Synergic effect of copper-based metal-organic frameworks for highly efficient C-H activation of amidines

Article abstract of DOI:10.1039/c7ra10682c

A Cu-MOF-catalyzed C-H functionalization of substituted amidines was developed for the facile and efficient synthesis of benzimidazoles. More importantly, this transformation is compatible with various substrates derived from aryl nitriles without ortho substituents. Under reaction conditions devoid of O₂ atmosphere or specific groups, 537-MOF has been revealed as a key parameter for expanding the reaction scope and increasing the yield up to 96%. Importantly, this strategy also provides numerous opportunities for further utilization of MOFs as catalysts for challenging organic reactions.

Full text of DOI:10.1039/c7ra10682c

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Synergic effect of copper-based metal–organic
frameworks for highly efficient C–H activation of
amidines†
Cite this: RSC Adv., 2017, 7, 51658
*
Fen Xu,
Wei-Fen Kang, Xiao-Ning Wang, Hao-Dong Kou, Zhen Jin
*
and Chun-Sen Liu
A Cu–MOF-catalyzed C–H functionalization of substituted amidines was developed for the facile and
efficient synthesis of benzimidazoles. More importantly, this transformation is compatible with various
substrates derived from aryl nitriles without ortho substituents. Under reaction conditions devoid of O2
atmosphere or specific groups, 537-MOF has been revealed as a key parameter for expanding the
reaction scope and increasing the yield up to 96%. Importantly, this strategy also provides numerous
opportunities for further utilization of MOFs as catalysts for challenging organic reactions.
Received 27th September 2017
Accepted 23rd October 2017
DOI: 10.1039/c7ra10682c
rsc.li/rsc-advances
Activation of C–H bonds has been identied as a straightfor- natural products and for achieving the extension of molecule
ward and untraditional strategy for the decoration of unreactive complexity.8 Conventional synthetic routes to this scaffold rely
hydrocarbon skeletons in terms of its broad application in predominantly on condensation of carbonyl derivatives with
synthesis of pharmacological active agents, natural products, 1,2-phenylenediamines.9 Nevertheless, this strategy was
and functional materials.1 Given the prevalence and relevance impeded because of the limited availability of 1,2-phenylene-
of heteroatoms in molecules of interest, C–Het bond formation diamines and the disadvantage of further derivations. Several
via direct functionalization of C–H bonds has received consid- other approaches toward the synthesis of benzimidazoles have
erable attention. In this context, numerous transition metal also been reported, though the use of stoichiometric amounts
complexes, especially of Rh,2 Ir,3 Co,4 Ru,5 Pd6 and others,7 have of reagents and limited substrate scope were formidable
exhibited outstanding catalytic efficiency towards C–H bond obstacles.10 Chemists have attempted to fabricate benzimid-
functionalization reactions.
azole derivates by replacement of a C–H bond from amidines,11
Benzimidazoles have been deemed to be valuable interme- refraining from utilization of halogenated and pseudohalo-
diates and signicant building blocks for the construction of genated substrates to abbreviate or avoid waste byproducts
(Scheme 1).12 In general, high temperature, inert atmosphere or
high loading of oxidants was required.13 Besides noble
transition-metal catalysts, there have been reports on low-cost
and low-toxic copper-catalyze C–H derivation of amidines to
deliver benzimidazoles, whereas there remained several issues
Scheme 1 Catalytic strategies for the formation of benzimidazoles.
Department of Material and Chemical Engineering, Zhengzhou University of Light
Industry, Zhengzhou 450002, P. R. China. E-mail: fenxu_zzuli@163.com
† Electronic supplementary information (ESI) available: Experimental details,
crystal data and structural gures, gas adsorption, and characterization data.
CCDC 1547691. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c7ra10682c
Scheme
2 Synthesis of benzimidazoles from amidines via C–H
functionalization reaction catalyzed by 537-MOF.
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Table 1 Optimization of the reaction conditionsa
Entry
Catalyst
Additive
Yieldb
1c,d
2d
3d,e
4
5
6
7
8
9
537-MOF
537-MOF
537-MOF
HKUST-1
537-MOF
537-MOF
537-MOF
537-MOF
537-MOF
537-MOF
537-MOF
537-MOF
HOAc
HOAc
HOAc
HOAc
HOAc
HCOOH
MBSA
Benzoic acid
2-Fluorobenzoic acid
2-Bromobenzoic acid
2,3,4-Triuorobenzoic acid
64
59
54
40
73
21
Trace
96
62
Fig. 1 (a) Illustrations of the coordination mode of TPPB2ꢀ ligand. (b)
View of (3,6)-connected rtl topology of 537-MOF.
to be resolved. Representatively, Buchwald et al. developed an
C–H functionalization/C–N bond formation reaction to afford
benzimidazoles under an oxygen atmosphere.14 However, ami-
dines derived from aryl nitriles without ortho substituents
demonstrated frustrating conversion due to the decomposition
of substrates, which mainly retard the catalytic cycle. In addi-
tion, 2-phenyl-1H-benzo[d]imidazole was obtained in only 44%
yield under an air atmosphere. Thus, the development of
effective and low-cost catalytic system under reaction condi-
tions devoid of O2 atmosphere and specic groups was highly
demanded.
10
11
12
13
26
11
2,3,4,5-Tetrauorobenzoic acid
a
Reaction conditions: N-phenylbenzimidamide 1a (0.25 mmol), acid (5
equiv.), 537-MOF (10 mg), DMSO/DMF (2 mL, 1/1) at 100 ꢁC under air
atmosphere for 24 h. HPLC yield. O2. DMSO as solvent. e Without
4 A MS.
b
c
d
˚
Metal–organic frameworks (MOFs), assembled from metal
cluster secondary building units (SBUs) and organic linkers,
have emerged as a class of highly promising porous materials
with the advantages of high porosity, tunable compositions,
and decorative pore surface,15 as evidenced by wide potential for
various applications in drug deliver16 and separation,17 gas
storage,18 chemical sensing.19 Furthermore, using crystalline
MOFs as heterogeneous catalyst provides opportunities for
sustainable chemistry, thereby reducing waste and costs as well
as boosting the overall efficiency of a catalyst.20 For example,
Cohen et al.21 discovered that UiO-66-PdTCAT with site-isolated
Pd can be applied to C–H derivation and high catalytic activity
of UiO-66-PdTCAT can be attributed to the strong covalent
connected paddlewheel dimers leads to the assembly of a (3,6)-
connected rtl network displaying 1D atactic channels along
˚
b axis with the pore diameter of 5.1 A and the available void of
3
˚
1579.9 A , corresponding to 43.5% of the crystal volume (3629.0
3
˚
A ) (Fig. 1).
Our initial discovery of C–H functionalization of amidines in
the presence of 537-MOF and the subsequent screening inves-
tigations for the optimization are detailed in Table 1. The initial
discovery utilized a mixture of 537-MOF, 5 equiv. of HOAc and 4
˚
A MS (molecular sieve) as additive in (methylsulnyl)methane
(DMSO) at 100 ꢁC under O2 atmosphere to deliver 2-phenyl-1H-
benzo[d]imidazole 2a in 64% HPLC yield (entry 1). To our
delight, treatment of the transformation under air atmosphere
also gave satisfactory result (entry 2). The catalytic efficiency was
metalthiocatecholato binding. Recently,
a heterogeneous
nanoscaled [Cu3(BTC)2] catalyst was furnished and applied to
the aerobic oxidation of aromatic alcohols with excellent cata-
lytic reactivity originated from the aromatic carboxylate
ligand.22 Inspired by the above work, combined with the
advantages of shape and size selectivity,23 and lower activity
comparing with homogeneous catalysts to decrease the side
reaction, we devote to develop a new effective MOFs catalyst to
control the selectivity and catalytic activity in C–H functionali-
zation of amidines. Herein, we described successful fabrication
of a highly porous MOF, Cu2N2(CO2)4 (537-MOF), that shows
remarkably high efficiency on catalytic synthesis of benzimid-
azoles via C–H functionalization under air atmosphere with
broad substrates scope (Scheme 2).
˚
decreased when 4 A MS was absent (entry 3). Further optimi-
zation using typical HKUST-1 failed to give superior result (entry
4). We next turned our attention to enhancing the yield of 2a by
extensively screening solvents. The yield of 2a was indeed
improved when a mixed solvent (DMSO/DMF ¼ 1/1) was used
(entry 5). Of note, when benzoic acid was employed as an acidic
additive, the targeted product was detected in 96% HPLC yield.
The reason for this phenomena is probably due to the
suppression of decomposition products under this condition
(entry 8).
With the optimized reaction conditions in hand, we inves-
tigated the scope of the various substituted amidines (Table 2).
Functionalized amidines derived from aryl nitriles with
electron-neutral, electron-withdrawing, and electron-donating
substituents in ortho, para or meta positions, were smoothly
transformed into corresponding benzimidazoles 2a–2p in
moderate to excellent yields under air atmosphere. Among
these transformations, decomposition of amidines was
Single-crystal X-ray diffraction analysis reveals that 537-MOF
{[Cu2(TPPB)2](DMF)6} crystallizes in the triclinic space group
ꢀ
P1. The Cu1 and Cu2 atoms are bridged by four bridging
carboxylate groups from TPPB2ꢀ ligands, forming a {Cu2(O2C)4}
secondary building unit (SBU) with a short Cu–Cu distance of
2ꢀ
˚
2.70 A. As a result, each TPPB ligand binding to three 6-
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Table 2 Formation of benzimidazoles from different amidinesa
Entry
R1
H
R2
Product
Yieldb (%)
96 (2a)
1
2
C6H5
4-ClC6H4
H
84 (2b)
3
4
H
H
4-MeC6H5
3-MeC6H4
90 (2c)
87 (2d)
5
6
7
H
H
H
2-CH3C6H4
2-CF3C6H4
2-MeOC6H4
89 (2e)
85 (2f)
70 (2g)
8
H
5-F-2-MeC6H5
83 (2h)
9
4-Cl
4-Br
4-F
3-Me
85 (2i)
94 (2j)
85 (2k)
89 (2l)
10
11
12
2-MeC6H5
2-CF3C6H5
2-MeC6H5
4-I
13
14
3-MeO
4-MeO
4-ClC6H4
75 (2m)
70 (2n)
4-CF3C6H5
15
3-F-4-MeO
Br
C6H5
73 (2o)
87 (2p)
16
2-Me,5-ClC6H5
a
Reaction conditions: N-phenylbenzimidamide 1a (0.25 mmol), benzoic acid (5 equiv.), 537-MOF (10 mg), DMSO/DMF (2 mL, 1/1) at 100 ꢁC under
b
air atmosphere for 24 h. Isolated yield.
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TPPB ligand was probably deemed to be the really key param-
eter for enhancement of coordination ability of 537-MOF as well
as stabilizing intermediates B or C. Therefore, 537-MOF
comprised of metal catalytic site and auxiliary ligand was
utilized as a synergic catalyst, providing benzimidazoles in
moderate to high yields from amidines without the requirement
of ortho substituents for the staring nitriles under the atmo-
sphere of air.
Conclusions
Scheme 3 Proposed mechanism for 537-MOF-catalyzed C–H func-
tionalization of amidine.
In summary, we have developed an efficient, practical and
reliable route for 537-MOF-catalyzed C–H functionalization of
amidines to the synthesis of diverse benzimidazoles. This new
process features not only air condition instead of O2 atmo-
sphere, but also extremely broad substrate scope and good
functional-group compatibility, wherein challenging amidines
derived from aryl nitriles without ortho-substituent afforded
products in excellent yields. The synergic effect of 537-MOF was
proposed to be the critical factor of high efficiency and selec-
tivity. We anticipate that Cu–MOF will be utilized in other
challenging reactions.
inhibited effectively with 537-MOF as the catalyst (entries 1–16).
Regardless of their positions (ortho, para or meta), electron-
donating substituents for the starting nitriles, exerted no
apparently negative effect on the reaction efficiency and
provided the expected products 2c–2e in high yields (entries 3–
5). The amidine with ortho-MeO group was also found to be
compatible with the reaction conditions, while 2g was obtained
in 70% yield (entry 7). Using the disubstituted amidines 2h–2o,
the corresponding products could be isolated in admirable
yields (entries 8–15). 6-Bromo-2-(o-tolyl)-1H-benzo[d]imidazole
1j, beneting from ortho substituent (–Me), demonstrated
preferable reactivity than 1i, provided 2j in 94% yield (entries
10–11). Para-Substituted electron-withdrawing (p-F, Cl, Br, I) on
the N-aryl ring of the substituted N-phenylbenzimidamide gave
superior yields than the one with electron-donating group (p-
MeO), which presumably ascribed to the partial decomposition
of 2m–2o (entries 10–15). Notably, we were pleased to nd N-(4-
Conflicts of interest
There are no conicts to declare.
Acknowledgements
We are grateful to the support from the National Natural Science
Foundation of China (21471134, 21571158, and 21701148),
Program for Science & Technology Innovative Research Team in
University of Henan Province (15IRTSTHN002), Innovation
Scientists and Technicians Troop Construction Projects of Henan
Province (15-2101510003), Plan for Scientic Innovation Talent of
Henan Province (154200510011), and Universities in Henan
Province (17A150053).
bromophenyl)-5-chloro-2-methylbenzimidamide
1p
could
deliver the desired benzimidazole derivative in an excellent
yield of 87% (entry 16).
The catalyst was retrieved aer reaction of 1a and charac-
terized by powder X-ray diffraction (PXRD), which evidently
conrmed that the catalyst maintained excellent crystallinity
and was not damaged during the catalytic process (Fig. S4†).
Aer three cycles, the high yields and high selectivity of the
reactions were maintained (93% HPLC yield). Although it was
failed to isolate the intermediate to illustrate the accurate
mechanism, on the basis of the preliminary mechanistic
studies for related processes,14 two possible paths of the C–H
functionalization of amidines were proposed in Scheme 3. Path
1: coordination of 537-MOF24 and amidines is followed by
electrophilic addition of copper center to N-phenyl ring to
afford the metallacycle B.25 B is proposed to undergo reductive
elimination of the metal and rearomatization to provide target
product D. Alternatively, path 2: the amidines reacts with 537-
MOF to generate copper nitrene C.26 Insertion of the nitrogen
into a C–H bond of amidine, electrocyclic ring closure and
subsequent [1,3]-shi of a hydrogen lead to the formation of D.
Taken together, the experiment shows that propeller type
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