Cuprous Oxide Catalyzed Oxidative C-C Bond Cleavage for C-N Bond Formation: Synthesis of Cyclic Imides from Ketones and Amines

Article abstract of DOI:10.1002/anie.201508071

Selective oxidative cleavage of a C-C bond offers a straightforward method to functionalize organic skeletons. Reported herein is the oxidative C-C bond cleavage of ketone for C-N bond formation over a cuprous oxide catalyst with molecular oxygen as the oxidant. A wide range of ketones and amines are converted into cyclic imides with moderate to excellent yields. In-depth studies show that both α-C-H and β-C-H bonds adjacent to the carbonyl groups are indispensable for the C-C bond cleavage. DFT calculations indicate the reaction is initiated with the oxidation of the α-C-H bond. Amines lower the activation energy of the C-C bond cleavage, and thus promote the reaction. New insight into the C-C bond cleavage mechanism is presented.

Full text of DOI:10.1002/anie.201508071

Angewandte
Chemie
International Edition: DOI: 10.1002/anie.201508071
German Edition: DOI: 10.1002/ange.201508071
Heterogeneous Catalysis
À
À
Cuprous Oxide Catalyzed Oxidative C C Bond Cleavage for C N
Bond Formation: Synthesis of Cyclic Imides from Ketones and Amines
Min Wang, Jianmin Lu, Jiping Ma, Zhe Zhang, and Feng Wang*
À
Abstract: Selective oxidative cleavage of a C C bond offers
a straightforward method to functionalize organic skeletons.
À
Reported herein is the oxidative C C bond cleavage of ketone
À
for C N bond formation over a cuprous oxide catalyst with
molecular oxygen as the oxidant. A wide range of ketones and
amines are converted into cyclic imides with moderate to
À
excellent yields. In-depth studies show that both a-C H and b-
À
C H bonds adjacent to the carbonyl groups are indispensable
À
for the C C bond cleavage. DFT calculations indicate the
À
reaction is initiated with the oxidation of the a-C H bond.
À
Amines lower the activation energy of the C C bond cleavage,
À
and thus promote the reaction. New insight into the C C bond
cleavage mechanism is presented.
À
T
he selective cleavage of C C bonds offers a straightforward
method for functionalizing the organic skeletons, and thus
shows promising applications in organic synthesis and bio-
mass conversion.[1] But the nonpolar, thermodynamically
À
stable, and kinetically inert character of C C bonds makes it
a challenge to increasing product selectivity.[2] Nowadays
chemical processes are being upgraded from traditional
uncatalyzed reactions with stoichiometric oxidants, such as
peroxides and metal salts,[3] to catalyzed reactions using
molecular oxygen.[4]
Cyclic imides are widely used in biological, medicinal, and
polymer chemistry.[5] They have been synthesized by heating
dicarboxylic acids or anhydrides with an amine (Sche-
me 1a).[6] In general, harsh thermal reaction conditions and
activation reagents are mandatory. Recently studied oxida-
tion of cyclic amines and carbonylation reactions have
broadened the substrate scope using precious metal and
carbonyl catalysts (Scheme 1b and c).[7]
Scheme 1. The methods for the synthesis of the cyclic imide.
TBHP=tert-butyl hydroperoxide.
À
catalyst is unique for C C bond-cleavage reactions. Inspired
À
by this result, we discovered that Cu2O catalyzed the C C
bond cleavage of ketones to synthesize cyclic imides. The
method can be used in synthesizing various cyclic imides from
anilines, benzylamines, aliphatic, and heterocyclic amines.
Moreover, the combination of experiments and DFT results
Herein we report a new reaction for the synthesis of cyclic
imides by oxidative coupling of a cyclic ketone with an amine
(Scheme 1d). To obtain good imide selectivity, each activa-
À
À
has revealed that the presence of both a-C H and b-C H
À
À
À
tion steps in the reaction, including C H bond, C C bond,
bonds are essential for C C bond cleavage, a transient
=
À
and O O bond (molecular oxygen) activation, should be kept
carbanion intermediate is involved, and that the a-C H bond
selective over one catalyst.[8] Very recently, we found that
is initially oxidized. To the best of our knowledge, this is the
first report on conversion of ketones into cyclic imides.
We commenced our study with 1-indanone and aniline in
the presence of a Cu2O catalyst, which can either be obtained
from a commercial source or prepared according to the
literature.[10] The solvent polarity remarkably affects the
catalytic performance. Reactions in DMSO show higher
activity (Table 1, entries 1–7). The catalyst was reused and
gave a comparably good result (entry 7), and no reaction
occurred without either oxygen or the catalyst (entries 8
and 9).
Cu2O can activate oxygen and more interestingly, it enables
À
À
the selective cleavage of strong C C bonds over weak C N
bonds in tertiary amines.[9] This ability indicates that the Cu2O
[*] Dr. M. Wang, Dr. J. M. Lu, Dr. J. P. Ma, Z. Zhang, Prof. F. Wang
State Key Laboratory of Catalysis (SKLC)
Dalian National Laboratory for Clean Energy (DNL)
Dalian Institute of Chemical Physics (DICP)
Chinese Academy of Sciences, Dalian 116023 (China)
E-mail: wangfeng@dicp.ac.cn
The substrate scope of the amines was then tested
(Table 2). Under the optimized reaction conditions, a wide
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201508071.
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Table 1: Screening of the reaction conditions.[a]
little effect on the reaction (entries 1–11). 1-Naphthylamine
and tert-butylamine give moderate yield because of the steric
À
hindrance for C N bond formation (entries 12 and 19).
Amines bearing halo, Me, OH, or MeO groups afford the
corresponding imides in yields ranging from 76 to 92%
(entries 2–11, 15, 16, 24). The S- and N-containing hetero-
cyclic amines, which usually poison noble-metal centers, can
also be converted into imides with yields ranging from 77 to
89%(entries 13 and 17).
The scope of the reaction with respect to ketone was then
investigated (Table 3). Substituted 1-indanones, including
halo, Me, and MeO substituents were all converted into the
corresponding imides with yields in the 86–90% range.
Apparent substituent effects are observed. Different to the
oxidation reaction, such as alcohol and amine oxidation,[11]
ketones with electron-withdrawing substituents are more
easily oxidized. A higher reaction temperature and longer
reaction time is needed for the conversion of methoxy-
substituted 1-indanones.
Entry
Solvent
Imide [%]
1
2
3
4
5
6
7
8
9
octane
toluene
THF
MeCN
1,4-dioxane
methanol
DMSO
DMSO, no catalyst
DMSO, in N2
25
38
40
40
48
57
87 (89 in 2nd use)
0
0
[a] Reaction conditions: 0.5 mmol 1-indanone, 1 mmol aniline, 10 mg
Cu2O, 2 mL solvent, 0.6 MPa O2, 1108C, 6 h. The yield was determined
by GC analysis using n-dodecane as the internal standard. The main
byproduct is o-phthalic anhydride. DMSO=dimethylsulfoxide,
THF=tetrahydrofuran.
Table 3: Substrate scope of ketones.[a]
Table 2: Substrate scope of amines.[a]
[a] 0.5 mmol 1-indanone, 1 mmol aniline, 10 mg Cu2O, 0.6 MPa O2, 2 mL
DMSO, 1108C, 8 h. The yield was determined by GC analysis using n-
dodecane as the internal standard. The data within parentheses shows
the yield of the isolated product.
We then studied the reaction mechanism. It is a nonradical
process given the fact that addition of a radical inhibitor,
(2,2,6,6-tetramethylpiperidin-1-yl)oxidanyl (TEMPO), did
not hinder the reaction [Eq. (1)]. A reaction of 1-indanone
and aniline with 2.0 equivalents of either Cu2O or CuO under
N2 gives no product, thus excluding the possibility of the
redox cycle of copper oxides, and therefore showing that it is
also not a Mars–van-Krevelen reaction [Eq. (2)].[12] Based on
the above results and the previous study in selective
oxidation,[13] we conclude that oxygen is activated on the
Cu2O surface to form an adsorbed active species. The actual
reaction may be very complex since it includes multimole-
cluar adsorption and activation steps.
[a] 0.5 mmol 1-indanone, 1 mmol amines, 10 mg Cu2O, 0.6 MPa O2,
2 mL DMSO, 1108C, 8 h. The yield was determined by GC analysis using
n-dodecane as the internal standard. The data within parentheses shows
the yield of the isolated product.
Then, to further shed light on the reaction mechanism, we
monitored the reaction products. The gas products contain
CO2, which was confirmed by limewater (see Figure S1 in the
Supporting Information) and also detected by mass spec-
range of amines were coupled with a ketone to form N-
substituted cyclic imides with moderate to excellent yields.
Electron-donating or electron-withdrawing substitutes show
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Table 4: Oxidation of the derivatives of 1-indanone.[a]
[a] 0.5 mmol substrate, 10 mg Cu2O, 2 mL DMSO, 1108C, 0.6 MPa O2,
8 h. Conversions were determined by GC analysis using n-dodecane as
the internal standard.
trometry (MS; see Figure S2). o-Phthalic anhydride was
detected (see Figure S3). We then found that the reaction of
o-phthalic anhydride with aniline quickly generated N-phenyl
phthalimide [Eqs. (3) and (4)]. This result infers that o-
phthalic anhydride is an intermediate en route to the imide.
Now it becomes clear that there are two steps: the oxidation
of 1-indanone to o-phthalic anhydride [Eq. (3)] and the
imidization reaction of o-phthalic anhydride with amines
[Eq. (4)]. In first step, 1-indanone is oxidized to o-phthalic
anhydride with 93% GC yield within 6 hours. The second step
is much faster and 96% GC yield of the imide is obtained
after 2 hours. Step 2 could also occur without catalyst and
oxygen. Cu2O and oxygen show little effect on the step 2.
Figure 1. a) Arrhenius plot with or without the addition of aniline.
b) Hammett plot of the oxidation of substituted 1-indanones.
F, p-Cl, p-Br) (Figure 1b). The resulting Hammett parameter,
1, is 0.56, thus suggesting the reaction is substituent-sensitive
À
À
and carbanions are involved. The a-C H and b-C H bond
are cleaved by a proton transfer on the catalyst surface.
Electron-withdrawing substituents can decrease the negative
charge on the carbanions and thus stabilize the intermediates.
DFT calculations find that 1-indanone adsorbs on the Cu2O-
(111) surface in a horizontal manner (Figure 2), where three
aryl carbon atoms bind to three adjacent copper atoms on the
top sites. The oxygen atom in the carbonyl group binds to the
surface on the bridge site. The adsorption is exothermic with
À1.86 eV. Two possible pathways for the oxidation of 1-
indanone are calculated (Figure 3; the detailed adsorption
and transition state are provided in the Supporting Informa-
No reaction takes place if the ketone is lacking both two
À
À
a-C H bonds and two b-C H bonds (Table 4, entries 2–4). By
employing 1,2-indandione and 1,2,3-indantrione as reactants,
phthalic anhydrides are obtained with 99% conversion after
2 hours, which is much faster than that with 1-indanone
(entries 5 and 6). Therefore, 1,2-indandione and 1,2,3-indan-
À
trione are two intermediates formed by the C H bond
oxidation of 1-indanone.
Correlating Àln(1ÀC) (C is the conversion of substituted
1-indanones) against reaction time (ks) indicates a linear
relationship and a pseudo-first-order reaction with respect to
the substituted 1-indanones. The apparent activation energy,
Ea, is determined to be 78 kJmolÀ1 (Figure 1a). The addition
of aniline lowers activation energy (Ea = 70 kJmolÀ1) and
increases the reaction rate (see Figure S4). This change may
result from the fact that aniline either as basic molecule helps
À
tion). One is the oxidation of the a-C H bond (Path A), and
À
the other is the oxidation of the b-C H bond (Path B). The
À
overall the Ea value of the a-C H oxidation is 2.91 eV, which
À
is much lower than that of the b-C H bond oxidation
(3.56 eV). In the initial step for the C H bond oxidation,
À
the activation energy for deprotonating one a-H at the Cu2O
surface is only 0.44 eV, which is much lower than that of
removing a b-H (1.67 eV). Furthermore, Path A is thermo-
dynamically favored as evidenced by a more-negative reac-
tion enthalpy (À0.75 eV vs 0.01 eV). These results indicate
À
deprotonate the C H bond, or as a ligand coordinates to the
surface copper sites to increase reactivity.[14] A linear relation-
ship between log(kX/kH) and substituent constant s was
established for substituted 1-indanone (X = p-OCH3, p-H, p-
À
that the a-C H bond oxidation is preferred and Path A is the
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Figure 2. The adsorption of 1-indanone on Cu2O(111). a) Top view.
b) Side view.
Scheme 2. Possible reaction mechanism for the Cu2O-catalyzed oxida-
main reaction route. In addition, a-hydroxy-1-indanone is
unstable and is further oxidized to 1,2-indandione with merely
0.14 eV activation energy.
Based on the above-mentioned results and the following
experiments, we may come to a tentative reaction mechanism
tion of ketones with amines to generate imides.
by coordination on the Cu2O surface.[14] It is under inves-
tigation.
À
(Scheme 2). In the initial step, one of the a-C H bonds in 1-
indanone is oxidized by the activated oxygen to give a-
In summary, we report a novel strategy for the Cu2O-
À
catalyzed oxidative C C bond cleavage of a ketone for the
À
hydroxy-1-indanone, which is further oxidized to 1,2-indan-
C N bond formation with molecular oxygen as the oxidant. A
dione by the oxidation of the other a-C H bond.[15] Then, the
wide range of cyclic imides are synthesized from 1-indanone
and amines with moderate to excellent yields. The presence of
À
À
oxidation of the a-C H bond adjacent to carbonyl group is
repeated for 1,2-indandione with the formation of the 1,2,3-
indantrione intermediate. This step shows why the b-C H
bond is indispensable. The 1,2,3-indantrione intermediate is
further converted into o-phthalic anhydride, thus releasing
CO2. We detected 1,2,3-indantrione by in situ IR. It first
appears and then disappears as the reaction proceeds (see
Figure S5). Finally, the fast reaction of o-phthalic anhydride
with an amine forms the imide. The acceleration of the
reaction by the amine may be due either to the base activation
À
À
À
both the a-C H and b-C H bond is essential for C C bond
cleavage. Carbanion intermediates are involved, and the a-
À
À
C H is initially oxidized.
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (21422308 21303183) and the Doctor
Startup Foundation of Liaoning Province.
À
of the a-C H bond or to adjusting the catalytic properties
À
À
Figure 3. DFT calculation of the oxidation of the a-C H and b-C H bond of 1-indanone to 1,2-indandione and 1,3-indandione, respectively.
Red O, blue Cu, gray C, white H.
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Received: August 28, 2015
Published online: October 23, 2015
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