Electrochemical C-H functionalization and subsequent C-S and C-N bond formation: Paired electrosynthesis of 3-amino-2-thiocyanato-α,β-unsaturated carbonyl derivatives mediated by bromide ions

Article abstract of DOI:10.1039/c6gc00666c

An efficient paired electrosynthesis involving C-H functionalization and subsequent C-S and C-N bond formation for the assembly of valuable 3-amino-2-thiocyanato-α,β-unsaturated carbonyl derivatives has been developed. In the paired electrolysis, the amin

Full text of DOI:10.1039/c6gc00666c

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Electrochemical CꢀH functionalization and subsequent CꢀS and CꢀN bond
formation: Paired electrosynthesis of 3ꢀaminoꢀ2ꢀthiocyanato α,βꢀunsaturated
carbonyl derivatives mediated by bromide ion
a
a
b
a
b
LiꢀShuo Kang, MiꢀHai Luo, Chiu Marco Lam, LiꢀMing Hu, R. Daniel Little
*, a, c
and ChengꢀChu Zeng
a
College of Life Science & Bioengineering, Beijing University of Technology,
Beijing 100124, P. R. China, Eꢀmail: zengcc@bjut.edu.cn
b
Department of Chemistry & Biochemistry, University of California, Santa Barbara,
Santa Barbara 93106ꢀ9510, CA
c
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing
Technology and Business University, Beijing 100048, China
Abstract: An efficient paired electrosynthesis involving CꢀH functionalization and
subsequent CꢀS and CꢀN bond formation for the assembly of valuable
3
ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl derivatives has been developed. In
the paired electrolysis, the amino and thiocyanato moieties originate from a single
reagent or a combination of ammonium acetate and potassium isocyanate. The
chemistry proceeds in a simple undivided cell employing a subꢀstoichiometric amount
of NH
electrolyte; in this manner additional conducting salt is not required. The reaction also
works using catalytic amount of NH Br. Cyclic voltammetry and the results of control
4
Br that serves both as an inner sphere type redox catalyst and a supporting
4
experiments demonstrate that the reaction proceeds via an anodically initiated CꢀH
functionalization of the 1,3ꢀdicarbonyl substrates that occurs via the electrochemical
oxidation of bromide and simultaneous cathodic reduction of ammonium ion.
Keywords: electrochemical CꢀH functionalization; paired electrolysis; indirect
electrolysis; αꢀthiocyanation; 3ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl
derivatives
1
. Introduction
Oxidative functionalization of CꢀH bonds to form new CꢀC and Cꢀheteroatom

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bonds has proven to be of importance in organic chemistry due to its high atom
1
economy and responsible use of ecological resources. Along with the classical
methods using a chemical oxidant or photochemistry, electrochemistry provides an
alternative method to achieve the CꢀH functionalization by heterogeneous electron
transfer between an electrode and a substrate (direct electrolysis) or by using a redox
2
catalyst (indirect electrolysis). In the course of an electrolysis, paired processes
have attracted much attention in both academic and industrial settings since they use
both the oxidation reaction at the anode and the reduction reaction at the cathode to
generate synthetically useful product(s), and (ideally) achieve a 200 % electrolysis
3
efficiency.
3ꢀAminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carboxyl compounds are useful
4
substances that often serve in the synthesis of 4,5ꢀdisubstituted 2ꢀaminothiazoles,
which in turn are invaluable intermediates for the preparation of thiazole derivatives
5
possessing herbicidal and other important biological activities. The synthesis of
3
ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carboxyl compounds is generally achieved
through a sequence of steps involving βꢀamination, introduction of an αꢀhalo/tosyloxy
4
substituent, and αꢀthiocyanation (Scheme 1). This multiꢀstep approach suffers from
the use of harsh conditions, large excess of oxidizing agents, and the production of
large amounts of waste.
We are interested in CꢀH oxidative functionalization processes induced by redox
6
6aꢀ6d
catalysts. Along with the use of other mediators,
we have applied simple halide
6
gꢀ6i
ions as inner sphere type redox catalysts for paired electrolysis.
Based on our
experience in paired electrolysis and electrochemical CꢀH bond functionalization, we
hypothesized that a constant current electrolysis (CCE) of βꢀdicarbonyl compounds in
the presence of halide ion might initially generate αꢀhalodicarbonyl intermediates that
would further undergo αꢀthiocyanation and βꢀamination in the presence of a source of
2
a synthetic equivalent for NH and SCN (Scheme 1). We report herein a novel
strategy for the synthesis of 3ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl
compounds using a halide salt as a redox catalyst via paired electrolysis. The protocol
features step efficiency and atom economy, avoiding preꢀfunctionalization of the

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starting βꢀdicarbonyl compound and tedious isolation of intermediates.
Conventional approach
αꢀCꢀH
functionalization
NH2
O
NH O
2
O
O
amination
R1
R2
R1
R2
R1
R2
H
X
X = Br, I, OTs
thiocyanation
NH source,
2
SCN source
MX, CCE
NH2
O
O
O
R1
R2
via
R1
R2
SCN
X
Our working strategy
Scheme 1. Conventional approach and our working strategy for the synthesis of
3
ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl compounds.
2
. Results and discussion
To investigate the feasibility of the approach outlined above, we chose ethyl
acetoacetate 1a and ammonium carbamodithioate 2 as model substrates (Scheme 2a
and Table 1). Attempts to optimize the reaction conditions began with a constant
current electrolysis that was carried out in a simple beakerꢀtype cell equipped with a
graphite plate anode and a Ni plate cathode at room temperature. When NaI was used
as a redox catalyst and methanol as a solvent, the desired adduct, (E)ꢀethyl
3
ꢀaminoꢀ2ꢀthiocyanatobutꢀ2ꢀenoate (3a) was isolated in a 34% yield after passing 3.5
F/mol of charge (Table 1, entry 1). Encouraged by the result, redox catalyst screening
was subsequently carried out in an effort to improve the yield. We observed that
among all iodide and bromide salts examined (NaI, NaBr, NH
Bu NI), NH Br gave the best result, and a 45% yield of 3a was achieved (Table 1,
entries 2ꢀ6).
4 4 4
I, NH Br, Et NBr and
4
4

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NH2
O
S
O
O
O
O
cat.
+
(a)
(b)
(c)
OEt
OEt
H N
SNH4 undivided cell
CCE
OEt
OEt
2
SCN
1
1
a
a
2
3
a
NH Br (50 mol%)
NH2 O
4
CH CN
3
+
4
NH SCN
Pt ꢀ Pt electrode
undivided cell
mA/cm2
SCN
5
3a (67%)
NH Br (50 mol%)
NH2 O
4
3
O
O
CH
CN
+
NH OAc
+
KSCN
4
OEt
OEt
Pt ꢀ Pt electrode
undivided cell
SCN
1
a
5
mA/cm2
3a (62%)
Scheme 2. Electrochemical synthesis of (E)ꢀethyl 3ꢀaminoꢀ2ꢀthiocyanatobutꢀ2ꢀenoate
from the reaction of 1a with different NH and SCN sources.
2
1
Next, the effect of solvent was examined. It was observed that the H NMR yield
of 3a increased to 73% and 79% when the electrochemical reaction was conducted in
ethanol and CH
3
CN, respectively (entries 7 and 8). In contrast, 3a was not detected
when DMF, DMSO, H
2
O and THF were used as solvents (entries 9ꢀ12).
Further screening of electrode materials demonstrated that Pt net was preferred
entries 13 and 14). The investigation of redox catalyst loading showed that the yield
(
of 3a decreased from 95% to 39% when NH
mol% (compare entries 14 and 15). A further decrease of NH
decreased the yield of products significantly (entry 16). Notably, only a trace of 3a
4
Br loading decreased from 50 to 20
4
Br loading to 10 mol%
was detected in the absence of NH
4
Br, which reveals that NH
4
Br is essential to the
success of the oneꢀpot electrosynthesis of 3a.
a
Table 1. Optimization of the reaction conditions
O
O
NH2 O
S
cat.
+
OEt
OEt
H N
SNH4
CCE
2
SCN
3a
1a
2
b
Entry
Anode/cathode
CꢀNi
Mediator (equiv)
NaI (0.5)
Solvent
MeOH
MeOH
MeOH
MeOH
Yield (%)
c
1
2
3
4
34
c
CꢀNi
NaBr (0.5)
36
c
CꢀNi
NH
4
I (0.5)
44
c
CꢀNi
NH Br (0.5)
45
4

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c
c
5
6
7
8
9
CꢀNi
CꢀNi
CꢀNi
CꢀNi
CꢀNi
CꢀNi
CꢀNi
CꢀNi
PtꢀNi
PtꢀPt
PtꢀPt
PtꢀPt
PtꢀPt
Et
4
NBr (0.5)
NI (0.5)
MeOH
MeOH
EtOH
43
15
Bu
4
NH
NH
NH
4
Br (0.5)
Br (0.5)
Br (0.5)
73
79
4
4
MeCN
d
d
d
d
H
2
O
N. D
N. D
N. D
N. D
93
10
NH Br (0.5)
THF
4
1
1
2
3
4
5
6
7
NH
4
4
Br (0.5)
Br (0.5)
DMF
1
1
1
1
1
1
NH
DMSO
MeCN
MeCN
MeCN
MeCN
MeCN
NH Br (0.5)
4
c
NH
NH
NH
NH
4
4
4
4
Br (0.5)
Br (0.2)
Br (0.1)
Br (0.0)
95, 89
e
39
e
18
e
2
a
Reaction conditions: ethyl acetoacetate 1a (1.0 mmol), 2a (1.5 mmol) and redox
mediator in 10 mL of solvent, undivided cell, room temperature, current density of 5
2
mA/cm , about 3.5 F/mol of charge.
b 1
H NMR yield.
c
Isolated yield after column chromatograph.
d
Non detected.
e 1
H NMR yield in the presence of 0.1 M LiClO
4
as supporting electrolyte.
For the reactions described above, the ꢀNH
2
and ꢀSCN subunits of the product 3a
both originate from 2. For completeness, alternative sources were also explored. As
shown in Scheme 2b, under the optimal reaction conditions described above, but
using NH
yield. In addition, when a combination of NH
potential sources of NH and SCN, 3a was produced in a 62% isolated yield (Scheme
4
SCN in place of ammonium carbamodithioate, 3a was isolated in a 67%
4
OAc and KSCN were employed as
2
2
c). In each case, the yield of 3a was lower than using 2 (entry 14, Table 1). We
therefore prefer to use 2 for the paired electrolysis.

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With the optimal conditions in hand, we then studied the scope and the generality
of the protocol, by examining reactions of ammonium carbamodithioate 2 with a
variety of 1,3ꢀdicarbonyl compounds, 1. As shown in Table 2, 3ꢀoxoesters, such as
methyl (1b) and tꢀbutyl ester (1c), afforded the corresponding adducts 3b and 3c in 75%
and 85% yields, respectively (entries 2 and 3, Table 2). Good yields of 3d (80%) and
3
e (71%) were also obtained when 1d and 1e were employed as the 3ꢀoxoester
counterparts (entries 4 and 5, Table 2). Notably, when the hindered tꢀbutyl ketone 1f
was subjected to the optimal conditions, adduct 3f was not isolated and presumably
did not form (entry 6).
The standard conditions could also be applied to 3ꢀoxoamides, although slightly
lower yields were obtained when compared to the corresponding 3ꢀoxoesters. As
shown in Table 2, use of 3ꢀoxobutanamide derivatives, 1g, 1h, and 1i, afforded the
desired products in 59%, 55% and 52% yields, respectively (entries 7ꢀ9).
The electrochemical reaction of 2 with aliphatic 1,3ꢀdiketones also proceeded
smoothly. For example, when pentaneꢀ2,4ꢀdione (1j) was subjected to electrolysis
under the standard conditions, adduct 3j formed in an 80% yield (entry 10). Cyclic
diketones
such
as
cyclohexaneꢀ1,3ꢀdione
(1k),
and
5,5ꢀdimethyl
cyclohexaneꢀ1,3ꢀdione (1l), also worked well, leading to good yields of 3k and 3l
(entries 11 and 12).
The standard conditions were also applied to aromatic 1,3ꢀdicarbonyl compounds.
It was found that the reaction of phenylbutaneꢀ1,3ꢀdione (1m) with 2 proceeded
sluggishly and only 11% of adduct 3m was isolated (entry 13). By using KSCN and
4
NH OAc, the yield of 3m increased to 22% (entry 14). However, in the cases of 1n,
the product 3n was not detected (entry 15); instead, 4ꢀmethoxybenzoic acid was
isolated in a 12% yield. We note, too, that in the reactions with aromatic
1
,3ꢀdicarbonyl compounds described above, an unidentified white precipitate was
formed as the main product, which is believed to be a polymer, although its exact
structure is not known, since the precipitate is insoluble in MeOH, EtOH, CH CN,
CH Cl , EtOAc, acetone and water.
Other sources of the NH functionality were also tolerated by the paired
3
2
2
2

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electrolysis protocol. For example, the reactions of ethyl acetoacetate 1a with benzyl
ammonium acetate under the standard conditions afforded adduct 3o in a 39% yield
(entry 16). Similarly, a 26% yield of adduct 3p was isolated when pꢀmethoxybenzyl
ammonium acetate was used as the amino source (entry 17).
Table 2. Scope and generality of the electrochemical reaction.
NH Br (50 mol %)
O
O
4
NH2 O
CH CN
+
3
NH source and
SCN source
2
R1
R2
R1
R2
Pt ꢀ Pt electrode
SCN
undivided cell
1
a - 1n
2
3a - 3p
5
mA/cm
entr
y
diketone
SCN
NH source
product
yield
2
source
O
O
O
S
1
1a
1b
1c
1d
1e
1f
NH
2
O
3a
3b
3c
3d
3e
3f
89
75
85
80
71
ꢀ
OEt
H
2
N
SNH
4
OEt
SCN
O
S
S
S
S
S
S
S
NH O
2
2
3
4
5
6
7
8
OMe
H N
SNH4
2
OMe
SCN
O
O
O
NH
2
O
tꢀBu
H
2
N
SNH
4
O
t-Bu
SCN
NH
O
O
2
O
OEt
H N
2
SNH4
OEt
SCN
O
O
O
NH
2
H N
SNH4
2
OEt
OEt
OEt
SCN
NH
O
O
2
O
H N
2
SNH4
OEt
SCN
O
O
NH
2
O
N
1g
1h
3g
3h
59
55
N
H N
2
SNH4
SCN
NH2
O
H N
2
SNH4
O
O
N
H
SCN
N
H
S
2
NH O
9
O
O
1i
3i
52
H N
2
SNH4
N
H
N
H
SCN

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S
O
O
NH2
O
1
0
1
1j
1k
1l
3j
3k
3l
80
67
49
11
22
H N
SNH4
SNH4
2
SCN
S
S
S
O
NH
2
1
SCN
H N
2
O
O
O
NH2
12
13
14
15
SCN
H N
2
SNH4
SNH4
O
O
O
O
O
NH2
O
1m
3m
3m
3n
H N
2
SCN
O
NH2
O
1m KSCN
NH OAc
4
SCN
S
c
O
O
2
NH O
1n
ꢀ
OEt
H N
2
SNH4
OEt
SCN
MeO
MeO
NH
O
O
O
O
3
NH OAc
1
6
7
1a KSCN
1a KSCN
3o
3p
39%
26%
OEt
OEt
OEt
SCN
NH
O
O
3
NH OAc
1
MeO
OEt
MeO
SCN
a
2
Reaction conditions: diketone derivatives 1 (1.0 mmol), NH and SCN source (each
1
.5 mmol) and NH
4
Br (0.5 equiv) in 10 mL of acetonitrile, undivided cell, platinum
2
o
net (2×2.5 cm ) as anode and cathode electrodes, 40 C, constant current electrolysis
2
at current density of 5 mA/cm , ~3.5 F/mol charge.
b
Isolated yield.
c
4ꢀmethoxybenzoic acid was isolated as the main product.
In addition to the wide range of substrates to which our protocol is applicable, we
note that it can be scaled to gram quantities thus highlighting its practicality. As
shown in Scheme 3, when 1.0 gram of 1a or 1i was allowed to react with 2 under the
standard conditions, adducts 3a (from 1a) and 3i (from 1i) were isolated in 62 % and
4
6 % yields, respectively.

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O
O
S
4
NH Br (50 mol %)
NH O
2
+
CH CN
3
R
H N
SNH4
R
2
Pt ꢀ Pt electrode
SCN
undivided cell
5 mA/cm2
1
1
a (R = OEt), 1.0 g
i (R = NHPh), 1.0 g
3a, 62% (1.3 g)
3i, 46% (1.0 g)
2
(1 equiv)
Scheme 3. Scaling up
The process can also be achieved using catalytic amounts of bromide salt. As
shown in Scheme 4, when NH SCN was used, its reaction with 1,3ꢀdicarbonyl
4
compounds in the presence of 20 mol% of Et
to good yields of the corresponding adducts.
4
NBr as a redox catalyst gave moderate
Et NBr (20 mol%)
4
NH2
O
O
O
CH CN
3
+
NH SCN
4
R1
R2
R1
R2
Pt ꢀ Pt electrode
SCN
undivided cell
1
2
3
5
mA/cm
1
2
1
1
1
1
a: R = Me, R = OEt
c: R = Me, R = OtꢀBu
d: R = Pr, R = OEt
j: R = Me, R = Me
3
a (61%)
3c (45%)
d (43%)
3j (40%)
1
2
1
2
3
1
2
Scheme 4. Paired electrolysis of 3ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl
derivatives using a catalytic amount of bromide ion
ꢀ
2e
2
Br
Br
2
(
1)
ꢀ
e
(2)
Br3
3/2 Br2
To provide mechanistic insight, cyclic voltammetry was used as the initial tool.
As shown in curve a of Figure 1, the CV of NH Br in acetonitrile exhibits two
4
3 3
oxidation waves, one at 0.60 V and the other, 0.93 V vs Ag/AgNO (0.1 M in CH CN).
7
According to the literature, we assign the first peak to correspond to the oxidation of
2
bromide to form molecular bromine, Br (eq. 1). Once formed, its reaction with
–
3
bromide ion leads to tribromide Br
. The second wave is therefore attributed to the
–
3
anodic oxidation of Br to produce Br (eq. 2). Curve b refers to the CV of NH Br in
2
4
the presence of 5 equiv of ethyl acetoacetate. Here we observe that the intensity of the
two oxidation peaks increases, while the reduction peak current decreases. Since ethyl
acetoacetate is not oxidized in the potential range from 0.0 V to 1.5 V vs Ag/AgNO3
3
(0.1 M in CH CN) that was used (curve e), the increase in the oxidative peak current

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is attributed to a catalytic current, resulting from the reaction of the in situ
electrochemicallyꢀgenerated bromine and ethyl acetoacetate, generating αꢀbromo
ethyl acetoacetate and bromide ion that leads to an increase of oxidation peak current
and the appearance of catalytic current accompanying the conversion of 1 to 5
(Scheme 5).
Figure 1. Cyclic voltammogram of NH
4
Br, 1a and 2 in 0.1 M LiClO
4 3
/CH CN, using
GC disk working electrode, Pt wire and Ag/AgNO
3
(0.1 M in CH CN) as counter and
3
reference electrode at 100 mV/s scan rate. a: NH Br (2 mmol/L). b: NH Br (2
4
mmol/L) and 1a (10 mmol/L). c: 2 (2 mmol/L). d: NH
mmol/L) and 2 (10 mmol/L). e: 1a (2 mmol/L).
4
4
Br (2 mmol/L), 1a (10
Curve c, portraying the CV of 2, reveals an irreversible oxidation peak at 0.83 V
vs Ag/AgNO (0.1 M in CH CN). It is significant to note that when 2 was added to
3
3
the mixture described above, an additional dramatic increase in the catalytic current
was observed (curve d). Thus, the first peak current increased from 33 to 214 ꢁA,
indicating that 2 promotes the regeneration of bromide anion (note the conversion of 5
to 6 in Scheme 5).
Several control experiments were performed in an effort to obtain additional
insight into the reaction mechanism. As shown in Scheme 5a, the direct electrolysis of
the mixture of 1a and 2 using LiClO as the conducting salt, without the presence of a
4
halideꢀbased salt, afforded only trace amounts of 3a, indicating that the efficient
formation of 3a involves halide as a mediator. When the reaction was performed in

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the presence of TEMPO, a radical scavenger, less than 6% yield of 3a was detected
Scheme 5b), as was also the case in the presence of BHT (Scheme 5c). These results
(
implicate the role of a radical intermediate. Electrolysis of the ethyl acetoacetate, 1a,
in the absence of 2 under otherwise identical conditions afforded ethyl
2
ꢀbromoꢀ3ꢀoxobutanoate 5a in 25% (Scheme 5d). Moreover, an electrolysis of a
mixture of the αꢀbromo keto ester 5a and 2 without the addition of a bromide salt,
produced 3a in a 29% yield (Scheme 5e). These results indicate that the brominated
keto ester 5a is likely a key intermediate for the oneꢀpot synthesis of
3
ꢀaminoꢀ2ꢀthiocyanatobutꢀ2ꢀenoate, under our standardized reaction conditions.
NH2
O
S
LiClO / CH CN
O
O
4
3
(
a)
+
OEt
H N
2
SNH4
Pt ꢀ Pt electrode
OEt
SCN
3a (trace)
undivided cell
2
1a
2
5
mA/cm
NH Br (20 mol%)
4
TEMPO (1.0 equiv)
NH2
O
S
O
O
LiClO / CH CN
4
3
(
b)
+
OEt
H N
SNH4
2
Pt ꢀ Pt electrode
OEt
OEt
SCN
undivided cell
2
1
a
2
5
mA/cm
3a (6%)
NH Br (20 mol%)
4
BHT (1.0 equiv)
NH2
O
S
O
O
LiClO / CH CN
4
3
(c)
+
OEt
H N
2
SNH4
Pt ꢀ Pt electrode
SCN
3a (2%)
undivided cell
2
1a
2
5
mA/cm
NH Br (1.0 equiv)
4
O
O
O
O
LiClO / CH CN
4
3
(
(
d)
e)
OEt
OEt
Pt ꢀ Pt electrode
Br
a (25%)
undivided cell
2
5
mA/cm
5
O
O
S
LiClO / CH CN
NH O
2
4
3
+
OEt
H N
2
SNH4
Pt ꢀ Pt electrode
OEt
Br
undivided cell
SCN
5a
2
2
5
mA/cm
3
a (29%)
Scheme 5. Controlled experiments
Based on the CV analysis and preparative scale electrolysis results, a

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plausible mechanism is proposed and shown in Scheme 5. The reaction sequence
begins with the anodic oxidation of bromide ion to form molecular bromine and
its subsequent reaction with substrates 1 to afford αꢀbrominated structures 5.
During this step, bromide is regenerated.
The subsequent nucleophilic
substitution reaction of 5 with the carbamodithioate anion, resulting from the
dissociation of the ammonium salt 2, generates intermediate 6 or its tautomer 7.
Once again, the bromide ion is regenerated, this time in the subsequent
thiocyanation (5
→6) step. The generated bromide is oxidized again at the surface
of the anode and enter the redox cycle. Therefore, the bromide works as an inner
2
c
sphere type redox mediator. Meanwhile, the cathodic reduction of ammonium
ion affords ammonia, which reacts with 7 to afford the ketoimine 8 and its
tautomer 9. Further anodic oxidation of 9 leads to the expulsion of H S and
2
8,9
production of the final product 3.
NH2
S
O
NH2
O
NH
O
[
O]
R1
XR2
R1
XR2
R1
XR2
HS
SCN
ꢀ H S
HS
S
2
NH
3
NH
8
9
O
O
O
O
2
Br
NH3
R1
S
XR2
R
1
XR
2
S
HS
S
O
O
NH2
NH
R1
XR2
6
7
Br
O
5
S
S
NH4
H N
2
SNH4
O
H
2
N
S
Br2
2
R1
XR2
Anode
1
Cathode
2
Br
Scheme 6. Proposed mechanism for the electrochemical synthesis of
3
3
3
4
ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl derivatives mediated by NH Br.
. Conclusion
In summary, an effective electrochemical protocol for the synthesis of
ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl derivatives has been developed. The

Page 13 of 53
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chemistry proceeds via a paired electrolysis mode in a simple undivided cell, wherein
bromide is oxidized anodically and ammonium ion is reduced cathodically. In the
reaction, an additional conducting salt is not required and a subꢀstoichiometric amount
of bromide salt serves both as an inner sphere type redox catalyst and the supporting
electrolyte. The reaction also works using catalytic quantities of Et NBr as a redox
4
catalyst. The ability to scale up the protocol demonstrates its practicality. The paired
electrolysis avoids preꢀfunctionalization, tedious isolation of intermediates, the
utilization of external oxidants, the production of large amount of waste, and therefore
represents an environmentally benign means by which to achieve the transformation.
Application of these ideas and results to other types of reactions is underway in our
laboratory.
Acknowledgements
This work was supported by grants from the National Natural Science Foundation of
China (No. 21272021, 21472011) and the National Key Technology R&D Program
(2011BAD23B01). ZCC and RDL are grateful to the US National Science Foundation
supported PIREꢀECCI Program (OISEꢀ0968399) for fostering our international
collaboration, and the Center for the Sustainable Use of Renewable Feedstocks
(CenSURF), an NSF Center for Chemical Innovation (CHEꢀ1240194).
References
1
(
a
b
) S. A. Girard, T. Knauber and C. J. Li, Angew. Chem., Int. Ed., 2014, 53, 74;
) I. B. Krylov, V. A. Vil and A. O. Terentev, Beilstein J. Org. Chem., 2015, 11,
(
9
2; (
c
) C. L. Sun and Z. J. Shi, Chem. Rev., 2014, 114, 9219; (
d
) R. Narayan, K.
) R. Samanta, K.
Matcha and A. P. Antonchick, Chem. Eur. J., 2015, 21, 14678; (
e
Matcha and A. P. Antonchick, Eur. J. Org. Chem., 2013, 26, 5769.
2
For some excellent reviews of organic electrochemical reactions used in synthesis,
see: (
08, 2265; (
reviews of indirect electrolysis, see: (
Rev., 2014, 43, 2492; ( ) Y. N. Ogibin, M. N. Elinson and G. I. Nikishin, Russ.
a
) J. I. Yoshida, K. Kataoka, R. Horcajada and A. Nagaki, Chem. Rev., 2008,
) J. B. Sperry and D. L. Wright, Chem. Soc. Rev., 2006, 35, 605. For
) R. Francke and R. D. Little, Chem. Soc.
1
b
c
d

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Chem. Rev., 2009, 78, 89; (
For recent examples, see: (
Moeller and J. Aubé, Angew. Chem., Int. Ed., 2015, 54, 10555; (
DeRoy, C. Perreault, A. Larivée, A. Siddiqui, C. G. Caldwell, S. Harran and P. G.
Harran, Angew. Chem., Int. Ed., 2015, 54, 4818; ( ) T. Morofuji, A. Shimizu and
J. I. Yoshida, J. Am. Chem. Soc., 2014, 136, 4496; ( ) T. Morofuji, A. Shimizu
and J. I. Yoshida, J. Am. Chem. Soc., 2013, 135, 5000; ( ) T. Morofuji, A.
Shimizu and J. I. Yoshida, Angew. Chem., Int. Ed., 2012 51, 7259; ( ) F.
Kakiuchi, T. Kochi, H. Mutsutani, N. Kobayashi, S. Urano, M. Sato, S.
Nishiyama and T. Tanabe, J. Am. Chem. Soc., 2009, 131, 11310; ( ) B. Elsler, D.
Schollmeyer, K. M. Dyballa, R. Franke and S. R. Waldvogel, Angew. Chem., Int.
Ed., 2014, 53, 5210; ) Z. L. Zhang, J. H. Su, Z. G. Zha and Z. Y. Wang, Chem.
Commun., 2013, 49, 8982.
For a review, see: ( ) N. Aust, A. Kirste, In Encyclopedia of applied
electrochemistry., (Kreysa, G. et al. Eds), 1505; For recent examples on paired
electrolysis, see: ( ) R. Matthessen, J. Fransaer, K. Binnemans and D. De Vos,
ChemElectroChem., 2015, 2, 73; ( ) M. F. Hartmer and S. R. Waldvogel, Chem.
Commun., 2015, 51, 16346; ( ) G. Hilt, Angew. Chem. Int. Ed., 2003, 42, 1720.
) Y. S. Park and K. Kim, Tetrahedron Lett., 1999, 40, 6439; ( ) G. Meng, M.
Wang, A. Q. Zheng, J. W. Dou and Z. J. Guo, Green. Chem. Lett. Rev., 2014, 7,
6; ( ) J. M. Chen and X. Huang, Synlett., 2004, 552.
) F. E. Dayan, A. C. Vincent, J. G. Romagni, S. N. Allen, S. O. Duke, M. V.
Duke, J. J. Bowling and J. K. Zjawiony, J. Agric. Food Chem., 2000, 48, 3689;
) A. A. Thomas, Y. L. Huerou and J. D. Meese, Bioorg. Med. Chem. Lett., 2008,
8, 2206; ( ) D. Hisashi, M. Aya, K. Masakatsu and N. Satoshi, J. Org. Chem.,
e
) E. Steckhan, Angew. Chem., Int. Ed., 1986, 25, 683.
) K. J. Frankowski, R. Z. Liu, G. L. Milligan, K. D.
) H. Ding, P. L.
a
b
c
d
e
,
f
g
h
3
a
b
c
d
4
5
(
a
b
4
c
(a
(b
1
c
2
015, 80, 6250.
6
(a
) C. C. Zeng, N. T. Zhang, C. M. Lam and R. D. Little, Org. Lett., 2012, 14,
1
314; (
b
) N. T. Zhang, C. C. Zeng, C. M. Lam, R. K. Gbur and R. D. Little, J.
) N. N. Lu, N. T. Zhang, C. C. Zeng, L. M. Hu, S.
J. Yoo and R. D. Little, J. Org. Chem., 2015, 80, 781; ( ) N. N. Lu, S. J. Yoo, L.
Org. Chem., 2013, 78, 2104; (
c
d

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J. Li, C. C. Zeng and R. D. Little, Electrochim. Acta., 2014, 142, 254; (
e
) J. Chen,
W. Q. Yan, C. M. Lam, C. C. Zeng, L. M. Hu and R. D. Little, Org. Lett., 2015,
7, 986; ( ) W. J. Gao, W. C. Li, C. C. Zeng, H. Y. Tian, L. M. Hu and R. D.
Little, J. Org. Chem., 2014, 79, 9613; ( ) W. C. Li, C. C. Zeng, L. M. Hu, H. Y.
Tian and R. D. Little, Adv. Synth. Catal., 2013, 355, 2884; ( ) W. C. Li, Z. Z.
Zhang, C. C. Zeng, L. M. Hu and H. Y. Tian, Curr. Org. Synth., 2014, 11, 454;
) Z. Z. Zhang, N. T. Zhang, L. M. Hu, Z. Q. Wei, C. C. Zeng, R. G. Zhong and
Y. B. She, RSC Adv., 2011, 1, 1383.
) G. D. Allen, M. C. Buzzeo, C. Villagrán, C. Hardacre and R. G. Compton, J.
Electroanal. Chem., 2005, 575, 311; ( ) I. Damljanovic, D. Stevanovic, M.
1
f
g
h
(i
7
(a
b
Vukicevic and R. D. Vukicevic, Carbohydrate Res., 2011, 346, 2683.
8
9
T. Matsuki, N. X. Hu, Y. Aso, T. Otsubo and F. Ogura, Bull. Chem. Soc. Jpn.,
1
988, 61, 2117.
It is really very terrible when toxic H
2
S is formed. Therefore, when scaling up,
we can try to use thiocyanate such as NH SCN, KSCN and NaSCN, instead of
4
carbamodithioate anion for the thiocyanation.

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Table of contents entry
NH2 source, SCN source
NH Br (50 mol%), CH CN
Undivided cell, 5 mA/cm
4
3
2
NH2
O
O
O
R1
R2
R1
R2
O
O
via
SCN
7 examples
up to 89% yield
R1
R2
1
X
An efficient paired electrosynthesis involving CꢀH functionalization and subsequent
CꢀS and CꢀN bond formation for the assembly of valuable
ꢀaminoꢀ2ꢀthiocyanatoꢀα,βꢀunsaturated carbonyl derivatives has been developed.
3

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Electrochemical CꢀH functionalization and subsequent CꢀS and CꢀN bond
formation: Paired electrosynthesis of 3ꢀaminoꢀ2ꢀthiocyanato α,βꢀunsaturated
carbonyl derivatives mediated by bromide ion
a
a
b
a
b
LiꢀShuo Kang, MiꢀHai Luo, Chiu Marco Lam, LiꢀMing Hu, R. Daniel Little
*, a, c
and ChengꢀChu Zeng
a
College of Life Science & Bioengineering, Beijing University of Technology,
Beijing 100124, P. R. China, Eꢀmail: zengcc@bjut.edu.cn
b
Department of Chemistry & Biochemistry, University of California, Santa Barbara,
Santa Barbara 93106ꢀ9510, CA
c
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing
Technology and Business University, Beijing 100048, China
Table of contents for the supporting information
1
2
. Experimental ......................................................................................................... 2
. Spectroscopic Data................................................................................................ 3
References................................................................................................................. 8
. Spectroscopy......................................................................................................... 9
3

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1
1
. Experimental
.1 Instruments and reagents
All melting points are uncorrected. IR spectra were recorded as KBr pellets. All
the material 1aꢀ1n and solvents were commercially available and used without
further purification.
1
3
.2 Typical procedure for the synthesis of 3ꢀaminoꢀ2ꢀthiocyanatoꢀ2ꢀbutenoate
by constant current electrolysis.
A 50 mL beakerꢀtype cell was equipped with a Pt anode and a Pt plate
cathode and connected to a DC regulated power supply. To the cell was added ethyl
acetoacetate 1 (1 mmol), amine 2 (1.5 mmol) and NH Br (50 mol%) dissolved in 15
CN. The mixture was electrolyzed using constant current conditions (~5
4
mL of CH
3
2
o
mA/cm ) at 40 C while stirring. The electrolysis was terminated when the starting
material 1 was consumed as determined by TLC. After the electrolysis, the solvent
was removed under reduced pressure and extraction was carried out using ethyl
acetate (3×15 mL); the combined organic layers were washed with a saturated
2 3 4
aqueous Na CO solution, and dried over MgSO . Purified product was obtained after
column chromatography on silica gel using a solvent mixture of petroleum ether and
ethyl acetate.
1
.3 Cyclic voltammetry experiments
Cyclic voltammograms were recorded at room temperature using a Princeton
Applied Research Model 273A Potentiostat/Galvanostat equipped with
electrochemical analysis software and a conventional threeꢀelectrode cell. A glassy
carbon (GC) disk electrode (ca.
used as the working electrode and a Pt wire as the counter electrode. Ag/AgNO
M in CH CN) was used as a reference electrode. All electrodes for CV experiments
were purchased from CH Instruments, Inc. USA.
φ
= 3 mm) or a Pt disk electrode (ca.
φ
= 1 mm) was
3
(0.1
3
The working electrodes were carefully polished on a polishing pad before each
experiment using a fine mesh alumina slurry, and then ultrasonically rinsed with

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acetone. All solutions were degassed by sparging dry nitrogen through the solution for
0 min prior to conducting each electrochemical experiment; a nitrogen atmosphere
1
was maintained throughout. In each measurement, the three electrodes were fixed in
place, and were not allowed to be disturbed in any manner.
2
. Spectroscopic Data
1
(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀbutꢀ2ꢀenoic acid ethyl ester (3a)
NH2
O
O
SCN
o
1
White solid; m.p. 111 ꢀ 113 C; H NMR (400 MHz, CDCl
3
): δ 1.37 (t, J = 7.2 Hz,
1
3
3
H), 2.42 (s, 3H), 4.25 (q, J = 7.2 Hz, 2H), 5.56 (s, 1H), 9.32 (s, 1H); C NMR (100
ꢀ1
3
MHz, CDCl ): δ 14.4, 23.2, 60.75, 75.5, 113.7, 168.4, 168.6; IR (KBr) (cm ): υ 3417,
2
986, 2142, 1622, 1269; HRMS calcd for C
7
H
9
N
2
O
2
S: 185.0385, found: 185.0355.
2
(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀbutꢀ2ꢀenoic acid methyl ester (3b)
NH2
O
O
SCN
o
1
White solid; m.p. 90 ꢀ 93 C; H NMR (400 MHz, CDCl
3
): δ 2.43 (s, 3H), 3.81 (s,
H), 5.60 (s, 1H), 9.31 (s, 1H); C NMR (100 MHz, CDCl ): δ 23.4, 52.0, 76.0,
13.3, 128.8, 168.5, 168.8; IR (KBr) (cm ): υ 3427, 3329, 2950, 2146, 1633, 1276;
HRMS calcd for C S: 173.0385, found: 173.0381.
13
3
3
ꢀ1
1
6
9 2 2
H N O
3
(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀbutꢀ2ꢀenoic acid tertꢀbutyl ester (3c)

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NH2
O
O
SCN
o
1
Pale yellow solid; m.p. 82 ꢀ 84 C; H NMR (400 MHz, CDCl
3
): δ 1.56 (s, 9H), 2.37
13
(
s, 3H), 5.42 (s, 1H), 9.25 (s, 1H); C NMR (100 MHz, CDCl ): δ 23.5, 28.3, 81.2,
3
ꢀ1
1
13.6, 167.3, 168.0; IR (KBr) (cm ): υ 3292, 3101, 1597, 1527, 1430; HRMS calcd
for C
9
H
15
2 2
N O S: 215.0854, found: 215.0847.
1
(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀhexꢀ2ꢀenoic acid ethyl ester (3d)
NH2
O
O
SCN
o
1
Pale yellow solid; m.p. 121 ꢀ 123 C; H NMR (400 MHz, CDCl
3
): δ 1.07 (t, J = 7.6
Hz, 3H), 1.38 (t, J = 6.8 Hz, 3H), 1.69ꢀ1.78 (m, 2H), 2.68ꢀ2.71 (m, 2H), 4.26 (q, J =
1
3
6
2
1
.8 Hz, 2H), 5.54 (s, 1H), 9.41 (s, 1H); C NMR (100 MHz, CDCl
3
): δ 13.7, 14.4,
1.3, 38.1, 60.8, 75.7, 113.7, 168.7, 171.8; IR (KBr) (cm ): υ 3410, 3295, 2965, 2146,
621, 1266; HRMS calcd for C S: 213.0698, found: 213.0707.
ꢀ1
9
13 2 2
H N O
(E)ꢀ3ꢀAminoꢀ4ꢀmethylꢀ2ꢀthiocyanatoꢀpentꢀ2ꢀenoic acid ethyl ester (3e)
NH2
O
O
SCN
1
Brown oil; liquid; H NMR (400 MHz, CDCl
3
): δ 1.23 (d, J = 6.8 Hz, 6H), 1.35 (t, J
=
6.8 Hz, 3H), 3.64ꢀ3.71 (m, 1H), 4.24 (q, J = 7.2 Hz, 2H), 5.73 (s, 1H), 9.55 (s, 1H);
1
3
C NMR (100 MHz, CDCl
3
): δ 14.4, 20.3, 32.5, 60.8, 74.3, 113.9, 168.4, 176.5; IR
KBr) (cm ): υ 3424, 2982, 2143, 1668, 1612, 1161; HRMS calcd for C S:
13.0698, found: 213.0707.
ꢀ1
(
9 13 2 2
H N O
2

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(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀbutꢀ2ꢀenoic acid diethylamide (3g)
NH2
O
N
SCN
o
1
3
Pale yellow solid; m.p. 135 ꢀ 136 C; H NMR (400 MHz, CDCl ): δ 1.19 (t, J = 6.8
13
Hz, 6H), 2.23 (s, 3H), 3.47 (q, J = 7.2 Hz, 4H), 5.34 (s, 2H); C NMR (100 MHz,
ꢀ1
CDCl
3
): δ 13.6, 16.3, 41.6, 113.6, 148.7, 163.8, 167.2; IR (KBr) (cm ): υ 3293, 3144,
2
149, 1592, 1272; HRMS calcd for C H N OS: 214.1014, found: 214.1010.
9 16 3
(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀbutꢀ2ꢀenoic acid pꢀtolylamide (3h)
NH2
O
N
H
SCN
o
1
Pale yellow solid; m.p. 123 ꢀ 125 C; H NMR (400 MHz, CDCl
3
): δ 2.35 (s, 3H),
2
1
1
8
.44 (s, 3H), 5.60 (s, 1H), 7.17 (d, J = 8.0 Hz, 2H), 7.39 (d, J = 8.4 Hz, 2H), 8.25 (s,
13
3
H), 10.15 (s, 1H); C NMR (100 MHz, CDCl ): δ 20.9, 24.0, 75.4, 111.7, 121.1,
ꢀ1
29.5, 134.1, 135.1, 166.8, 167.8; IR (KBr) (cm ): υ 3330, 2156, 1592, 1503, 1231,
03; HRMS calcd for C12 OS: 248.0858, found: 248.0853.
14 3
H N
(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀbutꢀ2ꢀenoic acid phenylamide (3i)
NH2
O
N
H
SCN
o
1
Pale yellow solid; m.p. 139 ꢀ 140 C; H NMR (400 MHz, CDCl
3
): δ 2.46 (s, 3H),
5
8
1
.61 (s, 1H), 7.15 (t, J = 7.2 Hz, 1H), 7.35ꢀ7.39 (m, 2H), 7.52 (d, J = 7.6 Hz, 2H),
1
3
.32 (s, 1H), 10.17 (s, 1H); C NMR (100 MHz, CDCl
3
): δ 24.0, 75.4, 111.7, 120.9,
ꢀ1
24.4, 129.0, 137.8, 166.9, 168.0; IR (KBr) (cm ): υ 3387, 3335, 2152, 1529, 1230,

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7
51; HRMS calcd for C11
H
12
N
3
OS: 234.0701, found: 234.0695.
3
(E)ꢀ4ꢀAminoꢀ3ꢀthiocyanatoꢀpentꢀ3ꢀenꢀ2ꢀone (3j)
NH2
O
SCN
o
1
Pale yellow solid; m.p. 122 ꢀ 123 C; H NMR (400 MHz, CDCl
3
): δ 2.43 (s, 3H),
.51 (s, 3H), 5.98 (s, 1H), 10.97 (s, 1H); C NMR (100 MHz, CDCl ): δ 24.0, 29.0,
7.0, 113.0, 169.5, 198.1; IR (KBr) (cm ): υ 3419, 2978, 2150, 1612, 1255; HRMS
OS: 155.0279, found: 155.0289.
1
3
2
8
3
ꢀ
1
6 7 2
calcd for C H N
4
(E)ꢀ3ꢀAminoꢀ2ꢀthiocyanatoꢀcyclohexꢀ2ꢀenone (3k)
NH2
SCN
O
o
1
6
Deep green solid; m.p. 96 ꢀ 100 C; H NMR (400 MHz, DMSOꢀd ): δ 1.78ꢀ1.84 (m,
1
3
2
H), 2.31 (t, J = 6.4 Hz, 2H), 2.61 (t, J = 6.0 Hz, 2H), 7.79 (s, 1H), 8.19 (s, 1H); C
NMR (100 MHz, DMSOꢀd
6
): δ 20.6, 30.3, 37.2, 86.7, 112.9, 171.6, 190.3; IR (KBr)
OS :
ꢀ1
(
cm ): υ 3396, 3311, 3193, 2148, 1615, 1522, 1297; HRMS calcd for C
7 7 2
H N
1
67.0279, found: 167.0285.
4
(E)ꢀ3ꢀAminoꢀ5,5ꢀdimethylꢀ2ꢀthiocyanatoꢀcyclohexꢀ2ꢀenone (3l)
NH2
SCN
O
o
1
Pale yellow solid; m.p. 149 ꢀ 151 C; H NMR (400 MHz, CDCl
3
): δ 1.11 (s, 6H),
13
2
.41 (s, 2H), 2.52 (s, 2H), 5.47 (s, 1H), 6.08 (s, 1H); C NMR (100 MHz, DMSOꢀd ):
6

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ꢀ1
δ 27.8, 31.8, 43.4, 50.6, 85.4, 112.9, 170.0, 189.8; IR (KBr) (cm ): υ 3392, 3311,
3
1
182, 2964, 2145, 1622, 1527, 1318; HRMS calcd for C H N OS: 195.0592, found:
9 11 2
95.0600.
(E)ꢀ3ꢀAminoꢀ1ꢀphenylꢀ2ꢀthiocyanatoꢀbutꢀ2ꢀenꢀ1ꢀone (3m)
NH2
O
SCN
o
1
Pale yellow solid; m.p. 141 ꢀ 144 C; H NMR (400 MHz, CDCl
.29 (s, 1H), 7.45ꢀ7.47 (m, 3H), 7.52ꢀ7.54 (m, 2H), 11.22 (s, 1H); C NMR (100
MHz, CDCl ): δ 24.4, 86.7, 113.6, 126.8, 128.1, 129.9, 141.0, 171.9, 196.3; IR (KBr)
3
): δ 2.54 (s, 3H),
13
6
3
ꢀ1
(
cm ): υ 782, 729, 699, 658, 540; HRMS calcd for C11
9 2
H N OS: 217.0436, found:
2
17.0444.
(E)ꢀethylꢀ3ꢀ(benzylamino)ꢀ2ꢀthiocyanatobutꢀ2ꢀenoate (3o)
NH
O
O
SCN
1
Pale yellow oil; liquid; H NMR (400 MHz, CDCl
3
): δ 1.35 (t, J = 7.2 Hz, 3H), 2.44
(s, 3H), 4.22 (q, J = 7.2 Hz, 2H), 4.53 (d, J = 5.6 Hz, 2H), 7.25ꢀ7.40 (m, 5H), 10.57 (s,
1
3
1
H); C NMR (100 MHz, CDCl
29.1, 136.6, 169.3, 169.5; IR (KBr) (cm ): υ 2981, 2147, 1575, 1455, 1235, 1069;
S: 275.0854, found: 275.0792.
3
): δ 14.4, 17.9, 48.4, 60.7, 74.8, 113.8, 126.9, 128.0,
ꢀ1
1
15 2 2
HRMS calcd for C14H N O
(E)ꢀethyl 3ꢀ(4ꢀmethoxybenzylamino)ꢀ2ꢀthiocyanatobutꢀ2ꢀenoate (3p)

Green Chemistry
Page 24 of 53
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DOI: 10.1039/C6GC00666C
OCH
3
NH
O
O
SCN
o
1
White solid; m.p. 64 ꢀ 66 C; H NMR (400 MHz, CDCl
3
): δ 1.36 (t, J = 7.2 Hz, 3H),
2
.47 (s, 3H), 3.83 (s, 3H), 4.22 (q, J = 7.2 Hz, 2H), 4.47 (d, J = 5.6 Hz, 2H), 6.92 (d, J
13
=
3
8.4 Hz, 2H), 7.20 (d, J = 8.4 Hz, 2H),10.48 (s, 1H); C NMR (100 MHz, CDCl ): δ
1
4.4, 17.9, 48.0, 55.3, 60.7, 74.6, 113.9, 114.5, 128.4, 128.4, 159.4, 169.3, 169.3. IR
ꢀ1
(
KBr) (cm ): υ 3447, 2148, 1635, 1576, 1516, 1252; HRMS calcd for C15
17 2 3
H N O S:
3
05.0960, found: 305.0965.
5
Ethyl 2ꢀaminoꢀ4ꢀmethylthiazoleꢀ5ꢀcarboxylate (4a)
N
O
H N
2
S
O
o
1
3
White solid; m.p. 173 ꢀ 175 C; H NMR (400 MHz, CDCl ): δ 1.35 (t, J = 7.2 Hz,
13
3
H), 2.55 (s, 3H), 4.28 (q, J = 7.2 Hz, 2H), 5.39 (s, 2H); C NMR (100 MHz,
CDCl ): δ 14.4, 17.2, 60.6, 111.5, 160.0, 162.5, 169.2.
3
References
[
[
[
[
[
1] Y. S. Park and K. Kim, Tetrahedron Lett., 1999, 40, 6439.
2] J. M. Chen and X. Huang, Synlett., 2004, 3, 552.
3] Chandler, C. Sci. Synth., 2008, 32, 385.
4] M. V. Stasevych, Heteroat Chem., 2005, 16, 205.
5] N. Azizi, Comptes Rendus Chimie, 2015, 18, 626.

Page 25 of 53
Green Chemistry
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DOI: 10.1039/C6GC00666C
3
. Spectroscopy
NH2
O
O
SCN
(3a)

Green Chemistry
Page 26 of 53
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DOI: 10.1039/C6GC00666C
4
000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm-1

Page 27 of 53
Green Chemistry
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DOI: 10.1039/C6GC00666C
NH2
O
O
SCN
(
3b)

Green Chemistry
Page 28 of 53
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DOI: 10.1039/C6GC00666C
4
000
3500
3000
2500
2000
1500
1000
500
Wavenumber cm-1
Intens. 4.
x104
+MS, 5.4-6.4min #(318-381), -Peak Bkgrnd
173.0381
3
2
1
0
146.0274
100
200
300
400
500
600
700
m/z

Page 29 of 53
Green Chemistry
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DOI: 10.1039/C6GC00666C
NH2
O
O
SCN
(
3c)