairly sharp signal for this
carbon (C-7). A protonation-dependent broad distribution in
the disordered rPI-3-COF causes this signal to broaden and,
ultimately, to vanish, however without disrupting the overall
connectivity of the layer.
To determine the local and intermediate length-scale
structure modifications due to conformation-induced disorder-
ing, we performed pair distribution function (PDF) analysis on
X-ray total scattering synchrotron data. Notably, a high
similarity in the reduced total scattering patterns (Figure 2d)
from ∼5−20 Å−1 and peak positions up to approximately 7 Å
in the PDFs of all samples evidence intact, imine or amine
bonded layer connectivity in the disordered state. The PDFs of
PI-3-COF and rPI-3-COF (Figure 2e) show distinct medium-
and long-range ordered structuring, consisting of two primary
oscillations due to the ordering of the stacked layers (higher
frequency) and porous channels (lower frequency). The
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Figure 4. Pathways leading to a set of amine-linked covalent organic frameworks as demonstrated with the PI-3 COF system.
structural correlations are more strongly damped for
disordered rPI-3-COF and pfrPI-3-COF, becoming relatively
flat around 12 Å. This indicates that the spatial relationships of
atoms in stacked layers and across porous channels are largely
reduced, although, as seen in the diffraction patterns, there are
still weakly correlated motifs over at least a few layers or pore
distances (Figure 2e). Distinct differences could be visualized
between crystalline and disordered structures by the refine-
ment of a 16-layer structure model to the PDFs for rPI-3-COF
and disordered rPI-3-COF PDFs, with random translations
allowed in a single direction (Figure 2f,g). For the disordered
sample, much larger translations were required to damp out
the interlayer and ordered pore channel structure signals. It
must be noted that these models may overpredict layer
translations due to undersampling the number of layers.
Furthermore, the interlayer correlations could also be damped
by larger and random torsions of the amine or phenyl moieties,
as shown in quantum-chemical single-pore models. Average
stacking offsets were estimated by refining models to the PDFs
in the range of neighboring layers, i.e., r < 6 Å, using
PDFgui.29,35 The values obtained are 1.0 (PI-3-COF), 1.2
(rPI-3-COF), 3.3 (disordered rPI-3-COF), and 3.3 Å (pfrPI-3-
COF). As visible from the disordered model, random layer
translations drastically reduce the pore accessibility and thus
help to explain reduced BET surface areas for the disordered
models.
synthesized, showing distinct signals at 149.0 (imine) and
146.4 ppm (amine) in the 13C ssNMR spectrum for the
aromatic carbon next to the nitrogen (approximately 42%
amine sites, Figure S40). Another example, already introduced,
is partially formylated reduced PI-3-COF (pfrPI-3-COF)
obtained from PI-3-COF via salt-melt reduction with
ammonium formate. The presence of N-formyl groups opens
up further avenues for additional framework functionalization.
For instance, partially functionalized frameworks may be
generated by reacting the partially formylated framework
with an electrophile, since formyl groups act as a protecting
group for secondary amine sites. Partial functionalization can
avoid reduced pore accessibility and diffusion limitations,
which is critical, for example, in catalysis.36 In a more complex
case, bifunctionalized frameworks may be synthesized in a
subsequent step, after exposing previously protected amine
sites. The deprotection of N-formyl groups in pfrPI-3-COF
was achieved under acidic conditions (aqueous 1 M HCl,
120 °C, 20 min), affording rPI-3-COF as evident from a
vanishing formyl signal at 162.8 ppm in the 13C ssNMR
spectrum (Figure S46), while acid chlorides or isocyanates
have proven as strong and effective electrophiles to derivatize
secondary amines in rTTI-COF (Figure 3b,c).
DISCUSSION
■
In summary, amine-linked frameworks were introduced as a
hydrolytically stable and tailorable system for further
postsynthetic modification, which can be accessed from
imine-linked frameworks or directly from their corresponding
amine and aldehyde building blocks (Figure 4). In contrast to
many earlier locking strategies, generating amide-, benzox-
azole-, or benzothiazole-linked frameworks, our approach locks
Hybrid Materials and Functionalization. Besides frame-
works containing only amine or imine linkages, hybrid
materials with varying imine/amine linkage content can also
be obtained with our method by adjusting reaction time and
the amount of formic acid (Figure 3a and Figure S1). As an
example, partially reduced Py1P-COF (prPy1P-COF) was
3436
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J. Am. Chem. Soc. 2021, 143, 3430−3438

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
and simultaneously activates the connectivity of the framework
for further functionalization.5,7,11,37 The introduced reduction
methods using either formic acid or ammonium formate give
access to a range of fully amine-linked or intermediate amine-/
imine-linked crystalline frameworks with large surface areas or
topologically identical, disordered analogues with reduced
pore-accessibility. Importantly, the degree of amine function-
alization can be rationally controlled by adjusting the amount
of acid and the reaction time. For the first time, we
demonstrate amine-linked frameworks as a modular platform
enabling the facile interconversion of chemically and
structurally distinct frameworks, including reduction−reoxida-
tion cycles and crystalline-to-disordered and disordered-to-
crystalline conversions. Finally, we show that the obtained
amine linkages readily react with electrophiles such as acid
chlorides and isocyanates, opening new avenues to the facile
postsynthetic functionalization of COFs at the linkage site with
a built-in protection−deprotection strategy and without the
need for additional building block engineering. In essence, the
demonstrated methods enable hitherto undiscovered function-
alization strategies that are widely applicable to all imine-linked
covalent organic frameworks, the largest family of COFs to
date.
Maxwell W. Terban − Max Planck Institute for Solid State
Research, 70569 Stuttgart, Germany; orcid.org/0000-
0002-7094-1266
Viola Duppel − Max Planck Institute for Solid State Research,
70569 Stuttgart, Germany
Igor Moudrakovski − Max Planck Institute for Solid State
Research, 70569 Stuttgart, Germany; orcid.org/0000-
0002-8919-4766
Martin Etter − Deutsches Elektronen-Synchrotron (DESY),
Hamburg 22607, Germany
Robert E. Dinnebier − Max Planck Institute for Solid State
Research, 70569 Stuttgart, Germany
Christian Ochsenfeld − Department of Chemistry, Ludwig-
Maximilians-Universität (LMU), 81377 Munich, Germany;
Max Planck Institute for Solid State Research, 70569
Stuttgart, Germany; E-conversion, Lichtenbergstrasse 4a,
85748 Garching, Germany and Center for NanoScience,
80799 Munich, Germany; orcid.org/0000-0002-4189-
6558
Complete contact information is available at:
https://pubs.acs.org/10.1021/jacs.0c12249
Notes
The authors declare no competing financial interest.
ASSOCIATED CONTENT
■
sı
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/jacs.0c12249.
ACKNOWLEDGMENTS
■
The authors would like to thank Sebastian Emmerling for
performing sorption measurements. M.W.T. gratefully ac-
knowledges support from BASF. Financial support by an ERC
Starting Grant (project COF Leaf, Grant No. 639233), the
Deutsche Forschungsgemeinschaft (DFG, Project-ID
358283783 - SFB 1333), the Max Planck Society, the Cluster
of Excellence e-conversion (Grant No. EXC2089), and the
Center for Nanoscience (CeNS) is gratefully acknowledged.
The authors acknowledge DESY (Hamburg, Germany), a
member of the Helmholtz Association HGF, for the provision
of experimental facilities. Parts of this research were carried out
at beamline P02.1.
Discussions of methods and equipment used, detailed
synthetic procedures, FT-IR spectra, calculated IR
modes, XRPD patterns, 1H, 13C, 15N and 1H/13C-
HETCOR ssNMR spectra, N2 sorption isotherms, pore-
size distributions, BET plots, SEM and TEM images,
SEM and TEM-EDX spectra, quantum-chemically
optimized structures, calculated NMR chemical shifts,
reduced total scattering patterns, PDF analyis, structure
refinements and tables of cell parameters of Rietveld
refined imine- and amine-linked COFs (PDF)
REFERENCES
AUTHOR INFORMATION
■
■
(1) Cote, A. P.; et al. Porous, Crystalline, Covalent Organic
Frameworks. Science 2005, 310, 1166−1170.
(2) Lohse, M. S.; Bein, T. Covalent Organic Frameworks: Structures,
Synthesis, and Applications. Adv. Funct. Mater. 2018, 28, 1705553.
(3) Song, Y.; Sun, Q.; Aguila, B.; Ma, S. Opportunities of Covalent
Organic Frameworks for Advanced Applications. Adv. Sci. 2019, 6,
1801410.
(4) Geng, K.; et al. Covalent Organic Frameworks: Design,
Synthesis, and Functions. Chem. Rev. 2020, 120, 8814−8933.
(5) Haase, F.; et al. Topochemical Conversion of an Imine- into a
Thiazole-Linked Covalent Organic Framework Enabling Real
Structure Analysis. Nat. Commun. 2018, 9, 2600.
(6) Wang, K.; et al. Synthesis of Stable Thiazole-Linked Covalent
Organic Frameworks via a Multicomponent Reaction. J. Am. Chem.
Soc. 2020, 142, 11131−11138.
(7) Waller, P. J.; et al. Chemical Conversion of Linkages in Covalent
Organic Frameworks. J. Am. Chem. Soc. 2016, 138, 15519−15522.
(8) Li, X.; et al. Facile Transformation of Imine Covalent Organic
Frameworks Into Ultrastable Crystalline Porous Aromatic Frame-
works. Nat. Commun. 2018, 9, 2998.
(9) Segura, J. L.; Royuela, S.; Mar Ramos, M. Post-synthetic
Modification of Covalent Organic Frameworks. Chem. Soc. Rev. 2019,
48, 3903−3945.
Corresponding Author
Bettina V. Lotsch − Max Planck Institute for Solid State
Research, 70569 Stuttgart, Germany; Department of
Chemistry, Ludwig-Maximilians-Universität (LMU), 81377
Munich, Germany; E-conversion, Lichtenbergstrasse 4a,
85748 Garching, Germany and Center for NanoScience,
80799 Munich, Germany; orcid.org/0000-0002-3094-
303X; Email: b.lotsch@fkf.mpg.de
Authors
Lars Grunenberg − Max Planck Institute for Solid State
Research, 70569 Stuttgart, Germany; Department of
Chemistry, Ludwig-Maximilians-Universität (LMU), 81377
Munich, Germany; orcid.org/0000-0002-6831-4626
Gökcen Savasci − Max Planck Institute for Solid State
Research, 70569 Stuttgart, Germany; Department of
Chemistry, Ludwig-Maximilians-Universität (LMU), 81377
Munich, Germany; E-conversion, Lichtenbergstrasse 4a,
85748 Garching, Germany and Center for NanoScience,
80799 Munich, Germany; orcid.org/0000-0002-6183-
7715
3437
https://dx.doi.org/10.1021/jacs.0c12249
J. Am. Chem. Soc. 2021, 143, 3430−3438

Journal of the American Chemical Society
pubs.acs.org/JACS
Article
(10) Ding, H.; Mal, A.; Wang, C. Tailored Covalent Organic
Frameworks by Post-Synthetic Modification. Mater. Chem. Front.
2020, 4, 113−127.
(34) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. A Consistent and
Accurate Ab Initio Parametrization of Density Functional Dispersion
Correction (DFT-D) for the 94 Elements H-Pu. J. Chem. Phys. 2010,
132, 154104.
(35) Farrow, C. L.; et al. PDFfit2 and PDFgui: Computer Programs
for Studying Nanostructure in Crystals. J. Phys.: Condens. Matter 2007,
19, 335219.
(36) Sun, Q.; et al. Pore Environment Control and Enhanced
Performance of Enzymes Infiltrated in Covalent Organic Frameworks.
J. Am. Chem. Soc. 2018, 140, 984−992.
(37) Wei, P. F.; et al. Benzoxazole-Linked Ultrastable Covalent
Organic Frameworks for Photocatalysis. J. Am. Chem. Soc. 2018, 140,
4623−4631.
(11) Yan, Q.; et al. Post-Synthetic Modification of Imine Linkages of
a Covalent Organic Framework for Its Catalysis Application. RSC Adv.
2020, 10, 17396−17403.
(12) Li, X. T.; et al. Construction of Covalent Organic Frameworks
via Three-Component One-Pot Strecker and Povarov Reactions. J.
Am. Chem. Soc. 2020, 142, 6521−6526.
(13) Li, C.; et al. Asymmetric Photocatalysis Over Robust Covalent
Organic Frameworks With Tetrahydroquinoline Linkage. Chin. J.
Catal. 2020, 41, 1288−1297.
(14) Lohse, M. S.; et al. Sequential Pore Wall Modification in a
Covalent Organic Framework for Application in Lactic Acid
Adsorption. Chem. Mater. 2016, 28, 626−631.
(15) Lyle, S. J.; et al. Multistep Solid-State Organic Synthesis of
Carbamate-Linked Covalent Organic Frameworks. J. Am. Chem. Soc.
2019, 141, 11253−11258.
(16) Leuckart, R. Ueber eine Neue Bildungsweise von Tribenzyla-
min. Ber. Dtsch. Chem. Ges. 1885, 18, 2341−2344.
̈
(17) Wallach, O. Zur Kenntniss der Terpene und der Atherischen
Oele; Zweiundzwanzigste Abhandlung. I. Ueber die Bestandtheile des
̈
Tujaols. Liebigs Ann. 1893, 272, 99−122.
(18) Billman, J. H.; Diesing, A. C. Reduction of Schiff Bases with
Sodium Borohydride. J. Org. Chem. 1957, 22, 1068−1070.
(19) Francesconi, O.; et al. A Self-Assembled Pyrrolic Cage Receptor
Specifically Recognizes Beta-Glucopyranosides. Angew. Chem., Int. Ed.
2006, 45, 6693−6696.
(20) Liu, M.; et al. Acid- and Base-Stable Porous Organic Cages:
Shape Persistence and pH Stability via Post-Synthetic ″Tying″ of a
Flexible Amine Cage. J. Am. Chem. Soc. 2014, 136, 7583−7586.
(21) Liu, H.; et al. Covalent Organic Frameworks Linked by Amine
Bonding for Concerted Electrochemical Reduction of CO2. Chem.
2018, 4, 1696−1709.
(22) Boechat, N.; et al. A Simple Reduction of Methyl Aromatic
Esters to Alcohols Using Sodium Borohydride−Methanol System.
Tetrahedron Lett. 2004, 45, 6021−6022.
(23) Bai, L.; et al. Nanoscale Covalent Organic Frameworks as Smart
Carriers for Drug Delivery. Chem. Commun. 2016, 52, 4128−4131.
(24) Rietveld, H. M. A Profile Refinement Method for Nuclear and
Magnetic Structures. J. Appl. Crystallogr. 1969, 2, 65−71.
(25) Breitmaier, E.; Jung, G. Organische Chemie: Grundlagen,
Stoffklassen, Reaktionen, Konzepte, Moleku
gart, Germany, 2005.
̈
lstrukturen; Thieme: Stutt-
(26) Sick, T.; et al. Switching on and off Interlayer Correlations and
Porosity in 2D Covalent Organic Frameworks. J. Am. Chem. Soc.
2019, 141, 12570−12581.
(27) Feriante, C. H.; et al. Rapid Synthesis of High Surface Area
Imine-Linked 2D Covalent Organic Frameworks by Avoiding Pore
Collapse During Isolation. Adv. Mater. 2020, 32, 1905776.
(28) Romero-Muniz, I.; et al. Unveiling the Local Structure of
̃
Palladium Loaded into Imine-Linked Layered Covalent Organic
Frameworks for Cross-Coupling Catalysis. Angew. Chem. 2020, 132,
13113−13120.
(29) Putz, A. M.; et al. Total Scattering Reveals the Hidden Stacking
̈
Disorder in a 2D Covalent Organic Framework. Chem. Sci. 2020, 11,
12647−12654.
(30) Haase, F.; et al. Tuning the Stacking Behaviour of a 2D
Covalent Organic Framework Through Non-Covalent Interactions.
Mater. Chem. Front. 2017, 1, 1354−1361.
(31) Schäfer, A.; Huber, C.; Ahlrichs, R. Fully Optimized Contracted
Gaussian Basis Sets of Triple Zeta Valence Quality for Atoms Li to Kr.
J. Chem. Phys. 1994, 100, 5829−5835.
(32) Adamo, C.; Barone, V. Toward Reliable Density Functional
Methods Without Adjustable Parameters: The PBE0 Model. J. Chem.
Phys. 1999, 110, 6158−6170.
(33) Ernzerhof, M.; Scuseria, G. E. Assessment of the Perdew−
Burke−Ernzerhof Exchange-Correlation Functional. J. Chem. Phys.
1999, 110, 5029−5036.
3438
https://dx.doi.org/10.1021/jacs.0c12249
J. Am. Chem. Soc. 2021, 143, 3430−3438