Multistep solid-state organic synthesis of carbamate-linked covalent organic frameworks

Article abstract of DOI:10.1021/jacs.9b04731

Herein, we demonstrate the first example of a multistep solid-state organic synthesis, in which a new imine-linked two-dimensional covalent organic framework (COF-170, 1) was transformed through three consecutive postsynthetic modifications into porous, crystalline cyclic carbamate and thiocarbamate-linked frameworks. These linkages are previously unreported and inaccessible through de novo synthesis. While not altering the overall connectivity of the framework, these chemical transformations induce significant conformational and structural changes at each step, highlighting the key importance of noncovalent interactions and conformational flexibility to COF crystallinity and porosity. These transformations were assessed using ¹⁵N multiCP-MAS NMR spectroscopy, providing the first quantitation of yields in COF postsynthetic modification reactions, as well as of amine defect sites in imine-linked COFs. This multistep COF linkage postsynthetic modification represents a significant step toward bringing the precision of organic solution-phase synthesis to extended solid-state compounds.

Full text of DOI:10.1021/jacs.9b04731

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Article
Multi-Step Solid-State Organic Synthesis of
Carbamate-Linked Covalent Organic Frameworks
Steven J. Lyle, Thomas M. Osborn Popp, Peter J Waller, Xiaokun Pei, Jeffrey A. Reimer, and Omar M. Yaghi
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b04731 • Publication Date (Web): 21 Jun 2019
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†
†,‡
†
†
‡
Steven J. Lyle, Thomas M. Osborn Popp, Peter J. Waller, Xiaokun Pei, Jeffrey A. Reimer, Omar
M. Yaghi
*,†,§
†Department of Chemistry, University of California-Berkeley; Materials Sciences Division, Lawrence Berkeley National
Laboratory; Kavli Energy NanoSciences Institute at Berkeley; and Berkeley Global Science Institute, Berkeley, California
9
4720, United States.
‡Department of Chemical and Biomolecular Engineering, University of California-Berkeley; and Environmental Energy
Technologies Division, Lawrence Berkeley National Laboratory, Berkeley, California, 94720, United States.
§King Abdulaziz City for Science and Technology, Riyadh 11442, Saudi Arabia.
Supporting Information Placeholder
ABSTRACT: Herein, we demonstrate the first example of a multi-step solid-state organic synthesis, in which a new imine-
linked two-dimensional covalent organic framework (COF-170, 1) was transformed through three consecutive postsynthetic
modifications into porous, crystalline cyclic carbamate and thiocarbamate-linked frameworks. These linkages are previously
unreported, and inaccessible through de novo synthesis. While not altering the overall connectivity of the framework, these
chemical transformations induce significant conformational and structural changes at each step, highlighting the key im-
portance of noncovalent interactions and conformational flexibility to COF crystallinity and porosity. These transformations
1
5
were assessed using N multiCP-MAS NMR spectroscopy, providing the first quantitation of yields in COF postsynthetic mod-
ification reactions, as well as of amine defect sites in imine-linked COFs. This multi-step COF linkage postsynthetic modifica-
tion represents a significant step towards bringing the precision of organic solution-phase synthesis to extended solid state
compounds.
secondary amides, secondary amines, thiazoles, oxazoles, and
8-12
quinolines. However, amide- and oxazole-linked COFs can
15-16
Covalent organic frameworks (COFs) are a class of de-
signed porous, crystalline materials built from the covalent
linkage of geometrically predefined building units into two-
be formed directly from molecular building units,
and in
principle, each of these linkages could be made directly, by em-
ploying a one-pot strategy whereby COFs are formed from a
reversible imine condensation followed by a less-reversible or
1
,2
and three-dimensional extended networks. The ability to
control the relative positioning of chemical functionalities
in covalently-linked solids represents an extension of or-
17-20
irreversible second step in situ.
In organic synthesis, we are not limited to compounds acces-
sible in a single synthetic step. The translation of multistep or-
ganic synthesis to the solid state, however, requires extending
not only the chemistry, but the rigor of characterization found
in small molecule synthesis to solids. Herein, we describe the
first extension of both these features of organic chemistry to co-
valent solids, achieved by the multi-step postsynthetic modifi-
cation of a COF to generate porous, crystalline cyclic carbamate
and thiocarbamate-linked frameworks accessible only through
multistep synthesis. Each reaction in this synthesis involves
transformation of the material’s linkage, and as such occurs
with concomitant structural changes, but preservation of the un-
derlying topology. Furthermore, each compound was analyzed
by N multiple cross-polarization magic angle spinning nuclear
magnetic resonance spectroscopy (multiCP-MAS NMR), al-
lowing for the first quantitative evaluation of chemical transfor-
mations in COFs. This work sets a new standard for the execu-
tion and evaluation of multistep chemical transformations of
solids, and in doing so lays the groundwork for further explora-
tion of solid-state organic synthesis.
3
,4
ganic chemistry into the solid state. This extension in-
cludes not only the ability to crystallize these ordered net-
works from molecular building blocks, but also the ability to
treat the extended solids as molecules. It has been demon-
strated in numerous cases that chemical transformations
can take place on COFs much as they do in solution due to
the ability of reactants and byproducts to diffuse through
5-7
the pores of a COF. Notably, postsynthetic modifications
can be performed on COF linkages without alteration of to-
8-12
pology.
Linkage transformations, in particular, distin-
guish themselves from reactions performed on molecules ap-
pended to solid supports, such as solid phase peptide synthesis,
because the stability, reactivity, and structure of a COF is
1
5
1
3-14
largely defined by its linkages.
Postsynthetic modification allows access to new linkage
functionalities without the need to develop reaction conditions
capable of directly generating an ordered network reticulated by
those linkages. This has been demonstrated for a number of
imine-linked COFs, the linkages of which were converted to
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Scheme 1. Synthesis of Cyclic Carbamate and Thiocarbamate-Linked COFs by a Three-Step Solid-State Synthesis
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cyclization to carbamates and thiocarbamates, characteris-
tic C=O and C=S stretches were observed at 1719 and 1156
-
1
A new kgm topology COF, COF-170 (1), was synthesized
solvothermally from the condensation of (E)-3,3’,5,5’-
tetrakis(4-aminophenyl)stilbene (TAPS) and 3,5-dimethox-
yterephthalaldehyde (DMTP) in a 5:5:1 mixture of o-dichlo-
robenzene, 1-butanol, and 6M AcOH at 120°C for 3 days.
COF-170 served as the starting material for the synthesis of
isostructural cyclic carbamate and thiocarbamate linked
COFs (Scheme 1). This synthesis began first with demethyl-
ation of 1’s methoxy groups, followed by reduction of the
imine linkage with sodium cyanoborohydride and acetic
cm , respectively, and corroborated by comparison to mo-
2
4
lecular models (See SI, Section S5).
Although diagnostic, FT-IR spectroscopy alone does not
constitute evidence of reaction completeness, and in this
context cannot provide quantitative information on the
15
composition of the analyzed COFs.
N solid-state NMR
spectroscopy provides an alternative means to clearly track
the conversion between linkages across the multiple steps
of this synthetic process. While commonly employed in the
characterization of COF linkage transformations, traditional
CP-MAS NMR does not provide quantitative integrations of
resonances due to variable polarization rates between H
and the target nucleus across different chemical functional-
2
1
acid in THF. This amine-linked COF (3) was then treated
with 1,1’-carbonyldiimidazole (CDI) or 1,1’-thiocarbon-
yldiimidazole (TCDI) and N,N-dimethylaminopyridine
1
(
DMAP) in dichloromethane to yield cyclic carbamate (4)
ities. Quantitative solid-state NMR spectra may be achieved
2
2
and thiocarbamate (5) linked COFs respectively. Between
each of these steps, and prior to characterization, the inter-
mediate compounds were subjected to thorough solvent ex-
change and activation to prepare the material for the subse-
quent transformation. In order to provide rigorous data
15
by direct observation of N, however, long T
1
relaxation
times combined with the low sensitivity of the nucleus can
make these measurements impractical. MultiCP-MAS NMR
spectroscopy provides a means to measure quantitative
solid-state NMR spectra in solids with reasonable measure-
15
consistency, all characterization, including N multiCP-
25-26
ment times.
To date, the multiCP method has only been
MAS NMR spectroscopy, was performed on the same 33%
13
applied to the measurement of C NMR spectra. In applying
1
5
N labeled samples. All relevant synthetic procedures can
15
this method to N, we found it necessary to enrich the sam-
be found in sections 2-4 of the supporting information.
ple due to its low natural abundance. However, full enrich-
ment was not necessary to obtain routine spectra.
Progress of these transformations was initially moni-
tored by FT-IR spectroscopy (Figure 1a). Demethylation of
1’s methoxy groups was observed through the disappear-
ance of its ether C–O–C symmetric and asymmetric
15N multiCP-MAS NMR of 33%
15N-labeled substrates
yielded quantitative insight into the postsynthetic modifica-
tion process (Figure 2). In the spectrum of each COF, the pri-
mary resonance observed corresponds to the major prod-
uct of the preceding reaction step. As the resonances for
each chemical site showed some degree of inhomogeneous
broadening due to structural disorder within the structures,
-
1
23
stretches at 1038 and 1288 cm , respectively. Upon re-
duction of the imine linkages of 2, we observed the disap-
-1
pearance of its imine C=N stretch at 1614 cm and emer-
-
1 10
gence of an amine C–N stretch at 1516 cm . After
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Figure 1. (a) FT-IR spectra of COFs 1-5, labeled with diagnostic stretching frequencies reported for each linkage. (b) PXRD patterns
of COFs 1-5, demonstrating the retention of crystallinity through all but amine-linked 3. (c) N adsorption isotherms performed at
2
77K for COFs 1-5, displaying permanent porosity for all but amine linked 3. Solid and open circles designate adsorption and desorp-
3
tion points respectively. Uptake is defined as cm of N
2
at 1 atm and 0°C per gram of sample.
resonances corresponding to different sites were fit to
Gaussian lineshapes and their relative areas were com-
pared (See SI, Section S6). Using this method, the composi-
tion of each COF along the synthetic pathway was analyzed
good agreement with simulated structures, confirming that
their connectivity and kgm topology is preserved during
the demethylation step (See SI, Section S7). Additionally,
both 1 and 2 are porous, with Brunauer-Emmett-Teller
2
(
Table 1). In imine-linked COFs 1 and 2, residual primary
(BET) areas of 1229 and 1233 m /g respectively. While
1
5
amine sites at were found to make up 6 and 8 % of total
N
these experiments confirm the topology and porosity of
these materials, they do not provide a complete picture of
the structures of 1 and 2. Due to the broad diffraction peaks
common to most COF materials, the diffraction data cannot
provide enough information to determine the orientation of
the methoxy- or hydroxy-substituted phenyl rings relative
to the imine bond. The orientation of this ring relative to the
linkage is critical to the formation of cyclic carbamates, as
the cyclization cannot proceed unless the amine and hy-
droxyl group are positioned along the same side in close
proximity. To gain insight into the possible orientations of
this site in each imine-linked COF structure, molecular mod-
els of 1 and 2 were synthesized, and their structures deter-
mined by single-crystal X-ray diffraction (See SI, Section
S11). For the model of 1, it was found that the methoxy
groups position themselves opposite the imine bond to min-
imize steric interactions, while the hydroxy groups in 2’s
model compound position themselves on the same side as
the imine to form intramolecular hydrogen bonds. The dif-
ferences in energy between the two possible phenyl orien-
tations were explored for each model compound by gas-
phase DFT simulations (See SI, Section S12). For the hy-
droxy and methoxy substituted model compounds, the ori-
entations observed in the crystal structures were found to
sites respectively. The chemical shifts of the imine sites
within these two materials are distinct enough to enable
monitoring of the demethylation step, which occurred in
9
1% yield. The reduction of imine species in 2 to make 3
was found to be complete within the detection limit of the
NMR experiment. In contrast to the imine resonances, the
chemical shifts of the methoxy-adjacent, hydroxy-adjacent,
and primary amine linkages cannot be clearly resolved.
Nonetheless, the relative composition of secondary amine
linkages can be inferred under the assumption that the
amount of primary amine remains unchanged after the re-
duction. Treatment of 3 with CDI and DMAP affords a mate-
1
5
rial 4 in which 86% of N sites are carbamates, and the re-
mainder a mixture of amine sites. Thiocarbamate-linked 5
shows a similar conversion of 86% thiocarbamate with
1
4% mixed amines remaining. The carbamate and thiocar-
bamate resonances in 4 and 5 are likely a mixture of species,
as only the secondary amine with an adjacent hydroxyl
group can form cyclic carbamates or thiocarbamates. The
primary amines and the secondary amines with adjacent
methoxy groups are capable of generating O-methyl carba-
mates and O-methyl thiocarbamates from the addition of
those amines to CDI or TCDI followed by quenching with
2
7-28
15
methanol during the solvent exchange process.
For this
be preferred by 62.5 and 39.6 kJ/mol respectively. N NMR
reason, the yield of cyclic carbamate and cyclic thiocarba-
mate are reported as a range that considers the possibility
that the O-methyl species may be contributing to the ob-
served resonance.
chemical shifts for each orientation of the model com-
pounds were calculated (See SI, Section S12), and suggest
1
5
that these species should be distinguishable by our N NMR
experiments. Comparing these predictions to experiment,
not only are the methoxy-adjacent and hydroxy-adjacent
Having determined the composition of these COFs, we
sought to understand their structures in more detail and
how they may have changed during the synthetic pathway.
COFs 1-5 were evaluated by powder X-ray diffraction
1
5
imine sites distinguishable between the N spectra of 1 and
, 1 contains two independent imine resonances. Based on
2
the insights gained from the crystal structures and DFT cal-
culations of the model compounds, we believe that both ori-
entations of the methoxy-substituted phenyl ring are
(
PXRD) and N
2
adsorption isotherm experiments (Figure
1
b-c). Pawley fitting of imine-linked COFs 1 and 2 show
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Composition (%)
topology as 1, 2, 4, and 5, despite a lack of crystallinity. The
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Linkage Species
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(X=O)
(X=S)
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—
—
—
84
—
—
0
0
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0-8
0-14
0-8
0-14
84
Figure 2. 15N multiCP-MAS NMR spectra of 33% 15N-labled
COFs 1-5, colored to highlight the composition of each sample.
Spinning side bands are indicated by asterisks.
—
—
—
—
—
—
72-86 72-86
loss of crystallinity and porosity upon reduction of 2 and its
subsequent reemergence in 4 and 5 can be attributed to the
conformational flexibility of the secondary amine linkages
of 3. In contrast, imines, cyclic carbamates, and cyclic thio-
carbamates are significantly less conformationally flexible,
and adopt comparatively planar conformations as observed
in molecular model crystal structures (See SI, Section S11).
0-8
0-8
0-8
0-8
—
—
—
This same pattern of crystallinity loss and recovery can
be observed from the reduction of the imine linkages of 1 to
amines, followed by re-oxidation back to imines with 2,3-
dichloro-5,6-dicyano-1,4-benzoquinone (DDQ).2 Both the
starting and ending imine-linked materials are crystalline,
while the intermediate amine is non-crystalline. Loss and
recovery of crystallinity upon reduction and re-oxidation of
the imine linkage is even observed for ILCOF-1, despite the
presence of strongly stacking pyrene units and a smaller
Table 1. Linkage composition of COFs 1-5, determined
1
5
from peak fitting of N multiCP-MAS NMR spectra. Compo-
sition ranges given for 4 and 5 reflect the fact that primary
amines, and secondary amines with adjacent methoxy
groups present in 3 may be forming O-methyl carbamate
and thiocarbamate species which contribute to the ob-
served carbamate and thiocarbamate resonances.
9
present in 1, and only the orientation which yields intramo-
lecular hydrogen bonding is present in 2. This suggests that
upon demethylation, the COF undergoes a structural rear-
rangement to adopt its most stable conformation (Scheme
3
0
pore size than 1 (See SI, Section S13). Dynamics of this
type have previously been observed in molecular crystals,
as well the woven COF-505, for which crystallinity can be
+
2
).
lost and recovered by the removal and reintroduction of Cu
templates within the structure.
3
1-32
In contrast to 1 and 2, amine-linked 3 is non-crystalline
2
and less porous, with a BET area of only 61 m /g. Based on
these results, it would appear the COF had irreversibly de-
graded after the reduction, however carrying the synthesis
through to generate 4 or 5 yields materials which are both
crystalline and porous. Pawley fitting of the diffraction data
for 4 and 5 show good agreement with their respective
model structures, confirming that they possess both the
connectivity and eclipsed stacking arrangement of their
imine progenitor 1 (See SI, Section S7). Additionally, the
Scheme 2. Reorientation of hydroxyl groups in the
solid state after demethylation.
In an effort to evaluate the necessity of performing the de-
methylation of 1 in the solid state, we examined the synthe-
sis of 4 and 5 starting from de novo-synthesized 2 (2’),
which can be formed directly from the condensation of
TAPS and 3,5-dihydroxyterephthalaldehyde (See SI, Section
S3). This would shift the demethylation, which we know to
be incomplete in the solid state under our conditions, to the
solution state. Even after extensive screening of
2
BET areas of 4 and 5 were found to be 780 and 791 m /g,
retaining 64 and 63% of the BET area of 1 respectively. This
retention of surface area occurs despite the COF being sub-
jected to three consecutive postsynthetic modifications, one
of which resulted in a non-crystalline framework. From
these experiments, we can infer that 3 possesses the same
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crystallization conditions, 2’ possesses poorer crystallinity,
Fellowship Program and the Chevron-UC Berkeley Graduate
Fellowship Program. We also acknowledge use of the computa-
tional resources in the Molecular Graphics and Computational
Facility at UC Berkeley, which is supported under NIH
S10OD023532. Crystal structures of model compounds 11 an
1
2
3
4
5
6
7
8
9
and significantly lower surface area than 2 (See SI, Section
S10). The quality of this COF has a significant impact on sub-
sequent postsynthetic modifications (See SI, Section S6).
Despite being performed under identical conditions, reduc-
tion under this route proceeds at only 80% yield. Subse-
quent treatment with CDI or TCDI and DMAP yield 4’ and 5’,
1
2 in the supporting information were obtained by Nicholas
Settineri and were supported by the NIH Shared Instrumenta-
tion Grant S10-RR027172.
1
5
in which only 62 and 68% of N sites are carbamates and
thiocarbamates respectively. Furthermore, the BET areas of
2
4
’ and 5’ are only 217 and 332 m /g respectively. The dif-
ferences between these two synthetic routes illustrate the
importance of the quality of COF starting material in
postsynthetic modifications. In this case, one additional
synthetic step in the solid state provides access to signifi-
cantly higher yields and higher quality products due to our
ability to access to a more crystalline and porous COF start-
ing material.
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(1)
Yaghi, O. M.; Kalmutzki, M. J.; Diercks, C. S. Introduction to
Reticular Chemistry: Metal‐Organic Frameworks and Covalent Or‐
ganic Frameworks; Wiley-VCH Verlag GmbH & Co. KGaA: Wein-
heim, Germany, 2019; 509 pp.
(
2)
lent Organic Frameworks. Acc. Chem. Res., 2015, 48, 3053–3063.
3) Diercks, C. S.; Yaghi, O. M. The atom, the molecule, and the
covalent organic framework. Science 2017, 355, 293–302.
(4) Lyle, S. J.; Waller, P. J.; Yaghi, O. M. Covalent Organic
Waller, P. J.; Gándara, F.; Yaghi, O. M. Chemistry of Cova-
(
In conclusion, an imine-linked COF was transformed
through three consecutive synthetic steps to isostructural
cyclic carbamate and thiocarbamate-linked COFs. These
new linkages are the first for which one-pot small molecule
equivalent reactions do not exist, necessitating the need for
multistep synthesis in the solid state. Each substrate in this
Frameworks: Organic Chemistry Extended into Two and Three Di-
mensions. Trends in Chemistry 2019, 1(2), 172–184.
(
5)
Nagai, A.; Guo, Z.; Jin, S.; Feng, X.; Jin, S.; Chen, X.; Ding, X.;
Jiang, D. Pore surface engineering in covalent organic frameworks.
Nat. Commun. 2011, 2, 536.
(6)
Qi, S.; Aguila, B.; Perman, J.; Earl, L. D.; Abney, C. W.;
Cheng, Y.; Wei, H.; Nguyen, N.; Wojitas, L.; Ma, S. Postsynthetically
Modified Covalent Organic Frameworks for Efficient and Effective
Mercury Removal. J. Am. Chem. Soc. 2017, 139(7), 2786–2793.
1
5
synthesis was analyzed by N multiCP-MAS NMR spectros-
copy, for the first time allowing quantitative compositional
analysis of each compound along the synthetic route. Fur-
thermore, each solid-state chemical transformation per-
formed in this work was accompanied by a structural or
conformational transformation, highlighting the critical im-
portance of linkages in COF structure and properties. This
work constitutes an extension of organic synthesis – both
multi-step transformations and the analytical rigor neces-
sary to characterize them – from the solution to the solid
state.
(7)
Lohse, M. S.; Stassin, T.; Naudin, G.; Wuttke, S.; Ameloot,
R.; De Vos, D.; Medina, D. D.; Bein, T. Sequential Pore Wall Modifi-
cation in a Covalent Organic Framework for Application in Lactic
Acid Adsorption. Chem. Mater. 2016, 28(2), 626–631.
(
8)
Waller, P. J.; Lyle, S. J.; Osborn Popp, T.; Diercks, C. S.;
Reimer, J. A.; Yaghi, O. M. Chemical Conversion of Linkages in Cova-
lent Organic Frameworks. J. Am. Chem. Soc. 2016, 138, 15519–
1
5522.
(9)
Haase, F.; Troschke, E.; Savasci, G.; Banerjee, T.; Duppel,
V.; Dörfler, S.; Grundei, M. M. J.; Ochsenfeld, C.; Kaskel, S.; Lotsch, B.
V. Topochemical conversion of an imine- into a thiazole-linked co-
valent organic framework enabling real structure analysis. Nat.
Commun. 2018, 9, 2600.
The Supporting Information is available free of charge on the
ACS Publications website.
(
10) Liu, H.; Chu, J.; Yin, Z.; Cai, X.; Zhuang, L.; Deng, H. Cova-
lent Organic Frameworks Linked by Amine Bonding for Concerted
Electrochemical Reduction of CO . Chem. 2018, 4, 1696–1709.
11) Li, X.; Zhang, C.; Cai, S.; Lei, X.; Altoe, V.; Hong, F.; Urban, J.
2
Synthetic procedures for monomers and model com-
pounds, including NMR and mass spectra; Synthetic pro-
cedures for all solid-state transformations, including
(
J.; Ciston, J.; Chan, E. M.; Liu, Y. Facile transformation of imine cova-
lent organic frameworks into ultrastable crystalline porous aro-
matic frameworks. Nat. Commun. 2018, 9, 2998.
(12) Waller, P. J.; AlFaraj, Y. S.; Diercks, C. S.; Jarenwattananon,
N. N.; Yaghi, O. M. Conversion of Imine to Oxazole and Thiazole
Linkages in Covalent Organic Frameworks. J. Am. Chem. Soc. 2018,
PXRD patterns, FT-IR spectra, N adsorption isotherms,
2
1
5
and N-multiCP-MAS NMR spectra; Crystallographic in-
formation for each model compound and associated com-
putations.
1
40, 9099–9013.
13) Jaradat, D. M. M. Thirteen decades of peptide synthesis:
(
key developments in solid phase peptide synthesis and amide bond
formation utilized in peptide ligation. Amino Acids 2018, 50, 39–
68.
* yaghi@berkeley.edu
(
14) Fracaroli, A. M.; Siman, P.; Nagib, D. A.; Suzuki, M.; Fu-
rukawa, H.; Toste, F. D.; Yaghi, O. M. Seven Post-synthetic Covalent
Reactions in Tandem Leading to Enzyme-like Complexity within
Metal−Organic Framework Crystals. J. Am. Chem. Soc. 2016, 138,
8352–8355.
Synthesis in this work was supported by King Abdulaziz City
for Science and Technology (Center of Excellence for Nano-
materials and Clean Energy Applications), and the characteri-
zation of compounds by the Center for Gas Separations Rele-
vant to Clean Energy Technologies, an Energy Frontier Re-
search Center funded by the U.S. Department of Energy, Office
of Science, Basic Energy Sciences under Award DE-SC0001015.
T.O.P. acknowledges funding from the NSF Graduate Research
(
15) Wei, P.-F.; Qi, M.-Z.; Wang, Z-P.; Ding, S.-Y.; Yu, W.; Liu, Q.;
Wang, L.-K.; Wang, H.-Z.; An, W.-K.; Wang, W. Benzoxazole-Linked
Ultrastable Covalent Organic Frameworks for Photocatalysis. J. Am.
Chem. Soc. 2018, 140, 4623–4631.
(16) Stewart, D.; Antypov, D.; Dyer, M. S.; Pitcher, M. J.; Katsou-
lidis, A. P.; Chater, P. A.; Blanc, F.; Rosseinsky, M. J. Stable and
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 7
ordered amide frameworks synthesised under reversible condi-
tions which facilitate error checking. Nat. Commun. 2017, 8, 1102.
17) Bala, M.; Verma, P. K.; Sharma, D.; Kumar, N.; Singh, B.
Highly efficient water-mediated approach to access benzazoles:
metal catalyst and base-free synthesis of 2-substituted benzimid-
azoles, benzoxazoles, and benzothiazoles. Mol. Divers. 2015, 19 (2),
cage into a robust carbamate cage. Chem. Commun. 2017, 53, 8616–
8619.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
(25) Johnson, R. L.; Schmidt-Rohr, K. Quantitative solid-state
C NMR with signal enhancement by multiple cross polarization. J.
13
Magn. Reson. 2014, 239, 44–49.
(26) Duan, P.; Schmidt-Rohr, K. Composite-pulse and partially
13
2
63−272.
dipolar dephased multiCP for improved quantitative solid-state C
(18) Tang, J.; Wang, L.; Mao, D.; Wang, W.; Zhang, L.; Wu, S.;
NMR. J. Magn. Reson. 2017, 285, 68–78.
Xie, Y. Ytterbium pentafluorobenzoate as a novel fluorous Lewis
acid catalyst in the synthesis of 2,4-disubstituted quinolines. Tet-
rahedron 2011, 67, 8465–8469.
(27) Szabo, M.; Agostino, M.; Malone, D. T.; Yuriev, E.; Capu-
ano, B. The design, synthesis and biological evaluation of novel
URB602 analogues as potential monoacylglycerol lipase inhibitors.
Bioorg. Med. Chem. Lett. 2011, 21, 6782–6787.
(28) Hernández, A. S.; Hodges, J. C. Solid-Supported tert-
Alkoxycarbonylation Reagents for Anchoring of Amines during
Solid Phase Organic Synthesis. J. Org. Chem. 1997, 62, 3153–3157.
(29) Luca, O. R.; Wang, T.; Konezny, S. J.; Batista, V. S.; Crab-
tree, R. H. DDQ as an electrocatalyst for amine dehydrogenation, a
model system for virtual hydrogen storage. New J. Chem. 2011, 35,
998–999.
(30) Rabbani, M. G.; Sekizkardes, A. K.; Kahveci, Z.; Reich, T. E.;
Ding, R.; El-Kaderi, H. M. A 2D Mesoporous Imine-Linked Covalent
Organic Framework for High Pressure Gas Storage Applications.
Chem. Eur. J. 2013, 19, 3324–3328.
(31) Alam, P.; Leung, N. L. C.; Cheng, Y.; Zhang, H.; Liu, J.; Wu,
W.; Kwok, R. T. K.; Lam, J. W. Y.; Sung, H. H. Y.; Williams, I. D.; Tang,
B. Z. Spontaneous and Fast Molecular Motion at Room Tempera-
ture in the Solid State. Angew. Chem. Int. Ed. 2019, 58, 1–6.
(32) Liu, Y.; Zhao, Y.; Sun, X.; Gándara, F.; Furukawa, H.; Liu, Z.;
Zhu, H.; Zhu, C.; Suenaga, K.; Olenynikov, A.; Alshammari, S.; Zhang,
X.; Teresaki, O; Yaghi, O. M. Weaving of Organic Threads into a Crys-
talline Covalent Organic Framework. Science 2016, 351, 365–369.
(
19) Thakur, M. S.; Nayal, O. S.; Sharma, A.; Rana, R.; Kumar,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N.; Maurya, S. K. An Efficient Metal-Free Mono N-Alkylation of Ani-
lines via Reductive Amination Using Hydrosilanes. Eur. J. Org.
Chem. 2018, 6729–6732.
(
20) Kandambeth, S.; Mallick, A.; Lukose, B.; Mane, M. V.;
Heine, T.; Banerjee, R. Construction of Crystalline 2D Covalent Or-
ganic Frameworks with Remarkable Chemical (Acid/Base) Stabil-
ity via a Combined Reversible and Irreversible Route. J. Am. Chem.
Soc. 2012, 134, 19524–19527.
(
21) Baxter, E. W.; Rietz, A. B. Reductive aminations of car-
bonyl compounds with borohydride and borane reducing agents,
Organic Reactions; John Wiley and Sons, Inc.: Hoboken, NJ, United
States, 2002; 1–714.
(22) Liu, Q; Batt, D. G.; Delucca, G. V.; Shi, Q; Tebben, A. J. Prep-
aration of carbazole carboxamide compounds useful as kinase in-
hibitors. U. S. Patent 20100160303, June, 24, 2010.
(
23) Pretsch, E.; Bühlmann, P.; Badertscher, M. IR Spectros-
copy. Structure Determination of Organic Compounds, 4th ed.;
Springer: Berlin, 2009; 269–335.
(24) Hu, X.-Y.; Zhang, W.-S.; Rominger, F.; Wacker, I.; Schröder,
R. R.; Mastalerz, M. Transforming a chemically labile [2+3] imine
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