Selective One-Step Aerobic Oxidation of Cyclohexane to ?-Caprolactone Mediated by N-Hydroxyphthalimide (NHPI)

Article abstract of DOI:10.1002/cctc.201900282

The selective one-step aerobic oxidation of cyclohexane to ?-caprolactone was achieved in the presence of N-hydroxyphthalimide (NHPI) and aldehyde under mild conditions. Remarkably, 12 % of cyclohexane was converted with a selectivity of 77 % of ?-caprolactone and 15 % of KA oil. Control experiments indicated that NHPI accelerated the oxidation of aldehydes and peroxy radicals generated from aldehydes in situ were the key intermediates in the period of CH bond activation. 2,2,6,6-Tetramethylpiperidine 1-oxyl (TEMPO) addition and a series of m-chloroperoxybenzoic acid (m-CPBA) oxidation experiments showed that the oxidation proceeded via a complex radical chain mechanism.

Full text of DOI:10.1002/cctc.201900282

Accepted Article
Title: Selective One-step Aerobic Oxidation of Cyclohexane to ε-
Caprolactone Mediated by N-hydroxyphthalimide (NHPI)
Authors: Lingyao Wang, Yuanbin Zhang, Renfeng Du, Haoran Yuan,
Yongtao Wang, Jia Yao, and Haoran Li
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: ChemCatChem 10.1002/cctc.201900282
Link to VoR: http://dx.doi.org/10.1002/cctc.201900282
A Journal of
www.chemcatchem.org

10.1002/cctc.201900282
ChemCatChem
COMMUNICATION
Selective One-step Aerobic Oxidation of Cyclohexane to ε-
Caprolactone Mediated by N-hydroxyphthalimide (NHPI)
Lingyao Wang,[a] Yuanbin Zhang,[a] Renfeng Du,[a] Haoran Yuan,[a] Yongtao Wang,[a] Jia Yao,[a] and
Haoran Li*[a, b]
Abstract: The selective one-step aerobic oxidation of cyclohexane
to ε-caprolactone was achieved in the presence of N-
hydroxyphthalimide (NHPI) and aldehyde under mild conditions.
Remarkably, 12% of cyclohexane was converted with a selectivity of
77% of ε-caprolactone and 15% of KA oil. Control experiments
indicated that NHPI accelerated the oxidation of aldehydes and
peroxy radicals generated from aldehydes in situ were the key
intermediates in the period of CH bond activation. 2,2,6,6-
Tetramethylpiperidine 1-oxyl (TEMPO) addition and a series of m-
chloroperoxybenzoic acid (m-CPBA) oxidation experiments showed
that the oxidation proceeded via a complex radical chain mechanism.
reported an aerobic oxidation of hydrocarbons to alcohols and
ketones mediated by NHPI and acetaldehyde.
Herein, we would like to report an unprecedented facile
method for selective and direct oxidation of cyclohexane into ε-
CL. The reaction was mediated by NHPI with O2 as the oxidant
and aldehyde as the co-oxidation additive. (Scheme 1)
a) Reported work: oxidation of cyclohexane to cyclohexanol, cyclohexanone and adipic acid
OH
O
N
H
I
P
C
O
various conditions
COOH
COOH
or
or
b) This work: first example of selective oxidation of cyclohexane to -caprolactone
ε
The selective aerobic oxidation of hydrocarbons is one of the
most important and challenging subjects in fundamental
research and industrial production.[1] Cyclohexane as a raw
material has been widely used for synthesis of KA oil (mixtures
of cyclohexanone (CHONE) and cyclohexanol (CHOL) and
adipic acid (AA), a well-known monomer of nylon polymers.[2]
The approach of selective synthesis of CHOL, CHONE and AA
by oxygenation of cyclohexane has been well studied for recent
decades and a plenty of catalytic system have been reported
including homogeneous and heterogeneous catalysts (Table
S1).[3] ε-Caprolactone (ε-CL) is a precursor monomer for the
production of polycaprolactone, which is known as a popular
synthetic biodegradable polymer.[4] The current synthesis of ε-
CL from cyclohexane undergoes two steps: 1) oxidation of
cyclohexane to CHONE and 2) Baeyer-Villiger oxidation of
CHONE to ε-CL.[5] Many efforts have been made to study these
two separated reactions, but none has tried to realize the direct
oxidation of cyclohexane to ε-CL. Considering the industrial cost
as well as the synthetic economy, seeking out a one-step
procedure for producing ε-CL from cyclohexane under mild
conditions is of grand significance.
O
N
H
I
P
C
O
O
NHPI / aldehyde
(major product)
DCE, O2, 40 °C
Scheme 1. Oxidation of cyclohexane.
The initial reaction was performed in 1,2-dichloroethane (DCE)
at 30°C in the presence of 2 equivalents of benzaldehyde and
10 mol% of NHPI for 24 h. However, no ε-CL was generated
(Table 1, entry 1). When the temperature rose to 35°C, the
cyclohexane conversion increased to 4.8% with selectivity of
33.5% KA oil and 66.1% ε-CL (entry 2). At 40°C, the
cyclohexane conversion was 12.3% with ε-CL selectivity of 77.3%
and KA oil selectivity of 14.9% (entry 3). The continuous
increase of temperature to 45°C or 50°C resulted in the loss of
yields (entries 4, 5). Control experiments (Table 2, entries 1-2)
indicated that no oxidation products were formed in the absence
of benzaldehyde. And without NHPI, the sole benzaldehyde
resulted a conversion of 1.9% without the generation of ε-CL
(entry 3). Then, different solvents and aldehydes were examined.
Other solvents such as MeCN, EtOAc and toluene were not
effective as DCE (entries 4-7). In our previous report, we have
explored the Baeyer-Villiger oxidation of CHONE promoted by
substituted aromatic aldehydes and aliphatic aldehydes in detail.
In this work, we chose 3-chloro-benzaldehyde, 4-fluoro-
benzaldehyde, acetaldehyde, heptanal and isobutyraldehyde to
study (entries 8-12). The results showed that 3-chloro-
benzaldehyde and 4-fluoro-benzaldehyde were more efficient
with ε-CL selectivity of 85 and 80% respectively while
acetaldehyde, heptanal and isobutyraldehyde were less efficient
but still provided ε-CL in 4, 16 and 8% selectivity respectively.
Considering the lower commercial price of aliphatic aldehydes, it
is meaningful that isobutyraldehyde and heptanal can serve as
potential sacrificing agents in the oxidation reaction systems.
Benzaldehyde as the sacrifice was also important to the reaction.
Reducing or increasing the amount of benzaldehyde resulted in
a small decrease of yields (Table S2, entries 1-6). The amount
of NHPI was vital to the reaction. Varying the loading of NHPI to
15 or 20 mol% led to the lower yields of ε-CL (Table S2, entries
7-9).
A
common way of utilizing O2 in transformation of
hydrocarbons to oxygen-containing compounds is the addition of
an aldehyde as a sacrificial agent (Mukaiyama conditions).[6] For
[6b, 7]
example, Murahashi et. al.
found that the iron powder,
copper salts, Ru-Co bi-metallic, Co(TPFPP) or Cu-crown ether
could catalyze the oxidation of cyclohexane in the presence of
acetaldehyde. Ishii and co-workers developed a series of
catalyst systems combining N-hydroxyphthalimide (NHPI) and
metal complexes to transform hydrocarbons.[3a, 8] Einhorn et al. [9]
[a]
[b]
L. Wang, Y. Zhang, R. Du, H. Yuan, Y. Wang, Prof. J. Yao, Prof. H.
Li
Department of Chemistry, ZJU-NHU United R&D Center,
Zhejiang University, 310027 Hangzhou, P. R. China
E-mail: lihr@zju.edu.cn
Prof. H. Li
State Key Laboratory of Chemical Engineering,
Department of Chemical and Biological Engineering,
Zhejiang University, 310027 Hangzhou, P. R. China
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/xxx.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900282
ChemCatChem
COMMUNICATION
[a]
Table 3 demonstrated a comparison of reported catalysts and
NHPI for the aerobic oxidation of cyclohexane. As it was shown,
KA oil was the main product by previous catalytic system. In the
presence of Cu(OH)2 and 3 equivalents of acetaldehyde, 4.5%
of cyclohexane was converted with 96% selectivity of KA oil.[7a]
Fe/CH3COOH catalytic system with 4 equivalents of heptanal,
led to 11% conversion of cyclohexane and 85% selectivity of KA
oil.[6b] Metal-free catalysts system, eg, NHPI, consumed 1
equivalent of acetaldehyde and resulted in a conversion of 8%
with 100% KA oil selectivity for 72h.[9] In this work, we used
NHPI as a metal-free catalyst with a loading of 0.5 to 2
equivalents of benzaldehyde in the solvent of DCE, and the
cyclohexane conversion ranged from 5.7-12.3% with about 77%
selectivity of ε-CL. Thus, NHPI/PhCHO/O2/DCE is an efficient
catalytic system for the direct oxidation of cyclohexane to ε-CL.
Table 1. Effect of different temperatures on the oxidatin of cyclohexane
Selec.(%) [b]
Entry
Temperature (°C) Conv. (%) [b]
ε
-CL
CHOL
61.1
CHONE
1
2
30
35
1.0
4.8
34.7
0.0
6.5
5.6
8.0
10.2
27.0
9.3
61.1
3
4
5
40
45
50
12.3
9.7
77.3
70.9
67.0
14.3
8.3
16.0
[a] Reactions were conducted on a 2.0 mmol scale in 20 mL of DCE in a
round bottom flask with an O2 balloon for 24 h at 40 °C. [b] GC.
Table 2. Oxidation of cyclohexane in different solvents and aldehydes
[b]
Select. (%)[b]
Entry Solvent Aldehyde
Conv. (%)
trace
trace
1.9
ε
CHOL
0
CHONE
-CL
Table 4. NHPI/PhCHO-Promoted aerobic oxidation of various substrates.[a]
1
DCE
DCE
DCE
--
0
0
[b]
Conv. (%)
12
Product (Selec.,%) [b]
Entry
1
Substrate
2
--
0
0
0
0
O
OH
O
3[c]
4
PhCHO
PhCHO
PhCHO
PhCHO
PhCHO
3-Cl-PhCHO
4-F-PhCHO
CH3CHO
30.9
5.6
59.4
9.3
O
(6)
(9)
(77)
12.3
6.1
77.3
27.2
30.5
0
DCE
O
5
MeCN
28.7
26.3
0
35.3
30.2
0
2
3
6
OH
O
O
6
EtOAC
Toluene
DCE
3.2
(30)
(26)
(40)
OH
7
0
O
OH
O
O
30
8
15.0
14.3
3.5
2.1
3.3
85.4
80.4
11.8
15.8
7.9
(89)
(2)
(2)
(5)
9
DCE
6.3
7.1
4
5
4
Octanol
(40)
Octanone
(56)
n-C8H18
10
DCE
46.0
24.6
67.8
23.0
54.8
11.7
11
12
DCE (CH3)3CHCHO
DCE n-C6H13-CHO
6.6
O
OH
15
10.6
(23)
(68)
O
[a] Reactions were conducted on a 2.0 mmol scale in 20 mL of DCE in a
round bottom flask with an O2 balloon for 24 h at 40 °C. [b] GC. [c] in the
absence of NHPI.
OH
6
20
Table 3. Catalytic performance of NHPI and other reported catalyst system
(23)
(68)
[b]
Entry
Catalytic system
Conv. (%) [b] Product (Selec.,%)
Ref.
OH
O
Cu(OH)2
acetaldehyde (3 eq)
CH3CN
1
4.5
11.0
8.0
KA oil (96.0%)
KA oil (85.0%)
KA oil (100%)
7a
7
20
(72)
(20)
Fe/CH3COOH
heptanal (4 eq)
DCM
2
3
6b
9
[a] Reactions were conducted on a 2.0 mmol scale in 20 mL of DCE in a round
bottom flask with an O2 balloon for 24 h at 40 °C. [b] GC.
NHPI
acetaldehyde(1 eq)
CH3CN
The time curves of cyclohexane oxidation were shown in
Figure 1(a). In this figure, we learned that both CHOL and
CHONE selectivities in the reaction system decreased while ε-
CL selectivity increased with the conversion of cyclohexane.
These results indicated that ε-CL was easily produced from the
in-situ formed CHONE by Baeyer-Villiger oxidation in the
reaction system.[5f]
With the optimal reaction conditions in hand, we then tested
the oxidation of other alkanes under the conditions. As shown in
the Table 4, cycloalkanes were favorably transformed to the
NHPI
benzaldehyde (0.5 eq)
DCE
KA oil (21.0%)
ε-CL (76.3%)
4
5.7
This work
NHPI
benzaldehyde(1 eq)
DCE
KA oil (20.0%)
ε-CL (77.2%)
5
6
7.5
This work
This work
NHPI
benzaldehyde(2 eq)
DCE
KA oil (19.8%)
ε-CL (77.3%)
12.3
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900282
ChemCatChem
COMMUNICATION
corresponding lactones (entries 1-3). The oxidation of
adamantane showed that the reactivity of C-H bonds were in the
order tertiary > secondary > primary. However, poorly reactive
linear alkanes and alkylated benzenes such as ethylbenzene,
isobutylbenzene and indane were only converted to ketones and
alcohols (entries 4-7).
To understand the solvent-induced radical effect, we
investigated the intensity of free radicals generated by
NHPI/PhCHO system in different solvents. Figure 1(b) showed
that the PINO signal was very strong in DCE while no distinct
PINO radicals formed in toluene, which were consistent with the
results of the aerobic reaction oxidation in different solvents.
Control experiments were conducted in the absence of
benzaldehyde in different solvents (Figure S2). Moreover, trace
amount of 1-chloroadamantane was detected as a side product
by GC-MS in the reaction (SI, P11), which means DCE can
partially dissociate to promote the propagation of radical chains.
This result may account for the better performance of DCE
compared to MeCN or toluene as radicals were more readily
initiated.
radicals derived from the hydrocarbons.[10] The acylperoxy radial
species and PINO lead to a hydrogen abstraction transfer via
the homolytic cleavage of the sp3 hybridized C–H bonds of the
cyclohexane. Then cyclohexane radical reacted with acylperoxy
radial to produce CHONE and CHOL, and then the CHONE was
further oxidized to ε-CL under the same reaction conditions.
Some EPR experiments were carried out to detect the
radicals involved in the reaction. When combining PhCHO and
NHPI with air, a radical signal from PINO was detected (A = 4.56
G, g = 2.0069) (Figure 1(c), green curve). After the addition of
cyclohexane to the solution, the PINO signal was immediately
increased (blue curve). After reacting for 2 h, the PINO signal
increased to a higher level (red curve). These indicated that the
PINO was accumulated after addition of cyclohexane, probably
due to the stabilization of PINO by cyclohexane in the radical
chain propagation thus the PINO radical was increased.[11] The
EPR spectrum of PINO induced by the UV light of NHPI was
shown in Figure S1, which was consistent with the literature
[13]
reported by Ishii.[12] In particular, Pedulli et al.
reported that
PINO presented a triplet signal with a hyperfine coupling
constant in t-BuOH of aN=4.36 G. No EPR signals were
observed in the blank experiments of PhCHO/O2 or NHPI/O2
system (Figure S3).
Table 5. Oxidatin of cyclohexane mediated by -CPBA with NHPI [a]
m
[b]
Select.(%)
CHOL
Entry
NHPI amount (%) Conv. (%) [b]
ε
-CL
CHONE
1
2
0
0.5
2.0
0
32.6
42.7
29.1
10
14.6
32.4
3
100
100
4.2
4.2
11.5
20.2
10.9
14.8
70.3
55.5
4[c]
5
200
10
12.0
10.4
0
4.7
0
84.8
0
6[d]
trace
[a] Reactions were conducted at 2.0 mmol scale with 20 mL of DCE in a
round bottom flask with 1 eq. m-CPBA for 24 h at 40 oC in the presence of
O2 . [b] GC. [c] In the absence of O2. [d] In the absence of m-CPBA.
Figure 1. (a) The time curves of cyclohexane oxidation reaction. (b) EPR
spectra of the mixture of NHPI and PhCHO in solvents of 1.2-DCE (red),
MeCN (blue) and PhMe (green). (c) EPR spectra of the mixture of NHPI and
PhCHO (green) with the addition of cyclohexane immediately (blue), and for 2
h (red).
In conclusion, we have developed the first one-step process
for the aerobic oxidation of cyclohexane to ε-CL. The reaction
was carried out under mild conditions and promoted by a
mixture of NHPI and PhCHO without transition metals. This
catalytic system is able to activate the cyclohexane ring at
relatively low temperature and under low pressure of air.
Mechanistically, a radical-chain pathway was conjectured. Our
work not only provides an economic strategy for the synthesis of
industrially important ε-CL, but also indicates the great potential
of NHPI/aldehyde/O2 catalytic oxidation system that can be
possibly utilized in other oxidation reactions. Further studies will
focus on the reaction mechanism and the improvement of the
process for the industrial applications and expansion of the
novel method to other systems.
The mechanistic aspects of the transformation were
investigated by an additional experiment using
a radical
scavenger TEMPO (Table S3). No oxidation occurred in the
presence of TEMPO, which confirmed the free radical-chain
pathway of the reaction. When NHPI and 3-cholrobenzaldehyde
were replaced by m-chloroperoxybenzoic acid (m-CPBA), only
0.5% conversion of cyclohexane was detected, which indicated
that the active species involved in the oxidations was possibly
the in situ formed acylperoxy radical instead of acylperoxyl acid
(Table 5, entry 1).[9] After addition of NHPI into m-CPBA system,
the conversion of cyclohexane and selectivity of ε-CL were
improved (entries 2-5), suggesting that the oxidation proceeded
via a complex radical chain mechanism. Moreover, the presence
of O2 could promote the conversion of KA oil to ε-CL. (entry 3, 4).
Ingold and co-workers reported that the acylperoxy radicals
derived from aldehydes are considerably more reactive in
hydrogen atom abstraction from hydrocarbons than the peroxy
Experimental Section
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900282
ChemCatChem
COMMUNICATION
Materials.
Cyclohexane
(>99.0%),
cyclohexanone
(>99.0%),
added into the mixture and the mixture was stirred for another 30 min.
The EPR spectra of the reaction solution (Figure 1(c), green) were
cyclohexanol (>99.0%), adamantane (99.5%), 1-adamantanol (98%), 2-
adamantanol (98%), 2-adamantanone (99%), cyclopentane (99%), tert-
butyl acetate (>99.0%) and were purchased from TCI without further
obtained by using
a computer controlled X-band (9.5GHz) EPR
spectrometer (Bruker A300). Thereafter, EPR was measured
immediately upon addition of 0.168 g (2 mmol) of cyclohexane into the
reaction system (blue). The reaction was continued for 2 h before
measuring EPR (red).
purification
unless
indicated.
2,2,6,6-tetramethyl-1-piperidinyloxy
(TEMPO) (98%), N- hydroxyphthalimide (NHPI) (98%), biphenyl (99.5%),
benzaldehyde (98%) and ε-caprolactone (99.5%) were purchased from J
&
K
Scientific Ltd. without further purification unless indicated.
Acetonitrile, toluene, ethyl acetate were analytical grade and purchased
from Scientific Ltd. 1,2-Dichloroethane (DCE) (99.5%), 3-
chlorobenzaldehyde (98%), 4-fluorobenzaldehyde, cyclopentanol (99%),
delta-valerolactone (98%), cyclopentanone (99%) and isobutyraldehyde
(98%) were purchased from Energy Chemical without further purification
unless indicated. Heptanal (98%) and 3-chloroperoxybenzoic acid (85%)
were purchased from Tansoole without further purification. Other
chemicals were purchased from Adamas-beta without further purification.
J
& K
Acknowledgements
This work was supported by the National Natural Science
Foundation of China (No. 21573196), the Fundamental
Research Funds for the Central Universities, and the National
High Technology Research and Development Program (863
Program) of China (Grant No. SS2015AA020601).
General Methods. The progress of the reaction was monitored by taking
samples at various intervals to be analyzed using gas chromatograph
(GC) (Agilent 7820A) equipped with a DB-35/ZB-35/HP-35 column (30 m
× 0.32 mm × 0.25 mm) and a Flame Ionization Detector (FID). The
conversion was calculated on the basis of the peak area ratio of ketones
against the internal standard, biphenyl. The product yields were
calculated on the basis of the peak area ratio of lactones or esters
against the internal standard. The structural analysis of target product
was conducted on a Gas chromatography/ Mass spectrometry (GC/MS)
(Agilent 7200-Q-TOF). EPR spectra were obtained by using a computer
controlled X-band (9.5GHz) EPR spectrometer (Bruker A300).
Keywords: cyclohexane oxidation• ε-caprolactone • one-step •
NHPI • metal-free
[1]
a) A. E. Shilov, G. B. Shul'pin, Chem. Rev. 1997, 97, 2879-2932;
b) J. A. Labinger, J. E. Bercaw, Nature 2002, 417, 507-514; c) T.
Punniyamurthy, S. Velusamy, J. Iqbal, Chem. Rev. 2005, 105,
2329-2363; d) T. Newhouse, P. S. Baran, Angew. Chem. Int. Ed.
2011, 50, 3362-3374; Angew. Chem. 2011, 123, 3422-3435; e) A.
E. Wendlandt, A. M. Suess, S. S. Stahl, Angew. Chem. Int. Ed.
2011, 50, 11062-11087; Angew. Chem. 2011, 123, 11256-11283;
f) H. Yi, G. Zhang, H. Wang, Z. Huang, J. Wang, A. K. Singh, A.
Lei, Chem. Rev. 2017, 117, 9016-9085; g) G. K. Cook, J. M. Mayer,
J. Am. Chem. Soc. 1994, 116, 1855-1868; h) J.-M. Brégeault,
Dalton Trans. 2003, 1, 3289-3302; i) Y. Ishii, S. Sakaguchi, Catal.
Today 2006, 117, 105-113; j) E. V. Johnston, J. E. Bäckvall,
Modern oxidation methods, Vol 2, (Ed: J. E. Bäckvall), Wiley-VCH
Verlag GmbH & Co KGaA, 2010, pp. 353-369; k) A. P. Unnarkat,
T. Sridhar, H. Wang, S. M. Mahajani, A. K. Suresh, Catal. Today
2018, 310, 116-129; l) M. C. White, Science 2012, 335, 807-809;
m) Z. Shi, C. Zhang, C. Tang, N. Jiao, Chem. Soc. Rev. 2012, 41,
3381-3430; n) M. D. Hughes, Y. Xu, P. Jenkins, P. McMorn, P.
Landon, D. I. Enache, A. F. Carley, G. A. Attard, G. J. Hutchings, F.
King, E. H. Stitt, P. Johnston, K. Griffin, C. J. Kiely, Nature 2005,
437, 1132-1135; o) H. Frei, Science 2006, 313, 309-310; p) G.
Yang, Y. Ma, J. Xu, J. Am. Chem. Soc. 2004, 126, 10542-10543.
M. Dugal, G. Sankar, R. Raja, J. M. Thomas, Angew. Chem. Int.
Ed. 2000, 39, 2310-2313; Angew. Chem. 2000, 112, 2399-2402.
a) Y. Ishii, T. Iwahama, S. Sakaguchi, K. Nakayama, Y. Nishiyama,
J. Org. Chem. 1996, 61, 4520-4526; b) N. Sawatari, T. Yokota. S.
Sakaguchi, Y. Ishii, J. Org. Chem. 2001, 66, 7889-7891; c) C. Guo,
M. Chu, Q. Liu, Y. Liu, D. Guo, X. Liu, Appl. Catal. A: Gen. 2003,
246, 303-309; [d] X. Tong, J. Xu, H. Miao, Adv. Synth. Catal. 2005,
347, 1953-1957; e) K. M. K. Yu, R. Hummeida, A. Abutaki, S. C.
Tsang, Catal. Lett. 2006, 111, 51-55; f) D. Yang, M. Liu, W. Zhao,
L. Gao, Catal. Commun. 2008, 9, 2407-2410; g) P. Zhang, Y.
Wang, J. Yao, C. Wang, C. Yan, M. Antonietti, H. Li, Adv. Synth.
Catal. 2011, 353, 1447-1451; h) F. Farzaneh, F. Husseini, L.
Hamidipour, M. Ghiasi, J Porous Mater 2014, 21, 189-196; i) A.
Mazzi, S. Paul, F. Cavani, R. Wojcieszak, ChemCatChem 2018,
10, 3680-3682; j) G. Qian, D. Ji, G. Lu, R. Zhao, Y. Qi, J. Suo, J.
Catal. 2005, 232, 378-385; k) R. Raja, G. Sankar, J. M. Thomas, J.
Am. Chem. Soc. 1999, 121, 11926-11927; l) P. Zhang, H. Lu, Y.
Zhou, L. Zhang, Z. Wu, S. Yang, H. Shi, Q. Zhu, Y. Chen, S. Dai,
Nat. Commun. 2015, 6, 8446-8456.
General Procedure for Cyclohexane Oxidation (a) with oxygen In a
typical reaction, cyclohexane (2 mmol), benzaldehyde (4 mmol), NHPI
(10 mol%) and 1,2-dichloroethane (20 mL) were placed into a three-
necked round bottom flask (50 mL) equipped with an oxygen balloon and
a magnetic stir bar. The mixture was stirred at 40 ºC for 24 hours. The
reaction was monitored by a GC instrument. The conversion was
calculated on the basis of the peak area ratio of cyclohexane against the
internal standard, biphenyl. The product yields were calculated on the
basis of the peak area ratio of cyclohexanol, cyclohexanone, and ε-
caprolactone against the internal standard. (b) with m-CPBA In a typical
reaction, cyclohexane (2 mmol), m-CPBA (4 mmol), NHPI (10 mol%) and
1,2-dichloroethane (20 mL) were placed into a three-necked round
bottom flask (50 mL) equipped with an oxygen balloon and a magnetic
stir bar. The mixture was stirred at 40oC for 24 hours. The reaction was
monitored by GC instrument. The conversion was calculated on the basis
of the peak area ratio of cyclohexane against the internal standard,
biphenyl. The product yields were calculated on the basis of the peak
area ratio of cyclohexanol, cyclohexanone, and ε-caprolactone against
the internal standard. Control experiment was conducted in the absence
of NHPI.
[2]
[3]
General EPR experiments in different solvents. To a 25 mL schlenk
tube with
a magnetic stirrer was added 0.2122 g (2 mmol) of
benzaldehyde, 0.0163 g (0.1 mmol) of NHPI and 10 mL of 1, 2-
dichloroethane (DCE). The mixture was stirred at 40 ºC for 30 min at
atmospheric pressure. Thereafter, EPR was measured immediately. The
EPR spectra of the reaction solution were obtained by using a computer
controlled X-band (9.5 GHz) EPR spectrometer (Bruker A300). The
solvent DCE was replaced by CH3CN and Toluene. Control experiments
were conducted in the absence of bezaldehyde in different solvents.
General EPR experiments with NHPI To a 50 mL three-necked glass
flask fitted with a water cooled reflux condenser, a magnetic stir bar and
an oxygen balloon was added 0.4245 g (4 mmol) of benzaldehyde and
20 mL of 1,2-dichloroethane (DCE). The mixture was stirred at 40oC for
30 min at atmospheric pressure. Then 0.0326 g (0.2 mmol) of NHPI was
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900282
ChemCatChem
COMMUNICATION
[4]
a) K. Yang, X. Wang, Y. Wang, J. Ind. Eng. Chem. 2007, 13, 485-
500; b) G. E. Luckachan, C. K. S. Pillai, J. Polym. Environ. 2011,
19, 637-676; c) V. R. Sinha, K. Bansal, R. Kaushik, R. Kumria, A.
Trehan, Int. J. Pharm. 2004, 278, 1-23.
[8]
a) Y. Ishii, K. Nakayama, M. Takeno, S. Sakaguchi, T. Iwahama,
Y. Nishiyama, J. Org. Chem. 1995, 60, 3934-3935; b) Y. Yoshino,
Y. Hayashi, T. Iwahama, S. Sakaguchi, Y. Ishii, J. Org. Chem.
1997, 62, 6810-6813; c) Y.Yan, P. Feng, Q. Zheng, Y. Liang, J. Lu,
Y. Cui, N. Jiao, Angew. Chem. Int. Ed. 2013, 52, 5827-5831;
Angew. Chem. 2013, 125, 5939-5943; d) R. Lin, F. Chen, N. Jiao,
Org. Lett. 2012, 14, 4158-4161; e) Y. Liang, X. Wang, C. Tang, T.
Shen, J. Liu, N. Jiao, Chem. Commun. 2016, 52, 1416-1419.
C. Einhorn, J. Einhorn. C. Marcadal, J.-L. Pierre, Chem. Commun.
1997, 1, 447-448. 10
[5]
a) G. Strukul, Angew. Chem. Int. Ed. 1998, 37, 1198-1209; Angew.
Chem. 1998, 110, 1256-1267; b) G.-J. ten Brink, I. W. C. E.
Arends, R. A. Sheldon, Chem. Rev. 2004, 104, 4105-4123; c) A.
Corma, L. T. Nemeth, M. Renz, S. Valencia, Nature 2001, 412,
423-425; d) A. Sinhamahapatra, A. Sinha, S. K. Pahari, N.
Sutradhar, H. C. Bajaj, A. B. Panda, Catal. Sci. Technol. 2012, 2,
2375-2382; e) A. Drożdż, A. Chrobok, S. Baj, K. Szymańska, J.
Mrowiec-Białoń, A. B. Jarzębski, Appl. Catal. A: Gen. 2013, 467,
163-170; f) L. Wang, Y. Wang, R. Du, R. Dao, H. Yuan, C. Liang, J.
Yao, H. Li, ChemCatChem 2018, 10, 4947-4952.
[9]
[10]
[11]
V. Malatesta, K. U. Ingold, J. Am. Chem. Soc. 1981, 103, 3094-
3098.
a) S. Matsui, T. Fujita, Catal. Today 2001, 71, 145-152; b) A.
Cecchetto, F. Minisci, F. Recupero, F. Fontanab, G. F. Pedulli,
Tetra. Lett. 2002, 43, 3605-3607.
[6]
[7]
a) T. Yamada, K. Takahashi. K. Kato, T. Takai, S. Inoki, T.
Mukaiyama, Chem. Lett. 1991, 1, 641-644; b) S.-I. Murahashi, Y.
Oda, T. Naota, J. Am. Chem. Soc. 1992, 114, 7914-7916.
[12]
[13]
Y. Ishii, J. Mol. Catal. A: Chem. 1997, 117, 123-137.
a) S. Coseri, Catal. Rev. 2009, 51, 218-292; b) R. Amorati, M.
Lucarini, V. Mugnaini, G. F. Pedulli, J. Org. Chem. 2003, 68, 1747-
1754.
a) S.-I. Murahashi, T. Naota, N. Komiya, J. Chem. Soc. Chem.
Commun. 1993, 1, 139-140; b) S.-I. Murahashi, T. Naota, N. Hiral,
J. Org. Chem. 1993, 58, 7318-7319; c) S.-I. Murahashi, T. Naota,
N. Komiya, Tetrahedron Lett. 1995, 36, 8059-8062; d) N. Komiya,
T. Naota, S.-I. Murahashi, Tetrahedron Lett. 1996, 37, 1633-1636.
This article is protected by copyright. All rights reserved.

10.1002/cctc.201900282
ChemCatChem
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
O
Lingyao Wang, Yuanbin Zhang, Renfeng
Du, Haoran Yuan, Yongtao Wang, Prof.
Jia Yao, Prof. Haoran Li*
- one-pot
- metal-free
- mild conditions
O2
O
NHPI/aldehyde
Page No. – Page No.
direct aerobic oxidation of cyclohexane to ε-caprolactone
Title
The selective one-step aerobic oxidation of cyclohexane to ε-caprolactone was
achieved in the presence of N-hydroxyphthalimide (NHPI) and aldehyde under mild
conditions with 12% conversion of cyclohexane and a selectivity of 77% of ε-
caprolactone and 15% of KA oil.
This article is protected by copyright. All rights reserved.