Oxidative Coupling-Thionation of Amines Mediated by Iron-Based Imidazolium Salts for the Preparation of Thioamides

Article abstract of DOI:10.1055/s-0037-1610179

An efficient and selective multicomponent oxidative coupling, involving the use of two different amines, sodium phosphate, and elemental sulfur have been described for the preparation of thioamides, employing microwave irradiation. The use of an iron(III)-based imidazolium salt is essential as catalyst. Indeed, the iron-based catalyst is involved in the oxidative coupling of the two amines and in the subsequent C-S bond formation. The protocol is useful for a wide variety of primary benzylamines and alkylamines, as coupling partners. Thus, various electron-rich and electron-poor substituents in the aromatic rings and also fused piperidine derivatives, are suitable starting materials in this reaction. Some of the obtained products are important synthetic intermediates for natural products.

Full text of DOI:10.1055/s-0037-1610179

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–J
paper
A
en
P. Gisbert, I. M. Pastor
Paper
Synthesis
Oxidative Coupling–Thionation of Amines Mediated by Iron-
Based Imidazolium Salts for the Preparation of Thioamides
Patricia Gisbert
Isidro M. Pastor*
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Organic Chemistry Department and Instituto de Síntesis
Orgánica (ISO), University of Alicante, Apdo. 99, 03080
Alicante, Spain
ipastor@ua.es
Received: 25.04.2018
Accepted: 11.05.2018
Published online: 02.07.2018
are the thioacylation of amines and the thionation of am-
ides using sulfur reagents, such as P4S10 or Lawesson’s re-
9
agent.10 However, O/S exchange with these sulfur reagents
cannot be classified as an atom economy approach. In this
sense, in 1923 Kindler reported a multicomponent reaction
of a carbonyl compound, an amine, and elemental sulfur
[Scheme 1 (a)], representing a transformation with good
atom economy evaluation.11 More recently in 2012, Nguyen
and co-workers described a three-component reaction in-
volving sulfur and amines to give the corresponding thio-
amides following the general reaction depicted in Scheme 1
(b).12 However, both procedures have two main limitations,
the need for high temperatures and long reaction times. In
order to reduce the reaction time, we considered the use of
microwave heating as a useful approach.13 In this sense, to
the best of our knowledge, there are only two reported pro-
tocols for the preparation of thioamides using elemental
sulfur in which microwave irradiation is employed. The re-
ported procedure by the Keglevich group allowed only the
thionation of the benzylic position starting from the corre-
sponding benzylamines.14 On the other hand, Kappe and
DOI: 10.1055/s-0037-1610179; Art ID: ss-2018-z0288-op
Abstract An efficient and selective multicomponent oxidative cou-
pling, involving the use of two different amines, sodium phosphate,
and elemental sulfur have been described for the preparation of thio-
amides, employing microwave irradiation. The use of an iron(III)-based
imidazolium salt is essential as catalyst. Indeed, the iron-based catalyst
is involved in the oxidative coupling of the two amines and in the subse-
quent C–S bond formation. The protocol is useful for a wide variety of
primary benzylamines and alkylamines, as coupling partners. Thus, var-
ious electron-rich and electron-poor substituents in the aromatic rings
and also fused piperidine derivatives, are suitable starting materials in
this reaction. Some of the obtained products are important synthetic
intermediates for natural products.
Key words imidazolium salt, ionic liquid, iron(III) catalyst, sulfur, thio-
amides
Compounds bearing thioamide moieties constitute one
of the most attractive families of sulfur-containing mole-
cules.1 They are notably valuable building blocks for the
preparation of biologically active compounds (e.g., duloxe-
tine),2 including bioactive heterocycles3 and natural prod-
ucts, such as caprazamycin B.4 The thioamide moiety is oc-
casional present in natural products, albeit most of these
thioamide-containing compounds present interesting bio-
activity.5 Moreover, different bioactive oxoamides have
been converted into the corresponding thioamides for
structure-activity relationship studies and biological activi-
ty assessment, as thioamide-containing proteins of special
interest.6
S
Ar
R2
(a)
N
R3
[R1 = Me]
O
170–180 °C
S8
+ R2R3NH
Ar
R1
S
R2
Ar
R
N
R3
[R1 = H]
(b)
There are several approaches, in the literature, to the
synthesis of compounds containing the thioamide moiety,7
including protocols to prepare thioamides using different
sulfur reagents in the presence of aerobic oxidation.8
Among them, the most frequently employed methodologies
S
110–130 °C
S8, 20–60 h
Ar
NH2
+ RNH2
Ar
N
H
Scheme 1 (a) The Kindler reaction and (b) the amine oxidative cou-
pling-thionation reaction
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

B
P. Gisbert, I. M. Pastor
Paper
Synthesis
co-workers described the coupling between aldehydes and
amines to form the corresponding thioamides in the pres-
ence of sulfur.15
tion employing an IBLAIL as a potential efficient catalytic
system. Herein, we are pleased to report our findings in a
new synthetic approach to thioamides via imine-mediated
selective thionation using microwave irradiation under aer-
obic conditions.
Aware of the importance of finding sustainable process-
es, we consider of special significance the search for sus-
tainable catalytic systems, both heterogeneous and homo-
geneous, which allow their profitability with the least im-
pact on the environment. In this context, we have focused
our attention on the use of functionalized imidazoles as
versatile components for catalytic systems in combination
with different metals. Indeed, we have employed acyl-func-
tionalized imidazole derivatives as precursors for N-hetero-
cyclic carbene (NHC) ligands for palladium.16 Furthermore,
we have also described the use of 1,3-bis(carboxymeth-
yl)imidazole (bcmim) as a ligand in the preparation of met-
al-organic frameworks (MOFs), which have been employed
as effective heterogeneous catalysts. Indeed, the obtained
material in combination with copper (Cu-bcmim) has effi-
ciently catalyzed the oxidative coupling between carboxylic
acids and formamides.17 Moreover, the barium- and calci-
um-organic frameworks (Ba-bcmim and Ca-bcmim) have
been revealed as a variety of complementary catalysts for
the Friedländer reaction.18
As a part of this research, we have used acyl-imidazoli-
um derivatives for the preparation of iron(III)-based Lewis
acidic ionic liquids (IBLAILs, Figure 1), which have been em-
ployed as catalysts in the selective preparation of quino-
lines, 2-allylanilines, and 4-allylanilines by modulating the
reaction conditions.19 This type of metal ion containing ion-
ic liquid20 is easily prepared, and it offers an environmen-
tally friendly catalytic system. Moreover, iron in combina-
tion with sulfur is able to form iron–sulfur clusters21 that
are responsible for a variety of chemical transformations
due to their ubiquity in living systems and they are also re-
sponsible for a wide range of chemical transformations as
fundamentals in life processes. Consequently, we postulat-
ed a sustainable amine oxidative coupling-thionation reac-
Initial efforts were focused on the optimization of the
reaction conditions using benzylamine (1a) and elemental
sulfur as model reactants. Firstly, the reaction was carried
out with 15 mol% of Fe(III)-based Lewis acidic ionic liquid I
(Figure 1) as catalyst at 100 °C under solvent-free condi-
tions, obtaining the desired thioamide 2a in 43% yield (Ta-
ble 1, entry 1). Different substituents in the imidazole moi-
eties can modulate the catalytic activity of the salts due to
the fact that the properties of ionic liquids can be different
depending on the size of the components.22 Moreover, the
presence of a functional group, such as acyl moieties, could
help during the catalytic process.19 Consequently, a variety
of Fe(III)-based Lewis acidic ionic liquids, such as I–VI (Fig-
ure 1), were evaluated as catalysts in the oxidative cou-
pling-thionation reaction of benzylamine (1a). The reac-
tions were performed with 15 mol% of IBLAIL I–VI under
the starting conditions (Table 1, entries 1–6). While cata-
lysts II, IV, V, and VI provided lower yields (Table 1, entries
2 and 4–6), catalysts I and III proved to be superior at this
temperature (Table 1, entries 1 and 3). In an attempt to im-
prove thioamide formation, we evaluated different bases
(Table 1, entries 8–10), but did not observe any significant
improvement. In addition, the absence of a base resulted in
poor conversion to the final product (Table 1, entry 7),
proving the need for a base. Next, we studied the effect of
the temperature in the range 60–100 °C. The reaction car-
ried out at 100 °C gave the best conversion to the coupling-
thionation product, lower conversion to the desired prod-
uct was observed at lower temperatures (Table 1, entries 11
and 12). We also proved that the catalyst was active when
the reaction was performed using conventional heating
(100 °C, Table 1, entry 13), although the product was ob-
tained with lower yield. The product was observed in a
much reduced yield when the reaction was carried out in
the absence of catalyst, compared to our optimal conditions
(Table 1, cf. entries 3 and 14). Thus, the iron(III) catalyst is
important for the reaction, as the combination of a strong
base and sulfur is insufficient.23 Furthermore, different sol-
vents, such as toluene, 1,4-dioxane, or 1,2-dichloroethane,
were evaluated, providing, in all the cases, lower yields than
under ‘neat’ reaction conditions.
OEt
OMe
FeCl4
Me
FeCl4
Me
N
N
N
N
N
O
O
O
I
II
Me
OMe
OEt
FeCl4
Me
FeCl4
Me
N
O
N
N
Next, we turned our attention to the amounts of base
and sulfur. Thus, different quantities (i.e., 0.5, 1, and 1.5
mmol) of sodium phosphate (Na3PO4) and elemental sulfur
were employed, and the results are depicted in the graph in
Figure 2. Interestingly, a relationship could be observed be-
tween the amount of sodium phosphate and elemental sul-
fur. Indeed, there is a dependence of the conversion on the
amount of both reagents used (Figure 2). However, the pro-
III
IV
OMe
N
FeCl4
FeCl4
Me
N
N
N
N
O
O
V
VI
Figure 1 Iron(III)-based Lewis acidic ionic liquids (IBLAILs)
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

C
P. Gisbert, I. M. Pastor
Paper
Synthesis
Table 1 Optimization of the Reaction Conditionsa
S
IBLAIL (15 mol%)
NH2
S8
+
N
neat
H
T (°C), base
1a
2a
Entry
IBLAIL
Base
T (°C)
Yieldb (%)
1
2
I
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
no base
Na2CO3
Et3N
100
100
100
100
100
100
100
100
100
100
60
43
30
49
34
39
39
6
II
3
III
IV
V
Figure 2 Correlation between the amount of sodium phosphate and
elemental sulfur. (●) for 0.5 mmol S8, (♦) for 1 mmol S8 and (■) for 1.5
mmol S8. Reagents and conditions: benzylamine (1a; 1 mmol), Na3PO4
(x mmol), S8 (y mmol), catalyst (15 mol% metal based on ICP analysis),
100 °C, microwave heating (80 W), 60 min.
4
5
6
VI
III
III
III
III
III
III
III
7
8
37
39
30
25
28
34
21
bearing electron-donating and electron-withdrawing
groups were subjected to this procedure and generated the
corresponding products from moderate to good yields (2b,
2d, 2e, 2h, 2i). In this context, the greater the withdrawing
ability of the group, the poorest the yield of the final prod-
uct (Scheme 2). However, the presence of two methoxy
groups in the benzylamine (i.e., 3,4-dimethoxybenzyl-
amine) resulted in the formation of the corresponding
product in poor yield (<20%), under these conditions. The
presence of two methoxy groups aromatic amines has pre-
viously shown lower activity, in other transformations, in
the presence of IBLAILs.19 Interestingly, 1-phenylethyl-
amine (1f) was also employed, leading to the formation of
the 2-phenylthioacetamide 2f in moderate 40% yield. In this
case, the transformation involves a Willgerodt rearrange-
ment (see Supporting Information).24 In a similar manner,
phenethylamine produced the thioamide 2c in moderate
30% yield.
To broaden the scope to other amines, we carried out
the reaction under the same conditions employing second-
ary and tertiary amines. The reaction of N-methylbenzyl-
amine (1g) with sulfur (3 mmol) yielded a mixture of N-
methylbenzothioamide (3) and N-benzyl-N-methylben-
zothioamide (2g) in 1:1 ratio (Scheme 3). Then, we decided
to modulate the reaction conditions in order to increase the
selectivity of the process. First, the reaction was tested at
different temperatures (80 and 120 °C) without any change
in selectivity. Aware of the influence of the sulfur amount
in the outcome of the reaction, as we observed above, we
conducted different experiments modulating the amount of
sulfur in the model reaction. Interestingly, only product 2g
was isolated in 63% yield when the reaction was performed
with a smaller amount of sulfur (Schemes 2 and 3). On the
contrary, increasing the amount of sulfur in the reaction
produced exclusively the thionation compound 3, which
was isolated in 87% yield (Schemes 3 and 4). Moreover, with
tertiary amines, such as N,N-dimethylbenzylamine, we did
9
10
11
12
13c
14
K3PO4
Na3PO4
Na3PO4
Na3PO4
Na3PO4
80
100
100
no catalyst
a Reaction conditions: 1a (1 mmol), S8 (0.5 mmol), base (0.5 mmol), cata-
lyst (15 mol%), microwave heating (80 W), 1 h.
b Yield determined by GC using 4,4′-di-tert-butylbiphenyl (DTBB) as inter-
nal standard.
c Conventional heating (24 h) using an oil bath was employed.
file obtained for the three distributions is dissimilar. Differ-
ent conclusions can be drawn from this study: (i) small
amounts of base and elemental sulfur do not show interac-
tion (Figure 2); (ii) up to a certain amount of base (0.5
mmol), the amount of sulfur is key, with 1.5 mmol of sulfur
the optimum (Figure 2); (iii) a minor decrease in yield oc-
curs when the number of equivalents of base is greater than
the optimum value (Figure 2). Gratifyingly, 89% conversion
to the desired product 2a was observed when the reaction
was performed employing the optimal amount of base
(Na3PO4, 0.5 mmol) and sulfur (1.5 mmol) at 100 °C for 1 h
under solvent-free conditions, using IBLAIL III (15 mol%) as
catalyst (Figure 2). At this point, we performed a reaction
employing FeCl3 as catalyst instead of the IBLAIL III, giving
only 35% conversion to the desired product. This experi-
ment proved that not only iron(III) is important in the re-
sult of the reaction, but also the structure of the functional-
ized imidazolium ion.
With the optimized reaction conditions for the thion-
ation-coupling of benzamines in hand, we examined the
scope of the present reaction with different benzamines 1
(Scheme 2). As mentioned before, benzylamine (1a) was
transformed into the corresponding thioamide (89% con-
version) with excellent isolated yield (87%). Aromatic rings
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

D
P. Gisbert, I. M. Pastor
Paper
Synthesis
R1
R1
S
III (15 mol%)
S8
Na3PO4
+
+
R
Ar
N
R
100 °C, MW
neat, 60 min
S
S
Ar
N
H
III (15 mol%)
H
S8 (3 mmol)
N
H
N
N
1
2
H
+
Na3PO4
100 °C, MW
neat, 60 min
S
S
1g
2g
3
[90% conv; 1:1 ratio]
N
N
H
H
III (15 mol%)
Na3PO4
MeO
OMe
100 °C, MW
neat, 60 min
2a (87%)
2b (85%)
S
S
S
N
S8
(2 mmol)
N
H
N
H
2g (63%)
2d (71%)
2c (30%)
S
S
N
H
S
S8
(4 mmol)
N
H
N
H
3 (87%)
Scheme 3 Coupling-thionation and/or thionation reactions by sulfur
amount modulation. Reagents and conditions: amine 1 (2 mmol), S8 (2,
3, or 4 mmol), Na3PO4 (1 mmol), III (15 mol%), microwave heating (80
W). In parentheses: isolated yield after flash chromatography or prepar-
ative TLC.
2e (50%)
2f (40%)
S
S
N
N
H
Cl
Cl
S
2g (63%)
2h (72%)
III (15 mol%)
NH
S8
Na3PO4
NH
R
+
+
S
100 °C, MW
neat, 60 min
R
N
H
1
2a, 3, 4
S
F
F
S
S
2i (53%)
N
H
NH
N
H
Scheme 2 Scope evaluation of homocoupling-thionation reaction. Re-
agents and conditions: 1 (2 mmol), S8 (3 mmol), Na3PO4 (1 mmol), III (15
mol%), microwave heating (80 W). In parentheses: isolated yield after
flash chromatography or preparative TLC.
2a (77%)
3 (87%)
4 (52%)
Scheme 4 Thionation of benzylic position. Reaction conditions: amine
(2 mmol), S8 (4 mmol), Na3PO4 (1 mmol), III (15 mol%), microwave
heating (80 W). In parentheses: isolated yield after flash chromatogra-
phy.
not observe any product either by thionation or by oxida-
tive coupling-thionation, recovering the starting materials
after the reaction.
the selectivity of our catalytic system in the oxidative cou-
pling-thionation reaction of two amines. To address this
question, we set up a model reaction of N-methylbenzyl-
amine and morpholine in the presence of elemental sulfur
employing the optimal conditions for the homocoupling-
We next attempted the thionation at the benzylic posi-
tion of different arylmethylamine derivatives, such as N-
methylbenzylamine, dibenzylamine, and the fused piperi-
dine derivative 1,2,3,4-tetrahydroisoquinoline under these
conditions [amine (2 mmol), S8 (4 mmol), Na3PO4 (1 mmol),
III (15 mol%)]. As expected, compounds 2a, 3, and 4 were
exclusively obtained (Scheme 4) without any byproduct
carrying out the thionation reaction with elemental sulfur.
This is in sharp contrast with previously reported protocols
in the literature, which produced a mixture of different sul-
fur-containing compounds.14
S
S
R1
NH2
S8
R1
N
H
R1
R2
N
H
R1
reaction
conditions
S
S
H2N
R2
R1
N
H
R2
R2
N
H
R2
The oxidative coupling of two different amines using el-
emental sulfur can afford, in principle, four possible thio-
amides (Figure 3). For this reason, we decided to explore
Figure 3 Oxidative coupling-thionation of two amines
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

E
P. Gisbert, I. M. Pastor
Paper
Synthesis
thionation. Firstly, we decided to use an equimolar mixture
of the two amines, and the heterocoupling-thionation
product was obtained in 26% conversion, with the rest of
the N-methylbenzylamine transformed into the homocou-
pling-thionation product 2g. Next, we decided to add an ad-
ditional quantity of morpholine (1.3 equiv) in order to favor
the conversion into the expected cross-coupled product 2j,
which was obtained with 67% conversion. Increasing the re-
action time to 90 minutes resulted in comparable conver-
sion (61%). Augmenting the amount of base (up to 2 equiv)
resulted in an improvement in the formation of the expect-
ed thioamide, giving compound 2j with a conversion of
80%. The product 2j was easily isolated in 73% yield (Table 2,
entry 1) from the reaction mixture. In subsequent studies,
we applied these reaction conditions [benzylamine (1
mmol), amine (1.3 mmol), S8 (3 mmol), Na3PO4 (1 or 2
mmol), III (15 mol%)] to investigate the generality of this
procedure and demonstrate the applicability of the syn-
thetic method (Table 2). In all the tested cases, the corre-
sponding heterocoupled thioamides 2 were obtained in
moderate to good yields. Indeed, the reaction between mor-
pholine and 4-chlorobenzylamine gave the corresponding
thioamide 2k in 73% yield. Likewise, another secondary
amine, pyrrolidine, coupled with N-methylbenzylamine to
give the thioamide 2l (Table 2). Simple aliphatic primary
amines, such as octylamine, also gave selective coupling
with benzylamine and 4-methoxybenzylamine to give the
corresponding thioamides 2m and 2n in good yields (82%
and 76%, respectively, Table 2). Moreover, phenethylamine
was reacted with N-methylbenzylamine yielding product
2c in 61%; a better result than that obtained for the homo-
coupling thionation of phenethylamine (Scheme 2). Other
functionalized benzylamines with electron-donating and
electron-withdrawing groups were coupled with
phenethylamine affording the corresponding thioamides
2o, 2p, and 2q in moderate to good yields (Table 2).
III (15 mol%)
NH2
N
100 °C, MW
neat, 30 min
1a
5 (70%)
Scheme 5 Oxidative coupling of benzylamine. Yield determined by GC
using 4,4′-di-tert-butylbiphenyl (DTBB) as internal standard.
Based on these observations and on similar transforma-
tions previously reported,12a we tentatively proposed a
mechanism for the oxidative coupling-thionation reaction
of two amines as represented in Scheme 6. The first step (a)
of the reaction could be the oxidation of 1 into benzaldi-
mine A, the oxidation is mediated by the iron catalyst as de-
scribed above.19 However, the oxidation can be driven by el-
emental sulfur itself or by iron-sulfur clusters, as discussed
vide supra. Next, imine A could follow two different path-
ways: (i) thionation by elemental sulfur, in which imine A is
transformed directly into thiobenzamides 2a, 3, and 4 (step
b); (ii) reaction of imine A with a second amine molecule to
provide intermediate B (step c), followed by an elimination
(step d) catalyzed by IBLAIL. Finally, imine C reacts with sul-
fur affording the desired thioamide (step e).
S
O2
Ph
N
H
Ph
R
2
Ph
N
H
H2O
a
1
S8
e
S
S8
R
IBLAIL
Ph
N
Ph
Ph
NR
Ph
N
b
H
C
A
2a, 3, 4
d
c
HN
Ph
RNH2
amine 1
R
Ph
N
H
As commented previously, our research group has ob-
served an oxidative step during the preparation of quino-
lines by cyclization of the corresponding 2-allylanilines us-
ing atmospheric oxygen in the presence of IBLAILs.19 Based
on that, we considered that our catalytic system could favor
imine formation via oxidation of the corresponding benzyl-
amine. In order to gain mechanistic insight into the reac-
tion proceeding via imine reaction intermediates, we car-
ried out the reaction of benzylamine in the presence of
IBLAIL III in the absence of elemental sulfur and base. Inter-
estingly, the predicted benzaldimine 5 was formed in 70%
yield after 30 minutes (Scheme 5), proving the importance
of the atmospheric oxygen in the presence of our catalyst
during the oxidation process. Furthermore, we proved that
the expected thioamide 2a was obtained, in 80% yield,
when the imine 5 was treated under the standard reaction
conditions.
B
Scheme 6 Proposed reaction mechanism
To conclude, we have demonstrated the efficacy of our
catalytic system in a simple, but effective, and green syn-
thesis of thioamides under iron-catalyzed aerobic condi-
tions and microwave irradiation. A relevant feature of this
type of iron(III)-based catalytic systems is their easy and
straightforward preparation. The synthesis of thioamines,
in one-pot reaction, involves an oxidative process promoted
by the studied catalytic system in the presence of atmo-
spheric oxygen. The reported protocol allows the prepara-
tion of thioamides in reasonable yields, even starting from
two different amines. The different reactivity of amines was
taken into consideration to minimize the homocoupling
thionation reaction. It is likely that the catalytic activity of
the mixture Fe/imidazolium salt may be applied to other
transformations, whether in the presence of sulfur or not.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

F
P. Gisbert, I. M. Pastor
Paper
Synthesis
Table 2 Scope Evaluation of Coupling-Thionation Reaction of Two Aminesa
III (15 mol%)
S8, Na3PO4
S
R1
R2
R3
R3
+
Ar
N
N
Ar
N
R2
H
H
100 °C, MW
neat, 60 min
2c,j–q
Entry
1c
ArCH2NHR1
R2R3NH
Thioamide
Yield (%)b
S
N
H
HN
2j
73
73
N
O
O
S
N
NH2
HN
HN
2c
3c
4
2k
O
Cl
O
Cl
S
S
N
H
2l
42
82
76
N
NH2
2m
2n
H2N
H2N
N
H
6
6
6
S
NH2
5
N
H
6
MeO
MeO
S
N
H
6
7
8
9
2c
2o
2p
2q
61
61
54
41
N
H
H2N
H2N
S
NH2
N
H
MeO
MeO
S
NH2
N
H
H2N
Cl
Cl
S
NH2
N
H
H2N
F
F
a Reaction conditions: ArCH2NHR1 (1 mmol), R2R3NH (1.3 mmol), S8 (3 mmol), Na3PO4 (1 mmol), III (15 mol%), microwave heating (80 W), 1 h.
b In parentheses: isolated yield of pure product after flash chromatography or preparative TLC.
c Reaction performed with 2 mmol of Na3PO4.
ternal reference: 1H (CHCl3 δ = 7.26) and 13C (CHCl3 δ = 77.16). Chemi-
cal shifts were recorded with TMS as the internal reference standard.
The conversions of the reactions and purity of the products were de-
terminate by GC analysis using a Younglin 6100GC, equipped with a
flame ionization detector and a Phenomenex ZB-5 MS column (5%
PH-ME siloxane): 30 m (length), 0.25 mm (inner diameter), and 0.25
μm.
All reagents and solvents were used as supplied commercially. Ana-
lytical TLC was performed on 0.2 mm coated Science silica gel (EM
60-F254) plates purchased from Merck, Germany. Visualization was
achieved by UV light (254 nm). Flash column chromatography was
performed using silica gel and a gradient solvent system (hex-
1
ane/EtOAc). H and 13C NMR spectra were measured on 300 and 400
MHz spectrometers and the residual solvent peak was used as an in-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

G
P. Gisbert, I. M. Pastor
Paper
Synthesis
Homocoupling–Thionation Reaction in Thioamides Synthesis;
General Procedure A (GPA)
MS (EI): m/z (%) = 287 (M+, 34), 151 (19), 136 (13), 134 (17), 133 (25),
121 (100), 108 (11), 90 (15), 78 (16), 77 (19), 63 (11).
A mixture of amine (2 mmol), elemental sulfur (2, 3, or 4 mmol),
Na3PO4 (1 mmol), and IBLAIL III (15 mol%) was heated under micro-
wave irradiation (initial power 80 W) for 1 h. After completion of the
reaction, the crude mixture was stirred vigorously with CH2Cl2 (5 mL)
and MeOH (1 mL), and then filtered. Other portions of CH2Cl2 could be
used to thoroughly remove all the CH2Cl2 soluble materials from the
solid residue. The solvent was removed under vacuum, and the resi-
due was purified by flash column chromatography (silica gel, hex-
ane/EtOAc or hexane/MTBE).
N-Phenethylbenzothioamide (2c)9
Yellow solid; yield: 72.3 mg (30%, GPA), 147.0 mg (61%, GPB); mp 86
°C (CH2Cl2).
IR (ATR): 3296, 3060, 3028, 1528, 1486, 1451, 1382, 12447, 1181,
1092, 1065, 1010, 941 cm–1
.
1H NMR (300 MHz, CDCl3): δ (mixture of rotamers) = 7.66–7.62 (m, 3
H, NH, 2 CHArCCS), 7.46–7.21 (m, 8 H, 8 CHAr, major), 7.13–6.96 (m, 8
H, 8 CHAr, minor), 4.13–4.07 (m, 2 H, NHCH2CH2CAr, major), 3.85 (q, J =
6.9 Hz, 2 H, NHCH2CH2CAr, minor), 3.09 (t, J = 7.0 Hz, 2 H, NHCH2CH2-
CAr, major), 2.83 (t, J = 6.8 Hz, 2 H, NHCH2CH2CAr, minor).
13C NMR (75 MHz, CDCl3): δ = 199.3, 141.9, 138.3, 131.1, 128.9 (2 C),
128.8 (2 C), 128.5 (2 C), 126.9, 126.7 (2 C), 47.6, 33.9.
Oxidative Coupling–Thionation Reaction of Two Amines; General
Procedure B (GPB)
A mixture of both amines [in ratio 1 mmol (ArCH2NHR1) to 1.3 mmol
(R2R3NH)], elemental sulfur (3 mmol), Na3PO4 (1 mmol; 2 mmol for
2j–l), and IBLAIL III (15 mol%) was heated under microwave irradia-
tion (initial power 80 W) for 1 h. After completion of the reaction, the
crude mixture was stirred vigorously with CH2Cl2 (5 mL) and MeOH
(1 mL), and then filtered. Other portions of CH2Cl2 could be used to
remove thoroughly all the CH2Cl2 soluble materials from the solid res-
idue. The solvent was removed under vacuum, and the residue was
purified by flash column chromatography (silica gel, hexane/EtOAc or
hexane/MTBE).
MS (EI): m/z (%) = 241 (M+, 25), 121 (22), 105 (38), 104 (100), 103
(24), 91 (30), 77 (42), 51 (19).
4-Methyl-N-(4-methylbenzyl)benzothioamide (2d)25
Yellow solid; yield: 181.3 mg (71%, GPA); mp 81 °C (CH2Cl2).
IR (ATR): 3326, 2918, 1605, 1524, 1502, 1412, 1385, 1323, 1261, 1188,
1080, 926 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.66–7.64 (m, 3 H, NH, 2 CHArCCS),
7.27 (m, 2 H, 2 CHAr), 7.29–7.26 (m, 4 H, 4 CHAr), 4.92 (d, J = 4.9 Hz, 2
H, CH2), 2.35 (s, 6 H, 2 CH3).
13C NMR (75 MHz, CDCl3): δ = 198.7, 141.8, 138.9, 138.1, 133.3, 129.8
(2 C), 129.2 (2 C), 128.5 (2 C), 126.8 (2 C), 50.9, 21.4, 21.3.
MS (EI): m/z (%) = 256 (M+ + 1, 19), 255 (M+, 100), 222 (21), 136 (15),
135 (48), 121 (13), 120 (43), 118 (31), 105 (92), 103 (16), 91 (40), 89
(11), 79 (15), 77 (28), 65 (16).
Thionation of Benzylic Position; General Procedure C (GPC)
A mixture of amine (2 mmol), elemental sulfur (4 mmol), Na3PO4 (1
mmol), and IBLAIL III (15 mol%) was heated under microwave irradia-
tion (initial power 80 W) for 1 h. After completion of the reaction, the
crude mixture was stirred vigorously with CH2Cl2 (5 mL) and MeOH
(1 mL), and then filtered. Other portions of CH2Cl2 could be used to
remove thoroughly all the CH2Cl2 soluble materials from the solid res-
idue. The solvent was removed under vacuum, and the residue was
purified by flash chromatography (silica gel column, hexane/EtOAc or
hexane/MTBE).
3-Methyl-N-(3-methylbenzyl)benzothioamide (2e)
Yellow oil; yield: 127.7 mg (50%, GPA).
IR (ATR): 3293, 2980, 2920, 1737, 1521, 1372, 1326, 1242, 1044, 960,
N-Benzylbenzothioamide (2a)9
825, 790 cm–1
.
Yellow solid; yield: 197.8 mg (87%, GPA), 175.0 mg (77%, GPC); mp 83
°C (CH2Cl2).
1H NMR (300 MHz, CDCl3): δ = 7.69 (br s, 1 H, NH), 7.60 (s, 1 H,
CHArCCS), 7.51–7.49 (m, 1 H, CHArCCH2), 7.28–7.17 (m, 6 H, 6 CHAr),
4.93 (d, J = 5.0 Hz, 2 H, CH2), 2.37 (s, 6 H, 2 CH3).
13C NMR (75 MHz, CDCl3): δ = 199.3, 141.8, 138.9, 138.5, 136.2, 132.0,
129.3, 129.1, 129.0, 128.5, 127.8, 125.5, 123.6, 51.2, 21.5, 21.4.
MS (EI): m/z (%) = 256 (M+ + 1, 19), 255 (M+, 100), 222 (21), 136 (15),
135 (48), 121 (13), 120 (43), 118 (31), 105 (92), 103 (16), 91 (40), 89
(11), 79 (15), 77 (28), 65 (16).
HRMS (ESI): m/z [M + H]+ calcd for C16H18NS: 255.1082; found:
255.1061.
IR (ATR): 3313, 3249, 1666, 1520, 1388, 1323, 1265, 1199, 1065, 933,
746, 689 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.75–7.72 (m, 3 H, NH, 2 CHArCCS),
7.44–7.33 (m, 8 H, 8 CHAr), 4.97 (d, J = 5.2 Hz, 2 H, CH2).
13C NMR (75 MHz, CDCl3): δ = 199.3, 141.7, 136.3, 131.3, 129.1, 128.6,
128.5, 128.3, 126.8, 51.1.
MS (EI): m/z (%) = 250 (M+, 11), 194 (40), 177 (19), 176 (15), 120 (16),
119 (23), 94 (13), 93 (100), 92 (10), 77 (16), 75 (15), 65 (11), 59 (69),
57 (51), 56 (42), 55 (16).
2-Phenyl-N-(1-phenylethyl)thioacetamide (2f)26
4-Methoxy-N-(4-methoxybenzyl)benzothioamide (2b)25
Ochre crystals; yield: 244.3 mg (85%, GPA); mp 96 °C (CH2Cl2).
IR (ATR): 3300, 1602, 1532, 1506, 1301, 1257, 1241, 1173, 1072, 1024,
Orange solid; yield: 102.2 mg (40%, GPA); mp 104 °C (CH2Cl2).
IR (ATR): 3171, 3025, 1531, 1493, 1454, 1435, 1407, 1160, 1106, 1078,
761, 718, 711 cm–1
.
932, 838, 815 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.40–7.23 (m, 9 H, NH, 9 CHAr), 7.17–
7.14 (m, 2 H, CHArCH2), 5.78–5.69 (p, J = 7.0 Hz, 1 H) (p, J = 7.0 Hz, 1 H,
CH), 4.12 (s, 2 H, CH2), 1.49, 1.46 (2 s, 3 H, CH3, both rotamers).
13C NMR (CDCl3, 100 MHz): δ = 200.9, 141.3, 135.0, 129.5 (2 C), 129.3
(2 C), 128.8 (2 C), 127.9, 127.8, 126.3 (2 C), 54.5, 53.4, 20.3.
1H NMR (300 MHz, CDCl3): δ = 7.75 (d, J = 8.8 Hz, 2 H, 2 CHArCCS), 7.66
(br s, 1 H, NH), 7.31 (d, J = 8.6 Hz, 2 H, CHArCCH2), 6.91–6.83 (m, 4 H,
CHArCOCH3), 4.90 (d, J = 4.9 Hz, 2 H, CH2), 3.81 (s, 3 H, CH3), 3.80 (s, 3
H, CH3).
13C NMR (75 MHz, CDCl3): δ = 197.7, 162.6, 134.0, 129.9, 128.5 (2 s
128.6, 128.5), 114.5, 113.7, 55.6, 55.5, 50.7.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

H
P. Gisbert, I. M. Pastor
Paper
Synthesis
MS (EI): m/z (%) = 255 (M+, 26), 106 (11), 105 (100), 104 (22), 103
N-(4-Chlorothiobenzoyl)morpholine (2k)8c
(18), 91 (34), 79 (16), 78 (11), 77 (26), 65 (12).
Yellow oil; yield: 176.4 mg (73%, GPB).
IR (ATR): 2967, 2921, 2855, 1592, 1472, 1435, 1289, 1258, 1228, 1113,
1034, 996, 819, 726 cm–1
1H NMR (300 MHz, CDCl3): δ = 7.36–7.32 (m, 2 H, 2 CHAr), 7.25–7.22
(m, 2 H, 2 CHAr), 4.43–4.40 and 3.90–3.86 (2 m, 4 H, CH2NCH2), 3.66–
3.60 (m, 4 H, CH2OCH2).
N-Benzyl-N-methylbenzothioamide (2g)14
.
Yellow oil; yield: 152.1 mg (63%, GPA).
IR (ATR): 2924, 1496, 1482, 1452, 1395, 1290, 1212, 1110, 1082, 1072,
762, 735, 695 cm–1
.
1H NMR (300 MHz, CDCl3): δ (mixture of rotamers) = 7.46–7.30 (m, 9
H, 9 CHAr), 7.13–7.10 (m, 1 H, 1 CHAr), 5.44 (s, 2 H, CH2, major), 4.71 (s,
2 H, CH2, minor), 3.47 (s, 3 H, CH3, major), 3.00 (s, 3 H, CH3, minor).
13C NMR (75 MHz, CDCl3): δ = 202.5, 202.4, 143.5, 143.4, 135.5, 135.3,
131.2, 129.1, 129.0, 128.7, 128.5, 128.1, 127.0, 125.8, 125.6, 59.5, 57.5,
41.3, 41.1.
13C NMR (75 MHz, CDCl3): δ = 199.6, 140.8, 135.0, 128.9 (2 C), 127.5 (2
C), 66.8, 66.6, 52.7, 49.7.
MS (EI): m/z (%) = 243 (M+ + 2, 29), 242 (M+ + 1, 21), 241 (M+, 80), 240
(M+ – 1, 29), 210 (19), 208 (12), 198 (13), 157 (39), 156 (18), 155
(100), 139 (28), 138 (16), 120 (11), 111 (20), 86 (20), 75 (12).
MS (EI): m/z (%) = 241 (M+, 37), 240 (34), 208 (13), 121 (100), 118
N-(Thiobenzoyl)pyrrolidine (2l)8b
(16), 104 (15), 91 (40), 77 (37), 65 (20), 51 (16).
Brown pale solid; yield: 80.4 mg (42%, GPB); mp 79 °C (CH2Cl2).
IR (ATR): 2982, 1614, 1496, 1470, 1449, 1326, 1264, 1004, 957, 919,
4-Chloro-N-(4-chlorobenzyl)benzothioamide (2h)25
Yellow oil; yield: 213.3 mg (72%, GPA).
877, 764 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.38–7.34 (m, 5 H, 5 CHAr), 3.98 and
3.47 (2 t, J = 7.0, 6.7 Hz, 4 H, CH2NCH2), 2.11–2.07 and 2.00–1.95 (2 m,
4 H, CH2CH2).
IR (ATR): 3239, 1589, 1528, 1485, 1402, 1329, 1281, 1209, 1082, 1012,
924, 833, 808 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.80 (br s, 1 H, NH), 7.67–7.64 (m, 2 H,
2 CHArCCS), 7.36–7.28 (m, 6 H, 6 CHAr), 4.93 (d, J = 5.2 Hz, 2 H, CH2).
13C NMR (75 MHz, CDCl3): δ = 197.4, 144.1, 128.8, 128.4, 125.8, 53.9,
53.5, 26.6, 24.8.
13C NMR (75 MHz, CDCl3): δ = 197.9, 139.7, 137.6, 134.6, 134.2, 129.8,
129.3, 128.8, 128.2, 50.2.
MS (EI): m/z (%) = 297 (M+ + 2, 30), 296 (37), 295 (M+, 55), 294 (M+ – 1,
34), 279 (19), 157 (26), 156 (31), 155 (48), 142 (17), 141 (20), 140
(53), 139 (64), 138 (53), 137 (73), 127 (40), 126 (21), 125 (100), 114
(18), 112 (15), 111 (41), 111 (41), 102 (34), 99 (17), 89 (40), 77 (24),
76 (25), 75 (52), 74 (27), 73 (17), 63 (24), 51 (34).
MS (EI): m/z (%) = 191 (M+, 97), 190 (M+ – 1, 43), 158 (26), 131 (11),
130 (100), 122 (19), 121 (81), 105 (13), 104 (44), 77 (51), 70 (30), 55
(15), 51 (23).
N-Octylbenzothioamide (2m)28
Brown oil; yield: 147.0 mg (82%, GPB).
IR (ATR): 2925, 2846, 1523, 1449, 1335, 768, 692 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.73–7.70 (m, 2 H, 2 CHArCCS), 7.64 (br
s, 1 H, NH), 7.45–7.34 (m, 3 H, 3 CHAr), 3.83–3.76 (m, 2 H, NHCH2),
1.79–1.70 (m, 2 H, NHCH2CH2), 1.45–1.28 (m, 10 H, 5 CH2), 0.91–0.86
(m, 3 H, CH3).
13C NMR (75 MHz, CDCl3): δ = 205.5, 199.5, 142.2, 131.0, 128.6 (2 C),
126.7 (2 C), 47.5, 47.0, 46.3, 31.9, 31.8, 29.5, 29.4, 29.3, 29.2, 29.1,
29.0, 28.3, 28.2, 27.2, 27.1, 22.8, 22.7, 14.2 (26 C, both rotamers).
4-Fluoro-N-(4-fluorobenzyl)benzothioamide (2i)25
Yellow oil; yield: 139.5 mg (53%, GPA).
IR (ATR): 3249, 1595, 1536, 1498, 1413, 1290, 1243, 1219, 1154, 1079,
919, 846, 817 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.77–7.73 (m, 3 H, NH, 2 CHArCCS),
7.36 (dd, J = 8.7, 5.3 Hz, 2 H, 2 CHAr), 7.05 (q, J = 8.7 Hz, 4 H, 4 CHArF),
4.94 (d, J = 5.2 Hz, 2 H, CH2).
13C NMR (75 MHz, CDCl3): δ = 197.8, 164.6 (d, J = 252.5 Hz), 162.6 (d,
J = 247.5 Hz), 137.7 (d, J = 3.0 Hz), 132.0 (d, J = 3.2 Hz), 130.3 (d, J = 8.2
Hz), 129.0 (d, J = 8.8 Hz), 116.0 (d, J = 21.5 Hz), 115.6 (d, J = 22.0 Hz),
50.3.
MS (EI): m/z (%) = 263 (M+, 57), 247 (13), 140 (14), 139 (46), 124 (21),
123 (43), 122 (28), 121 (33), 109 (100), 96 (13), 95 (38), 94 (15), 83
(20), 75 (27), 50 (13).
MS (EI): m/z (%) = 249 (M+, 14), 227 (17), 216 (38), 151 (20), 150 (39),
122 (13), 121 (100), 105 (12), 104 (46), 91 (18), 77 (31).
4-Methoxy-N-octylbenzothioamide (2n)9
Brown oil; yield: 159.1 mg (76%, GPB).
IR (ATR): 3328, 2960, 2913, 2848, 1605, 1532, 1501, 1469, 1421, 1258,
1191, 1029, 936 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.74 (d, J = 8.9 Hz, 2 H, 2 CHArCCS), 7.58
(br s, 1 H, NH), 6.86 (d, J = 8.9 Hz, 2 H, 2 CHAr), 3.83 (s, 3 H, CH3), 3.81–
3.76 (m, 2 H, NHCH2), 1.77–1.72 (m, 10 H, 5 CH2), 0.91–0.86 (m, 3 H,
CH3).
N-(Thiobenzoyl)morpholine (2j)27
Yellow solid; yield: 151.3 mg (73%, GPB); mp 122 °C (CH2Cl2).
IR (ATR): 2920, 2848, 1478, 1432, 1290, 1254, 1225, 1205, 1111, 1061,
13C NMR (75 MHz, CDCl3): δ = 197.9, 162.1, 134.4, 128.5 (2 C), 113.7 (2
C), 55.6, 47.0, 31.9, 29.4, 29.3, 28.3, 27.2, 22.7, 14.2.
MS (EI): m/z (%) = 275 (M+, 48), 278 (21), 246 (78), 207 (13), 181 (36),
180 (51), 152 (14), 151 (100), 136 (13), 135 (21), 134 (76).
991, 871, 758 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 7.42–7.27 (m, 5 H, 5 CHAr), 4.47–4.43
and 3.91–3.88 (2 m, 4 H, CH2NCH2), 3.66–3.60 (m, 4 H, CH2OCH2).
13C NMR (75 MHz, CDCl3): δ = 201.0, 142.5, 128.9, 128.6 (2 C), 125.9 (2
C), 66.8, 66.6, 52.6, 49.6, 33.8.
MS (EI): m/z (%) = 207 (M+, 43), 206 (M+ – 1, 20), 176 (12), 122 (14),
121 (100), 104 (20), 86 (16), 77 (47), 51 (20).
4-Methoxy-N-phenethylbenzothioamide (2o)
Yellow solid; yield: 165.5 mg (61%, GPB); mp 120 °C (CH2Cl2).
IR (ATR): 3340, 3009, 2933, 1599, 1533, 1504, 1387, 1299, 1246, 1180,
1028, 838, 748 cm–1
.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

I
P. Gisbert, I. M. Pastor
Paper
Synthesis
1H NMR (300 MHz, CDCl3): δ = 7.64 (d, J = 8.9 Hz, 2 H, 2 CHArCCS), 7.53
(br s, 1 H, NH), 7.37–7.32 (m, 2 H, 2 CHAr), 7.28–7.24 (m, 3 H, 3 CHAr),
6.83 (d, J = 8.9 Hz, 2 H, 2 CHAr), 4.09 (q, J = 6.9 Hz, 2 H, NHCH2CH2CAr),
3.81 (s, 3 H, CH3), 3.07 (t, J = 6.9 Hz, 2 H, NHCH2CH2CAr).
13C NMR (75 MHz, CDCl3): δ = 198.1, 162.2, 138.4, 134.2, 129.0, 128.9,
128.5, 126.9, 113.7, 55.6, 47.5, 34.0.
MS (EI): m/z (%) = 271 (M+, 38), 151 (21), 136 (14), 135 (46), 134
(100), 104 (22), 92 (11), 91 (36), 77 (21), 65 (19), 63 (12).
HRMS (ESI): m/z [M + H]+ calcd for C16H17NOS: 271.1031; found:
1,2,3,4-Tetrahydroisoquinoline-1-thione (4)25
Yellow solid; yield: 84.9 mg (52%, GPC); mp 85 °C (CH2Cl2).
IR (ATR): 3168, 3036, 1580, 1541, 1345, 1248, 1207, 1196, 1011, 928,
865, 768, 733 cm–1
.
1H NMR (300 MHz, CDCl3): δ = 9.13 (br s, 1 H, NH), 8.51 (dd, J = 7.9, 1.2
Hz, 1 H, 1 CHArCCS), 7.46 (td, J = 7.4, 1.4 Hz, 1 H, 1 CHArCHArCS), 7.35
(td, J = 7.8, 1.3 Hz, 1 H, 1 CHArCHArCHArCS), 7.19–7.16 (m, 1 H, 1
CHArCCH2), 3.57 (td, J = 6.9, 3.5 Hz, 2 H, CCH2CH2NH), 3.57 (t, J = 6.8 Hz,
2 H, CCH2CH2NH).
13C NMR (75 MHz, CDCl3): δ = 193.9, 134.0, 132.8, 132.4, 132.0, 127.4,
271.1001.
127.2, 41.9, 27.9.
4-Chloro-N-phenethylbenzothioamide (2p)27
MS (EI): m/z (%) = 165 (M+ + 2, 12), 164 (M+ + 1, 13), 163 (M+, 100),
162 (14), 136 (13), 135 (25), 134 (90), 131 (12), 130 (23), 128 (28),
118 (17), 90 (20), 89 (20), 77 (21), 63 (21).
Yellow solid; yield: 146.8 mg (54%, GPB); mp 85 °C (CH2Cl2).
IR (ATR): 3270, 1589, 1522, 1485, 1405, 1339, 1234, 1178, 1089, 1063,
1011, 937, 841 cm–1
.
1H NMR (300 MHz, CDCl3): δ (mixture of rotamers) = 7.61–7.57 (m, 3
H, NH, 2 CHArCCS), 7.40–7.27 (m, 7 H, 7 CHAr), 4.11 (td, J = 6.9, 5.7 Hz,
2 H, NHCH2CH2CAr, major), 3.75 (t, J = 7.0 Hz, 2 H, NHCH2CH2CAr, mi-
nor), 3.10 (t, J = 6.9 Hz, 2 H, NHCH2CH2CAr, major), 3.01 (t, J = 6.9 Hz, 2
H, NHCH2CH2CAr, minor).
Funding Information
This work was financially supported by the Spanish Ministry (Minis-
terio de Economía y Competitividad CTQ2015-66624-P) and the Uni-
versity of Alicante (VIGROB-285).
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13C NMR (75 MHz, CDCl3): δ = 197.8, 140.2, 138.2, 137.4, 129.1 (2 C),
128.9 (2 C), 128.8 (2 C), 128.0 (2 C), 127.1, 47.6, 33.9.
MS (EI): m/z (%) = 277 (M+ + 2, 14), 275 (M+, 35), 155 (25), 139 (19),
105 (11), 104 (100).
Acknowledgment
The authors thank M.Sc. M. Albert-Soriano and Dr. P. Trillo for fruitful
discussions.
4-Fluoro-N-phenethylbenzothioamide (2q)
Yellow solid; yield: 106.3 mg (41%, GPB); mp 120 °C (CH2Cl2).
Supporting Information
IR (ATR): 3300, 1599, 1534, 1502, 1244, 1182, 1162, 1065, 1011, 940,
840, 741, 696 cm–1
.
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610179.
1H NMR (300 MHz, CDCl3): δ (mixture of rotamers) = 7.65–7.60 (m, 3
H, NH, 2 CHArCCS), 7.35–7.24 and 7.03–6.97 (2m, 7 H, 7 CHAr), 4.11–
4.04 (m, 2 H, NHCH2CH2CAr, major), 3.84 (t, J = 6.6 Hz, 2 H, NHCH2CH2CAr,
minor), 3.07 (t, J = 7.0 Hz, 2 H, NHCH2CH2CAr, major), 2.82 (t, J = 6.8 Hz,
2 H, NHCH2CH2CAr, minor).
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References
13C NMR (75 MHz, CDCl3): δ = 197.8, 164.5 (d, J = 252.1 Hz), 138.2,
138.0 (d, J = 3.0 Hz), 129.0 (2 C), 128.9 (d, J = 8.6 Hz), 128.8 (2 C),
127.0, 115.5 (d, J = 21.9 Hz), 47.6, 33.8.
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Thieme: Stuttgart, 2005, 141.
(3) (a) Guo, W.-S.; Wen, L.-R.; Li, M. Org. Biomol. Chem. 2015, 13,
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bit, A. Org. Lett. 2012, 14, 5948.
(4) Gopinath, P.; Watanabe, T.; Shibasaki, M. J. Org. Chem. 2012, 77,
9260.
MS (EI): m/z (%) = 259 (M+, 19), 139 (45), 123 (14), 122 (13), 105 (11),
104 (100), 103 (17), 95 (23), 91 (20), 78 (11).
HRMS (ESI): m/z [M + H]+ calcd for C15H14FNS: 259.0831; found:
259.0837.
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N-Methylbenzothioamide (3)14
Brown solid; yield: 131.6 mg (87%, GPC); mp 77 °C (CH2Cl2).
IR (ATR): 3311, 1537, 1488, 1458, 1357, 1235, 1042, 1026, 998, 940,
920, 773, 686 cm–1
.
1H NMR (300 MHz, CDCl3): δ (mixture of rotamers) = 7.93 (br s, 1 H,
NH), 7.72–7.69 (m, 2 H, 2 CHArCCS), 7.43–7.32 (m, 3 H, 3 CHAr), 3.30 (s,
3 H, CH3, majorr), 3.28 (s, 3 H, CH3, minor).
13C NMR (75 MHz, CDCl3): δ = 200.0, 141.6, 131.1, 128.5 (2 C), 126.7 (2
C), 33.8.
MS (EI): m/z (%) = 152 (M+ + 1, 13), 151 (M+, 100), 150 (85), 122 (12),
121 (89), 118 (32), 117 (19), 105 (12), 104 (13), 77 (65), 74 (27), 51
(37).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–J

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