Direct synthesis of: N -sulfenylimines through oxidative coupling of amines with disulfides/thiols over copper based metal-organic frameworks

Article abstract of DOI:10.1039/c6ra01971d

A highly porous metal-organic framework based on supramolecular building blocks with pcu-topology (pcu-MOF) has been tested for the oxidative coupling of amines and disulfides or thiols to afford the N-sulfenylimines directly in good yields without the fo

Full text of DOI:10.1039/c6ra01971d

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: W. Long, W. qiu,
C. Li, L. Song, G. Bai, G. Zhang and H. He, RSC Adv., 2016, DOI: 10.1039/C6RA01971D.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
Direct synthesis of N-Sulfenylimines through oxidative coupling of
amines with disulfides/thiols over copper based metal-organic
frameworks
Wei Long a, Wenge Qiu a,*, Chuanqiang Li b, Liyun Song a, Guangmei Bai a, Guizhen Zhang a,
Hong He a,*
a
Beijing Key Laboratory for Green Catalysis and Separation, Department of Chemistry and
Chemical Engineering, College of Environmental and Energy Engineering, Beijing University of
Technology, Beijing 100124, China
b
Department of Applied Chemistry, College of Science, Chongqing Jiaotong University,
Chongqing 400074, China
Abstract: A highly porous metalꢀorganic framework based on supramolecular building blocks
with pcuꢀtopology (pcuꢀMOF) has been tested for the oxidative coupling of amines and disulfides
or thiols to afford the Nꢀsulfenylimines directly in good yields without the formation of
Nꢀsulfinylꢀ and Nꢀsulfonylimines. The pcuꢀMOF catalyst could be easily recovered from the
reaction mixture by simple filtration, and could be reused at least five times without any
substantial loss in the yield. The control experiments and mechanistic studies suggested that the
oxidative coupling process involved the imine formation and the N−S coupling reaction.
Keywords: Metalꢀorganic framework; NꢀSulfenylimine; Oxidative coupling reaction;
Heterogeneous catalyst; Copper.
Introduction
NꢀSulfenylimines, with a functional group of Nꢀsulfur binding imines, H2C=NSR, have been
widely used as reagents or intermediates in organic synthesis. For instance, these compounds had
been utilized to prepare cyclic nitrile compounds,1 βꢀlactams,2 tetrahydroꢀβꢀcarbolines3 and many
other biologically organic molecules.4 Therefore, any efficient method for the preparation of
sulfenimines would be extremely useful. Despite the advances in crossꢀcoupling reactions using
transition metalꢀcatalysis have led to the development of effective strategies for the formation of

RSC Advances
Page 2 of 18
View Article Online
DOI: 10.1039/C6RA01971D
nitrogen−sulfur (N−S) bond,5 efficient and catalytic methods to prepare Nꢀsulfenylimines have
remained relatively undeveloped. Usually, Nꢀsulfenimines can be prepared from the condensation
of sulfenamides with aldehydes or ketones,6 or from the conversion of ketoximes and secondary
nitro compounds.7 In addition, Davis8 reported that sulfenylimines could be synthesized directly
through the condensation of disulfides, aldehydes and ammonia in the presence of silver
complexes, but a stoichiometric amount of silver complexes was needed. The direct oxidative
coupling of amines and thiols often provided sulfonamides due to the susceptivity of substrates
under oxidation conditions.9 Very recently, Jang10 group presented an pioneer work on the
synthesis of Nꢀsulfenylimines through direct oxidative coupling of amines with thiols in the
presence of homogeneous Cu(I) catalyst.
In the past decade, metalꢀorganic frameworks (MOFs) have received much attention as
catalytic materials in addition to their applications in gas storage and separation due to their
unique features, including their crystallinity, porous structure, and huge specific surface
area.11 Many kinds of porous MOFs have been used as catalysts for different reaction
systems. For instance, the wellꢀknown MOFs, HKUSTꢀ1 and MOFꢀ253, have emerged as
promising heterogeneous catalysts for CꢀO,12 CꢀN13 and CꢀS14 coupling reactions. In our
previous work, a new metalꢀorganic framework based on supramolecular building blocks
(SBBs) with pcuꢀtopology,15 denoted as pcuꢀMOF, were reported, which has high density
metal open sites and large open windows. These points encouraged us to explore its
application as a heterogeneous catalyst. Herein we reported the direct oxidative coupling of
amines and disulfides or thiols to provide various Nꢀsulfenylimines without the formation
of Nꢀsulfinylꢀ and Nꢀsulfonylimines in the presence of pcuꢀMOF, which can be reused at
least five times without a significant degradation in catalytic activity. To the best of our
knowledge, this is the first report about a heterogeneous catalytic system for generation of
sulfenylimines.
Results and discussion
Synthesis and characterization of the pcu-MOF
The pcuꢀMOF was prepared by a solvothermal method according to the reported procedure.15 The
XRD patterns of the pcuꢀMOF sample (Fig. 1) matched well with the published results,15
indicating the pure phase of the MOF and the construction of the intended crystalline framework.

Page 3 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
Nitrogen sorption measurements were carried out to determine the specific surface area and the
pore structure of the pcuꢀMOF sample (Fig. S1, Table S1). Its BET surface area and adsorption
average pore width were 2010 m2/g and 1.94 nm, respectively, demonstrating the porosity and
stability of the pcuꢀMOF after removing the included and coordinated solvents. The SEM image
of the pcuꢀMOF sample showed that the MOF particles presented cubic or polyhedral shapes with
sizes in the range of 20ꢀ150 ꢁm (Fig. S2). Thermogravimetric data showed that the pcuꢀMOF was
o
stable up to 300 C (Fig. S3). There was a continuous weight loss of 5.91 % from room
temperature to 200 oC for the pcuꢀMOF sample, which was corresponding to the loss of
physisorbed H2O and residual ethanol in the MOF channels. The weight loss of 7.75 % between
200 and 260 oC could be attributed to the dehydration of coordinated H2O in the pcuꢀMOF, being
close to the calculated weight change (6.73 %).
Fig. 1 Xꢀray diffraction patterns for pcuꢀMOF samples: asꢀsynthesized (red), after activation (blue)
and used after five catalysis cycles (cyan).
pcu-MOF as a solid catalyst for the oxidative coupling of 4-methoxybenzylamine with
diphenyldisulfide
In this work, 4ꢀmethoxybenzylamine (1) and diphenyldisulfide (2), were chosen as model
substrates. For optimizing the reaction conditions, various solvents and additives were screened
under different temperatures in the presence of the pcuꢀMOF. The experimental results at various
conditions were presented in Table 1. It was found that the yields of Nꢀsulfenylimine (3) increased
gradually (Table 1, compare entries 2ꢀ4) with a rising of temperature in the beginning, indicating
the effect of temperature on the coupling reaction, but then the yields of 3 decreased in the range
of 120ꢀ140 oC. One possible reason was that the substrates was oxidized under high temperature.16

RSC Advances
Page 4 of 18
View Article Online
DOI: 10.1039/C6RA01971D
Considering the stability of the reagents and pcuꢀMOF, all the following experiments were
o
conducted at 120 C. The desired product was not formed in the absence of pcuꢀMOF (Table 1,
entry 1), implying that the pcuꢀMOF was necessary for the oxidative coupling reaction of
4ꢀmethoxybenzylamine with diphenyldisulfide.
Table 1 Oxidative coupling reaction of 4ꢀmethoxylbenzylamine and diphenyldisulfide over copper
based MOFs and copper salts *
SPh
CuꢀMOF, Solvent
NH2
N
+ PhSSPh
Additives
120 oC, O2 (1 atm)
O
O
2
1
3
Entry
1
Catalysts
/
Solvents
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
Toluene
PhCl
Additives
DTBN, TBD
DTBN, TBD
DTBN, TBD
DTBN, TBD
DTBN, TBD
DTBN, TBD
\
temp(℃)
120
100
110
120
130
140
120
120
120
120
120
120
120
120
120
120
120
120
120
120
Yields (%)d
n.r
52
2
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
pcuꢀMOF
Cu(NO3)2
CuI
3
57
4
68(93e)
63
5
6
57
7
12
8
DTBNb
35
9
TBDb
38
10
11
12
13
14
15
16
17
18
19
20
TEMPOb
PINOb
23
21
Triethylamineb
DTBN, TBD
5
51
DTBN, TBD
43
Anisole
NMP
DTBN, TBD
41
DTBN, TBD
49
DMSO
DMSO
DMSO
DMSO
DBNO, TBD, H2O2
65
c
DBNO, TBD, N2
n.r
21
DTBN, TBD
DTBN, TBD
83

Page 5 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
21
22
Cu(NO3)2+ H4La
HKUSTꢀ1
DMSO
DMSO
DTBN, TBD
DTBN, TBD
120
120
2
23
* Reaction conditions: 4ꢀmethoxylbenzylamine (5 mmol), diphenyldisulfide (1.25 mmol), MOFs
(0.125 mmol, based on copper), DTBN (0.25 mmol), TBD (0.25 mmol), solvent (5 mL), for 18 h
under O2 atmosphere; (a) H4L represents 1,1ꢀbisꢀ[3,5ꢀbis(carboxy)phenoxy]methane; (b) 0.5 mmol
additive was added; (c) The reaction was carried out under nitrogen atmosphere; (d) Isolated
yields; (e) Data of reaction for 48 h. The symbol of n.r represents no reaction. TBD, DTBN,
TEMPO and PINO represent 1,5,7ꢀtriazabicyclo[4.4.0]decꢀ5ꢀene, diꢀtertꢀbutylnitroxide,
2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxyl, and Nꢀhydroxyphthalimide, respectively.
It was found that ligand additives had large effects on the copperꢀcatalyzed oxidation reaction of
amines,9a,9c,17 so the effects of several organic additives were examined. In the model reaction,
compound 3 was obtained in only 12 % yield (Table 1, entry 7) when no additive was added. The
use of DTBN, TBD, TEMPO and PINO separately with the loading of 20 mol% resulted in
modest increase in the yields of 3 (Table 1, entry 8ꢀ11), suggesting the existence of improvements
of these additives in the reaction. When DTBN and TBD were used at the same time, 3 was
obtained in good yield (Table 1, entry 4), indicating that there might exist a synergistic effect
between DTBN and TBD. The control experiment using the same amount of DTBN and TBD in
the absence of pcuꢀMOF gave no product (Table 1, entry 1), suggesting that the additives alone
did not have appreciable catalytic activity but served as coꢀcatalyst to promote the activity of
pcuꢀMOF. The addition of triethylamine could not promote the reaction satisfactorily. One
possibility is that the interaction of substrate molecules with catalyst was impeded due to the
coordination of triethylamine with the copper ion on the MOF.
The effects of solvents were also tested (Table 1, entry 13ꢀ16). Reaction in toluene,
chlorobenzene, anisole or Nꢀmethylꢀ2ꢀpyrrolidone (NMP), respectively, gave the coupled product
in moderate yields. DMSO was found to be the best solvent for the oxidative coupling reaction
(Table 1, entry 4). In addition, a good yield of 3 could be obtained when oxygen was replaced by
H2O2 (Table 1, entry 17), but no reaction was observed without the oxidant (Table 1, entry 18),
implying the importance of the oxidant in the coupling reaction. According to the above results,
we conducted the oxidative coupling reaction in DMSO at 120 °C in the presence of DTBN and
TBD with the total loading of 20 mol% as the standard reaction condition. The coupling reaction

RSC Advances
Page 6 of 18
View Article Online
DOI: 10.1039/C6RA01971D
could afford 3 in 93 % yield for 48 h with complete conversion of diphenyldisulfide (Fig. 2)
without any Nꢀsulfinylꢀ and Nꢀsulfonylimines.
Fig. 2 Yields as a function of reaction times in the oxidative coupling reaction of
4ꢀmethoxylbenzylamine and diphenyldisulfide with pcuꢀMOF as catalyst at 120 °C.
●: catalyst
presented throughout; : catalyst removed from the suspension after 4 h. Reaction conditions:
○
4ꢀmethoxylbenzylamine (5 mmol), diphenyldisulfide (1.25 mmol), MOFs (0.125 mmol, based on
copper), DTBN (0.25 mmol), TBD (0.25 mmol), solvent (5 mL), for 18 h under O2 atmosphere.
In order to determine whether the catalysis of pcuꢀMOF is truly heterogeneous or, on the
contrary, is due to some leached copper species present in the reaction solution, a control
experiment was performed: the pcuꢀMOF catalyst was removed from hot solution by filtration
after 4 h. The filtrate was further performed for another 44 h. No significant catalytic conversion
was observed (Fig. 2), indicating that the reaction was terminated after removal of the MOF
catalyst. Furthermore, inductively coupled plasma atomic emission spectroscopy (ICPꢀAES)
analysis of the filtrate showed that there was only about 1.5 ppm of copper ions in the solution,
which corresponds to 0.006% of copper ions in the solution after one cycle of the oxidative
coupling reaction. These results clearly confirmed that the catalysis of pcuꢀMOF is heterogeneous
in nature, and the contribution of leached copper species soluble in the solution was negligible. As
a result, the open copper sites on the axis of paddleꢀwheel SBUs within the pcuꢀMOF might be
responsible for the promotion of the oxidative coupling reaction.18
On the other hand, the catalytic activity of Cu(NO3)2 and CuI in homogeneous solution was
studied in the presence of DTBN and TBD for the same reaction (Table 1, entries 19 and 20). The
experimental results showed that both Cu(I) and Cu(II) could improve the oxidative coupling

Page 7 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
reaction, but the yield of 3 in the presence of CuI was much higher than that of Cu(NO3)2,
revealing the high activity of Cu(I).19 A widely used MOF, namely CuBTC20 (Fig. S4 and S5) that
was constructed from paddleꢀwheel type copper clusters and 1,3,5ꢀbenzenetricarboxylate
molecules, was also tested, but it showed a low activity for the oxidative coupling reaction
between 4ꢀmethoxylbenzylamine and diphenyldisulfide (Table 1, entry 22). The yield of the
desired product in homogeneous catalytic process by both Cu(NO3)2 and H4L (Table 1, entry 21)
was much lower than that of the heterogeneous system of pcuꢀMOF. Owing to the same amount of
copper species being used in the heterogeneous and homogeneous reaction systems, this result
further revealed that the high density of open copper sites within the pcuꢀMOF were the active
sites of pcuꢀMOF catalyst.
The pcuꢀMOF catalyst demonstrated good reusability for the oxidative coupling reaction of
4ꢀmethoxylbenzylamine and diphenyldisulfide (Fig. 3). The yields of compound 3 were 68 %,
69 %, 67 %, 65 % and 67 %, respectively, in successive cycles for 18 hours. The image (Fig. S2b)
and the nitrogen physisorption measurement (Fig. S1) demonstrated the porosity and stability of
pcuꢀMOF after five reaction runs. The BET surface area and pore volume of the reused catalyst
decreased slightly from 2010 to 1743 m2/g and 0.979 to 0.929 cm3/g (Table S1), respectively,
probably due to the adsorption of a few reactant or product molecules in the MOF cavities.21,22
The main diffraction peaks of the pcuꢀMOF catalyst after five reaction runs also matched well to
the data of fresh catalyst (Fig. 1). The decrease in peaks intensities and few diffraction peaks
becoming broaden can be attributed to the degradation of partial crystal particles induced by the
stirring and the effect of reaction medium (Fig. S2b).
Fig. 3 Reuse of pcuꢀMOF in the oxidative coupling reaction of 4ꢀmethoxylbenzylamine and

RSC Advances
Page 8 of 18
View Article Online
DOI: 10.1039/C6RA01971D
diphenyldisulfide. Reaction condition: 4ꢀmethoxylbenzylamine (5 mmol), diphenyldisulfide (1.25
mmol), MOFs (0.125 mmol, based on copper), DTBN (0.25 mmol), TBD (0.25 mmol), solvent (5
mL), for 18 h under O2 atmosphere.
Generality of the oxidative coupling reaction
With the optimal reaction conditions in hand, we then investigated the substrate scope of amines
and thiols. As shown in table 2, the reaction proceeded smoothly with substrates containing
electronꢀ drawing groups or electronꢀdonating groups in moderate yields (Table 2, entry 2ꢀ6),
demonstrating that this reaction has a high degree of functional group tolerance. Comparing to
4ꢀmethoxylbenzylamine, 3ꢀmethoxylbenzylamine could also react smoothly with
diphenyldisulfide and gave a high yield of the desired product (Table 2, entry 1). When
thiophenols were used as the sulfur resource, the coupling reaction performed well too (Table 2,
entry 7ꢀ9). In addition, one could find that steric effect had influence on the transformation as
confirmed by the relative lower yield for the αꢀmethyl and αꢀethyl substituted substrates (Table 2,
entry 11,12) than the unsubstituted substrate (Table 1, entry 4). However, the αꢀphenyl substituted
substrate (Table 2, entry 10) was suitable for the smooth conversion. This could be attributed to
the high stability of the imine intermediate that would be discussed in the mechanism discussion.
When benzenamine, aliphatic amine or alicyclic amine was used, no product was detected (Table
2, entry 14 and 15), or the yield was very low for 48 h (Table 2, entry 16), revealing that the
benzylamine group was essential for the oxidative coupling reaction.
Table 2 Oxidative coupling reaction of various benzylamines with diphenyldisulfide or
thiophenols over pcuꢀMOF*
Entry
1
Amines
Sulfur sources
PhSSPh
Yield (%)§
65
2
3
4
5
PhSSPh
PhSSPh
PhSSPh
PhSSPh
42
53
34
39

Page 9 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
6
7
8
9
PhSSPh
38
69
53
51
10
PhSSPh
58
11
12
PhSSPh
PhSSPh
39
43
13
PhSSPh
65
NH
NH2
14
15
16
PhSSPh
PhSSPh
PhSSPh
n.r
n.r
11#
* Reaction condition: benzylamines (5 mmol), diphenyldisulfide/thiophenol (1.25/2.5 mmol),
MOFs (0.125 mmol, based on copper), DTBN (0.25 mmol), TBD (0.25 mmol), solvent (5 mL),
for 18 h under O2 atmosphere. § Isolated yields based on the sulfur resource. # Data for 48 h. The
symbol of n.r represents no reaction.
Mechanistic Considerations
Copperꢀcatalyzed reaction usually occurred via a single electron transfer process or an
organometallic pathway.23 Several strategies involving copper mediated NꢀS bond formation have
been reported.5 For these homogeneous Cu(I) or Cu(II) catalyzed processes, the proposed
mechanisms included the coordination of thiol and amine to copper atom as well as the oxidative
formation of a CuꢀS bond and a CuꢀN bond.5,9c In order to understand the mechanism of the
present catalytic system, several control experiments were performed. Only a trace amount of
product (compound 3) was observed when the oxidative coupling reaction of
4ꢀmethoxylbenzylamine and diphenyldisulfide was conducted under nitrogen atmosphere,
suggesting that oxygen is necessary for the present procedure. However, a radical pathway could

RSC Advances
Page 10 of 18
View Article Online
DOI: 10.1039/C6RA01971D
be ruled out because stoichiometric radical scavenger (TEMPO) did not inhibit the reaction at
all.24 In the absence of diphenyldisulfide, a high yield of 4ꢀmethoxybenzaldehyde was detected
(Table S2), suggesting that imine derivatives might act as the intermediate formed by the
oxidation of the corresponding amine under air conditions.25 The formation of
4ꢀmethoxybenzaldehyde was due to hydrolysis of the imine during workꢀup.26 The imine
intermediate mechanism was further supported by the experiment, in which the coupling reaction
could afford the desired product, Nꢀ(phenylthio)ꢀdiphenylmethanimine, in a good yield of 65 %
when diphenylmethylimine was used as the substrate (Table 2, entry 13). These results suggested
that the oxidative coupling reaction might carry out in a two steps mechanism involving the imine
formation by amine oxidation and the N−S coupling reaction.
To gain further insights into the mechanism, the function of the additives in each step was also
studied. In the oxidation reaction of 4ꢀmethoxylbenzylamine (Table S2), the yield of oxidation
product in the presence of DTBN was higher than that in the absence of additive, indicating the
promotion of DTBN to the imine formation due to its activation of molecular oxygen.27 But TBD
showed no effect on the oxidation of benzylamine. For the coupling reaction of
diphenylmethylimine and diphenyldisulfide, only 5% product was afforded when no additive was
added, however, the desired coupling product produced a yield of 57 % or 59 % in the presence of
DTBN or TBD, showing that the additives had significant effect on the coupling reaction. Here
both DTBN and TBD might act as bases. Only 8 % yield of Nꢀ(phenylthio)ꢀdiphenylmethanimine
was obtained when the reaction was carried out under nitrogen atmosphere, implying that oxygen
also played an important role in the NꢀS coupling step.
To investigate the function of pcuꢀMOF in the oxidation coupling reaction, the electron
paramagnetic resonance (EPR) spectra of pure pcuꢀMOF, pcuꢀMOF with 4ꢀmethoxybenzylamine,
pcuꢀMOF with diphenyldisulfide, and pcuꢀMOF in the reaction system at Xꢀband (9.06 GHz)
were recorded at 90 oC, respectively. The spectra of the reaction system at Xꢀband were dominated
by a broad central line at g = 2.112, (Fig. 4), which could be attributed to Cu2+ꢀCu2+ dimmers or
mononuclear Cu2+ ions.28 Compared to the spectra of pure pcuꢀMOF in toluene (Fig. S6a), the
decrease of the intensity of EPR signal of the reaction mixture with time and the change of gꢀvalue
indicated the occurrence of interaction between reaction substrates and copper sites. However,
different phenomena were observed when 4ꢀmethoxybenzylamine and diphenyldisulfide existed

Page 11 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
with pcuꢀMOF separately. For the system of pcuꢀMOF and 4ꢀmethoxybenzylamine, the gꢀvalue
decreased from 2.147 to 2.115, indicating that 4ꢀmethoxybenzylamine coordinated to the Cu(II)
ions on the framework that resulted in a shift of the gꢀparameters to lower values,29 but the
intensity of EPR signal remained (Fig. S6b). On the contrary, for the system of pcuꢀMOF and
diphenyldisulfide, the intensity of EPR signal decreased obviously with time, but no change of the
gꢀvalue was observed (Fig. S6c). These results revealed the different interaction between the two
reagents and the copper ions on the MOF framework. The intensity of the EPR signal of the
reaction system decreased with time, indicating that part of the Cu(II) ions were reduced by the
disulfide. It has been reported that reductive reagent or in situ generated reductive species could
reduce the Cu(II) on the MOF framework to Cu(I) species, which can be oxidized into Cu(II) by
O2 oxidation at the end of the reaction without affecting heterogeneous nature of the MOF
catalyst.30
Fig. 4 Continuous wave (CW) EPR spectrum of the reaction mixture in toluene at Xꢀband at 90 oC
Based on the literatures10,30 and our experimental results, a plausible mechanism of the
oxidative coupling reactions was outlined in Scheme 1. At first, benzylamine interacted with Cu(II)
ion on the pcuꢀMOF framework to form benzylamineꢀCu complex, which underwent oxidation to
afford imine intermediate. Meanwhile, disulfide interacted with Cu(II) ion, leading to the
reduction of Cu(II) to Cu(I), which in turn initiated the activation of disulfide. Then imine and the
activated disulfide coupled together to afford the product Nꢀsulfenimine.

RSC Advances
Page 12 of 18
View Article Online
DOI: 10.1039/C6RA01971D
Scheme 1 Proposed mechanistic cycle.
Conclusions
In summary, we have shown for the first time that copperꢀbased MOF is an efficient
heterogeneous catalyst for the oxidative coupling of amines and disulfides or thiols. This protocol
provides a novel and direct synthesis of Nꢀsulfenylimines in good yields without the formation of
Nꢀsulfinylꢀ and Nꢀsulfonylimines. The experimental results prove that pcuꢀMOF can be reused at
least five times without any degradation in catalytic activity. Based on the control experiments and
the characterization data, a plausible two steps mechanism was proposed, which involved the
imine formation by amine oxidation and the N−S coupling reaction. The open copper sites on the
axis of paddleꢀwheel SBUs within pcuꢀMOF are responsible for the both two steps.
Experimental
Materials and instruments
All solvents and chemicals were obtained commercially and used as received without further
purification. The pcuꢀMOF15 and CuBTC20 were synthesized according to the reported procedures,
respectively. Powder Xꢀray diffraction was performed on a Bruker D8 Advance Xꢀray
diffractometer using CuꢀKα radiation (λ=1.5406 Å) at room temperature with a scan speed of 0.5 s
per step and a step size of 0.02°. The images of the MOF samples were conducted on Hitachi S
1
4800 scanning electron microscope (SEM) at room temperature. HꢀNMR and 13CꢀNMR data
were collected on Bruker ARXꢀ400 or Bruker ARXꢀ600 spectrameters with DMSOꢀd6 solution by
using tetramethylsilane as an internal standard. Inductively coupled plasma atomic emission
spectroscopy (ICPꢀAES) analysis was performed on an IRIS Intrepid ER/S (Thermo Elemental)
o
instrument. Nitrogen sorption measurement was performed at ꢀ196 C on a Micromeritics ASAP
o
2020. A sample of approximately 50 mg was outgassed at 150 C for 12 h and then nitrogen

Page 13 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
isotherm at ꢀ196 oC was measured in liquid nitrogen bath using UHPꢀgrade (99.999%) gas source.
The BrunauerꢀEmmettꢀTeller (BET) surface areas of pcuꢀMOF and CuBTC were calculated based
on the nitrogen absorption isotherms. The continuous wave (CW) EPR spectra of pure pcuꢀMOF,
pcuꢀMOF with 4ꢀmethoxybenzylamine, pcuꢀMOF with diphenyldisulfide, and pcuꢀMOF in the
reaction system in toluene at XꢀBand were measured using a JESꢀFA200 spectrometer (microwave
o
frequency 9.06 GHz, power of the microwave 0.998 mW) at 90 C. Thermogravimetric analysis
(TGA) was performed on an NETZSCH TG 209F3 instrument under nitrogen atmosphere (250
mL/min). The sample was heated at a constant rate of 10 °C/min from 40 oC to 600 oC.
General procedure for the pcu-MOF catalyzing the oxidative coupling reaction
The oxidative coupling reaction was performed as follows. In a typical procedure, pcuꢀMOF (33.5
mg, 0.125 mmol), diꢀtertꢀbutylnitroxide (DTBN, 36.0 mg, 0.25 mmol) and
1,5,7ꢀtriazabicyclo[4.4.0] decꢀ5ꢀene (TBD, 35.0 mg, 0.25 mmol) were added to a solution of
4ꢀmethoxybenzylamine (685 mg, 5.0 mmol) and diphenyldisulfide (261 mg, 1.25 mmol) in
DMSO (5 ml). A slow stream of O2 was passed through the solution for 10 min. Then, the reaction
mixture was stirred at 120 °C for 18 h under O2 atmosphere. The solvent was removed under
vacuum, and the residue was purified by flash silica gel column chromatography by using 1 %
ethyl acetate/hexane as an eluent. The fractions were collected and evaporated to afford the pure
desired product.
(a) N-(4-methoxybenzylidene)-S-phenylthiohydroxylamine. 1HꢀNMR (400 MHz, DMSOꢀd6):
δ = 8.65 (s, 1H), 7.70 (d, J = 8.7 Hz, 2H), 7.56 (d, J = 7.6 Hz, 2H), 7.44 (t, J = 7.7 Hz, 2H), 7.26 (t, J
= 7.3 Hz,1H), 7.02 (d, J = 8.7 Hz, 2H), 3.80 (s, 3H); 13CꢀNMR (101 MHz, DMSOꢀd6): δ = 161.25,
158.04, 137.66, 129.14, 129.04, 128.91, 126.36, 125.20, 114.27, 55.32; Mass(ESI): m/z = 244.00
(M+H+; Calcd for C14H13NOS+H 244.08, found: 244.00).
(b) N-(3-methoxybenzylidene)-S-phenylthiohydroxylamine. 1HꢀNMR (600 MHz, DMSOꢀd6):
δ = 8.65 (s, 1H), 7.58 (d, J = 7.7 Hz, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.37 (t, J = 7.8 Hz, 1H), 7.31 (d,
J = 7.9 Hz, 1H), 7.29 (s,1H), 7.27 (s, 1H), 7.02 (dd, J = 8.1, 2.1 Hz, 1H), 3.78 (s, 3H); 13CꢀNMR
(151 MHz, DMSO): δ = 160.03, 158.54, 137.77, 137.57, 130.40, 129.72, 127.26, 126.20, 120.29,
117.00, 112.28, 55.62; Mass(ESI): m/z = 244.02 (M+H+; Calcd for C14H13NOS+H 244.08, found:
244.02).
(c) N-(3-methylbenzylidene)-S-phenylthiohydroxylamine. 1HꢀNMR (600 MHz, DMSOꢀd6) δ

RSC Advances
Page 14 of 18
View Article Online
DOI: 10.1039/C6RA01971D
8.67 (s, 1H), 7.58 (d, J = 8.1 Hz, 2H), 7.55 (s, 1H), 7.53 (d, J = 7.9 Hz, 1H), 7.46 (t, J = 7.7 Hz,
2H), 7.35 (t, J = 7.6 Hz, 1H), 7.29 (t, J = 7.4 Hz, 1H), 7.27 (d, J = 7.5 Hz, 1H), 2.34 (s,
3H);13CꢀNMR (151 MHz, DMSOꢀd6) δ 158.93, 138.59, 137.72, 136.41, 131.82, 129.71, 129.20,
127.98, 127.18, 126.12, 125.07, 21.36; Mass(ESI): m/z = 228.04 (M+H+; Calcd for C14H13NS+H
228.08, found: 228.04).
(d) N-(benzo[d][1,3]dioxol-5-ylmethylene)-S-phenylthiohydroxylamine. 1HꢀNMR (600 MHz,
DMSOꢀd6) δ 8.60 (s, 1H), 7.56ꢀ7.55(m, 2H), 7.44 (t, J = 7.7 Hz, 2H), 7.34 (s, 1H), 7.26 (t, J = 7.4
Hz, 1H), 7.19 (d, J = 8.0 Hz, 1H), 6.98 (d, J = 8.0 Hz, 1H), 6.09 (s, 2H); 13CꢀNMR (151 MHz,
DMSOꢀd6) δ 158.26, 150.02, 148.55, 138.08, 131.30, 129.63, 126.87, 125.66, 124.32, 108.82,
105.72, 102.14; Mass(ESI): m/z = 258.02 (M+H+; Calcd for C14H11NO2S+H 258.06, found:
258.02).
(e) N-(4-chlorobenzylidene)-S-phenylthiohydroxylamine. 1HꢀNMR (600 MHz, DMSOꢀd6) δ
8.68 (s, 1H), 7.73 (d, J = 8.4 Hz, 2H), 7.57 (d, J = 8.1 Hz, 2H), 7.50 (d, J = 8.4 Hz, 2H), 7.45 (t, J
= 7.7 Hz, 2H), 7.29 (t, J = 7.4 Hz, 1H); 13CꢀNMR (151 MHz, DMSOꢀd6) δ 157.42, 137.53, 135.66,
135.17, 129.71, 129.40, 129.23, 127.29, 126.11; Mass(ESI): m/z = 248.05 (M+H+; Calcd for
C13H10ClNS+H 248.03, found: 248.05).
(f) N-(2-chlorobenzylidene)-S-phenylthiohydroxylamine. 1HꢀNMR (600 MHz, DMSOꢀd6) δ
8.84 (s, 1H), 7.94 (dd, J = 7.6, 1.4 Hz, 1H), 7.57 (d, J = 7.5 Hz, 2H), 7.45 (d, J = 7.6 Hz, 2H), 7.43
(d, J = 1.6 Hz, 1H), 7.41ꢀ7.40 (m, 1H), 7.37 (t, J = 7.6 Hz, 1H), 7.30 (t, J = 7.4 Hz, 1H); 13CꢀNMR
(151 MHz, DMSOꢀd6) δ 153.65 , 136.86, 133.40, 133.04, 132.27, 130.37, 129.77, 127.97,
127.94,127.75, 127.59, 126.94; Mass(ESI): m/z = 248.07 (M+H+; Calcd for C13H10ClNS+H 248.03,
found: 248.07).
1
(g) N-(3-nitrobenzylidene)-S-phenylthiohydroxylamine. HꢀNMR (600 MHz, DMSOꢀd6) δ
8.73 (s, 1H), 8.40 (s, 1H), 8.21ꢀ8.19 (m, 1H), 8.08 (d, J = 7.7 Hz, 1H), 7.68 (t, J = 7.9 Hz, 1H),
7.55 (d, J = 8.1 Hz, 2H), 7.45 (t, J = 7.7 Hz, 2H), 7.30 (t, J = 7.4 Hz, 1H);13CꢀNMR (151 MHz,
DMSOꢀd6) δ 156.27, 148.55, 137.63, 137.01, 133.31, 130.77, 129.74, 127.60, 126.48, 125.04,
121.83; Mass(ESI): m/z = 258.02 (M+H+; Calcd for C13H10N2O2S+H 258.05, found: 258.02).
(h) N-(3-methoxybenzylidene)-S-(4-chlorophenyl)thiohydroxylamine.1HꢀNMR(600 MHz,
DMSOꢀd6) δ 8.70 (s, 1H), 7.58 (d, J = 8.5 Hz, 2H), 7.49 (d, J = 8.5 Hz, 2H), 7.38 (t, J = 7.8 Hz,
1H),7.33ꢀ 7.31 (m, 1H), 7.29 (s, 1H), 7.04ꢀ7.03 (m, 1H), 3.79 (s, 3H); 13CꢀNMR (151 MHz,

Page 15 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
DMSOꢀd6) δ 159.61 , 158.91, 137.23, 136.50, 131.15, 130.04, 128.86, 126.92, 119.94, 116.71,
112.02, 55.24, 39.87, 39.66 (s, 32H), 39.52 (s, 38H), 39.38 (s, 24H), 39.17 (d, J = 21.0 Hz, 15H);
Mass(ESI): m/z = 278.00 (M+H+; Calcd for C14H12ClNOS+H 278.04, found: 278.00).
1
(i) N-(3-methoxybenzylidene)-S-(4-fluorophenyl)thiohydroxylamine. HꢀNMR (600 MHz,
DMSOꢀd6) δ 8.56 (s, 1H), 7.61 (dd, J = 8.6, 5.3 Hz, 2H), 7.35 (t, J = 7.9 Hz, 1H), 7.31 (t, J = 8.8
Hz, 2H), 7.28 (d, J = 7.8 Hz, 1H), 7.26 (s, 1H), 7.01 (dd, J = 8.1, 2.2 Hz, 1H), 3.77 (s, 3H);
13CꢀNMR (151 MHz, DMSOꢀd6) δ 161.54 (d, J = 244.6Hz), 159.60, 157.88, 137.26, 132.18,
129.95, 129.16(d, J = 7.5Hz), 119.87, 116.60, 116.46(d, J = 22.6Hz), 111.83, 55.18; Mass(ESI):
m/z = 226.00 (M+H+; Calcd for C14H13FNOS+H 226.07, found: 226.00).
1
(j) N-(diphenylmethylene)-S-phenylthiohydroxylamine. HꢀNMR (400 MHz, DMSOꢀd6) δ
7.60 (t, J = 7.4 Hz, 4H), 7.57 (m, 2H), 7.54 (m, 1H), 7.45 (t, J = 8.1 Hz, 4H), 7.41 (s, 1H), 7.38 (m,
2H), 7.24 (t, J = 7.3 Hz, 1H); 13CꢀNMR (151 MHz, DMSOꢀd6) δ170.90, 138.56, 137.46, 136.26,
130.65, 129.57, 128.96, 128.75, 128.58, 125.88; Mass(ESI): m/z = 290.09 (M+H+; Calcd for
C19H15NS+H 290.10, found: 290.09).
1
(k) S-phenyl-N-(1-phenylethylidene)thiohydroxylamine. HꢀNMR (600 MHz, DMSOꢀd6) δ
7.86 (s, 2H), 7.63 (d, J = 8.2 Hz, 2H), 7.48 – 7.41 (m, 5H), 7.25 (dd, J = 11.5, 4.1 Hz,1H), 2.47 (s,
3H);13Cꢀ NMR (151 MHz, DMSOꢀd6) δ 162.70, 139.13 , 139.08, 130.13, 129.54, 128.96, 126.58,
126.54, 124.86, 20.60; Mass(ESI): m/z = 228.03(M+H+; Calcd for C14H13NS+H 228.08, found:
228.03).
(l) S-phenyl-N-(1-phenylpropylidene)thiohydroxylamine. 1HꢀNMR (600 MHz, DMSOꢀd6) δ
7.89 – 7.82 (m, 1H), 7.63 (d, J = 8.2 Hz, 1H), 7.47ꢀ7.42 (m, 5H), 7.24 (t, J = 7.4 Hz, 1H), 2.90 (q,
J = 7.6 Hz, 2H), 1.16 (t, J = 6.8 Hz, 3H);13CꢀNMR (151 MHz, DMSOꢀd6) δ 167.01, 139.14,
130.13, 129.52, 129.08, 126.64, 126.26, 124.76; Mass(ESI): m/z = 242.10 (M+H+; Calcd for
C15H15NS+H 242.10, found: 242.10).
(m) N-(cyclohexylidene)-S-phenylthiohydroxylamine. 1HꢀNMR (400 MHz, DMSOꢀd6) δ
7.47(dt, J=6.5, 2.2 Hz, 2H), 7.37 (m, 2H), 7.19 (m, 1H), 2.42 (t, J=7.3 Hz, 2H), 2.29 (t, J=7.5 Hz,
2H), 1.87 (dt, J=13.8, 6.7 Hz, 2H), 1.64 (m, 2H); 13CꢀNMR (101 MHz, DMSOꢀd6) δ 179.44, 139.20,
129.35, 126.15, 124.75, 37.31, 34.18, 31.15, 25.49; Mass(ESI): m/z = 192.08 (M+H+; Calcd for
C11H13NS+H 192.08, found: 192.08).
Recycling experiments

RSC Advances
Page 16 of 18
View Article Online
DOI: 10.1039/C6RA01971D
pcuꢀMOF (310 mg, 1.25 mmol) , Diꢀtertꢀbutyl nitroxide (DTBN, 360 mg, 2.5 mmol) and
1,5,7ꢀtriazabicyclo[4.4.0]decꢀ5ꢀene (TBD, 350 mg, 2.5 mmol), 4ꢀOMeꢀbenzyl amine (6850 mg, 50
mmol), Phenyl disulfide (2610 mg, 12.5 mmol) and DMSO (50 mL) were added into a threeꢀneck
flask (250 mL) with a magnetic bar, and then the tube was vacuumed and purged with oxygen
three times before it was finally pressurized with double oxygen balloons. Subsequently, the flask
o
was stirred at 120 C for 18 h. After completion of the reaction, the solid catalyst was recovered
by filtration, washing with hot methanol and drying under vacuum to remove the residual solvent,
and reused for the next run. The liquid mixture was collected, and the solvent was removed under
vacuum. The residue was purified by flash silica gel column chromatography by using 1% ethyl
acetate/hexane as an eluent, fractions were collected and evaporated to afford the
Nꢀ(4ꢀmethoxybenzylidene)ꢀSꢀphenylthiohydroxylamine.
Acknowledgements
We acknowledge the financial support of the national natural science foundation of China (Grant
No. 21577005, 21307168 and 21277009).
References
1. J. Boivin, E. Fouquet and S. Z. Zard, J. Am. Chem. Soc., 1991, 113, 1055ꢀ1057.
2. (a) S. Coantic, D. Mouysset, S. Mignani, M. Tabart and L. Stella, Tetrahedron, 2007, 63,
3205ꢀ3216; (b) D. A. Burnett, D. J. Hart and J. Liu, J. Org. Chem., 1986, 51, 1929ꢀ1930.
3. M. J. Wanner, R. N. S. van der Haas, K. R. de Cuba, J. H. van Maarseveen and H. Hiemstra,
Angew. Chem. Int. Ed., 2007, 46, 7485ꢀ7487.
4. (a) L. Craine and M. Raban, Chem. Rev., 1989, 89, 689ꢀ713; (b) J. A. Ellman, T. D. Owens
and T. P. Tang, Acc. Chem. Res., 2002, 35, 984ꢀ995.
5. (a) H. Kim, S. H. Kwak, G. Lee and Y. Gong, Tetrahedron, 2014, 70, 8737ꢀ8743; (b) Z. Wang,
Y. Kuninobu and M. Kanai, J. Org. Chem., 2013, 78, 7337ꢀ7342; (c) N. Taniguchi, Synlett.,
2007, 12, 1917ꢀ1920; (d) R. Paul and T. Punniyamurthy, RSC Adv., 2012, 2, 7057ꢀ7060; (e) A.
Correa, I. Tellitu, E. Dominguez and R. Sanmartin, Org. Lett., 2006, 8, 4811ꢀ4813.
6. (a) J. J. Damico, J. Org. Chem., 1961, 26, 3436ꢀ3445; (b) J. C. Foster and J. B. Matson,
Macromolecules, 2014, 47, 5089ꢀ5095; (c) J. C. Foster, C. R. Powell, S. C. Radzinski and J. B.

Page 17 of 18
RSC Advances
View Article Online
DOI: 10.1039/C6RA01971D
Matson, Org. Lett., 2014, 16, 1558ꢀ1561.
7. (a) K. A. Lukin and B. A. Narayanan, Tetrahedron, 2002, 58, 215ꢀ219; (b) J. Bures, C. Isart
and J. Vilarrasa, Org. Lett., 2007, 9, 4635ꢀ4638; (c) J. Esteban, A. M. Costa, F. Urpi and J.
Vilarrasa, Tetra. Lett., 2004, 45, 5563ꢀ5567.
8. (a) F. A. Davis, W. A. R. Slegeir and S. Evans, J. Org. Chem., 1973, 38, 2809ꢀ2813; (b) F. A.
Davis, W. A. R. Slegeir and J. M. Kaminsky, J. Chem. Soc., Chem. Commun., 1972, 634ꢀ635.
9. (a) X. Huang, J. Wang, Z. Ni, S. Wang and Y. Pan, Chem. Commun., 2014, 50, 4582ꢀ4584; (b)
K. Bahrami, M. M. Khodaei and M. Soheilizad, Tetra. Lett., 2010, 51, 4843ꢀ4846; (c) N.
Taniguchi, Eur. J. Org. Chem., 2010, 2670ꢀ2673.
10. C. Lee, X. Wang and H. Jang, Org. Lett., 2015, 17, 1130ꢀ1133.
11. (a) A. Corma, H. Garcia and F. X. Llabresi Xamena, Chem. Rev., 2010, 110, 4606ꢀ4655; (b) A.
Dhakshinamoorthy, M. Alvaro and H. Garcia, Catal. Sci. Technol., 2011, 1, 856ꢀ867; (c) A.
Dhakshinamoorthy, M. Opanasenko, J. Cejka and H. Garcia, Catal. Sci. Technol., 2013, 3,
2509ꢀ2540.
12. M. Wang, B. Z. Yuan, T. M. Ma, H. F. Jiang and Y. W. Li, RSC Adv., 2012, 2, 5528ꢀ5530.
13. N. T. S. Phan, T. T. Nguyen, C. V. Nguyen and T. T. Nguyen, Appl. Catal. A: Gen., 2013, 457,
69ꢀ77.
14. A. Dhakshinamoorthy, M. Alvaro, P. Concepcion and H. Garcia, Catal. Commun., 2011, 12,
1018ꢀ1021.
15. C. Li, W. Qiu, W. Shi, H. Song, G. Bai, H. He, J. Li and M. J. Zaworotko, CrystEngComm,
2012, 14, 1929ꢀ1932.
16. (a) R. D. Patil and S. Adimurthy, Adv. Synth. Catal., 2011, 353, 1695ꢀ1700; (b) T. Sonobe, K.
Oisaki and M. Kanai, Chem. Sci., 2012, 3, 3249ꢀ3255.
17. (a) N. Taniguchi, Synlett, 2007, 12, 1917ꢀ1920; (b) F. Chen, G. Liao, X. Li, J. Wu and B. Shi,
Org. Lett., 2014, 16, 5644ꢀ5647; (c) F. G. Xi, Y. Yang, H. Liu, H. F. Yao and E. Q. Gao, RSC
Adv., 2015, 5, 79216ꢀ79223.
18. L. Alaerts, E. Seguin, H. Poelman, F. ThibaultꢀStarzyk, P. A. Jacobs and D. E. De Vos, Chem.
Eur. J., 2006, 12, 7353ꢀ7363.
19. M. Largeron and M. B. Fleury, Angew. Chem. Int. Ed., 2012, 51, 5409ꢀ5412.
20. K. Schlichte, T. Kratzke and S. Kaskel, Micropor. Mesopor. Mat., 2004, 73, 81ꢀ88.

RSC Advances
Page 18 of 18
View Article Online
DOI: 10.1039/C6RA01971D
21. L. H. Wee, S. R. Bajpe, N. Janssens, I. Hermans, K. Houthoofd, C. E. A. Kirschhock and J. A.
Martens, Chem. Commun., 2010, 46, 8186ꢀ8188.
22. C. Q. Li, W. G. Qiu, W. Long, F. Deng, G. M. Bai, G. Z. Zhang, X. H. Zi and H. He, J. Mol.
Catal. A: Chem., 2014, 393, 166ꢀ170.
23. S. E. Allen, R. R. Walvoord, R. PadillaꢀSalinas and M. C. Kozlowski, Chem. Rev., 2013, 113,
6234ꢀ6458.
24. Y. Sun, W. Wu and H. Jiang, Eur. J. Org. Chem., 2014, 4239ꢀ4243.
25. (a) B. Huang, H. Tian, S. Lin, M. Xie, X. Yu and Q. Xu, Tetra. Lett., 2013, 54, 2861ꢀ2864; (b)
D. Damodara, R. Arundhathi and P. R. Likhar, Adv. Synth. Catal., 2014, 356, 189ꢀ198.
26. P. Capdevielle, A. Lavigne and M. Maumy, Tetrahedron, 1990, 46, 2835ꢀ2844.
27. D. L. Kleyer, R. Curtis Haltiwanger and T. H. Koch, J. Org. Chem., 1983, 48, 147ꢀ152.
28. (a) H. E. L. Mkami, M. I. H. Mohideen, C. Pal, A. McKinlay, O. Scheimann and R. E. Morris,
Chem. Phys. Lett., 2012, 544, 17ꢀ21; (b) M. Simenas, M. Kobalz, M. Mendt, P. Eckold, H.
Krautscheid, J. Banys and A. Poppl, J. Phys. Chem. C, 2015, 119, 4898ꢀ4907.
29. P. Valvekens, E. D. Bloch, J. R. Long, R. Ameloot and D. E. D. Vos, Catal. Today, 2015, 246,
55ꢀ59.
30. (a) V. Mahendran and S. Shanmugam, RSC Adv., 2015, 5, 20003ꢀ20010; (b) S. Parshamoni, S.
Sanda, H. S. Jena and S. Konar, Dalton Trans., 2014, 43, 7191ꢀ7199.