Amidation, Esterification, and Thioesterification of a Carboxyl-Functionalized Covalent Organic Framework

Article abstract of DOI:10.1002/anie.201912579

Three new post-synthetic modification reactions, namely amidation, esterification, and thioesterification, were demonstrated on a novel highly crystalline two-dimensional covalent organic framework (COF), COF-616, bearing pre-installed carboxyl groups. Th

Full text of DOI:10.1002/anie.201912579

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Accepted Article
Title: Amidation, Esterification, and Thioesterification of a Carboxyl-
Functionalized Covalent Organic Framework
Authors: Lei Guo, Shang Jia, Christian S. Diercks, Xuejing Yang,
Sultan A. Alshmimri, and Omar Yaghi
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201912579
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COMMUNICATION
Amidation, Esterification, and Thioesterification of a Carboxyl-
Functionalized Covalent Organic Framework
Lei Guo, Shang Jia, Christian S. Diercks, Xuejing Yang, Sultan A. Alshmimri, and Omar M. Yaghi*
Abstract: Three new post-synthetic modification reactions, namely
amidation, esterification, and thioesterification, were demonstrated
on a novel highly crystalline two-dimensional covalent organic
framework (COF), COF-616, bearing pre-installed carboxyl groups.
The strategy can be used to introduce a large variety of functional
groups into COFs and the modifications can be carried out under
mild reaction conditions, with high yields, and an easy work-up
protocol. As a proof of concept, various chelating functionalities were
generality of this approach. As such, a more general and facile
strategy for post-synthetic modification of COFs is highly sought
after.
We developed
a new COF, termed COF-616, whose
backbone is functionalized with carboxyl groups, which serve as
orthogonal handles for facile post-synthetic functionalization
reactions (Figure 1a). The carboxyl groups of COF-616 were
found to be amenable to post-synthetic amidation, esterification,
and thioesterification reactions. Such transformations have been
well-developed in terms of reactivity, yield, compatibility, and
separation to offer fast and clean products, especially in solid-
state peptide synthesis. As such, it holds promise as a mild and
effective toolbox for introduction of complex payloads onto COFs.
To demonstrate the versatility of this approach, a series of
chelating functionalities were successfully introduced into the
framework. Such modification is incompatible with copper-
assisted click reactions due to the strong chelating ability of
these payloads. The resulting frameworks can serve as efficient
adsorbents of various contaminants for water treatment.
successfully incorporated into COF-616 to yield
a family of
adsorbents for efficient removal of several contaminants in the water.
Covalent organic frameworks (COFs) are made by stitching
together molecular building units into crystalline porous
[1,2]
extended structures.
To take full advantage of the high
porosity and surface areas of these frameworks, specific
chemical functionality needs to be introduced into their pores to
[
3–
tailor interactions with guest species for a targeted application.
5
]
This introduction can be affected both pre-synthetically by
[6,7]
modifying the molecular building units,
or post-synthetically by
[8–16]
modifying the organic backbone of the framework.
Pre-
synthetic modification of COFs is generally limited because it
demands tedious synthetic efforts and may interfere with the
COF forming reaction. Post-synthetic modification provides
higher versatility, with click chemistry currently being the most
[
17,18]
widely-used protocol.
However, conducting such copper-
catalyzed azide-alkyne cycloaddition (CuAAC) reactions on
COFs generally requires anaerobic handling, involves
heterogeneous Cu(I) catalysts that need to be removed from the
pores of the framework, and is incompatible with molecules
featuring chelating functionalities — all of which greatly limit the
[*]
Dr. L. Guo, Dr. S. Jia, Dr. C. S. Diercks, Prof. O. M. Yaghi
Department of Chemistry
University of California-Berkeley
Berkeley, California, 94720, U.S.A.
E-mail: yaghi@berkeley.edu
Dr. L. Guo, Dr. C. S. Diercks, Prof. O. M. Yaghi
Materials Sciences Division, Lawrence Berkeley National
Laboratory; Kavli Energy NanoSciences Institute
Berkeley, California 94720, U.S.A.
Figure 1. (a) Synthetic scheme of COF-616. Color code: H, white; C, gray; N,
blue; O, red. (b) FT-IR spectra of COF-616 and comparison to the starting
materials 4PE and 3P-COOH, respectively. (c) PXRD pattern and Pawley
refinement of COF-616.
Dr. S. Alshmimri, Prof. O. M. Yaghi
UC Berkeley-KACST Joint Center of Excellence for Nanomaterials
for Clean Energy Applications, King Abdulaziz City for Science and
Technology
Riyadh, 11442, Saudi Arabia
Prof. X. Yang
COF-616
dicarboxylic acid-4,4’’-dicarboxaldehyde (3P-COOH) and
,1,2,2-tetraphenylethene (4PE) under solvothermal reaction
conditions in a mixture of 1,2-dichlorobenzene (DCB) and
butanol (BuOH) using glacial acetic acid as a catalyst (Figure
1a). The reaction mixture was sealed in a Pyrex tube and heated
at 100 °C for 2 days. COF-616 was obtained by filtration as a
yellow microcrystalline powder, which was found to be insoluble
was
synthesized
from
p-terphenyl-2’,5’-
Department of Civil and Environmental Engineering, University of
California-Berkeley, Berkeley, California 94720, U.S.A.;National
Engineering Laboratory for Industrial Wastewater Treatment, East
China University of Science and Technology, Shanghai, 200237,
China
1
Supporting information for this article is given via a link at the end of
the document.
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Angewandte Chemie International Edition
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COMMUNICATION
in common organic solvents such as alcohols, acetone,
supported by FT-IR spectra, where the modified product
exhibited the emergence of a characteristic absorbance of C=O
dichloromethane,
tetrahydrofuran,
N,N-dimethylformamide
-1
(
DMF), and N-methyl-2-pyrrolidione. The completeness of the
amide stretch (1648 cm ) and the disappearance of absorbance
-1
reaction was confirmed by Fourier-transform infrared (FT-IR)
spectroscopy, with appearance of a characteristic absorbance of
of C=O carboxyl stretch (1696 cm ) of the carboxylic acid
precursor (Figure 2b). On top of this, the PXRD pattern and
-1
imine stretch at 1621 cm and disappearance of both the
3 1
SEM micrographs demonstrated that COF-616-CON(CH )R
retained its crystallinity throughout the post-synthetic
modification process (Figure 2c and S29).
-1
characteristic absorbance of aldehyde stretch at 1682 cm and
-1
amine stretch at 3500-3150 cm (Figure 1b and S1). The
carbonyl stretching band of the carboxylic acid functional groups
-1
is red-shifted from 1723 cm in the starting material 3P-COOH
-1
to 1696 cm in COF-616, which is consistent with what is
observed for the molecular analogue (Figure S2). The thermal
stability of COF-616 was evaluated by thermogravimetric
analysis, where no significant weight loss was observed until
2
310 °C under N atmosphere (Figure S28). The chemical
formula of activated COF-616 was determined by elemental
analysis and was found to be consistent with the expected
elemental composition (Calcd. for C35
24 2 4 2
H N O .H O: C, 75.80%;
H, 4.73%; N, 5.06%; O, 14.42%. Found: C, 74.18%; H, 5.11%; N,
5.25%; O, 15.46%).
Scanning electron microscopy (SEM) images of COF-616
showed that all particles displayed a homogeneous morphology,
consisting of aggregated flake-shaped crystals (Figure S29).
The crystallinity of COF-616 was confirmed by powder X-ray
diffraction (PXRD) and the framework was found to crystallize in
the hexagonal space group P6 (Figure 1c). Pawley refinement
yielded unit cell parameters of a = b = 55.038(56) Å, and c =
3
.930(21) Å with good agreement factors (R
p
= 2.55 % and Rwp
Scheme 1. Post-synthetic amidation, esterification, and thioesterification of
=
3.69 %).
COF-616.
With the highly crystalline carboxyl-functionalized COF-616
in hand, we sought to demonstrate the first example of
converting carboxyl groups on COF backbones into amides
through activation followed by nucleophilic substitution reactions.
Amide coupling on COF-616 was performed using uronium salts
The protocol for post-synthetic amide coupling was further
adapted to Steglich esterification and thioesterification reactions
by changing to
dimethylaminopropyl)carbodiimide
modifications to yield COF-616-COOR
2-(trimethylsilyl)ethyl] were investigated as model
a
stronger coupling reagent, 1-ethyl-3-(3-
(EDC). Post-synthetic
and COF-616-COSR
[
19–21]
as coupling reagents.
While primary amines are not
2
2
compatible for this post-synthetic modification due to off-
pathway transimination reactions with the linkages of the
[
R
2
=
reactions: these functionalities were incorporated from the
respective alcohol or thiol in the presence of EDC·HCl as the
coupling reagent and 4-dimethylaminopyridine (DMAP) as an
activator (Scheme 1). The modification can be carried out in
various solvents, among which dichloromethane provided the
[
22]
framework, secondary amines are great candidates to append
organic moieties onto COFs and therefore N-methyl-1-
(
(
trimethylsilyl)methanamine was selected as a model compound
Scheme 1). To carry out the post-synthetic amidation, COF-616
was
trimethylsilyl)methanamine, hexafluorophosphate benzotriazole
tetramethyl uronium (HBTU), and N,N-diisopropylethylamine
DIPEA) in DMF and the mixture was allowed to react at room
temperature for 24 h. The amidated product, COF-616-
CON(CH )R [R = (trimethylsilyl)methyl], was obtained by
added
to
a
solution
of
N-methyl-1-
1
highest yields (74% and 63%, respectively) as confirmed by H
(
NMR spectroscopy and HPLC analysis of the digested sample
(
Figure 2a, S11, S12, and S18). Similarly, conversion of the
carboxylic acid was corroborated by FT-IR spectroscopy (Figure
b), and the crystallinity and morphology of resulted modified
(
2
3
1
1
products was well-preserved during the modification (Figure 2c
and S29).
filtration, washed with an excess of DMF, followed by hot
anhydrous methanol in a Soxhlet extractor, and eventually
evacuated under dynamic vacuum. Near-quantitative conversion
Encouraged by the synthetic ease of these post-synthetic
modifications, we aimed at demonstrating that COF-616 can
serve as a versatile functionalizable platform that can be readily
modified by any functionalities that would be highly challenging,
if not impossible, to be introduced using existing protocols.
Various chelating functional groups were selected to be
incorporated into COF-616. Specifically, post-synthetic
amidation using N,N-bis(2-((2-(ethylthio)ethyl)thio)ethyl)amine
(
95%) of carboxyl groups to amides was confirmed by the
appearance of characteristic peaks (δ -0.09 ppm for
=
1
trimethylsilyl group) in the H NMR spectrum of the digested
sample (Figure 2a and S10). High-performance liquid
chromatography (HPLC) analysis of the digested sample of
COF-616-CON(CH
was converted to 3P-CON(CH
3
)R
1
confirmed that building block 3P-COOH
)R (Figure S18). This was further
3
1
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1
Figure 2. (a) H NMR spectra of the digested samples, (b) FT-IR spectra, and
Figure 3. Synthesis of COF-616-NS4’, COF-616-CY, COF-616-IMD, COF-
3 1 2
(c) PXRD patterns of COF-616-CON(CH )R , COF-616-COOR , and COF-
6
16-MTE, and COF-616-DTT by post-synthetic modification of carboxyl-
functionalized COF-616, along with illustration of the unfunctionalized COF-
PE-3P.
616-COSR
2
, respectively.
4
(
NS4’),
cyclam
(CY),
and
1-(1H-imidazol-2-yl)-N-
methylmethanamine (IMD), post-synthetic esterification using 2-
methythio)ethanol (MTE), and post-synthetic thioesterification to
COF-616 adsorbents family can also be employed for water
(
treatment in terms of removal of residual oxidants from water
introduce dithiothreitol (DTT) yielded the functionalized
frameworks COF-616-NS4’, COF-616-CY, COF-IMD, COF-616-
MTE, and COF-616-DTT, respectively (Figure 3). The successful
incorporation of the functionalities was confirmed by FT-IR
[27–
cleanup and disinfection, soil remediation, or food processing.
29]
However, residual oxidants from these processes are harmful
to aquatic life and can generate disinfection byproducts that can
[30]
be bio-accumulated in food chains. Current practice to remove
1
spectroscopy, H NMR spectra of the digested samples (Figure
such strong oxidants requires large amounts of soluble
S4-8 and S13-17), and elemental analysis. The crystallinity of
the materials remained intact throughout the modification as
confirmed by PXRD and SEM micrographs (Figure S22 and
S29).
[31]
reductants, the dose of which is hard to administer.
This
inevitably introduces unnecessary secondary inorganic
[32]
pollutants into the effluent.
In this regard, heterogeneous
oxidant adsorbents can provide a more environmentally-friendly
alternative. Towards this end, aqueous solutions of most
commonly used oxidants with a concentration of 100 ppm were
treated with COF-616-series adsorbents, and the residual
oxidant species concentration was detected colorimetrically
With the high density of chelating groups anchored onto the
backbone of the framework, modified COF-616 family can be
directly utilized to remove heavy metal ions in water. The
performance of this series of functionalized COFs (COF-616,
COF-616-NS4’, COF-616-CY, COF-616-IMD, COF-616-MTE,
and COF-616-DTT) as well as the unfunctionalized COF-4PE-
[
33]
(
Figure 4b).
Sulfur-functionalized COFs (i.e. COF-616-NS4’,
COF-616-MTE, and COF-616-DTT) showed higher redox
reactivity with the oxidants owing to the propensity of thiols and
thioethers towards oxidation. In particular, functionalization with
DTT yielded the highest removal efficiency among all
functionalized COFs and COF-616-DTT was able to effectively
remove sodium hypochlorite in as little as 5 min at room
[
23,24]
+
2+
3P
were assayed for the uptake of metal ions (K , Ca ,
2
+
2+
2+
2+
2+
Pb , Hg , Cu , Zn , and Ni ) from water (Figure 4a). While
the thiol groups of COF-616-DTT outperformed other chelators
[
18,25,26]
due to their superior soft Lewis basicity,
nitrogen-rich
chelators also showed appreciable adsorption of heavy metal
-1
2
+
2+
2+
2+
temperature with [COF] of 200 mg L . This result collectively
suggests that COF-616 platform can be tailored for targeted
water treatment applications. To close, this work provides a
starting point for modular, high-throughput, and application-
directed development of functionalized COFs in an efficient
manner.
ions (i.e., COF-616-CY for removal of Pb , Cu , Zn , and Ni ,
2
+
and COF-616-IMD for removal of Hg ), thus providing a viable
alternative for designing heavy metal ions adsorbents. The
varying uptake capacities and selectivities towards heavy metal
ions with different chelating groups (Figure S32) illustrate the
importance of screening and optimizing the performance of a
given framework by appending a library of functional groups
through facile post-synthetic modification.
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Keywords: carboxylic acids • conjugation • covalent organic
frameworks • post-synthetic modification • water treatment
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COMMUNICATION
Table of Contents
COMMUNICATION
A
novel highly crystalline two-
Lei Guo, Shang Jia, Christian S.
Diercks, Xuejing Yang, Sultan A.
Alshmimri, and Omar M. Yaghi*
dimensional covalent organic
framework (COF) bearing pre-installed
carboxyl groups is reported. The
carboxylic acids enable facile post-
synthetic modification by amidation,
esterification, and thioesterfication for
Page No. – Page No.
Amidation,
Thioesterification of
Functionalized
Framework
Esterification,
and
Carboxyl-
Covalent Organic
a
introduction
functionality to the framework.
of
virtually
any
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