A base-free Chan–Lam reaction catalyzed by an easily assembled Cu(II)-carboxylate metal-organic framework

Article abstract of DOI:10.1177/17475198211026506

A new copper(II) metal-organic framework is constructed as a sustainable copper heterogeneous catalyst. Cu-DPTCA, with high catalytic activity, can effectively promote the Chan–Lam coupling reaction of arylboronic acids and amines without adding any base or additive.

Full text of DOI:10.1177/17475198211026506

1026506CHL0010.1177/17475198211026506Journal of Chemical ResearchZhang et al.
research-article2021
Article
Journal of Chemical Research
1–5
© The Author(s) 2021
Article reuse guidelines:
sagepub.com/journals-permissions
A base-free Chan–Lam reaction catalyzed
by an easily assembled Cu(II)-carboxylate
metal-organic framework
https://doi.org/10.1177/17475198211026506
DOI: 10.1177/17475198211026506
journals.sagepub.com/home/chl
Xinhai Zhang1 , Jianhua Qin2,
Ruixuan Ma3 and Lei Shi3
Abstract
A new copper(II) metal-organic framework is constructed as a sustainable copper heterogeneous catalyst. Cu-DPTCA,
with high catalytic activity, can effectively promote the Chan–Lam coupling reaction of arylboronic acids and amines
without adding any base or additive.
Keywords
amines, arylboronic acid, Chan–Lam reaction, Cu-metal-organic framework, heterogeneous catalysis
Date received: 22 February 2021; accepted: 2 June 2021
noble metals. So far, various homogeneous Cu catalysts
have been used for the Chan–Lam reaction to access
N-arylamine subunits. Nevertheless, the use of an additional
base in a stoichiometric amount is required for regeneration
Introduction
Reactions that form C–N bonds are widely used in synthetic
chemistry due to the prevalence of this functionality within
pharmaceuticals and biologically active natural products.1–4
of the active Cu species. Furthermore, homogeneous
In recent decades, various effective strategies based on tran-
sition-metal catalysis for C–N bond formation have been
developed, such as Pd-catalyzed Buchwald–Hartwig cou-
1School of Traffic and Materials Engineering, Hebi Polytechnic, Hebi,
pling5,6 and Ullmann coupling.7 However, these cases
People’s Republic of China
mostly involve the expensive transition-metal palladium
and harsh reaction conditions (over 100°C), which restrict
2College of Chemistry and Chemical Engineering, Luoyang Normal
University, Luoyang, People’s Republic of China
3Zhang Dayu School of Chemistry, Dalian University of Technology,
Dalian, People’s Republic of China
their wide applications in industry. However, the Chan–Lam
cross-coupling reaction, the oxidative coupling of amines
and arylboronic acids catalyzed by Cu salts, represents one
of the most powerful and straightforward tools to construct
C–N bonds.8–13 This process is mild, convenient, and cheap,
offering an alternative to complementary methods using
Corresponding author:
Xinhai Zhang, School of Traffic and Materials Engineering, Hebi
Polytechnic, Hebi 458030, People’s Republic of China.
Email: goldhai7527@163.com
Creative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons
Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use,
reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and
Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

2
Journal of Chemical Research
Figure 1. DPTCA ligands are presented and assembled with CuII, forming a Cu-based framework.
catalytic systems are generally affected by the separation of porous framework. The effective free volume of Cu-DPTCA
the products and the metal catalysts, which can be problem-
atic and costly.
is calculated by PLATON analysis as 17.1% of the crystal
volume including the free DMF molecules. When viewed
from the a-axis, Cu-DPTCA has large triangular channels.
The structure contains Cu4 cluster units (Figure 2). The crys-
tallographic data of Cu-DPTCA are summarized in Table 1.
The thermal stability was verified by TGA. A differential
thermal weight loss experiment was performed on
Cu-DPTCA under an N2 atmosphere. The temperature range
was 30–805°C, and the temperature ramp rate was
10°Cmin−1. The TGA curve (Figure 3) shows that the first
mass loss (15%) occurred between 30 and 175°C due to the
loss of coordinated H2O molecules (theoretical value is
11.3%). Between 175 and 300°C, it can be seen that the
frame structure collapsed and was completely dissociated by
500°C.TheaboveexperimentalresultsshowthatCu-DPTCA
retains its frame structure and is stable below 300°C.
To further investigate the porosity of Cu-DPTCA, sub-
strate adsorption experiments were performed with phenylb-
oronic acid (2). Cu-DPTCA crystals were soaked in a
saturated acetonitrile solution of phenylboronic acid (2) for
3days. Then, the Cu-DPTCA crystals were washed with
diethyl ether to remove excess phenylboronic acid (2) which
was merely absorbed or a coating on the surface of the crys-
tals. Subsequently, the pre-treated Cu-DPTCA crystals were
dissolved in DMSO-d6 and the NMR analysis revealed the
presence of phenylboronic acid (2). These experimental
results clearly showed that the cavity of Cu-DPTCA can
accommodate organic molecules of an appropriate size such
as phenylboronic acid (2); thus, it can potentially act as a
heterogeneous catalytic material for organic reactions.
At the outset of the investigation, we were interested in
exploring the catalytic potential of Cu-DPTCAfor the Chan–
Lam coupling reaction. Before catalytic reactions, pre-treat-
ment is required to activate Cu-DPTCA. Thus, the
Cu-DPTCAcatalyst was immersed in an acetonitrile solution
for 24h for guest molecular exchange and then dried in a
vacuum oven (100°C, 2h) to remove acetonitrile molecules
and solvent molecules inside the Cu-DPTCA catalyst.
In recent years, metal-organic frameworks (MOFs) have
emerged as a distinct new option for heterogenization of a
metal catalyst for organic synthesis.14–19 In comparison
with other existing heterogeneous catalytic systems, the
design flexibility and framework tunability resulting from
the huge variations of metal nodes and organic linkers
allow the introduction of different compositions in a single
MOF.20–25 With this in mind, we anticipated that a MOF
containing an amine motif in the organic linker and Cu ion
nodes should have two benefits. It may eliminate the need
for an additional base, and it may facilitate the recovery and
separation of the Cu metal catalyst from products, thereby
reducing economic and environmental barriers. To achieve
this objective, herein we report the synthesis of a new
Cu-DPTCA MOF based on diphenylamine tetracarboxylic
acid (DPTCA) and Cu metal (Figure 1, left), named
[Cu2.5(DPTCA)(OH)(dma)2(H2O)]·2DMF (abbreviated as
Cu-DPTCA), (dma=dimethylamine, DMF=N,N-dimethyl-
formamide). With a diphenylamine acid as the linker,
DPTCA forms a quad-core structure with a high surface
area and large pore volume, providing open metal sites
accessible in the catalytic process (Figure 1, right). The
MOF was characterized by single-crystal and powder X-ray
diffraction, infrared spectroscopy, and thermogravimetric
analysis (TGA).
Results and discussion
The asymmetric unit of Cu-DPTCA contains two and a half
CuII ions, one DPTCA ligand molecule, one μ3-hydroxyl
group, two coordinated dimethylamines, one coordinated
water molecule, and two free DMF molecules. Cu-DPTCA
features a non-interpenetrated open three-dimensional (3D)
porous framework constructed from a tetranuclear Cu(II)
cluster [Cu4(CO2)6(μ3–OH)2] and DPTCA (Figure 1). Six
carboxylate groups from six DPTCA ligands and two μ3-
hydroxy oxygen atoms link four adjacent Cu(II) ions into
tetranuclear clusters. Each DPTCA ligand links four tetranu-
clear Cu(II) clusters, resulting in the formation of a 3D
Next, phenylboronic acid (2) and primary amine 3a were
selected as template substrates to investigate the catalytic

Zhang et al.
3
Figure 2. (a) The asymmetric unit of Cu-DPTCA, (b) the tetranuclear Cu cluster in Cu-DPTCA, and (c) the cavity in Cu-DPTCA.
performance of Cu-DPTCA. These reactions were carried out required a longer reaction time (about 12h) and afforded 4f
in different solvents at 30°C for 12h and the experimental and 4g in satisfactory yields. Interesting, highly reactive
results are listed in Table 2. When polar aprotic solvents were allylamine (3h) reacted with phenylboronic acid smoothly
used, such as DMF, DMSO, THF, and acetonitrile, the reac- and produced 4h in good yield (Table 3).
tions afforded the desired product 4a in good to excellent
The advantage of the Cu-DPTCA catalyst over its homo-
yields, because such solvents can significantly enhance the geneous counterparts lies in its facile recovery and reusabil-
activity of nucleophiles. However, in polar protic solvents ity. To this end, the Cu-DPTCA catalyst was recovered and
such as methanol and ethanol, the yields dropped signifi- used under the optimized conditions for C–N coupling of
cantly due to the formation of a large number of unidentified phenylboronic acid (2) and cyclohexylamine 3d. At the end
by-products. Among the solvents screened, DMF is the best of each cycle, simple centrifugation of the reaction mixture
solvent giving a yield of 86%. In the case of the reaction with- allowed the separation of the solid-state catalyst from the
out Cu-DPTCA, the reaction failed to produce any product product-containing solution, and this was repeatedly washed
indicating that Cu is indispensable for the coupling. with diethyl ether to remove the product from the pores inside
Furthermore, the reaction is not sensitive to oxygen or H2O Cu-DPTCA. The same isolated Cu-DPTCA catalysts were
and can be carried out in open air. It is worth noting that the recharged with acetonitrile and phenylboronic acid (2) and
reactions did not need an additional basic additive.
cyclohexylamine 3d for the next run. In the recycling experi-
Under the optimized conditions, the substrate scope of ments, we found that the use of acetonitrile as solvent is the
the amines was further investigated, and a number of struc- best in term of yields and recyclability. The Cu-DPTCA cata-
turally different amines were selected. Primary aliphatic lyst can be reused for at least three times with near-quantita-
amines, such as 3c and 3e, provided excellent yields of tive conversion and 60%–70% yields. However, it was
N-arylated amines 4c and 4e with good yields in short reac- observed that for the fourth recycling experiment extending
tion times (within 3h). Aromatic aniline (3b) reacted faster the reaction time to 24h is necessary for better yield of prod-
and afforded diarylamine 4b in 74% yield. Secondary ucts. This may indicate the loss of the catalyst’s reactivity
amines, such as morpholine (3f) and diphenylamine (3g), gradually during separation process.

4
Journal of Chemical Research
Table 1. Crystallographic data and experimental details.
Complex
Cu-DPTCA
Empirical formula
Formula weight
Temperature (K)
Crystal system
Space group
a (Å)
C26H35Cu2.5N5O11
752.44
296.15
Monoclinic
P21/n
10.8080(7)
b (Å)
17.4762(9)
c (Å)
19.9289(17)
α (°)
90
β (°)
102.658(4)
γ (°)
90
3672.7(4)
4
1.361
1.495
Volume (Å3)
Z
ρ
calcg (cm3)
μ (mm−1)
F(000)
1546.0
Crystal size (mm3)
0.02×0.01×0.01
MoKα (λ=0.71073)
4.19 to 49.994
−12⩽h⩽12, −20⩽k⩽20, −19⩽l⩽23
15,248
6412 [Rint =0.0496, Rsigma =0.0712]
6412/125/411
1.082
Radiation
2θ range for data collection (°)
Index ranges
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness-of-fit on F2
Final R indexes (I⩾2σ (I))
Final R indexes (all data)
Largest difference peak/hole (eÅ−3)
R1 =0.0558, wR2 =0.1500
R1 =0.0762, wR2 =0.1582
1.67/−1.01
1/2
R = [Σ || Fo | − | F || /Σ | Fo |], Rw = Σw[| Fo2 −F2 |2 /Σw (| Fw |2 )2 ]
.
c
c
Table 2. Optimization of the reaction conditions.a
H
N
B(OH)2
Cu-DPTCA
O
O
NH2
solvent
12 h, 30 oC
2
3a
4a
Entry
Solvent
Yield
1
2
3
4
5
6
7
DMF
86%
74%
66%
62%
47%
24%
31%
DMSO
MeCN
THF
1,4-dioxane
MeOH
EtOH
aReaction conditions: amine (1.5mmol), arylboronic acid (1mmol), catalyst
Cu-DPTCA (8μmol based on a paddlewheel unit), DMF (4mL), and air.
Figure 3. TGA curve of Cu-DPTCA.
can be easily recovered from the product, and thus the sus-
tainability is significantly improved.
Conclusion
In the present work, a new Cu(II)-carboxylate-based MOF
[Cu2.5(DPTCA)(dma)2(DMF)2(H2O)]n has been synthe-
sized by a solvothermal method and characterized by sin-
gle-crystal and powder X-ray diffraction, infrared
spectroscopy, and TGA. Cu-DPTCA has good triangular
channels, and the presence of coordinated, unsaturated
open metal sites allows it to be used for the Chan–Lam
coupling reaction, affording various amine products. It is
worth mentioning that this eco-friendly process does not
require an additional basic additive and the Cu-DPTCA
Experimental
Materials and measurements
All solvents and chemical materials used in the synthesis
were purchased from commercial sources and were used
without further purification. X-ray powder diffraction
(PXRD) was recorded with CuKα radiation (λ=1.54056Å)
using a Bruker AXS D8 advanced diffractometer at an
angle of 2293=5–50° at 293K.

Zhang et al.
5
Table 3. Reaction scope.a,b
column chromatography (petroleum ether–EtOAc, 10: 1) to
give coupling products 4.
R1
N
B(OH)2
Cu-DPTCA
DMF, 30oC ,air
R1R2NH
R2
Declaration of conflicting interests
2
3
4
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.
H
N
H
N
H
O
N
Funding
The author(s) disclosed receipt of the following financial support
for the research, authorship, and/or publication of this article: This
project was supported by the Project of Science and Technology
of Henan Province (no. 202102210233) and the Open Research
Fund of the School of Chemistry and Chemical Engineering,
Henan Normal University (no. 2020YB03).
4a
4d
4b
4c
: 69%
: 86%
: 74%
H
N
H
N
N
O
4e
4f
: 64%
: 80%
: 83%
ORCID iD
Xinhai Zhang
https://orcid.org/0000-0003-3357-3174
N
N
Supplemental material
4g
4h
: 90%
: 72%
Supplemental material for this article is available online.
aReaction conditions: amine (1.5mmol), arylboronic acid (1mmol),
catalyst Cu-DPTCA (8μmol based on a paddlewheel unit), DMF (4mL),
References
1. Averin AD, Abel AS, Grigorova OK, et al. Pure Appl Chem
2020; 92: 1181.
rt, and air.
bIsolated yields.
2. Roscales S and Csáky AG. Chem Soc Rev 2020; 49: 5159.
3. Ganley JM, Murray PRD and Knowles RR. ACS Catal 2020;
10: 11712.
Crystallography
4. Vitaku E, Smith DT and Njardarson JT. J Med Chem 2014;
57: 10257.
5. Dorel R, Grugel CP and Haydl AM. Angew Chem Int Ed
2019; 58: 17118.
6. Heravi MM, Kheilkordi Z, Zadsirjan V, et al. J Organomet
Chem 2018; 861: 17–104.
7. Sambiagio C, Marsden SP, Blacker AJ, et al. Chem Soc Rev
2014; 43: 3525.
8. Qiao J and Lam P. Synthesis 2011; 6: 829–856.
9. Jesin CP I, Haritha Mercy AA, Ravindra S, et al. J Org Chem
2020; 85: 3000.
10. Robinson H, Oatley SA, Rowedder JE, et al. Chem-Eur J
2020; 26: 7678.
The single-crystal structure was obtained using Bruker d8
Venture SMART-CCD single-crystal diffractometer with
MoKα radiation, wavelength (λ)=0.71073Å. Diffraction
data were collected using the SAMRT and SAINT programs.
The test temperature was maintained near 200K with liquid
nitrogen. The crystal structure was solved by direct methods
using SHELXTL-97. The full-matrix least-square method
was used to refine F2 (CCDC: 2047623).
Synthesis of Cu-DPTCA
DPTCA(13.8mg, 0.04mmol) and copper nitrate hexahydrate
(22.0mg, 0.12mmol) were placed in a 10-mL glass bottle,
and DMF (4mL) and distilled water (0.5mL) were added.
The resulting mixture was sonicated for 30min. The bottle
was placed in a 25-mL polytetrafluoroethylene-lined auto-
clave, sealed and placed in a program-controlled oven. The
oven was heated to 115°C for 5.5h and held for a further 70h.
The oven was cooled to room temperature over 15h and
colorless transparent square crystals were obtained with the
chemical formula C26H35Cu2.5N5O11. The crystals were fil-
tered and washed with the mother liquor. The yield was 52%.
11. Muñoz A, Leo P, Orcajo G, et al. ChemCatChem 2019; 15:
3376–3380.
12. Latha G, Devarajan N and Suresh P. ChemistrySelect 2020;
32: 10041–10047.
13. Chen JQ, Li JH and Dong ZB. Adv Synth Catal 2020; 16:
3311–3331.
14. Farha OK and Hupp JT. Accounts Chem Res 2010; 43: 1166.
15. Chen J, Shen K and Li YW. ChemSusChem 2017; 10: 3165.
16. Furukawa H, Cordova KE, O’Keeffe M, et al. Science 2013;
341: 1230444.
17. Zhu L, Liu XQ, Jiang HL, et al. Chem Rev 2017; 117: 8129.
18. Qin JH, Wang HR, Pan Q, et al. Dalton T 2015; 44: 17639–
17651.
19. Qin JH, Ma LF, Hu Y, et al. CrystEngComm 2012; 14: 2891.
20. Shahabi Nejad M, Seyedi N, Sheibani H, et al. Mol Divers
2019; 23: 527.
Cham–Lam reaction
N-arylation of phenylboronic acid and amine, in a typical
experimental procedure, Cu-DPTCA (8μmol) was added to
the amine (1.5mmol) and phenylboronic acid (1mmol) in
DMF (4mL) at 30°C, and the mixture was stirred at room
temperature for 12h under an air atmosphere. The progress
of the reaction was monitored by TLC, and when the reac-
tion was completed, the mixture was filtered to obtain a
crude product. The crude product was purified by silica gel
21. Guo HH, Chen G, Wu MX, et al. Microchim Acta 2017; 184:
4409.
22. Graaf MD and Moeller KD. J Org Chem 2016; 81: 1527.
23. Hao EJ, Li GX, Lv ZZ, et al. Org Chem Front 2020; 7: 345.
24. Xu GW, Wu YP, Dong WW, et al. Small 2017; 13: 1602996.
25. Wang HR, Huang C, Han YB, et al. Dalton T 2016; 45: 7776–
7785.