Direct oxidative amidation between N,N-dimethylanilines and anhydrides using metal-organic framework [Cu2(EDB)2(BPY)] as an efficient heterogeneous catalyst

Article abstract of DOI:10.1002/cplu.201402090

A crystalline porous metal-organic framework [Cu₂(EDB) ₂(BPY)] was synthesized and used as a heterogeneous catalyst for the direct oxidative amidation between N,N-dimethylanilines and anhydrides to form tertiary amides as the principal products. The [Cu₂(EDB) ₂(BPY)] exhibited similar activity as compared to that of [Cu ₂(BDC)₂(BPY)], [Cu₂(BDC)₂(DABCO)], MOF-143, and other common homogeneous salt catalysts. The optimal reaction conditions employed were [Cu₂(EDB)₂(BPY)] (10 % mol), TBHP (2 equiv), pyridine (1 equiv) in CH₃CN at 80 °C over 2 h. The Cu₂(EDB)₂(BPY) could be separated from the reaction mixture by filtration, and could be recovered and reused several times without a significant degradation in catalytic activity and selectivity. Furthermore, generality of the optimal conditions was confirmed by employing various N,N-dimethylaniline and anhydride derivatives. Copyright

Full text of DOI:10.1002/cplu.201402090

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DOI: 10.1002/cplu.201402090
Direct Oxidative Amidation between N,N-dimethylanilines
and Anhydrides Using Metal-Organic Framework
[Cu2(EDB)2(BPY)] as an Efficient Heterogeneous Catalyst**
Giao H. Dang, Thanh D. Nguyen, Dung T. Le, Thanh Truong,* and Nam T. S. Phan*[a]
A crystalline porous metal-organic framework [Cu2(EDB)2(BPY)]
was synthesized and used as a heterogeneous catalyst for the
direct oxidative amidation between N,N-dimethylanilines and
anhydrides to form tertiary amides as the principal products.
The [Cu2(EDB)2(BPY)] exhibited similar activity as compared to
that of [Cu2(BDC)2(BPY)], [Cu2(BDC)2(DABCO)], MOF-143, and
other common homogeneous salt catalysts. The optimal reac-
tion conditions employed were [Cu2(EDB)2(BPY)] (10% mol),
TBHP (2 equiv), pyridine (1 equiv) in CH3CN at 808C over 2 h.
The Cu2(EDB)2(BPY) could be separated from the reaction mix-
ture by filtration, and could be recovered and reused several
times without a significant degradation in catalytic activity and
selectivity. Furthermore, generality of the optimal conditions
was confirmed by employing various N,N-dimethylaniline and
anhydride derivatives.
Introduction
Amides have attracted significant attention because these
motifs are found in a variety of biologically important natural
products, pharmaceuticals, in fine chemicals, and synthetic
polymers.[1–3] Although the transformation of primary and sec-
ondary amines into amides can be readily achieved with car-
boxylic acids or acid chlorides as acylation agents,[4–6] establish-
ing a general and efficient protocol for the amide bond forma-
tion from tertiary amines is a challenge.[1,7,8] Notably, tertiary
amines are commonly present in various natural products, and
more easily available than secondary amines.[7,8] Indeed, several
synthetic routes were investigated for amide formation from
many starting material sources.[2,9,10] Recently, Li and co-work-
ers reported a new and efficient method for direct amide for-
mation by the reaction of tertiary amines with aldehydes.[8] To
avoid the disadvantages associated with the aldehydes, the ap-
proach was subsequently improved to access direct oxidative
amidation transformation between tertiary amines and anhy-
drides as acylation reagents in the presence of FeCl2 as cata-
lyst.[7] According to sustainable chemistry principles, organic
transformations using heterogeneous catalysts would be fa-
vored in terms of the ease of handling, simple workup, recycla-
bility, and reusability.[11] At the same time, the catalyst recovery
also offers opportunities to minimize the contamination of the
desired products with transition metals.[12,13]
Metal-organic frameworks (MOFs) have emerged as an ex-
tensive class of crystalline materials with potential applications
in numerous fields, including gas storage media, separations,
chemical sensors, thin film devices, optics, drug carriers, bio-
medical imaging, and catalysis.[14–21] MOFs are extended porous
structures constructed from two components, metal ions or
metallic clusters and polyfunctional organic linkers.[22,23] Com-
bining some special physical properties of both organic and in-
organic porous materials, MOF-based structures exhibit several
advantages as compared to conventional materials.[24–26] Al-
though application in catalysis is one of the newest develop-
ments for MOFs, this promising field is set to attract extensive
studies the near future.[27–29] A variety of MOFs have been em-
ployed as catalysts or catalyst supports for many organic reac-
tions, ranging from carbon-carbon[30–33] to carbon-heteroatom
forming transformations.[34–41] Among numerous popular MOFs
as catalysts, several copper-based structures offer high activity
for various organic reactions because of their unsaturated
open copper metal sites.[36,42–49] Herein, we present the direct
oxidative amidation of N,N-dimethylanilines with anhydrides
using the metal-organic framework [Cu2(EDB)2(BPY)] as an effi-
cient and recyclable heterogeneous catalyst (EDB=4,4’-ethy-
nyldibenzoic acid, BPY=4,4’-bipyridine). To the best of our
knowledge, the direct oxidative amidation between tertiary
amines and anhydrides as acylation reagents using heteroge-
neous catalyst is not previously reported.
[a] G. H. Dang, T. D. Nguyen, D. T. Le, T. Truong, N. T. S. Phan
Department of Chemical Engineering
HCMC University of Technology, VNU-HCM
268 Ly Thuong Kiet, District 10, Ho Chi Minh City (Viet Nam)
Fax: (+84)8-38637504
Results and Discussion
The synthesized [Cu2(EDB)2(BPY)] was characterized by using
several techniques, including X-ray diffraction (XRD), scanning
electron microscopy (SEM), transmission electron microscopy
(TEM), thermal gravimetric analysis (TGA), Fourier-transformin-
frared (FT-IR), atomic absorption spectroscopy (AAS), and nitro-
E-mail: tvthanh@hcmut.edu.vn
ptsnam@hcmut.edu.vn
[**] EDB=4,4’-ethynyldibenzoic acid, BPY=4,4’-bipyridine
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cplu.201402090.
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gen physisorption measurements (Figure S10–Figure S16 in the
Supporting Information). Noticeably, the availability of two
oxygen atoms in carboxylate ligands allows for a variety of co-
ordination modes ranging from monodentate, bidentate,
bridging, and even polydentate binding. Moreover, the use of
extended rodlike carboxylate spacers such as 4,4’-ethynyldi-
benzoic acid offers a larger amount of space, which leads to
facile approaches for applications in catalysis.
The [Cu2(EDB)2(BPY)] was assessed for its catalytic activity in
the direct oxidative amidation of N,N-dimethylaniline with
acetic anhydride (Scheme 1). Initial studies addressed the
effect of temperature on the conversion of N,N-dimethylaniline
Scheme 1. The direct oxidative amidation between N,N-dimethylaniline and
acetic anhydride using [Cu2(EDB)2(BPY)] catalyst.
into N-methyl-N-phenylacetamide. The oxidative amidation re-
action was carried out at 5 mol% [Cu2(EDB)2(BPY)] catalyst in
acetonitrile, using two equivalents of acetic anhydride, in the
presence of two equivalents of tert-butyl hydroperoxide oxi-
dant and one equivalent of pyridine, at room temperature,
608C, 708C, and 808C, respectively, for 120 min. It was found
that the oxidative amidation reaction proceeded with difficulty
at room temperature, to afford only 11% conversion after
120 min. As expected, increasing the reaction temperature led
to a significant enhancement in the reaction conversion, with
65% and 90% conversions after 120 min for the reaction car-
ried out at 608C and 708C, respectively. The reaction conver-
sion could be improved to more than 99% after 120 min at
808C (Figure 1a). It was observed that N-methylaniline was
also produced as the by-product in the product mixture.
Indeed, it was previously reported that secondary amines were
generated by oxidative dealkylation of tertiary amines in the
oxidative amidation transformation.[1,7,8] However, a selectivity
of 97% for N-methyl-N-phenylacetamide was still achieved
after 120 min.
Figure 1. Effect of temperature on the reaction conversion (a) and selectivi-
ty (b). Reaction conditions: N,N-dimethylaniline (0.5 mmol), acetic anhydride
(1.0 mmol), [Cu2(EDB)2(BPY)] (5 mol%), TBHP (1.0 mmol), pyridine (0.5 mmol),
acetonitrile (3 mL), reaction time (2 h).
after 120 min for the reaction using 1 mol% [Cu2(EDB)2(BPY)]
catalyst. The reaction conversion was up to 93% and more
than 99% after 120 min for the case of 3 mol% and 5 mol%
Cu-MOF catalyst, respectively (Figure 2a). The selectivity for N-
methyl-N-phenylacetamide was found to be slightly enhanced
when the catalyst concentration was increased, to afford 97%
selectivity after 120 min in the presence of 5 mol% [Cu2(EDB)2-
(BPY)] catalyst (Figure 2b).
The impact of different oxidants on the reaction conversion
was also examined (Figure 3). The results indicated that only
trace amount of desired product was detected for the reaction
using AgNO3 as the oxidant, meanwhile 34% and 37% conver-
sions were observed after 120 min for the case of MnO2 and 2,
2, 6, 6-tertramethylpiperidine-N-oxyl radical (TEMPO), respec-
tively. The oxidative amidation reaction proceeded to 54%
conversion after 20 min in the presence of hydrogen peroxide,
then no further conversion was observed at longer reaction
time. It is likely that decomposition of MOFs occurred because
the formation of water was observed after the oxidation step.
The oxidative amidation reaction using tert-butyl peroxide ben-
zoate afforded 85% conversion. Using cumyl hydroperoxide
for the transformation led to a significant enhancement in the
reaction conversion (Figure 3a). However, only 48% selectivity
was observed, leaving more than 50% by-product in the mix-
ture. tert-Butyl hydroperoxide was found to be the optimal oxi-
dant with more than 99% conversion and 97% selectivity (Fig-
In the first example of the oxidative amidation between N,N-
dimethylaniline and acetic anhydride as acylation agent, Li and
co-workers employed 2.5 mol% FeCl2 catalyst.[7] Similar
amounts of FeCl2 catalyst was also used for the oxidative ami-
dation of N,N-dimethylaniline with aldehyde as acylating
agent.[8] Chen and co-workers previously carried out the
copper-catalyzed oxidative amidation of aldehydes with amine
salts to form tertiary amides in the presence of 5 mol% CuSO4
catalyst.[50] We therefore decided to investigate the effect of
catalyst loading on the reaction conversion. It should be noted
that the oxidative amidation reaction could still occur in the
absence of the Cu-MOF catalyst. However, a conversion of only
28% and a selectivity of 78% for N-methyl-N-phenylacetamide
were detected after 120 min. This observation indicated the
necessity of using the [Cu2(EDB)2(BPY)] as catalyst for the oxi-
dative amidation reaction. A conversion of 90% was achieved
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Figure 2. Effect of catalyst concentration on reaction conversion (a) and se-
lectivity (b). Reaction conditions: N,N-dimethylaniline (0.5 mmol), acetic an-
hydride (1.0 mmol), TBHP (1.0 mmol), pyridine (0.5 mmol), acetonitrile (3 mL),
808C, 2 h.
Figure 3. Effect of different oxidants on reaction conversion (a) and selectivi-
ty (b). Reaction conditions: N,N-dimethylaniline (0.5 mmol), acetic anhydride
(1.0 mmol), [Cu2(EDB)2(BPY)] (5 mol%), pyridine (0.5 mmol), acetonitrile
(3 mL), 808C, 2 h.
ure 3b). Indeed, the results were consistent with those report
by Li and co-workers.[7]
sion. Similar conversions were achieved when one or more
equivalents of pyridine was applied (Figure 6a). However, it
should be noted that the selectivity to N-methyl-N-phenylace-
tamide was decreased to 80% in the presence of two or three
equivalents of pyridine (Figure 6b).
The reagent molar ratio of acetic anhydride and oxidant was
investigated. It was found that the oxidative amidation reac-
tion using one equivalent of anhydride gave 82% conversion
and 78% selectivity (Figure 4). Similar reaction rate and selec-
tivity were observed when 3 equivalents of anhydride was
used, as compared to the reaction using 2 equivalents with re-
spect to oxidant concentration where no N-methyl-N-phenyla-
cetamide product was detected after 120 min in the absence
of the oxidant. The reaction using three equivalents of tert-
butyl hydroperoxide could offer more than 99% conversion
after 80 min, whereas only 84% conversion was observed
when one equivalent of tert-butyl hydroperoxide was em-
ployed. With two equivalents of tert-butyl hydroperoxide, more
than 99% conversion and optimal selectivity was obtained
after 2 h (Figure 5). Therefore, we chose to use 2 equivalents of
anhydride and oxidant for further studies.
The effect of different solvents on the reaction conversion
for the oxidative amidation transformation was also stud-
ied.[51,52] It was found that the reaction proceeded slowest in
1,4-dioxane, though a conversion of 83% was still detected
after 120 min. In addition, almost quantitative conversions
were obtained in other tested solvents including dimethyl sulf-
oxide (DMSO), N,N-Dimethylformamide (DMF), toluene, and
CH3CN (Figure 7a). The optimal selectivity, 97%, was achieved
in acetonitrile whereas less than 80% selectivity was detected
in other solvents. To check the efficiency of our conditions, N-
methyl-N-phenylacetamide was isolated in 90% yield when the
reaction was carried out in acetonitrile. The product identity
1
was confirmed by H and 13C NMR spectroscopy.[7]
As with the observation of Li and co-workers,[7] the presence
of pyridine as the base was found to significantly accelerate
the oxidative amidation transformation. It is likely that pyridine
base facilitates the acetyl formation from anhydride via nucleo-
philic displacement. A conversion of 47% was obtained after
120 min in the absence of pyridine, whereas reactions with
a catalytic amount of pyridine (0.5 equiv) afforded 67% conver-
We also explored the catalytic activity of several Cu-MOFs
that are frequently used as catalysts in organic transformations.
These including [Cu2(BDC)2(BPY)], [Cu2(EDB)2(BPY)], [Cu2(BDC)2-
(DABCO)], [Cu(BDC)], MOF-199, and MOF-143 (DABCO=1,4-
diazabicyclo[2.2.2]octane, EDB=4,4’-ethynyldibenzoic acid).
Among these Cu-MOFs, the well-known MOF-199 offered the
lowest activity, though the reaction could proceed to 79%
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Figure 4. Effect of N,N-dimethylaniline/acetic anhydride molar ratio on reac-
tion conversion (a) and selectivity (b). Reaction conditions: N,N-dimethylani-
line (0.5 mmol), [Cu2(EDB)2(BPY)] (5 mol%), TBHP (1.0 mmol), pyridine
(0.5 mmol), acetonitrile (3 mL), 808C, 2 h.
Figure 5. Effect of oxidant concentration on reaction conversion (a) and se-
lectivity (b). Reaction conditions: N,N-dimethylaniline (0.5 mmol), acetic an-
hydride (1.0 mmol), [Cu2(EDB)2(BPY)] (5 mol%), pyridine (0.5 mmol), acetoni-
trile (3 mL), 808C, 2 h.
conversion after 120 min. [Cu(BDC)] was found to be more
active than MOF-199 with 88% conversion being obtained.
[Cu2(BDC)2(BPY)], [Cu2(EDB)2(BPY)], [Cu2(BDC)2(DABCO)], and
MOF-143 exhibited similar activity (Figure 8a). In terms of se-
lectivity, [Cu2(BDC)2(BPY)] or [Cu2(BDC)2(DABCO)] could be used
as an alternative catalyst with 94% and 95% selectivity to the
desired product, respectively (Figure 8b). In addition, the cata-
lytic activity of the [Cu2(EDB)2(BPY)] in the oxidative amidation
reaction was also compared to that of several salts, including
CuCl2, Cu(NO3)2, Cu(OAc)2, and FeCl2. It was found that these
salts were just as active as Cu-MOF (Figure 9a). Although the
CuCl2-catalyzed oxidative amidation reaction offered the fastest
reaction rate, only 90% selectivity was obtained. The selectivity
could be increased to 94%, 95%, and 96% after 120 min for
FeCl2, Cu(NO3)2, and Cu(OAc)2, respectively (Figure 9b). Howev-
er, it should be noted that these homogeneous salts suffer dis-
advantages in terms of catalyst separation and recyclability.
The leaching test was carried out in our next studies. A con-
trol experiment under optimal conditions was carried out
using a simple filtration during the course of the reaction.
After 20 min, conversion of 66% and 96% selectivity for N-
methyl-N-phenylacetamide was detected, the [Cu2(EDB)2(BPY)]
catalyst was separated from the reaction mixture by simple fil-
tration. The liquid reaction mixture was then transferred to
a new reactor vessel, and magnetically stirred for an additional
100 min at 808C with aliquots being sampled at different time
intervals, and analyzed by GC methods. Experimental results
showed that almost no further conversion of N,N-dimethylani-
line into N-methyl-N-phenylacetamide was detected after the
Cu-MOF catalyst was removed from the reaction mixture
(Figure 10). It was therefore proposed that the contribution of
leached active copper species, if any, was negligible.
Catalyst recyclability was then tested. In particular, the Cu-
MOF catalyst was separated from the reaction mixture by
simple filtration after 2 h, washed with copious amounts of
DMF and then CH2Cl2, activated under vacuum at room tem-
perature for 6 h, and then reused in further experiments under
the identical conditions of previous runs. It was found that the
[Cu2(EDB)2(BPY)] catalyst could be recovered and reused sever-
al times for the reaction between N,N-dimethylaniline and
acetic anhydride without a significant degradation in catalytic
activity (Figure 11). Moreover, FT-IR analysis of the reused [Cu2-
(EDB)2(BPY)] showed similar absorption bands as compared
with that of the fresh Cu-MOF (Figure 12). The crystallinity of
the [Cu2(EDB)2(BPY)] was observed to change slightly during
the course of the oxidative amidation reaction. However, XRD
analysis indicated that the reused Cu-MOF was still highly crys-
talline (Figure 13).
In mechanistic studies, a radical trapping reagent, (TEMPO),
was added to the reaction mixture. If the reactions proceed
through a radical route, it is likely that the catalytic cycle
would be terminated in the presence of TEMPO. The reaction
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Figure 6. Effect of base concentration on reaction conversion (a) and selecti-
vity (b). Reaction conditions: N,N-dimethylaniline (0.5 mmol), acetic anhy-
dride (1.0 mmol), [Cu2(EDB)2(BPY)] (5 mol%), TBHP (1.0 mmol), acetonitrile
(3 mL), 808C, 2 h.
Figure 7. Effect of various solvents on reaction conversion (a) and selectivi-
ty (b). Reaction conditions: N,N-dimethylaniline (0.5 mmol), acetic anhydride
(1.0 mmol), [Cu2(EDB)2(BPY)] (5 mol%), TBHP (1.0 mmol), pyridine (0.5 mmol),
808C, 2 h.
was carried out with added TEMPO (3 mol%.). It was observed
that no significant further reaction progress was detected after
TEMPO was added (Figure 14).
Table 1. Reactions scope with isolated yields.[a]
To test the generality of optimal conditions, several N,N-di-
methyl aniline derivatives were employed. It was found that
the oxidative amidation reaction of N,N-dimethyl-1-naphthyla-
mine and acetic anhydride afforded 54% conversion and 94%
selectivity after 120 min. Interestingly, acylation of 4,N,N-trime-
thylaniline resulted in 99% conversion and 97% selectivity. De-
rivatives with electron-withdrawing substituents such as 3-
chloro-N,N-dimethylaniline and 4-bromo-N,N-dimethylaniline
were also active and about 80% and 97% conversions along
with 95% and 97% selectivity, respectively, were obtained
after 2 h. Pleasingly, sterically bulky 2,6-diisopropyl-N,N-dime-
thylaniline reacted with acetic anhydride in 93% conversion
and 84% selectivity (Figure 15). Isolation of several products
was done to confirm the correlation between reaction conver-
sion and yield of isolated product. The results described in
Table 1 indicate that good to excellent yields were obtained
under optimized conditions.
Entry
1
Anilines
Product
Yield [%][b]
90
2
3
91
78
4
63
Reaction scope with respect to anhydrides was also investi-
gated (Figure 16). The experimental results indicate that opti-
mal conditions are also active for other anhydrides. In particu-
lar, reaction of N,N-dimethylanilines with iso-butyric anhydride
[a] Reaction conditions: CH3CN (3 mL), anilines (0.5 mmol). See Support-
ing Information for details. [b] Yield of isolated product.
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Figure 9. Different salts as catalyst for the oxidative amidation: Conversio-
n (a) and selectivity (b). Reaction conditions: N,N-dimethylaniline (0.5 mmol),
acetic anhydride (1.0 mmol), TBHP (1.0 mmol), pyridine (0.5 mmol), acetoni-
trile (3 mL), 808C, 2 h.
Figure 8. Different Cu-MOFs as catalyst for the oxidative amidation: Conver-
sion (a) and selectivity (b). Reaction conditions: N,N-dimethylaniline
(0.5 mmol), acetic anhydride (1.0 mmol), TBHP (1.0 mmol), pyridine
(0.5 mmol), acetonitrile (3 mL), 808C, 2 h.
afforded 99% conversion in 2 h. Amidation of acidic anhydride
having steric hindrance, such as pivalic anhydride, was also
possible and 95% conversion was achieved. In addition,
a large-scale synthesis of 20-fold magnitude (10.0 mmol) was
also conducted. The result was comparable to that of the small
scale (0.5 mmol) with greater than 95% conversion obtained in
2 h. Desired product was isolated by flash chromatography on
silica gel to afford 80% yield. This experiment revealed this ap-
proach has great potential from a practical view of point.
2 h. The [Cu2(EDB)2(BPY)] could be easily separated from the re-
action mixture by filtration and recovered and reused several
times without any significant degradation in catalytic activity
and selectivity.
Experimental Section
Synthesis of the metal-organic framework [Cu2(EDB)2(BPY)]
4,4’-Ethynyldibenzoic acid (EDB) linker was synthesized according
to a published procedure.[53,54] In a typical preparation, a solid mix-
ture of Cu(NO3)2.3H2O (90 mg, 0.376 mmol), 4,4’-ethynyldibenzoic
acid (100 mg, 0.376 mmol), and 4,4’-bipyridine (BPY) (30 mg,
0.188 mmol) was dissolved in a mixture of DMF (25 mL), ethanol
(5 mL) and pyridine (0.7 mL), then distributed to ten 10 mL vials.
The vials were heated at 858C in an isothermal oven for 3 days to
yield light green crystals. After cooling the vial to RT, the solid
product from each vial was obtained by repeatedly decanting the
mother liquor and washing the filtered crystals with DMF (3x8 mL)
over 3 days. Solvent exchange was then carried out with CH2Cl2
(3x8 mL) for 3 days at RT. The product was then dried under
vacuum at 1208C for 19 h, to yield 98 mg of [Cu2(EDB)2(BPY)] in
the form of light green crystals (64% yield based on 4,4’-ethynyldi-
benzoic acid).
Conclusion
In summary, [Cu2(EDB)2(BPY)] was synthesized and character-
ized by several techniques including XRD, SEM, TEM, FT-IR,
TGA, AAS, and nitrogen physisorption measurements. The Cu-
MOF was used as a heterogeneous catalyst for the direct oxi-
dative amidation between N,N-dimethylanilines and anhydrides
to form tertiary amides as the principal products. The [Cu2-
(EDB)2(BPY)] exhibited similar or higher activity and selectivity
as compared to those of [Cu2(BDC)2(BPY)], [Cu2(BDC)2(DABCO)],
MOF-143, CuCl2, CuNO3, and Cu(OAc)2. The optimal conditions
employed [Cu2(EDB)2(BPY)] (10% mol), tert-butyl hydrogen per-
oxide (TBHP; 2 equiv), pyridine (1 equiv) in CH3CN at 808C in
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Figure 12. FT-IR spectra of the fresh (a) and reused (b) [Cu2(EDB)2(BPY)] cata-
lyst.
Figure 10. Leaching test: conversion (a) and selectivity (b). Reaction condi-
tions: N,N-dimethylaniline (0.5 mmol), acetic anhydride (1.0 mmol), [Cu2-
(EDB)2(BPY)] (5 mol%), TBHP (1.0 mmol), pyridine (0.5 mmol), acetonitrile
(3 mL), 808C, 2 h.
Figure 13. Powder X-ray diffractograms of the fresh (a) and reused (b) [Cu2-
(EDB)2(BPY)] catalyst.
Figure 11. Catalyst recycling studies: conversion (a) and selectivity (b). Reac-
tion conditions: N,N-dimethylaniline (0.5 mmol), acetic anhydride (1.0 mmol),
[Cu2(EDB)2(BPY)] (5 mol%), TBHP (1.0 mmol), pyridine (0.5 mmol), acetonitrile
(3 mL), 808C, 2 h.
Figure 14. Effect of TEMPO on the reaction pathway. Reaction conditions:
N,N-dimethylaniline (0.5 mmol), acetic anhydride (1.0 mmol), [Cu2(EDB)2(BPY)]
(5 mol%), TEMPO (3 mol%), TBHP (1.0 mmol), pyridine (0.5 mmol), acetoni-
trile (3 mL), 808C, 2 h.
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Figure 16. Reactions of N,N-dimethylanilines with different anhydrides. Reac-
tion conditions: N,N-dimethylaniline (0.5 mmol), [Cu2(EDB)2(BPY)] (5 mol%),
TBHP (1.0 mmol), pyridine (0.5 mmol), acetonitrile (3 mL), 808C, 2 h.
then stirred for a further 100 min. Reaction progress, if any, was
monitored by GC as previously described.
Acknowledgements
The Vietnam National University–Ho Chi Minh City (VNU-HCM) is
acknowledged for financial support through project no. C2013-
50-02.
Keywords: heterogeneous
catalyst
·
metal–organic
frameworks · N,N-dimethylanilines · oxidative amidation ·
tertiary amides
Figure 15. The amidation reactions of different N,N-dimethylaniline com-
pounds with acetic anhydride: conversion (a) and selectivity (b). Reaction
conditions: acetic anhydride (1.0 mmol), [Cu2(EDB)2(BPY)] (5 mol%), TBHP
(1.0 mmol), pyridine (0.5 mmol), acetonitrile (3 mL), 808C, 2 h.
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Catalytic studies
In a typical experiment, a mixture of N,N-dimethylaniline (0.063 mL,
0.5 mmol), acetic anhydride (0.094 mL, 1 mmol), and diphenyl
ether (0.07 mL) internal standard in acetonitrile (3 mL) was added
into a flask containing the pre-determining amount of [Cu2(EDB)2-
(BPY)] catalyst, pyridine (0.04 mL, 0.5 mmol) base, and tert-butyl hy-
droperoxide (70 wt.% in water; 0.136 mL, 1.0 mmol) as an oxidant.
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1H and 13C NMR spectroscopy. To investigate the recyclability of
[Cu2(EDB)2(BPY)], the catalyst was separated from the reaction mix-
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and CH2Cl2, and then activated under vacuum at RT for 6 h to
remove any other remaining volatile solvents. For the leaching
test, a catalytic reaction was stopped after 20 min, analyzed by GC,
and filtered to remove the solid catalyst. The reaction solution was
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Received: March 31, 2014
Published online on && &&, 0000
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FULL PAPERS
G. H. Dang, T. D. Nguyen, D. T. Le,
T. Truong,* N. T. S. Phan*
&& – &&
Direct Oxidative Amidation between
N,N-dimethylanilines and Anhydrides
Using Metal-Organic Framework
[Cu2(EDB)2(BPY)] as an Efficient
Heterogeneous Catalyst
Direct is best: The first heterogeneous
catalytic system for direct amidation of
anhydrides using N,N-dimethylanilines
has been developed where the desired
products were formed in good to excel-
lent yields (see scheme). Facile catalyst
separation and reusability along with
application on a large scale allow the
method to be economically practical for
making tertiary amide compounds.
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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These are not the final page numbers!